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FDA rejects mepolizumab on efficacy, but supports safety for COPD
Asthma drug mepolizumab could be added safely to inhaled corticosteroids for maintenance therapy to help reduce exacerbations in chronic obstructive pulmonary disease (COPD) patients who meet criteria for eosinophil counts, but the current data do not support its efficacy strongly enough for approval, according to a majority of members of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.
The committee voted 16-3 that there was insufficient evidence of efficacy to support guided by eosinophil levels; they also voted 16-3 that the risk-benefit profile was not adequate to support approval.
However, on a voting question of safety, the committee voted 17-2 that the safety data on mepolizumab were sufficient to support approval.
Mepolizumab, a humanized monoclonal antibody, is currently approved for the treatment of asthma with eosinophilic phenotype for patients aged 12 years and older and for adults with eosinophilic granulomatosis with polyangiitis. Manufacturer GlaxoSmithKline is seeking approval for its use as an add-on therapy in COPD patients at a subcutaneous dose of 100 mg every 4 weeks. Mepolizumab works by binding to interleukin-5 (IL-5) and reducing eosinophil maturation and survival, which prompted GlaxoSmithKline to pursue an indication for COPD patients in a high-eosinophil stratum.
The application was supported in part by two concurrent randomized trials of 52 weeks’ duration.
Banu A. Karimi-Shah, MD, clinical team leader of the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products, presented data from the two studies, referred to as Study 106 and Study 113.
In Study 106, researchers found statistically significant reductions in exacerbations for patients in the highest eosinophil group. However, challenges of the studies included a lack of consensus over the definition and possible relevance of an eosinophilic COPD phenotype, Dr. Karimi-Shah said in a presentation at the meeting.
In Study 113, mepolizumab had no significant impact on reducing moderate to severe exacerbations at either a 100-mg or 300-mg dose, Dr. Karimi-Shah said. In addition, most secondary endpoints, with the exception of reducing time to the first exacerbation among patients in the highest eosinophil group, did not consistently support the primary endpoint of exacerbation reduction in either study, she said.
Robert Busch, MD, also of the FDA’s Division of Pulmonary, Allergy, and Rheumatology products, served as a clinical reviewer and presented data on safety, efficacy, and risk-benefit profile of mepolizumab.
Dr. Busch noted that the variability in blood eosinophils make it challenging to use as a potential marker to identify patients who would benefit from mepolizumab as an add-on therapy.
Overall, most of the committee agreed on the existence of an eosinophilic COPD phenotype, but expressed concern about the threshold being used.
“The studies were not particularly well controlled regarding the characterization of patients,” said William J. Calhoun, MD, of the University of Texas Medical Branch, Galveston, who cast one of the ‘no’ votes on the question of efficacy.
By contrast, Jeffrey S. Wagener, MD, of the University of Colorado at Denver, Aurora, referenced his background in cystic fibrosis, and voted “yes” on the question of efficacy. “For patients that have no other option, this is a step forward,” he said.
Committee members on both sides of the vote emphasized the need for more research with larger numbers, better patient characterization, and more female patients. The committee members reported no relevant conflicts of interest.
Asthma drug mepolizumab could be added safely to inhaled corticosteroids for maintenance therapy to help reduce exacerbations in chronic obstructive pulmonary disease (COPD) patients who meet criteria for eosinophil counts, but the current data do not support its efficacy strongly enough for approval, according to a majority of members of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.
The committee voted 16-3 that there was insufficient evidence of efficacy to support guided by eosinophil levels; they also voted 16-3 that the risk-benefit profile was not adequate to support approval.
However, on a voting question of safety, the committee voted 17-2 that the safety data on mepolizumab were sufficient to support approval.
Mepolizumab, a humanized monoclonal antibody, is currently approved for the treatment of asthma with eosinophilic phenotype for patients aged 12 years and older and for adults with eosinophilic granulomatosis with polyangiitis. Manufacturer GlaxoSmithKline is seeking approval for its use as an add-on therapy in COPD patients at a subcutaneous dose of 100 mg every 4 weeks. Mepolizumab works by binding to interleukin-5 (IL-5) and reducing eosinophil maturation and survival, which prompted GlaxoSmithKline to pursue an indication for COPD patients in a high-eosinophil stratum.
