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Christopher Palmer has been an associate editor at MDedge News since 2017. When he's not tidying grammar, he writes short pieces about breaking FDA announcements and approvals, as well as journal articles. He proudly holds a BA in English and philosophy. Follow him on Twitter @cmacmpalm.
Daratumumab approved in combo with VTd for transplant-eligible multiple myeloma
The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.
The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.
The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).
The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.
Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.
The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.
The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).
The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.
Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.
The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.
The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).
The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.
Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
FDA: Sandoz recalls ranitidine capsules with NDMA
, according to a news release from the agency.
The recall applies to 14 lots in which NDMA, a probable human carcinogen and nitrosamine impurity formed as a byproduct of several industrial and natural processes, has been detected at levels above those set by the FDA, according to a company announcement on Sept. 23 from Sandoz. According to the announcement, which also specifies the affected lots, the company has not received any reports of adverse events related to use of the products in the recall.
According to the FDA release, so far, only the specified lots of ranitidine are known to be contaminated, and patients can continue taking this stomach acid–reducing histamine2 blocker from lots that are not affected by the recall.
“When we identify lapses in the quality of drugs that pose potential risks for patients, the FDA makes all efforts to understand the issue and provide our best recommendation to the public as quickly and accurately as possible,” said acting FDA Commissioner Norman E. Sharpless, MD.
As part of this ongoing investigation, the FDA recently posted a testing protocol for detecting NDMA in ranitidine; the agency hopes regulators and industry will use this protocol to begin their own laboratory testing as well and send samples to the FDA for further testing.
More information about the recall, as well as instructions for patients and health care professionals, can be found in the full news release on the FDA website. The agency also encourages any adverse reactions be reported to its MedWatch program.
, according to a news release from the agency.
The recall applies to 14 lots in which NDMA, a probable human carcinogen and nitrosamine impurity formed as a byproduct of several industrial and natural processes, has been detected at levels above those set by the FDA, according to a company announcement on Sept. 23 from Sandoz. According to the announcement, which also specifies the affected lots, the company has not received any reports of adverse events related to use of the products in the recall.
According to the FDA release, so far, only the specified lots of ranitidine are known to be contaminated, and patients can continue taking this stomach acid–reducing histamine2 blocker from lots that are not affected by the recall.
“When we identify lapses in the quality of drugs that pose potential risks for patients, the FDA makes all efforts to understand the issue and provide our best recommendation to the public as quickly and accurately as possible,” said acting FDA Commissioner Norman E. Sharpless, MD.
As part of this ongoing investigation, the FDA recently posted a testing protocol for detecting NDMA in ranitidine; the agency hopes regulators and industry will use this protocol to begin their own laboratory testing as well and send samples to the FDA for further testing.
More information about the recall, as well as instructions for patients and health care professionals, can be found in the full news release on the FDA website. The agency also encourages any adverse reactions be reported to its MedWatch program.
, according to a news release from the agency.
The recall applies to 14 lots in which NDMA, a probable human carcinogen and nitrosamine impurity formed as a byproduct of several industrial and natural processes, has been detected at levels above those set by the FDA, according to a company announcement on Sept. 23 from Sandoz. According to the announcement, which also specifies the affected lots, the company has not received any reports of adverse events related to use of the products in the recall.
According to the FDA release, so far, only the specified lots of ranitidine are known to be contaminated, and patients can continue taking this stomach acid–reducing histamine2 blocker from lots that are not affected by the recall.
“When we identify lapses in the quality of drugs that pose potential risks for patients, the FDA makes all efforts to understand the issue and provide our best recommendation to the public as quickly and accurately as possible,” said acting FDA Commissioner Norman E. Sharpless, MD.
As part of this ongoing investigation, the FDA recently posted a testing protocol for detecting NDMA in ranitidine; the agency hopes regulators and industry will use this protocol to begin their own laboratory testing as well and send samples to the FDA for further testing.
More information about the recall, as well as instructions for patients and health care professionals, can be found in the full news release on the FDA website. The agency also encourages any adverse reactions be reported to its MedWatch program.
Sensitive, responsive parenting improves child language skills
Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.
Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”
Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.
“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”
Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.
“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”
Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.
“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”
A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.
SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.
Parental sensitive responsiveness and warmth, as explored in the meta-analysis by Madigan et al., is important, but so is the overall “language nutrition” children receive, wrote Heidi M. Feldman, MD, PhD.
