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Corticosteroids reduce risks in elective extubation
Prophylactic corticosteroids before elective extubation could significantly reduce postextubation stridor and the incidence of reintubation, particularly in patients at high risk of airway obstruction, suggests a systematic review and meta-analysis.
While current guidelines for the management of tracheal extubation call for prophylactic use of corticosteroids in patients with airway compromise, Akira Kuriyama, MD, of Kurashiki Central Hospital in Japan, and coauthors noted that there is an outstanding question as to which patients are most likely to benefit.
Writing in the February 20 online edition of Chest, they reported on an analysis of 11 randomized, controlled trials of prophylactic corticosteroids given before elective extubation, involving 2,472 participants (Chest 2017 Feb 20. doi: 10.1016/j.chest.2017.02.017).
They found that the use of prophylactic corticosteroids was associated with a significant 57% reduction in the incidence of postextubation airway obstruction, laryngeal edema, or stridor, and a 58% reduction in reintubation rates, compared with placebo or no treatment.
A subgroup analysis showed that the benefit in reduction of postextubation airway events was evident only in the six trials that selected patients at high risk of airway obstruction, identified by a cuff-leak test (RR = 0.34), and was not seen in trials with an unselected patient population. Similarly, the reduced incidence of reintubation was evident in trials of high-risk individuals (RR = 0.35) but not in the general patient population.
The authors noted that while the latest systematic reviews had shown that corticosteroids reduce the incidence of postextubation stridor and reintubation, only one review examined the efficacy in high-risk populations and even then, it was a pooled subgroup analysis of only three trials.
“The numbers needed to prevent one episode of postextubation airway events and reintubation in individuals at high risk for postextubation airway obstruction were 5 (95%; CI: 4-7) and 16 (95%; CI: 8-166) respectively,” they wrote, noting that routine administration of corticosteroids before elective extubation is not recommended.
“While the use of prophylactic corticosteroids was associated with few adverse events, it is reasonable to use the cuff-leak test as a screening method, and administer prophylactic steroids only to those who are at risk of developing postextubation obstruction, given our study findings.”
Two of the six trials that identified high-risk individuals used a cuff-leak volume less than 24% of tidal volume during inflation, three used a cuff-leak volume of less than 110 mL, and one used a cuff-leak volume less than 25% of tidal volume.
“This potentially indicates that cuff-leak testing, while applied with varying cut-off values, might be able to select those at similar risk for airway obstruction and underlines the importance of screening for high-risk patients,” the authors said.
Researchers also noted that the longer patients were intubated, the lower the effect size of prophylactic corticosteroids on both postexutubation airway events and reintubation.
“Patients thus tended to benefit from prophylactic corticosteroids to prevent postextubation airway events and subsequent reintubation when the duration of mechanical ventilation was short,” they wrote.
The authors noted that the included trials did differ in terms of populations, corticosteroid protocols, and observation periods. However, they pointed out that the statistical heterogeneity in their primary outcome analysis was due to the risk of postextubation airway obstruction.
No conflicts of interest were declared.
Prophylactic corticosteroids before elective extubation could significantly reduce postextubation stridor and the incidence of reintubation, particularly in patients at high risk of airway obstruction, suggests a systematic review and meta-analysis.
While current guidelines for the management of tracheal extubation call for prophylactic use of corticosteroids in patients with airway compromise, Akira Kuriyama, MD, of Kurashiki Central Hospital in Japan, and coauthors noted that there is an outstanding question as to which patients are most likely to benefit.
Writing in the February 20 online edition of Chest, they reported on an analysis of 11 randomized, controlled trials of prophylactic corticosteroids given before elective extubation, involving 2,472 participants (Chest 2017 Feb 20. doi: 10.1016/j.chest.2017.02.017).
They found that the use of prophylactic corticosteroids was associated with a significant 57% reduction in the incidence of postextubation airway obstruction, laryngeal edema, or stridor, and a 58% reduction in reintubation rates, compared with placebo or no treatment.
A subgroup analysis showed that the benefit in reduction of postextubation airway events was evident only in the six trials that selected patients at high risk of airway obstruction, identified by a cuff-leak test (RR = 0.34), and was not seen in trials with an unselected patient population. Similarly, the reduced incidence of reintubation was evident in trials of high-risk individuals (RR = 0.35) but not in the general patient population.
The authors noted that while the latest systematic reviews had shown that corticosteroids reduce the incidence of postextubation stridor and reintubation, only one review examined the efficacy in high-risk populations and even then, it was a pooled subgroup analysis of only three trials.
