MD

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at [email protected] or on Facebook.

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at [email protected] or on Facebook.

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at [email protected] or on Facebook.

In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.

For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.

Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.

Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.

Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?

Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.

He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.

The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.

Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.

I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.

Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.

In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.

For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.

Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.

Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.

Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?

Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.

He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.

The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.

Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.

I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.

Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.

In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.

For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.

Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.

Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.

Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?

Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.

He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.

The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.

Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.

I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.

Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.

Unlike Dr. Elsey (“Surgery can be demanding work: Grit needed,” Letter to the Editor, May 2017, p. 6) and many others in various surgical publications, I have NOT enjoyed recent discussions about my generation’s perceived lack of readiness for independent practice following general surgery residency. Having been subjected to another round this month of “Why The Surgical Sky Is Falling,” I would like to take a moment to offer a different viewpoint.

I graduated from Tufts Medical Center’s general surgery residency in June 2014. After taking the written board exams, I started practice in a hospital-based group in Maine that same summer. My partners, both with 20+ years of experience, instituted a probationary period for observation of skill (ostensibly, and with good-natured teasing, to ensure I would not harm their patients, though I suspect such a thing is fairly universal for a new grad to receive institutional privileges), and, after convincing them I was not a reckless maniac, within a few months I was “on my own” in the operating room. I relied heavily on colleagues those first 18 months in practice, and ,if they ever grew weary of my asking advice about hemorrhoids, biliary colic, and diverticular disease, they never displayed perceptible annoyance. They were, and are, the best mentors I could have had.

Dr. Crosslin is a general surgeon practicing in Rockport, Maine, and an FACS Initiate, October 2017.

Unlike Dr. Elsey (“Surgery can be demanding work: Grit needed,” Letter to the Editor, May 2017, p. 6) and many others in various surgical publications, I have NOT enjoyed recent discussions about my generation’s perceived lack of readiness for independent practice following general surgery residency. Having been subjected to another round this month of “Why The Surgical Sky Is Falling,” I would like to take a moment to offer a different viewpoint.

I graduated from Tufts Medical Center’s general surgery residency in June 2014. After taking the written board exams, I started practice in a hospital-based group in Maine that same summer. My partners, both with 20+ years of experience, instituted a probationary period for observation of skill (ostensibly, and with good-natured teasing, to ensure I would not harm their patients, though I suspect such a thing is fairly universal for a new grad to receive institutional privileges), and, after convincing them I was not a reckless maniac, within a few months I was “on my own” in the operating room. I relied heavily on colleagues those first 18 months in practice, and ,if they ever grew weary of my asking advice about hemorrhoids, biliary colic, and diverticular disease, they never displayed perceptible annoyance. They were, and are, the best mentors I could have had.

Dr. Crosslin is a general surgeon practicing in Rockport, Maine, and an FACS Initiate, October 2017.

Unlike Dr. Elsey (“Surgery can be demanding work: Grit needed,” Letter to the Editor, May 2017, p. 6) and many others in various surgical publications, I have NOT enjoyed recent discussions about my generation’s perceived lack of readiness for independent practice following general surgery residency. Having been subjected to another round this month of “Why The Surgical Sky Is Falling,” I would like to take a moment to offer a different viewpoint.

I graduated from Tufts Medical Center’s general surgery residency in June 2014. After taking the written board exams, I started practice in a hospital-based group in Maine that same summer. My partners, both with 20+ years of experience, instituted a probationary period for observation of skill (ostensibly, and with good-natured teasing, to ensure I would not harm their patients, though I suspect such a thing is fairly universal for a new grad to receive institutional privileges), and, after convincing them I was not a reckless maniac, within a few months I was “on my own” in the operating room. I relied heavily on colleagues those first 18 months in practice, and ,if they ever grew weary of my asking advice about hemorrhoids, biliary colic, and diverticular disease, they never displayed perceptible annoyance. They were, and are, the best mentors I could have had.

Dr. Crosslin is a general surgeon practicing in Rockport, Maine, and an FACS Initiate, October 2017.

The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.^1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.^1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.^5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.^1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.^9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.^9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

Short-term memory frequently may be affected during postdeployment transition.^9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.^10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.^9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).¹⁴ The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.¹⁶ Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.¹⁶ The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.¹⁶ At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).^17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.^16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.^18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.^17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.^22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.^10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.¹⁴

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.^10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.^9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.²⁶ Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.²⁷ Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.^28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.^14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.^1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.^1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.^5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.^1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.^9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.^9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

Short-term memory frequently may be affected during postdeployment transition.^9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.^10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.^9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).¹⁴ The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.¹⁶ Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.¹⁶ The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.¹⁶ At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).^17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.^16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.^18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.^17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.^22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.^10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.¹⁴

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.^10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.^9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.²⁶ Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.²⁷ Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.^28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.^14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.^1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.^1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.^5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.^1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.^9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.^9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

Short-term memory frequently may be affected during postdeployment transition.^9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.^10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.^9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).¹⁴ The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.¹⁶ Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.¹⁶ The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.¹⁶ At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).^17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.^16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.^18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.^17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.^22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.^10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.¹⁴

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.^10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.^9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.²⁶ Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.²⁷ Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.^28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.^14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

Take-Home Points

• Technique provides optimal fixation while simultaneously protecting open growth plates.
• Self tensioning feature insures both optimal ACL tension and fracture reduction.
• No need for future hardware removal.
• 10Cross suture configuration optimizes strength of fixation for highly consistent results.
• Use fluoroscopy to avoid violation of tibial physis.

Generally occurring in the 8- to 14-year-old population, tibial eminence avulsion (TEA) fractures are a common variant of anterior cruciate ligament (ACL) ruptures and represent 2% to 5% of all knee injuries in skeletally immature individuals.^1,2 Compared with adults, children likely experience this anomaly more often because of the weakness of their incompletely ossified tibial plateau relative to the strength of their native ACL.³

The open repair techniques that have been described have multiple disadvantages, including open incisions, difficult visualization of the fracture owing to the location of the fat pad, and increased risk for arthrofibrosis. Arthroscopic fixation is considered the treatment of choice for TEA fractures because it allows for direct visualization of injury, accurate reduction of fracture fragments, removal of loose fragments, and easy treatment of associated soft-tissue injuries.^4-6Several fixation techniques for ACL-TEA fractures were recently described: arthroscopic reduction and internal fixation (ARIF) with Kirschner wires,⁷ cannulated screws,⁴ the Meniscus Arrow device (Bionx Implants),⁸ pull-out sutures,^9,10 bioabsorbable nails,¹¹ Herbert screws,¹² TightRope fixation (Arthrex),¹³ and various other rotator cuff and meniscal repair systems.^14,15 These approaches tend to have good outcomes for TEA fractures, but there are risks associated with ACL tensioning and potential tibial growth plate violation or hardware problems. Likewise, there are no studies with large numbers of patients treated with these new techniques, so the optimal method of reduction and fixation is still unknown.

In this article, we describe a new ARIF technique that involves 2 absorbable anchors with adjustable suture-tensioning technology. This technique optimizes reduction and helps surgeons avoid proximal tibial physeal damage, procedure-related morbidity, and additional surgery.

Case Report

History

The patient, an 8-year-old boy, sustained a noncontact twisting injury of the left knee during a cutting maneuver in a flag football game. He experienced immediate pain and subsequent swelling. Clinical examination revealed a moderate effusion with motion limitations secondary to swelling and irritability. The patient’s Lachman test result was 2+. Pivot shift testing was not possible because of guarding. The knee was stable to varus and valgus stress at 0° and 30° of flexion. Limited knee flexion prohibited placement of the patient in the position needed for anterior and posterior drawer testing. His patella was stable on lateral stress testing at 20° of flexion with no apprehension. Neurovascular status was intact throughout the lower extremity.

Anteroposterior and lateral radiographs showed a minimally displaced Meyers-McKeever type II TEA fracture (Figures 1A, 1B).

Examination Under Anesthesia

Examination with the patient under general anesthesia revealed 3+ Lachman, 2+ pivot shift with foot in internal and external rotation, and 1+ anterior drawer with foot in neutral and internal rotation. The knee was stable to varus and valgus stress testing.

Surgical Technique

Proper patient positioning and padding of bony prominences were ensured, and the limb was sterilely prepared and draped.

Given the young age of the patient, it was imperative to avoid the open proximal tibial growth plate. The surgical plan for stabilization involved use of two 3.0-mm BioComposite Knotless SutureTak anchors (Arthrex). This anchor configuration is based on a No. 2 FiberWire suture shuttled through itself to create a locking splice mechanism that allows for adjustable tensioning. The anchors were placed on each side of the tibial bony avulsion site with two No. 2 FiberWire sutures and were then crossed about the avulsion fracture fragment in an “x-type” configuration to secure the ACL back down to the bony bed.

First, a curette was used to débride fibrous tissue on the underside of the fracture fragment and on the fracture bed. Minimal amounts of cancellous bone were débrided from the tibial fracture bed to optimize fracture reduction by slightly recessing the fracture fragment to ensure optimal ACL tensioning (Figure 5).

Follow-Up

Two weeks after surgery, the patient returned to clinic for suture removal. Four weeks after surgery, radiographs confirmed anatomical reduction of the TEA fracture, and outpatient physical therapy (range-of-motion exercises as tolerated) and isometric quadriceps strengthening were instituted. Twelve weeks after surgery, examination revealed full knee motion, negative Lachman and pivot shift test results, and residual quadriceps muscle atrophy, and radiographs confirmed complete fracture healing with maintenance of a normal proximal tibial growth plate (Figures 10A, 10B).

Discussion

The highlight of this case is the simplicity of an excellent reduction of a displaced ACL-TEA fracture. Minimally invasive absorbable implants did not violate the proximal tibial physis, and the unique adjustable suture-tensioning technology allowed the degree of reduction and ACL tension to be “dialed in.” SutureTak implants have strong No. 2 FiberWire suture for excellent stability with an overall small suture load, and their small size avoids the risk of violating the proximal tibial physis and avoids potential growth disturbances.

Despite the obvious risks it poses to the open proximal tibial physis, surgical reduction of Meyers-McKeever type II and type III fractures is the norm for restoring ACL stability. Screws and suture fixation are the most common and reliable methods of TEA fracture reduction.^16,17 In recent systematic reviews, however, Osti and colleagues¹⁷ and Gans and colleagues¹⁸ noted there is not enough evidence to warrant a “gold standard” in pediatric tibial avulsion cases.

Other fixation methods for TEA fractures must be investigated. Anderson and colleagues¹⁹ described the biomechanics of 4 different physeal-sparing avulsion fracture reduction techniques: an ultra-high-molecular-weight polyethylene (UHMWPE) suture-suture button, a suture anchor, a polydioxanone suture-suture button, and screw fixation. Using techniques described by Kocher and colleagues,⁴ Berg,²⁰ Mah and colleagues,²¹ Vega and colleagues,²² and Lu and colleagues,²³ Anderson and colleagues¹⁹ reduced TEA fractures in skeletally immature porcine knees. Compared with suture anchors, UHMWPE suture-suture buttons provided biomechanically superior cyclic and load-to-failure results as well as more consistent fixation.

Screw fixation has shown good results but has disadvantages. Incorrect positioning of a screw can lead to impingement and articular cartilage damage, and screw removal may be needed if discomfort at the fixation site persists.^24,25 Likewise, screws generally are an option only for large fracture fragments, as there is an inherent risk of fracturing small TEA fractures, which can be common in skeletally immature patients.

Brunner and colleagues²⁶ recently found that TEA fracture repair with absorbable sutures and distal bone bridge fixation yielded 3-month radiographic and clinical healing rates similar to those obtained with nonabsorbable sutures tied around a screw. However, other authors have reported growth disturbances with use of a similar technique, owing to a disturbance of the open proximal tibial growth plate.⁹ In that regard, a major advantage of this new knotless suturing technique is that distal fixation is not necessary.

The minimally invasive TEA fraction reduction technique described in this article has 6 advantages: It provides excellent fixation while avoiding proximal tibial growth plate injury; the degree of tensioning is easily controlled during reduction; it uses strong suture instead of metal screws or pins; the reduction construct is low-profile; distal fixation is unnecessary; and implant removal is unnecessary, thus limiting subsequent surgical intervention. With respect to long-term outcomes, however, it is not known how this procedure will compare with other commonly used ARIF methods in physeal-sparing techniques for TEA fracture fixation.

