Most lung recipients gain 2-year survival benefit

Lung transplantation prolongs survival
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Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.

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Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.

It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
 

Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.

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Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.

It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
 

Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.

Body

 

Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.

It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
 

Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.

Title
Lung transplantation prolongs survival
Lung transplantation prolongs survival

 

Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.

 

Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.

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Key clinical point: Nearly three-quarters of lung transplant recipients are predicted to achieve a 2-year survival benefit with transplantation.

Major finding: Research suggests 73.8% of transplant recipients are likely to achieve a 2-year survival benefit with transplantation.

Data source: A structural nested accelerated failure time model of the survival benefit of lung transplantation using data from 13,040 adults listed for lung transplantation.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute of Allergy and Infectious Diseases. One author declared grants and personal fees from private industry for consultation on lung transplantation. No other conflicts of interest were declared.

Testosterone Trials’ cardiac, cognitive results disappoint

Evidence sinks testosterone-led rejuvenation
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Testosterone treatment may have beneficial effects on unexplained anemia or bone density in men with age-related low testosterone, but at the cost of an increase in coronary artery plaque and with no benefit on cognitive function, new research suggests.

The results of four of the seven Testosterone Trials were published Feb. 21 in JAMA and JAMA Internal Medicine, adding to a growing body of research on the impact of testosterone supplementation but without finding clear evidence of an overall benefit.

In the double-blind, multicenter Anemia Trial, 788 men aged 65 years or older with average testosterone levels of less than 275 ng/dL were allocated to 12 months of testosterone gel or placebo. The group included 126 individuals with a hemoglobin level at or below 12.7 g/dL (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9540).

The study found that significantly more men who received testosterone treatment experienced increases in hemoglobin concentration of 1 g/dL or more above baseline, compared with those who received the placebo gel (54% vs. 15%; 95% CI 3.7-277.8; P = .002).

This effect was seen in men with known causes of anemia, such as myelodysplasia, iron deficiency, B12 deficiency, or chronic inflammation or disease; in men with anemia of unknown case; and in men who weren’t anemic.

After 12 months, more than half of the testosterone-treated men who started the study with unexplained anemia were no longer anemic, compared with around one-quarter of the placebo-treated men (58.3% vs. 22.2%). The men treated with placebo also had lower average hemoglobin level changes, compared with those treated with testosterone.

“Increases in hemoglobin levels were positively and significantly associated with participants’ global impression of change in overall health and energy,” wrote Cindy N. Roy, PhD, of Johns Hopkins University, Baltimore, and her coauthors.

Bone mineral density

A second trial examined the effect of 12 months of testosterone gel or placebo on bone mineral density in a group of 211 men with average testosterone concentrations less than 275 ng/L (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9539). The treatment increased median serum concentrations of total testosterone, free testosterone, and estradiol to within the normal ranges for young men.

The study showed significantly greater increases – measured by quantitative computed tomography – with testosterone treatment, compared with placebo, in spine trabecular, spine peripheral, hip trabecular, and peripheral volumetric bone mineral density, as well as in mean estimated strength of spine trabecular bone, spine peripheral bone, and hip trabecular and peripheral bone.

For the primary outcome of mean lumbar spine trabecular volumetric bone mineral density, testosterone treatment was associated with a mean increase of 7.5%, compared with a 0.8% increase with placebo.

Researchers also noted that the magnitude of the increase in spine trabecular bone mineral density from baseline was significantly associated with changes in total testosterone and estradiol.

However, there were no significant differences in fracture rate, with six fractures reported in each group during the year of treatment. In the observation year after treatment, three fractures were reported in the testosterone arm and four in the placebo arm.

“These results are unequivocal compared with prior studies of the effect of testosterone treatment on bone in older men, in spite of treatment limited to 1 year, perhaps because the mean pretreatment testosterone level was lower and the sample size larger than in prior studies, and because the primary outcome in this trial was vBMD by QCT,” wrote Peter J. Snyder, MD, of the University of Pennsylvania, Philadelphia, and his coauthors.

Coronary artery plaque

However, a third trial – this one in 170 men with low testosterone and symptoms suggestive of hypogonadism – found significantly greater increases in noncalcified plaque volume, median total plaque volume, and median coronary artery calcification score among the 88 men assigned to 12 months of testosterone gel, compared with those assigned to placebo.

The men treated with testosterone showed a mean increase in noncalcified coronary artery plaque volume of 40 mm3, compared with 4 mm3 in men given the placebo gel, and a mean increase in total plaque volume of 57 mm3 with testosterone and 21 mm3 with placebo (JAMA. 2017 Feb 21;317[7]:708-16).

There were no significant differences between the groups in change to coronary artery calcium score, and there were no adverse cardiovascular events reported in either group, despite the fact that around half the participants had severe atherosclerosis at baseline.

“The increase in coronary artery noncalcified and total plaque volumes in men treated with testosterone is concerning, because any limitation of the vascular lumen could be considered deleterious,” wrote Matthew J. Budoff, MD, of the Los Angeles Biomedical Research Institute, Torrance, Calif., and his coauthors. “The clinical significance of these increases could depend on the differential effects of testosterone on the individual components of noncalcified plaque.”

However, the investigators pointed out that the trial was neither large enough nor long enough to draw conclusions about the cardiovascular risks of testosterone treatment, and they called for larger studies to explore the association.

 

 

Cognitive function

The fourth study looked at mean change in cognitive function from baseline in 493 men with a serum testosterone level less than 275 ng/dL, impaired sexual function, physical function, or vitality, and who met the criteria for age-associated memory impairment. Half the participants were assigned to 12 months of testosterone gel, and half were assigned to placebo gel (JAMA. 2017 Feb 21;317[7]:717-27).

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Today, 8 decades since the first clinical use of testosterone, the sole unequivocal indication for testosterone treatment is as replacement therapy for men with pathological hypogonadism (i.e., organic disorders of the reproductive system). Yet despite no proven new indications, global testosterone sales increased 100-fold over the last 3 decades, including increases of 40-fold in Canada and 10-fold in the United States from 2000 to 2011.

Overall, the findings from subtrials of the TTrials do not materially change the unfavorable balance of safety and efficacy to initiate testosterone treatment for age-related hypogonadism. With the results of the studies by Resnick et al. and by Budoff et al. in this issue of JAMA, the hopes for testosterone-led rejuvenation for older men are dimmed and disappointed if not yet finally dashed.

David J. Handelsman, MD, is from the ANZAC Research Institute, University of Sydney and Concord Hospital, Australia. These comments are taken from an editorial (JAMA 2017 Feb 21;317:699-701). Dr. Handelsman reported grants from Lawley Pharmaceuticals and Besins Healthcare and serving as a medical expert in testosterone litigation.

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Today, 8 decades since the first clinical use of testosterone, the sole unequivocal indication for testosterone treatment is as replacement therapy for men with pathological hypogonadism (i.e., organic disorders of the reproductive system). Yet despite no proven new indications, global testosterone sales increased 100-fold over the last 3 decades, including increases of 40-fold in Canada and 10-fold in the United States from 2000 to 2011.

Overall, the findings from subtrials of the TTrials do not materially change the unfavorable balance of safety and efficacy to initiate testosterone treatment for age-related hypogonadism. With the results of the studies by Resnick et al. and by Budoff et al. in this issue of JAMA, the hopes for testosterone-led rejuvenation for older men are dimmed and disappointed if not yet finally dashed.

David J. Handelsman, MD, is from the ANZAC Research Institute, University of Sydney and Concord Hospital, Australia. These comments are taken from an editorial (JAMA 2017 Feb 21;317:699-701). Dr. Handelsman reported grants from Lawley Pharmaceuticals and Besins Healthcare and serving as a medical expert in testosterone litigation.

Body

 

Today, 8 decades since the first clinical use of testosterone, the sole unequivocal indication for testosterone treatment is as replacement therapy for men with pathological hypogonadism (i.e., organic disorders of the reproductive system). Yet despite no proven new indications, global testosterone sales increased 100-fold over the last 3 decades, including increases of 40-fold in Canada and 10-fold in the United States from 2000 to 2011.

Overall, the findings from subtrials of the TTrials do not materially change the unfavorable balance of safety and efficacy to initiate testosterone treatment for age-related hypogonadism. With the results of the studies by Resnick et al. and by Budoff et al. in this issue of JAMA, the hopes for testosterone-led rejuvenation for older men are dimmed and disappointed if not yet finally dashed.

David J. Handelsman, MD, is from the ANZAC Research Institute, University of Sydney and Concord Hospital, Australia. These comments are taken from an editorial (JAMA 2017 Feb 21;317:699-701). Dr. Handelsman reported grants from Lawley Pharmaceuticals and Besins Healthcare and serving as a medical expert in testosterone litigation.

