The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Mediterranean diet, characterized by an emphasis on plant foods, fish, and olive oil, is known to have cardiovascular benefits. This study by Toledo and colleagues is a secondary analysis of a large randomized trial that assessed the impact of the Mediterranean diet versus a recommended low-fat diet in patients at elevated risk for cardiovascular disease (CVD). The larger trial was stopped after 4.8 years of follow-up, when findings of early cardiovascular benefit became evident.

The 4,282 women in the trial, all of whom were white, were randomly allocated to one of the following groups:

• Mediterranean diet supplemented by EVOO. Participants were given 1 L of EVOO a week for the study duration. At baseline and quarterly thereafter, dieticians ran individual and group sessions. In individual sessions, participants completed a 14-item dietary screening questionnaire to assess adherence to the diet.
• Mediterranean diet supplemented by mixed nuts. Participants were given 30 g of mixed nuts per day (15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds). They also took part in individual and group sessions at baseline and quarterly thereafter, and completed the same screening questionnaire as the first group.
• A control group. Participants were advised to reduce dietary fat. They also underwent dietary training at the baseline visit and completed the 14-item screener. Thereafter, during the first 3 years of the trial, they received annual mailing of a leaflet explaining the low-fat diet. In 2006, however, the protocol was amended to include personalized advice and quarterly group sessions, with use of a separate 9-item dietary screener. The control group also received gifts of nonfood items as incentives.

Physical activity was not promoted in any group.

Findings of the trialAfter a median follow-up of 4.8 years, 35 confirmed cases of invasive breast cancer occurred among participants in the trial, who ranged in age from 60 to 80 years. The observed rate (per 1,000 person-years) of breast cancer was 1.1 for women following the Mediterranean diet supplemented with EVOO, 1.8 for women on the diet supplemented by mixed nuts, and 2.9 for the control group.

Women allocated to the Mediterranean diet with EVOO had a 62% reduced risk of invasive breast cancer (95% confidence interval [CI], 0.16–0.87). Women allocated to the same diet with mixed nuts had a 38% reduced risk of breast cancer, but this finding was not statistically significant.

Note that women in the control group failed to reduce their total fat intake substantially, even though they were advised to do so, although saturated fat intake remained below 10%.

Strengths and limitations of the trialAlthough the incidence of breast cancer is lower in Mediterranean countries, this is the first randomized trial to assess the impact of the Mediterranean diet on risk of this disease.

Because breast cancer was not the primary outcome, investigators were unable to verify if or when participants underwent mammography screening. However, randomization resulted in large groups of participants between whom mammographic status likely was comparable.

The lack of ethnic diversity represents another limitation.

Toledo and colleagues describe differences between olive oils in general and EVOO, including biologic mechanisms that might result in breast cancer prophylaxis.

WHAT THIS EVIDENCE MEANS FOR PRACTICEGiven the known cardiovascular benefits, it is reasonable to suggest to our menopausal patients that a Mediterranean diet with EVOO may reduce their risk of breast cancer.
—Andrew M. Kaunitz, MD

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Mediterranean diet, characterized by an emphasis on plant foods, fish, and olive oil, is known to have cardiovascular benefits. This study by Toledo and colleagues is a secondary analysis of a large randomized trial that assessed the impact of the Mediterranean diet versus a recommended low-fat diet in patients at elevated risk for cardiovascular disease (CVD). The larger trial was stopped after 4.8 years of follow-up, when findings of early cardiovascular benefit became evident.

The 4,282 women in the trial, all of whom were white, were randomly allocated to one of the following groups:

• Mediterranean diet supplemented by EVOO. Participants were given 1 L of EVOO a week for the study duration. At baseline and quarterly thereafter, dieticians ran individual and group sessions. In individual sessions, participants completed a 14-item dietary screening questionnaire to assess adherence to the diet.
• Mediterranean diet supplemented by mixed nuts. Participants were given 30 g of mixed nuts per day (15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds). They also took part in individual and group sessions at baseline and quarterly thereafter, and completed the same screening questionnaire as the first group.
• A control group. Participants were advised to reduce dietary fat. They also underwent dietary training at the baseline visit and completed the 14-item screener. Thereafter, during the first 3 years of the trial, they received annual mailing of a leaflet explaining the low-fat diet. In 2006, however, the protocol was amended to include personalized advice and quarterly group sessions, with use of a separate 9-item dietary screener. The control group also received gifts of nonfood items as incentives.

Physical activity was not promoted in any group.

Findings of the trialAfter a median follow-up of 4.8 years, 35 confirmed cases of invasive breast cancer occurred among participants in the trial, who ranged in age from 60 to 80 years. The observed rate (per 1,000 person-years) of breast cancer was 1.1 for women following the Mediterranean diet supplemented with EVOO, 1.8 for women on the diet supplemented by mixed nuts, and 2.9 for the control group.

Women allocated to the Mediterranean diet with EVOO had a 62% reduced risk of invasive breast cancer (95% confidence interval [CI], 0.16–0.87). Women allocated to the same diet with mixed nuts had a 38% reduced risk of breast cancer, but this finding was not statistically significant.