“The numbers needed to prevent one episode of postextubation airway events and reintubation in individuals at high risk for postextubation airway obstruction were 5 (95%; CI: 4-7) and 16 (95%; CI: 8-166) respectively,” they wrote, noting that routine administration of corticosteroids before elective extubation is not recommended.
“While the use of prophylactic corticosteroids was associated with few adverse events, it is reasonable to use the cuff-leak test as a screening method, and administer prophylactic steroids only to those who are at risk of developing postextubation obstruction, given our study findings.”
Two of the six trials that identified high-risk individuals used a cuff-leak volume less than 24% of tidal volume during inflation, three used a cuff-leak volume of less than 110 mL, and one used a cuff-leak volume less than 25% of tidal volume.
“This potentially indicates that cuff-leak testing, while applied with varying cut-off values, might be able to select those at similar risk for airway obstruction and underlines the importance of screening for high-risk patients,” the authors said.
Researchers also noted that the longer patients were intubated, the lower the effect size of prophylactic corticosteroids on both postexutubation airway events and reintubation.
“Patients thus tended to benefit from prophylactic corticosteroids to prevent postextubation airway events and subsequent reintubation when the duration of mechanical ventilation was short,” they wrote.
The authors noted that the included trials did differ in terms of populations, corticosteroid protocols, and observation periods. However, they pointed out that the statistical heterogeneity in their primary outcome analysis was due to the risk of postextubation airway obstruction.
No conflicts of interest were declared.
Prophylactic corticosteroids before elective extubation could significantly reduce postextubation stridor and the incidence of reintubation, particularly in patients at high risk of airway obstruction, suggests a systematic review and meta-analysis.
While current guidelines for the management of tracheal extubation call for prophylactic use of corticosteroids in patients with airway compromise, Akira Kuriyama, MD, of Kurashiki Central Hospital in Japan, and coauthors noted that there is an outstanding question as to which patients are most likely to benefit.
Writing in the February 20 online edition of Chest, they reported on an analysis of 11 randomized, controlled trials of prophylactic corticosteroids given before elective extubation, involving 2,472 participants (Chest 2017 Feb 20. doi: 10.1016/j.chest.2017.02.017).
They found that the use of prophylactic corticosteroids was associated with a significant 57% reduction in the incidence of postextubation airway obstruction, laryngeal edema, or stridor, and a 58% reduction in reintubation rates, compared with placebo or no treatment.
A subgroup analysis showed that the benefit in reduction of postextubation airway events was evident only in the six trials that selected patients at high risk of airway obstruction, identified by a cuff-leak test (RR = 0.34), and was not seen in trials with an unselected patient population. Similarly, the reduced incidence of reintubation was evident in trials of high-risk individuals (RR = 0.35) but not in the general patient population.
The authors noted that while the latest systematic reviews had shown that corticosteroids reduce the incidence of postextubation stridor and reintubation, only one review examined the efficacy in high-risk populations and even then, it was a pooled subgroup analysis of only three trials.
“The numbers needed to prevent one episode of postextubation airway events and reintubation in individuals at high risk for postextubation airway obstruction were 5 (95%; CI: 4-7) and 16 (95%; CI: 8-166) respectively,” they wrote, noting that routine administration of corticosteroids before elective extubation is not recommended.
“While the use of prophylactic corticosteroids was associated with few adverse events, it is reasonable to use the cuff-leak test as a screening method, and administer prophylactic steroids only to those who are at risk of developing postextubation obstruction, given our study findings.”
Two of the six trials that identified high-risk individuals used a cuff-leak volume less than 24% of tidal volume during inflation, three used a cuff-leak volume of less than 110 mL, and one used a cuff-leak volume less than 25% of tidal volume.
“This potentially indicates that cuff-leak testing, while applied with varying cut-off values, might be able to select those at similar risk for airway obstruction and underlines the importance of screening for high-risk patients,” the authors said.
Researchers also noted that the longer patients were intubated, the lower the effect size of prophylactic corticosteroids on both postexutubation airway events and reintubation.
“Patients thus tended to benefit from prophylactic corticosteroids to prevent postextubation airway events and subsequent reintubation when the duration of mechanical ventilation was short,” they wrote.
The authors noted that the included trials did differ in terms of populations, corticosteroid protocols, and observation periods. However, they pointed out that the statistical heterogeneity in their primary outcome analysis was due to the risk of postextubation airway obstruction.
No conflicts of interest were declared.
