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AACAP: Faster weight gain with olanzapine in anorexia
SAN ANTONIO – Teenagers with anorexia nervosa gained weight faster when taking the atypical antipsychotic drug olanzapine, according to results from an open-label study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Olanzapine is used frequently off-label in the treatment of anorexia, said Dr. Wendy Spettigue of the Children’s Hospital of Eastern Ontario in Ottawa. In addition to the known metabolic effects of the drug, in clinical use “it seems to decrease eating disorder thoughts and preoccupations, and with that, resistance to taking the nutrition.” However, she noted, “there’s been little to date in terms of research in adolescents.”
One previous placebo-controlled pilot study in adolescent girls (n =20) found no differences in rate or amount of weight gain between olanzapine-treated and placebo groups (J Child Adolesc Psychopharmacol. 2011;21[3]:207-12).
Dr. Spettigue and colleagues’ study, the largest to date to look at olanzapine in this patient group, compared low-weight patients who received standard care plus olanzapine (n = 22) to those who received standard care only (n = 10), which included nutritional support and therapy. All but three patients were girls, 85% were inpatients, and median age at baseline was 15.5 years. The mean percentage of ideal body weight was 77% and 78%, respectively, for the two groups. Doses of olanzapine ranged from 2.5 mg to 7.5 mg, with most patients on 5 mg at bedtime.
Both groups showed significant weight gains across the 6-week study period. However, the intervention group saw a significantly greater rate of increase after week 3, with the olanzapine group gaining a mean 1.53 kg between weeks 3 and 4 (vs. 0.81 in the comparison group) and 2.64 kg between weeks 4 and 6 of treatment (vs. 1.51; P = .012).
Patients in the study “were told that whether they take the medication or not they need to get to their healthy weight. We taper them off once they have reached their healthy weight, and many of them end up on SSRIs alongside family therapy as part of ongoing treatment,” Dr. Spettigue said.
Secondary outcomes in the study included the Multidimensional Anxiety Scale for Children, the Eating Disorder Examination Questionnaire, and the Children’s Depression Inventory. Both the intervention and comparison groups, which were well matched on these measures at baseline, saw decreases for anxiety (P = .27), depression (P less than .1), and eating disorders (P = .04). Between-group differences did not reach statistical significance.
The researchers did note elevations in lipid profiles in about a third of the olanzapine-treated patients. Dr. Spettigue said she did not find this worrisome in this patient group, who were only on the medication for a short time, but she stressed that medical monitoring was extremely important.
The W. Garfield Weston Foundation funded the study. The investigators reported no conflicts of interest.
SAN ANTONIO – Teenagers with anorexia nervosa gained weight faster when taking the atypical antipsychotic drug olanzapine, according to results from an open-label study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Olanzapine is used frequently off-label in the treatment of anorexia, said Dr. Wendy Spettigue of the Children’s Hospital of Eastern Ontario in Ottawa. In addition to the known metabolic effects of the drug, in clinical use “it seems to decrease eating disorder thoughts and preoccupations, and with that, resistance to taking the nutrition.” However, she noted, “there’s been little to date in terms of research in adolescents.”
One previous placebo-controlled pilot study in adolescent girls (n =20) found no differences in rate or amount of weight gain between olanzapine-treated and placebo groups (J Child Adolesc Psychopharmacol. 2011;21[3]:207-12).
Dr. Spettigue and colleagues’ study, the largest to date to look at olanzapine in this patient group, compared low-weight patients who received standard care plus olanzapine (n = 22) to those who received standard care only (n = 10), which included nutritional support and therapy. All but three patients were girls, 85% were inpatients, and median age at baseline was 15.5 years. The mean percentage of ideal body weight was 77% and 78%, respectively, for the two groups. Doses of olanzapine ranged from 2.5 mg to 7.5 mg, with most patients on 5 mg at bedtime.
Both groups showed significant weight gains across the 6-week study period. However, the intervention group saw a significantly greater rate of increase after week 3, with the olanzapine group gaining a mean 1.53 kg between weeks 3 and 4 (vs. 0.81 in the comparison group) and 2.64 kg between weeks 4 and 6 of treatment (vs. 1.51; P = .012).
Patients in the study “were told that whether they take the medication or not they need to get to their healthy weight. We taper them off once they have reached their healthy weight, and many of them end up on SSRIs alongside family therapy as part of ongoing treatment,” Dr. Spettigue said.
Secondary outcomes in the study included the Multidimensional Anxiety Scale for Children, the Eating Disorder Examination Questionnaire, and the Children’s Depression Inventory. Both the intervention and comparison groups, which were well matched on these measures at baseline, saw decreases for anxiety (P = .27), depression (P less than .1), and eating disorders (P = .04). Between-group differences did not reach statistical significance.
The researchers did note elevations in lipid profiles in about a third of the olanzapine-treated patients. Dr. Spettigue said she did not find this worrisome in this patient group, who were only on the medication for a short time, but she stressed that medical monitoring was extremely important.
The W. Garfield Weston Foundation funded the study. The investigators reported no conflicts of interest.
SAN ANTONIO – Teenagers with anorexia nervosa gained weight faster when taking the atypical antipsychotic drug olanzapine, according to results from an open-label study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Olanzapine is used frequently off-label in the treatment of anorexia, said Dr. Wendy Spettigue of the Children’s Hospital of Eastern Ontario in Ottawa. In addition to the known metabolic effects of the drug, in clinical use “it seems to decrease eating disorder thoughts and preoccupations, and with that, resistance to taking the nutrition.” However, she noted, “there’s been little to date in terms of research in adolescents.”
One previous placebo-controlled pilot study in adolescent girls (n =20) found no differences in rate or amount of weight gain between olanzapine-treated and placebo groups (J Child Adolesc Psychopharmacol. 2011;21[3]:207-12).
Dr. Spettigue and colleagues’ study, the largest to date to look at olanzapine in this patient group, compared low-weight patients who received standard care plus olanzapine (n = 22) to those who received standard care only (n = 10), which included nutritional support and therapy. All but three patients were girls, 85% were inpatients, and median age at baseline was 15.5 years. The mean percentage of ideal body weight was 77% and 78%, respectively, for the two groups. Doses of olanzapine ranged from 2.5 mg to 7.5 mg, with most patients on 5 mg at bedtime.
Both groups showed significant weight gains across the 6-week study period. However, the intervention group saw a significantly greater rate of increase after week 3, with the olanzapine group gaining a mean 1.53 kg between weeks 3 and 4 (vs. 0.81 in the comparison group) and 2.64 kg between weeks 4 and 6 of treatment (vs. 1.51; P = .012).
Patients in the study “were told that whether they take the medication or not they need to get to their healthy weight. We taper them off once they have reached their healthy weight, and many of them end up on SSRIs alongside family therapy as part of ongoing treatment,” Dr. Spettigue said.
Secondary outcomes in the study included the Multidimensional Anxiety Scale for Children, the Eating Disorder Examination Questionnaire, and the Children’s Depression Inventory. Both the intervention and comparison groups, which were well matched on these measures at baseline, saw decreases for anxiety (P = .27), depression (P less than .1), and eating disorders (P = .04). Between-group differences did not reach statistical significance.
The researchers did note elevations in lipid profiles in about a third of the olanzapine-treated patients. Dr. Spettigue said she did not find this worrisome in this patient group, who were only on the medication for a short time, but she stressed that medical monitoring was extremely important.
The W. Garfield Weston Foundation funded the study. The investigators reported no conflicts of interest.
AT THE AACAP ANNUAL MEETING
Key clinical point:Olanzapine can help adolescent patients with anorexia gain weight faster than therapy and nutritional support alone.
Major finding: Weight gain was between 50% and 60% higher in the olanzapine-treated group after 3 weeks, compared with the control group (P = .012).
Data source: Open-label study of 32 adolescents with anorexia nervosa, mean age 15.5 years, 29 girls, randomized to olanzapine or standard care for 6 weeks.
Disclosures: The W. Garfield Weston foundation funded the study and the investigators disclosed no conflicts.
Guidelines back multivessel PCI
New recommendations validate the treatment of partially blocked vessels along with the culprit vessel in patients undergoing a primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI).
While 2013 guidelines by the American College of Cardiology and the American Heart Association cautioned against multivessel interventions as nonbeneficial in STEMI, evidence from four recent randomized controlled trials now supports the practice as “reasonable,” the updated guidelines say.
Partially blocked vessels may be treated in hemodynamically stable patients at the time of PCI or as a planned staged procedure.
The guidelines, issued Oct 21 by the ACC/AHA and the Society for Cardiovascular Angiography and Interventions, with collaboration from the American College of Emergency Physicians, have been published online in Journal of the American College of Cardiology (2015 Oct 21;10.1016/jacc.2015.10.005), Circulation, and Catheterization and Cardiovascular Interventions.
The guidelines also downgrade a prior recommendation on routine use of manual aspiration thrombectomy before primary PCI to implant a stent, citing evidence from three randomized trials (INFUSE-AMI, TASTE, and TOTAL) in support of the new class III “no benefit” recommendation. Previously, the organizations had considered this treatment strategy reasonable.
For the advice on primary PCI and multivessel treatment, the guideline authors, led by Dr. Glenn N. Levine of Baylor College of Medicine in Houston, identified four trials (PRAMI, CvLPRIT, DANAMI 3-PRIMULTI, PRAGUE-13) in which multivessel PCI, either staged or at the time of primary PCI, was shown to be nonharmful or beneficial in selected patients with STEMI. In three of these trials, multivessel treatment was shown associated with significant reductions in risk of death and other cardiac events compared to culprit-vessel-only treatment.
Previously, “differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints” made study results on culprit-only vs. multivessel PCI conflicting, Dr. Levine and colleagues wrote.
While the more recent RCTs have helped clarify a benefit or at least lack of harm, “there are insufficient observational data and no randomized data at this time to inform a recommendation with regard to the optimal timing of nonculprit vessel PCI,” the authors wrote, saying further studies were needed. Clinical data, lesion severity and complexity, and the risk of contrast nephropathy should be considered when determining whether to perform primary or staged multivessel PCI.
Earlier recommendations in 2011 and 2013 favoring aspiration thrombectomy before primary PCI had been based largely on the results of one single-center randomized study enrolling about 1,000 patients (Lancet 2008;371:1915-20).
Since then, much larger trials have shown no significant differences in major cardiac events or death in people who received aspiration thrombectomy prior to primary PCI compared with PCI alone, and a meta-analysis of more than 20,000 patients across 17 trials found no significant reduction in death, reinfarction, or stent thrombosis associated with routine aspiration thrombectomy vs. PCI alone (Circ Cardiovasc Interv. 2015;8:e002258).
The guideline authors clarified that the downgraded recommendation of “no benefit” applies only to routine use of aspiration thrombectomy before primary PCI. Current data remain inadequate to determine a benefit for selective or “bailout” aspiration thrombectomy, which is thrombectomy that, though unplanned, had to be used during the procedure because of an unsatisfactory initial result or a complication.
Several of the ACC/AHA/SCAI guideline authors or reviewers, including both vice chairs of the PCI writing committee, disclosed industry relationships.
New recommendations validate the treatment of partially blocked vessels along with the culprit vessel in patients undergoing a primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI).
While 2013 guidelines by the American College of Cardiology and the American Heart Association cautioned against multivessel interventions as nonbeneficial in STEMI, evidence from four recent randomized controlled trials now supports the practice as “reasonable,” the updated guidelines say.
Partially blocked vessels may be treated in hemodynamically stable patients at the time of PCI or as a planned staged procedure.
The guidelines, issued Oct 21 by the ACC/AHA and the Society for Cardiovascular Angiography and Interventions, with collaboration from the American College of Emergency Physicians, have been published online in Journal of the American College of Cardiology (2015 Oct 21;10.1016/jacc.2015.10.005), Circulation, and Catheterization and Cardiovascular Interventions.
The guidelines also downgrade a prior recommendation on routine use of manual aspiration thrombectomy before primary PCI to implant a stent, citing evidence from three randomized trials (INFUSE-AMI, TASTE, and TOTAL) in support of the new class III “no benefit” recommendation. Previously, the organizations had considered this treatment strategy reasonable.
For the advice on primary PCI and multivessel treatment, the guideline authors, led by Dr. Glenn N. Levine of Baylor College of Medicine in Houston, identified four trials (PRAMI, CvLPRIT, DANAMI 3-PRIMULTI, PRAGUE-13) in which multivessel PCI, either staged or at the time of primary PCI, was shown to be nonharmful or beneficial in selected patients with STEMI. In three of these trials, multivessel treatment was shown associated with significant reductions in risk of death and other cardiac events compared to culprit-vessel-only treatment.
Previously, “differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints” made study results on culprit-only vs. multivessel PCI conflicting, Dr. Levine and colleagues wrote.