“Pediatric clinicians routinely counsel families about food nutrition. We should address language nutrition with similar urgency,” Dr. Feldman suggested.
She pointed out that the two features of parenting explored in the meta-analysis are only part of the picture; other ingredients in language nutrition include the quantity of child-directed speech, the quality of the language input, and the nature of caregiver interactions with children, “beyond responsivity and warmth.”
“Meta-analyses on the topic of language development are extremely helpful,” Dr. Feldman wrote. “However, now we also need well-designed treatment studies to inform us about the nature and intensity of interventions to improve language-learning environments and child outcomes.”
Dr. Feldman , who is with the department of pediatrics at Stanford (Calif.) University, made these comments in an accompanying editorial in Pediatrics ( doi: 10.1542/peds.2019-2157 ). She had no financial relationships related to the commentary nor potential conflicts of interest to disclose.
Parental sensitive responsiveness and warmth, as explored in the meta-analysis by Madigan et al., is important, but so is the overall “language nutrition” children receive, wrote Heidi M. Feldman, MD, PhD.
“Pediatric clinicians routinely counsel families about food nutrition. We should address language nutrition with similar urgency,” Dr. Feldman suggested.
She pointed out that the two features of parenting explored in the meta-analysis are only part of the picture; other ingredients in language nutrition include the quantity of child-directed speech, the quality of the language input, and the nature of caregiver interactions with children, “beyond responsivity and warmth.”
“Meta-analyses on the topic of language development are extremely helpful,” Dr. Feldman wrote. “However, now we also need well-designed treatment studies to inform us about the nature and intensity of interventions to improve language-learning environments and child outcomes.”
Dr. Feldman , who is with the department of pediatrics at Stanford (Calif.) University, made these comments in an accompanying editorial in Pediatrics ( doi: 10.1542/peds.2019-2157 ). She had no financial relationships related to the commentary nor potential conflicts of interest to disclose.
Parental sensitive responsiveness and warmth, as explored in the meta-analysis by Madigan et al., is important, but so is the overall “language nutrition” children receive, wrote Heidi M. Feldman, MD, PhD.
“Pediatric clinicians routinely counsel families about food nutrition. We should address language nutrition with similar urgency,” Dr. Feldman suggested.
She pointed out that the two features of parenting explored in the meta-analysis are only part of the picture; other ingredients in language nutrition include the quantity of child-directed speech, the quality of the language input, and the nature of caregiver interactions with children, “beyond responsivity and warmth.”
“Meta-analyses on the topic of language development are extremely helpful,” Dr. Feldman wrote. “However, now we also need well-designed treatment studies to inform us about the nature and intensity of interventions to improve language-learning environments and child outcomes.”
Dr. Feldman , who is with the department of pediatrics at Stanford (Calif.) University, made these comments in an accompanying editorial in Pediatrics ( doi: 10.1542/peds.2019-2157 ). She had no financial relationships related to the commentary nor potential conflicts of interest to disclose.
Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.
Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”
Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.
“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”
Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.
“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”
Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.
“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”
A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.
SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.
Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.
Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”
Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.
“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”
Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.
“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”
Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.
“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”
A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.
SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.
FROM PEDIATRICS
Key clinical point:
Major finding: The correlation coefficient for parental sensitive responsiveness and child language skills was 0.27 (95% confidence interval, 0.21-0.33).
Study details: A meta-analysis of 37 studies that ranged in sample sizes from 9 to 1,026 mother-child dyads.
Disclosures: A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.
Source: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.
Adult insomnia associated with childhood behavioral problems
Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.
Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.
Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.
The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.
“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.
One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.
“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.
No study sponsor was identified. The authors reported no relevant financial disclosures.
SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.
Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.
Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.
Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.
The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.
“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.
One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.
“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.
No study sponsor was identified. The authors reported no relevant financial disclosures.
SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.
Yohannes Adama Melaku, MPH, PhD, of the Adelaide (Australia) Institute for Sleep Health at Flinders University and coauthors drew data from the 1970 UK Birth Cohort Study. This study followed an initial cohort of 16,571 babies who were born during a single week, with follow-up at ages 5, 10, 16, 26, 30, 38, 42, and 46 years. For the purposes of this study, the investigators looked at participants who, at 42 years of age, were alive and not lost to follow-up and who responded to an invitation to be interviewed; the sample sizes in the analysis were 8,050 participants aged 5 years, 9,090 participants aged 10 years, 9,653 participants aged 16 years, and 9,841 participants aged 42 years.