This case report highlights a novel pediatric displaced ACL-TEA fracture reduction technique that allows for adjustable reduction and resultant ACL tensioning with excellent strong suture fixation without violating the proximal tibial physis, which could make it invaluable in the surgical treatment of this injury in skeletally immature patients.

Am J Orthop. 2017;46(4):203-208. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Technique provides optimal fixation while simultaneously protecting open growth plates.
• Self tensioning feature insures both optimal ACL tension and fracture reduction.
• No need for future hardware removal.
• 10Cross suture configuration optimizes strength of fixation for highly consistent results.
• Use fluoroscopy to avoid violation of tibial physis.

Generally occurring in the 8- to 14-year-old population, tibial eminence avulsion (TEA) fractures are a common variant of anterior cruciate ligament (ACL) ruptures and represent 2% to 5% of all knee injuries in skeletally immature individuals.^1,2 Compared with adults, children likely experience this anomaly more often because of the weakness of their incompletely ossified tibial plateau relative to the strength of their native ACL.³

The open repair techniques that have been described have multiple disadvantages, including open incisions, difficult visualization of the fracture owing to the location of the fat pad, and increased risk for arthrofibrosis. Arthroscopic fixation is considered the treatment of choice for TEA fractures because it allows for direct visualization of injury, accurate reduction of fracture fragments, removal of loose fragments, and easy treatment of associated soft-tissue injuries.^4-6Several fixation techniques for ACL-TEA fractures were recently described: arthroscopic reduction and internal fixation (ARIF) with Kirschner wires,⁷ cannulated screws,⁴ the Meniscus Arrow device (Bionx Implants),⁸ pull-out sutures,^9,10 bioabsorbable nails,¹¹ Herbert screws,¹² TightRope fixation (Arthrex),¹³ and various other rotator cuff and meniscal repair systems.^14,15 These approaches tend to have good outcomes for TEA fractures, but there are risks associated with ACL tensioning and potential tibial growth plate violation or hardware problems. Likewise, there are no studies with large numbers of patients treated with these new techniques, so the optimal method of reduction and fixation is still unknown.

In this article, we describe a new ARIF technique that involves 2 absorbable anchors with adjustable suture-tensioning technology. This technique optimizes reduction and helps surgeons avoid proximal tibial physeal damage, procedure-related morbidity, and additional surgery.

Case Report

History

The patient, an 8-year-old boy, sustained a noncontact twisting injury of the left knee during a cutting maneuver in a flag football game. He experienced immediate pain and subsequent swelling. Clinical examination revealed a moderate effusion with motion limitations secondary to swelling and irritability. The patient’s Lachman test result was 2+. Pivot shift testing was not possible because of guarding. The knee was stable to varus and valgus stress at 0° and 30° of flexion. Limited knee flexion prohibited placement of the patient in the position needed for anterior and posterior drawer testing. His patella was stable on lateral stress testing at 20° of flexion with no apprehension. Neurovascular status was intact throughout the lower extremity.

Anteroposterior and lateral radiographs showed a minimally displaced Meyers-McKeever type II TEA fracture (Figures 1A, 1B).

Examination Under Anesthesia

Examination with the patient under general anesthesia revealed 3+ Lachman, 2+ pivot shift with foot in internal and external rotation, and 1+ anterior drawer with foot in neutral and internal rotation. The knee was stable to varus and valgus stress testing.

Surgical Technique

Proper patient positioning and padding of bony prominences were ensured, and the limb was sterilely prepared and draped.

Given the young age of the patient, it was imperative to avoid the open proximal tibial growth plate. The surgical plan for stabilization involved use of two 3.0-mm BioComposite Knotless SutureTak anchors (Arthrex). This anchor configuration is based on a No. 2 FiberWire suture shuttled through itself to create a locking splice mechanism that allows for adjustable tensioning. The anchors were placed on each side of the tibial bony avulsion site with two No. 2 FiberWire sutures and were then crossed about the avulsion fracture fragment in an “x-type” configuration to secure the ACL back down to the bony bed.

First, a curette was used to débride fibrous tissue on the underside of the fracture fragment and on the fracture bed. Minimal amounts of cancellous bone were débrided from the tibial fracture bed to optimize fracture reduction by slightly recessing the fracture fragment to ensure optimal ACL tensioning (Figure 5).

Follow-Up

Two weeks after surgery, the patient returned to clinic for suture removal. Four weeks after surgery, radiographs confirmed anatomical reduction of the TEA fracture, and outpatient physical therapy (range-of-motion exercises as tolerated) and isometric quadriceps strengthening were instituted. Twelve weeks after surgery, examination revealed full knee motion, negative Lachman and pivot shift test results, and residual quadriceps muscle atrophy, and radiographs confirmed complete fracture healing with maintenance of a normal proximal tibial growth plate (Figures 10A, 10B).

Discussion

The highlight of this case is the simplicity of an excellent reduction of a displaced ACL-TEA fracture. Minimally invasive absorbable implants did not violate the proximal tibial physis, and the unique adjustable suture-tensioning technology allowed the degree of reduction and ACL tension to be “dialed in.” SutureTak implants have strong No. 2 FiberWire suture for excellent stability with an overall small suture load, and their small size avoids the risk of violating the proximal tibial physis and avoids potential growth disturbances.

Despite the obvious risks it poses to the open proximal tibial physis, surgical reduction of Meyers-McKeever type II and type III fractures is the norm for restoring ACL stability. Screws and suture fixation are the most common and reliable methods of TEA fracture reduction.^16,17 In recent systematic reviews, however, Osti and colleagues¹⁷ and Gans and colleagues¹⁸ noted there is not enough evidence to warrant a “gold standard” in pediatric tibial avulsion cases.

Other fixation methods for TEA fractures must be investigated. Anderson and colleagues¹⁹ described the biomechanics of 4 different physeal-sparing avulsion fracture reduction techniques: an ultra-high-molecular-weight polyethylene (UHMWPE) suture-suture button, a suture anchor, a polydioxanone suture-suture button, and screw fixation. Using techniques described by Kocher and colleagues,⁴ Berg,²⁰ Mah and colleagues,²¹ Vega and colleagues,²² and Lu and colleagues,²³ Anderson and colleagues¹⁹ reduced TEA fractures in skeletally immature porcine knees. Compared with suture anchors, UHMWPE suture-suture buttons provided biomechanically superior cyclic and load-to-failure results as well as more consistent fixation.

Screw fixation has shown good results but has disadvantages. Incorrect positioning of a screw can lead to impingement and articular cartilage damage, and screw removal may be needed if discomfort at the fixation site persists.^24,25 Likewise, screws generally are an option only for large fracture fragments, as there is an inherent risk of fracturing small TEA fractures, which can be common in skeletally immature patients.

Brunner and colleagues²⁶ recently found that TEA fracture repair with absorbable sutures and distal bone bridge fixation yielded 3-month radiographic and clinical healing rates similar to those obtained with nonabsorbable sutures tied around a screw. However, other authors have reported growth disturbances with use of a similar technique, owing to a disturbance of the open proximal tibial growth plate.⁹ In that regard, a major advantage of this new knotless suturing technique is that distal fixation is not necessary.

The minimally invasive TEA fraction reduction technique described in this article has 6 advantages: It provides excellent fixation while avoiding proximal tibial growth plate injury; the degree of tensioning is easily controlled during reduction; it uses strong suture instead of metal screws or pins; the reduction construct is low-profile; distal fixation is unnecessary; and implant removal is unnecessary, thus limiting subsequent surgical intervention. With respect to long-term outcomes, however, it is not known how this procedure will compare with other commonly used ARIF methods in physeal-sparing techniques for TEA fracture fixation.

This case report highlights a novel pediatric displaced ACL-TEA fracture reduction technique that allows for adjustable reduction and resultant ACL tensioning with excellent strong suture fixation without violating the proximal tibial physis, which could make it invaluable in the surgical treatment of this injury in skeletally immature patients.

Am J Orthop. 2017;46(4):203-208. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Technique provides optimal fixation while simultaneously protecting open growth plates.
• Self tensioning feature insures both optimal ACL tension and fracture reduction.
• No need for future hardware removal.
• 10Cross suture configuration optimizes strength of fixation for highly consistent results.
• Use fluoroscopy to avoid violation of tibial physis.

Generally occurring in the 8- to 14-year-old population, tibial eminence avulsion (TEA) fractures are a common variant of anterior cruciate ligament (ACL) ruptures and represent 2% to 5% of all knee injuries in skeletally immature individuals.^1,2 Compared with adults, children likely experience this anomaly more often because of the weakness of their incompletely ossified tibial plateau relative to the strength of their native ACL.³

The open repair techniques that have been described have multiple disadvantages, including open incisions, difficult visualization of the fracture owing to the location of the fat pad, and increased risk for arthrofibrosis. Arthroscopic fixation is considered the treatment of choice for TEA fractures because it allows for direct visualization of injury, accurate reduction of fracture fragments, removal of loose fragments, and easy treatment of associated soft-tissue injuries.^4-6Several fixation techniques for ACL-TEA fractures were recently described: arthroscopic reduction and internal fixation (ARIF) with Kirschner wires,⁷ cannulated screws,⁴ the Meniscus Arrow device (Bionx Implants),⁸ pull-out sutures,^9,10 bioabsorbable nails,¹¹ Herbert screws,¹² TightRope fixation (Arthrex),¹³ and various other rotator cuff and meniscal repair systems.^14,15 These approaches tend to have good outcomes for TEA fractures, but there are risks associated with ACL tensioning and potential tibial growth plate violation or hardware problems. Likewise, there are no studies with large numbers of patients treated with these new techniques, so the optimal method of reduction and fixation is still unknown.

In this article, we describe a new ARIF technique that involves 2 absorbable anchors with adjustable suture-tensioning technology. This technique optimizes reduction and helps surgeons avoid proximal tibial physeal damage, procedure-related morbidity, and additional surgery.

Case Report

History

The patient, an 8-year-old boy, sustained a noncontact twisting injury of the left knee during a cutting maneuver in a flag football game. He experienced immediate pain and subsequent swelling. Clinical examination revealed a moderate effusion with motion limitations secondary to swelling and irritability. The patient’s Lachman test result was 2+. Pivot shift testing was not possible because of guarding. The knee was stable to varus and valgus stress at 0° and 30° of flexion. Limited knee flexion prohibited placement of the patient in the position needed for anterior and posterior drawer testing. His patella was stable on lateral stress testing at 20° of flexion with no apprehension. Neurovascular status was intact throughout the lower extremity.

Anteroposterior and lateral radiographs showed a minimally displaced Meyers-McKeever type II TEA fracture (Figures 1A, 1B).

Examination Under Anesthesia

Examination with the patient under general anesthesia revealed 3+ Lachman, 2+ pivot shift with foot in internal and external rotation, and 1+ anterior drawer with foot in neutral and internal rotation. The knee was stable to varus and valgus stress testing.

Surgical Technique

Proper patient positioning and padding of bony prominences were ensured, and the limb was sterilely prepared and draped.

Given the young age of the patient, it was imperative to avoid the open proximal tibial growth plate. The surgical plan for stabilization involved use of two 3.0-mm BioComposite Knotless SutureTak anchors (Arthrex). This anchor configuration is based on a No. 2 FiberWire suture shuttled through itself to create a locking splice mechanism that allows for adjustable tensioning. The anchors were placed on each side of the tibial bony avulsion site with two No. 2 FiberWire sutures and were then crossed about the avulsion fracture fragment in an “x-type” configuration to secure the ACL back down to the bony bed.

First, a curette was used to débride fibrous tissue on the underside of the fracture fragment and on the fracture bed. Minimal amounts of cancellous bone were débrided from the tibial fracture bed to optimize fracture reduction by slightly recessing the fracture fragment to ensure optimal ACL tensioning (Figure 5).