While the more recent RCTs have helped clarify a benefit or at least lack of harm, “there are insufficient observational data and no randomized data at this time to inform a recommendation with regard to the optimal timing of nonculprit vessel PCI,” the authors wrote, saying further studies were needed. Clinical data, lesion severity and complexity, and the risk of contrast nephropathy should be considered when determining whether to perform primary or staged multivessel PCI.
Earlier recommendations in 2011 and 2013 favoring aspiration thrombectomy before primary PCI had been based largely on the results of one single-center randomized study enrolling about 1,000 patients (Lancet 2008;371:1915-20).
Since then, much larger trials have shown no significant differences in major cardiac events or death in people who received aspiration thrombectomy prior to primary PCI compared with PCI alone, and a meta-analysis of more than 20,000 patients across 17 trials found no significant reduction in death, reinfarction, or stent thrombosis associated with routine aspiration thrombectomy vs. PCI alone (Circ Cardiovasc Interv. 2015;8:e002258).
The guideline authors clarified that the downgraded recommendation of “no benefit” applies only to routine use of aspiration thrombectomy before primary PCI. Current data remain inadequate to determine a benefit for selective or “bailout” aspiration thrombectomy, which is thrombectomy that, though unplanned, had to be used during the procedure because of an unsatisfactory initial result or a complication.
Several of the ACC/AHA/SCAI guideline authors or reviewers, including both vice chairs of the PCI writing committee, disclosed industry relationships.
New recommendations validate the treatment of partially blocked vessels along with the culprit vessel in patients undergoing a primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI).
While 2013 guidelines by the American College of Cardiology and the American Heart Association cautioned against multivessel interventions as nonbeneficial in STEMI, evidence from four recent randomized controlled trials now supports the practice as “reasonable,” the updated guidelines say.
Partially blocked vessels may be treated in hemodynamically stable patients at the time of PCI or as a planned staged procedure.
The guidelines, issued Oct 21 by the ACC/AHA and the Society for Cardiovascular Angiography and Interventions, with collaboration from the American College of Emergency Physicians, have been published online in Journal of the American College of Cardiology (2015 Oct 21;10.1016/jacc.2015.10.005), Circulation, and Catheterization and Cardiovascular Interventions.
The guidelines also downgrade a prior recommendation on routine use of manual aspiration thrombectomy before primary PCI to implant a stent, citing evidence from three randomized trials (INFUSE-AMI, TASTE, and TOTAL) in support of the new class III “no benefit” recommendation. Previously, the organizations had considered this treatment strategy reasonable.
For the advice on primary PCI and multivessel treatment, the guideline authors, led by Dr. Glenn N. Levine of Baylor College of Medicine in Houston, identified four trials (PRAMI, CvLPRIT, DANAMI 3-PRIMULTI, PRAGUE-13) in which multivessel PCI, either staged or at the time of primary PCI, was shown to be nonharmful or beneficial in selected patients with STEMI. In three of these trials, multivessel treatment was shown associated with significant reductions in risk of death and other cardiac events compared to culprit-vessel-only treatment.
Previously, “differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints” made study results on culprit-only vs. multivessel PCI conflicting, Dr. Levine and colleagues wrote.
While the more recent RCTs have helped clarify a benefit or at least lack of harm, “there are insufficient observational data and no randomized data at this time to inform a recommendation with regard to the optimal timing of nonculprit vessel PCI,” the authors wrote, saying further studies were needed. Clinical data, lesion severity and complexity, and the risk of contrast nephropathy should be considered when determining whether to perform primary or staged multivessel PCI.
Earlier recommendations in 2011 and 2013 favoring aspiration thrombectomy before primary PCI had been based largely on the results of one single-center randomized study enrolling about 1,000 patients (Lancet 2008;371:1915-20).
Since then, much larger trials have shown no significant differences in major cardiac events or death in people who received aspiration thrombectomy prior to primary PCI compared with PCI alone, and a meta-analysis of more than 20,000 patients across 17 trials found no significant reduction in death, reinfarction, or stent thrombosis associated with routine aspiration thrombectomy vs. PCI alone (Circ Cardiovasc Interv. 2015;8:e002258).
The guideline authors clarified that the downgraded recommendation of “no benefit” applies only to routine use of aspiration thrombectomy before primary PCI. Current data remain inadequate to determine a benefit for selective or “bailout” aspiration thrombectomy, which is thrombectomy that, though unplanned, had to be used during the procedure because of an unsatisfactory initial result or a complication.
Several of the ACC/AHA/SCAI guideline authors or reviewers, including both vice chairs of the PCI writing committee, disclosed industry relationships.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LABAs show no benefit over tiotropium in black patients with asthma
Black adults with asthma did not see significant differences in time to exacerbation after adding a long-acting beta-agonist to their inhaled corticosteroid treatment, compared with adding tiotropium, according to results from a randomized, open-label trial.
Moreover, genetic variations were not associated with differences in treatment response.
The study, published online Oct. 27 in JAMA, enrolled 1,070 patients already taking or eligible for combination therapy with inhaled corticosteroids (ICS). More than 75% of patients were women, and the mean age was 45 years.
Dr. Michael E. Wechsler of Brigham and Women’s Hospital, Boston, and colleagues carried out their research at 20 primary care sites in the United States, with information on variation in ADRB2 Arg16Gly alleles captured (JAMA 2015 Oct 27;314[16]:1720-30). Patients were followed an average of 310 days.
Of 538 patients randomized to salmeterol or formoterol plus ICS, the mean number of exacerbations was 0.42 per person-year, compared with 0.37 per person-year in the 532 patients of the tiotropium plus ICS group (rate ratio, 0.90; P = .31).
The likelihood of being exacerbation free at 1 year was 74% for a long-acting beta-agonist (LABA) plus ICS, vs. 75.7% for tiotropium plus ICS (hazard ratio, 0.91; P = .47).
Other measures – including patient-reported outcomes, spirometry, rescue medication use, asthma deteriorations, and adverse events – did not differ significantly between treatment assignments. When stratified by genotype, there were no significant differences in hazard ratios for time to first exacerbation, mean number of exacerbations, or lung function at 6, 12, or 18 months.
“The study was performed in a population that bears a disproportionate burden of asthma morbidity and in whom questions have been raised about the relative efficacy and safety of LABAs,” Dr. Wechsler and colleagues wrote in their analysis.
“Because questions have been raised about whether efficacy studies correctly capture all the causes of morbidity, we conducted a clinical effectiveness study primarily in practicing physician offices,” the authors explained. “We used an outcome important to patients, physicians, and policy makers – asthma exacerbations.”
The investigators acknowledged as limitations of their study its open-label design and that asthma diagnoses were made by community physicians with no required objective testing. In addition, the study’s high discontinuation rate and poor medicine adherence were roughly equal between treatment groups and reflective of real-world practice, they noted.
The Agency for Heathcare Research and Quality funded the study. Dr. Wechsler and several coauthors disclosed consultant fees from multiple pharmaceutical manufacturers.
Black adults with asthma did not see significant differences in time to exacerbation after adding a long-acting beta-agonist to their inhaled corticosteroid treatment, compared with adding tiotropium, according to results from a randomized, open-label trial.
Moreover, genetic variations were not associated with differences in treatment response.
The study, published online Oct. 27 in JAMA, enrolled 1,070 patients already taking or eligible for combination therapy with inhaled corticosteroids (ICS). More than 75% of patients were women, and the mean age was 45 years.
Dr. Michael E. Wechsler of Brigham and Women’s Hospital, Boston, and colleagues carried out their research at 20 primary care sites in the United States, with information on variation in ADRB2 Arg16Gly alleles captured (JAMA 2015 Oct 27;314[16]:1720-30). Patients were followed an average of 310 days.
Of 538 patients randomized to salmeterol or formoterol plus ICS, the mean number of exacerbations was 0.42 per person-year, compared with 0.37 per person-year in the 532 patients of the tiotropium plus ICS group (rate ratio, 0.90; P = .31).
The likelihood of being exacerbation free at 1 year was 74% for a long-acting beta-agonist (LABA) plus ICS, vs. 75.7% for tiotropium plus ICS (hazard ratio, 0.91; P = .47).
Other measures – including patient-reported outcomes, spirometry, rescue medication use, asthma deteriorations, and adverse events – did not differ significantly between treatment assignments. When stratified by genotype, there were no significant differences in hazard ratios for time to first exacerbation, mean number of exacerbations, or lung function at 6, 12, or 18 months.
“The study was performed in a population that bears a disproportionate burden of asthma morbidity and in whom questions have been raised about the relative efficacy and safety of LABAs,” Dr. Wechsler and colleagues wrote in their analysis.
“Because questions have been raised about whether efficacy studies correctly capture all the causes of morbidity, we conducted a clinical effectiveness study primarily in practicing physician offices,” the authors explained. “We used an outcome important to patients, physicians, and policy makers – asthma exacerbations.”
The investigators acknowledged as limitations of their study its open-label design and that asthma diagnoses were made by community physicians with no required objective testing. In addition, the study’s high discontinuation rate and poor medicine adherence were roughly equal between treatment groups and reflective of real-world practice, they noted.
The Agency for Heathcare Research and Quality funded the study. Dr. Wechsler and several coauthors disclosed consultant fees from multiple pharmaceutical manufacturers.
Black adults with asthma did not see significant differences in time to exacerbation after adding a long-acting beta-agonist to their inhaled corticosteroid treatment, compared with adding tiotropium, according to results from a randomized, open-label trial.
Moreover, genetic variations were not associated with differences in treatment response.
The study, published online Oct. 27 in JAMA, enrolled 1,070 patients already taking or eligible for combination therapy with inhaled corticosteroids (ICS). More than 75% of patients were women, and the mean age was 45 years.
Dr. Michael E. Wechsler of Brigham and Women’s Hospital, Boston, and colleagues carried out their research at 20 primary care sites in the United States, with information on variation in ADRB2 Arg16Gly alleles captured (JAMA 2015 Oct 27;314[16]:1720-30). Patients were followed an average of 310 days.
Of 538 patients randomized to salmeterol or formoterol plus ICS, the mean number of exacerbations was 0.42 per person-year, compared with 0.37 per person-year in the 532 patients of the tiotropium plus ICS group (rate ratio, 0.90; P = .31).
The likelihood of being exacerbation free at 1 year was 74% for a long-acting beta-agonist (LABA) plus ICS, vs. 75.7% for tiotropium plus ICS (hazard ratio, 0.91; P = .47).
Other measures – including patient-reported outcomes, spirometry, rescue medication use, asthma deteriorations, and adverse events – did not differ significantly between treatment assignments. When stratified by genotype, there were no significant differences in hazard ratios for time to first exacerbation, mean number of exacerbations, or lung function at 6, 12, or 18 months.
“The study was performed in a population that bears a disproportionate burden of asthma morbidity and in whom questions have been raised about the relative efficacy and safety of LABAs,” Dr. Wechsler and colleagues wrote in their analysis.
“Because questions have been raised about whether efficacy studies correctly capture all the causes of morbidity, we conducted a clinical effectiveness study primarily in practicing physician offices,” the authors explained. “We used an outcome important to patients, physicians, and policy makers – asthma exacerbations.”
The investigators acknowledged as limitations of their study its open-label design and that asthma diagnoses were made by community physicians with no required objective testing. In addition, the study’s high discontinuation rate and poor medicine adherence were roughly equal between treatment groups and reflective of real-world practice, they noted.
The Agency for Heathcare Research and Quality funded the study. Dr. Wechsler and several coauthors disclosed consultant fees from multiple pharmaceutical manufacturers.
FROM JAMA
Key clinical point: In black patients, long-acting beta-agonists used with inhaled corticosteroids were not more effective than were tiotropium plus inhaled corticosteroids in lengthening time to asthma exacerbations.
Major finding: The risk ratio of a severe asthma exacerbation (requiring corticosteroids or hospitalization) with tiotropium plus inhaled corticosteroids vs. a LABA plus inhaled corticosteroids was 0.90 (P = .31).
Data source: A randomized, open-label study enrolling 1,070 black patients at 20 U.S. primary care sites.
Disclosures: The Agency for Healthcare Research and Quality sponsored the study. Dr. Wechsler and several coauthors disclosed consultant fees from multiple pharmaceutical manufacturers.
Treatment of postthrombolysis symptomatic hemorrhage has room to improve
Treatment of ischemic stroke patients who developed a symptomatic intracerebral hemorrhage after receiving recombinant tissue plasminogen activator did not significantly reduce risk of death in the hospital or expansion of hematomas.
However, the study also found that times to diagnosis of symptomatic intracerebral hemorrhage (sICH) were long, and reducing these could be a potential factor in treatment success.
Dr. Shadi Yaghi of Brown University, Providence, R.I., and colleagues evaluated records from 128 patients from 10 U.S. stroke centers who developed sICH after being treated with recombinant tissue plasminogen activator (3.3% of 3,894 rTPA-treated patients). Their report was published online Oct. 26 in JAMA Neurology (doi: 10.1001/jamaneurol.2015.2371).
