Feeding preterm or low-birth-weight infants a faster increment of daily milk does not appear to increase their risk of developing adverse outcomes, including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.

Photodisc/Thinkstockphotos.com

Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.

Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.

Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).

In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.

“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”

It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.

The researchers said one potential limitation of the study was that it was unblinded.

This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.

SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.

Feeding preterm or low-birth-weight infants a faster increment of daily milk does not appear to increase their risk of developing adverse outcomes, including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.

Photodisc/Thinkstockphotos.com

Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.

Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.

Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).

In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.

“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”

It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.

The researchers said one potential limitation of the study was that it was unblinded.

This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.

SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.

Feeding preterm or low-birth-weight infants a faster increment of daily milk does not appear to increase their risk of developing adverse outcomes, including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.

Photodisc/Thinkstockphotos.com

Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.

Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.

Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).

In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.

“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”

It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.

The researchers said one potential limitation of the study was that it was unblinded.

This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.

SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2019 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 15th Annual Coastal Dermatology Symposium on October 5, 2019.

Overall Grand Prize
Chronic Inflammatory Skin Diseases Are Associated With Herpes Zoster in US Inpatients

Raj Chovatiya, MD, PhD; Jonathan I. Silverberg MD, PhD, MPH, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Disclosures: None.
 

Background
Herpes zoster (HZ) is a vaccine-preventable, viral eruption that affects 1 of every 3 people in the United States in their lifetime. Despite evidence-based guidelines and public health advocacy, many high-risk individuals remain unvaccinated and at risk for significant morbidity from HZ. Patients with chronic inflammatory skin diseases (CISDs), including allergic and autoimmune conditions, have potential risk factors for HZ, including long-term use of systemic corticosteroids and immunosuppressants, and immune dysregulation in the skin and periphery. We sought to determine whether CISDs are associated with HZ in hospitalized patients in the US.

Methods
Data were analyzed from the 2002-2012 Nationwide Inpatient Sample, a representative 20% cross-sectional cohort of US hospitalizations (N=68,490,364 children and adults).

Results
The estimated incidence of primary hospitalization for HZ in the US population was 5.0 per 100,000 persons from 2002-2012. In multivariable weighted logistic regression models including age, sex, race/ethnicity, insurance, mean household income, and long-term systemic corticosteroid use, primary hospitalization for HZ was associated with multiple CISDs: atopic dermatitis (adjusted odds ratio [95% confidence interval]: 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Lichen planus (3.01 [1.36-6.67]), Sézary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) showed increased odds in bivariable models but not in multivariable models. Whereas, hidradenitis suppurativa, chronic idiopathic/spontaneous urticaria, and alopecia areata were not associated with HZ. Similar results were seen in sensitivity analyses among adults age <60 and <50 years. Significant predictors of primary hospitalization for HZ among patients with CISDs included older age, female sex, non-white race/ethnicity, decreasing number of chronic comorbid conditions, and long-term systemic corticosteroid use. Inpatient length of stay and/or inflation adjusted cost of care were significantly higher in inpatients with CISD with vs. without a primary diagnosis of HZ.

Conclusion
CISDs are associated with increased hospitalization for HZ, prolonged length of inpatient stay and increased cost of hospital care. The associations of CISDs and HZ were significant even below the recommended ages (<60 and <50 years) for vaccination with live and recombinant HZ vaccine, respectively. Additional studies are needed to confirm these findings and determine the mechanisms of VZV reactivation. Patients with CISDs constitute a significant, previously under-recognized group that is high-risk for hospitalization for HZ. Dermatologists are the primary physicians who manage the vulnerable population of CISDs. They should be on the forefront of screening, intervention, and most importantly, vaccination for their patients. Future studies should explore implementation of outpatient HZ vaccination by dermatologists and revised disease-specific guidelines to cover the spectrum of CISDs.