Title
Evidence sinks testosterone-led rejuvenation
Evidence sinks testosterone-led rejuvenation

 

Testosterone treatment may have beneficial effects on unexplained anemia or bone density in men with age-related low testosterone, but at the cost of an increase in coronary artery plaque and with no benefit on cognitive function, new research suggests.

The results of four of the seven Testosterone Trials were published Feb. 21 in JAMA and JAMA Internal Medicine, adding to a growing body of research on the impact of testosterone supplementation but without finding clear evidence of an overall benefit.

In the double-blind, multicenter Anemia Trial, 788 men aged 65 years or older with average testosterone levels of less than 275 ng/dL were allocated to 12 months of testosterone gel or placebo. The group included 126 individuals with a hemoglobin level at or below 12.7 g/dL (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9540).

The study found that significantly more men who received testosterone treatment experienced increases in hemoglobin concentration of 1 g/dL or more above baseline, compared with those who received the placebo gel (54% vs. 15%; 95% CI 3.7-277.8; P = .002).

This effect was seen in men with known causes of anemia, such as myelodysplasia, iron deficiency, B12 deficiency, or chronic inflammation or disease; in men with anemia of unknown case; and in men who weren’t anemic.

After 12 months, more than half of the testosterone-treated men who started the study with unexplained anemia were no longer anemic, compared with around one-quarter of the placebo-treated men (58.3% vs. 22.2%). The men treated with placebo also had lower average hemoglobin level changes, compared with those treated with testosterone.

“Increases in hemoglobin levels were positively and significantly associated with participants’ global impression of change in overall health and energy,” wrote Cindy N. Roy, PhD, of Johns Hopkins University, Baltimore, and her coauthors.

Bone mineral density

A second trial examined the effect of 12 months of testosterone gel or placebo on bone mineral density in a group of 211 men with average testosterone concentrations less than 275 ng/L (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9539). The treatment increased median serum concentrations of total testosterone, free testosterone, and estradiol to within the normal ranges for young men.

The study showed significantly greater increases – measured by quantitative computed tomography – with testosterone treatment, compared with placebo, in spine trabecular, spine peripheral, hip trabecular, and peripheral volumetric bone mineral density, as well as in mean estimated strength of spine trabecular bone, spine peripheral bone, and hip trabecular and peripheral bone.

For the primary outcome of mean lumbar spine trabecular volumetric bone mineral density, testosterone treatment was associated with a mean increase of 7.5%, compared with a 0.8% increase with placebo.

Researchers also noted that the magnitude of the increase in spine trabecular bone mineral density from baseline was significantly associated with changes in total testosterone and estradiol.

However, there were no significant differences in fracture rate, with six fractures reported in each group during the year of treatment. In the observation year after treatment, three fractures were reported in the testosterone arm and four in the placebo arm.

“These results are unequivocal compared with prior studies of the effect of testosterone treatment on bone in older men, in spite of treatment limited to 1 year, perhaps because the mean pretreatment testosterone level was lower and the sample size larger than in prior studies, and because the primary outcome in this trial was vBMD by QCT,” wrote Peter J. Snyder, MD, of the University of Pennsylvania, Philadelphia, and his coauthors.

Coronary artery plaque

However, a third trial – this one in 170 men with low testosterone and symptoms suggestive of hypogonadism – found significantly greater increases in noncalcified plaque volume, median total plaque volume, and median coronary artery calcification score among the 88 men assigned to 12 months of testosterone gel, compared with those assigned to placebo.

The men treated with testosterone showed a mean increase in noncalcified coronary artery plaque volume of 40 mm3, compared with 4 mm3 in men given the placebo gel, and a mean increase in total plaque volume of 57 mm3 with testosterone and 21 mm3 with placebo (JAMA. 2017 Feb 21;317[7]:708-16).

There were no significant differences between the groups in change to coronary artery calcium score, and there were no adverse cardiovascular events reported in either group, despite the fact that around half the participants had severe atherosclerosis at baseline.

“The increase in coronary artery noncalcified and total plaque volumes in men treated with testosterone is concerning, because any limitation of the vascular lumen could be considered deleterious,” wrote Matthew J. Budoff, MD, of the Los Angeles Biomedical Research Institute, Torrance, Calif., and his coauthors. “The clinical significance of these increases could depend on the differential effects of testosterone on the individual components of noncalcified plaque.”

However, the investigators pointed out that the trial was neither large enough nor long enough to draw conclusions about the cardiovascular risks of testosterone treatment, and they called for larger studies to explore the association.

 

 

Cognitive function

The fourth study looked at mean change in cognitive function from baseline in 493 men with a serum testosterone level less than 275 ng/dL, impaired sexual function, physical function, or vitality, and who met the criteria for age-associated memory impairment. Half the participants were assigned to 12 months of testosterone gel, and half were assigned to placebo gel (JAMA. 2017 Feb 21;317[7]:717-27).

 

Testosterone treatment may have beneficial effects on unexplained anemia or bone density in men with age-related low testosterone, but at the cost of an increase in coronary artery plaque and with no benefit on cognitive function, new research suggests.

The results of four of the seven Testosterone Trials were published Feb. 21 in JAMA and JAMA Internal Medicine, adding to a growing body of research on the impact of testosterone supplementation but without finding clear evidence of an overall benefit.

In the double-blind, multicenter Anemia Trial, 788 men aged 65 years or older with average testosterone levels of less than 275 ng/dL were allocated to 12 months of testosterone gel or placebo. The group included 126 individuals with a hemoglobin level at or below 12.7 g/dL (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9540).

The study found that significantly more men who received testosterone treatment experienced increases in hemoglobin concentration of 1 g/dL or more above baseline, compared with those who received the placebo gel (54% vs. 15%; 95% CI 3.7-277.8; P = .002).

This effect was seen in men with known causes of anemia, such as myelodysplasia, iron deficiency, B12 deficiency, or chronic inflammation or disease; in men with anemia of unknown case; and in men who weren’t anemic.

After 12 months, more than half of the testosterone-treated men who started the study with unexplained anemia were no longer anemic, compared with around one-quarter of the placebo-treated men (58.3% vs. 22.2%). The men treated with placebo also had lower average hemoglobin level changes, compared with those treated with testosterone.

“Increases in hemoglobin levels were positively and significantly associated with participants’ global impression of change in overall health and energy,” wrote Cindy N. Roy, PhD, of Johns Hopkins University, Baltimore, and her coauthors.

Bone mineral density

A second trial examined the effect of 12 months of testosterone gel or placebo on bone mineral density in a group of 211 men with average testosterone concentrations less than 275 ng/L (JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9539). The treatment increased median serum concentrations of total testosterone, free testosterone, and estradiol to within the normal ranges for young men.

The study showed significantly greater increases – measured by quantitative computed tomography – with testosterone treatment, compared with placebo, in spine trabecular, spine peripheral, hip trabecular, and peripheral volumetric bone mineral density, as well as in mean estimated strength of spine trabecular bone, spine peripheral bone, and hip trabecular and peripheral bone.

For the primary outcome of mean lumbar spine trabecular volumetric bone mineral density, testosterone treatment was associated with a mean increase of 7.5%, compared with a 0.8% increase with placebo.

Researchers also noted that the magnitude of the increase in spine trabecular bone mineral density from baseline was significantly associated with changes in total testosterone and estradiol.

However, there were no significant differences in fracture rate, with six fractures reported in each group during the year of treatment. In the observation year after treatment, three fractures were reported in the testosterone arm and four in the placebo arm.

“These results are unequivocal compared with prior studies of the effect of testosterone treatment on bone in older men, in spite of treatment limited to 1 year, perhaps because the mean pretreatment testosterone level was lower and the sample size larger than in prior studies, and because the primary outcome in this trial was vBMD by QCT,” wrote Peter J. Snyder, MD, of the University of Pennsylvania, Philadelphia, and his coauthors.

Coronary artery plaque

However, a third trial – this one in 170 men with low testosterone and symptoms suggestive of hypogonadism – found significantly greater increases in noncalcified plaque volume, median total plaque volume, and median coronary artery calcification score among the 88 men assigned to 12 months of testosterone gel, compared with those assigned to placebo.

The men treated with testosterone showed a mean increase in noncalcified coronary artery plaque volume of 40 mm3, compared with 4 mm3 in men given the placebo gel, and a mean increase in total plaque volume of 57 mm3 with testosterone and 21 mm3 with placebo (JAMA. 2017 Feb 21;317[7]:708-16).

There were no significant differences between the groups in change to coronary artery calcium score, and there were no adverse cardiovascular events reported in either group, despite the fact that around half the participants had severe atherosclerosis at baseline.