Overall, sICH diagnosis was made more than 2 hours after initiation of intravenous rTPA therapy in 85.9% (110 of 128) of patients. A total of 38% (n = 49) received treatment for sICH, with 29% (n = 37) assigned to palliative care within 24 hours of diagnosis. More than half of patients (n = 67) died in hospital.
Assignment to palliative care was the only factor seen significantly associated with in-hospital-mortality (odds ratio, 3.6; 95% confidence interval. 1.2-10.6). Treatments for sICH varied, though the most commonly used were cryoprecipitate (31.3%), platelet transfusion, and fresh frozen plasma. Median time from initiation of rTPA to sICH diagnosis was 470 minutes (range, 30-2,572 minutes), and median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes).
Dr. Yaghi and colleagues’ study did not find statistically significant differences in effectiveness among treatments. However, they found that fibrinogen levels below 150 mg/dL were significantly associated with a hematoma expansion of 33% or more among patients who had imaging studies available for analysis. Low fibrinogen occurred in 36% of patients without hematoma expansion, compared with 25% of patients with expansion (P = .01). This suggests that cryoprecipitate, which increases fibrinogen levels, might help in reversing coagulopathy caused by rTPA, particularly if it is administered early, the authors said. “It may be reasonable to initiate empirical treatment with cryoprecipitate once sICH is diagnosed, before obtaining fibrinogen levels, and additional cryoprecipitate treatment can be given as needed once the fibrinogen level is known,” they wrote.
The researchers acknowledged that the limitations of their study included its retrospective design, relatively few sICH patients treated, and wide variety of treatments used.
Dr. Yaghi reported funding from the Stroke Trials Network of the National Institute of Neurological Disorders and Stroke. Two coauthors disclosed consultant relationships with Stryker, Covidien, and HeartWare.
Symptomatic intracerebral hemorrhage is the most feared complication after administration of intravenous TPA. Although the occurrence of sICH is uncommon, the known risk of this complication may weigh heavily on the decision to administer thrombolysis. This study by Dr. Yaghi and his colleagues provides the first comprehensive description of how thrombolysis-related sICH is managed in representative stroke centers in the United States. Although the study may have been underpowered to detect the benefit of any particular treatment, it highlights the complexity of the patient population, treatment options, and differences in clinical practice. The investigators noted delays in time to diagnosis and in the initiation of treatment for sICH, which they felt could have contributed to the lack of benefit of treatment. They also found an association between hematoma expansion and hypofibrinogenemia, supporting the rationale for administering blood products to reverse the coagulopathy induced by thrombolysis. However, hypofibrinogenemia was found only in a minority of patients. This study informs future prospective work, provides data that call for a reevaluation of our treatment of postthrombolysis sICH, and calls on the stroke community to reevaluate what an acceptable risk of thrombolysis should be.
Dr. Tiffany Cossey and Dr. Nicole R. Gonzales are with the University of Texas Health Sciences Center, Houston. They reported no conflicts of interest. Their comments are summarized from an editorial accompanying Dr. Yaghi and associates’ report (JAMA Neurol. 2015 Oct 26. doi: 10.1001/jamaneurol.2015.2900).
Symptomatic intracerebral hemorrhage is the most feared complication after administration of intravenous TPA. Although the occurrence of sICH is uncommon, the known risk of this complication may weigh heavily on the decision to administer thrombolysis. This study by Dr. Yaghi and his colleagues provides the first comprehensive description of how thrombolysis-related sICH is managed in representative stroke centers in the United States. Although the study may have been underpowered to detect the benefit of any particular treatment, it highlights the complexity of the patient population, treatment options, and differences in clinical practice. The investigators noted delays in time to diagnosis and in the initiation of treatment for sICH, which they felt could have contributed to the lack of benefit of treatment. They also found an association between hematoma expansion and hypofibrinogenemia, supporting the rationale for administering blood products to reverse the coagulopathy induced by thrombolysis. However, hypofibrinogenemia was found only in a minority of patients. This study informs future prospective work, provides data that call for a reevaluation of our treatment of postthrombolysis sICH, and calls on the stroke community to reevaluate what an acceptable risk of thrombolysis should be.
Dr. Tiffany Cossey and Dr. Nicole R. Gonzales are with the University of Texas Health Sciences Center, Houston. They reported no conflicts of interest. Their comments are summarized from an editorial accompanying Dr. Yaghi and associates’ report (JAMA Neurol. 2015 Oct 26. doi: 10.1001/jamaneurol.2015.2900).
Symptomatic intracerebral hemorrhage is the most feared complication after administration of intravenous TPA. Although the occurrence of sICH is uncommon, the known risk of this complication may weigh heavily on the decision to administer thrombolysis. This study by Dr. Yaghi and his colleagues provides the first comprehensive description of how thrombolysis-related sICH is managed in representative stroke centers in the United States. Although the study may have been underpowered to detect the benefit of any particular treatment, it highlights the complexity of the patient population, treatment options, and differences in clinical practice. The investigators noted delays in time to diagnosis and in the initiation of treatment for sICH, which they felt could have contributed to the lack of benefit of treatment. They also found an association between hematoma expansion and hypofibrinogenemia, supporting the rationale for administering blood products to reverse the coagulopathy induced by thrombolysis. However, hypofibrinogenemia was found only in a minority of patients. This study informs future prospective work, provides data that call for a reevaluation of our treatment of postthrombolysis sICH, and calls on the stroke community to reevaluate what an acceptable risk of thrombolysis should be.
Dr. Tiffany Cossey and Dr. Nicole R. Gonzales are with the University of Texas Health Sciences Center, Houston. They reported no conflicts of interest. Their comments are summarized from an editorial accompanying Dr. Yaghi and associates’ report (JAMA Neurol. 2015 Oct 26. doi: 10.1001/jamaneurol.2015.2900).
Treatment of ischemic stroke patients who developed a symptomatic intracerebral hemorrhage after receiving recombinant tissue plasminogen activator did not significantly reduce risk of death in the hospital or expansion of hematomas.
However, the study also found that times to diagnosis of symptomatic intracerebral hemorrhage (sICH) were long, and reducing these could be a potential factor in treatment success.
Dr. Shadi Yaghi of Brown University, Providence, R.I., and colleagues evaluated records from 128 patients from 10 U.S. stroke centers who developed sICH after being treated with recombinant tissue plasminogen activator (3.3% of 3,894 rTPA-treated patients). Their report was published online Oct. 26 in JAMA Neurology (doi: 10.1001/jamaneurol.2015.2371).
Overall, sICH diagnosis was made more than 2 hours after initiation of intravenous rTPA therapy in 85.9% (110 of 128) of patients. A total of 38% (n = 49) received treatment for sICH, with 29% (n = 37) assigned to palliative care within 24 hours of diagnosis. More than half of patients (n = 67) died in hospital.
Assignment to palliative care was the only factor seen significantly associated with in-hospital-mortality (odds ratio, 3.6; 95% confidence interval. 1.2-10.6). Treatments for sICH varied, though the most commonly used were cryoprecipitate (31.3%), platelet transfusion, and fresh frozen plasma. Median time from initiation of rTPA to sICH diagnosis was 470 minutes (range, 30-2,572 minutes), and median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes).
Dr. Yaghi and colleagues’ study did not find statistically significant differences in effectiveness among treatments. However, they found that fibrinogen levels below 150 mg/dL were significantly associated with a hematoma expansion of 33% or more among patients who had imaging studies available for analysis. Low fibrinogen occurred in 36% of patients without hematoma expansion, compared with 25% of patients with expansion (P = .01). This suggests that cryoprecipitate, which increases fibrinogen levels, might help in reversing coagulopathy caused by rTPA, particularly if it is administered early, the authors said. “It may be reasonable to initiate empirical treatment with cryoprecipitate once sICH is diagnosed, before obtaining fibrinogen levels, and additional cryoprecipitate treatment can be given as needed once the fibrinogen level is known,” they wrote.
The researchers acknowledged that the limitations of their study included its retrospective design, relatively few sICH patients treated, and wide variety of treatments used.
Dr. Yaghi reported funding from the Stroke Trials Network of the National Institute of Neurological Disorders and Stroke. Two coauthors disclosed consultant relationships with Stryker, Covidien, and HeartWare.
Treatment of ischemic stroke patients who developed a symptomatic intracerebral hemorrhage after receiving recombinant tissue plasminogen activator did not significantly reduce risk of death in the hospital or expansion of hematomas.
However, the study also found that times to diagnosis of symptomatic intracerebral hemorrhage (sICH) were long, and reducing these could be a potential factor in treatment success.
Dr. Shadi Yaghi of Brown University, Providence, R.I., and colleagues evaluated records from 128 patients from 10 U.S. stroke centers who developed sICH after being treated with recombinant tissue plasminogen activator (3.3% of 3,894 rTPA-treated patients). Their report was published online Oct. 26 in JAMA Neurology (doi: 10.1001/jamaneurol.2015.2371).
Overall, sICH diagnosis was made more than 2 hours after initiation of intravenous rTPA therapy in 85.9% (110 of 128) of patients. A total of 38% (n = 49) received treatment for sICH, with 29% (n = 37) assigned to palliative care within 24 hours of diagnosis. More than half of patients (n = 67) died in hospital.
Assignment to palliative care was the only factor seen significantly associated with in-hospital-mortality (odds ratio, 3.6; 95% confidence interval. 1.2-10.6). Treatments for sICH varied, though the most commonly used were cryoprecipitate (31.3%), platelet transfusion, and fresh frozen plasma. Median time from initiation of rTPA to sICH diagnosis was 470 minutes (range, 30-2,572 minutes), and median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes).
Dr. Yaghi and colleagues’ study did not find statistically significant differences in effectiveness among treatments. However, they found that fibrinogen levels below 150 mg/dL were significantly associated with a hematoma expansion of 33% or more among patients who had imaging studies available for analysis. Low fibrinogen occurred in 36% of patients without hematoma expansion, compared with 25% of patients with expansion (P = .01). This suggests that cryoprecipitate, which increases fibrinogen levels, might help in reversing coagulopathy caused by rTPA, particularly if it is administered early, the authors said. “It may be reasonable to initiate empirical treatment with cryoprecipitate once sICH is diagnosed, before obtaining fibrinogen levels, and additional cryoprecipitate treatment can be given as needed once the fibrinogen level is known,” they wrote.
The researchers acknowledged that the limitations of their study included its retrospective design, relatively few sICH patients treated, and wide variety of treatments used.
Dr. Yaghi reported funding from the Stroke Trials Network of the National Institute of Neurological Disorders and Stroke. Two coauthors disclosed consultant relationships with Stryker, Covidien, and HeartWare.
FROM JAMA NEUROLOGY
Key clinical point: Symptomatic intracerebral hemorrhage, a rare but serious complication of stroke treatment with recombinant tissue plasminogen activator, can likely be treated better and faster.
Major finding: The median times from initiation of rTPA therapy to sICH diagnosis was 470 minutes (range, 30-2,572 minutes) and from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes).
Data source: A retrospective study of 128 ischemic stroke patients with postthrombolysis sICH from 10 U.S. stroke centers.
Disclosures: The first author was funded by Stroke Trials Network, and two coauthors disclosed industry relationships.
Worsening of lesions on MRI predicts knee OA
People without x-ray evidence of osteoarthritis in their knees but with MRI-identified lesions that worsen over time are significantly likelier to develop knee OA, compared with people whose lesions remain stable, according to results from a prospective cohort study.
For their research, published Oct. 14 in Annals of the Rheumatic Diseases, Dr. Leena Sharma of Northwestern University in Chicago and her colleagues recruited more than 1,000 patients at elevated risk of knee OA but with no radiographic evidence yet of disease (Kellgren/Lawrence measures of 0 [KL0] in both knees) to test their hypothesis that lesions seen worsening over time on MRI were predictive of knee OA within 4 years and of persistent symptoms between 4 and 7 years. Patients in the cohort (56% women, mean age 59.6 years) were assessed for cartilage damage, meniscal tears, meniscal extrusions, and bone marrow lesions at 12 and 48 months. Study inclusion required that patients remain at KL0 in both knees at 12 months to continue, and 849 patients had complete data at 12 and 48 months.
Patients with lesions that had worsened on MRI between 12 and 48 months had significantly higher risk of incident radiographic KL1 and KL2 by 48 months, compared with patients whose lesions had not worsened. For example, 6.3% of patients with tibiofemoral cartilage damage that was stable at 48 months developed mild (KL1) disease at 48 months, compared with 9.5% of patients whose damage had worsened in that interval (odds ratio, 2.69; 95% confidence interval, 1.50-4.84). Half of patients with worsening meniscal extrusion developed mild knee OA by the endpoint, compared with 13.6% of patients with a stable lesion (OR, 5.73; 95% CI, 2.94-11.16). Higher risk of KL1 or KL2 at 48 months was significant for all the lesion types studied except bone marrow lesions. Worsening of these lesions between 12 and 48 months was also significantly associated with having persistent symptoms between 4 and 7 years. Having more lesion types that worsened was significantly associated with worse outcomes.