Up next: Buyer Beware or You Might Get Burned...→

Buyer Beware or You Might Get Burned: Unregulated Photosensitizing Agents Available Without Prescription From Major Online Retailers 

Kimberly Huerth, MD, MEd, Department of Dermatology, Howard University Hospital, Washington, DC; Olivia Ware, BA, Howard University College of Medicine, Washington, DC; Ginette A. Okoye, MD, Department of Dermatology, Howard University Hospital, Washington, DC; Sharon Bridgeman-Shah, MD, Department of Dermatology, Howard University Hospital, Washington, DC
Disclosures: None.

Background
According to the World Health Organization, the vast majority of the world’s population relies on plant-derived medicine as their primary form of healthcare. Closer to home, these alternative therapies are growing in popularity among American healthcare consumers, in concert with increasing access to such products by means of globalization and the growth of Internet retail. There are numerous reasons why an individual might eschew Western medicine in favor of a more naturopathic approach, including perceived health benefits, cost, prior failure of physician guided treatment, a lack of awareness about the risks these products carry, cultural norms, and desperation born of the psychosocial burden of one’s disease. 

A 73-year-old Eritrean man presented to our outpatient dermatology clinic with a severe, acute, phototoxic reaction following the ingestion of Athamanta decoction for the self-directed treatment of vitiligo. The genus Athamanta is in the Apiaceae family and consists of 6 species of flowering plants native to Europe and North Africa. Furanocoumarins are the phototoxic compounds present in these plants, among which psoralen is perhaps the most notorious. The desiccated Athamanta leaves, sought in the absence of medical consultation, had been obtained from a mail order vendor in Egypt which had advertised them as a “miracle effect for curing vitiligo.” 

Objective
To determine the extent to which unregulated photosensitizing agents for the treatment of vitiligo are available to consumers from online retailers, including major ones such as Amazon and eBay. 

Methods
An online product search of eBay and Amazon, as well as an Internet pharmacy by the name of Cheap Generic, was conducted using search terms “vitiligo treatment,” “psoralen for vitiligo,” “furanocoumarin treatment,” “Athamanta vitiligo,” “Apiaceae vitiligo,” and “leukoderma.” Products generated by the search terms were examined for their route of delivery (topical vs systemic), key photosensitizing ingredient, parent plant, cost to consumer, and country of manufacture. Products that did not identify a known photosensitizing compound, or a plant known to contain a photosensitizing compound, on the list of ingredients were excluded from the analysis. 

Results
We identified a total of 11 products—6 listed on Amazon, 3 listed on eBay, and 2 listed by Cheap Generic pharmacy—that had either a photosensitizing compound, or a plant known to contain a photosensitizing compound, on its list of ingredients. 27.3% of products were available in formulations intended for ingestion, such as tablets or powders. 90.9% of products listed psoralen, or a plant known to contain psoralen, as a major ingredient. Of the products that identified the main photosensitizing plant ingredient (72.7%), Psoralea corylifolia was the most common (75%). Products ranged in cost from $3 to $28. The terms “herbal” (54.5%) and “natural” (36.3%) were used most frequently on the packaging and/or website for promotional purposes. While 45.4% of products did not identify a country of origin, of those that did, 66.7% were manufactured in India, while the remainder were prepared in China. 

Conclusion
Topically and systemically administered psoralen-containing products for the treatment of vitiligo are widely available without a prescription from several online vendors. These products are affordable and utilize suggestive packaging to tout the benefits of the products, without mention of their risks.

Up next: Collagen VII: A Link Between the Skin and Bone Marrow...→

Collagen VII: A Link Between the Skin and Bone Marrow Via Extracellular Vesicles

Jeffrey D. McBride, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida
Disclosures: Dr. McBride has been a consultant with Aegle Therapeutics.

Extracellular vesicles—exosomes, microvesicles, and apoptotic bodies—are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell of origin. Specifically, we have discovered that these extracellular vesicles from the bone marrow–derived mesenchymal stem cells stimulate production of basement membrane components by cells that genetically lacked the ability to do so before (ie, collagen VII from fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa). In other words, our work shows that the bone marrow can replenish collagen VII by directly delivering protein but also by transferring messenger RNA, coding for collagen VII, to the epidermolysis bullosa fibroblasts, allowing them to make collagen VII for the first time. Extracellular vesicles, including exosomes, have immediate potential for serving as therapeutics in dermatology over the next decade.