Note that women in the control group failed to reduce their total fat intake substantially, even though they were advised to do so, although saturated fat intake remained below 10%.

Strengths and limitations of the trialAlthough the incidence of breast cancer is lower in Mediterranean countries, this is the first randomized trial to assess the impact of the Mediterranean diet on risk of this disease.

Because breast cancer was not the primary outcome, investigators were unable to verify if or when participants underwent mammography screening. However, randomization resulted in large groups of participants between whom mammographic status likely was comparable.

The lack of ethnic diversity represents another limitation.

Toledo and colleagues describe differences between olive oils in general and EVOO, including biologic mechanisms that might result in breast cancer prophylaxis.

WHAT THIS EVIDENCE MEANS FOR PRACTICEGiven the known cardiovascular benefits, it is reasonable to suggest to our menopausal patients that a Mediterranean diet with EVOO may reduce their risk of breast cancer.
—Andrew M. Kaunitz, MD

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Mediterranean diet, characterized by an emphasis on plant foods, fish, and olive oil, is known to have cardiovascular benefits. This study by Toledo and colleagues is a secondary analysis of a large randomized trial that assessed the impact of the Mediterranean diet versus a recommended low-fat diet in patients at elevated risk for cardiovascular disease (CVD). The larger trial was stopped after 4.8 years of follow-up, when findings of early cardiovascular benefit became evident.

The 4,282 women in the trial, all of whom were white, were randomly allocated to one of the following groups:

• Mediterranean diet supplemented by EVOO. Participants were given 1 L of EVOO a week for the study duration. At baseline and quarterly thereafter, dieticians ran individual and group sessions. In individual sessions, participants completed a 14-item dietary screening questionnaire to assess adherence to the diet.
• Mediterranean diet supplemented by mixed nuts. Participants were given 30 g of mixed nuts per day (15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds). They also took part in individual and group sessions at baseline and quarterly thereafter, and completed the same screening questionnaire as the first group.
• A control group. Participants were advised to reduce dietary fat. They also underwent dietary training at the baseline visit and completed the 14-item screener. Thereafter, during the first 3 years of the trial, they received annual mailing of a leaflet explaining the low-fat diet. In 2006, however, the protocol was amended to include personalized advice and quarterly group sessions, with use of a separate 9-item dietary screener. The control group also received gifts of nonfood items as incentives.

Physical activity was not promoted in any group.

Findings of the trialAfter a median follow-up of 4.8 years, 35 confirmed cases of invasive breast cancer occurred among participants in the trial, who ranged in age from 60 to 80 years. The observed rate (per 1,000 person-years) of breast cancer was 1.1 for women following the Mediterranean diet supplemented with EVOO, 1.8 for women on the diet supplemented by mixed nuts, and 2.9 for the control group.

Women allocated to the Mediterranean diet with EVOO had a 62% reduced risk of invasive breast cancer (95% confidence interval [CI], 0.16–0.87). Women allocated to the same diet with mixed nuts had a 38% reduced risk of breast cancer, but this finding was not statistically significant.

Note that women in the control group failed to reduce their total fat intake substantially, even though they were advised to do so, although saturated fat intake remained below 10%.

Strengths and limitations of the trialAlthough the incidence of breast cancer is lower in Mediterranean countries, this is the first randomized trial to assess the impact of the Mediterranean diet on risk of this disease.

Because breast cancer was not the primary outcome, investigators were unable to verify if or when participants underwent mammography screening. However, randomization resulted in large groups of participants between whom mammographic status likely was comparable.

The lack of ethnic diversity represents another limitation.

Toledo and colleagues describe differences between olive oils in general and EVOO, including biologic mechanisms that might result in breast cancer prophylaxis.

WHAT THIS EVIDENCE MEANS FOR PRACTICEGiven the known cardiovascular benefits, it is reasonable to suggest to our menopausal patients that a Mediterranean diet with EVOO may reduce their risk of breast cancer.
—Andrew M. Kaunitz, MD

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Women who become pregnant while in remission from Hodgkin lymphoma were not at increased risk for cancer relapse, according to an analysis of data from Swedish health care registries combined with medical records.

Of 449 women who were diagnosed with Hodgkin lymphoma between 1992 and 2009, 144 (32%) became pregnant during follow-up, which started 6 months after diagnosis, when the disease was assumed to be in remission. Only one of these women experienced a pregnancy-associated relapse, which was defined as a relapse occurring during pregnancy or within 5 years of delivery. Of the women who did not become pregnant, 46 had a relapse.

©Jupiterimages/thinkstockphotos.com

The effect of pregnancy on relapse has been a concern of patients and clinicians, but “our findings suggest that the risk of pregnancy-associated relapse does not need to be taken into account in family planning for women whose Hodgkin lymphoma is in remission,” said Caroline E. Weibull of Karolinska Institutet in Stockholm, and her associates.

The researchers used the nationwide “Swedish Cancer Register” to identify all cases of Hodgkin lymphoma (reporting is mandatory) and merged this data with clinical information from other registries and medical records.