The findings, Dr. Sharma and her colleagues wrote, support the idea of stable and progressive disease phases with early indicators of each and that worsening lesions represent early osteoarthritis. “Given the absence of disease-modifying therapy for OA, widespread clinical application of MRI is difficult to justify,” the investigators wrote in their analysis (Ann Rheum Dis. 2015 Oct 14. doi: 10.1136/annrheumdis-2015-208129).
Nevertheless, they concluded, “prevention or delay of worsening of early-stage lesions should be considered as a target for emerging pharmacological and nonpharmacological treatments in an effort to prevent or delay full-blown disease. Candidate interventions should be studied at this stage, when they are more likely to be effective.” Investigators acknowledged that one limitation of the study was that its findings may not apply in populations not already at higher risk for knee OA.
The study was funded by the Osteoarthritis Initiative, a public-private partnership of the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer, with industry funding administered by NIH.
People without x-ray evidence of osteoarthritis in their knees but with MRI-identified lesions that worsen over time are significantly likelier to develop knee OA, compared with people whose lesions remain stable, according to results from a prospective cohort study.
For their research, published Oct. 14 in Annals of the Rheumatic Diseases, Dr. Leena Sharma of Northwestern University in Chicago and her colleagues recruited more than 1,000 patients at elevated risk of knee OA but with no radiographic evidence yet of disease (Kellgren/Lawrence measures of 0 [KL0] in both knees) to test their hypothesis that lesions seen worsening over time on MRI were predictive of knee OA within 4 years and of persistent symptoms between 4 and 7 years. Patients in the cohort (56% women, mean age 59.6 years) were assessed for cartilage damage, meniscal tears, meniscal extrusions, and bone marrow lesions at 12 and 48 months. Study inclusion required that patients remain at KL0 in both knees at 12 months to continue, and 849 patients had complete data at 12 and 48 months.
Patients with lesions that had worsened on MRI between 12 and 48 months had significantly higher risk of incident radiographic KL1 and KL2 by 48 months, compared with patients whose lesions had not worsened. For example, 6.3% of patients with tibiofemoral cartilage damage that was stable at 48 months developed mild (KL1) disease at 48 months, compared with 9.5% of patients whose damage had worsened in that interval (odds ratio, 2.69; 95% confidence interval, 1.50-4.84). Half of patients with worsening meniscal extrusion developed mild knee OA by the endpoint, compared with 13.6% of patients with a stable lesion (OR, 5.73; 95% CI, 2.94-11.16). Higher risk of KL1 or KL2 at 48 months was significant for all the lesion types studied except bone marrow lesions. Worsening of these lesions between 12 and 48 months was also significantly associated with having persistent symptoms between 4 and 7 years. Having more lesion types that worsened was significantly associated with worse outcomes.
The findings, Dr. Sharma and her colleagues wrote, support the idea of stable and progressive disease phases with early indicators of each and that worsening lesions represent early osteoarthritis. “Given the absence of disease-modifying therapy for OA, widespread clinical application of MRI is difficult to justify,” the investigators wrote in their analysis (Ann Rheum Dis. 2015 Oct 14. doi: 10.1136/annrheumdis-2015-208129).
Nevertheless, they concluded, “prevention or delay of worsening of early-stage lesions should be considered as a target for emerging pharmacological and nonpharmacological treatments in an effort to prevent or delay full-blown disease. Candidate interventions should be studied at this stage, when they are more likely to be effective.” Investigators acknowledged that one limitation of the study was that its findings may not apply in populations not already at higher risk for knee OA.
The study was funded by the Osteoarthritis Initiative, a public-private partnership of the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer, with industry funding administered by NIH.
People without x-ray evidence of osteoarthritis in their knees but with MRI-identified lesions that worsen over time are significantly likelier to develop knee OA, compared with people whose lesions remain stable, according to results from a prospective cohort study.
For their research, published Oct. 14 in Annals of the Rheumatic Diseases, Dr. Leena Sharma of Northwestern University in Chicago and her colleagues recruited more than 1,000 patients at elevated risk of knee OA but with no radiographic evidence yet of disease (Kellgren/Lawrence measures of 0 [KL0] in both knees) to test their hypothesis that lesions seen worsening over time on MRI were predictive of knee OA within 4 years and of persistent symptoms between 4 and 7 years. Patients in the cohort (56% women, mean age 59.6 years) were assessed for cartilage damage, meniscal tears, meniscal extrusions, and bone marrow lesions at 12 and 48 months. Study inclusion required that patients remain at KL0 in both knees at 12 months to continue, and 849 patients had complete data at 12 and 48 months.
Patients with lesions that had worsened on MRI between 12 and 48 months had significantly higher risk of incident radiographic KL1 and KL2 by 48 months, compared with patients whose lesions had not worsened. For example, 6.3% of patients with tibiofemoral cartilage damage that was stable at 48 months developed mild (KL1) disease at 48 months, compared with 9.5% of patients whose damage had worsened in that interval (odds ratio, 2.69; 95% confidence interval, 1.50-4.84). Half of patients with worsening meniscal extrusion developed mild knee OA by the endpoint, compared with 13.6% of patients with a stable lesion (OR, 5.73; 95% CI, 2.94-11.16). Higher risk of KL1 or KL2 at 48 months was significant for all the lesion types studied except bone marrow lesions. Worsening of these lesions between 12 and 48 months was also significantly associated with having persistent symptoms between 4 and 7 years. Having more lesion types that worsened was significantly associated with worse outcomes.
The findings, Dr. Sharma and her colleagues wrote, support the idea of stable and progressive disease phases with early indicators of each and that worsening lesions represent early osteoarthritis. “Given the absence of disease-modifying therapy for OA, widespread clinical application of MRI is difficult to justify,” the investigators wrote in their analysis (Ann Rheum Dis. 2015 Oct 14. doi: 10.1136/annrheumdis-2015-208129).
Nevertheless, they concluded, “prevention or delay of worsening of early-stage lesions should be considered as a target for emerging pharmacological and nonpharmacological treatments in an effort to prevent or delay full-blown disease. Candidate interventions should be studied at this stage, when they are more likely to be effective.” Investigators acknowledged that one limitation of the study was that its findings may not apply in populations not already at higher risk for knee OA.
The study was funded by the Osteoarthritis Initiative, a public-private partnership of the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer, with industry funding administered by NIH.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: People with knee cartilage damage, meniscal tear, meniscal extrusion, and bone marrow lesions on MRI were likelier to have developed knee osteoarthritis at 48 months, compared with people with stable lesions; more lesion types at baseline were associated with worse outcomes.
Major finding: Higher-risk mild or moderate radiographic knee OA at 48 months was significant for most types of lesions that had worsened after 12 months.
Data source: A prospective cohort study of 849 people at high risk of knee osteoarthritis evaluated on radiography (for evidence of knee OA) and MRI (for lesions) at baseline, 12 months, and 48 months and followed up for symptoms through 84 months.
Disclosures: The study was funded by the Osteoarthritis Initiative, a public-private partnership of the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer, with industry funding administered by NIH. The study authors disclosed no conflicts of interest.
Serum HA cutoff predicts progression in knee OA
Serum concentration of hyaluronic acid correlated with the severity of knee osteoarthritis in a longitudinal population-based cohort, with concentrations above 51.9 ng/mL significantly associated with progression in people with moderate disease.
While previous studies have suggested cutoff values for serum hyaluronic acid (HA) as biomarkers for progression of knee osteoarthritis, this study, conducted by Dr. Eiji Sasaki of Hirosaki (Japan) University and his colleagues, is the first to report a serum HA cutoff value from a longitudinal study.
The investigators prospectively enrolled 720 volunteers into a community-based preventive medicine program with intent to follow them for 5 years. They excluded patients with renal failure, liver failure, rheumatoid arthritis, or cancer, as all of these can increase serum HA. HA concentrations and knee radiography were taken at baseline and at 5-year follow-up, with complete data from 444 patients (mean age 55, 64% female) entered into analysis. Dr. Sasaki and his colleagues measured severity of knee osteoarthritis using Kellgren-Lawrence grades. Higher serum HA at baseline correlated with KL grade progression in the cohort as a whole (P = .004), and HA concentration was linked to joint space narrowing in knees with no disease or mild disease (KL grades 0-1) and moderate disease (KL grades 2 or 3) at baseline (P = .021 and P = .008, respectively).
Serum HA of 51.9 ng/mL was predictive of knee osteoarthritis progression in subjects (n = 119) with KL grades 2 or 3 disease (area under curve [AUC], 0.707), and associated with a fivefold increase (odds ratio, 4.89) in risk of joint space narrowing over 5 years. For people with mild or no disease at baseline (n = 323), Dr. Sasaki and his colleagues identified a cutoff of 35.1 ng/mL for the development of OA, but it was not a robust indicator with an AUC of 0.603 (Arthritis Res Ther. 2015;17:283. doi: 10.1186/s13075-015-0793-0).
“Further clinical studies are needed to determine whether serum HA can predict the incidence of OA, which was not determined in the present study,” Dr. Sasaki and his colleagues wrote in their analysis. They noted that the cutoff value of 51.9 ng/mL “should be useful during screening for abnormal knee conditions or as an additional evaluation for the risk of OA progression when used in combination with conventional imaging tools.”
The study was funded by grants from the Japanese government, the Japanese Society for the Promotion of Science, and the Japanese Orthopedic Association. Dr. Sasaki and colleagues declared no conflicts of interest.
Serum concentration of hyaluronic acid correlated with the severity of knee osteoarthritis in a longitudinal population-based cohort, with concentrations above 51.9 ng/mL significantly associated with progression in people with moderate disease.
While previous studies have suggested cutoff values for serum hyaluronic acid (HA) as biomarkers for progression of knee osteoarthritis, this study, conducted by Dr. Eiji Sasaki of Hirosaki (Japan) University and his colleagues, is the first to report a serum HA cutoff value from a longitudinal study.
The investigators prospectively enrolled 720 volunteers into a community-based preventive medicine program with intent to follow them for 5 years. They excluded patients with renal failure, liver failure, rheumatoid arthritis, or cancer, as all of these can increase serum HA. HA concentrations and knee radiography were taken at baseline and at 5-year follow-up, with complete data from 444 patients (mean age 55, 64% female) entered into analysis. Dr. Sasaki and his colleagues measured severity of knee osteoarthritis using Kellgren-Lawrence grades. Higher serum HA at baseline correlated with KL grade progression in the cohort as a whole (P = .004), and HA concentration was linked to joint space narrowing in knees with no disease or mild disease (KL grades 0-1) and moderate disease (KL grades 2 or 3) at baseline (P = .021 and P = .008, respectively).
Serum HA of 51.9 ng/mL was predictive of knee osteoarthritis progression in subjects (n = 119) with KL grades 2 or 3 disease (area under curve [AUC], 0.707), and associated with a fivefold increase (odds ratio, 4.89) in risk of joint space narrowing over 5 years. For people with mild or no disease at baseline (n = 323), Dr. Sasaki and his colleagues identified a cutoff of 35.1 ng/mL for the development of OA, but it was not a robust indicator with an AUC of 0.603 (Arthritis Res Ther. 2015;17:283. doi: 10.1186/s13075-015-0793-0).
“Further clinical studies are needed to determine whether serum HA can predict the incidence of OA, which was not determined in the present study,” Dr. Sasaki and his colleagues wrote in their analysis. They noted that the cutoff value of 51.9 ng/mL “should be useful during screening for abnormal knee conditions or as an additional evaluation for the risk of OA progression when used in combination with conventional imaging tools.”
The study was funded by grants from the Japanese government, the Japanese Society for the Promotion of Science, and the Japanese Orthopedic Association. Dr. Sasaki and colleagues declared no conflicts of interest.
Serum concentration of hyaluronic acid correlated with the severity of knee osteoarthritis in a longitudinal population-based cohort, with concentrations above 51.9 ng/mL significantly associated with progression in people with moderate disease.
While previous studies have suggested cutoff values for serum hyaluronic acid (HA) as biomarkers for progression of knee osteoarthritis, this study, conducted by Dr. Eiji Sasaki of Hirosaki (Japan) University and his colleagues, is the first to report a serum HA cutoff value from a longitudinal study.
The investigators prospectively enrolled 720 volunteers into a community-based preventive medicine program with intent to follow them for 5 years. They excluded patients with renal failure, liver failure, rheumatoid arthritis, or cancer, as all of these can increase serum HA. HA concentrations and knee radiography were taken at baseline and at 5-year follow-up, with complete data from 444 patients (mean age 55, 64% female) entered into analysis. Dr. Sasaki and his colleagues measured severity of knee osteoarthritis using Kellgren-Lawrence grades. Higher serum HA at baseline correlated with KL grade progression in the cohort as a whole (P = .004), and HA concentration was linked to joint space narrowing in knees with no disease or mild disease (KL grades 0-1) and moderate disease (KL grades 2 or 3) at baseline (P = .021 and P = .008, respectively).