Up next: Genetic Variations in Non-coding Regulatory Regions in Linear Morphea...→

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea
Dawn Zhang Eichenfield, MD, PhD, University of California, San Diego, Medical Center, La Jolla, California
Disclosures: This research was funded by the Women’s Dermatologic Society and the Pediatric Dermatology Research Alliance.

Linear morphea is a chronic inflammatory and pro-fibrotic disease that can be debilitating and disfiguring. It generally presents at an earlier age of onset than other subtypes of morphea. Like other autoimmune diseases, linear morphea presents predominantly in females, has a familial contribution, and has been associated with particular environmental triggers. Beyond this, however, the full pathogenesis of this disease remains unknown. A more thorough understanding of the causes of linear morphea—genetic and environmental—is the first step toward improved diagnosis and treatment.

Lesions of linear morphea predominantly follow Blaschko’s lines, a pattern of lines on the skin thought to represent pathways of epidermal cell migration and proliferation during fetal development. This presentation suggests that genetic mosaicism may be at play, although studies utilizing whole exome sequencing have not found causative somatic genetic mutations in protein-coding regions.^1,2 Recent studies, however, have increasingly shown that genetic diseases, including autoimmune disorders, can be caused by mutations in non-protein coding regions. For example, Castellanos-Rubio et al³ recently identified a long non-coding RNA that plays an essential role in the maintenance of intestinal mucosal immune homeostasis and its genetic polymorphisms contribute to inflammation in celiac disease. New sequencing technologies further highlight the complexities of gene regulation. Recent studies of the ENCODE project estimate hundreds of thousands of non-promoter genomic elements that are regulated in a cell-specific and signal-dependent manner through different transcription factors, non-coding RNAs, as well as other transcriptional regulatory elements.⁴ Taken together, this data suggests that genetic mutations in non-coding regulatory regions have the potential to initiate and perpetuate autoimmune disease.

Our hypothesis is that key somatic genetic mutations in non-coding regulatory regions result in altered transcription factor binding and downstream changes in gene expression, which produce a predisposition to development of linear morphea. To test this hypothesis, we are utilizing whole genome sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) on normal and lesional skin in a cohort of patients with linear morphea to identify disease-specific regulatory variants. If initial experiments yield candidate genes or regulatory regions, we will validate these loci through functional assays to identify variants that stimulate a pro-fibrotic response.

Altogether, these studies will help identify new insights into key genetic contributions to the pathogenesis and transcriptional regulation of linear morphea. Understanding the molecular and genetic basis of linear morphea is significant as it is the first step toward improved pharmacological treatments and preventive strategies for linear morphea.

References

1. Higgins R, Smith A, Walchli R, et al. Absence of somatic mutations in linear localized scleroderma. J Investig Dermatol. 2017;137:S271.
2. Higgins R, Theiler M, Smith A, et al. Genetic architecture of linear localized scleroderma. J Investig Dermatol. 2018;138:S138.
3. Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, et al. A long noncoding RNA associated with susceptibility to celiac disease. Science. 2016;352:91-95.
4. Hoffman MM, Ernst J, Wilder SP, et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2013;41:827-841.

Up next: Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid→

Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid

Sarah Lonowski, MD, MBA, Division of Dermatology, University of California Los Angeles, Los Angeles, California
Disclosures: None.

Introduction
Bullous pemphigoid (BP) is a common, debilitating autoimmune blistering disease which is often managed with prednisone and other systemic immunosuppressive medications. Here, we present the largest case series to date evaluating the use of omalizumab for the treatment of BP, providing novel insight and further support for use of this well-tolerated, minimally immunosuppressive agent.

Objective
To review and analyze the experience of patients with BP treated with omalizumab at a single academic institution.

Methods
Retrospective chart analysis of eleven patients with BP treated at a single academic institution over a 32-month period (April 2016–December 2018). Data was obtained through comprehensive review of pathology reports, laboratory data, and physician documentation. Standard descriptive statistics were performed on the data.