Follow-Up

Two weeks after surgery, the patient returned to clinic for suture removal. Four weeks after surgery, radiographs confirmed anatomical reduction of the TEA fracture, and outpatient physical therapy (range-of-motion exercises as tolerated) and isometric quadriceps strengthening were instituted. Twelve weeks after surgery, examination revealed full knee motion, negative Lachman and pivot shift test results, and residual quadriceps muscle atrophy, and radiographs confirmed complete fracture healing with maintenance of a normal proximal tibial growth plate (Figures 10A, 10B).

Discussion

The highlight of this case is the simplicity of an excellent reduction of a displaced ACL-TEA fracture. Minimally invasive absorbable implants did not violate the proximal tibial physis, and the unique adjustable suture-tensioning technology allowed the degree of reduction and ACL tension to be “dialed in.” SutureTak implants have strong No. 2 FiberWire suture for excellent stability with an overall small suture load, and their small size avoids the risk of violating the proximal tibial physis and avoids potential growth disturbances.

Despite the obvious risks it poses to the open proximal tibial physis, surgical reduction of Meyers-McKeever type II and type III fractures is the norm for restoring ACL stability. Screws and suture fixation are the most common and reliable methods of TEA fracture reduction.^16,17 In recent systematic reviews, however, Osti and colleagues¹⁷ and Gans and colleagues¹⁸ noted there is not enough evidence to warrant a “gold standard” in pediatric tibial avulsion cases.

Other fixation methods for TEA fractures must be investigated. Anderson and colleagues¹⁹ described the biomechanics of 4 different physeal-sparing avulsion fracture reduction techniques: an ultra-high-molecular-weight polyethylene (UHMWPE) suture-suture button, a suture anchor, a polydioxanone suture-suture button, and screw fixation. Using techniques described by Kocher and colleagues,⁴ Berg,²⁰ Mah and colleagues,²¹ Vega and colleagues,²² and Lu and colleagues,²³ Anderson and colleagues¹⁹ reduced TEA fractures in skeletally immature porcine knees. Compared with suture anchors, UHMWPE suture-suture buttons provided biomechanically superior cyclic and load-to-failure results as well as more consistent fixation.

Screw fixation has shown good results but has disadvantages. Incorrect positioning of a screw can lead to impingement and articular cartilage damage, and screw removal may be needed if discomfort at the fixation site persists.^24,25 Likewise, screws generally are an option only for large fracture fragments, as there is an inherent risk of fracturing small TEA fractures, which can be common in skeletally immature patients.

Brunner and colleagues²⁶ recently found that TEA fracture repair with absorbable sutures and distal bone bridge fixation yielded 3-month radiographic and clinical healing rates similar to those obtained with nonabsorbable sutures tied around a screw. However, other authors have reported growth disturbances with use of a similar technique, owing to a disturbance of the open proximal tibial growth plate.⁹ In that regard, a major advantage of this new knotless suturing technique is that distal fixation is not necessary.

The minimally invasive TEA fraction reduction technique described in this article has 6 advantages: It provides excellent fixation while avoiding proximal tibial growth plate injury; the degree of tensioning is easily controlled during reduction; it uses strong suture instead of metal screws or pins; the reduction construct is low-profile; distal fixation is unnecessary; and implant removal is unnecessary, thus limiting subsequent surgical intervention. With respect to long-term outcomes, however, it is not known how this procedure will compare with other commonly used ARIF methods in physeal-sparing techniques for TEA fracture fixation.

This case report highlights a novel pediatric displaced ACL-TEA fracture reduction technique that allows for adjustable reduction and resultant ACL tensioning with excellent strong suture fixation without violating the proximal tibial physis, which could make it invaluable in the surgical treatment of this injury in skeletally immature patients.

Am J Orthop. 2017;46(4):203-208. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Fever in hospitalized patients is a nonspecific finding with many potential causes. Blood cultures (BC) are commonly obtained prior to commencing parenteral antibiotics in febrile patients. However, as many as 35% to 50% of positive BCs represent a contamination with organisms inoculated from the skin into culture bottles at the time of sample collection.^1-3 Such results represent false-positive BCs that can lead to unnecessary investigations and treatment.

Recently, Coburn et al. reviewed the severity of chills (graded on an ordinal scale) as the most useful predictor of true bacteremia (positive likelihood ratio [LR], 4.7; 95% confidence interval [CI], 3.0–7.2),^4-6 and the lack of the systemic inflammatory response syndrome (SIRS) criteria as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 We have also previously reported normal food consumption as a negative indicator of true bacteremia, with a 98.3% negative predictive value.⁸ Henderson’s Basic Principles of Nursing Care emphasizes the importance of evaluating whether a patient can eat and drink adequately,⁹ and the evaluation of a patient’s food consumption is a routine nursing staff practice, which is treated as vital sign in Japan, in contrast to nursing practices in the United States.

However, these data were the result of a single-center retrospective study using the nursing staff’s assessment of food consumption, and they cannot be generalized to larger patient populations. Therefore, the aim of this prospective, multicenter study was to measure the accuracy of food consumption and shaking chills as predictive factors for true bacteremia.

Study Design

This was a prospective multicenter observational study (UMIN ID: R000013768) involving 3 hospitals in Tokyo, Japan, that enrolled consecutive patients who had BCs obtained. This study was approved by the ethical committee at Juntendo University Nerima Hospital and each of the participating centers, and the study was conducted in accordance with the Declaration of Helsinki 1971, as revised in 1983. We evaluated 2,792 consecutive hospitalized patients (mean age, 68.9 ± 17.1 years; 55.3% men) who had BCs obtained between April 2013 and August 2014, inclusive. The indication for BC acquisition was at the discretion of the treating physician. The study protocol and the indication for BCs are described in detail elsewhere.⁸ We excluded patients with anorexia-inducing conditions such as gastrointestinal disease, including gastrointestinal bleeding, enterocolitis, gastric ulceration, peritonitis, appendicitis, cholangitis, pancreatitis, diverticulitis, and ischemic colitis. We also excluded patients receiving chemotherapy for malignancy. In this study, true bacteremia was defined as identical organisms isolated from 2 sets of blood cultures (a set refers to one aerobic bottle and one anaerobic bottle). Moreover, even if only one set of blood cultures was acquired, when the identified pathogen could account for the clinical presentation, we also defined this as true bacteremia. Briefly, contaminants were defined as organisms common to skin flora, including Bacillus species, coagulase-negative Staphylococcus, Corynebacterium species, and Micrococcus species, without isolation of an identical organism with the same antibiotic susceptibilities from another potentially infected site in a patient with incompatible clinical features and no risk factors for infection with the isolated organism. Single BCs that were positive for organisms that were unlikely to explain the patient’s symptoms were also considered as contaminants. Patients with contaminated BCs were excluded from the analyses.

Structure of Reliability Study Procedures

Nurses in the 3 different hospitals performed daily independent food consumption ratings during each patient’s stay. Interrater reliability assessments were conducted in the morning or afternoon, and none of the raters had access to the other nurses’ scores at any time. The study nurses performed simultaneous ratings during these assessments (one interacted with and rated the patient while the other observed and rated the same patient).

Prediction Variables of True Bacteremia


1. Food consumption. Assessment of food consumption has been previously described in detail.⁸ Briefly, we characterized the patients’ oral intake based on the meal taken immediately prior to the BCs. For example, if a fever developed at 2 pm, lunch consumption was evaluated. If a fever developed at 2 am, dinner consumption was evaluated. We categorized the patients into 3 groups: low food consumption (<50% consumed), moderate food consumption (>50% to <80% consumed), and high food consumption (>80% consumed). To simplify our prediction rule, we subsequently divided food consumption into just 2 groups: high food consumption, referred to as the “normal food consumption group,” and the combination of low and moderate food consumption, referred to as the “poor food consumption group.”

2. Chills. As done previously, the physician evaluated the patient for a history of chills at the time of BCs and classified the patients into 1 of 4 grades^4,5: “no chills,” the absence of any chills; “mild chills,” feeling cold, equivalent to needing an outer jacket; “moderate chills,” feeling very cold, equivalent to needing a thick blanket; and “shaking chills,” feeling extremely cold with rigors and generalized bodily shaking, even under a thick blanket. To distinguish between those patients who had shaking chills and those who did not, we divided the patients into 2 groups: the “shaking chills group” and the combination of none, mild, and moderate chills, referred to as the “negative shaking chills group.”

3. Other predictive variables. We considered the following additional predictive variables: age, gender, axillary body temperature (BT), heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR), white blood cell count (WBC), and serum C-reactive protein level (CRP). These predictive variables were obtained immediately prior to the BCs. We defined SIRS based on standard criteria (HR >90 beats/m, RR >20/m, BT <36°C or >38°C, and a WBC <4 × 10³ WBC/μL or >12 × 10³ WBC/μL). Patients were subcategorized by age into 2 groups (≤69 years and >70 years). CRP levels were dichotomized as >10.0 mg/dL or ≤10.0 mg/dL. We reviewed the patients’ charts to determine whether they had received antibiotics. In the case of walk-in patients, we interviewed the patients regarding whether they had visited a clinic; if they had, they were questioned as to whether any antibiotic therapy had been prescribed.

Statistical Analysis

Continuous variables are presented as the mean with the associated standard deviation (SD). All potential variables predictive of true bacteremia are shown in Table 1. The variables were dichotomized by clinically meaningful thresholds and used as potential risk-adjusted variables. We calculated the sensitivity and specificity and positive and negative predictive value for each criterion. Multiple logistic regression analysis was used to select components that were significantly associated with true bacteremia (the level of statistical significance determined with maximum likelihood methods was set at P < .05). To visualize and quantify other aspects in the prediction of true bacteremia, a recursive partitioning analysis (RPA) was used to make a decision tree model for true bacteremia. This nonparametric regression method produces a classification tree following a series of nonsequential top-down binary splits. The tree-building process starts by considering a set of predictive variables and selects the variable that produces 2 subsets of participants with the greatest purity. Two factors are considered when splitting a node into its daughter nodes: the goodness of the split and the amount of impurity in the daughter nodes. The splitting process is repeated until further partitioning is no longer possible and the terminal nodes have been reached. Details on this method are discussed in Monte Carlo Calibration of Distributions of Partition Statistics (www.jmp.com).

Probability was considered significant at a value of P < .05. All statistical tests were 2-tailed. Statistical analyses were conducted by a physician (KI) and an independent statistician (JM) with the use of the SPSS^® v.16.0 software package (SPSS Inc., Chicago, IL) and JMP^® version 8.0.2 (SAS Institute, Cary, NC).

Patients Characteristics

Two thousand seven hundred and ninety-two patients met the inclusion criteria for our study, from which 849 were excluded (see Figure 1 for flow diagram). Among the remaining 1,943 patients, there were 317 patients with positive BCs, of which 221 patients (69.7%) were considered to have true-positive BCs and 96 (30.3%) were considered to have contaminated BCs. After excluding these 96 patients, 221 patients with true bacteremia (true bacteremic group) were compared with 1,626 nonbacteremic patients (nonbacteremic group; Figure 1). The baseline characteristics of the subjects are shown in Table 1. The mean BT was 38.4 ± 1.2°C in the true bacteremic group and 37.9 ± 1.0°C in the nonbacteremic group. The mean serum CRP level was 11.6 ± 9.6 mg/dL in the true bacteremic group and 7.3 ± 6.9 mg/dL in the nonbacteremic group. In the true bacteremic group, there were 6 afebrile patients, and 27 patients without leukocytosis. The pathogens identified from the true-positive BCs were Escherichia coli (n = 59, 26.7%), including extended-spectrum beta-lactamase producing species, Staphylococcus aureus (n = 36, 16.3%), including methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae (n = 22, 10.0%; Supplemental Table 1).

The underlying clinical diagnoses in the true bacteremic group included urinary tract infection (UTI), pneumonia, abscess, catheter-related bloodstream infection (CRBSI), cellulitis, osteomyelitis, infective endocarditis (IE), chorioamnionitis, iatrogenic infection at hemodialysis puncture sites, bacterial meningitis, septic arthritis, and infection of unknown cause (Supplemental Table 2).