Serum HA of 51.9 ng/mL was predictive of knee osteoarthritis progression in subjects (n = 119) with KL grades 2 or 3 disease (area under curve [AUC], 0.707), and associated with a fivefold increase (odds ratio, 4.89) in risk of joint space narrowing over 5 years. For people with mild or no disease at baseline (n = 323), Dr. Sasaki and his colleagues identified a cutoff of 35.1 ng/mL for the development of OA, but it was not a robust indicator with an AUC of 0.603 (Arthritis Res Ther. 2015;17:283. doi: 10.1186/s13075-015-0793-0).
“Further clinical studies are needed to determine whether serum HA can predict the incidence of OA, which was not determined in the present study,” Dr. Sasaki and his colleagues wrote in their analysis. They noted that the cutoff value of 51.9 ng/mL “should be useful during screening for abnormal knee conditions or as an additional evaluation for the risk of OA progression when used in combination with conventional imaging tools.”
The study was funded by grants from the Japanese government, the Japanese Society for the Promotion of Science, and the Japanese Orthopedic Association. Dr. Sasaki and colleagues declared no conflicts of interest.
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point: Serum HA of 51.9 ng/mL predicts a fivefold increase in risk of progression of existing knee osteoarthritis over 5 years.
Major Finding: Higher sHA concentration was positively correlated with progression of joint space narrowing in people with none-to-mild (P = .021) and moderate (P = .008) knee OA at baseline. Higher concentrations correlated with OA progression as measured by Kellgren-Lawrence grades (P = .004).
Data source: A population-based cohort of 866 people from a community in Japan; 444 subjects received knee radiography and serum HA analysis at baseline and 5-year follow-up.
Disclosures: The study was funded by government and foundation grants in Japan; the investigators disclosed no conflicts of interest.
Better outcomes with open surgery vs. laparoscopic for rectal cancer
Two randomized studies of rectal cancer surgeries using highly qualified surgeons were not able to show that laparoscopic procedures produce results equal to open ones.
The studies, published online in JAMA, each enrolled slightly under 500 patients at multiple sites, randomized them to open pelvic dissection or laparoscopic dissection, and selected surgeons with exceptional skills.
Both studies found rates of pathologist-determined adequate surgical dissection to be slightly lower for patients undergoing the laparoscopic procedures.
The North American study was carried out under the American College of Surgeons Oncology Group and led by Dr. James Fleshman of Baylor University Medical Center, Dallas. The study, which took place at 35 surgical centers, enrolled 486 patients with stage II or III rectal cancer within 12 cm of the anal verge who were randomized after neoadjuvant therapy to minimally invasive (n = 240) or open proctectomy (n=222) (JAMA. 2015;314[13]:1346-55).
Success was measured by pathologic oncologic markers related to quality of the rectal specimen: a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimations for this patient group.
Successful resection occurred in 82% of laparoscopic resection cases (95% confidence interval, 76.8%-86.6%) and 87% of open cases (95% CI, 82.5%-91.4%). The results did not support noninferiority for laparoscopic procedures (P = .41).
The finding came as a surprise, Dr. Fleshman and colleagues wrote in their analysis, not least because of the skill level of the surgeons participating in the study. A group of “highly motivated, credentialed, expert laparoscopic rectal surgeons was ideal to test this hypothesis,” they wrote. Moreover, only 11% of patients assigned laparoscopy had to be converted to open procedures, “so the learning curve cannot be invoked to explain our results because conversion rates were reasonable.”
More likely, they wrote, “the technique itself, along with the current methodology available, must be questioned if motivated experts cannot produce a quality specimen defined by this novel combined metric.”
Proctectomy is always challenging, Dr. Fleshman and colleagues wrote, “and it can be even more difficult to work in the deep pelvis with in-line rigid instruments from angles that require complicated maneuvers to reach the extremes of the pelvis. It is possible that modification of instruments or a different platform such as robotics will improve efficacy of minimally invasive techniques.”
The Australian study, carried out by the Australasian Gastro-Intestinal Trials Group network and led by Dr. Andrew R. L. Stevenson of the University of Queensland and Royal Brisbane and Women’s Hospital, Brisbane, Australia, enrolled 475 patients with T1-3 rectal tumors less than 15 cm from the anal verge and randomized them to laparoscopic (n = 238) or open (n = 235) pelvic dissection. Half of patients had received radiotherapy before the operations. Some 26 surgeons operated at 24 sites in Australia and New Zealand. (JAMA. 2015;314[13]:1356-63).
For this trial, successful resection was defined as complete total mesorectal excision, a clear circumferential margin of at least 1 mm, and a clear distal resection margin of 1 mm or more. The prescribed noninferiority margin for this patient group was 8%. As in the North American study, pathologists were blinded to the method of surgery.
Successful resection occurred in 194 patients (82%) in the laparoscopic group and 208 (89%) in the open surgery group, not reaching noninferiority for the laparoscopic approach (P = 0.38 for noninferiority). Conversion to open dissection occurred in 9% of the laparoscopy-assigned patients.
“Even though our trial was not designed to demonstrate whether one method of rectal dissection was superior to the other, the inability to establish noninferiority suggests that surgeons should be cautious when considering the suitability of a laparoscopic approach for a patient with rectal cancer,” Dr. Stevenson and colleagues wrote in their analysis.
“Subgroup analyses raise the possibility that laparoscopic surgery might be less successful than open surgery in patients who have received neoadjuvant therapy, have larger T3 tumors, or have higher BMIs. However, our study was underpowered to show significant differences in proportions of lower success rates for laparoscopic surgery vs. open surgery.”
The North American trial was funded by the National Cancer Institute, the American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, and the Covidien Company. Dr. Fleshman reported no conflicts, while several coauthors disclosed financial relationships with surgical device manufacturers, including Covidien.
The Australasian trial was funded by the Colorectal Surgical Society of Australia and New Zealand and the National Health and Medical Research Council. No conflicts of interest were reported.
The studies by Fleshman et al. and Stevenson et al. have set a standard for surgeons performing these complex operations and the surgical expertise that must be ensured when conducting randomized clinical trials. In both studies, only surgeons accredited after video review of relevant operations were allowed to participate, and the primary outcome was defined as the adequacy of surgical dissection as assessed by completeness of the total mesorectal excision, uninvolved CRM, and uninvolved distal resection margin. The technical quality of surgery in both trials was high as demonstrated by few laparoscopic conversions, high sphincter preservation rates, and low rates of anastomotic leakage and other complications in these study groups that included high-risk overweight patients, the majority of whom were male. Likewise, the composite pathologic success rate based on meeting all three surgical dissection criteria was very high. However, in both studies, the adequacy of surgical dissection tended to be lower in the minimally invasive group, compared with the open resection group despite comparable low rates of distal margin involvement. Although several nonrandomized studies with inherent selection bias have described the overall advantages of a minimally invasive approach for patients with rectal cancer or complicated diverticulitis, these large, randomized, multicenter trials substantiate recent findings from similar randomized trials. A laparoscopic resection may not be oncologically justified in many patients requiring proctectomy for rectal cancer. The studies do not signal a moratorium on laparoscopic approaches, but surgeons must proceed in a judicious manner to ensure that patients are informed about the benefits and risks associated with minimally invasive and open operations.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University Feinberg School of Medicine, Chicago. Dr. Strong and Dr. Soper declared no conflicts of interest. These remarks were excerpted from an accompanying editorial (JAMA. 2015 Oct 6. doi: 10.1001/jama.2015.11454).
The studies by Fleshman et al. and Stevenson et al. have set a standard for surgeons performing these complex operations and the surgical expertise that must be ensured when conducting randomized clinical trials. In both studies, only surgeons accredited after video review of relevant operations were allowed to participate, and the primary outcome was defined as the adequacy of surgical dissection as assessed by completeness of the total mesorectal excision, uninvolved CRM, and uninvolved distal resection margin. The technical quality of surgery in both trials was high as demonstrated by few laparoscopic conversions, high sphincter preservation rates, and low rates of anastomotic leakage and other complications in these study groups that included high-risk overweight patients, the majority of whom were male. Likewise, the composite pathologic success rate based on meeting all three surgical dissection criteria was very high. However, in both studies, the adequacy of surgical dissection tended to be lower in the minimally invasive group, compared with the open resection group despite comparable low rates of distal margin involvement. Although several nonrandomized studies with inherent selection bias have described the overall advantages of a minimally invasive approach for patients with rectal cancer or complicated diverticulitis, these large, randomized, multicenter trials substantiate recent findings from similar randomized trials. A laparoscopic resection may not be oncologically justified in many patients requiring proctectomy for rectal cancer. The studies do not signal a moratorium on laparoscopic approaches, but surgeons must proceed in a judicious manner to ensure that patients are informed about the benefits and risks associated with minimally invasive and open operations.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University Feinberg School of Medicine, Chicago. Dr. Strong and Dr. Soper declared no conflicts of interest. These remarks were excerpted from an accompanying editorial (JAMA. 2015 Oct 6. doi: 10.1001/jama.2015.11454).
The studies by Fleshman et al. and Stevenson et al. have set a standard for surgeons performing these complex operations and the surgical expertise that must be ensured when conducting randomized clinical trials. In both studies, only surgeons accredited after video review of relevant operations were allowed to participate, and the primary outcome was defined as the adequacy of surgical dissection as assessed by completeness of the total mesorectal excision, uninvolved CRM, and uninvolved distal resection margin. The technical quality of surgery in both trials was high as demonstrated by few laparoscopic conversions, high sphincter preservation rates, and low rates of anastomotic leakage and other complications in these study groups that included high-risk overweight patients, the majority of whom were male. Likewise, the composite pathologic success rate based on meeting all three surgical dissection criteria was very high. However, in both studies, the adequacy of surgical dissection tended to be lower in the minimally invasive group, compared with the open resection group despite comparable low rates of distal margin involvement. Although several nonrandomized studies with inherent selection bias have described the overall advantages of a minimally invasive approach for patients with rectal cancer or complicated diverticulitis, these large, randomized, multicenter trials substantiate recent findings from similar randomized trials. A laparoscopic resection may not be oncologically justified in many patients requiring proctectomy for rectal cancer. The studies do not signal a moratorium on laparoscopic approaches, but surgeons must proceed in a judicious manner to ensure that patients are informed about the benefits and risks associated with minimally invasive and open operations.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University Feinberg School of Medicine, Chicago. Dr. Strong and Dr. Soper declared no conflicts of interest. These remarks were excerpted from an accompanying editorial (JAMA. 2015 Oct 6. doi: 10.1001/jama.2015.11454).
Two randomized studies of rectal cancer surgeries using highly qualified surgeons were not able to show that laparoscopic procedures produce results equal to open ones.
The studies, published online in JAMA, each enrolled slightly under 500 patients at multiple sites, randomized them to open pelvic dissection or laparoscopic dissection, and selected surgeons with exceptional skills.
Both studies found rates of pathologist-determined adequate surgical dissection to be slightly lower for patients undergoing the laparoscopic procedures.
The North American study was carried out under the American College of Surgeons Oncology Group and led by Dr. James Fleshman of Baylor University Medical Center, Dallas. The study, which took place at 35 surgical centers, enrolled 486 patients with stage II or III rectal cancer within 12 cm of the anal verge who were randomized after neoadjuvant therapy to minimally invasive (n = 240) or open proctectomy (n=222) (JAMA. 2015;314[13]:1346-55).
Success was measured by pathologic oncologic markers related to quality of the rectal specimen: a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimations for this patient group.
Successful resection occurred in 82% of laparoscopic resection cases (95% confidence interval, 76.8%-86.6%) and 87% of open cases (95% CI, 82.5%-91.4%). The results did not support noninferiority for laparoscopic procedures (P = .41).
The finding came as a surprise, Dr. Fleshman and colleagues wrote in their analysis, not least because of the skill level of the surgeons participating in the study. A group of “highly motivated, credentialed, expert laparoscopic rectal surgeons was ideal to test this hypothesis,” they wrote. Moreover, only 11% of patients assigned laparoscopy had to be converted to open procedures, “so the learning curve cannot be invoked to explain our results because conversion rates were reasonable.”
More likely, they wrote, “the technique itself, along with the current methodology available, must be questioned if motivated experts cannot produce a quality specimen defined by this novel combined metric.”
Proctectomy is always challenging, Dr. Fleshman and colleagues wrote, “and it can be even more difficult to work in the deep pelvis with in-line rigid instruments from angles that require complicated maneuvers to reach the extremes of the pelvis. It is possible that modification of instruments or a different platform such as robotics will improve efficacy of minimally invasive techniques.”
The Australian study, carried out by the Australasian Gastro-Intestinal Trials Group network and led by Dr. Andrew R. L. Stevenson of the University of Queensland and Royal Brisbane and Women’s Hospital, Brisbane, Australia, enrolled 475 patients with T1-3 rectal tumors less than 15 cm from the anal verge and randomized them to laparoscopic (n = 238) or open (n = 235) pelvic dissection. Half of patients had received radiotherapy before the operations. Some 26 surgeons operated at 24 sites in Australia and New Zealand. (JAMA. 2015;314[13]:1356-63).