The pregnancy rates were similar among women who had limited- and advanced-stage disease and among women with and without B symptoms at diagnosis – a finding that negates consideration of a so-called “healthy mother effect” in protecting against relapse, they wrote (J Clin Onc. 2015 Dec. 14 [doi:10.1200/JCO.2015.63.3446]).

The researchers also found that the absolute risk for relapse was highest in the first 2-3 years after diagnosis, which suggests that women should be advised, “if possible, to wait 2 years after cessation of treatment before becoming pregnant.” Additionally, the relapse rate more than doubled in women aged 30 years or older at diagnosis, compared with women aged 18-24 years at diagnosis – a finding consistent with previous research, they noted.

Women in the study were aged 18-40 at diagnosis. Follow-up ended on the date of relapse, the date of death, or at the end of 2010, whichever came first.

Women who become pregnant while in remission from Hodgkin lymphoma were not at increased risk for cancer relapse, according to an analysis of data from Swedish health care registries combined with medical records.

Of 449 women who were diagnosed with Hodgkin lymphoma between 1992 and 2009, 144 (32%) became pregnant during follow-up, which started 6 months after diagnosis, when the disease was assumed to be in remission. Only one of these women experienced a pregnancy-associated relapse, which was defined as a relapse occurring during pregnancy or within 5 years of delivery. Of the women who did not become pregnant, 46 had a relapse.

©Jupiterimages/thinkstockphotos.com

The effect of pregnancy on relapse has been a concern of patients and clinicians, but “our findings suggest that the risk of pregnancy-associated relapse does not need to be taken into account in family planning for women whose Hodgkin lymphoma is in remission,” said Caroline E. Weibull of Karolinska Institutet in Stockholm, and her associates.

The researchers used the nationwide “Swedish Cancer Register” to identify all cases of Hodgkin lymphoma (reporting is mandatory) and merged this data with clinical information from other registries and medical records.

The pregnancy rates were similar among women who had limited- and advanced-stage disease and among women with and without B symptoms at diagnosis – a finding that negates consideration of a so-called “healthy mother effect” in protecting against relapse, they wrote (J Clin Onc. 2015 Dec. 14 [doi:10.1200/JCO.2015.63.3446]).

The researchers also found that the absolute risk for relapse was highest in the first 2-3 years after diagnosis, which suggests that women should be advised, “if possible, to wait 2 years after cessation of treatment before becoming pregnant.” Additionally, the relapse rate more than doubled in women aged 30 years or older at diagnosis, compared with women aged 18-24 years at diagnosis – a finding consistent with previous research, they noted.

Women in the study were aged 18-40 at diagnosis. Follow-up ended on the date of relapse, the date of death, or at the end of 2010, whichever came first.

Women who become pregnant while in remission from Hodgkin lymphoma were not at increased risk for cancer relapse, according to an analysis of data from Swedish health care registries combined with medical records.

Of 449 women who were diagnosed with Hodgkin lymphoma between 1992 and 2009, 144 (32%) became pregnant during follow-up, which started 6 months after diagnosis, when the disease was assumed to be in remission. Only one of these women experienced a pregnancy-associated relapse, which was defined as a relapse occurring during pregnancy or within 5 years of delivery. Of the women who did not become pregnant, 46 had a relapse.

©Jupiterimages/thinkstockphotos.com

The effect of pregnancy on relapse has been a concern of patients and clinicians, but “our findings suggest that the risk of pregnancy-associated relapse does not need to be taken into account in family planning for women whose Hodgkin lymphoma is in remission,” said Caroline E. Weibull of Karolinska Institutet in Stockholm, and her associates.

The researchers used the nationwide “Swedish Cancer Register” to identify all cases of Hodgkin lymphoma (reporting is mandatory) and merged this data with clinical information from other registries and medical records.

The pregnancy rates were similar among women who had limited- and advanced-stage disease and among women with and without B symptoms at diagnosis – a finding that negates consideration of a so-called “healthy mother effect” in protecting against relapse, they wrote (J Clin Onc. 2015 Dec. 14 [doi:10.1200/JCO.2015.63.3446]).

The researchers also found that the absolute risk for relapse was highest in the first 2-3 years after diagnosis, which suggests that women should be advised, “if possible, to wait 2 years after cessation of treatment before becoming pregnant.” Additionally, the relapse rate more than doubled in women aged 30 years or older at diagnosis, compared with women aged 18-24 years at diagnosis – a finding consistent with previous research, they noted.

Women in the study were aged 18-40 at diagnosis. Follow-up ended on the date of relapse, the date of death, or at the end of 2010, whichever came first.

Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.

“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).

Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.

The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.

Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.

However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.

No significant associations were found between disease status and non-relapse mortality.

The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.

Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.

Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.

“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).

Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.

The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.

Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.

However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.

No significant associations were found between disease status and non-relapse mortality.

The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.

Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.

Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.

“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).

Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.

The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.

Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.

However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.

No significant associations were found between disease status and non-relapse mortality.

The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.

Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.