Interrater Reliability Testing of Food Consumption

Patients were evaluated during their hospital stays. The interrater reliability of the evaluation of food consumption was very high across all participating hospitals (Supplemental Table 3). To assess the reliability of the evaluations of food consumption, patients (separate from this main study) were selected randomly and evaluated independently by 2 nurses in 3 different hospitals. The kappa scores of agreement between the nurses at the 3 different hospitals were 0.83 (95% CI, 0.63-0.88), 0.90 (95% CI, 0.80-0.99), and 0.80 (95% CI, 0.67-0.99), respectively. The interrater reliability of food consumption evaluation by the nurses was very high at all participating hospitals.

Food Consumption

The low, moderate, and high food consumption groups consisted of 964 (52.1%), 306 (16.6%), and 577 (31.2%) patients, respectively (Table 1). Of these, 174 (18.0%), 33 (10.8%), and 14 (2.4%) patients, respectively, had true bacteremia. The presence of poor food consumption had a sensitivity of 93.7% (95% CI, 89.4%-97.9%), specificity of 34.6% (95% CI, 33.0%-36.2%), and a positive LR of 1.43 (95% CI, 1.37-1.50) for predicting true bacteremia. Conversely, the absence of poor food consumption (ie, normal food consumption) had a negative LR of 0.18 (95% CI, 0.17-0.19).

Chills

The no, mild, moderate, and shaking chills groups consisted of 1,514 (82.0%), 148 (8.0%), 53 (2.9%), and 132 (7.1%) patients, respectively (Table 1). Of these, 136 (9.0%), 25 (16.9%), 8 (15.1%), and 52 (39.4%) patients, respectively, had true bacteremia. The presence of shaking chills had a sensitivity of 23.5% (95% CI, 22.5%-24.6%), a specificity of 95.1% (95% CI, 90.7%-99.4%), and a positive LR of 4.78 (95% CI, 4.56–5.00) for predicting true bacteremia. Conversely, the absence of shaking chills had a negative LR of 0.80 (95% CI, 0.77-0.84).

Prediction Model for True Bacteremia

The components identified as significantly related to true bacteremia by multiple logistic regression analysis are indicated in Table 2. The significant predictors of true bacteremia were shaking chills (odds ratio [OR], 5.6; 95% CI, 3.6-8.6; P < .01), SBP <90 mmHg (OR, 3.1; 95% CI, 1.6-5.7; P < 01), CRP levels >10.0 mg/dL (OR, 2.2; 95% CI, 1.6-3.1; P < .01), BT <36°C or >38°C (OR, 1.8; 95% CI, 1.3-2.6; P < .01), WBC <4 × 10³/μL or >12 × 10³/μL (OR, 1.6; 95% CI, 1.2-2.3; P = .003), HR >90 bpm (OR, 1.5; 95% CI, 1.1-2.1; P = .021), and female (OR, 1.4; 95% CI, 1.0-1.9; P = .036). An RPA to create an ideal prediction model for patients with true bacteremia or nonbacteremia is shown in Figure 2. The original group consisted of 1,847 patients, including 221 patients with true bacteremia. The pretest probability of true bacteremia was 2.4% (14/577) for those with normal food consumption (Group 1) and 2.4% (13/552) for those with both normal food consumption and the absence of shaking chills (Group 2). Conversely, the pretest probability of true bacteremia was 16.3% (207/1270) for those with poor food consumption and 47.7% (51/107) for those with both poor food consumption and shaking chills. The patients with true bacteremia with normal food consumption and without shaking chills consisted of 4 cases of CRBSI and UTI, 2 cases of osteomyelitis, 1 case of IE, 1 case of chorioamnionitis, and 1 case for which the focus was unknown (Supplemental Table 4).

In this observational study, we evaluated if a simple algorithm using food consumption and shaking chills was useful for assessing whether a patient had true bacteremia. A 2-item screening checklist (nursing assessment of food consumption and shaking chills) had excellent statistical properties as a brief screening instrument for true bacteremia.

We have prospectively validated that food consumption, as assessed by nurses, is a reliable predictor of true bacteremia.⁸ A previous single-center retrospective study showed similar findings, but these could not be generalized across all institutions because of the limited nature of the study. In this multicenter study, we used 2 statistical methods to reduce selection bias. First, we performed a kappa analysis across the hospitals to evaluate the interrater reliability of the evaluation of food consumption. Second, we used an RPA (Figure 2), also known as a decision tree model. RPA is a step-by-step process by which a decision tree is constructed by either splitting or not splitting each node on the tree into 2 daughter nodes.¹⁰ By using this method, we successfully generated an ideal approach to predict true bacteremia using food consumption and shaking chills. After adjusting for food consumption and shaking chills, groups 1 to 2 had sequentially decreasing diagnoses of true bacteremia, varying from 221 patients to only 13 patients.

Appetite is influenced by many factors that are integrated by the brain, most importantly within the hypothalamus. Signals that impinge on the hypothalamic center include neural afferents, hormones, cytokines, and metabolites.¹¹ These factors elicit “sickness behavior,” which includes a decrease in food-motivated behavior.¹² Furthermore, exposure to pathogenic bacteria increases serotonin, which has been shown to decrease metabolism in amphid neurons by transcriptional and post-transcriptional mechanisms.¹³ Therefore, nonbacteremic patients retain their appetites. Shaking chills are a well-known predictor of true bacteremia.^4,5 Several cytokines, including tumor necrosis factor-alpha and interleukins 6 and 10, may be related to shaking chills.¹⁴ Coburn et al. reviewed that shaking chills appear to be useful for identifying true bacteremia (positive LR, 4.7; 95% CI, 3.0-7.2),^5,6 similar to our study. In our study, the pretest probability of true bacteremia was the same whether shaking chills was included or not (ie, 2.4% for normal food consumption and 2.4% for normal food consumption plus absence of shaking chills). This would seem to imply that the assessment of shaking chills does not appear to add anything over food assessment alone when trying to rule out bacteremia. Rather, shaking chills seem more important for ruling in bacteremia rather than ruling it out. Moreover, the recent retrospective study revealed that age >60 years (OR = 2.75, 95% CI, 1.23-6.48, P = .015), female sex (OR = 2.21, 95% CI, 1.07- 4.67, P = .038), heart rate >90 bpm (OR = 5.18, 95% CI, 2.25-12.48, P < .001) and neutrophil percentage >80% (OR = 3.61, 95% CI, 1.71- 8.00, P = .001) were independent risk factors for true bacteremia.¹⁵ Conversely, the lack of the SIRS criteria was reported as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 However, the evaluation of SIRS criteria requires the acquisition of laboratory data. To our knowledge, no previous prospective studies have evaluated food consumption in terms of a risk prediction for true bacteremia. This extremely simple model can enable a physician to make a rapid bedside estimation of the risk of true bacteremia.

The strengths of this study include its relatively large sample size, multicenter design, uniformity of data collection across sites, and completeness of data collection from study participants. All of these factors allowed for a robust analysis.

However, there are several limitations of this study. First, the physicians or nurses asked the patients about the presence of shaking chills when they obtained the BCs. It may be difficult for patients, especially elderly patients, to provide this information promptly and accurately. Some patients did not call the nurse when they had shaking chills, and the chills were not witnessed by a healthcare provider. However, we used a more specific definition for shaking chills: a feeling of being extremely cold with rigors and generalized bodily shaking, even under a thick blanket. Second, this algorithm is not applicable to patients with immunosuppressed states because none of the hospitals involved in this study perform bone marrow or organ transplantation. Third, although we included patients with dementia in our cohort, we did not specifically evaluate performance of the algorithm in patients with this medical condition. It is possible that the algorithm would not perform well in this subset of patients owing to their unreliable appetite and food intake. Fourth, some medications may affect appetite, leading to reduced food consumption. Although we have not considered the details of medications in this study, we found that the pretest probability of true bacteremia was low for those patients with normal food consumption regardless of whether the medication affected their appetites or not. However, the question of whether medications truly affect patients’ appetites concurrently with bacteremia would need to be specifically addressed in a future study.

CONCLUSION

In conclusion, we have established a simple algorithm to identify patients with suspected true bacteremia who require the acquisition of blood cultures. This extremely simple model can enable physicians to make a rapid bedside estimation of the risk of true bacteremia.

Acknowledgment

The authors thank Drs. H. Honda and S. Saint, and Ms. A. Okada for their helpful discussions with regard to this study; Ms. M. Takigawa for the collection of data; and Ms. T. Oguri for providing infectious disease consultation on the pathogenicity of the identified organisms.

Disclosure

This work was supported by JSPS KAKENHI Grant Number 15K19294 (to TK) and 20590840 (to KI) from the Japan Society for the Promotion of Science. The authors report no potential conflicts of interest relevant to this article.

Fever in hospitalized patients is a nonspecific finding with many potential causes. Blood cultures (BC) are commonly obtained prior to commencing parenteral antibiotics in febrile patients. However, as many as 35% to 50% of positive BCs represent a contamination with organisms inoculated from the skin into culture bottles at the time of sample collection.^1-3 Such results represent false-positive BCs that can lead to unnecessary investigations and treatment.

Recently, Coburn et al. reviewed the severity of chills (graded on an ordinal scale) as the most useful predictor of true bacteremia (positive likelihood ratio [LR], 4.7; 95% confidence interval [CI], 3.0–7.2),^4-6 and the lack of the systemic inflammatory response syndrome (SIRS) criteria as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 We have also previously reported normal food consumption as a negative indicator of true bacteremia, with a 98.3% negative predictive value.⁸ Henderson’s Basic Principles of Nursing Care emphasizes the importance of evaluating whether a patient can eat and drink adequately,⁹ and the evaluation of a patient’s food consumption is a routine nursing staff practice, which is treated as vital sign in Japan, in contrast to nursing practices in the United States.

However, these data were the result of a single-center retrospective study using the nursing staff’s assessment of food consumption, and they cannot be generalized to larger patient populations. Therefore, the aim of this prospective, multicenter study was to measure the accuracy of food consumption and shaking chills as predictive factors for true bacteremia.

Study Design

This was a prospective multicenter observational study (UMIN ID: R000013768) involving 3 hospitals in Tokyo, Japan, that enrolled consecutive patients who had BCs obtained. This study was approved by the ethical committee at Juntendo University Nerima Hospital and each of the participating centers, and the study was conducted in accordance with the Declaration of Helsinki 1971, as revised in 1983. We evaluated 2,792 consecutive hospitalized patients (mean age, 68.9 ± 17.1 years; 55.3% men) who had BCs obtained between April 2013 and August 2014, inclusive. The indication for BC acquisition was at the discretion of the treating physician. The study protocol and the indication for BCs are described in detail elsewhere.⁸ We excluded patients with anorexia-inducing conditions such as gastrointestinal disease, including gastrointestinal bleeding, enterocolitis, gastric ulceration, peritonitis, appendicitis, cholangitis, pancreatitis, diverticulitis, and ischemic colitis. We also excluded patients receiving chemotherapy for malignancy. In this study, true bacteremia was defined as identical organisms isolated from 2 sets of blood cultures (a set refers to one aerobic bottle and one anaerobic bottle). Moreover, even if only one set of blood cultures was acquired, when the identified pathogen could account for the clinical presentation, we also defined this as true bacteremia. Briefly, contaminants were defined as organisms common to skin flora, including Bacillus species, coagulase-negative Staphylococcus, Corynebacterium species, and Micrococcus species, without isolation of an identical organism with the same antibiotic susceptibilities from another potentially infected site in a patient with incompatible clinical features and no risk factors for infection with the isolated organism. Single BCs that were positive for organisms that were unlikely to explain the patient’s symptoms were also considered as contaminants. Patients with contaminated BCs were excluded from the analyses.

Structure of Reliability Study Procedures

Nurses in the 3 different hospitals performed daily independent food consumption ratings during each patient’s stay. Interrater reliability assessments were conducted in the morning or afternoon, and none of the raters had access to the other nurses’ scores at any time. The study nurses performed simultaneous ratings during these assessments (one interacted with and rated the patient while the other observed and rated the same patient).