For this trial, successful resection was defined as complete total mesorectal excision, a clear circumferential margin of at least 1 mm, and a clear distal resection margin of 1 mm or more. The prescribed noninferiority margin for this patient group was 8%. As in the North American study, pathologists were blinded to the method of surgery.
Successful resection occurred in 194 patients (82%) in the laparoscopic group and 208 (89%) in the open surgery group, not reaching noninferiority for the laparoscopic approach (P = 0.38 for noninferiority). Conversion to open dissection occurred in 9% of the laparoscopy-assigned patients.
“Even though our trial was not designed to demonstrate whether one method of rectal dissection was superior to the other, the inability to establish noninferiority suggests that surgeons should be cautious when considering the suitability of a laparoscopic approach for a patient with rectal cancer,” Dr. Stevenson and colleagues wrote in their analysis.
“Subgroup analyses raise the possibility that laparoscopic surgery might be less successful than open surgery in patients who have received neoadjuvant therapy, have larger T3 tumors, or have higher BMIs. However, our study was underpowered to show significant differences in proportions of lower success rates for laparoscopic surgery vs. open surgery.”
The North American trial was funded by the National Cancer Institute, the American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, and the Covidien Company. Dr. Fleshman reported no conflicts, while several coauthors disclosed financial relationships with surgical device manufacturers, including Covidien.
The Australasian trial was funded by the Colorectal Surgical Society of Australia and New Zealand and the National Health and Medical Research Council. No conflicts of interest were reported.
Two randomized studies of rectal cancer surgeries using highly qualified surgeons were not able to show that laparoscopic procedures produce results equal to open ones.
The studies, published online in JAMA, each enrolled slightly under 500 patients at multiple sites, randomized them to open pelvic dissection or laparoscopic dissection, and selected surgeons with exceptional skills.
Both studies found rates of pathologist-determined adequate surgical dissection to be slightly lower for patients undergoing the laparoscopic procedures.
The North American study was carried out under the American College of Surgeons Oncology Group and led by Dr. James Fleshman of Baylor University Medical Center, Dallas. The study, which took place at 35 surgical centers, enrolled 486 patients with stage II or III rectal cancer within 12 cm of the anal verge who were randomized after neoadjuvant therapy to minimally invasive (n = 240) or open proctectomy (n=222) (JAMA. 2015;314[13]:1346-55).
Success was measured by pathologic oncologic markers related to quality of the rectal specimen: a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimations for this patient group.
Successful resection occurred in 82% of laparoscopic resection cases (95% confidence interval, 76.8%-86.6%) and 87% of open cases (95% CI, 82.5%-91.4%). The results did not support noninferiority for laparoscopic procedures (P = .41).
The finding came as a surprise, Dr. Fleshman and colleagues wrote in their analysis, not least because of the skill level of the surgeons participating in the study. A group of “highly motivated, credentialed, expert laparoscopic rectal surgeons was ideal to test this hypothesis,” they wrote. Moreover, only 11% of patients assigned laparoscopy had to be converted to open procedures, “so the learning curve cannot be invoked to explain our results because conversion rates were reasonable.”
More likely, they wrote, “the technique itself, along with the current methodology available, must be questioned if motivated experts cannot produce a quality specimen defined by this novel combined metric.”
Proctectomy is always challenging, Dr. Fleshman and colleagues wrote, “and it can be even more difficult to work in the deep pelvis with in-line rigid instruments from angles that require complicated maneuvers to reach the extremes of the pelvis. It is possible that modification of instruments or a different platform such as robotics will improve efficacy of minimally invasive techniques.”
The Australian study, carried out by the Australasian Gastro-Intestinal Trials Group network and led by Dr. Andrew R. L. Stevenson of the University of Queensland and Royal Brisbane and Women’s Hospital, Brisbane, Australia, enrolled 475 patients with T1-3 rectal tumors less than 15 cm from the anal verge and randomized them to laparoscopic (n = 238) or open (n = 235) pelvic dissection. Half of patients had received radiotherapy before the operations. Some 26 surgeons operated at 24 sites in Australia and New Zealand. (JAMA. 2015;314[13]:1356-63).
For this trial, successful resection was defined as complete total mesorectal excision, a clear circumferential margin of at least 1 mm, and a clear distal resection margin of 1 mm or more. The prescribed noninferiority margin for this patient group was 8%. As in the North American study, pathologists were blinded to the method of surgery.
Successful resection occurred in 194 patients (82%) in the laparoscopic group and 208 (89%) in the open surgery group, not reaching noninferiority for the laparoscopic approach (P = 0.38 for noninferiority). Conversion to open dissection occurred in 9% of the laparoscopy-assigned patients.
“Even though our trial was not designed to demonstrate whether one method of rectal dissection was superior to the other, the inability to establish noninferiority suggests that surgeons should be cautious when considering the suitability of a laparoscopic approach for a patient with rectal cancer,” Dr. Stevenson and colleagues wrote in their analysis.
“Subgroup analyses raise the possibility that laparoscopic surgery might be less successful than open surgery in patients who have received neoadjuvant therapy, have larger T3 tumors, or have higher BMIs. However, our study was underpowered to show significant differences in proportions of lower success rates for laparoscopic surgery vs. open surgery.”
The North American trial was funded by the National Cancer Institute, the American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, and the Covidien Company. Dr. Fleshman reported no conflicts, while several coauthors disclosed financial relationships with surgical device manufacturers, including Covidien.
The Australasian trial was funded by the Colorectal Surgical Society of Australia and New Zealand and the National Health and Medical Research Council. No conflicts of interest were reported.
FROM JAMA
Key clinical point: Two studies evaluating resection results failed to show laparoscopic surgeries for colorectal cancer as noninferior to open procedures.
Major finding: Among patients with stage III or IV rectal cancers, successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%), not supporting noninferiority for laparoscopic procedures (P = .41 for noninferiority). Similarly, among patients with T1-3 rectal tumors, 82% assigned laparoscopic surgery and 89% in the open surgery group saw adequate resections (P = .38 for noninferiority).
Data source: Randomized trials of slightly under 500 patients each at multiple study sites in North America, Australia, and New Zealand.
Disclosures: Australian-led study was publicly and institutionally funded with no investigator disclosures; U.S.-led study had support from a device manufacturer and several coauthors disclosed support from this and other manufacturers.
Lavage does not reduce severe complications in perforated diverticulitis
Patients needing emergency surgery for perforated diverticulitis saw no decrease in serious complications when treated with laparoscopic lavage, a minimally invasive procedure, than with primary resection of the colon, according to results from a randomized multicenter trial in Scandinavia.
Likelihood of reoperation also was significantly higher among patients undergoing laparoscopic lavage, and more sigmoid carcinomas were missed.
For their research, published Oct. 6 in JAMA (2015;314:1364-75), a group led by Dr. Johannes Kurt Schultz of the Akershus University Hospital in Lørenskog, Norway, and the University of Oslo sought to eliminate the selection bias that may have contributed to more favorable outcomes associated with laparoscopic lavage in observational studies.
Dr. Schultz and colleagues randomized patients with suspected perforated diverticulitis from 21 centers in Sweden and Norway to laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98), with the choice of open or laparoscopic approach used for resection, as well as the option of colorectal anastomosis, left to the surgeon.
The study did not use laparoscopic Hinchey staging to classify the severity of the perforation prior to treatment assignment as a way of reducing the selection bias that may have occurred in observational studies.
The preoperative randomization resulted in both groups having similar rates of feculent peritonitis and incorrect preoperative diagnoses. Patients assigned to laparoscopic lavage were treated instead with resection if they were found to have fecal peritonitis. Also, patients in both groups whose pathology required additional treatment were treated at surgeon discretion. This left 74 patients randomized to lavage who received it as assigned and 70 patients undergoing resection per assigned protocol. In the intention-to-treat analysis, 31% of patients in the lavage group and 26% of patients in the resection group saw severe postoperative complications within 90 days, a difference of 4.7% that did not reach statistical significance (95% confidence interval, −7.9% to 17%; P = .53). Severe postoperative complications were defined as any complications resulting in a reintervention requiring general anesthesia, a life-threatening organ dysfunction, or death.
Of the patients treated as assigned with lavage, about 20% (n = 15) required reoperation, compared with 6% (n = 4) in the resection arm, a difference of about 14.6% (95% CI, 3.5% to 25.6%; P =.01).
The main reasons for reoperation were secondary peritonitis in the lavage group and wound rupture in the resection group. Intra-abdominal infections were more frequent in the laparoscopic lavage group, Dr. Schultz and colleagues found.
Also in the lavage group, four carcinomas were missed, compared with two in the resection group. “Because of the relatively high rate of missed colon carcinomas in the lavage group, it was essential to perform a colonoscopy after a patient recovered from the perforation,” the researchers wrote in their analysis.
Although patients in the laparoscopic lavage group had significantly shorter operating times, less blood loss, and lower incidence of stoma at 3 months, the researchers concluded that, based on these results, laparoscopic lavage could not be supported in perforated diverticulitis.
Dr. Schultz and colleagues had planned to enroll about half of eligible patients at the study sites. They noted as a limitation of their study that those not enrolled had more severe disease and worse postoperative outcomes, raising the possibility that the results “may not pertain to patients with perforated diverticulitis who are very ill.”
The study was funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital. None of its authors reported conflicts of interest.
Dr. Schultz and associates detail findings from a randomized, multicenter clinical trial conducted in Scandinavia designed to assess the superiority of laparoscopic lavage plus drainage, compared with laparoscopic or open resection with or without anastomosis for diverticulitis (Hinchey grades I-III) requiring urgent surgery.
The primary outcome was the incidence of severe complications (Clavien-Dindo classification IIIb-V). Of 144 patients, 74 were randomized to receive laparoscopic lavage and 70 to resection. The two groups were similar in characteristics, although significantly fewer of the lavage procedures were performed by a specialty-trained surgeon. Severe complications occurred in 25.7% of patients in the lavage group and 14.3% in the resection group (difference, 11.4%; 95% CI, −1.8 to 24.1), and significantly more patients in the lavage group developed secondary peritonitis (12% vs. 0%) or returned to the operating room (20% vs. 6%). The hospital mortality rates and follow-up quality-of-life scores were comparable between the groups (3% vs. 4% and 0.75 vs. 0.73, respectively). Somewhat worrisome is that four colon cancers were initially missed in patients treated by laparoscopic lavage alone.
Performing laparoscopic lavage is more difficult than merely irrigating the abdomen and placing drains within the pelvis. Surgeons vary in their attitudes related to concomitant adhesiolysis or debridement, and consensus about these procedures is lacking. Furthermore, subjective signs and objective criteria that identify patients at risk for secondary peritonitis or reoperation must be studied, and risk models should be validated to determine which patients are best suited for this less invasive approach. The utility of less intrusive strategies and minimally invasive approaches will undoubtedly expand as technologies evolve, but they must be responsibly incorporated into surgical practice based on evidence rather than subjective reasons.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University, Chicago. These comments were taken from an accompanying editorial (JAMA 2015;314[13]:1343-5). They declared no conflicts of interest.
Dr. Schultz and associates detail findings from a randomized, multicenter clinical trial conducted in Scandinavia designed to assess the superiority of laparoscopic lavage plus drainage, compared with laparoscopic or open resection with or without anastomosis for diverticulitis (Hinchey grades I-III) requiring urgent surgery.
The primary outcome was the incidence of severe complications (Clavien-Dindo classification IIIb-V). Of 144 patients, 74 were randomized to receive laparoscopic lavage and 70 to resection. The two groups were similar in characteristics, although significantly fewer of the lavage procedures were performed by a specialty-trained surgeon. Severe complications occurred in 25.7% of patients in the lavage group and 14.3% in the resection group (difference, 11.4%; 95% CI, −1.8 to 24.1), and significantly more patients in the lavage group developed secondary peritonitis (12% vs. 0%) or returned to the operating room (20% vs. 6%). The hospital mortality rates and follow-up quality-of-life scores were comparable between the groups (3% vs. 4% and 0.75 vs. 0.73, respectively). Somewhat worrisome is that four colon cancers were initially missed in patients treated by laparoscopic lavage alone.
Performing laparoscopic lavage is more difficult than merely irrigating the abdomen and placing drains within the pelvis. Surgeons vary in their attitudes related to concomitant adhesiolysis or debridement, and consensus about these procedures is lacking. Furthermore, subjective signs and objective criteria that identify patients at risk for secondary peritonitis or reoperation must be studied, and risk models should be validated to determine which patients are best suited for this less invasive approach. The utility of less intrusive strategies and minimally invasive approaches will undoubtedly expand as technologies evolve, but they must be responsibly incorporated into surgical practice based on evidence rather than subjective reasons.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University, Chicago. These comments were taken from an accompanying editorial (JAMA 2015;314[13]:1343-5). They declared no conflicts of interest.