SAN ANTONIO – Hospitalization for an infection within the first year following diagnosis of primary nonmetastatic breast cancer is a red flag for increased risk of subsequent development of distant metastases or breast cancer–related death, Judith S. Brand, Ph.D., reported at the San Antonio Breast Cancer Symposium.

This increased risk for future adverse breast cancer outcomes was statistically significant and clinically meaningful for women hospitalized for respiratory tract or skin infections or sepsis. Those are the patients for whom particularly close monitoring for recurrence of breast cancer is warranted in the next 5 years, said Dr. Brand of the Karolinska Institute, Stockholm.

In contrast, hospitalization for a gastrointestinal or urinary tract infection didn’t achieve significance as an independent predictor of increased risk of adverse breast cancer outcomes.

Dr. Brand presented a prospective population-based study of 8,338 women diagnosed with stage I-III breast cancer in the Stockholm area during 2001-2008. During a median 4.9 years of follow-up after diagnosis, 720 women had an infection-related hospitalization, with the great majority of these events occurring during the first year.

The incidence of hospitalization for sepsis among breast cancer patients in their first year post diagnosis was 14-fold greater than in the general Swedish female population matched for age and year. Respiratory infections resulting in hospitalization were fourfold more frequent than in the general population, skin infections were eightfold more common, and GI infections were twice as common.

Infection-related hospitalizations had a strong and independent association with breast cancer mortality during follow-up, as seen in a multivariate analysis adjusted for age at diagnosis, comorbid conditions, infectious disease history, type of breast cancer therapy, and tumor characteristics including size, grade, hormone receptor status, and lymph node involvement.

Moreover, the risk of developing distant metastases was 50%-78% greater in breast cancer patients hospitalized for respiratory infection, sepsis, or skin infection, compared with breast cancer patients who didn’t have an infection-related hospitalization.

“We think the sepsis results are the most interesting findings,” Dr. Brand said in an interview. “Sepsis could be an expression of an immunosuppressed state. And sepsis itself can induce immunosuppression for a long time, which could trigger tumor growth. Animal studies have shown that in postseptic mice, tumor grows faster.”

Infection-related hospitalizations didn’t increase the future risk of locoregional recurrences.

Independent predictors of infection-related hospitalization included older age, comorbidities, markers indicative of greater tumor aggressiveness, and treatment with chemotherapy or axillary radiotherapy.

“This shows that the risk of infection-related hospitalizations is not only due to immunosuppression caused by chemotherapy, but that the characteristics of the tumor itself play a role, as do patient characteristics. This is the first epidemiologic study to show with very extensive data that all three elements contribute to the risk,” Dr. Brand said.

[email protected]

SAN ANTONIO – Hospitalization for an infection within the first year following diagnosis of primary nonmetastatic breast cancer is a red flag for increased risk of subsequent development of distant metastases or breast cancer–related death, Judith S. Brand, Ph.D., reported at the San Antonio Breast Cancer Symposium.

This increased risk for future adverse breast cancer outcomes was statistically significant and clinically meaningful for women hospitalized for respiratory tract or skin infections or sepsis. Those are the patients for whom particularly close monitoring for recurrence of breast cancer is warranted in the next 5 years, said Dr. Brand of the Karolinska Institute, Stockholm.

In contrast, hospitalization for a gastrointestinal or urinary tract infection didn’t achieve significance as an independent predictor of increased risk of adverse breast cancer outcomes.

Dr. Brand presented a prospective population-based study of 8,338 women diagnosed with stage I-III breast cancer in the Stockholm area during 2001-2008. During a median 4.9 years of follow-up after diagnosis, 720 women had an infection-related hospitalization, with the great majority of these events occurring during the first year.

The incidence of hospitalization for sepsis among breast cancer patients in their first year post diagnosis was 14-fold greater than in the general Swedish female population matched for age and year. Respiratory infections resulting in hospitalization were fourfold more frequent than in the general population, skin infections were eightfold more common, and GI infections were twice as common.

Infection-related hospitalizations had a strong and independent association with breast cancer mortality during follow-up, as seen in a multivariate analysis adjusted for age at diagnosis, comorbid conditions, infectious disease history, type of breast cancer therapy, and tumor characteristics including size, grade, hormone receptor status, and lymph node involvement.

Moreover, the risk of developing distant metastases was 50%-78% greater in breast cancer patients hospitalized for respiratory infection, sepsis, or skin infection, compared with breast cancer patients who didn’t have an infection-related hospitalization.

“We think the sepsis results are the most interesting findings,” Dr. Brand said in an interview. “Sepsis could be an expression of an immunosuppressed state. And sepsis itself can induce immunosuppression for a long time, which could trigger tumor growth. Animal studies have shown that in postseptic mice, tumor grows faster.”

Infection-related hospitalizations didn’t increase the future risk of locoregional recurrences.

Independent predictors of infection-related hospitalization included older age, comorbidities, markers indicative of greater tumor aggressiveness, and treatment with chemotherapy or axillary radiotherapy.

“This shows that the risk of infection-related hospitalizations is not only due to immunosuppression caused by chemotherapy, but that the characteristics of the tumor itself play a role, as do patient characteristics. This is the first epidemiologic study to show with very extensive data that all three elements contribute to the risk,” Dr. Brand said.