Prediction Variables of True Bacteremia


1. Food consumption. Assessment of food consumption has been previously described in detail.⁸ Briefly, we characterized the patients’ oral intake based on the meal taken immediately prior to the BCs. For example, if a fever developed at 2 pm, lunch consumption was evaluated. If a fever developed at 2 am, dinner consumption was evaluated. We categorized the patients into 3 groups: low food consumption (<50% consumed), moderate food consumption (>50% to <80% consumed), and high food consumption (>80% consumed). To simplify our prediction rule, we subsequently divided food consumption into just 2 groups: high food consumption, referred to as the “normal food consumption group,” and the combination of low and moderate food consumption, referred to as the “poor food consumption group.”

2. Chills. As done previously, the physician evaluated the patient for a history of chills at the time of BCs and classified the patients into 1 of 4 grades^4,5: “no chills,” the absence of any chills; “mild chills,” feeling cold, equivalent to needing an outer jacket; “moderate chills,” feeling very cold, equivalent to needing a thick blanket; and “shaking chills,” feeling extremely cold with rigors and generalized bodily shaking, even under a thick blanket. To distinguish between those patients who had shaking chills and those who did not, we divided the patients into 2 groups: the “shaking chills group” and the combination of none, mild, and moderate chills, referred to as the “negative shaking chills group.”

3. Other predictive variables. We considered the following additional predictive variables: age, gender, axillary body temperature (BT), heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR), white blood cell count (WBC), and serum C-reactive protein level (CRP). These predictive variables were obtained immediately prior to the BCs. We defined SIRS based on standard criteria (HR >90 beats/m, RR >20/m, BT <36°C or >38°C, and a WBC <4 × 10³ WBC/μL or >12 × 10³ WBC/μL). Patients were subcategorized by age into 2 groups (≤69 years and >70 years). CRP levels were dichotomized as >10.0 mg/dL or ≤10.0 mg/dL. We reviewed the patients’ charts to determine whether they had received antibiotics. In the case of walk-in patients, we interviewed the patients regarding whether they had visited a clinic; if they had, they were questioned as to whether any antibiotic therapy had been prescribed.

Statistical Analysis

Continuous variables are presented as the mean with the associated standard deviation (SD). All potential variables predictive of true bacteremia are shown in Table 1. The variables were dichotomized by clinically meaningful thresholds and used as potential risk-adjusted variables. We calculated the sensitivity and specificity and positive and negative predictive value for each criterion. Multiple logistic regression analysis was used to select components that were significantly associated with true bacteremia (the level of statistical significance determined with maximum likelihood methods was set at P < .05). To visualize and quantify other aspects in the prediction of true bacteremia, a recursive partitioning analysis (RPA) was used to make a decision tree model for true bacteremia. This nonparametric regression method produces a classification tree following a series of nonsequential top-down binary splits. The tree-building process starts by considering a set of predictive variables and selects the variable that produces 2 subsets of participants with the greatest purity. Two factors are considered when splitting a node into its daughter nodes: the goodness of the split and the amount of impurity in the daughter nodes. The splitting process is repeated until further partitioning is no longer possible and the terminal nodes have been reached. Details on this method are discussed in Monte Carlo Calibration of Distributions of Partition Statistics (www.jmp.com).

Probability was considered significant at a value of P < .05. All statistical tests were 2-tailed. Statistical analyses were conducted by a physician (KI) and an independent statistician (JM) with the use of the SPSS^® v.16.0 software package (SPSS Inc., Chicago, IL) and JMP^® version 8.0.2 (SAS Institute, Cary, NC).

Patients Characteristics

Two thousand seven hundred and ninety-two patients met the inclusion criteria for our study, from which 849 were excluded (see Figure 1 for flow diagram). Among the remaining 1,943 patients, there were 317 patients with positive BCs, of which 221 patients (69.7%) were considered to have true-positive BCs and 96 (30.3%) were considered to have contaminated BCs. After excluding these 96 patients, 221 patients with true bacteremia (true bacteremic group) were compared with 1,626 nonbacteremic patients (nonbacteremic group; Figure 1). The baseline characteristics of the subjects are shown in Table 1. The mean BT was 38.4 ± 1.2°C in the true bacteremic group and 37.9 ± 1.0°C in the nonbacteremic group. The mean serum CRP level was 11.6 ± 9.6 mg/dL in the true bacteremic group and 7.3 ± 6.9 mg/dL in the nonbacteremic group. In the true bacteremic group, there were 6 afebrile patients, and 27 patients without leukocytosis. The pathogens identified from the true-positive BCs were Escherichia coli (n = 59, 26.7%), including extended-spectrum beta-lactamase producing species, Staphylococcus aureus (n = 36, 16.3%), including methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae (n = 22, 10.0%; Supplemental Table 1).

The underlying clinical diagnoses in the true bacteremic group included urinary tract infection (UTI), pneumonia, abscess, catheter-related bloodstream infection (CRBSI), cellulitis, osteomyelitis, infective endocarditis (IE), chorioamnionitis, iatrogenic infection at hemodialysis puncture sites, bacterial meningitis, septic arthritis, and infection of unknown cause (Supplemental Table 2).

Interrater Reliability Testing of Food Consumption

Patients were evaluated during their hospital stays. The interrater reliability of the evaluation of food consumption was very high across all participating hospitals (Supplemental Table 3). To assess the reliability of the evaluations of food consumption, patients (separate from this main study) were selected randomly and evaluated independently by 2 nurses in 3 different hospitals. The kappa scores of agreement between the nurses at the 3 different hospitals were 0.83 (95% CI, 0.63-0.88), 0.90 (95% CI, 0.80-0.99), and 0.80 (95% CI, 0.67-0.99), respectively. The interrater reliability of food consumption evaluation by the nurses was very high at all participating hospitals.

Food Consumption

The low, moderate, and high food consumption groups consisted of 964 (52.1%), 306 (16.6%), and 577 (31.2%) patients, respectively (Table 1). Of these, 174 (18.0%), 33 (10.8%), and 14 (2.4%) patients, respectively, had true bacteremia. The presence of poor food consumption had a sensitivity of 93.7% (95% CI, 89.4%-97.9%), specificity of 34.6% (95% CI, 33.0%-36.2%), and a positive LR of 1.43 (95% CI, 1.37-1.50) for predicting true bacteremia. Conversely, the absence of poor food consumption (ie, normal food consumption) had a negative LR of 0.18 (95% CI, 0.17-0.19).

Chills

The no, mild, moderate, and shaking chills groups consisted of 1,514 (82.0%), 148 (8.0%), 53 (2.9%), and 132 (7.1%) patients, respectively (Table 1). Of these, 136 (9.0%), 25 (16.9%), 8 (15.1%), and 52 (39.4%) patients, respectively, had true bacteremia. The presence of shaking chills had a sensitivity of 23.5% (95% CI, 22.5%-24.6%), a specificity of 95.1% (95% CI, 90.7%-99.4%), and a positive LR of 4.78 (95% CI, 4.56–5.00) for predicting true bacteremia. Conversely, the absence of shaking chills had a negative LR of 0.80 (95% CI, 0.77-0.84).

Prediction Model for True Bacteremia

The components identified as significantly related to true bacteremia by multiple logistic regression analysis are indicated in Table 2. The significant predictors of true bacteremia were shaking chills (odds ratio [OR], 5.6; 95% CI, 3.6-8.6; P < .01), SBP <90 mmHg (OR, 3.1; 95% CI, 1.6-5.7; P < 01), CRP levels >10.0 mg/dL (OR, 2.2; 95% CI, 1.6-3.1; P < .01), BT <36°C or >38°C (OR, 1.8; 95% CI, 1.3-2.6; P < .01), WBC <4 × 10³/μL or >12 × 10³/μL (OR, 1.6; 95% CI, 1.2-2.3; P = .003), HR >90 bpm (OR, 1.5; 95% CI, 1.1-2.1; P = .021), and female (OR, 1.4; 95% CI, 1.0-1.9; P = .036). An RPA to create an ideal prediction model for patients with true bacteremia or nonbacteremia is shown in Figure 2. The original group consisted of 1,847 patients, including 221 patients with true bacteremia. The pretest probability of true bacteremia was 2.4% (14/577) for those with normal food consumption (Group 1) and 2.4% (13/552) for those with both normal food consumption and the absence of shaking chills (Group 2). Conversely, the pretest probability of true bacteremia was 16.3% (207/1270) for those with poor food consumption and 47.7% (51/107) for those with both poor food consumption and shaking chills. The patients with true bacteremia with normal food consumption and without shaking chills consisted of 4 cases of CRBSI and UTI, 2 cases of osteomyelitis, 1 case of IE, 1 case of chorioamnionitis, and 1 case for which the focus was unknown (Supplemental Table 4).

In this observational study, we evaluated if a simple algorithm using food consumption and shaking chills was useful for assessing whether a patient had true bacteremia. A 2-item screening checklist (nursing assessment of food consumption and shaking chills) had excellent statistical properties as a brief screening instrument for true bacteremia.

We have prospectively validated that food consumption, as assessed by nurses, is a reliable predictor of true bacteremia.⁸ A previous single-center retrospective study showed similar findings, but these could not be generalized across all institutions because of the limited nature of the study. In this multicenter study, we used 2 statistical methods to reduce selection bias. First, we performed a kappa analysis across the hospitals to evaluate the interrater reliability of the evaluation of food consumption. Second, we used an RPA (Figure 2), also known as a decision tree model. RPA is a step-by-step process by which a decision tree is constructed by either splitting or not splitting each node on the tree into 2 daughter nodes.¹⁰ By using this method, we successfully generated an ideal approach to predict true bacteremia using food consumption and shaking chills. After adjusting for food consumption and shaking chills, groups 1 to 2 had sequentially decreasing diagnoses of true bacteremia, varying from 221 patients to only 13 patients.

Appetite is influenced by many factors that are integrated by the brain, most importantly within the hypothalamus. Signals that impinge on the hypothalamic center include neural afferents, hormones, cytokines, and metabolites.¹¹ These factors elicit “sickness behavior,” which includes a decrease in food-motivated behavior.¹² Furthermore, exposure to pathogenic bacteria increases serotonin, which has been shown to decrease metabolism in amphid neurons by transcriptional and post-transcriptional mechanisms.¹³ Therefore, nonbacteremic patients retain their appetites. Shaking chills are a well-known predictor of true bacteremia.^4,5 Several cytokines, including tumor necrosis factor-alpha and interleukins 6 and 10, may be related to shaking chills.¹⁴ Coburn et al. reviewed that shaking chills appear to be useful for identifying true bacteremia (positive LR, 4.7; 95% CI, 3.0-7.2),^5,6 similar to our study. In our study, the pretest probability of true bacteremia was the same whether shaking chills was included or not (ie, 2.4% for normal food consumption and 2.4% for normal food consumption plus absence of shaking chills). This would seem to imply that the assessment of shaking chills does not appear to add anything over food assessment alone when trying to rule out bacteremia. Rather, shaking chills seem more important for ruling in bacteremia rather than ruling it out. Moreover, the recent retrospective study revealed that age >60 years (OR = 2.75, 95% CI, 1.23-6.48, P = .015), female sex (OR = 2.21, 95% CI, 1.07- 4.67, P = .038), heart rate >90 bpm (OR = 5.18, 95% CI, 2.25-12.48, P < .001) and neutrophil percentage >80% (OR = 3.61, 95% CI, 1.71- 8.00, P = .001) were independent risk factors for true bacteremia.¹⁵ Conversely, the lack of the SIRS criteria was reported as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 However, the evaluation of SIRS criteria requires the acquisition of laboratory data. To our knowledge, no previous prospective studies have evaluated food consumption in terms of a risk prediction for true bacteremia. This extremely simple model can enable a physician to make a rapid bedside estimation of the risk of true bacteremia.

The strengths of this study include its relatively large sample size, multicenter design, uniformity of data collection across sites, and completeness of data collection from study participants. All of these factors allowed for a robust analysis.