“The increase in coronary artery noncalcified and total plaque volumes in men treated with testosterone is concerning, because any limitation of the vascular lumen could be considered deleterious,” wrote Matthew J. Budoff, MD, of the Los Angeles Biomedical Research Institute, Torrance, Calif., and his coauthors. “The clinical significance of these increases could depend on the differential effects of testosterone on the individual components of noncalcified plaque.”

However, the investigators pointed out that the trial was neither large enough nor long enough to draw conclusions about the cardiovascular risks of testosterone treatment, and they called for larger studies to explore the association.

 

 

Cognitive function

The fourth study looked at mean change in cognitive function from baseline in 493 men with a serum testosterone level less than 275 ng/dL, impaired sexual function, physical function, or vitality, and who met the criteria for age-associated memory impairment. Half the participants were assigned to 12 months of testosterone gel, and half were assigned to placebo gel (JAMA. 2017 Feb 21;317[7]:717-27).

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Key clinical point: Testosterone treatment may have beneficial effects on unexplained anemia or bone density in men with age-related low testosterone, but at the cost of an increase in coronary artery plaque and with no benefit for cognitive function.

Major finding: Testosterone treatment was associated with significantly greater increases in bone mineral density, hemoglobin, and noncalcified coronary artery plaque, compared with placebo, but no significant effects on cognitive function.

Data source: The Testosterone Trials in men aged 65 years or older with age-related testosterone decline.

Disclosures: The Testosterone Trials were supported by the National Institute on Aging, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, the National Institute of Child Health and Human Development, and AbbVie, which provided the AndroGel and placebo gel. Authors from the trials declared a range of funding, consultancies, and other support from the pharmaceutical industry, including AbbVie. One author declared a pending patent for a free testosterone calculator.

Survival gains with pembrolizumab in urothelial cancer

Durable responses but an incremental advance
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Treatment with checkpoint inhibitor pembrolizumab is associated with significant gains in overall survival among patients with treatment-refractory advanced urothelial carcinoma, according to new research.

Data from the KEYNOTE-045 trial was presented simultaneously at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, and published in the New England Journal of Medicine.

The open-label, international phase III trial involved 542 patients with advanced urothelial carcinoma that had recurred or progressed after platinum-based chemotherapy. Participants were randomized either to 200 mg pembrolizumab every 3 weeks, or the investigator’s choice of paclitaxel, docetaxel, or vinflunine chemotherapy.

After a median follow-up of 14.1 months, researchers saw a 27% lower hazard ratio for death among the pembrolizumab group, compared with the chemotherapy group (P = .002), with a median overall survival of 10.3 months with pembrolizumab, compared with 7.4 months with chemotherapy (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMoa1613683).

The estimated overall survival rate at 1 year was 43.9% among those treated with pembrolizumab and 30.7% in the chemotherapy group. The authors also saw no significant differences when each chemotherapy regimen was examined separately.

Patients treated with pembrolizumab also showed a significant higher objective response rate, compared with those treated with chemotherapy (21.1% vs. 11.4%, P = .001). At the time of data cut-off, 72% of patients in the pembrolizumab group showed a continued response, compared with 35% of the chemotherapy group.

“Most responses in patients in the pembrolizumab group occurred quickly and were reported at the first scheduled imaging assessment,” wrote Joaquim Bellmunt, MD, PhD, from the Dana-Farber Cancer Institute, Boston and his coauthors. “Continued disease regression over time in some patients resulted in radiologically confirmed responses that were reported as long as 6.3 months after the start of therapy.”

They also looked at how the level of programmed death 1 ligand (PD-L1) expression in the tumor influenced response by examining outcomes in a subgroup of patients whose tumor PD-L1 combined positive score – the percentage of PD-L1 expressing tumor and infiltrating immune cells relative to the total number of tumor cells – exceeded 10%.

In this group, median overall survival was 8 months with pembrolizumab, compared with 5.2 months with chemotherapy, representing a significant 43% reduction in mortality with immunotherapy.

There was an interaction between smoking status and response, with current smokers showing a significantly greater response that favored pembrolizumab. The authors pointed out that this effect has also been observed in other advanced cancers, and may reflect the impact of a greater mutational load in the cancers of smokers.

The study did not find any difference in the duration of progression-free survival between the two groups, nor among participants with a PD-L1 combined positive score of 10% of more. Median progression-free survival was 2.1 months in the pembrolizumab group and 3.3 months in the chemotherapy group.

Researchers also noted a lower rate of adverse events among patients treated with pembrolizumab, compared with chemotherapy. Treatment-related adverse events of grade 3-5 occurred in 49.4% of patients on chemotherapy, compared with 15% of those on pembrolizumab.

There was one death from treatment-related pneumonitis in the pembrolizumab group, and three deaths attributed to the study treatment; one urinary tract obstruction, one malignant neoplasm, and one unspecified cause. In the chemotherapy group, there were two treatment-related deaths from sepsis, one from septic shock, and one unspecified.

The most common adverse events with chemotherapy were alopecia, fatigue, and anemia, while in the pembrolizumab group the most common side effects were pruritis, fatigue, and nausea.

The study was supported by Merck. Sixteen authors declared personal fees, grants, honoraria, consultancies, and advisory board positions with pharmaceutical companies including Merck, three authors were employees of Merck with stock options, and one had nothing to declare.

Body

 

In the context of cancer therapy, PD-L1 and PD-1 inhibitors may be aptly described as the metaphorical rising tide that lifts all boats. These monoclonal antibodies have yielded major advances across multiple malignant conditions by unleashing the antitumor activity of T-lymphocytes by targeting this T-cell inhibitory pathway.

The KEYNOTE-045 trial will have a practice-changing effect. The longer survival and lower rate of toxic adverse effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions. As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable.

Guru Sonpavde, MD, is from the University of Alabama at Birmingham Comprehensive Cancer Center. These comments are taken from an accompanying editorial (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMe1701182). Dr. Sonpavde reported a range of grants and personal fees from the pharmaceutical industry, including from Merck.

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In the context of cancer therapy, PD-L1 and PD-1 inhibitors may be aptly described as the metaphorical rising tide that lifts all boats. These monoclonal antibodies have yielded major advances across multiple malignant conditions by unleashing the antitumor activity of T-lymphocytes by targeting this T-cell inhibitory pathway.

The KEYNOTE-045 trial will have a practice-changing effect. The longer survival and lower rate of toxic adverse effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions. As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable.

Guru Sonpavde, MD, is from the University of Alabama at Birmingham Comprehensive Cancer Center. These comments are taken from an accompanying editorial (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMe1701182). Dr. Sonpavde reported a range of grants and personal fees from the pharmaceutical industry, including from Merck.

Body

 

In the context of cancer therapy, PD-L1 and PD-1 inhibitors may be aptly described as the metaphorical rising tide that lifts all boats. These monoclonal antibodies have yielded major advances across multiple malignant conditions by unleashing the antitumor activity of T-lymphocytes by targeting this T-cell inhibitory pathway.

The KEYNOTE-045 trial will have a practice-changing effect. The longer survival and lower rate of toxic adverse effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions. As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable.

Guru Sonpavde, MD, is from the University of Alabama at Birmingham Comprehensive Cancer Center. These comments are taken from an accompanying editorial (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMe1701182). Dr. Sonpavde reported a range of grants and personal fees from the pharmaceutical industry, including from Merck.

Title
Durable responses but an incremental advance
Durable responses but an incremental advance

 

Treatment with checkpoint inhibitor pembrolizumab is associated with significant gains in overall survival among patients with treatment-refractory advanced urothelial carcinoma, according to new research.

Data from the KEYNOTE-045 trial was presented simultaneously at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, and published in the New England Journal of Medicine.

The open-label, international phase III trial involved 542 patients with advanced urothelial carcinoma that had recurred or progressed after platinum-based chemotherapy. Participants were randomized either to 200 mg pembrolizumab every 3 weeks, or the investigator’s choice of paclitaxel, docetaxel, or vinflunine chemotherapy.

After a median follow-up of 14.1 months, researchers saw a 27% lower hazard ratio for death among the pembrolizumab group, compared with the chemotherapy group (P = .002), with a median overall survival of 10.3 months with pembrolizumab, compared with 7.4 months with chemotherapy (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMoa1613683).

The estimated overall survival rate at 1 year was 43.9% among those treated with pembrolizumab and 30.7% in the chemotherapy group. The authors also saw no significant differences when each chemotherapy regimen was examined separately.

Patients treated with pembrolizumab also showed a significant higher objective response rate, compared with those treated with chemotherapy (21.1% vs. 11.4%, P = .001). At the time of data cut-off, 72% of patients in the pembrolizumab group showed a continued response, compared with 35% of the chemotherapy group.