[email protected]

SAN ANTONIO – Hospitalization for an infection within the first year following diagnosis of primary nonmetastatic breast cancer is a red flag for increased risk of subsequent development of distant metastases or breast cancer–related death, Judith S. Brand, Ph.D., reported at the San Antonio Breast Cancer Symposium.

This increased risk for future adverse breast cancer outcomes was statistically significant and clinically meaningful for women hospitalized for respiratory tract or skin infections or sepsis. Those are the patients for whom particularly close monitoring for recurrence of breast cancer is warranted in the next 5 years, said Dr. Brand of the Karolinska Institute, Stockholm.

In contrast, hospitalization for a gastrointestinal or urinary tract infection didn’t achieve significance as an independent predictor of increased risk of adverse breast cancer outcomes.

Dr. Brand presented a prospective population-based study of 8,338 women diagnosed with stage I-III breast cancer in the Stockholm area during 2001-2008. During a median 4.9 years of follow-up after diagnosis, 720 women had an infection-related hospitalization, with the great majority of these events occurring during the first year.

The incidence of hospitalization for sepsis among breast cancer patients in their first year post diagnosis was 14-fold greater than in the general Swedish female population matched for age and year. Respiratory infections resulting in hospitalization were fourfold more frequent than in the general population, skin infections were eightfold more common, and GI infections were twice as common.

Infection-related hospitalizations had a strong and independent association with breast cancer mortality during follow-up, as seen in a multivariate analysis adjusted for age at diagnosis, comorbid conditions, infectious disease history, type of breast cancer therapy, and tumor characteristics including size, grade, hormone receptor status, and lymph node involvement.

Moreover, the risk of developing distant metastases was 50%-78% greater in breast cancer patients hospitalized for respiratory infection, sepsis, or skin infection, compared with breast cancer patients who didn’t have an infection-related hospitalization.

“We think the sepsis results are the most interesting findings,” Dr. Brand said in an interview. “Sepsis could be an expression of an immunosuppressed state. And sepsis itself can induce immunosuppression for a long time, which could trigger tumor growth. Animal studies have shown that in postseptic mice, tumor grows faster.”

Infection-related hospitalizations didn’t increase the future risk of locoregional recurrences.

Independent predictors of infection-related hospitalization included older age, comorbidities, markers indicative of greater tumor aggressiveness, and treatment with chemotherapy or axillary radiotherapy.

“This shows that the risk of infection-related hospitalizations is not only due to immunosuppression caused by chemotherapy, but that the characteristics of the tumor itself play a role, as do patient characteristics. This is the first epidemiologic study to show with very extensive data that all three elements contribute to the risk,” Dr. Brand said.

[email protected]

South Carolina officially became the first state to reach a “high” level of influenza activity during the 2015-2016 flu season, the Centers for Disease Control and Prevention reported Dec. 11.

Activity of influenza-like illness (ILI) in the state was at level 9 on a scale of 1-10 for the week ending Dec. 5, 2015. For the country as a whole, however, activity was down a bit, with 13 states at level 2 or higher, compared with 20 states the week before. Among those with reduced ILI activity was Oklahoma, which went from level 6 for the week ending Nov. 28 to level 3 for the week ending Dec. 5, according to the CDC report.

For the week, 1.8% of patient visits reported to the U.S. Outpatient Influenza-like Illness Surveillance Network were for ILI, which is below the national baseline of 2.1%. This measure peaked at almost 6% during last year’s flu season, with that high coming at the end of Dec. 2014. The pattern was similar for the 2013-2014 season, with a peak of about 4.5% during the same week at the end of December, the report showed.

There was one influenza-related pediatric death for the week ending Dec. 5, bringing the total to three that have been reported for the season, the CDC said.

[email protected]

South Carolina officially became the first state to reach a “high” level of influenza activity during the 2015-2016 flu season, the Centers for Disease Control and Prevention reported Dec. 11.

Activity of influenza-like illness (ILI) in the state was at level 9 on a scale of 1-10 for the week ending Dec. 5, 2015. For the country as a whole, however, activity was down a bit, with 13 states at level 2 or higher, compared with 20 states the week before. Among those with reduced ILI activity was Oklahoma, which went from level 6 for the week ending Nov. 28 to level 3 for the week ending Dec. 5, according to the CDC report.

For the week, 1.8% of patient visits reported to the U.S. Outpatient Influenza-like Illness Surveillance Network were for ILI, which is below the national baseline of 2.1%. This measure peaked at almost 6% during last year’s flu season, with that high coming at the end of Dec. 2014. The pattern was similar for the 2013-2014 season, with a peak of about 4.5% during the same week at the end of December, the report showed.

There was one influenza-related pediatric death for the week ending Dec. 5, bringing the total to three that have been reported for the season, the CDC said.

[email protected]

South Carolina officially became the first state to reach a “high” level of influenza activity during the 2015-2016 flu season, the Centers for Disease Control and Prevention reported Dec. 11.