However, there are several limitations of this study. First, the physicians or nurses asked the patients about the presence of shaking chills when they obtained the BCs. It may be difficult for patients, especially elderly patients, to provide this information promptly and accurately. Some patients did not call the nurse when they had shaking chills, and the chills were not witnessed by a healthcare provider. However, we used a more specific definition for shaking chills: a feeling of being extremely cold with rigors and generalized bodily shaking, even under a thick blanket. Second, this algorithm is not applicable to patients with immunosuppressed states because none of the hospitals involved in this study perform bone marrow or organ transplantation. Third, although we included patients with dementia in our cohort, we did not specifically evaluate performance of the algorithm in patients with this medical condition. It is possible that the algorithm would not perform well in this subset of patients owing to their unreliable appetite and food intake. Fourth, some medications may affect appetite, leading to reduced food consumption. Although we have not considered the details of medications in this study, we found that the pretest probability of true bacteremia was low for those patients with normal food consumption regardless of whether the medication affected their appetites or not. However, the question of whether medications truly affect patients’ appetites concurrently with bacteremia would need to be specifically addressed in a future study.

CONCLUSION

In conclusion, we have established a simple algorithm to identify patients with suspected true bacteremia who require the acquisition of blood cultures. This extremely simple model can enable physicians to make a rapid bedside estimation of the risk of true bacteremia.

Acknowledgment

The authors thank Drs. H. Honda and S. Saint, and Ms. A. Okada for their helpful discussions with regard to this study; Ms. M. Takigawa for the collection of data; and Ms. T. Oguri for providing infectious disease consultation on the pathogenicity of the identified organisms.

Disclosure

This work was supported by JSPS KAKENHI Grant Number 15K19294 (to TK) and 20590840 (to KI) from the Japan Society for the Promotion of Science. The authors report no potential conflicts of interest relevant to this article.

Fever in hospitalized patients is a nonspecific finding with many potential causes. Blood cultures (BC) are commonly obtained prior to commencing parenteral antibiotics in febrile patients. However, as many as 35% to 50% of positive BCs represent a contamination with organisms inoculated from the skin into culture bottles at the time of sample collection.^1-3 Such results represent false-positive BCs that can lead to unnecessary investigations and treatment.

Recently, Coburn et al. reviewed the severity of chills (graded on an ordinal scale) as the most useful predictor of true bacteremia (positive likelihood ratio [LR], 4.7; 95% confidence interval [CI], 3.0–7.2),^4-6 and the lack of the systemic inflammatory response syndrome (SIRS) criteria as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 We have also previously reported normal food consumption as a negative indicator of true bacteremia, with a 98.3% negative predictive value.⁸ Henderson’s Basic Principles of Nursing Care emphasizes the importance of evaluating whether a patient can eat and drink adequately,⁹ and the evaluation of a patient’s food consumption is a routine nursing staff practice, which is treated as vital sign in Japan, in contrast to nursing practices in the United States.

However, these data were the result of a single-center retrospective study using the nursing staff’s assessment of food consumption, and they cannot be generalized to larger patient populations. Therefore, the aim of this prospective, multicenter study was to measure the accuracy of food consumption and shaking chills as predictive factors for true bacteremia.

Study Design

This was a prospective multicenter observational study (UMIN ID: R000013768) involving 3 hospitals in Tokyo, Japan, that enrolled consecutive patients who had BCs obtained. This study was approved by the ethical committee at Juntendo University Nerima Hospital and each of the participating centers, and the study was conducted in accordance with the Declaration of Helsinki 1971, as revised in 1983. We evaluated 2,792 consecutive hospitalized patients (mean age, 68.9 ± 17.1 years; 55.3% men) who had BCs obtained between April 2013 and August 2014, inclusive. The indication for BC acquisition was at the discretion of the treating physician. The study protocol and the indication for BCs are described in detail elsewhere.⁸ We excluded patients with anorexia-inducing conditions such as gastrointestinal disease, including gastrointestinal bleeding, enterocolitis, gastric ulceration, peritonitis, appendicitis, cholangitis, pancreatitis, diverticulitis, and ischemic colitis. We also excluded patients receiving chemotherapy for malignancy. In this study, true bacteremia was defined as identical organisms isolated from 2 sets of blood cultures (a set refers to one aerobic bottle and one anaerobic bottle). Moreover, even if only one set of blood cultures was acquired, when the identified pathogen could account for the clinical presentation, we also defined this as true bacteremia. Briefly, contaminants were defined as organisms common to skin flora, including Bacillus species, coagulase-negative Staphylococcus, Corynebacterium species, and Micrococcus species, without isolation of an identical organism with the same antibiotic susceptibilities from another potentially infected site in a patient with incompatible clinical features and no risk factors for infection with the isolated organism. Single BCs that were positive for organisms that were unlikely to explain the patient’s symptoms were also considered as contaminants. Patients with contaminated BCs were excluded from the analyses.

Structure of Reliability Study Procedures

Nurses in the 3 different hospitals performed daily independent food consumption ratings during each patient’s stay. Interrater reliability assessments were conducted in the morning or afternoon, and none of the raters had access to the other nurses’ scores at any time. The study nurses performed simultaneous ratings during these assessments (one interacted with and rated the patient while the other observed and rated the same patient).

Prediction Variables of True Bacteremia


1. Food consumption. Assessment of food consumption has been previously described in detail.⁸ Briefly, we characterized the patients’ oral intake based on the meal taken immediately prior to the BCs. For example, if a fever developed at 2 pm, lunch consumption was evaluated. If a fever developed at 2 am, dinner consumption was evaluated. We categorized the patients into 3 groups: low food consumption (<50% consumed), moderate food consumption (>50% to <80% consumed), and high food consumption (>80% consumed). To simplify our prediction rule, we subsequently divided food consumption into just 2 groups: high food consumption, referred to as the “normal food consumption group,” and the combination of low and moderate food consumption, referred to as the “poor food consumption group.”

2. Chills. As done previously, the physician evaluated the patient for a history of chills at the time of BCs and classified the patients into 1 of 4 grades^4,5: “no chills,” the absence of any chills; “mild chills,” feeling cold, equivalent to needing an outer jacket; “moderate chills,” feeling very cold, equivalent to needing a thick blanket; and “shaking chills,” feeling extremely cold with rigors and generalized bodily shaking, even under a thick blanket. To distinguish between those patients who had shaking chills and those who did not, we divided the patients into 2 groups: the “shaking chills group” and the combination of none, mild, and moderate chills, referred to as the “negative shaking chills group.”

3. Other predictive variables. We considered the following additional predictive variables: age, gender, axillary body temperature (BT), heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR), white blood cell count (WBC), and serum C-reactive protein level (CRP). These predictive variables were obtained immediately prior to the BCs. We defined SIRS based on standard criteria (HR >90 beats/m, RR >20/m, BT <36°C or >38°C, and a WBC <4 × 10³ WBC/μL or >12 × 10³ WBC/μL). Patients were subcategorized by age into 2 groups (≤69 years and >70 years). CRP levels were dichotomized as >10.0 mg/dL or ≤10.0 mg/dL. We reviewed the patients’ charts to determine whether they had received antibiotics. In the case of walk-in patients, we interviewed the patients regarding whether they had visited a clinic; if they had, they were questioned as to whether any antibiotic therapy had been prescribed.

Statistical Analysis

Continuous variables are presented as the mean with the associated standard deviation (SD). All potential variables predictive of true bacteremia are shown in Table 1. The variables were dichotomized by clinically meaningful thresholds and used as potential risk-adjusted variables. We calculated the sensitivity and specificity and positive and negative predictive value for each criterion. Multiple logistic regression analysis was used to select components that were significantly associated with true bacteremia (the level of statistical significance determined with maximum likelihood methods was set at P < .05). To visualize and quantify other aspects in the prediction of true bacteremia, a recursive partitioning analysis (RPA) was used to make a decision tree model for true bacteremia. This nonparametric regression method produces a classification tree following a series of nonsequential top-down binary splits. The tree-building process starts by considering a set of predictive variables and selects the variable that produces 2 subsets of participants with the greatest purity. Two factors are considered when splitting a node into its daughter nodes: the goodness of the split and the amount of impurity in the daughter nodes. The splitting process is repeated until further partitioning is no longer possible and the terminal nodes have been reached. Details on this method are discussed in Monte Carlo Calibration of Distributions of Partition Statistics (www.jmp.com).

Probability was considered significant at a value of P < .05. All statistical tests were 2-tailed. Statistical analyses were conducted by a physician (KI) and an independent statistician (JM) with the use of the SPSS^® v.16.0 software package (SPSS Inc., Chicago, IL) and JMP^® version 8.0.2 (SAS Institute, Cary, NC).

Patients Characteristics

Two thousand seven hundred and ninety-two patients met the inclusion criteria for our study, from which 849 were excluded (see Figure 1 for flow diagram). Among the remaining 1,943 patients, there were 317 patients with positive BCs, of which 221 patients (69.7%) were considered to have true-positive BCs and 96 (30.3%) were considered to have contaminated BCs. After excluding these 96 patients, 221 patients with true bacteremia (true bacteremic group) were compared with 1,626 nonbacteremic patients (nonbacteremic group; Figure 1). The baseline characteristics of the subjects are shown in Table 1. The mean BT was 38.4 ± 1.2°C in the true bacteremic group and 37.9 ± 1.0°C in the nonbacteremic group. The mean serum CRP level was 11.6 ± 9.6 mg/dL in the true bacteremic group and 7.3 ± 6.9 mg/dL in the nonbacteremic group. In the true bacteremic group, there were 6 afebrile patients, and 27 patients without leukocytosis. The pathogens identified from the true-positive BCs were Escherichia coli (n = 59, 26.7%), including extended-spectrum beta-lactamase producing species, Staphylococcus aureus (n = 36, 16.3%), including methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae (n = 22, 10.0%; Supplemental Table 1).

The underlying clinical diagnoses in the true bacteremic group included urinary tract infection (UTI), pneumonia, abscess, catheter-related bloodstream infection (CRBSI), cellulitis, osteomyelitis, infective endocarditis (IE), chorioamnionitis, iatrogenic infection at hemodialysis puncture sites, bacterial meningitis, septic arthritis, and infection of unknown cause (Supplemental Table 2).

Interrater Reliability Testing of Food Consumption

Patients were evaluated during their hospital stays. The interrater reliability of the evaluation of food consumption was very high across all participating hospitals (Supplemental Table 3). To assess the reliability of the evaluations of food consumption, patients (separate from this main study) were selected randomly and evaluated independently by 2 nurses in 3 different hospitals. The kappa scores of agreement between the nurses at the 3 different hospitals were 0.83 (95% CI, 0.63-0.88), 0.90 (95% CI, 0.80-0.99), and 0.80 (95% CI, 0.67-0.99), respectively. The interrater reliability of food consumption evaluation by the nurses was very high at all participating hospitals.

Food Consumption

The low, moderate, and high food consumption groups consisted of 964 (52.1%), 306 (16.6%), and 577 (31.2%) patients, respectively (Table 1). Of these, 174 (18.0%), 33 (10.8%), and 14 (2.4%) patients, respectively, had true bacteremia. The presence of poor food consumption had a sensitivity of 93.7% (95% CI, 89.4%-97.9%), specificity of 34.6% (95% CI, 33.0%-36.2%), and a positive LR of 1.43 (95% CI, 1.37-1.50) for predicting true bacteremia. Conversely, the absence of poor food consumption (ie, normal food consumption) had a negative LR of 0.18 (95% CI, 0.17-0.19).

Chills

The no, mild, moderate, and shaking chills groups consisted of 1,514 (82.0%), 148 (8.0%), 53 (2.9%), and 132 (7.1%) patients, respectively (Table 1). Of these, 136 (9.0%), 25 (16.9%), 8 (15.1%), and 52 (39.4%) patients, respectively, had true bacteremia. The presence of shaking chills had a sensitivity of 23.5% (95% CI, 22.5%-24.6%), a specificity of 95.1% (95% CI, 90.7%-99.4%), and a positive LR of 4.78 (95% CI, 4.56–5.00) for predicting true bacteremia. Conversely, the absence of shaking chills had a negative LR of 0.80 (95% CI, 0.77-0.84).