Behavior was measured at ages 5 years and 16 years using the Rutter Behavioral Scale (RBS) and at age 10 years using a visual analog scale, and insomnia symptoms were assessed through interviewing participants in adulthood about duration of sleep, difficulty initiating sleep, difficulty maintaining sleep, and not feeling rested on waking. Participants were organized into normal behavior (less than or equal to 80th percentile on RBS), moderate behavioral problems (greater than the 80th percentile but less than or equal to the 95th percentile), and severe behavioral problems (above 95th percentile). The investigators then devised two models for their analysis: Model 1 adjusted for sex, parent’s social class and educational level, marital status, educational status, and social class, and model 2 adjusted for physical activity level and body mass index (BMI) trajectory (from 10 to 42 years), perceived health status, and number of noncommunicable diseases, although this latter model yielded fewer statistically significant results in some analyses.
Odds for difficulty initiating or maintaining sleep as an adult was increased among participants with severe behavioral problems at age 5 years in model 1 (adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.96; P = .004), as well as for those with severe problems at 10 years (aOR, 1.30; 95% CI, 1.14-1.63; P = .001), and at 16 years (aOR, 2.17; 95% CI, 1.59-2.91; P less than .001). The aORs also were higher individually for difficulty initiating sleep and for difficulty maintaining sleep in all age groups.
The association with adulthood insomnia was stronger in participants with externalizing behavioral problems such as lying, bullying, restlessness, and fighting than it was in those with internalizing behavioral problems such as worry, fearfulness, and solitariness.
“Although early sleep problems should be identified, we should additionally identify children with moderate to severe behavioral problems that persist throughout childhood as potential beneficiaries of early intervention with a sleep health focus,” the authors wrote.
One of the study’s limitations was a lack of standardized insomnia measures in the cohort study; however, the researchers suggested that the symptoms included reflect those of standardized measures and diagnostic criteria.
“This study is the first, to our knowledge, to suggest an unfavorable association of early-life behavioral problems with adulthood sleep health, underlining the importance of treating behavioral problems in children and addressing insomnia from a life-course perspective,” they concluded.
No study sponsor was identified. The authors reported no relevant financial disclosures.
SOURCE: Melaku YA et al. JAMA Netw Open. 2019 Sep 6. doi: 10.1001/jamanetworkopen.2019.10861.
FROM JAMA NETWORK OPEN
Gastrostomy tube placement associated with higher pneumonia recurrence in children with neurologic impairment
according to findings published in Pediatrics.
Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.
The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.
Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).
The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).
The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.
“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.
The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.
The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.
cpalmer@mdedge.com
SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.
according to findings published in Pediatrics.
Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.
The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.
Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).
The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).
The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.
“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.
The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.
The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.
cpalmer@mdedge.com
SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.
according to findings published in Pediatrics.
Five of the remaining seven strategies – gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before hospitalization, and clinic visit before and after index hospitalization – were associated with increased recurrence, Jody L. Lin, MD, of the department of pediatrics at Stanford (Calif.) University, and colleagues reported. Oral secretion management and gastric acid suppression were associated with increased risk, but to a lesser extent.
The researchers examined the outcomes of the prevention strategies because, although children with neurologic impairment are more susceptible to community-acquired pneumonia, current guidelines are based mostly on expert opinion. The study included 3,632 children aged 21 years or younger with neurologic impairment and at least one hospitalization for pneumonia, who were enrolled in the California Children’s Services program between July 1, 2009, and June 30, 2014.
Propensity-score matching based on factors such as age, sex, household income, as well as characteristics of index hospitalization, showed decreased odds of recurrence only with receipt of dental care (adjusted odds ratio, 0.64; 95% confidence interval, 0.49-0.85), whereas increased odds were seen with other recommended prevention strategies, such as chest physiotherapy (aOR, 2.03; 95% CI, 1.29-3.20), receipt of antibiotics before hospitalization (aOR, 1.42; 95% CI, 1.06-1.92), and clinic visit before (aOR, 1.30; 95% CI, 1.11-1.52) and after index hospitalization (aOR, 1.72; 95% CI, 1.35-2.20).
The greatest increased odds, however, were seen with new gastrostomy tube placement (aOR, 2.15; 95% CI, 1.63-2.85).