The application was supported in part by two concurrent randomized trials of 52 weeks’ duration.
Banu A. Karimi-Shah, MD, clinical team leader of the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products, presented data from the two studies, referred to as Study 106 and Study 113.
In Study 106, researchers found statistically significant reductions in exacerbations for patients in the highest eosinophil group. However, challenges of the studies included a lack of consensus over the definition and possible relevance of an eosinophilic COPD phenotype, Dr. Karimi-Shah said in a presentation at the meeting.
In Study 113, mepolizumab had no significant impact on reducing moderate to severe exacerbations at either a 100-mg or 300-mg dose, Dr. Karimi-Shah said. In addition, most secondary endpoints, with the exception of reducing time to the first exacerbation among patients in the highest eosinophil group, did not consistently support the primary endpoint of exacerbation reduction in either study, she said.
Robert Busch, MD, also of the FDA’s Division of Pulmonary, Allergy, and Rheumatology products, served as a clinical reviewer and presented data on safety, efficacy, and risk-benefit profile of mepolizumab.
Dr. Busch noted that the variability in blood eosinophils make it challenging to use as a potential marker to identify patients who would benefit from mepolizumab as an add-on therapy.
Overall, most of the committee agreed on the existence of an eosinophilic COPD phenotype, but expressed concern about the threshold being used.
“The studies were not particularly well controlled regarding the characterization of patients,” said William J. Calhoun, MD, of the University of Texas Medical Branch, Galveston, who cast one of the ‘no’ votes on the question of efficacy.
By contrast, Jeffrey S. Wagener, MD, of the University of Colorado at Denver, Aurora, referenced his background in cystic fibrosis, and voted “yes” on the question of efficacy. “For patients that have no other option, this is a step forward,” he said.
Committee members on both sides of the vote emphasized the need for more research with larger numbers, better patient characterization, and more female patients. The committee members reported no relevant conflicts of interest.
Asthma drug mepolizumab could be added safely to inhaled corticosteroids for maintenance therapy to help reduce exacerbations in chronic obstructive pulmonary disease (COPD) patients who meet criteria for eosinophil counts, but the current data do not support its efficacy strongly enough for approval, according to a majority of members of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.
The committee voted 16-3 that there was insufficient evidence of efficacy to support guided by eosinophil levels; they also voted 16-3 that the risk-benefit profile was not adequate to support approval.
However, on a voting question of safety, the committee voted 17-2 that the safety data on mepolizumab were sufficient to support approval.
Mepolizumab, a humanized monoclonal antibody, is currently approved for the treatment of asthma with eosinophilic phenotype for patients aged 12 years and older and for adults with eosinophilic granulomatosis with polyangiitis. Manufacturer GlaxoSmithKline is seeking approval for its use as an add-on therapy in COPD patients at a subcutaneous dose of 100 mg every 4 weeks. Mepolizumab works by binding to interleukin-5 (IL-5) and reducing eosinophil maturation and survival, which prompted GlaxoSmithKline to pursue an indication for COPD patients in a high-eosinophil stratum.
The application was supported in part by two concurrent randomized trials of 52 weeks’ duration.
Banu A. Karimi-Shah, MD, clinical team leader of the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products, presented data from the two studies, referred to as Study 106 and Study 113.
In Study 106, researchers found statistically significant reductions in exacerbations for patients in the highest eosinophil group. However, challenges of the studies included a lack of consensus over the definition and possible relevance of an eosinophilic COPD phenotype, Dr. Karimi-Shah said in a presentation at the meeting.
In Study 113, mepolizumab had no significant impact on reducing moderate to severe exacerbations at either a 100-mg or 300-mg dose, Dr. Karimi-Shah said. In addition, most secondary endpoints, with the exception of reducing time to the first exacerbation among patients in the highest eosinophil group, did not consistently support the primary endpoint of exacerbation reduction in either study, she said.
Robert Busch, MD, also of the FDA’s Division of Pulmonary, Allergy, and Rheumatology products, served as a clinical reviewer and presented data on safety, efficacy, and risk-benefit profile of mepolizumab.
Dr. Busch noted that the variability in blood eosinophils make it challenging to use as a potential marker to identify patients who would benefit from mepolizumab as an add-on therapy.