“Most responses in patients in the pembrolizumab group occurred quickly and were reported at the first scheduled imaging assessment,” wrote Joaquim Bellmunt, MD, PhD, from the Dana-Farber Cancer Institute, Boston and his coauthors. “Continued disease regression over time in some patients resulted in radiologically confirmed responses that were reported as long as 6.3 months after the start of therapy.”

They also looked at how the level of programmed death 1 ligand (PD-L1) expression in the tumor influenced response by examining outcomes in a subgroup of patients whose tumor PD-L1 combined positive score – the percentage of PD-L1 expressing tumor and infiltrating immune cells relative to the total number of tumor cells – exceeded 10%.

In this group, median overall survival was 8 months with pembrolizumab, compared with 5.2 months with chemotherapy, representing a significant 43% reduction in mortality with immunotherapy.

There was an interaction between smoking status and response, with current smokers showing a significantly greater response that favored pembrolizumab. The authors pointed out that this effect has also been observed in other advanced cancers, and may reflect the impact of a greater mutational load in the cancers of smokers.

The study did not find any difference in the duration of progression-free survival between the two groups, nor among participants with a PD-L1 combined positive score of 10% of more. Median progression-free survival was 2.1 months in the pembrolizumab group and 3.3 months in the chemotherapy group.

Researchers also noted a lower rate of adverse events among patients treated with pembrolizumab, compared with chemotherapy. Treatment-related adverse events of grade 3-5 occurred in 49.4% of patients on chemotherapy, compared with 15% of those on pembrolizumab.

There was one death from treatment-related pneumonitis in the pembrolizumab group, and three deaths attributed to the study treatment; one urinary tract obstruction, one malignant neoplasm, and one unspecified cause. In the chemotherapy group, there were two treatment-related deaths from sepsis, one from septic shock, and one unspecified.

The most common adverse events with chemotherapy were alopecia, fatigue, and anemia, while in the pembrolizumab group the most common side effects were pruritis, fatigue, and nausea.

The study was supported by Merck. Sixteen authors declared personal fees, grants, honoraria, consultancies, and advisory board positions with pharmaceutical companies including Merck, three authors were employees of Merck with stock options, and one had nothing to declare.

 

Treatment with checkpoint inhibitor pembrolizumab is associated with significant gains in overall survival among patients with treatment-refractory advanced urothelial carcinoma, according to new research.

Data from the KEYNOTE-045 trial was presented simultaneously at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology, and published in the New England Journal of Medicine.

The open-label, international phase III trial involved 542 patients with advanced urothelial carcinoma that had recurred or progressed after platinum-based chemotherapy. Participants were randomized either to 200 mg pembrolizumab every 3 weeks, or the investigator’s choice of paclitaxel, docetaxel, or vinflunine chemotherapy.

After a median follow-up of 14.1 months, researchers saw a 27% lower hazard ratio for death among the pembrolizumab group, compared with the chemotherapy group (P = .002), with a median overall survival of 10.3 months with pembrolizumab, compared with 7.4 months with chemotherapy (N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMoa1613683).

The estimated overall survival rate at 1 year was 43.9% among those treated with pembrolizumab and 30.7% in the chemotherapy group. The authors also saw no significant differences when each chemotherapy regimen was examined separately.

Patients treated with pembrolizumab also showed a significant higher objective response rate, compared with those treated with chemotherapy (21.1% vs. 11.4%, P = .001). At the time of data cut-off, 72% of patients in the pembrolizumab group showed a continued response, compared with 35% of the chemotherapy group.

“Most responses in patients in the pembrolizumab group occurred quickly and were reported at the first scheduled imaging assessment,” wrote Joaquim Bellmunt, MD, PhD, from the Dana-Farber Cancer Institute, Boston and his coauthors. “Continued disease regression over time in some patients resulted in radiologically confirmed responses that were reported as long as 6.3 months after the start of therapy.”

They also looked at how the level of programmed death 1 ligand (PD-L1) expression in the tumor influenced response by examining outcomes in a subgroup of patients whose tumor PD-L1 combined positive score – the percentage of PD-L1 expressing tumor and infiltrating immune cells relative to the total number of tumor cells – exceeded 10%.

In this group, median overall survival was 8 months with pembrolizumab, compared with 5.2 months with chemotherapy, representing a significant 43% reduction in mortality with immunotherapy.

There was an interaction between smoking status and response, with current smokers showing a significantly greater response that favored pembrolizumab. The authors pointed out that this effect has also been observed in other advanced cancers, and may reflect the impact of a greater mutational load in the cancers of smokers.

The study did not find any difference in the duration of progression-free survival between the two groups, nor among participants with a PD-L1 combined positive score of 10% of more. Median progression-free survival was 2.1 months in the pembrolizumab group and 3.3 months in the chemotherapy group.

Researchers also noted a lower rate of adverse events among patients treated with pembrolizumab, compared with chemotherapy. Treatment-related adverse events of grade 3-5 occurred in 49.4% of patients on chemotherapy, compared with 15% of those on pembrolizumab.

There was one death from treatment-related pneumonitis in the pembrolizumab group, and three deaths attributed to the study treatment; one urinary tract obstruction, one malignant neoplasm, and one unspecified cause. In the chemotherapy group, there were two treatment-related deaths from sepsis, one from septic shock, and one unspecified.

The most common adverse events with chemotherapy were alopecia, fatigue, and anemia, while in the pembrolizumab group the most common side effects were pruritis, fatigue, and nausea.

The study was supported by Merck. Sixteen authors declared personal fees, grants, honoraria, consultancies, and advisory board positions with pharmaceutical companies including Merck, three authors were employees of Merck with stock options, and one had nothing to declare.

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Key clinical point: Pembrolizumab is associated with significant gains in overall survival among patients with treatment-refractory advanced urothelial carcinoma.

Major finding: Patients treated with pembrolizumab had a 27% lower mortality, compared with those treated with chemotherapy.

Data source: The KEYNOTE-045 open-label, international phase III trial in 542 patients with advanced urothelial carcinoma.

Disclosures: The study was supported by Merck. Sixteen authors declared personal fees, grants, honoraria, consultancies, and advisory board positions with pharmaceutical companies including Merck, three authors were employees of Merck with stock options, and one had nothing to declare.

CGM safe and effective without additional blood glucose testing

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Continuous glucose monitoring alone is safe and effective without the addition of confirmatory blood glucose monitoring, according to the authors of a noninferiority trial published in the April issue of Diabetes Care.

Before December 2016, continuous glucose monitoring (CGM) was approved by the Food and Drug Administration for use only as an adjunct to standard home blood glucose monitoring (BGM), which was required to confirm the continuous glucose monitoring reading before making a decision on insulin dosing.

©Boarding1Now/Thinkstock
“To date, no clinical trials have confirmed the safety and effectiveness of CGM used without BGM to make therapeutic decisions in people with T1D [type 1 diabetes],” wrote Grazia Aleppo-Kacmarek, MD, from Northwestern University, Chicago, and her coauthors (Diabetes Care. 2017;40:1-8. doi: 10.2337/dc16-2482).

In this randomized, noninferiority trial, 217 participants with type 1 diabetes who used an insulin pump were randomized either to CGM only (142 individuals) or to CGM with additional BGM before an insulin bolus was administered (75 individuals).

The primary outcome of the 26-week trial was time in the range of 70-180 mg/dL, according to findings from the CGM, and the study found that mean time in this range was the same for the two groups: 65%.

There were no severe hypoglycemic events in the CGM-only group, and only one in the CGM plus BGM group. There were also no significant changes from baseline to 26 weeks in other metrics of glucose control for mean glucose, hyperglycemia, hypoglycemia, and glycemic variability, and no significant differences between the two groups. The results were also similar for subgroups of age, duration of disease, education, use of CGM before study enrollment, baseline hemoglobin A1c, and baseline time in range.

“In addition to randomization and multiple center participation, the strengths of this study include a high degree of participant retention, CGM use, and treatment group adherence,” the authors wrote. “Notably, there was good separation between the treatment groups in the number of BGM tests per day, particularly when recognizing that two of the BGM measurements per day were required for CGM calibration and that, according to the protocol, the calibrations were performed at times such that they would not influence insulin bolusing.”

The authors said the results were likely to be equally applicable to individuals who use multiple daily insulin injections rather than an insulin pump, as the accuracy of the CGM sensor was just as relevant to this group.

They stressed that one major limitation of the trial was that it only included adults with well-controlled type 1 diabetes who were likely to adhere to the study protocol, and it excluded those with less well controlled disease.

Given this, they called for future studies to examine the safety of CGM alone in young people and adults who might be less compliant with their diabetes control, such as those with higher HbA1c levels, who test their blood glucose fewer than four times a day, and who are hypoglycemia-unaware.