The investigators noted that the biggest limitation of this study was the potential for residual confounding by indication even after adjustment, whereby certain interventions were provided to patients deemed more clinically severe to begin with. A strength of the study is its longitudinal nature.
“Our results suggest that more attention should be paid to dental health for children with [neurologic impairment],” the researchers wrote, although they noted that dental care “remains the most common unmet health care need” for children with special health care needs.
The findings also “support a clinical trial of dental care for prevention of severe pneumonia in children with [neurologic impairment] and do not support the widespread use of gastrostomy tubes for that purpose,” they added.
The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.
cpalmer@mdedge.com
SOURCE: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.
FROM PEDIATRICS
Key clinical point: Gastrostomy tube placement is associated with higher pneumonia recurrence in children with neurologic impairment, and dental care is linked to decreased recurrence.
Major finding: There was an increased odds of pneumonia recurrence with new gastrostomy tube placement (adjusted odds ratio, 2.15; 95% confidence interval, 1.63-2.85) and decreased odds with dental care (aOR, 0.64; 95% CI, 0.49-0.85).
Study details: A comparative effectiveness study of a retrospective cohort of 3,632 children with neurologic impairment and at least one hospitalization for pneumonia, enrolled in California Children’s Services from July 1, 2009, to June 30, 2014.
Disclosures: The study was funded by the National Institutes of Health. Dr. Lin received support from the NIH and the Clinical Excellence Research Center. The authors reported that they had no conflicts of interest.
Source: Lin JL et al. Pediatrics. 2019 Sep 19. doi: 10.1542/peds.2019-0543.
FDA grants sirolimus-eluting balloon breakthrough device designation for PAD
The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.
According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.
Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.
The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.
According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.
Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.
The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.
According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.
Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.
FDA approves mepolizumab for severe eosinophilic asthma in younger kids
according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.
The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.
Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.
The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.
according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.
The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.
Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.
The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.
according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.
The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.
Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.
The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.
FDA approves tenapanor for IBS with constipation
The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.
The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
The full prescribing information can be found on the FDA website.
The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.
The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
The full prescribing information can be found on the FDA website.
The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.
The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
The full prescribing information can be found on the FDA website.
FDA approves nintedanib for scleroderma interstitial lung disease
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
The Food and Drug Administration has approved nintedanib (Ofev) for the rare but sometimes deadly form of interstitial lung disease that’s caused by systemic sclerosis, or scleroderma.
Although scleroderma itself is rare, half of those patients present with scleroderma-related interstitial lung disease (SSc-ILD), and it remains the leading cause of death in scleroderma patients because it can lead to loss of pulmonary function. Nintedanib appears to slow the progress of SSc-ILD and is the first treatment approved for it, according to a news release from the FDA.
The approval is based on a randomized, double-blind, placebo-controlled trial of 576 patients aged 20-79 years with SSc-ILD. The primary efficacy endpoint was forced vital capacity, and patients on nintedanib showed less decline than did those on placebo.
The most frequent serious adverse event reported in this trial was pneumonia (2.8% with nintedanib vs. 0.3% with placebo). Adverse reactions that led to permanent dose reductions occurred in 34% of nintedanib patients and 4% of placebo-treated patients; the most common of these was diarrhea.
The full prescribing information, which is available on the FDA website, includes warnings for patients with moderate to severe hepatic impairment, elevated liver enzymes, and drug-induced liver injury, as well as those with gastrointestinal disorders. Nintedanib may cause embryo-fetal toxicity, so women of childbearing age should be counseled to avoid pregnancy while taking this drug.
Nintedanib received both Priority Review and Orphan Drug designation. The former meant the FDA intends to take action on the application within 6 months because the agency has determined that, if approved, it would have important effects on treatment of a serious condition. The latter provides incentives to assist and encourage development of drugs for rare diseases. The drug was approved in 2014 for adult patients with idiopathic pulmonary fibrosis, another interstitial lung disease.
The full release is available on the FDA website.
Higher BMD linked to family history of diabetes in postmenopausal women
according to results of a study.
Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm2, respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm2, respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.
Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).
“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.
The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.
The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.
SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.
according to results of a study.
Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm2, respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm2, respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.
Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).
“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.
The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.
The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.
SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.
according to results of a study.
Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm2, respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm2, respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.
Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).
“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.
The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.
The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.
SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.
FROM MENOPAUSE