Results
Eleven patients were included in the analysis, 5 females (45.5%) and 6 males (54.5%) with a mean age of 78 years (range, 57-95 years). Patients had failed a mean of 2.3 systemic agents prior to initiation of omalizumab. Seven of 11 patients (63.6%) had experienced adverse effects related to prednisone prior to initiation of omalizumab. Six patients (54.5%) had complete clearance of skin lesions after a median duration of 4.4 months on omalizumab, 3 patients (27.3%) had partial response, and 2 patients (18.2%) did not respond to treatment. The median duration of treatment in all patients at the time of analysis was 12.6 months. All 10 patients on prednisone at the time of omalizumab initiation were able to reduce the dose of prednisone, and 5 of 10 patients (50%) were able to discontinue systemic steroids completely. Baseline serum immunoglobulin E (IgE) and eosinophil levels did not predict treatment response. There were no serious treatment-related adverse effects during the treatment period. 

Conclusions/Relevance
Omalizumab is a well-tolerated, steroid-sparing agent which has a significant disease-modifying effect in the majority of patients. Baseline serum IgE and eosinophil levels do not appear to predict treatment response, therefore patient selection should not hinge on these lab values. Omalizumab should be considered as a treatment option for any patient requiring systemic treatment for BP, but especially for those who have experienced or are at risk for experiencing adverse effects from systemic steroids.

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2019 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 15th Annual Coastal Dermatology Symposium on October 5, 2019.

Overall Grand Prize
Chronic Inflammatory Skin Diseases Are Associated With Herpes Zoster in US Inpatients

Raj Chovatiya, MD, PhD; Jonathan I. Silverberg MD, PhD, MPH, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Disclosures: None.
 

Background
Herpes zoster (HZ) is a vaccine-preventable, viral eruption that affects 1 of every 3 people in the United States in their lifetime. Despite evidence-based guidelines and public health advocacy, many high-risk individuals remain unvaccinated and at risk for significant morbidity from HZ. Patients with chronic inflammatory skin diseases (CISDs), including allergic and autoimmune conditions, have potential risk factors for HZ, including long-term use of systemic corticosteroids and immunosuppressants, and immune dysregulation in the skin and periphery. We sought to determine whether CISDs are associated with HZ in hospitalized patients in the US.

Methods
Data were analyzed from the 2002-2012 Nationwide Inpatient Sample, a representative 20% cross-sectional cohort of US hospitalizations (N=68,490,364 children and adults).

Results
The estimated incidence of primary hospitalization for HZ in the US population was 5.0 per 100,000 persons from 2002-2012. In multivariable weighted logistic regression models including age, sex, race/ethnicity, insurance, mean household income, and long-term systemic corticosteroid use, primary hospitalization for HZ was associated with multiple CISDs: atopic dermatitis (adjusted odds ratio [95% confidence interval]: 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Lichen planus (3.01 [1.36-6.67]), Sézary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) showed increased odds in bivariable models but not in multivariable models. Whereas, hidradenitis suppurativa, chronic idiopathic/spontaneous urticaria, and alopecia areata were not associated with HZ. Similar results were seen in sensitivity analyses among adults age <60 and <50 years. Significant predictors of primary hospitalization for HZ among patients with CISDs included older age, female sex, non-white race/ethnicity, decreasing number of chronic comorbid conditions, and long-term systemic corticosteroid use. Inpatient length of stay and/or inflation adjusted cost of care were significantly higher in inpatients with CISD with vs. without a primary diagnosis of HZ.

Conclusion
CISDs are associated with increased hospitalization for HZ, prolonged length of inpatient stay and increased cost of hospital care. The associations of CISDs and HZ were significant even below the recommended ages (<60 and <50 years) for vaccination with live and recombinant HZ vaccine, respectively. Additional studies are needed to confirm these findings and determine the mechanisms of VZV reactivation. Patients with CISDs constitute a significant, previously under-recognized group that is high-risk for hospitalization for HZ. Dermatologists are the primary physicians who manage the vulnerable population of CISDs. They should be on the forefront of screening, intervention, and most importantly, vaccination for their patients. Future studies should explore implementation of outpatient HZ vaccination by dermatologists and revised disease-specific guidelines to cover the spectrum of CISDs.