Prediction Model for True Bacteremia

The components identified as significantly related to true bacteremia by multiple logistic regression analysis are indicated in Table 2. The significant predictors of true bacteremia were shaking chills (odds ratio [OR], 5.6; 95% CI, 3.6-8.6; P < .01), SBP <90 mmHg (OR, 3.1; 95% CI, 1.6-5.7; P < 01), CRP levels >10.0 mg/dL (OR, 2.2; 95% CI, 1.6-3.1; P < .01), BT <36°C or >38°C (OR, 1.8; 95% CI, 1.3-2.6; P < .01), WBC <4 × 10³/μL or >12 × 10³/μL (OR, 1.6; 95% CI, 1.2-2.3; P = .003), HR >90 bpm (OR, 1.5; 95% CI, 1.1-2.1; P = .021), and female (OR, 1.4; 95% CI, 1.0-1.9; P = .036). An RPA to create an ideal prediction model for patients with true bacteremia or nonbacteremia is shown in Figure 2. The original group consisted of 1,847 patients, including 221 patients with true bacteremia. The pretest probability of true bacteremia was 2.4% (14/577) for those with normal food consumption (Group 1) and 2.4% (13/552) for those with both normal food consumption and the absence of shaking chills (Group 2). Conversely, the pretest probability of true bacteremia was 16.3% (207/1270) for those with poor food consumption and 47.7% (51/107) for those with both poor food consumption and shaking chills. The patients with true bacteremia with normal food consumption and without shaking chills consisted of 4 cases of CRBSI and UTI, 2 cases of osteomyelitis, 1 case of IE, 1 case of chorioamnionitis, and 1 case for which the focus was unknown (Supplemental Table 4).

In this observational study, we evaluated if a simple algorithm using food consumption and shaking chills was useful for assessing whether a patient had true bacteremia. A 2-item screening checklist (nursing assessment of food consumption and shaking chills) had excellent statistical properties as a brief screening instrument for true bacteremia.

We have prospectively validated that food consumption, as assessed by nurses, is a reliable predictor of true bacteremia.⁸ A previous single-center retrospective study showed similar findings, but these could not be generalized across all institutions because of the limited nature of the study. In this multicenter study, we used 2 statistical methods to reduce selection bias. First, we performed a kappa analysis across the hospitals to evaluate the interrater reliability of the evaluation of food consumption. Second, we used an RPA (Figure 2), also known as a decision tree model. RPA is a step-by-step process by which a decision tree is constructed by either splitting or not splitting each node on the tree into 2 daughter nodes.¹⁰ By using this method, we successfully generated an ideal approach to predict true bacteremia using food consumption and shaking chills. After adjusting for food consumption and shaking chills, groups 1 to 2 had sequentially decreasing diagnoses of true bacteremia, varying from 221 patients to only 13 patients.

Appetite is influenced by many factors that are integrated by the brain, most importantly within the hypothalamus. Signals that impinge on the hypothalamic center include neural afferents, hormones, cytokines, and metabolites.¹¹ These factors elicit “sickness behavior,” which includes a decrease in food-motivated behavior.¹² Furthermore, exposure to pathogenic bacteria increases serotonin, which has been shown to decrease metabolism in amphid neurons by transcriptional and post-transcriptional mechanisms.¹³ Therefore, nonbacteremic patients retain their appetites. Shaking chills are a well-known predictor of true bacteremia.^4,5 Several cytokines, including tumor necrosis factor-alpha and interleukins 6 and 10, may be related to shaking chills.¹⁴ Coburn et al. reviewed that shaking chills appear to be useful for identifying true bacteremia (positive LR, 4.7; 95% CI, 3.0-7.2),^5,6 similar to our study. In our study, the pretest probability of true bacteremia was the same whether shaking chills was included or not (ie, 2.4% for normal food consumption and 2.4% for normal food consumption plus absence of shaking chills). This would seem to imply that the assessment of shaking chills does not appear to add anything over food assessment alone when trying to rule out bacteremia. Rather, shaking chills seem more important for ruling in bacteremia rather than ruling it out. Moreover, the recent retrospective study revealed that age >60 years (OR = 2.75, 95% CI, 1.23-6.48, P = .015), female sex (OR = 2.21, 95% CI, 1.07- 4.67, P = .038), heart rate >90 bpm (OR = 5.18, 95% CI, 2.25-12.48, P < .001) and neutrophil percentage >80% (OR = 3.61, 95% CI, 1.71- 8.00, P = .001) were independent risk factors for true bacteremia.¹⁵ Conversely, the lack of the SIRS criteria was reported as the best negative indicator of true bacteremia with a negative LR of 0.09 (95% CI, 0.03-0.3).^6,7 However, the evaluation of SIRS criteria requires the acquisition of laboratory data. To our knowledge, no previous prospective studies have evaluated food consumption in terms of a risk prediction for true bacteremia. This extremely simple model can enable a physician to make a rapid bedside estimation of the risk of true bacteremia.

The strengths of this study include its relatively large sample size, multicenter design, uniformity of data collection across sites, and completeness of data collection from study participants. All of these factors allowed for a robust analysis.

However, there are several limitations of this study. First, the physicians or nurses asked the patients about the presence of shaking chills when they obtained the BCs. It may be difficult for patients, especially elderly patients, to provide this information promptly and accurately. Some patients did not call the nurse when they had shaking chills, and the chills were not witnessed by a healthcare provider. However, we used a more specific definition for shaking chills: a feeling of being extremely cold with rigors and generalized bodily shaking, even under a thick blanket. Second, this algorithm is not applicable to patients with immunosuppressed states because none of the hospitals involved in this study perform bone marrow or organ transplantation. Third, although we included patients with dementia in our cohort, we did not specifically evaluate performance of the algorithm in patients with this medical condition. It is possible that the algorithm would not perform well in this subset of patients owing to their unreliable appetite and food intake. Fourth, some medications may affect appetite, leading to reduced food consumption. Although we have not considered the details of medications in this study, we found that the pretest probability of true bacteremia was low for those patients with normal food consumption regardless of whether the medication affected their appetites or not. However, the question of whether medications truly affect patients’ appetites concurrently with bacteremia would need to be specifically addressed in a future study.

CONCLUSION

In conclusion, we have established a simple algorithm to identify patients with suspected true bacteremia who require the acquisition of blood cultures. This extremely simple model can enable physicians to make a rapid bedside estimation of the risk of true bacteremia.

Acknowledgment

The authors thank Drs. H. Honda and S. Saint, and Ms. A. Okada for their helpful discussions with regard to this study; Ms. M. Takigawa for the collection of data; and Ms. T. Oguri for providing infectious disease consultation on the pathogenicity of the identified organisms.

Disclosure

This work was supported by JSPS KAKENHI Grant Number 15K19294 (to TK) and 20590840 (to KI) from the Japan Society for the Promotion of Science. The authors report no potential conflicts of interest relevant to this article.

Study Overview

Objective. To evaluate efficacy of adding bevacizumab to first-line chemotherapy for treatment of extensive-disease small-cell lung cancer (ED-SCLC).

Design. Phase III prospective multicenter randomized clinical trial.

Setting and participants. The study was conducted at 29 Italian centers and was supported by the Agenzia Italiana del Farmaco. Study entry was limited to patients with histologically or cytologically documented ED-SCLC who were previously untreated with systemic therapy, were 18 years of age or older, and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2. Adequate bone marrow, renal, and liver functions were required. Patients with asymptomatic, treated brain metastases were eligible for trial participation. Exclusions included the following: mixed histologic diagnosis of SCLC and non–SCLC; history of grade 2 hemoptysis; evidence of lung tumor cavitation; significant traumatic injury within the 4 weeks before first dose of study treatment; other active malignancies (previous or current); and any underlying medical condition that might be aggravated by treatment.

Intervention. Patients received a combination of intravenous cisplatin (25 mg/m² on days 1 to 3), etoposide (100 mg/m² on days 1 to 3), and bevacizumab (7.5 mg/kg intravenously on day 1) administered every 3 weeks (experimental arm); or the same cisplatin and etoposide chemotherapy regimen alone given every 3 weeks (control arm). Carboplatin (area under the curve 5 on day 1) could be substituted for cisplatin in case of cisplatin contraindications or cisplatin-associated toxicity. Tumor response, on the basis of investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), was evaluated every 3 cycles during chemotherapy treatment. After 6 cycles of chemotherapy, tumor assessment was performed every 9 weeks in both arms. In the absence of progression, patients in the treatment arm continued bevacizumab alone until disease progression or for a maximum of 18 courses. Survival follow-up information was collected every 6 months after treatment termination or last dose of study drug, until death or loss to follow-up.

Main outcome measure. The primary end point was overall survival (OS). Response rate, toxicity, and progression-free survival (PFS) were secondary end points.

Main results. 205 patients were randomized between November 2009 and October 2015. 204 patients were considered in the intent-to-treat analysis (103 in the control arm and 101 in the treatment arm). Most patients were male with ECOG PS of 0 to 1. Median age was 64 years. The median number of chemotherapy courses administered was 6 in both arms. Cisplatin was used in majority of the patients. Average relative dose intensities for all drugs were well balanced between 2 groups. A lower percentage of patients in the treatment arm (14.7%) than in the control arm (22.3%) discontinued treatment because of radiologic disease progression, which was the main reason for treatment discontinuation.

At a median follow-up of 34.9 months, the median PFS was 5.7 in the control arm and 6.7 months in the treatment arm (hazard ratio [HR], 0.72; 95% CI, 0.54 to 0.97; P = 0.30). Median OS times were 8.9 months and 9.8 months, and 1-year survival rates were 25% and 37% (HR, 0.78; 95% CI, 0.58 to 1.06; P = 0.113) in the control arm and treatment arm, respectively. A significant effect of the maintenance treatment on OS (HR, 0.60; 95% CI, 0.40 to 0.91, P = 0.011) was observed. A subgroup analysis revealed a statistically significant interaction for OS between treatment and sex; the addition of bevacizumab led to a significant survival benefit in men (HR, 0.55) and to a possible detrimental effect in women (HR, 1.55; interaction test, P = 0.003).

Addition of bevacizumab did not result in increase in hematologic toxicity such as anemia, neutropenia, or thrombocytopenia. Concerning the nonhematologic toxicity, only hypertension was more frequent in the bevacizumab arm (6.3%) compared to chemotherapy alone arm (1%). The rates of proteinuria and thrombosis were similar in both arms.

Conclusion. The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in PFS, which, however, did not translate into a statistically significant increase in OS.

Commentary

SCLC currently accounts for approximately 12% to 15% of all lung cancers [1]. It is characterized by a rapid growth rate, metastasis at the time of diagnosis, sensitivity to first-line platinum-based chemotherapy, and invariable recurrence and progressive resistance to subsequent lines of therapy. A number of clinical trials over the past 2 decades have failed to produce outcomes superior to platinum-based doublet chemotherapy, leaving a significant unmet need [2]. Vascular endothelial growth factor (VEGF) is the most important proangiogenic factor, and it is implicated in tumor growth [3]. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is now indicated in the treatment of several tumor types including non–SCLC and breast, colorectal, kidney, and ovarian cancer. Positive signal with bevacizumab was seen in phase II studies, providing rationale for this phase III trial [4,5] .

The study by Tiseo and colleagues reported the outcomes of a randomized study that added bevacizumab to standard combination therapy with platinum and etoposide for the treatment of ED-SCLC. A small statistically significant improvement was seen in PFS (6.7 months vs. 5.7 months, favoring the bevacizumab group). However, the study failed to meet the primary end point of improved OS.

So where do antiangiogenesis agents go from here? Alternative angiogenesis inhibitors with broader mechanism of action are being explored in clinical trials. One such trial (ClinicalTrials.gov identifier: NCT02945852) is evaluating the role of the tyrosine kinase inhibitor apatinib in combination with chemotherapy in ED-SCLC. Apatinib selectively inhibits the vascular growth factor receptor-2 (VEGFR2). In addition, this agent also inhibits c-kit and c-SRC tyrosine kinase. It would be interesting to see if antiangiogenic agents with broader mechanisms would be more effective in SCLC. Immunotherapy with checkpoint inhibitors such as nivolumab and pembrolizumab have revolutionized the lung cancer treatment paradigm. It would be interesting to see if bevacizumab could be safely added to these immunotherapy agents. The ongoing CheckMate 370 (ClinicalTrials.gov identifier: NCT02574078) is addressing this question, evaluating the safety of combining nivolumab with bevacizumab in non-SCLC.