Overall, most of the committee agreed on the existence of an eosinophilic COPD phenotype, but expressed concern about the threshold being used.
“The studies were not particularly well controlled regarding the characterization of patients,” said William J. Calhoun, MD, of the University of Texas Medical Branch, Galveston, who cast one of the ‘no’ votes on the question of efficacy.
By contrast, Jeffrey S. Wagener, MD, of the University of Colorado at Denver, Aurora, referenced his background in cystic fibrosis, and voted “yes” on the question of efficacy. “For patients that have no other option, this is a step forward,” he said.
Committee members on both sides of the vote emphasized the need for more research with larger numbers, better patient characterization, and more female patients. The committee members reported no relevant conflicts of interest.
FROM AN FDA ADVISORY COMMITTEE MEETING
Less is more: Nanotechnology enhances antifungal’s efficacy
The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.
Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.
In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.
The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).
“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.
Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.
The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.
Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.
The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.
Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.
In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.
The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).
“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.
Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.
The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.
Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.
The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.
Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.
In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.
The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).
“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.
Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.
The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.
Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.
FROM JOURNAL OF DRUGS IN DERMATOLOGY
Key clinical point: Adding nanoparticles to antifungal medication improved the drug’s effectiveness and reduced the amount needed.
Major finding: Efinaconazole combined with nitric oxide–releasing nanoparticles reduced the antifungal’s minimum inhibitory concentration 16-fold, compared with the antifungal alone against T. rubrum reference strains.
Study details: The data come from an in vitro analysis of nanoparticle-enhanced efinaconazole or terbinafine against T. rubrum.
Disclosures: Dr. Costa-Orlandi had no financial conflicts to disclose. Coauthors Dr. Adam Friedman and Dr. Joel Friedman are coinventors of the nitric oxide–releasing nanoparticles used in the study.
Source: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.
MIS underused for hernia repair
Surgeons in the United States have been slow to adopt according to data from more than 6,000 patients.
“The benefit of MIS over open repair is recognized for patients with bilateral or recurrent inguinal hernias, and current guidelines recommend MIS repair for these cases,” wrote Joceline V. Vu, MD, of the University of Michigan, Ann Arbor, and her colleagues.
In a study published in Surgical Endoscopy, the researchers assessed surgeons’ practice patterns for hernia repair, with a primary outcome of minimally invasive surgery (MIS) rates per individual surgeon. They reviewed data from a statewide clinical registry of 6,723 adults older than 18 years who underwent elective hernia surgery in Michigan between 2012 and 2016.
Overall, the surgeons’ use of MIS varied, but more than half (58%) of the surgeons performed no MIS for hernia repair. For those who did use MIS, it was used in 41% of bilateral hernias and 38% of recurrent hernias.
Surgeons were significantly less likely to use MIS for hernia on patients aged 65 years and older (odds ratio, 0.68, P = .003), or those who were black (OR 0.75, P = .045). MIS repair also was significantly less likely for patients with chronic obstructive pulmonary disease (OR 0.57, P less than .001) or patients in American Society of Anesthesiologists Classification under 3 (OR 0.79, P less than .001).
Of the 227 surgeons who performed MIS, 71 (31%) had MIS utilization rates of 75% or higher and were defined as high-utilization surgeons. Overall, 75% of the MIS repairs were performed by 14% of the surgeons.
The surgeons with the highest use of MIS were unevenly distributed across the state; the Ann Arbor region had the highest percentage of high MIS-use surgeons (22%), compared with the Lansing area, in which 2% of surgeons were high users of MIS.
The risk-adjusted rate of MIS for inguinal hernia repair varied significantly across six regions of the state, from 10% to 48%, and the regions with the highest rates were those with the highest percentage of high-MIS use surgeons.
“These findings suggest that a large portion of decision making to offer MIS repair may depend on surgeon differences, rather than clinical appropriateness,” the researchers said. “The likelihood that a patient receives MIS repair may thus be predetermined by the surgeon to whom they are referred,” they added.
“Whether through novel training interventions or by establishing regional referral networks to improve access to MIS repair, improvement in MIS delivery and access is needed to reduce disparity and promote evidence-based practice,” they concluded.