Dr. Schultz and associates detail findings from a randomized, multicenter clinical trial conducted in Scandinavia designed to assess the superiority of laparoscopic lavage plus drainage, compared with laparoscopic or open resection with or without anastomosis for diverticulitis (Hinchey grades I-III) requiring urgent surgery.
The primary outcome was the incidence of severe complications (Clavien-Dindo classification IIIb-V). Of 144 patients, 74 were randomized to receive laparoscopic lavage and 70 to resection. The two groups were similar in characteristics, although significantly fewer of the lavage procedures were performed by a specialty-trained surgeon. Severe complications occurred in 25.7% of patients in the lavage group and 14.3% in the resection group (difference, 11.4%; 95% CI, −1.8 to 24.1), and significantly more patients in the lavage group developed secondary peritonitis (12% vs. 0%) or returned to the operating room (20% vs. 6%). The hospital mortality rates and follow-up quality-of-life scores were comparable between the groups (3% vs. 4% and 0.75 vs. 0.73, respectively). Somewhat worrisome is that four colon cancers were initially missed in patients treated by laparoscopic lavage alone.
Performing laparoscopic lavage is more difficult than merely irrigating the abdomen and placing drains within the pelvis. Surgeons vary in their attitudes related to concomitant adhesiolysis or debridement, and consensus about these procedures is lacking. Furthermore, subjective signs and objective criteria that identify patients at risk for secondary peritonitis or reoperation must be studied, and risk models should be validated to determine which patients are best suited for this less invasive approach. The utility of less intrusive strategies and minimally invasive approaches will undoubtedly expand as technologies evolve, but they must be responsibly incorporated into surgical practice based on evidence rather than subjective reasons.
Dr. Scott A. Strong and Dr. Nathaniel J. Soper are with Northwestern University, Chicago. These comments were taken from an accompanying editorial (JAMA 2015;314[13]:1343-5). They declared no conflicts of interest.
Patients needing emergency surgery for perforated diverticulitis saw no decrease in serious complications when treated with laparoscopic lavage, a minimally invasive procedure, than with primary resection of the colon, according to results from a randomized multicenter trial in Scandinavia.
Likelihood of reoperation also was significantly higher among patients undergoing laparoscopic lavage, and more sigmoid carcinomas were missed.
For their research, published Oct. 6 in JAMA (2015;314:1364-75), a group led by Dr. Johannes Kurt Schultz of the Akershus University Hospital in Lørenskog, Norway, and the University of Oslo sought to eliminate the selection bias that may have contributed to more favorable outcomes associated with laparoscopic lavage in observational studies.
Dr. Schultz and colleagues randomized patients with suspected perforated diverticulitis from 21 centers in Sweden and Norway to laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98), with the choice of open or laparoscopic approach used for resection, as well as the option of colorectal anastomosis, left to the surgeon.
The study did not use laparoscopic Hinchey staging to classify the severity of the perforation prior to treatment assignment as a way of reducing the selection bias that may have occurred in observational studies.
The preoperative randomization resulted in both groups having similar rates of feculent peritonitis and incorrect preoperative diagnoses. Patients assigned to laparoscopic lavage were treated instead with resection if they were found to have fecal peritonitis. Also, patients in both groups whose pathology required additional treatment were treated at surgeon discretion. This left 74 patients randomized to lavage who received it as assigned and 70 patients undergoing resection per assigned protocol. In the intention-to-treat analysis, 31% of patients in the lavage group and 26% of patients in the resection group saw severe postoperative complications within 90 days, a difference of 4.7% that did not reach statistical significance (95% confidence interval, −7.9% to 17%; P = .53). Severe postoperative complications were defined as any complications resulting in a reintervention requiring general anesthesia, a life-threatening organ dysfunction, or death.
Of the patients treated as assigned with lavage, about 20% (n = 15) required reoperation, compared with 6% (n = 4) in the resection arm, a difference of about 14.6% (95% CI, 3.5% to 25.6%; P =.01).
The main reasons for reoperation were secondary peritonitis in the lavage group and wound rupture in the resection group. Intra-abdominal infections were more frequent in the laparoscopic lavage group, Dr. Schultz and colleagues found.
Also in the lavage group, four carcinomas were missed, compared with two in the resection group. “Because of the relatively high rate of missed colon carcinomas in the lavage group, it was essential to perform a colonoscopy after a patient recovered from the perforation,” the researchers wrote in their analysis.
Although patients in the laparoscopic lavage group had significantly shorter operating times, less blood loss, and lower incidence of stoma at 3 months, the researchers concluded that, based on these results, laparoscopic lavage could not be supported in perforated diverticulitis.
Dr. Schultz and colleagues had planned to enroll about half of eligible patients at the study sites. They noted as a limitation of their study that those not enrolled had more severe disease and worse postoperative outcomes, raising the possibility that the results “may not pertain to patients with perforated diverticulitis who are very ill.”
The study was funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital. None of its authors reported conflicts of interest.
Patients needing emergency surgery for perforated diverticulitis saw no decrease in serious complications when treated with laparoscopic lavage, a minimally invasive procedure, than with primary resection of the colon, according to results from a randomized multicenter trial in Scandinavia.
Likelihood of reoperation also was significantly higher among patients undergoing laparoscopic lavage, and more sigmoid carcinomas were missed.
For their research, published Oct. 6 in JAMA (2015;314:1364-75), a group led by Dr. Johannes Kurt Schultz of the Akershus University Hospital in Lørenskog, Norway, and the University of Oslo sought to eliminate the selection bias that may have contributed to more favorable outcomes associated with laparoscopic lavage in observational studies.
Dr. Schultz and colleagues randomized patients with suspected perforated diverticulitis from 21 centers in Sweden and Norway to laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98), with the choice of open or laparoscopic approach used for resection, as well as the option of colorectal anastomosis, left to the surgeon.
The study did not use laparoscopic Hinchey staging to classify the severity of the perforation prior to treatment assignment as a way of reducing the selection bias that may have occurred in observational studies.
The preoperative randomization resulted in both groups having similar rates of feculent peritonitis and incorrect preoperative diagnoses. Patients assigned to laparoscopic lavage were treated instead with resection if they were found to have fecal peritonitis. Also, patients in both groups whose pathology required additional treatment were treated at surgeon discretion. This left 74 patients randomized to lavage who received it as assigned and 70 patients undergoing resection per assigned protocol. In the intention-to-treat analysis, 31% of patients in the lavage group and 26% of patients in the resection group saw severe postoperative complications within 90 days, a difference of 4.7% that did not reach statistical significance (95% confidence interval, −7.9% to 17%; P = .53). Severe postoperative complications were defined as any complications resulting in a reintervention requiring general anesthesia, a life-threatening organ dysfunction, or death.
Of the patients treated as assigned with lavage, about 20% (n = 15) required reoperation, compared with 6% (n = 4) in the resection arm, a difference of about 14.6% (95% CI, 3.5% to 25.6%; P =.01).
The main reasons for reoperation were secondary peritonitis in the lavage group and wound rupture in the resection group. Intra-abdominal infections were more frequent in the laparoscopic lavage group, Dr. Schultz and colleagues found.
Also in the lavage group, four carcinomas were missed, compared with two in the resection group. “Because of the relatively high rate of missed colon carcinomas in the lavage group, it was essential to perform a colonoscopy after a patient recovered from the perforation,” the researchers wrote in their analysis.
Although patients in the laparoscopic lavage group had significantly shorter operating times, less blood loss, and lower incidence of stoma at 3 months, the researchers concluded that, based on these results, laparoscopic lavage could not be supported in perforated diverticulitis.
Dr. Schultz and colleagues had planned to enroll about half of eligible patients at the study sites. They noted as a limitation of their study that those not enrolled had more severe disease and worse postoperative outcomes, raising the possibility that the results “may not pertain to patients with perforated diverticulitis who are very ill.”
The study was funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital. None of its authors reported conflicts of interest.
FROM JAMA
Key clinical point: Laparoscopic lavage carries risks of severe postoperative complications similar to colon resection in people presenting with suspected perforated diverticulitis requiring emergency surgery.
Major finding: Mortality and severe complications did not differ significantly at 90 days postoperation between intention-to-treat groups, while reoperation was significantly higher among patients treated with lavage (5.7% for resection vs. 20.3% for lavage, P < .01).
Data source: A multicenter, open-label randomized trial in which patients presenting with likely perforated diverticulitis were randomized to lavage (n = 74) or resection (n = 70).
Disclosures: The study was sponsored by investigator institutions and Norwegian regional government grants. No conflicts of interest were reported.
Hospitalization driving bariatric surgery cost differences
Medicare payments to hospitals for bariatric operations varied by nearly $2,000 per episode of care, mostly because of differences in costs incurred in the initial – or index – hospitalization.
The findings, published online Sept. 16 in JAMA Surgery, offer hospitals a guide to where cost variation is highest (doi:10.1001/jamasurg.2015.2394) for these procedures.
Knowing where costs vary the most is particularly important if hospitals opt to accept bundled Medicare payments for bariatric procedures, which are a proposed addition to 48 other episodes of care that can currently be reimbursed in this way. Under bundled care payment programs, hospitals receive a single payment for all services related to a surgery or other episode of care, thereby accepting more risk when inefficiencies occur.
For their research, Dr. Tyler R. Grenda and his colleagues at University of Michigan, Ann Arbor, Center for Healthcare Outcomes and Policy, looked at claims data for 24,647 patients receiving bariatric procedures at 463 hospitals during 2011-2012.
Operations included laparoscopic gastric banding, laparoscopic Roux-en-Y gastric bypass, and open Roux-en-Y gastric bypass, with fewer than 5% of patients receiving other interventions. Mean total payments varied from $11,086 to $13,073 per episode of care, defined as index hospitalization through 30 days postdischarge, for a 16.5% difference between the lowest and highest hospital quartiles.
The index hospitalization was responsible for the largest portion of total payments (75%), seen in the study, followed by physician services (21%) and postacute care services (2.8%).
The large share of costs incurred during the index hospitalization was “likely owing to inpatient complications that drive [diagnosis-related group] up-coding,” the authors wrote, noting that DRG with complications result in higher Medicare payments.
Dr. Grenda and his colleagues concluded that bariatric surgery “appears to have a distinct pattern of hospital cost variation” unlike that seen in other procedures that have been studied to identify drivers of cost differences. “This difference in the pattern of variation emphasizes the importance of understanding cost variation specific to each procedure,” they wrote.
For example, a study that looked at hip fracture repair found that postacute care accounted for a large portion of variation in payments, while less variation was seen for the index hospitalization (Health Serv Res. 2010;45[6, pt 1]:1783-95).
In the current policy environment, in which bundled payments are seen as a way to shift cost accountability to hospitals, “a detailed understanding of variation in the costs for bariatric surgery will be essential for hospitals to identify areas of risk and opportunities for improvement,” the researchers wrote in their analysis.
Dr. Grenda and his colleagues’ research was funded by Agency for Healthcare Research and Quality. One coauthor and the supervisor of the study, Dr. Justin Dimnick, disclosed a financial relationship with ArborMetrix, a health care analytics firm not involved with the study; he is also an editor of JAMA Surgery, which published the study.
Medicare payments to hospitals for bariatric operations varied by nearly $2,000 per episode of care, mostly because of differences in costs incurred in the initial – or index – hospitalization.
The findings, published online Sept. 16 in JAMA Surgery, offer hospitals a guide to where cost variation is highest (doi:10.1001/jamasurg.2015.2394) for these procedures.
Knowing where costs vary the most is particularly important if hospitals opt to accept bundled Medicare payments for bariatric procedures, which are a proposed addition to 48 other episodes of care that can currently be reimbursed in this way. Under bundled care payment programs, hospitals receive a single payment for all services related to a surgery or other episode of care, thereby accepting more risk when inefficiencies occur.
For their research, Dr. Tyler R. Grenda and his colleagues at University of Michigan, Ann Arbor, Center for Healthcare Outcomes and Policy, looked at claims data for 24,647 patients receiving bariatric procedures at 463 hospitals during 2011-2012.
Operations included laparoscopic gastric banding, laparoscopic Roux-en-Y gastric bypass, and open Roux-en-Y gastric bypass, with fewer than 5% of patients receiving other interventions. Mean total payments varied from $11,086 to $13,073 per episode of care, defined as index hospitalization through 30 days postdischarge, for a 16.5% difference between the lowest and highest hospital quartiles.
The index hospitalization was responsible for the largest portion of total payments (75%), seen in the study, followed by physician services (21%) and postacute care services (2.8%).
The large share of costs incurred during the index hospitalization was “likely owing to inpatient complications that drive [diagnosis-related group] up-coding,” the authors wrote, noting that DRG with complications result in higher Medicare payments.