“The application of this trial’s results to clinical practice can benefit people with T1D by reducing their burden of multiple daily fingersticks when using CGM and can enhance the cost-effectiveness of CGM therapy by reducing the number of daily BGM test strips,” they wrote. “Furthermore, the demonstration that insulin dosing based on CGM alone is safe has applicability to assessing risk involved with artificial pancreas systems that automate insulin delivery based on CGM sensor glucose measurements.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust, and Dexcom provided the CGM systems used in the trial. Authors declared speakers fees, consultancies, board positions and other funding from a range of pharmaceutical companies, including Dexcom. One author declared stock in Dexcom.

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Continuous glucose monitoring alone is safe and effective without the addition of confirmatory blood glucose monitoring, according to the authors of a noninferiority trial published in the April issue of Diabetes Care.

Before December 2016, continuous glucose monitoring (CGM) was approved by the Food and Drug Administration for use only as an adjunct to standard home blood glucose monitoring (BGM), which was required to confirm the continuous glucose monitoring reading before making a decision on insulin dosing.

©Boarding1Now/Thinkstock
“To date, no clinical trials have confirmed the safety and effectiveness of CGM used without BGM to make therapeutic decisions in people with T1D [type 1 diabetes],” wrote Grazia Aleppo-Kacmarek, MD, from Northwestern University, Chicago, and her coauthors (Diabetes Care. 2017;40:1-8. doi: 10.2337/dc16-2482).

In this randomized, noninferiority trial, 217 participants with type 1 diabetes who used an insulin pump were randomized either to CGM only (142 individuals) or to CGM with additional BGM before an insulin bolus was administered (75 individuals).

The primary outcome of the 26-week trial was time in the range of 70-180 mg/dL, according to findings from the CGM, and the study found that mean time in this range was the same for the two groups: 65%.

There were no severe hypoglycemic events in the CGM-only group, and only one in the CGM plus BGM group. There were also no significant changes from baseline to 26 weeks in other metrics of glucose control for mean glucose, hyperglycemia, hypoglycemia, and glycemic variability, and no significant differences between the two groups. The results were also similar for subgroups of age, duration of disease, education, use of CGM before study enrollment, baseline hemoglobin A1c, and baseline time in range.

“In addition to randomization and multiple center participation, the strengths of this study include a high degree of participant retention, CGM use, and treatment group adherence,” the authors wrote. “Notably, there was good separation between the treatment groups in the number of BGM tests per day, particularly when recognizing that two of the BGM measurements per day were required for CGM calibration and that, according to the protocol, the calibrations were performed at times such that they would not influence insulin bolusing.”

The authors said the results were likely to be equally applicable to individuals who use multiple daily insulin injections rather than an insulin pump, as the accuracy of the CGM sensor was just as relevant to this group.

They stressed that one major limitation of the trial was that it only included adults with well-controlled type 1 diabetes who were likely to adhere to the study protocol, and it excluded those with less well controlled disease.

Given this, they called for future studies to examine the safety of CGM alone in young people and adults who might be less compliant with their diabetes control, such as those with higher HbA1c levels, who test their blood glucose fewer than four times a day, and who are hypoglycemia-unaware.

“The application of this trial’s results to clinical practice can benefit people with T1D by reducing their burden of multiple daily fingersticks when using CGM and can enhance the cost-effectiveness of CGM therapy by reducing the number of daily BGM test strips,” they wrote. “Furthermore, the demonstration that insulin dosing based on CGM alone is safe has applicability to assessing risk involved with artificial pancreas systems that automate insulin delivery based on CGM sensor glucose measurements.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust, and Dexcom provided the CGM systems used in the trial. Authors declared speakers fees, consultancies, board positions and other funding from a range of pharmaceutical companies, including Dexcom. One author declared stock in Dexcom.

 

Continuous glucose monitoring alone is safe and effective without the addition of confirmatory blood glucose monitoring, according to the authors of a noninferiority trial published in the April issue of Diabetes Care.

Before December 2016, continuous glucose monitoring (CGM) was approved by the Food and Drug Administration for use only as an adjunct to standard home blood glucose monitoring (BGM), which was required to confirm the continuous glucose monitoring reading before making a decision on insulin dosing.

©Boarding1Now/Thinkstock
“To date, no clinical trials have confirmed the safety and effectiveness of CGM used without BGM to make therapeutic decisions in people with T1D [type 1 diabetes],” wrote Grazia Aleppo-Kacmarek, MD, from Northwestern University, Chicago, and her coauthors (Diabetes Care. 2017;40:1-8. doi: 10.2337/dc16-2482).

In this randomized, noninferiority trial, 217 participants with type 1 diabetes who used an insulin pump were randomized either to CGM only (142 individuals) or to CGM with additional BGM before an insulin bolus was administered (75 individuals).

The primary outcome of the 26-week trial was time in the range of 70-180 mg/dL, according to findings from the CGM, and the study found that mean time in this range was the same for the two groups: 65%.

There were no severe hypoglycemic events in the CGM-only group, and only one in the CGM plus BGM group. There were also no significant changes from baseline to 26 weeks in other metrics of glucose control for mean glucose, hyperglycemia, hypoglycemia, and glycemic variability, and no significant differences between the two groups. The results were also similar for subgroups of age, duration of disease, education, use of CGM before study enrollment, baseline hemoglobin A1c, and baseline time in range.

“In addition to randomization and multiple center participation, the strengths of this study include a high degree of participant retention, CGM use, and treatment group adherence,” the authors wrote. “Notably, there was good separation between the treatment groups in the number of BGM tests per day, particularly when recognizing that two of the BGM measurements per day were required for CGM calibration and that, according to the protocol, the calibrations were performed at times such that they would not influence insulin bolusing.”

The authors said the results were likely to be equally applicable to individuals who use multiple daily insulin injections rather than an insulin pump, as the accuracy of the CGM sensor was just as relevant to this group.

They stressed that one major limitation of the trial was that it only included adults with well-controlled type 1 diabetes who were likely to adhere to the study protocol, and it excluded those with less well controlled disease.

Given this, they called for future studies to examine the safety of CGM alone in young people and adults who might be less compliant with their diabetes control, such as those with higher HbA1c levels, who test their blood glucose fewer than four times a day, and who are hypoglycemia-unaware.

“The application of this trial’s results to clinical practice can benefit people with T1D by reducing their burden of multiple daily fingersticks when using CGM and can enhance the cost-effectiveness of CGM therapy by reducing the number of daily BGM test strips,” they wrote. “Furthermore, the demonstration that insulin dosing based on CGM alone is safe has applicability to assessing risk involved with artificial pancreas systems that automate insulin delivery based on CGM sensor glucose measurements.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust, and Dexcom provided the CGM systems used in the trial. Authors declared speakers fees, consultancies, board positions and other funding from a range of pharmaceutical companies, including Dexcom. One author declared stock in Dexcom.

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Key clinical point: Continuous glucose monitoring alone is safe and effective without the addition of confirmatory blood glucose monitoring.

Major finding: Mean time spent with blood glucose in the 70-180 mg/dL range was the same for individuals with continuous glucose monitoring and those with additional confirmatory blood glucose testing.

Data source: A randomized noninferiority trial in 217 adults with well-controlled type 1 diabetes.

Disclosures: The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dexcom provided the continuous glucose monitoring systems used in the trial. Authors declared speaking fees, consultancies, board positions and other funding from a range of pharmaceutical companies, including Dexcom. One author declared stock ownership in Dexcom.

Lower C. difficile mortality with vancomycin than metronidazole

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Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

 

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

AGA Resource

AGA offers patient education materials to help you discuss C. diff with your patients at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.

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Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

 

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

AGA Resource

AGA offers patient education materials to help you discuss C. diff with your patients at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.

 

Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

 

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

AGA Resource

AGA offers patient education materials to help you discuss C. diff with your patients at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.

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Key clinical point: Vancomycin therapy is associated with significantly lower 30-day mortality from severe Clostridium difficile infection compared to metronidazole.

Major finding: Treatment with vancomycin prevented one death per 25 patients with severe C. difficile infection.

Data source: A retrospective, propensity-matched cohort study of 47,471 patients with C. difficile infection.

Disclosures: The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

Lower C. difficile mortality with vancomycin than metronidazole

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Display Headline
Lower C. difficile mortality with vancomycin than metronidazole

 

Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

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Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

 

Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

CDC/D. Holdeman


“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

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Lower C. difficile mortality with vancomycin than metronidazole
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Key clinical point: Vancomycin therapy is associated with significantly lower 30-day mortality from severe Clostridium difficile infection compared to metronidazole.

Major finding: Treatment with vancomycin prevented one death per 25 patients with severe C. difficile infection.

Data source: A retrospective, propensity-matched cohort study of 47,471 patients with C. difficile infection.