FROM CHEST
Key clinical point: Prophylactic corticosteroids before elective extubation could significantly reduce postextubation stridor and the incidence of reintubation in high-risk patients.
Major finding: Prophylactic corticosteroids were associated with a 57% reduction in the incidence of postextubation airway events, and a 58% reduction in reintubation rates.
Data source: Systematic review and meta-analysis of 11 randomized controlled trials.
Disclosures: No conflicts of interest were declared.
Dysautonomia significantly affects daily activities in advanced Parkinson’s
Nearly half of advanced Parkinson’s disease patients who receive treatment with subthalamic deep brain stimulation or levodopa-carbidopa intestinal gel infusion are affected by dysautonomia that has significant impacts on their daily lives, according to findings from a cross-sectional study.
“We suggest that identifying and managing autonomic targets, in addition to addressing motor disability, may enhance outcomes” of deep brain stimulation or levodopa-carbidopa intestinal gel therapies for advanced Parkinson’s disease, wrote the research team, led by Aristide Merola, MD, PhD, of the Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati.
However, individuals with dysautonomia had a nearly threefold greater risk of impairment in activities of daily living than did those without dysautonomia after adjustment for cognitive impairment, age, and motor severity (odds ratio, 2.850; 95% confidence interval, 1.044-10.326; P = .042). There was also a strong correlation between autonomic symptoms and impaired quality of life, particularly for gastrointestinal, urinary, sexual, and cardiovascular domains (Mov Disord. 2017 Mar 3. doi: 10.1002/mds.26970).
Orthostatic hypotension – both symptomatic and asymptomatic – significantly worsened activities of daily living scores. The authors also saw worse cardiovascular impairment in the levodopa-carbidopa intestinal gel group, which they suggested may be due to higher dopaminergic dosage, and worse pupillomotor impairment in the subthalamic deep brain stimulation group, possibly associated with electrical spread to the optic tract.
The researchers noted that the study’s findings “need to be confirmed in prospective clinical trials evaluating patients before and after” treatment with either modality.
The authors had no conflicts of interest to declare.
Nearly half of advanced Parkinson’s disease patients who receive treatment with subthalamic deep brain stimulation or levodopa-carbidopa intestinal gel infusion are affected by dysautonomia that has significant impacts on their daily lives, according to findings from a cross-sectional study.
“We suggest that identifying and managing autonomic targets, in addition to addressing motor disability, may enhance outcomes” of deep brain stimulation or levodopa-carbidopa intestinal gel therapies for advanced Parkinson’s disease, wrote the research team, led by Aristide Merola, MD, PhD, of the Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati.
However, individuals with dysautonomia had a nearly threefold greater risk of impairment in activities of daily living than did those without dysautonomia after adjustment for cognitive impairment, age, and motor severity (odds ratio, 2.850; 95% confidence interval, 1.044-10.326; P = .042). There was also a strong correlation between autonomic symptoms and impaired quality of life, particularly for gastrointestinal, urinary, sexual, and cardiovascular domains (Mov Disord. 2017 Mar 3. doi: 10.1002/mds.26970).
Orthostatic hypotension – both symptomatic and asymptomatic – significantly worsened activities of daily living scores. The authors also saw worse cardiovascular impairment in the levodopa-carbidopa intestinal gel group, which they suggested may be due to higher dopaminergic dosage, and worse pupillomotor impairment in the subthalamic deep brain stimulation group, possibly associated with electrical spread to the optic tract.
The researchers noted that the study’s findings “need to be confirmed in prospective clinical trials evaluating patients before and after” treatment with either modality.
The authors had no conflicts of interest to declare.
Nearly half of advanced Parkinson’s disease patients who receive treatment with subthalamic deep brain stimulation or levodopa-carbidopa intestinal gel infusion are affected by dysautonomia that has significant impacts on their daily lives, according to findings from a cross-sectional study.
“We suggest that identifying and managing autonomic targets, in addition to addressing motor disability, may enhance outcomes” of deep brain stimulation or levodopa-carbidopa intestinal gel therapies for advanced Parkinson’s disease, wrote the research team, led by Aristide Merola, MD, PhD, of the Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati.
However, individuals with dysautonomia had a nearly threefold greater risk of impairment in activities of daily living than did those without dysautonomia after adjustment for cognitive impairment, age, and motor severity (odds ratio, 2.850; 95% confidence interval, 1.044-10.326; P = .042). There was also a strong correlation between autonomic symptoms and impaired quality of life, particularly for gastrointestinal, urinary, sexual, and cardiovascular domains (Mov Disord. 2017 Mar 3. doi: 10.1002/mds.26970).