Activity of influenza-like illness (ILI) in the state was at level 9 on a scale of 1-10 for the week ending Dec. 5, 2015. For the country as a whole, however, activity was down a bit, with 13 states at level 2 or higher, compared with 20 states the week before. Among those with reduced ILI activity was Oklahoma, which went from level 6 for the week ending Nov. 28 to level 3 for the week ending Dec. 5, according to the CDC report.

For the week, 1.8% of patient visits reported to the U.S. Outpatient Influenza-like Illness Surveillance Network were for ILI, which is below the national baseline of 2.1%. This measure peaked at almost 6% during last year’s flu season, with that high coming at the end of Dec. 2014. The pattern was similar for the 2013-2014 season, with a peak of about 4.5% during the same week at the end of December, the report showed.

There was one influenza-related pediatric death for the week ending Dec. 5, bringing the total to three that have been reported for the season, the CDC said.

[email protected]

In his December podcast for The Journal of Community and Supportive Oncology, Dr David Henry takes a look at filgrastim-sndz, the first biosimilar to be approved in United States. He also highlights two Original Reports that focus on cancer patients from racially diverse or underserved communities – one study looks at the patients’ enrollment in clinical trials; the other, at racial disparities in breast cancer diagnosis – as well as articles on the implementation of distress screening in an oncology setting and on oncology nurses’ perceptions of and practices and perceived barriers in regard to sexual health assessment and counseling among patients with cancer. The podcast rounds off with a discussion about a new era of combination therapy in cancer.

In his December podcast for The Journal of Community and Supportive Oncology, Dr David Henry takes a look at filgrastim-sndz, the first biosimilar to be approved in United States. He also highlights two Original Reports that focus on cancer patients from racially diverse or underserved communities – one study looks at the patients’ enrollment in clinical trials; the other, at racial disparities in breast cancer diagnosis – as well as articles on the implementation of distress screening in an oncology setting and on oncology nurses’ perceptions of and practices and perceived barriers in regard to sexual health assessment and counseling among patients with cancer. The podcast rounds off with a discussion about a new era of combination therapy in cancer.

In his December podcast for The Journal of Community and Supportive Oncology, Dr David Henry takes a look at filgrastim-sndz, the first biosimilar to be approved in United States. He also highlights two Original Reports that focus on cancer patients from racially diverse or underserved communities – one study looks at the patients’ enrollment in clinical trials; the other, at racial disparities in breast cancer diagnosis – as well as articles on the implementation of distress screening in an oncology setting and on oncology nurses’ perceptions of and practices and perceived barriers in regard to sexual health assessment and counseling among patients with cancer. The podcast rounds off with a discussion about a new era of combination therapy in cancer.

The past year has been an exciting one for new oncology and hematology drug approvals and the continued evolution of our oncology delivery system toward high quality and value. In all, at press time in mid-November, the US Food and Drug Administration (FDA) had approved or granted expanded indications for 24 drugs, compared with 19 in the 2 preceding years. Of those 24 approvals, 7 were accelerated and 6 were expanded approvals, and 3 alone were for the immunotherapeutic drug, nivolumab – 2 for non-small-cell lung cancer (NSCLC) and 1 for metastatic melanoma.

Click on the PDF icon at the top of this introduction to read the full article.

The past year has been an exciting one for new oncology and hematology drug approvals and the continued evolution of our oncology delivery system toward high quality and value. In all, at press time in mid-November, the US Food and Drug Administration (FDA) had approved or granted expanded indications for 24 drugs, compared with 19 in the 2 preceding years. Of those 24 approvals, 7 were accelerated and 6 were expanded approvals, and 3 alone were for the immunotherapeutic drug, nivolumab – 2 for non-small-cell lung cancer (NSCLC) and 1 for metastatic melanoma.

Click on the PDF icon at the top of this introduction to read the full article.

The past year has been an exciting one for new oncology and hematology drug approvals and the continued evolution of our oncology delivery system toward high quality and value. In all, at press time in mid-November, the US Food and Drug Administration (FDA) had approved or granted expanded indications for 24 drugs, compared with 19 in the 2 preceding years. Of those 24 approvals, 7 were accelerated and 6 were expanded approvals, and 3 alone were for the immunotherapeutic drug, nivolumab – 2 for non-small-cell lung cancer (NSCLC) and 1 for metastatic melanoma.

Click on the PDF icon at the top of this introduction to read the full article.

Clinical question: Are there patient characteristics not currently measured by the Medicare readmission program that account for differences in hospital readmission rates?

Background: The Medicare Hospital Readmissions Reduction Program (HRRP) financially penalizes hospitals with higher than expected 30-day readmission rates. During 2014, more than 2,000 U.S. hospitals were fined $480 million for high readmission rates. HRRP accounts for differences in patient age, gender, discharge diagnosis, and diagnoses identified in Medicare claims over the previous 12 months; however, the impact of other factors is uncertain.

Study design: Survey data from the Health and Retirement Study, with linked Medicare claims.

Setting: Community-dwelling U.S. adults, older than 50 years.