Disclosures: The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

Case series shows benefit of nonthermal atmospheric pressure plasma for actinic keratoses

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Nonthermal atmospheric pressure plasma (NTAP) may serve as an effective, well-tolerated treatment for actinic keratoses, according to findings of a small study published in the February issue of Journal of the American Academy of Dermatology.

Dr. Peter C. Friedman and his associates at the Skin Center Dermatology Group, New York, wrote that prior studies suggest that NTAP – applied with a hand-held electrode – could selectively induce apoptosis in cancer cells in vitro, and may also up-regulate local and tumor-specific systemic immune response.

In this study, five patients with 5 biopsy-proven and 12 clinically diagnosed actinic keratoses (AKs) were treated with a single dose of NTAP on the target lesion. The procedure involved nanosecond pulses that were applied to the treatment area for 1-2 minutes, an approach designed to provide sufficient dose while avoiding tissue damage (J Am Acad Dermatol. 2017 Feb. doi: 10.1016/j.jaad.2016.09.004).

At the 1-month follow-up – in which photographs were used to compare before and after treatment – 9 of the 17 AK lesions showed full clinical resolution, with no visible or palpable lesions and only minimal site erythema. Three lesions showed significant improvement, with at least a 50% improvement, and five lesions should minor or no improvement.

Dr. Friedman and his associates noted that current treatment options for AKs all have significant downsides including side effects such as pain and inflammation, and frequent recurrences. There were no adverse effects, such as pain, inflammation, or site reaction, reported during treatment with NTAP or 1 month after treatment.

“Given its very impressive tolerability, NTAP may be an excellent alternative for our current treatment options for AKs, especially if its efficacy and treatment procedure time can be improved and if further, long-term studies demonstrate lasting effects,” the authors wrote. “Further studies are needed to optimize treatment parameters, provide histologic confirmation of treatment effect, and evaluate the long-term benefits of this modality.”

No conflicts of interest were declared.

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Nonthermal atmospheric pressure plasma (NTAP) may serve as an effective, well-tolerated treatment for actinic keratoses, according to findings of a small study published in the February issue of Journal of the American Academy of Dermatology.

Dr. Peter C. Friedman and his associates at the Skin Center Dermatology Group, New York, wrote that prior studies suggest that NTAP – applied with a hand-held electrode – could selectively induce apoptosis in cancer cells in vitro, and may also up-regulate local and tumor-specific systemic immune response.

In this study, five patients with 5 biopsy-proven and 12 clinically diagnosed actinic keratoses (AKs) were treated with a single dose of NTAP on the target lesion. The procedure involved nanosecond pulses that were applied to the treatment area for 1-2 minutes, an approach designed to provide sufficient dose while avoiding tissue damage (J Am Acad Dermatol. 2017 Feb. doi: 10.1016/j.jaad.2016.09.004).

At the 1-month follow-up – in which photographs were used to compare before and after treatment – 9 of the 17 AK lesions showed full clinical resolution, with no visible or palpable lesions and only minimal site erythema. Three lesions showed significant improvement, with at least a 50% improvement, and five lesions should minor or no improvement.

Dr. Friedman and his associates noted that current treatment options for AKs all have significant downsides including side effects such as pain and inflammation, and frequent recurrences. There were no adverse effects, such as pain, inflammation, or site reaction, reported during treatment with NTAP or 1 month after treatment.

“Given its very impressive tolerability, NTAP may be an excellent alternative for our current treatment options for AKs, especially if its efficacy and treatment procedure time can be improved and if further, long-term studies demonstrate lasting effects,” the authors wrote. “Further studies are needed to optimize treatment parameters, provide histologic confirmation of treatment effect, and evaluate the long-term benefits of this modality.”

No conflicts of interest were declared.

 

Nonthermal atmospheric pressure plasma (NTAP) may serve as an effective, well-tolerated treatment for actinic keratoses, according to findings of a small study published in the February issue of Journal of the American Academy of Dermatology.

Dr. Peter C. Friedman and his associates at the Skin Center Dermatology Group, New York, wrote that prior studies suggest that NTAP – applied with a hand-held electrode – could selectively induce apoptosis in cancer cells in vitro, and may also up-regulate local and tumor-specific systemic immune response.

In this study, five patients with 5 biopsy-proven and 12 clinically diagnosed actinic keratoses (AKs) were treated with a single dose of NTAP on the target lesion. The procedure involved nanosecond pulses that were applied to the treatment area for 1-2 minutes, an approach designed to provide sufficient dose while avoiding tissue damage (J Am Acad Dermatol. 2017 Feb. doi: 10.1016/j.jaad.2016.09.004).

At the 1-month follow-up – in which photographs were used to compare before and after treatment – 9 of the 17 AK lesions showed full clinical resolution, with no visible or palpable lesions and only minimal site erythema. Three lesions showed significant improvement, with at least a 50% improvement, and five lesions should minor or no improvement.

Dr. Friedman and his associates noted that current treatment options for AKs all have significant downsides including side effects such as pain and inflammation, and frequent recurrences. There were no adverse effects, such as pain, inflammation, or site reaction, reported during treatment with NTAP or 1 month after treatment.

“Given its very impressive tolerability, NTAP may be an excellent alternative for our current treatment options for AKs, especially if its efficacy and treatment procedure time can be improved and if further, long-term studies demonstrate lasting effects,” the authors wrote. “Further studies are needed to optimize treatment parameters, provide histologic confirmation of treatment effect, and evaluate the long-term benefits of this modality.”

No conflicts of interest were declared.

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Key clinical point: Nonthermal atmospheric pressure plasma may be an effective, well-tolerated treatment for actinic keratoses.

Major finding: One month after a single treatment with NTAP, 9 of 17 AK lesions showed full clinical resolution and 3 lesions showed significant improvement.

Data source: Case series in five patients with actinic keratoses.

Disclosures: No conflicts of interest were declared.

Intermediate nature of ‘incomplete’ lupus shown in large study

Improved classification criteria needed for ILE
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People with incomplete lupus erythematosus exhibit nearly as many disease-related symptoms as do those with systemic lupus erythematosus and often receive many of the same treatments, according to findings reported from a cohort study of 3,837 patients registered with the Lupus Family Registry and Repository.

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Dr. David Kaikh
While having data-driven, universally used, and accepted criteria for classification of disease is essential for interpretation of clinical studies, and most importantly for enrollment and interpretation of clinical trials of potentially toxic agents, classification criteria fall short in clinical care. Even without applying rules from a classification scheme, it is common in clinical practice to see patients with typical manifestations of systemic lupus erythematosus who do not appear to have all of the features of a complete syndrome.

 

Where the study from Ms. Aberle and her colleagues most advances knowledge of these intermediate phenotype ILE patients is in the more sophisticated interrogation of the immunologic features of ILE vs. SLE patients than has been performed in past studies. These findings are consistent with the conception of ILE as an intermediate state between health and “complete lupus” with similar, but less immune dysregulation than patients classified with SLE.

Dr. Karen Costenbader
The results also underscore the need for further classification criteria for ILE patients, with the goal of identifying those who need closer monitoring and have higher risk for severe or progressive disease progression.
 

Karen H. Costenbader, MD, is with the division of rheumatology, immunology and allergy at Brigham and Women’s Hospital, Boston, and David I. Daikh, MD, is with the division of rheumatology at the University of California, San Francisco. These comments are adapted from an accompanying editorial (Arthritis Care Res. 2017 Jan 24. doi: 10.1002/acr.23196). No conflicts of interest were declared.

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Dr. David Kaikh
While having data-driven, universally used, and accepted criteria for classification of disease is essential for interpretation of clinical studies, and most importantly for enrollment and interpretation of clinical trials of potentially toxic agents, classification criteria fall short in clinical care. Even without applying rules from a classification scheme, it is common in clinical practice to see patients with typical manifestations of systemic lupus erythematosus who do not appear to have all of the features of a complete syndrome.

 

Where the study from Ms. Aberle and her colleagues most advances knowledge of these intermediate phenotype ILE patients is in the more sophisticated interrogation of the immunologic features of ILE vs. SLE patients than has been performed in past studies. These findings are consistent with the conception of ILE as an intermediate state between health and “complete lupus” with similar, but less immune dysregulation than patients classified with SLE.

Dr. Karen Costenbader
The results also underscore the need for further classification criteria for ILE patients, with the goal of identifying those who need closer monitoring and have higher risk for severe or progressive disease progression.
 

Karen H. Costenbader, MD, is with the division of rheumatology, immunology and allergy at Brigham and Women’s Hospital, Boston, and David I. Daikh, MD, is with the division of rheumatology at the University of California, San Francisco. These comments are adapted from an accompanying editorial (Arthritis Care Res. 2017 Jan 24. doi: 10.1002/acr.23196). No conflicts of interest were declared.