The findings were limited by several factors including the potential for bias because of the observational nature of the study, the potential lack of generalizability of the findings, and lack of data on the particular attributes of the hernias, the researchers said.
Dr. Vu disclosed funding from the National Institutes of Health but had no financial conflicts to disclose. One of the study coauthors disclosed a relationship with Medtronic.
SOURCE: Vu JV et al. Surg Endosc. 2018 Jul 9. doi: 10.1007/s00464-018-6322-x.
Surgeons in the United States have been slow to adopt according to data from more than 6,000 patients.
“The benefit of MIS over open repair is recognized for patients with bilateral or recurrent inguinal hernias, and current guidelines recommend MIS repair for these cases,” wrote Joceline V. Vu, MD, of the University of Michigan, Ann Arbor, and her colleagues.
In a study published in Surgical Endoscopy, the researchers assessed surgeons’ practice patterns for hernia repair, with a primary outcome of minimally invasive surgery (MIS) rates per individual surgeon. They reviewed data from a statewide clinical registry of 6,723 adults older than 18 years who underwent elective hernia surgery in Michigan between 2012 and 2016.
Overall, the surgeons’ use of MIS varied, but more than half (58%) of the surgeons performed no MIS for hernia repair. For those who did use MIS, it was used in 41% of bilateral hernias and 38% of recurrent hernias.
Surgeons were significantly less likely to use MIS for hernia on patients aged 65 years and older (odds ratio, 0.68, P = .003), or those who were black (OR 0.75, P = .045). MIS repair also was significantly less likely for patients with chronic obstructive pulmonary disease (OR 0.57, P less than .001) or patients in American Society of Anesthesiologists Classification under 3 (OR 0.79, P less than .001).
Of the 227 surgeons who performed MIS, 71 (31%) had MIS utilization rates of 75% or higher and were defined as high-utilization surgeons. Overall, 75% of the MIS repairs were performed by 14% of the surgeons.
The surgeons with the highest use of MIS were unevenly distributed across the state; the Ann Arbor region had the highest percentage of high MIS-use surgeons (22%), compared with the Lansing area, in which 2% of surgeons were high users of MIS.
The risk-adjusted rate of MIS for inguinal hernia repair varied significantly across six regions of the state, from 10% to 48%, and the regions with the highest rates were those with the highest percentage of high-MIS use surgeons.
“These findings suggest that a large portion of decision making to offer MIS repair may depend on surgeon differences, rather than clinical appropriateness,” the researchers said. “The likelihood that a patient receives MIS repair may thus be predetermined by the surgeon to whom they are referred,” they added.
“Whether through novel training interventions or by establishing regional referral networks to improve access to MIS repair, improvement in MIS delivery and access is needed to reduce disparity and promote evidence-based practice,” they concluded.
The findings were limited by several factors including the potential for bias because of the observational nature of the study, the potential lack of generalizability of the findings, and lack of data on the particular attributes of the hernias, the researchers said.
Dr. Vu disclosed funding from the National Institutes of Health but had no financial conflicts to disclose. One of the study coauthors disclosed a relationship with Medtronic.
SOURCE: Vu JV et al. Surg Endosc. 2018 Jul 9. doi: 10.1007/s00464-018-6322-x.
Surgeons in the United States have been slow to adopt according to data from more than 6,000 patients.
“The benefit of MIS over open repair is recognized for patients with bilateral or recurrent inguinal hernias, and current guidelines recommend MIS repair for these cases,” wrote Joceline V. Vu, MD, of the University of Michigan, Ann Arbor, and her colleagues.
In a study published in Surgical Endoscopy, the researchers assessed surgeons’ practice patterns for hernia repair, with a primary outcome of minimally invasive surgery (MIS) rates per individual surgeon. They reviewed data from a statewide clinical registry of 6,723 adults older than 18 years who underwent elective hernia surgery in Michigan between 2012 and 2016.
Overall, the surgeons’ use of MIS varied, but more than half (58%) of the surgeons performed no MIS for hernia repair. For those who did use MIS, it was used in 41% of bilateral hernias and 38% of recurrent hernias.