Orthostatic hypotension – both symptomatic and asymptomatic – significantly worsened activities of daily living scores. The authors also saw worse cardiovascular impairment in the levodopa-carbidopa intestinal gel group, which they suggested may be due to higher dopaminergic dosage, and worse pupillomotor impairment in the subthalamic deep brain stimulation group, possibly associated with electrical spread to the optic tract.
The researchers noted that the study’s findings “need to be confirmed in prospective clinical trials evaluating patients before and after” treatment with either modality.
The authors had no conflicts of interest to declare.
FROM MOVEMENT DISORDERS
Key clinical point:
Major finding: Among patients with advanced Parkinson’s disease, 48.3% have dysautonomia, which is associated with a nearly threefold greater risk of impairment in activities of daily living.
Data source: Cross-sectional cohort study in 60 patients with advanced Parkinson’s disease.
Disclosures: The authors had no conflicts of interest to declare.
Voclosporin linked to threefold increase in lupus nephritis remission
Treatment with the investigational calcineurin inhibitor voclosporin is associated with a significant, threefold-higher rate of complete remission for lupus nephritis, compared with the current standard of care, according to 48-week data from the AURA-LV (Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study.
In a company release, manufacturer Aurinia Pharmaceuticals presented the results of the international phase IIb controlled trial involving 265 patients with active lupus nephritis from 20 countries, which they say has now met its primary and secondary endpoints.
After 48 weeks, 49% of patients in the low-dose group and 40% in the high-dose group had achieved complete remission, compared with 24% in the control group (P less than .001 for low-dose vs. control; P = .026 for high-dose vs. control). This represented a threefold-higher remission rate for the low-dose group (odds ratio, 3.21) and a twofold-higher rate for the high-dose group (OR, 2.1), compared with controls.
Complete remission was defined as a composite endpoint that included urine protein/creatinine ratio of 0.5 mg/mg or less; normal, stable renal function; presence of sustained, low dose steroids; and no administration of rescue medications.
Partial remission – defined as at least a 50% reduction in urine protein/creatinine ratio with no concomitant use of rescue medication – was seen in 68% of patients in the low-dose voclosporin group, 72% of patients in the high-dose group, and 48% of patients in the control arm (P = .007 for low-dose vs. control; P = .002 for high-dose vs. control).
Investigators said there were no unexpected safety signals from voclosporin, but there were three deaths and one malignancy reported in the control arm after the study treatment period ended.
Brad Rovin, MD, of Ohio State University in Columbus said in the company’s statement that current treatments for this severe complication of systemic lupus erythematosus are toxic, and complete renal response rates are low.
“The AURA trial’s long-term results convincingly demonstrate that the addition of voclosporin to standard of care treatment is superior to standard of care alone,” Dr. Rovin said. “This is an impressive renal response rate, and these results may shift the treatment paradigm of lupus nephritis.”
Aurinia’s chief medical officer, Neil Solomons, MD, said in the release that the results provide the company with confidence that they can now execute a successful phase III program.
The 24-week results of the study – in which all primary and the 24-week secondary endpoints were also met – were released in November 2016.
Treatment with the investigational calcineurin inhibitor voclosporin is associated with a significant, threefold-higher rate of complete remission for lupus nephritis, compared with the current standard of care, according to 48-week data from the AURA-LV (Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study.
In a company release, manufacturer Aurinia Pharmaceuticals presented the results of the international phase IIb controlled trial involving 265 patients with active lupus nephritis from 20 countries, which they say has now met its primary and secondary endpoints.
After 48 weeks, 49% of patients in the low-dose group and 40% in the high-dose group had achieved complete remission, compared with 24% in the control group (P less than .001 for low-dose vs. control; P = .026 for high-dose vs. control). This represented a threefold-higher remission rate for the low-dose group (odds ratio, 3.21) and a twofold-higher rate for the high-dose group (OR, 2.1), compared with controls.
Complete remission was defined as a composite endpoint that included urine protein/creatinine ratio of 0.5 mg/mg or less; normal, stable renal function; presence of sustained, low dose steroids; and no administration of rescue medications.
Partial remission – defined as at least a 50% reduction in urine protein/creatinine ratio with no concomitant use of rescue medication – was seen in 68% of patients in the low-dose voclosporin group, 72% of patients in the high-dose group, and 48% of patients in the control arm (P = .007 for low-dose vs. control; P = .002 for high-dose vs. control).