Body

 

Dr. David Kaikh
While having data-driven, universally used, and accepted criteria for classification of disease is essential for interpretation of clinical studies, and most importantly for enrollment and interpretation of clinical trials of potentially toxic agents, classification criteria fall short in clinical care. Even without applying rules from a classification scheme, it is common in clinical practice to see patients with typical manifestations of systemic lupus erythematosus who do not appear to have all of the features of a complete syndrome.

 

Where the study from Ms. Aberle and her colleagues most advances knowledge of these intermediate phenotype ILE patients is in the more sophisticated interrogation of the immunologic features of ILE vs. SLE patients than has been performed in past studies. These findings are consistent with the conception of ILE as an intermediate state between health and “complete lupus” with similar, but less immune dysregulation than patients classified with SLE.

Dr. Karen Costenbader
The results also underscore the need for further classification criteria for ILE patients, with the goal of identifying those who need closer monitoring and have higher risk for severe or progressive disease progression.
 

Karen H. Costenbader, MD, is with the division of rheumatology, immunology and allergy at Brigham and Women’s Hospital, Boston, and David I. Daikh, MD, is with the division of rheumatology at the University of California, San Francisco. These comments are adapted from an accompanying editorial (Arthritis Care Res. 2017 Jan 24. doi: 10.1002/acr.23196). No conflicts of interest were declared.

Title
Improved classification criteria needed for ILE
Improved classification criteria needed for ILE

 

People with incomplete lupus erythematosus exhibit nearly as many disease-related symptoms as do those with systemic lupus erythematosus and often receive many of the same treatments, according to findings reported from a cohort study of 3,837 patients registered with the Lupus Family Registry and Repository.

 

People with incomplete lupus erythematosus exhibit nearly as many disease-related symptoms as do those with systemic lupus erythematosus and often receive many of the same treatments, according to findings reported from a cohort study of 3,837 patients registered with the Lupus Family Registry and Repository.

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Key clinical point: People with incomplete lupus erythematosus exhibit the same range of symptoms as do those with systemic lupus erythematosus but with less immune dysregulation.

Major finding: Each lupus classification criterion was seen in at least some incomplete lupus erythematosus patients, although systemic lupus erythematosus patients were significantly more likely to have protein in urine, low blood counts, and experience seizures.

Data source: A cohort study of 3,837 patients registered with the Lupus Family Registry and Repository.

Disclosures: The National Institutes of Health and the U.S. Department of Veterans Affairs supported the study. One author reported grants from pharmaceutical companies outside of the submitted work, and there were no other conflicts of interest declared.

Incidence of IBD is elevated in hidradenitis suppurativa patients

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Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

Elsevier Inc.
The study of 7,732 patients with a hospital diagnosis of HS, and 4,354,137 controls from the general population, found that the baseline prevalence of Crohn’s disease was twofold higher in individuals with HS, compared with the general population (0.8% vs. 0.3%; odds ratio, 2.04; P less than .0001), after adjustment for age, sex, socioeconomic status, health care consumption, smoking, and alcohol abuse.

Similarly, the incidence of ulcerative colitis was about 1.8-fold higher among individuals with HS, compared with controls (1.3% vs. 0.7%; OR, 1.75; P less than .002), and the incidence of “unspecified” inflammatory bowel disease was 3.4-fold higher (0.7% vs. 0.1%; OR, 3.40; P less than .007), according to a paper published online in the Journal of Investigative Dermatology.

Dr. Egeberg and his coauthors reported that HS and inflammatory bowel disease similarities suggest a shared pathogenesis, including the worsening effect of smoking on both conditions; the appearance of scarring and sinus tract formation; the apparent involvement of T-helper 17 cells, interleukin-23, and tumor necrosis factor; and the coinvolvement of genes such as SULT1B1 and SULT1E1 (J Invest Dermatol. 2017 Jan 13. doi: 10.1016/j.jid.2016.11.040).

“Finally, an increased prevalence of spondylarthropathy has been reported in patients with IBD as well as in those with HS, raising the hypothesis that genetic, epigenetic, and/or environmental factors cooperate to lead to dysregulated inflammatory pathways across these immune-mediated diseases,” the authors wrote.

While previous study evidence linking HS and IBD has been inconsistent, the authors said their findings suggested an increased incidence of IBD in individuals with HS – ranging from 0.13 to 0.97 per 1,000 HS patients per year.

They acknowledged that the study population was predominantly of Northern European descent, and the results might not be generalizable to patients of other ethnicities. They also noted that patients with HS identified by hospital diagnoses may therefore have had greater comorbidity than patients sampled from a population setting.

The study was funded by Eli Lilly, and one author is an employee of Eli Lilly. Five other authors declared research funding, grants, consultancies, honoraria, consultancy, and board positions for various pharmaceutical companies, including Eli Lilly.

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Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

Elsevier Inc.
The study of 7,732 patients with a hospital diagnosis of HS, and 4,354,137 controls from the general population, found that the baseline prevalence of Crohn’s disease was twofold higher in individuals with HS, compared with the general population (0.8% vs. 0.3%; odds ratio, 2.04; P less than .0001), after adjustment for age, sex, socioeconomic status, health care consumption, smoking, and alcohol abuse.

Similarly, the incidence of ulcerative colitis was about 1.8-fold higher among individuals with HS, compared with controls (1.3% vs. 0.7%; OR, 1.75; P less than .002), and the incidence of “unspecified” inflammatory bowel disease was 3.4-fold higher (0.7% vs. 0.1%; OR, 3.40; P less than .007), according to a paper published online in the Journal of Investigative Dermatology.

Dr. Egeberg and his coauthors reported that HS and inflammatory bowel disease similarities suggest a shared pathogenesis, including the worsening effect of smoking on both conditions; the appearance of scarring and sinus tract formation; the apparent involvement of T-helper 17 cells, interleukin-23, and tumor necrosis factor; and the coinvolvement of genes such as SULT1B1 and SULT1E1 (J Invest Dermatol. 2017 Jan 13. doi: 10.1016/j.jid.2016.11.040).

“Finally, an increased prevalence of spondylarthropathy has been reported in patients with IBD as well as in those with HS, raising the hypothesis that genetic, epigenetic, and/or environmental factors cooperate to lead to dysregulated inflammatory pathways across these immune-mediated diseases,” the authors wrote.

While previous study evidence linking HS and IBD has been inconsistent, the authors said their findings suggested an increased incidence of IBD in individuals with HS – ranging from 0.13 to 0.97 per 1,000 HS patients per year.

They acknowledged that the study population was predominantly of Northern European descent, and the results might not be generalizable to patients of other ethnicities. They also noted that patients with HS identified by hospital diagnoses may therefore have had greater comorbidity than patients sampled from a population setting.

The study was funded by Eli Lilly, and one author is an employee of Eli Lilly. Five other authors declared research funding, grants, consultancies, honoraria, consultancy, and board positions for various pharmaceutical companies, including Eli Lilly.

 

Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

Elsevier Inc.
The study of 7,732 patients with a hospital diagnosis of HS, and 4,354,137 controls from the general population, found that the baseline prevalence of Crohn’s disease was twofold higher in individuals with HS, compared with the general population (0.8% vs. 0.3%; odds ratio, 2.04; P less than .0001), after adjustment for age, sex, socioeconomic status, health care consumption, smoking, and alcohol abuse.

Similarly, the incidence of ulcerative colitis was about 1.8-fold higher among individuals with HS, compared with controls (1.3% vs. 0.7%; OR, 1.75; P less than .002), and the incidence of “unspecified” inflammatory bowel disease was 3.4-fold higher (0.7% vs. 0.1%; OR, 3.40; P less than .007), according to a paper published online in the Journal of Investigative Dermatology.

Dr. Egeberg and his coauthors reported that HS and inflammatory bowel disease similarities suggest a shared pathogenesis, including the worsening effect of smoking on both conditions; the appearance of scarring and sinus tract formation; the apparent involvement of T-helper 17 cells, interleukin-23, and tumor necrosis factor; and the coinvolvement of genes such as SULT1B1 and SULT1E1 (J Invest Dermatol. 2017 Jan 13. doi: 10.1016/j.jid.2016.11.040).

“Finally, an increased prevalence of spondylarthropathy has been reported in patients with IBD as well as in those with HS, raising the hypothesis that genetic, epigenetic, and/or environmental factors cooperate to lead to dysregulated inflammatory pathways across these immune-mediated diseases,” the authors wrote.

While previous study evidence linking HS and IBD has been inconsistent, the authors said their findings suggested an increased incidence of IBD in individuals with HS – ranging from 0.13 to 0.97 per 1,000 HS patients per year.

They acknowledged that the study population was predominantly of Northern European descent, and the results might not be generalizable to patients of other ethnicities. They also noted that patients with HS identified by hospital diagnoses may therefore have had greater comorbidity than patients sampled from a population setting.