Up next: Buyer Beware or You Might Get Burned...→

Buyer Beware or You Might Get Burned: Unregulated Photosensitizing Agents Available Without Prescription From Major Online Retailers 

Kimberly Huerth, MD, MEd, Department of Dermatology, Howard University Hospital, Washington, DC; Olivia Ware, BA, Howard University College of Medicine, Washington, DC; Ginette A. Okoye, MD, Department of Dermatology, Howard University Hospital, Washington, DC; Sharon Bridgeman-Shah, MD, Department of Dermatology, Howard University Hospital, Washington, DC
Disclosures: None.

Background
According to the World Health Organization, the vast majority of the world’s population relies on plant-derived medicine as their primary form of healthcare. Closer to home, these alternative therapies are growing in popularity among American healthcare consumers, in concert with increasing access to such products by means of globalization and the growth of Internet retail. There are numerous reasons why an individual might eschew Western medicine in favor of a more naturopathic approach, including perceived health benefits, cost, prior failure of physician guided treatment, a lack of awareness about the risks these products carry, cultural norms, and desperation born of the psychosocial burden of one’s disease. 

A 73-year-old Eritrean man presented to our outpatient dermatology clinic with a severe, acute, phototoxic reaction following the ingestion of Athamanta decoction for the self-directed treatment of vitiligo. The genus Athamanta is in the Apiaceae family and consists of 6 species of flowering plants native to Europe and North Africa. Furanocoumarins are the phototoxic compounds present in these plants, among which psoralen is perhaps the most notorious. The desiccated Athamanta leaves, sought in the absence of medical consultation, had been obtained from a mail order vendor in Egypt which had advertised them as a “miracle effect for curing vitiligo.” 

Objective
To determine the extent to which unregulated photosensitizing agents for the treatment of vitiligo are available to consumers from online retailers, including major ones such as Amazon and eBay. 

Methods
An online product search of eBay and Amazon, as well as an Internet pharmacy by the name of Cheap Generic, was conducted using search terms “vitiligo treatment,” “psoralen for vitiligo,” “furanocoumarin treatment,” “Athamanta vitiligo,” “Apiaceae vitiligo,” and “leukoderma.” Products generated by the search terms were examined for their route of delivery (topical vs systemic), key photosensitizing ingredient, parent plant, cost to consumer, and country of manufacture. Products that did not identify a known photosensitizing compound, or a plant known to contain a photosensitizing compound, on the list of ingredients were excluded from the analysis. 

Results
We identified a total of 11 products—6 listed on Amazon, 3 listed on eBay, and 2 listed by Cheap Generic pharmacy—that had either a photosensitizing compound, or a plant known to contain a photosensitizing compound, on its list of ingredients. 27.3% of products were available in formulations intended for ingestion, such as tablets or powders. 90.9% of products listed psoralen, or a plant known to contain psoralen, as a major ingredient. Of the products that identified the main photosensitizing plant ingredient (72.7%), Psoralea corylifolia was the most common (75%). Products ranged in cost from $3 to $28. The terms “herbal” (54.5%) and “natural” (36.3%) were used most frequently on the packaging and/or website for promotional purposes. While 45.4% of products did not identify a country of origin, of those that did, 66.7% were manufactured in India, while the remainder were prepared in China. 

Conclusion
Topically and systemically administered psoralen-containing products for the treatment of vitiligo are widely available without a prescription from several online vendors. These products are affordable and utilize suggestive packaging to tout the benefits of the products, without mention of their risks.

Up next: Collagen VII: A Link Between the Skin and Bone Marrow...→

Collagen VII: A Link Between the Skin and Bone Marrow Via Extracellular Vesicles

Jeffrey D. McBride, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida
Disclosures: Dr. McBride has been a consultant with Aegle Therapeutics.