Surgeons were significantly less likely to use MIS for hernia on patients aged 65 years and older (odds ratio, 0.68, P = .003), or those who were black (OR 0.75, P = .045). MIS repair also was significantly less likely for patients with chronic obstructive pulmonary disease (OR 0.57, P less than .001) or patients in American Society of Anesthesiologists Classification under 3 (OR 0.79, P less than .001).
Of the 227 surgeons who performed MIS, 71 (31%) had MIS utilization rates of 75% or higher and were defined as high-utilization surgeons. Overall, 75% of the MIS repairs were performed by 14% of the surgeons.
The surgeons with the highest use of MIS were unevenly distributed across the state; the Ann Arbor region had the highest percentage of high MIS-use surgeons (22%), compared with the Lansing area, in which 2% of surgeons were high users of MIS.
The risk-adjusted rate of MIS for inguinal hernia repair varied significantly across six regions of the state, from 10% to 48%, and the regions with the highest rates were those with the highest percentage of high-MIS use surgeons.
“These findings suggest that a large portion of decision making to offer MIS repair may depend on surgeon differences, rather than clinical appropriateness,” the researchers said. “The likelihood that a patient receives MIS repair may thus be predetermined by the surgeon to whom they are referred,” they added.
“Whether through novel training interventions or by establishing regional referral networks to improve access to MIS repair, improvement in MIS delivery and access is needed to reduce disparity and promote evidence-based practice,” they concluded.
The findings were limited by several factors including the potential for bias because of the observational nature of the study, the potential lack of generalizability of the findings, and lack of data on the particular attributes of the hernias, the researchers said.
Dr. Vu disclosed funding from the National Institutes of Health but had no financial conflicts to disclose. One of the study coauthors disclosed a relationship with Medtronic.
SOURCE: Vu JV et al. Surg Endosc. 2018 Jul 9. doi: 10.1007/s00464-018-6322-x.
FROM SURGICAL ENDOSCOPY
Key clinical point: Minimally invasive surgery remains underused as a method for managing inguinal hernias.
Major finding: Overall, 75% of MIS hernia repairs were performed by 14% of the surgeons.
Study details: The data come from a retrospective cohort study of 6,723 hernia surgery patients treated between 2012 and 2016.
Disclosures: Dr. Vu disclosed funding from the National Institutes of Health but had no financial conflicts to disclose. One of the study coauthors disclosed a relationship with Medtronic.
Source: Vu JV et al. Surg Endosc. 2018 Jul 9. doi: 10.1007/s00464-018-6322-x.
Extended data support ixekizumab for plaque psoriasis
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
followed over a 4-year extension of a randomized trial.
Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.
At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.
A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).
The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.
However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”
The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
FROM JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point: Ixekizumab appears to be an effective option for long-term treatment of patients with moderate to severe psoriasis.
Major finding: A total of 82% of patients achieved PASI 75 at week 208 of the open-label extension study.
Study details: The data come from a 4-year open-label extension of a phase 2 randomized, placebo-controlled trial including 120 adults with psoriasis.
Disclosures: The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.
Source: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.
Assessing adverse events tied to outpatient opioid use in children
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
FROM PEDIATRICS
Key clinical point: One in every 2,611 opioid prescriptions in children and teens was followed by an ED visit, hospitalization, or death related to an adverse event associated with opioid use.
Major finding: A total of 437 cases of opioid-related adverse events were confirmed; most were associated with therapeutic medication use.
Study details: The data come from a retrospective cohort study of 401,972 children aged 2-17 years enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014.
Disclosures: The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
Source: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156
Depression screening rates remain low for undiagnosed adults
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
FROM PSYCHIATRIC SERVICES
Cutavirus shows no association with primary cutaneous lymphoma
The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.
Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.
In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.
Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.
The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.
The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.
SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.
The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.
Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.
In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.
Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.
The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.
The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.
SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.
The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.
Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.
In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.
Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.
The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.
The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.
SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.
FROM JAMA DERMATOLOGY
Key clinical point: Cutavirus may not have a primary role in cutaneous lymphomas.
Major finding: Cutavirus was identified in 6 (3.2%) of 189 lymphoma biopsies.
Study details: The data come from 130 patients with cutaneous B-cell lymphoma or cutaneous T-cell lymphoma and a total of 189 biopsy specimens.
Disclosures: The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.
Source: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.
Clomiphene citrate improves pregnancy outcomes for PCOS patients
Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.
Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.
Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.
In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m2.
After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).
The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.
The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.
However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.
The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.
Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.
Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.
Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.
In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m2.
After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).
The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.
The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.
However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.
The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.
Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.
Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.
Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.
In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m2.
After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).
The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.
The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.
However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.
The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.
FROM THE EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
Key clinical point: Clomiphene citrate increased the levels of both nitric oxide and interleukin-10 and reduced levels of matrix metalloproteinase–9.
Major finding: The ovulation rate was 53%, and the clinical pregnancy rate was 19% in PCOS women given clomiphene citrate.
Study details: The data come from 72 women with PCOS.
Disclosures: The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
Source: Sylus A et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sep;228:27-31.
Urge expectant parents to have prenatal pediatrician visit
All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.
“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.
A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.
The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.
The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.
The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.
The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.
“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.
The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.
“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”
The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.
SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218
All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.
“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.
A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.
The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.
The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.
The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.
The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.
“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.
The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.
“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”
The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.
SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218
All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.
“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.
A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.
The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.
The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.
The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.
The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.
“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.
The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.
“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”
The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.
SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218
FROM PEDIATRICS
Monoclonal antibody reduced alpha-synuclein levels in Parkinson’s patients
Adults with mild to moderate Parkinson’s disease showed reductions in free serum alpha-synuclein levels without notable side effects after intravenous treatment with a monoclonal antibody known as PRX002.
“Pathologically, PD [Parkinson’s disease] is typically associated with an accumulation of aggregated alpha-synuclein protein in the central nervous system and the peripheral nervous system,” making alpha-synuclein a target for treatment in preclinical studies, wrote Joseph Jankovic, MD, of Baylor College of Medicine, Houston, and his colleagues.
“Notably, rapid and robust reductions in free serum alpha-synuclein levels were achieved without seriously affecting safety,” the researchers said. Overall, reductions in free serum alpha-synuclein occurred quickly and were similar throughout the study period, and treatment with PRX002 was safe, well tolerated, and effective at doses up to 60 mg/kg.
The most relevant adverse events were mild to moderate infusion-related reactions in four patients in the highest-dose group; two of these patients discontinued the study. No anti-PRX002 antibodies were seen, and no serious adverse events or deaths occurred during the study period.
Statistically significant reductions from baseline were noted at 1 and 4 hours after the first and third infusion in all dose groups, compared with placebo, and these reductions lasted longer after the higher doses.
Over the longer term, statistically significant reductions after the third infusion were noted at day 64 for the 1.0-mg/kg through 60-mg/kg dose groups, day 71 for the 1.0-mg/kg through 60-mg/kg dose groups, and at day 85 for the 3-mg/kg through 60-mg/kg dose groups.
The study findings were limited by several factors, including the relatively small sample size, short period of exposure to the treatment, homogeneous population, and lack of imaging to monitor brain pathology, the researchers noted. However, the results support the safety of PRX002 and the progression of the follow-up phase 2 study known as PASADENA.
The study was funded by Prothena Biosciences and F. Hoffmann-LaRoche. Lead author Dr. Jankovich disclosed relationships with both of those companies and has received funding from the Parkinson’s Foundation. Many of the other authors are employees of Prothena Biosciences or F. Hoffmann-LaRoche or a subsidiary.
SOURCE: Jankovic J et al. JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.1487.
The study results met the endpoints for safety and tolerance; however, “the question remains: To what extent does this process reflect the role of alpha-synuclein in the causal mechanisms of Parkinson disease?” wrote Fredric P. Manfredsson, PhD; Malú G. Tansey, PhD; and Todd E. Golde, PhD, in an accompanying editorial (JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.0346).
The trio noted that the potential of alpha-synuclein for cell-to-cell transmission and disease propagation and progression remains unknown and the research behind the passive immunization technique remains limited and controversial at the preclinical level. In addition, they emphasized the need to consider the potential for neurotoxicity with the removal of soluble alpha-synuclein from neurons.
“Thus, the potential negative consequences following sustained treatment with PRX002 must also be heavily scrutinized before it can be said to be safe for long-term use in elderly individuals,” they wrote.
The study also lacked data on whether the antibody directly engaged its target in the CNS, they said.