Investigators said there were no unexpected safety signals from voclosporin, but there were three deaths and one malignancy reported in the control arm after the study treatment period ended.
Brad Rovin, MD, of Ohio State University in Columbus said in the company’s statement that current treatments for this severe complication of systemic lupus erythematosus are toxic, and complete renal response rates are low.
“The AURA trial’s long-term results convincingly demonstrate that the addition of voclosporin to standard of care treatment is superior to standard of care alone,” Dr. Rovin said. “This is an impressive renal response rate, and these results may shift the treatment paradigm of lupus nephritis.”
Aurinia’s chief medical officer, Neil Solomons, MD, said in the release that the results provide the company with confidence that they can now execute a successful phase III program.
The 24-week results of the study – in which all primary and the 24-week secondary endpoints were also met – were released in November 2016.
Treatment with the investigational calcineurin inhibitor voclosporin is associated with a significant, threefold-higher rate of complete remission for lupus nephritis, compared with the current standard of care, according to 48-week data from the AURA-LV (Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study.
In a company release, manufacturer Aurinia Pharmaceuticals presented the results of the international phase IIb controlled trial involving 265 patients with active lupus nephritis from 20 countries, which they say has now met its primary and secondary endpoints.
After 48 weeks, 49% of patients in the low-dose group and 40% in the high-dose group had achieved complete remission, compared with 24% in the control group (P less than .001 for low-dose vs. control; P = .026 for high-dose vs. control). This represented a threefold-higher remission rate for the low-dose group (odds ratio, 3.21) and a twofold-higher rate for the high-dose group (OR, 2.1), compared with controls.
Complete remission was defined as a composite endpoint that included urine protein/creatinine ratio of 0.5 mg/mg or less; normal, stable renal function; presence of sustained, low dose steroids; and no administration of rescue medications.
Partial remission – defined as at least a 50% reduction in urine protein/creatinine ratio with no concomitant use of rescue medication – was seen in 68% of patients in the low-dose voclosporin group, 72% of patients in the high-dose group, and 48% of patients in the control arm (P = .007 for low-dose vs. control; P = .002 for high-dose vs. control).
Investigators said there were no unexpected safety signals from voclosporin, but there were three deaths and one malignancy reported in the control arm after the study treatment period ended.
Brad Rovin, MD, of Ohio State University in Columbus said in the company’s statement that current treatments for this severe complication of systemic lupus erythematosus are toxic, and complete renal response rates are low.
“The AURA trial’s long-term results convincingly demonstrate that the addition of voclosporin to standard of care treatment is superior to standard of care alone,” Dr. Rovin said. “This is an impressive renal response rate, and these results may shift the treatment paradigm of lupus nephritis.”
Aurinia’s chief medical officer, Neil Solomons, MD, said in the release that the results provide the company with confidence that they can now execute a successful phase III program.
The 24-week results of the study – in which all primary and the 24-week secondary endpoints were also met – were released in November 2016.
Key clinical point:
Major finding: Nearly half of patients treated with the lower dose of investigational calcineurin inhibitor voclosporin achieved complete remission compared to one-quarter of patients in the control group.
Data source: The AURA-LV phase IIb controlled study involving 265 patients with active lupus nephritis.
Disclosures: The results were presented in a company release from manufacturer Aurinia Pharmaceuticals.
DTaP5-IPV noninferior to DTaP5 plus IPV for fifth dose
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
Key clinical point: The stand-alone DTaP5-IPV combination vaccine is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years.
Major finding:
Data source: A phase III, controlled, randomized open-label study in 3,372 children.
Disclosures: The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
Standardize opioid prescribing after endocrine neck surgery, researchers say
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
FROM ANNALS OF SURGICAL ONCOLOGY
Key clinical point: Twenty oral morphine equivalents is the ideal amount of pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery.
Major finding: Only 7% of patients who undergo thyroidectomy or parathyroidectomy use more than 20 oral morphine equivalents for postoperative pain relief.
Data source: Observational cohort study of 313 adult patients undergoing thyroidectomy or parathyroidectomy.
Disclosures: Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Herbal/dietary supplements linked to liver injury requiring transplant
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
FROM TRANSPLANTATION PROCEEDINGS
Key clinical point: Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States.
Major finding: Twenty-one cases of liver transplantation linked to the use of herbal or dietary supplements were recorded between 2003 and 2015.
Data source: Analysis of registry data from 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis.
Disclosures: No conflicts of interest were declared.