The study was funded by Eli Lilly, and one author is an employee of Eli Lilly. Five other authors declared research funding, grants, consultancies, honoraria, consultancy, and board positions for various pharmaceutical companies, including Eli Lilly.

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FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

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Key clinical point: Individuals with hidradenitis suppurativa may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis.

Major finding: The baseline prevalence of Crohn’s disease is twofold higher, and ulcerative colitis is about 1.8-fold higher, in individuals with hidradenitis suppurativa, compared with the general population.

Data source: A population-based cohort study in 7,732 patients with a hospital diagnosis of hidradenitis suppurativa, and 4,354,137 controls.

Disclosures: The study was funded by Eli Lilly, and one author is an employee of Eli Lilly. Five other authors declared research funding, grants, consultancies, honoraria, consultancy, and board positions for various pharmaceutical companies, including Eli Lilly.

1 in 10 youths, 1 in 4 adults in U.S. use tobacco products

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More than one in four U.S. adults are current users of at least one type of tobacco product, and nearly 1 in 10 youths report using tobacco in the previous month, according to a report published in the Jan. 26 edition of the New England Journal of Medicine.

Analysis of data from 45,971 adults and youths aged 12 years and older in Wave 1 of the national longitudinal Population Assessment of Tobacco and Health (PATH) study showed 28% of adults were current users of tobacco products, and 20% were daily users. Cigarettes were the most commonly used tobacco product: 18% of adults said they were current users of cigarettes and 16% were daily users. Cigars and e-cigarettes were the next most common tobacco products, with 8% of adults currently using cigars, and 6% currently using e-cigarettes. (N Eng J Med. 2016, Jan 26. doi: 10.1056/NEJMsa1607538).

pmphoto/iStockphoto.com
The overall prevalence of tobacco use in the previous 30 days among those aged 12-17 years was 9%. Among youths aged 15-17 years, 15% said they had used any tobacco product in the previous 30 days – 8% cigarettes, 58% e-cigarettes, and 5% cigars – while 3% reported daily tobacco use.

“Among adults, tobacco use was generally higher among younger adults, men, members of racial minorities, members of sexual minorities, those with lower educational attainment and lower household income, and those living in the South or Midwest than among their counterparts,” wrote Karin A. Kasza of the department of health behavior at the Roswell Park Cancer Institute, Buffalo, N.Y., and coauthors. “Among youths, the prevalences of ever use and use in the previous 30 days were higher among older youths, male youths, and members of sexual minorities than among their counterparts.”

Many also reported using combinations of tobacco products in the previous 30 days, with 23% of adults and 15% of youths using cigarettes and e-cigarettes concurrently.

The authors noted that the estimates of tobacco use among youths obtained from this household-based survey were lower than those seen in previous school-based surveys, and suggested the survey method may have influenced young people’s responses.

“Surveys administered in a school-based environment may overestimate tobacco-use behaviors because of peer influences, whereas youths may underreport tobacco-use behaviors in a home-based survey out of fear that their parents will overhear answers or learn about them from the interviewer,” Ms. Kasza and her associates wrote.

The study was supported by the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration and U.S. Department of Health and Human Services under a contract to Westat. One author declared grant support from a pharmaceutical company and having acted as an expert witness against the tobacco industry. Another declared advisory board positions and grant support from private industry, and a third declared stock in private industry. No other conflicts of interest were declared.

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More than one in four U.S. adults are current users of at least one type of tobacco product, and nearly 1 in 10 youths report using tobacco in the previous month, according to a report published in the Jan. 26 edition of the New England Journal of Medicine.

Analysis of data from 45,971 adults and youths aged 12 years and older in Wave 1 of the national longitudinal Population Assessment of Tobacco and Health (PATH) study showed 28% of adults were current users of tobacco products, and 20% were daily users. Cigarettes were the most commonly used tobacco product: 18% of adults said they were current users of cigarettes and 16% were daily users. Cigars and e-cigarettes were the next most common tobacco products, with 8% of adults currently using cigars, and 6% currently using e-cigarettes. (N Eng J Med. 2016, Jan 26. doi: 10.1056/NEJMsa1607538).

pmphoto/iStockphoto.com
The overall prevalence of tobacco use in the previous 30 days among those aged 12-17 years was 9%. Among youths aged 15-17 years, 15% said they had used any tobacco product in the previous 30 days – 8% cigarettes, 58% e-cigarettes, and 5% cigars – while 3% reported daily tobacco use.

“Among adults, tobacco use was generally higher among younger adults, men, members of racial minorities, members of sexual minorities, those with lower educational attainment and lower household income, and those living in the South or Midwest than among their counterparts,” wrote Karin A. Kasza of the department of health behavior at the Roswell Park Cancer Institute, Buffalo, N.Y., and coauthors. “Among youths, the prevalences of ever use and use in the previous 30 days were higher among older youths, male youths, and members of sexual minorities than among their counterparts.”

Many also reported using combinations of tobacco products in the previous 30 days, with 23% of adults and 15% of youths using cigarettes and e-cigarettes concurrently.

The authors noted that the estimates of tobacco use among youths obtained from this household-based survey were lower than those seen in previous school-based surveys, and suggested the survey method may have influenced young people’s responses.

“Surveys administered in a school-based environment may overestimate tobacco-use behaviors because of peer influences, whereas youths may underreport tobacco-use behaviors in a home-based survey out of fear that their parents will overhear answers or learn about them from the interviewer,” Ms. Kasza and her associates wrote.

The study was supported by the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration and U.S. Department of Health and Human Services under a contract to Westat. One author declared grant support from a pharmaceutical company and having acted as an expert witness against the tobacco industry. Another declared advisory board positions and grant support from private industry, and a third declared stock in private industry. No other conflicts of interest were declared.

 

More than one in four U.S. adults are current users of at least one type of tobacco product, and nearly 1 in 10 youths report using tobacco in the previous month, according to a report published in the Jan. 26 edition of the New England Journal of Medicine.

Analysis of data from 45,971 adults and youths aged 12 years and older in Wave 1 of the national longitudinal Population Assessment of Tobacco and Health (PATH) study showed 28% of adults were current users of tobacco products, and 20% were daily users. Cigarettes were the most commonly used tobacco product: 18% of adults said they were current users of cigarettes and 16% were daily users. Cigars and e-cigarettes were the next most common tobacco products, with 8% of adults currently using cigars, and 6% currently using e-cigarettes. (N Eng J Med. 2016, Jan 26. doi: 10.1056/NEJMsa1607538).

pmphoto/iStockphoto.com
The overall prevalence of tobacco use in the previous 30 days among those aged 12-17 years was 9%. Among youths aged 15-17 years, 15% said they had used any tobacco product in the previous 30 days – 8% cigarettes, 58% e-cigarettes, and 5% cigars – while 3% reported daily tobacco use.

“Among adults, tobacco use was generally higher among younger adults, men, members of racial minorities, members of sexual minorities, those with lower educational attainment and lower household income, and those living in the South or Midwest than among their counterparts,” wrote Karin A. Kasza of the department of health behavior at the Roswell Park Cancer Institute, Buffalo, N.Y., and coauthors. “Among youths, the prevalences of ever use and use in the previous 30 days were higher among older youths, male youths, and members of sexual minorities than among their counterparts.”

Many also reported using combinations of tobacco products in the previous 30 days, with 23% of adults and 15% of youths using cigarettes and e-cigarettes concurrently.

The authors noted that the estimates of tobacco use among youths obtained from this household-based survey were lower than those seen in previous school-based surveys, and suggested the survey method may have influenced young people’s responses.

“Surveys administered in a school-based environment may overestimate tobacco-use behaviors because of peer influences, whereas youths may underreport tobacco-use behaviors in a home-based survey out of fear that their parents will overhear answers or learn about them from the interviewer,” Ms. Kasza and her associates wrote.

The study was supported by the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration and U.S. Department of Health and Human Services under a contract to Westat. One author declared grant support from a pharmaceutical company and having acted as an expert witness against the tobacco industry. Another declared advisory board positions and grant support from private industry, and a third declared stock in private industry. No other conflicts of interest were declared.

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Key clinical point: More than one in four U.S. adults are current users of at least one type of tobacco product, and nearly 1 in 10 youths report using tobacco in the previous month.

Major finding: The PATH study found 28% of adults are current users of tobacco products, and 20% are daily users.

Data source: Wave 1 of the national longitudinal Population Assessment of Tobacco and Health (PATH) study.

Disclosures: The study was supported by the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration and U.S. Department of Health and Human Services. One author declared grant support from a pharmaceutical company and having acted as an expert witness against the tobacco industry. Another declared advisory board positions and grant support from private industry, and a third declared stock in private industry. No other conflicts of interest were declared.