“Although the PRX002 trial met its primary goals and is now poised to move forward into efficacy trials, it is clear that progress within the synuclein basic science field needs to follow suit,” they concluded.
Dr. Manfredsson is affiliated with Michigan State University in Grand Rapids. Dr. Tansey is affiliated with Emory University in Atlanta. Dr. Golde is affiliated with the University of Florida, Gainesville. Dr. Tansey disclosed relationships with INmune Bio, Above and Beyond, Hygieia Sciences, UCB, and the Michael J. Fox Foundation for Parkinson’s Research.
The study results met the endpoints for safety and tolerance; however, “the question remains: To what extent does this process reflect the role of alpha-synuclein in the causal mechanisms of Parkinson disease?” wrote Fredric P. Manfredsson, PhD; Malú G. Tansey, PhD; and Todd E. Golde, PhD, in an accompanying editorial (JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.0346).
The trio noted that the potential of alpha-synuclein for cell-to-cell transmission and disease propagation and progression remains unknown and the research behind the passive immunization technique remains limited and controversial at the preclinical level. In addition, they emphasized the need to consider the potential for neurotoxicity with the removal of soluble alpha-synuclein from neurons.
“Thus, the potential negative consequences following sustained treatment with PRX002 must also be heavily scrutinized before it can be said to be safe for long-term use in elderly individuals,” they wrote.
The study also lacked data on whether the antibody directly engaged its target in the CNS, they said.
“Although the PRX002 trial met its primary goals and is now poised to move forward into efficacy trials, it is clear that progress within the synuclein basic science field needs to follow suit,” they concluded.
Dr. Manfredsson is affiliated with Michigan State University in Grand Rapids. Dr. Tansey is affiliated with Emory University in Atlanta. Dr. Golde is affiliated with the University of Florida, Gainesville. Dr. Tansey disclosed relationships with INmune Bio, Above and Beyond, Hygieia Sciences, UCB, and the Michael J. Fox Foundation for Parkinson’s Research.
The study results met the endpoints for safety and tolerance; however, “the question remains: To what extent does this process reflect the role of alpha-synuclein in the causal mechanisms of Parkinson disease?” wrote Fredric P. Manfredsson, PhD; Malú G. Tansey, PhD; and Todd E. Golde, PhD, in an accompanying editorial (JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.0346).
The trio noted that the potential of alpha-synuclein for cell-to-cell transmission and disease propagation and progression remains unknown and the research behind the passive immunization technique remains limited and controversial at the preclinical level. In addition, they emphasized the need to consider the potential for neurotoxicity with the removal of soluble alpha-synuclein from neurons.
“Thus, the potential negative consequences following sustained treatment with PRX002 must also be heavily scrutinized before it can be said to be safe for long-term use in elderly individuals,” they wrote.
The study also lacked data on whether the antibody directly engaged its target in the CNS, they said.
“Although the PRX002 trial met its primary goals and is now poised to move forward into efficacy trials, it is clear that progress within the synuclein basic science field needs to follow suit,” they concluded.
Dr. Manfredsson is affiliated with Michigan State University in Grand Rapids. Dr. Tansey is affiliated with Emory University in Atlanta. Dr. Golde is affiliated with the University of Florida, Gainesville. Dr. Tansey disclosed relationships with INmune Bio, Above and Beyond, Hygieia Sciences, UCB, and the Michael J. Fox Foundation for Parkinson’s Research.
Adults with mild to moderate Parkinson’s disease showed reductions in free serum alpha-synuclein levels without notable side effects after intravenous treatment with a monoclonal antibody known as PRX002.
“Pathologically, PD [Parkinson’s disease] is typically associated with an accumulation of aggregated alpha-synuclein protein in the central nervous system and the peripheral nervous system,” making alpha-synuclein a target for treatment in preclinical studies, wrote Joseph Jankovic, MD, of Baylor College of Medicine, Houston, and his colleagues.
“Notably, rapid and robust reductions in free serum alpha-synuclein levels were achieved without seriously affecting safety,” the researchers said. Overall, reductions in free serum alpha-synuclein occurred quickly and were similar throughout the study period, and treatment with PRX002 was safe, well tolerated, and effective at doses up to 60 mg/kg.