Applications for Clinical Practice

The current study does not support the addition of bevacizumab as a standard therapeutic option in the first-line treatment of ED-SCLC. However, given that there was a trend towards improved OS, alternative strategies of incorporating antiangiogenesis agents should be considered in future clinical trials.

—Deval Rajyaguru, MD

Study Overview

Objective. To evaluate efficacy of adding bevacizumab to first-line chemotherapy for treatment of extensive-disease small-cell lung cancer (ED-SCLC).

Design. Phase III prospective multicenter randomized clinical trial.

Setting and participants. The study was conducted at 29 Italian centers and was supported by the Agenzia Italiana del Farmaco. Study entry was limited to patients with histologically or cytologically documented ED-SCLC who were previously untreated with systemic therapy, were 18 years of age or older, and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2. Adequate bone marrow, renal, and liver functions were required. Patients with asymptomatic, treated brain metastases were eligible for trial participation. Exclusions included the following: mixed histologic diagnosis of SCLC and non–SCLC; history of grade 2 hemoptysis; evidence of lung tumor cavitation; significant traumatic injury within the 4 weeks before first dose of study treatment; other active malignancies (previous or current); and any underlying medical condition that might be aggravated by treatment.

Intervention. Patients received a combination of intravenous cisplatin (25 mg/m² on days 1 to 3), etoposide (100 mg/m² on days 1 to 3), and bevacizumab (7.5 mg/kg intravenously on day 1) administered every 3 weeks (experimental arm); or the same cisplatin and etoposide chemotherapy regimen alone given every 3 weeks (control arm). Carboplatin (area under the curve 5 on day 1) could be substituted for cisplatin in case of cisplatin contraindications or cisplatin-associated toxicity. Tumor response, on the basis of investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), was evaluated every 3 cycles during chemotherapy treatment. After 6 cycles of chemotherapy, tumor assessment was performed every 9 weeks in both arms. In the absence of progression, patients in the treatment arm continued bevacizumab alone until disease progression or for a maximum of 18 courses. Survival follow-up information was collected every 6 months after treatment termination or last dose of study drug, until death or loss to follow-up.

Main outcome measure. The primary end point was overall survival (OS). Response rate, toxicity, and progression-free survival (PFS) were secondary end points.

Main results. 205 patients were randomized between November 2009 and October 2015. 204 patients were considered in the intent-to-treat analysis (103 in the control arm and 101 in the treatment arm). Most patients were male with ECOG PS of 0 to 1. Median age was 64 years. The median number of chemotherapy courses administered was 6 in both arms. Cisplatin was used in majority of the patients. Average relative dose intensities for all drugs were well balanced between 2 groups. A lower percentage of patients in the treatment arm (14.7%) than in the control arm (22.3%) discontinued treatment because of radiologic disease progression, which was the main reason for treatment discontinuation.

At a median follow-up of 34.9 months, the median PFS was 5.7 in the control arm and 6.7 months in the treatment arm (hazard ratio [HR], 0.72; 95% CI, 0.54 to 0.97; P = 0.30). Median OS times were 8.9 months and 9.8 months, and 1-year survival rates were 25% and 37% (HR, 0.78; 95% CI, 0.58 to 1.06; P = 0.113) in the control arm and treatment arm, respectively. A significant effect of the maintenance treatment on OS (HR, 0.60; 95% CI, 0.40 to 0.91, P = 0.011) was observed. A subgroup analysis revealed a statistically significant interaction for OS between treatment and sex; the addition of bevacizumab led to a significant survival benefit in men (HR, 0.55) and to a possible detrimental effect in women (HR, 1.55; interaction test, P = 0.003).

Addition of bevacizumab did not result in increase in hematologic toxicity such as anemia, neutropenia, or thrombocytopenia. Concerning the nonhematologic toxicity, only hypertension was more frequent in the bevacizumab arm (6.3%) compared to chemotherapy alone arm (1%). The rates of proteinuria and thrombosis were similar in both arms.

Conclusion. The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in PFS, which, however, did not translate into a statistically significant increase in OS.

Commentary

SCLC currently accounts for approximately 12% to 15% of all lung cancers [1]. It is characterized by a rapid growth rate, metastasis at the time of diagnosis, sensitivity to first-line platinum-based chemotherapy, and invariable recurrence and progressive resistance to subsequent lines of therapy. A number of clinical trials over the past 2 decades have failed to produce outcomes superior to platinum-based doublet chemotherapy, leaving a significant unmet need [2]. Vascular endothelial growth factor (VEGF) is the most important proangiogenic factor, and it is implicated in tumor growth [3]. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is now indicated in the treatment of several tumor types including non–SCLC and breast, colorectal, kidney, and ovarian cancer. Positive signal with bevacizumab was seen in phase II studies, providing rationale for this phase III trial [4,5] .

The study by Tiseo and colleagues reported the outcomes of a randomized study that added bevacizumab to standard combination therapy with platinum and etoposide for the treatment of ED-SCLC. A small statistically significant improvement was seen in PFS (6.7 months vs. 5.7 months, favoring the bevacizumab group). However, the study failed to meet the primary end point of improved OS.

So where do antiangiogenesis agents go from here? Alternative angiogenesis inhibitors with broader mechanism of action are being explored in clinical trials. One such trial (ClinicalTrials.gov identifier: NCT02945852) is evaluating the role of the tyrosine kinase inhibitor apatinib in combination with chemotherapy in ED-SCLC. Apatinib selectively inhibits the vascular growth factor receptor-2 (VEGFR2). In addition, this agent also inhibits c-kit and c-SRC tyrosine kinase. It would be interesting to see if antiangiogenic agents with broader mechanisms would be more effective in SCLC. Immunotherapy with checkpoint inhibitors such as nivolumab and pembrolizumab have revolutionized the lung cancer treatment paradigm. It would be interesting to see if bevacizumab could be safely added to these immunotherapy agents. The ongoing CheckMate 370 (ClinicalTrials.gov identifier: NCT02574078) is addressing this question, evaluating the safety of combining nivolumab with bevacizumab in non-SCLC.

Applications for Clinical Practice

The current study does not support the addition of bevacizumab as a standard therapeutic option in the first-line treatment of ED-SCLC. However, given that there was a trend towards improved OS, alternative strategies of incorporating antiangiogenesis agents should be considered in future clinical trials.

—Deval Rajyaguru, MD

Study Overview

Objective. To evaluate efficacy of adding bevacizumab to first-line chemotherapy for treatment of extensive-disease small-cell lung cancer (ED-SCLC).

Design. Phase III prospective multicenter randomized clinical trial.

Setting and participants. The study was conducted at 29 Italian centers and was supported by the Agenzia Italiana del Farmaco. Study entry was limited to patients with histologically or cytologically documented ED-SCLC who were previously untreated with systemic therapy, were 18 years of age or older, and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2. Adequate bone marrow, renal, and liver functions were required. Patients with asymptomatic, treated brain metastases were eligible for trial participation. Exclusions included the following: mixed histologic diagnosis of SCLC and non–SCLC; history of grade 2 hemoptysis; evidence of lung tumor cavitation; significant traumatic injury within the 4 weeks before first dose of study treatment; other active malignancies (previous or current); and any underlying medical condition that might be aggravated by treatment.

Intervention. Patients received a combination of intravenous cisplatin (25 mg/m² on days 1 to 3), etoposide (100 mg/m² on days 1 to 3), and bevacizumab (7.5 mg/kg intravenously on day 1) administered every 3 weeks (experimental arm); or the same cisplatin and etoposide chemotherapy regimen alone given every 3 weeks (control arm). Carboplatin (area under the curve 5 on day 1) could be substituted for cisplatin in case of cisplatin contraindications or cisplatin-associated toxicity. Tumor response, on the basis of investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), was evaluated every 3 cycles during chemotherapy treatment. After 6 cycles of chemotherapy, tumor assessment was performed every 9 weeks in both arms. In the absence of progression, patients in the treatment arm continued bevacizumab alone until disease progression or for a maximum of 18 courses. Survival follow-up information was collected every 6 months after treatment termination or last dose of study drug, until death or loss to follow-up.

Main outcome measure. The primary end point was overall survival (OS). Response rate, toxicity, and progression-free survival (PFS) were secondary end points.

Main results. 205 patients were randomized between November 2009 and October 2015. 204 patients were considered in the intent-to-treat analysis (103 in the control arm and 101 in the treatment arm). Most patients were male with ECOG PS of 0 to 1. Median age was 64 years. The median number of chemotherapy courses administered was 6 in both arms. Cisplatin was used in majority of the patients. Average relative dose intensities for all drugs were well balanced between 2 groups. A lower percentage of patients in the treatment arm (14.7%) than in the control arm (22.3%) discontinued treatment because of radiologic disease progression, which was the main reason for treatment discontinuation.

At a median follow-up of 34.9 months, the median PFS was 5.7 in the control arm and 6.7 months in the treatment arm (hazard ratio [HR], 0.72; 95% CI, 0.54 to 0.97; P = 0.30). Median OS times were 8.9 months and 9.8 months, and 1-year survival rates were 25% and 37% (HR, 0.78; 95% CI, 0.58 to 1.06; P = 0.113) in the control arm and treatment arm, respectively. A significant effect of the maintenance treatment on OS (HR, 0.60; 95% CI, 0.40 to 0.91, P = 0.011) was observed. A subgroup analysis revealed a statistically significant interaction for OS between treatment and sex; the addition of bevacizumab led to a significant survival benefit in men (HR, 0.55) and to a possible detrimental effect in women (HR, 1.55; interaction test, P = 0.003).

Addition of bevacizumab did not result in increase in hematologic toxicity such as anemia, neutropenia, or thrombocytopenia. Concerning the nonhematologic toxicity, only hypertension was more frequent in the bevacizumab arm (6.3%) compared to chemotherapy alone arm (1%). The rates of proteinuria and thrombosis were similar in both arms.

Conclusion. The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in PFS, which, however, did not translate into a statistically significant increase in OS.

Commentary

SCLC currently accounts for approximately 12% to 15% of all lung cancers [1]. It is characterized by a rapid growth rate, metastasis at the time of diagnosis, sensitivity to first-line platinum-based chemotherapy, and invariable recurrence and progressive resistance to subsequent lines of therapy. A number of clinical trials over the past 2 decades have failed to produce outcomes superior to platinum-based doublet chemotherapy, leaving a significant unmet need [2]. Vascular endothelial growth factor (VEGF) is the most important proangiogenic factor, and it is implicated in tumor growth [3]. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is now indicated in the treatment of several tumor types including non–SCLC and breast, colorectal, kidney, and ovarian cancer. Positive signal with bevacizumab was seen in phase II studies, providing rationale for this phase III trial [4,5] .

The study by Tiseo and colleagues reported the outcomes of a randomized study that added bevacizumab to standard combination therapy with platinum and etoposide for the treatment of ED-SCLC. A small statistically significant improvement was seen in PFS (6.7 months vs. 5.7 months, favoring the bevacizumab group). However, the study failed to meet the primary end point of improved OS.

So where do antiangiogenesis agents go from here? Alternative angiogenesis inhibitors with broader mechanism of action are being explored in clinical trials. One such trial (ClinicalTrials.gov identifier: NCT02945852) is evaluating the role of the tyrosine kinase inhibitor apatinib in combination with chemotherapy in ED-SCLC. Apatinib selectively inhibits the vascular growth factor receptor-2 (VEGFR2). In addition, this agent also inhibits c-kit and c-SRC tyrosine kinase. It would be interesting to see if antiangiogenic agents with broader mechanisms would be more effective in SCLC. Immunotherapy with checkpoint inhibitors such as nivolumab and pembrolizumab have revolutionized the lung cancer treatment paradigm. It would be interesting to see if bevacizumab could be safely added to these immunotherapy agents. The ongoing CheckMate 370 (ClinicalTrials.gov identifier: NCT02574078) is addressing this question, evaluating the safety of combining nivolumab with bevacizumab in non-SCLC.

Applications for Clinical Practice

The current study does not support the addition of bevacizumab as a standard therapeutic option in the first-line treatment of ED-SCLC. However, given that there was a trend towards improved OS, alternative strategies of incorporating antiangiogenesis agents should be considered in future clinical trials.

—Deval Rajyaguru, MD