‘Strong evidence’ links obesity to cancers
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
FROM BMJ
Key clinical point: An umbrella analysis of systematic reviews has found strong evidence linking adiposity to a range of cancers including esophageal adenocarcinoma, and cancer of the colon, kidney, and pancreas.
Major finding: Adiposity is significantly associated with cancers of the esophagus, colon, rectum, biliary tract, pancreas, endometrium, kidney, postmenopausal breast, and to multiple myeloma.
Data source: An umbrella review of 204 meta-analyses.
Disclosures: The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
Recent increase in subdural hematoma may be linked to antithrombotics
according to data published online Feb. 28 in JAMA.
A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).
Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.
Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.
Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.
At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.
“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.
While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.
Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.
The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.
“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.
Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.
according to data published online Feb. 28 in JAMA.
A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).
Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.
Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.
Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.
At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.
“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.
While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.
Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.
The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.
“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.
Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.
according to data published online Feb. 28 in JAMA.
A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).
Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.
Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.
Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.
At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.
“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.
While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.
Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.
The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.
“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.
Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.
FROM JAMA
Key clinical point: The increasing incidence of subdural hematoma may be linked more common use of antithrombotics.
Major finding: Antithrombotic medication is associated with as much as a fourfold increase in the risk of subdural hematoma.
Data source: A retrospective case-control study of 10,010 patients with a first-ever subdural hematoma.
Disclosures: Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.
Follow-up data support using mesh for umbilical hernia repair
Patients with umbilical hernias and multiple comorbidities should be considered for mesh repair to reduce the risk of recurrence, say the authors of a study of the factors associated with umbilical hernia recurrence after repair.
The retrospective cohort study, published in JAMA Surgery, examined recurrence and mortality outcomes in 332 military veteran patients who underwent primary umbilical hernia repair between 1998 and 2008 and followed until June 2014.
The overall recurrence rate was 6% and a mean recurrence time after index repair of 3.1 years. The recurrence rate was significantly higher among patients who underwent primary suture repair, compared with those who underwent mesh repair (9.8% vs. 2.4%, P = .04). Mesh repair decreased the risk of recurrence more than threefold, compared with primary suture repair (odds ratio, 0.28; 95% confidence interval, 0.08-0.95).
Patients with ascites had a significantly greater risk of recurrence, compared with those without ascites (20% vs. 5.1%, P = .02), as did those with liver disease (35% vs. 13.8%, P = .02), and diabetes (55% vs. 32.7%).
“This information suggests that umbilical hernias should be repaired using mesh, especially if a patient has multiple comorbidities that are significantly associated with recurrence, such as obesity, diabetes, liver disease, and ascites,” wrote Divya A. Shankar, a medical student at Boston University School of Medicine, and her coauthors (JAMA Surg. 2017 Jan 25. doi: 10.1001/jamasurg.2016.5052).
Among these patients, only 1 died within 30 days, but the study captured mortality in this group over 6-16 years after their hernia surgery. Mortality rate in the group was 27% through the follow-up period. However, older individuals, smokers, patients with liver disease and ascites, and those who had to undergo emergency or semi-urgent repair or who required intraoperative bowel resection had significantly increased long-term mortality rates.
“Although there is a trend toward higher mortality rates in patients who underwent emergency repair, it is difficult to interpret whether the deaths were related to the emergency or to underlying medical conditions given that the etiology of the majority of these deaths is unknown,” the authors wrote.
Among the deaths, 43 (48%) were from unknown causes, 18 (20%) were cancer related, 12 (13%) were related to renal disease, and 3 (3.3%) were related to sepsis.
Researchers found that patients with a history of hernias were significantly less likely to have an umbilical hernia recurrence, although a greater percentage of these patients – 61% – received mesh in contrast to the 44% of patients without a history of hernia.
Defect size did not appear to affect the rate of recurrence but the authors noted that defect size was only recorded in about half of the patients in the study.
“Because there was no significant difference between these groups, we are unable to conclude whether the size of defects should play a role in a surgeon’s decision to use mesh,” they wrote.
Sixty-one patients (18%) had at least one complication within 30 days of the repair, with the most common being seroma (9.6%), surgical site infection (6.9%) and hematoma (2.4%). Two patients experienced a mesh infection and three experienced ascites leaks. The rate of complications was slightly, but not significantly, higher in the patients who received mesh repair, compared with the primary suture repair.
“A surprise finding was that patient who underwent emergent or semi-emergent repair had a 2.2 times increased odds of death. Twenty deaths occurred more than 30 days after emergent or semi-urgent repair and 12 (60%) were secondary to unknown causes and 5 (25%) were secondary to liver disease,” the investigators noted.