Dr. Grenda and his colleagues concluded that bariatric surgery “appears to have a distinct pattern of hospital cost variation” unlike that seen in other procedures that have been studied to identify drivers of cost differences. “This difference in the pattern of variation emphasizes the importance of understanding cost variation specific to each procedure,” they wrote.
For example, a study that looked at hip fracture repair found that postacute care accounted for a large portion of variation in payments, while less variation was seen for the index hospitalization (Health Serv Res. 2010;45[6, pt 1]:1783-95).
In the current policy environment, in which bundled payments are seen as a way to shift cost accountability to hospitals, “a detailed understanding of variation in the costs for bariatric surgery will be essential for hospitals to identify areas of risk and opportunities for improvement,” the researchers wrote in their analysis.
Dr. Grenda and his colleagues’ research was funded by Agency for Healthcare Research and Quality. One coauthor and the supervisor of the study, Dr. Justin Dimnick, disclosed a financial relationship with ArborMetrix, a health care analytics firm not involved with the study; he is also an editor of JAMA Surgery, which published the study.
Medicare payments to hospitals for bariatric operations varied by nearly $2,000 per episode of care, mostly because of differences in costs incurred in the initial – or index – hospitalization.
The findings, published online Sept. 16 in JAMA Surgery, offer hospitals a guide to where cost variation is highest (doi:10.1001/jamasurg.2015.2394) for these procedures.
Knowing where costs vary the most is particularly important if hospitals opt to accept bundled Medicare payments for bariatric procedures, which are a proposed addition to 48 other episodes of care that can currently be reimbursed in this way. Under bundled care payment programs, hospitals receive a single payment for all services related to a surgery or other episode of care, thereby accepting more risk when inefficiencies occur.
For their research, Dr. Tyler R. Grenda and his colleagues at University of Michigan, Ann Arbor, Center for Healthcare Outcomes and Policy, looked at claims data for 24,647 patients receiving bariatric procedures at 463 hospitals during 2011-2012.
Operations included laparoscopic gastric banding, laparoscopic Roux-en-Y gastric bypass, and open Roux-en-Y gastric bypass, with fewer than 5% of patients receiving other interventions. Mean total payments varied from $11,086 to $13,073 per episode of care, defined as index hospitalization through 30 days postdischarge, for a 16.5% difference between the lowest and highest hospital quartiles.
The index hospitalization was responsible for the largest portion of total payments (75%), seen in the study, followed by physician services (21%) and postacute care services (2.8%).
The large share of costs incurred during the index hospitalization was “likely owing to inpatient complications that drive [diagnosis-related group] up-coding,” the authors wrote, noting that DRG with complications result in higher Medicare payments.
Dr. Grenda and his colleagues concluded that bariatric surgery “appears to have a distinct pattern of hospital cost variation” unlike that seen in other procedures that have been studied to identify drivers of cost differences. “This difference in the pattern of variation emphasizes the importance of understanding cost variation specific to each procedure,” they wrote.
For example, a study that looked at hip fracture repair found that postacute care accounted for a large portion of variation in payments, while less variation was seen for the index hospitalization (Health Serv Res. 2010;45[6, pt 1]:1783-95).
In the current policy environment, in which bundled payments are seen as a way to shift cost accountability to hospitals, “a detailed understanding of variation in the costs for bariatric surgery will be essential for hospitals to identify areas of risk and opportunities for improvement,” the researchers wrote in their analysis.
Dr. Grenda and his colleagues’ research was funded by Agency for Healthcare Research and Quality. One coauthor and the supervisor of the study, Dr. Justin Dimnick, disclosed a financial relationship with ArborMetrix, a health care analytics firm not involved with the study; he is also an editor of JAMA Surgery, which published the study.
FROM JAMA SURGERY
Key clinical point: Initial hospitalization costs account for the lion’s share of cost variation for bariatric operations covered under Medicare.
Major finding: Mean total costs varied from $11,086 to about $13,073 per care episode, a 16.5% difference between the lowest- and highest-quartile hospitals; index hospitalizations accounted for 75% of payments, with less spent on physician fees and aftercare.
Data source: Medicare claims data for nearly 25,000 bariatric procedures performed at U.S. hospitals during 2011-2012.
Disclosures: Study was sponsored by the Agency for Healthcare Research and Quality; one coauthor disclosed financial relationship with a health analytics firm and journal editorship.
Silicosis seen in nearly all denim sandblasters
In a study of young men who had worked as denim sandblasters, nearly all developed silicosis, while most had evidence of radiographic progression and/or significant lung function loss more than 4 years after their exposure to silica dust had ended.
The findings, published in the September issue of CHEST, derive from a study of 145 former sandblasters first identified in Turkey in 2007. At that time all had already ended their work as sandblasters at various facilities at least 10 months prior, and some had worked as little as a month. Mean age in the cohort was under 24 years in 2007, and first exposures occurred before a mean 18 years of age (CHEST 2015;148[3]:647-54).
In 2011, Dr. Metin Akgun and colleagues at Atatürk University in Erzurum, Turkey, revisited this cohort for follow-up and found that nine of the subjects had died. The researchers identified 83 of the surviving subjects and were able to conduct chest radiographs and spirometry on 74.
Dr. Akgun and colleagues sought to determine whether the silicosis cases, based on the International Labor Organization definitions of silicosis, had increased beyond the 53% seen in 2007, and measured pulmonary function loss and radiographic progression 4 years later.
The researchers found evidence of significant (more than 12%) pulmonary function loss in 66% of the follow-up cohort, and radiographic progression in 82%. Silicosis was found in all but one subject. Mean total length of exposure to silicone dust was about 3.5 years for this group, though no subject had been exposed after 2007.
Of the 74 living sandblasters available for reexamination, the prevalence of silicosis increased from 55.4% to 95.9%.
The findings, Dr. Akgun and colleagues wrote, confirmed that silicosis could develop without further exposure to silica dust after a course of work in denim sandblasting.
Younger age and younger age at first exposure were significantly associated with radiographic progression, the researchers found. Progression, pulmonary function loss, and mortality were associated with having worked as a foreman and with sleeping at the workplace, both indicative of higher exposure.
The nine subjects who died between 2007 and 2011 were more likely to have worked in more factories, to have been younger when first exposed, and never to have smoked.
Although Turkey banned silica sandblasting of denim jeans in 2009 in response to silicosis concerns, “the occupational health consequences are global as long as sandblasted jeans are sold, because production has shifted to other countries, including Bangladesh,” the researchers wrote in their analysis, recommending that clothing manufacturers “clarify their policies on purchasing sandblasted denim in light of the mortality and morbidity from silicosis associated with this process in the global supply chain.”
Dr. Akgun and colleagues noted that their study was limited by their inability to recruit the remaining 62 workers they had first seen in 2007, of whom a higher percentage were foremen. This reduced their ability to evaluate in more detail the differences in outcomes by exposure level.
Also, they noted, tuberculosis tests and sputum cultures were not performed at follow-up, leading to the possibility that mycobacterial infection may have affected disease progression in some subjects.
The authors disclosed that hey had no outside funding or conflicts of interest related to their findings.
In a study of young men who had worked as denim sandblasters, nearly all developed silicosis, while most had evidence of radiographic progression and/or significant lung function loss more than 4 years after their exposure to silica dust had ended.
The findings, published in the September issue of CHEST, derive from a study of 145 former sandblasters first identified in Turkey in 2007. At that time all had already ended their work as sandblasters at various facilities at least 10 months prior, and some had worked as little as a month. Mean age in the cohort was under 24 years in 2007, and first exposures occurred before a mean 18 years of age (CHEST 2015;148[3]:647-54).
In 2011, Dr. Metin Akgun and colleagues at Atatürk University in Erzurum, Turkey, revisited this cohort for follow-up and found that nine of the subjects had died. The researchers identified 83 of the surviving subjects and were able to conduct chest radiographs and spirometry on 74.
Dr. Akgun and colleagues sought to determine whether the silicosis cases, based on the International Labor Organization definitions of silicosis, had increased beyond the 53% seen in 2007, and measured pulmonary function loss and radiographic progression 4 years later.
The researchers found evidence of significant (more than 12%) pulmonary function loss in 66% of the follow-up cohort, and radiographic progression in 82%. Silicosis was found in all but one subject. Mean total length of exposure to silicone dust was about 3.5 years for this group, though no subject had been exposed after 2007.
Of the 74 living sandblasters available for reexamination, the prevalence of silicosis increased from 55.4% to 95.9%.
The findings, Dr. Akgun and colleagues wrote, confirmed that silicosis could develop without further exposure to silica dust after a course of work in denim sandblasting.
Younger age and younger age at first exposure were significantly associated with radiographic progression, the researchers found. Progression, pulmonary function loss, and mortality were associated with having worked as a foreman and with sleeping at the workplace, both indicative of higher exposure.
The nine subjects who died between 2007 and 2011 were more likely to have worked in more factories, to have been younger when first exposed, and never to have smoked.
Although Turkey banned silica sandblasting of denim jeans in 2009 in response to silicosis concerns, “the occupational health consequences are global as long as sandblasted jeans are sold, because production has shifted to other countries, including Bangladesh,” the researchers wrote in their analysis, recommending that clothing manufacturers “clarify their policies on purchasing sandblasted denim in light of the mortality and morbidity from silicosis associated with this process in the global supply chain.”
Dr. Akgun and colleagues noted that their study was limited by their inability to recruit the remaining 62 workers they had first seen in 2007, of whom a higher percentage were foremen. This reduced their ability to evaluate in more detail the differences in outcomes by exposure level.
Also, they noted, tuberculosis tests and sputum cultures were not performed at follow-up, leading to the possibility that mycobacterial infection may have affected disease progression in some subjects.
The authors disclosed that hey had no outside funding or conflicts of interest related to their findings.
In a study of young men who had worked as denim sandblasters, nearly all developed silicosis, while most had evidence of radiographic progression and/or significant lung function loss more than 4 years after their exposure to silica dust had ended.
The findings, published in the September issue of CHEST, derive from a study of 145 former sandblasters first identified in Turkey in 2007. At that time all had already ended their work as sandblasters at various facilities at least 10 months prior, and some had worked as little as a month. Mean age in the cohort was under 24 years in 2007, and first exposures occurred before a mean 18 years of age (CHEST 2015;148[3]:647-54).
In 2011, Dr. Metin Akgun and colleagues at Atatürk University in Erzurum, Turkey, revisited this cohort for follow-up and found that nine of the subjects had died. The researchers identified 83 of the surviving subjects and were able to conduct chest radiographs and spirometry on 74.
Dr. Akgun and colleagues sought to determine whether the silicosis cases, based on the International Labor Organization definitions of silicosis, had increased beyond the 53% seen in 2007, and measured pulmonary function loss and radiographic progression 4 years later.
The researchers found evidence of significant (more than 12%) pulmonary function loss in 66% of the follow-up cohort, and radiographic progression in 82%. Silicosis was found in all but one subject. Mean total length of exposure to silicone dust was about 3.5 years for this group, though no subject had been exposed after 2007.
Of the 74 living sandblasters available for reexamination, the prevalence of silicosis increased from 55.4% to 95.9%.
The findings, Dr. Akgun and colleagues wrote, confirmed that silicosis could develop without further exposure to silica dust after a course of work in denim sandblasting.
Younger age and younger age at first exposure were significantly associated with radiographic progression, the researchers found. Progression, pulmonary function loss, and mortality were associated with having worked as a foreman and with sleeping at the workplace, both indicative of higher exposure.
The nine subjects who died between 2007 and 2011 were more likely to have worked in more factories, to have been younger when first exposed, and never to have smoked.
Although Turkey banned silica sandblasting of denim jeans in 2009 in response to silicosis concerns, “the occupational health consequences are global as long as sandblasted jeans are sold, because production has shifted to other countries, including Bangladesh,” the researchers wrote in their analysis, recommending that clothing manufacturers “clarify their policies on purchasing sandblasted denim in light of the mortality and morbidity from silicosis associated with this process in the global supply chain.”
Dr. Akgun and colleagues noted that their study was limited by their inability to recruit the remaining 62 workers they had first seen in 2007, of whom a higher percentage were foremen. This reduced their ability to evaluate in more detail the differences in outcomes by exposure level.
Also, they noted, tuberculosis tests and sputum cultures were not performed at follow-up, leading to the possibility that mycobacterial infection may have affected disease progression in some subjects.
The authors disclosed that hey had no outside funding or conflicts of interest related to their findings.
FROM CHEST
Key clinical point: At 4 years post exposure to silica dust, nearly all men who formerly worked sandblasting denim in textile factories developed silicosis.
Major finding: Prevalence of silicosis increased from 55.4% to 95.9% between 2007 and 2011, while radiographic progression was seen in 82% of subjects at follow-up, and pulmonary function loss in 66%.
Data source: Observational cohort of 145 Turkish men first recruited in 2007 and screened for silicosis, with 74 followed up clinically in 2011.
Disclosures: Study was funded by investigator institutions in Turkey. The researchers reported having no conflicts.