Synopsis: Investigators analyzed more than 33,000 admissions from 2000 to 2012. They found 22 patient characteristics not included in the HRRP calculation that were statistically significantly predictive of hospital-wide, 30-day readmission and were more likely to be present among patients cared for in hospitals in the highest quintile of readmission rates. These characteristics reduced by 48% the differences in readmission rate between the highest- and lowest-performing quintiles. Examples include patient ethnicity, education level, personal as well as household income level, presence of prescription drug plan, Medicaid enrollment, cognitive status, and numerous others.

Bottom line: Patient characteristics account for much of the difference in readmission rates between high- and low-performing hospitals, suggesting that HRRP penalties reflect who hospitals treat as much as how well they treat them.

Citation: Barnett ML, Hsu J, McWilliams JM. Patient characteristics and differences in hospital readmission rates. JAMA Intern Med. 2015;175(11):1803-1812.

Clinical question: Are there patient characteristics not currently measured by the Medicare readmission program that account for differences in hospital readmission rates?

Background: The Medicare Hospital Readmissions Reduction Program (HRRP) financially penalizes hospitals with higher than expected 30-day readmission rates. During 2014, more than 2,000 U.S. hospitals were fined $480 million for high readmission rates. HRRP accounts for differences in patient age, gender, discharge diagnosis, and diagnoses identified in Medicare claims over the previous 12 months; however, the impact of other factors is uncertain.

Study design: Survey data from the Health and Retirement Study, with linked Medicare claims.

Setting: Community-dwelling U.S. adults, older than 50 years.

Synopsis: Investigators analyzed more than 33,000 admissions from 2000 to 2012. They found 22 patient characteristics not included in the HRRP calculation that were statistically significantly predictive of hospital-wide, 30-day readmission and were more likely to be present among patients cared for in hospitals in the highest quintile of readmission rates. These characteristics reduced by 48% the differences in readmission rate between the highest- and lowest-performing quintiles. Examples include patient ethnicity, education level, personal as well as household income level, presence of prescription drug plan, Medicaid enrollment, cognitive status, and numerous others.

Bottom line: Patient characteristics account for much of the difference in readmission rates between high- and low-performing hospitals, suggesting that HRRP penalties reflect who hospitals treat as much as how well they treat them.

Citation: Barnett ML, Hsu J, McWilliams JM. Patient characteristics and differences in hospital readmission rates. JAMA Intern Med. 2015;175(11):1803-1812.

Clinical question: Are there patient characteristics not currently measured by the Medicare readmission program that account for differences in hospital readmission rates?

Background: The Medicare Hospital Readmissions Reduction Program (HRRP) financially penalizes hospitals with higher than expected 30-day readmission rates. During 2014, more than 2,000 U.S. hospitals were fined $480 million for high readmission rates. HRRP accounts for differences in patient age, gender, discharge diagnosis, and diagnoses identified in Medicare claims over the previous 12 months; however, the impact of other factors is uncertain.

Study design: Survey data from the Health and Retirement Study, with linked Medicare claims.

Setting: Community-dwelling U.S. adults, older than 50 years.

Synopsis: Investigators analyzed more than 33,000 admissions from 2000 to 2012. They found 22 patient characteristics not included in the HRRP calculation that were statistically significantly predictive of hospital-wide, 30-day readmission and were more likely to be present among patients cared for in hospitals in the highest quintile of readmission rates. These characteristics reduced by 48% the differences in readmission rate between the highest- and lowest-performing quintiles. Examples include patient ethnicity, education level, personal as well as household income level, presence of prescription drug plan, Medicaid enrollment, cognitive status, and numerous others.

Bottom line: Patient characteristics account for much of the difference in readmission rates between high- and low-performing hospitals, suggesting that HRRP penalties reflect who hospitals treat as much as how well they treat them.

Citation: Barnett ML, Hsu J, McWilliams JM. Patient characteristics and differences in hospital readmission rates. JAMA Intern Med. 2015;175(11):1803-1812.

A “broad swath” of Medicare providers wrote scripts for opioids in 2013, contradicting the idea that the overdose epidemic is mainly the work of “small groups of prolific prescribers and corrupt pill mills,” investigators wrote online in JAMA Internal Medicine.

“Contrary to the California workers’ compensation data showing a small subset of prescribers accounting for a disproportionately large percentage of opioid prescribing, Medicare opioid prescribing is distributed across many prescribers and is, if anything, less skewed than all drug prescribing,” said Dr. Jonathan H. Chen of the Veterans Affairs Palo Alto (Calif.) Health Care System, and his associates.

Their study included 808,020 prescribers and almost 1.2 billion Medicare Part D claims worth nearly $81 billion dollars. They focused on schedule II opioid prescriptions containing oxycodone, fentanyl, hydrocodone, morphine, methadone, hydromorphone, oxymorphone, meperidine, codeine, opium, or levorphanol (JAMA Intern Med. 2015 Dec 14. doi: 10.1001/jamainternmed.2015.6662).

Not surprisingly, specialists in pain management, anesthesia, and physical medicine wrote the most prescriptions per provider. But family practitioners, internists, nurse practitioners, and physician assistants wrote 35,268,234 prescriptions – more than all other specialties combined. “The trends hold up across state lines, with negligible geographic variability,” the researchers said.