“Interestingly, 193 (58%) patients who underwent umbilical hernia repair had other hernias that were either repaired before the index repair or developed postoperatively. Therefore, we propose that umbilical hernias may be a type of ‘field defect’ and we support the idea of that abnormal collegan metabolism could play a role in hernia development. ...We speculate that surgeons might be more inclined to use mesh in a patients with a history of other hernias.”
Despite the potential for complications, “elective hernia repair with mesh should be considered in patients with multiple comorbidities given that the use of mesh offers protection from recurrence without major morbidity.”
The study was supported by the VA Healthcare System. No conflicts of interest were declared.
Patients with umbilical hernias and multiple comorbidities should be considered for mesh repair to reduce the risk of recurrence, say the authors of a study of the factors associated with umbilical hernia recurrence after repair.
The retrospective cohort study, published in JAMA Surgery, examined recurrence and mortality outcomes in 332 military veteran patients who underwent primary umbilical hernia repair between 1998 and 2008 and followed until June 2014.
The overall recurrence rate was 6% and a mean recurrence time after index repair of 3.1 years. The recurrence rate was significantly higher among patients who underwent primary suture repair, compared with those who underwent mesh repair (9.8% vs. 2.4%, P = .04). Mesh repair decreased the risk of recurrence more than threefold, compared with primary suture repair (odds ratio, 0.28; 95% confidence interval, 0.08-0.95).
Patients with ascites had a significantly greater risk of recurrence, compared with those without ascites (20% vs. 5.1%, P = .02), as did those with liver disease (35% vs. 13.8%, P = .02), and diabetes (55% vs. 32.7%).
“This information suggests that umbilical hernias should be repaired using mesh, especially if a patient has multiple comorbidities that are significantly associated with recurrence, such as obesity, diabetes, liver disease, and ascites,” wrote Divya A. Shankar, a medical student at Boston University School of Medicine, and her coauthors (JAMA Surg. 2017 Jan 25. doi: 10.1001/jamasurg.2016.5052).
Among these patients, only 1 died within 30 days, but the study captured mortality in this group over 6-16 years after their hernia surgery. Mortality rate in the group was 27% through the follow-up period. However, older individuals, smokers, patients with liver disease and ascites, and those who had to undergo emergency or semi-urgent repair or who required intraoperative bowel resection had significantly increased long-term mortality rates.
“Although there is a trend toward higher mortality rates in patients who underwent emergency repair, it is difficult to interpret whether the deaths were related to the emergency or to underlying medical conditions given that the etiology of the majority of these deaths is unknown,” the authors wrote.
Among the deaths, 43 (48%) were from unknown causes, 18 (20%) were cancer related, 12 (13%) were related to renal disease, and 3 (3.3%) were related to sepsis.
Researchers found that patients with a history of hernias were significantly less likely to have an umbilical hernia recurrence, although a greater percentage of these patients – 61% – received mesh in contrast to the 44% of patients without a history of hernia.
Defect size did not appear to affect the rate of recurrence but the authors noted that defect size was only recorded in about half of the patients in the study.
“Because there was no significant difference between these groups, we are unable to conclude whether the size of defects should play a role in a surgeon’s decision to use mesh,” they wrote.
Sixty-one patients (18%) had at least one complication within 30 days of the repair, with the most common being seroma (9.6%), surgical site infection (6.9%) and hematoma (2.4%). Two patients experienced a mesh infection and three experienced ascites leaks. The rate of complications was slightly, but not significantly, higher in the patients who received mesh repair, compared with the primary suture repair.
“A surprise finding was that patient who underwent emergent or semi-emergent repair had a 2.2 times increased odds of death. Twenty deaths occurred more than 30 days after emergent or semi-urgent repair and 12 (60%) were secondary to unknown causes and 5 (25%) were secondary to liver disease,” the investigators noted.
“Interestingly, 193 (58%) patients who underwent umbilical hernia repair had other hernias that were either repaired before the index repair or developed postoperatively. Therefore, we propose that umbilical hernias may be a type of ‘field defect’ and we support the idea of that abnormal collegan metabolism could play a role in hernia development. ...We speculate that surgeons might be more inclined to use mesh in a patients with a history of other hernias.”
Despite the potential for complications, “elective hernia repair with mesh should be considered in patients with multiple comorbidities given that the use of mesh offers protection from recurrence without major morbidity.”
The study was supported by the VA Healthcare System. No conflicts of interest were declared.