Extracellular vesicles—exosomes, microvesicles, and apoptotic bodies—are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell of origin. Specifically, we have discovered that these extracellular vesicles from the bone marrow–derived mesenchymal stem cells stimulate production of basement membrane components by cells that genetically lacked the ability to do so before (ie, collagen VII from fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa). In other words, our work shows that the bone marrow can replenish collagen VII by directly delivering protein but also by transferring messenger RNA, coding for collagen VII, to the epidermolysis bullosa fibroblasts, allowing them to make collagen VII for the first time. Extracellular vesicles, including exosomes, have immediate potential for serving as therapeutics in dermatology over the next decade.

Up next: Genetic Variations in Non-coding Regulatory Regions in Linear Morphea...→

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea
Dawn Zhang Eichenfield, MD, PhD, University of California, San Diego, Medical Center, La Jolla, California
Disclosures: This research was funded by the Women’s Dermatologic Society and the Pediatric Dermatology Research Alliance.

Linear morphea is a chronic inflammatory and pro-fibrotic disease that can be debilitating and disfiguring. It generally presents at an earlier age of onset than other subtypes of morphea. Like other autoimmune diseases, linear morphea presents predominantly in females, has a familial contribution, and has been associated with particular environmental triggers. Beyond this, however, the full pathogenesis of this disease remains unknown. A more thorough understanding of the causes of linear morphea—genetic and environmental—is the first step toward improved diagnosis and treatment.

Lesions of linear morphea predominantly follow Blaschko’s lines, a pattern of lines on the skin thought to represent pathways of epidermal cell migration and proliferation during fetal development. This presentation suggests that genetic mosaicism may be at play, although studies utilizing whole exome sequencing have not found causative somatic genetic mutations in protein-coding regions.^1,2 Recent studies, however, have increasingly shown that genetic diseases, including autoimmune disorders, can be caused by mutations in non-protein coding regions. For example, Castellanos-Rubio et al³ recently identified a long non-coding RNA that plays an essential role in the maintenance of intestinal mucosal immune homeostasis and its genetic polymorphisms contribute to inflammation in celiac disease. New sequencing technologies further highlight the complexities of gene regulation. Recent studies of the ENCODE project estimate hundreds of thousands of non-promoter genomic elements that are regulated in a cell-specific and signal-dependent manner through different transcription factors, non-coding RNAs, as well as other transcriptional regulatory elements.⁴ Taken together, this data suggests that genetic mutations in non-coding regulatory regions have the potential to initiate and perpetuate autoimmune disease.

Our hypothesis is that key somatic genetic mutations in non-coding regulatory regions result in altered transcription factor binding and downstream changes in gene expression, which produce a predisposition to development of linear morphea. To test this hypothesis, we are utilizing whole genome sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) on normal and lesional skin in a cohort of patients with linear morphea to identify disease-specific regulatory variants. If initial experiments yield candidate genes or regulatory regions, we will validate these loci through functional assays to identify variants that stimulate a pro-fibrotic response.

Altogether, these studies will help identify new insights into key genetic contributions to the pathogenesis and transcriptional regulation of linear morphea. Understanding the molecular and genetic basis of linear morphea is significant as it is the first step toward improved pharmacological treatments and preventive strategies for linear morphea.

References

1. Higgins R, Smith A, Walchli R, et al. Absence of somatic mutations in linear localized scleroderma. J Investig Dermatol. 2017;137:S271.
2. Higgins R, Theiler M, Smith A, et al. Genetic architecture of linear localized scleroderma. J Investig Dermatol. 2018;138:S138.
3. Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, et al. A long noncoding RNA associated with susceptibility to celiac disease. Science. 2016;352:91-95.
4. Hoffman MM, Ernst J, Wilder SP, et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2013;41:827-841.

Up next: Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid→

Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid

Sarah Lonowski, MD, MBA, Division of Dermatology, University of California Los Angeles, Los Angeles, California
Disclosures: None.

Introduction
Bullous pemphigoid (BP) is a common, debilitating autoimmune blistering disease which is often managed with prednisone and other systemic immunosuppressive medications. Here, we present the largest case series to date evaluating the use of omalizumab for the treatment of BP, providing novel insight and further support for use of this well-tolerated, minimally immunosuppressive agent.