The findings contradict an analysis of California workers’ compensation data, in which 1% of prescribers accounted for a third of schedule II opioid prescriptions, and 10% of prescribers accounted for 80% of prescriptions, the investigators noted. Nonetheless, 10% of Medicare prescribers in Dr. Chen’s study accounted for 78% of the total cost of opioids, possibly because they were prescribing pricier formulations or higher doses.

Overall, the findings suggest that opioid prescribing is “widespread” and “relatively indifferent to individual physicians, specialty, or region” – and that efforts to stem the tide must be equally broad, the researchers concluded.

Their study was supported by the VA Office of Academic Affiliations, the VA Health Services Research and Development Service, the National Institute of General Medical Sciences, and the Peter F. McManus Charitable Trust. The researchers had no disclosures.

A “broad swath” of Medicare providers wrote scripts for opioids in 2013, contradicting the idea that the overdose epidemic is mainly the work of “small groups of prolific prescribers and corrupt pill mills,” investigators wrote online in JAMA Internal Medicine.

“Contrary to the California workers’ compensation data showing a small subset of prescribers accounting for a disproportionately large percentage of opioid prescribing, Medicare opioid prescribing is distributed across many prescribers and is, if anything, less skewed than all drug prescribing,” said Dr. Jonathan H. Chen of the Veterans Affairs Palo Alto (Calif.) Health Care System, and his associates.

Their study included 808,020 prescribers and almost 1.2 billion Medicare Part D claims worth nearly $81 billion dollars. They focused on schedule II opioid prescriptions containing oxycodone, fentanyl, hydrocodone, morphine, methadone, hydromorphone, oxymorphone, meperidine, codeine, opium, or levorphanol (JAMA Intern Med. 2015 Dec 14. doi: 10.1001/jamainternmed.2015.6662).

Not surprisingly, specialists in pain management, anesthesia, and physical medicine wrote the most prescriptions per provider. But family practitioners, internists, nurse practitioners, and physician assistants wrote 35,268,234 prescriptions – more than all other specialties combined. “The trends hold up across state lines, with negligible geographic variability,” the researchers said.

The findings contradict an analysis of California workers’ compensation data, in which 1% of prescribers accounted for a third of schedule II opioid prescriptions, and 10% of prescribers accounted for 80% of prescriptions, the investigators noted. Nonetheless, 10% of Medicare prescribers in Dr. Chen’s study accounted for 78% of the total cost of opioids, possibly because they were prescribing pricier formulations or higher doses.

Overall, the findings suggest that opioid prescribing is “widespread” and “relatively indifferent to individual physicians, specialty, or region” – and that efforts to stem the tide must be equally broad, the researchers concluded.

Their study was supported by the VA Office of Academic Affiliations, the VA Health Services Research and Development Service, the National Institute of General Medical Sciences, and the Peter F. McManus Charitable Trust. The researchers had no disclosures.

A “broad swath” of Medicare providers wrote scripts for opioids in 2013, contradicting the idea that the overdose epidemic is mainly the work of “small groups of prolific prescribers and corrupt pill mills,” investigators wrote online in JAMA Internal Medicine.

“Contrary to the California workers’ compensation data showing a small subset of prescribers accounting for a disproportionately large percentage of opioid prescribing, Medicare opioid prescribing is distributed across many prescribers and is, if anything, less skewed than all drug prescribing,” said Dr. Jonathan H. Chen of the Veterans Affairs Palo Alto (Calif.) Health Care System, and his associates.

Their study included 808,020 prescribers and almost 1.2 billion Medicare Part D claims worth nearly $81 billion dollars. They focused on schedule II opioid prescriptions containing oxycodone, fentanyl, hydrocodone, morphine, methadone, hydromorphone, oxymorphone, meperidine, codeine, opium, or levorphanol (JAMA Intern Med. 2015 Dec 14. doi: 10.1001/jamainternmed.2015.6662).

Not surprisingly, specialists in pain management, anesthesia, and physical medicine wrote the most prescriptions per provider. But family practitioners, internists, nurse practitioners, and physician assistants wrote 35,268,234 prescriptions – more than all other specialties combined. “The trends hold up across state lines, with negligible geographic variability,” the researchers said.

The findings contradict an analysis of California workers’ compensation data, in which 1% of prescribers accounted for a third of schedule II opioid prescriptions, and 10% of prescribers accounted for 80% of prescriptions, the investigators noted. Nonetheless, 10% of Medicare prescribers in Dr. Chen’s study accounted for 78% of the total cost of opioids, possibly because they were prescribing pricier formulations or higher doses.

Overall, the findings suggest that opioid prescribing is “widespread” and “relatively indifferent to individual physicians, specialty, or region” – and that efforts to stem the tide must be equally broad, the researchers concluded.

Their study was supported by the VA Office of Academic Affiliations, the VA Health Services Research and Development Service, the National Institute of General Medical Sciences, and the Peter F. McManus Charitable Trust. The researchers had no disclosures.