The most relevant adverse events were mild to moderate infusion-related reactions in four patients in the highest-dose group; two of these patients discontinued the study. No anti-PRX002 antibodies were seen, and no serious adverse events or deaths occurred during the study period.
Statistically significant reductions from baseline were noted at 1 and 4 hours after the first and third infusion in all dose groups, compared with placebo, and these reductions lasted longer after the higher doses.
Over the longer term, statistically significant reductions after the third infusion were noted at day 64 for the 1.0-mg/kg through 60-mg/kg dose groups, day 71 for the 1.0-mg/kg through 60-mg/kg dose groups, and at day 85 for the 3-mg/kg through 60-mg/kg dose groups.
The study findings were limited by several factors, including the relatively small sample size, short period of exposure to the treatment, homogeneous population, and lack of imaging to monitor brain pathology, the researchers noted. However, the results support the safety of PRX002 and the progression of the follow-up phase 2 study known as PASADENA.
The study was funded by Prothena Biosciences and F. Hoffmann-LaRoche. Lead author Dr. Jankovich disclosed relationships with both of those companies and has received funding from the Parkinson’s Foundation. Many of the other authors are employees of Prothena Biosciences or F. Hoffmann-LaRoche or a subsidiary.
SOURCE: Jankovic J et al. JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.1487.
Adults with mild to moderate Parkinson’s disease showed reductions in free serum alpha-synuclein levels without notable side effects after intravenous treatment with a monoclonal antibody known as PRX002.
“Pathologically, PD [Parkinson’s disease] is typically associated with an accumulation of aggregated alpha-synuclein protein in the central nervous system and the peripheral nervous system,” making alpha-synuclein a target for treatment in preclinical studies, wrote Joseph Jankovic, MD, of Baylor College of Medicine, Houston, and his colleagues.
“Notably, rapid and robust reductions in free serum alpha-synuclein levels were achieved without seriously affecting safety,” the researchers said. Overall, reductions in free serum alpha-synuclein occurred quickly and were similar throughout the study period, and treatment with PRX002 was safe, well tolerated, and effective at doses up to 60 mg/kg.
The most relevant adverse events were mild to moderate infusion-related reactions in four patients in the highest-dose group; two of these patients discontinued the study. No anti-PRX002 antibodies were seen, and no serious adverse events or deaths occurred during the study period.
Statistically significant reductions from baseline were noted at 1 and 4 hours after the first and third infusion in all dose groups, compared with placebo, and these reductions lasted longer after the higher doses.
Over the longer term, statistically significant reductions after the third infusion were noted at day 64 for the 1.0-mg/kg through 60-mg/kg dose groups, day 71 for the 1.0-mg/kg through 60-mg/kg dose groups, and at day 85 for the 3-mg/kg through 60-mg/kg dose groups.
The study findings were limited by several factors, including the relatively small sample size, short period of exposure to the treatment, homogeneous population, and lack of imaging to monitor brain pathology, the researchers noted. However, the results support the safety of PRX002 and the progression of the follow-up phase 2 study known as PASADENA.
The study was funded by Prothena Biosciences and F. Hoffmann-LaRoche. Lead author Dr. Jankovich disclosed relationships with both of those companies and has received funding from the Parkinson’s Foundation. Many of the other authors are employees of Prothena Biosciences or F. Hoffmann-LaRoche or a subsidiary.
SOURCE: Jankovic J et al. JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.1487.
FROM JAMA NEUROLOGY
Key clinical point: Treatment with a monoclonal antibody for alpha-synuclein known as PRX002 was safe and effective in a preliminary study of Parkinson’s disease patients.
Major finding: Significant reductions in free serum alpha-synuclein levels persisted at 85 days after the third infusion in the 3-mg/kg through 60-mg/kg dose groups.
Study details: The data come from a randomized, phase 1b trial of 80 adults aged 40-80 years with Parkinson’s disease.
Disclosures: The study was funded by Prothena Biosciences and F. Hoffmann-LaRoche. Lead author Dr. Jankovich disclosed relationships with both of those companies and has received funding from the Parkinson’s Foundation. Many of the other authors are employees of Prothena Biosciences or F. Hoffmann-LaRoche or a subsidiary.
Source: Jankovic J et al. JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.1487.