Patients with umbilical hernias and multiple comorbidities should be considered for mesh repair to reduce the risk of recurrence, say the authors of a study of the factors associated with umbilical hernia recurrence after repair.
The retrospective cohort study, published in JAMA Surgery, examined recurrence and mortality outcomes in 332 military veteran patients who underwent primary umbilical hernia repair between 1998 and 2008 and followed until June 2014.
The overall recurrence rate was 6% and a mean recurrence time after index repair of 3.1 years. The recurrence rate was significantly higher among patients who underwent primary suture repair, compared with those who underwent mesh repair (9.8% vs. 2.4%, P = .04). Mesh repair decreased the risk of recurrence more than threefold, compared with primary suture repair (odds ratio, 0.28; 95% confidence interval, 0.08-0.95).
Patients with ascites had a significantly greater risk of recurrence, compared with those without ascites (20% vs. 5.1%, P = .02), as did those with liver disease (35% vs. 13.8%, P = .02), and diabetes (55% vs. 32.7%).
“This information suggests that umbilical hernias should be repaired using mesh, especially if a patient has multiple comorbidities that are significantly associated with recurrence, such as obesity, diabetes, liver disease, and ascites,” wrote Divya A. Shankar, a medical student at Boston University School of Medicine, and her coauthors (JAMA Surg. 2017 Jan 25. doi: 10.1001/jamasurg.2016.5052).
Among these patients, only 1 died within 30 days, but the study captured mortality in this group over 6-16 years after their hernia surgery. Mortality rate in the group was 27% through the follow-up period. However, older individuals, smokers, patients with liver disease and ascites, and those who had to undergo emergency or semi-urgent repair or who required intraoperative bowel resection had significantly increased long-term mortality rates.
“Although there is a trend toward higher mortality rates in patients who underwent emergency repair, it is difficult to interpret whether the deaths were related to the emergency or to underlying medical conditions given that the etiology of the majority of these deaths is unknown,” the authors wrote.
Among the deaths, 43 (48%) were from unknown causes, 18 (20%) were cancer related, 12 (13%) were related to renal disease, and 3 (3.3%) were related to sepsis.
Researchers found that patients with a history of hernias were significantly less likely to have an umbilical hernia recurrence, although a greater percentage of these patients – 61% – received mesh in contrast to the 44% of patients without a history of hernia.
Defect size did not appear to affect the rate of recurrence but the authors noted that defect size was only recorded in about half of the patients in the study.
“Because there was no significant difference between these groups, we are unable to conclude whether the size of defects should play a role in a surgeon’s decision to use mesh,” they wrote.
Sixty-one patients (18%) had at least one complication within 30 days of the repair, with the most common being seroma (9.6%), surgical site infection (6.9%) and hematoma (2.4%). Two patients experienced a mesh infection and three experienced ascites leaks. The rate of complications was slightly, but not significantly, higher in the patients who received mesh repair, compared with the primary suture repair.
“A surprise finding was that patient who underwent emergent or semi-emergent repair had a 2.2 times increased odds of death. Twenty deaths occurred more than 30 days after emergent or semi-urgent repair and 12 (60%) were secondary to unknown causes and 5 (25%) were secondary to liver disease,” the investigators noted.
“Interestingly, 193 (58%) patients who underwent umbilical hernia repair had other hernias that were either repaired before the index repair or developed postoperatively. Therefore, we propose that umbilical hernias may be a type of ‘field defect’ and we support the idea of that abnormal collegan metabolism could play a role in hernia development. ...We speculate that surgeons might be more inclined to use mesh in a patients with a history of other hernias.”
Despite the potential for complications, “elective hernia repair with mesh should be considered in patients with multiple comorbidities given that the use of mesh offers protection from recurrence without major morbidity.”
The study was supported by the VA Healthcare System. No conflicts of interest were declared.
FROM JAMA SURGERY
Immune recovery may predict survival in myeloma patients with stem cell transplants
Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.
“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.
In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.
One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.
Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).
There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.
“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”
The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.
One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.
Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.
“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.
In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.
One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.
Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).
There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.
“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”
The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.
One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.
Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.
“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.
In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.
One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.
Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).
There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.
“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”
The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.
One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.
FROM HAEMATOLOGICA
Key clinical point:
Major finding: One year after ASCT, 52% of surviving patients had experienced immunoglobulin recovery.
Data source: A retrospective cohort study in 295 patients with symptomatic multiple myeloma who underwent autologous stem cell transfer.
Disclosures: One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.