Objective
To review and analyze the experience of patients with BP treated with omalizumab at a single academic institution.

Methods
Retrospective chart analysis of eleven patients with BP treated at a single academic institution over a 32-month period (April 2016–December 2018). Data was obtained through comprehensive review of pathology reports, laboratory data, and physician documentation. Standard descriptive statistics were performed on the data.

Results
Eleven patients were included in the analysis, 5 females (45.5%) and 6 males (54.5%) with a mean age of 78 years (range, 57-95 years). Patients had failed a mean of 2.3 systemic agents prior to initiation of omalizumab. Seven of 11 patients (63.6%) had experienced adverse effects related to prednisone prior to initiation of omalizumab. Six patients (54.5%) had complete clearance of skin lesions after a median duration of 4.4 months on omalizumab, 3 patients (27.3%) had partial response, and 2 patients (18.2%) did not respond to treatment. The median duration of treatment in all patients at the time of analysis was 12.6 months. All 10 patients on prednisone at the time of omalizumab initiation were able to reduce the dose of prednisone, and 5 of 10 patients (50%) were able to discontinue systemic steroids completely. Baseline serum immunoglobulin E (IgE) and eosinophil levels did not predict treatment response. There were no serious treatment-related adverse effects during the treatment period. 

Conclusions/Relevance
Omalizumab is a well-tolerated, steroid-sparing agent which has a significant disease-modifying effect in the majority of patients. Baseline serum IgE and eosinophil levels do not appear to predict treatment response, therefore patient selection should not hinge on these lab values. Omalizumab should be considered as a treatment option for any patient requiring systemic treatment for BP, but especially for those who have experienced or are at risk for experiencing adverse effects from systemic steroids.

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2019 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 15th Annual Coastal Dermatology Symposium on October 5, 2019.

Overall Grand Prize
Chronic Inflammatory Skin Diseases Are Associated With Herpes Zoster in US Inpatients

Raj Chovatiya, MD, PhD; Jonathan I. Silverberg MD, PhD, MPH, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Disclosures: None.
 

Background
Herpes zoster (HZ) is a vaccine-preventable, viral eruption that affects 1 of every 3 people in the United States in their lifetime. Despite evidence-based guidelines and public health advocacy, many high-risk individuals remain unvaccinated and at risk for significant morbidity from HZ. Patients with chronic inflammatory skin diseases (CISDs), including allergic and autoimmune conditions, have potential risk factors for HZ, including long-term use of systemic corticosteroids and immunosuppressants, and immune dysregulation in the skin and periphery. We sought to determine whether CISDs are associated with HZ in hospitalized patients in the US.

Methods
Data were analyzed from the 2002-2012 Nationwide Inpatient Sample, a representative 20% cross-sectional cohort of US hospitalizations (N=68,490,364 children and adults).

Results
The estimated incidence of primary hospitalization for HZ in the US population was 5.0 per 100,000 persons from 2002-2012. In multivariable weighted logistic regression models including age, sex, race/ethnicity, insurance, mean household income, and long-term systemic corticosteroid use, primary hospitalization for HZ was associated with multiple CISDs: atopic dermatitis (adjusted odds ratio [95% confidence interval]: 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Lichen planus (3.01 [1.36-6.67]), Sézary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) showed increased odds in bivariable models but not in multivariable models. Whereas, hidradenitis suppurativa, chronic idiopathic/spontaneous urticaria, and alopecia areata were not associated with HZ. Similar results were seen in sensitivity analyses among adults age <60 and <50 years. Significant predictors of primary hospitalization for HZ among patients with CISDs included older age, female sex, non-white race/ethnicity, decreasing number of chronic comorbid conditions, and long-term systemic corticosteroid use. Inpatient length of stay and/or inflation adjusted cost of care were significantly higher in inpatients with CISD with vs. without a primary diagnosis of HZ.

Conclusion
CISDs are associated with increased hospitalization for HZ, prolonged length of inpatient stay and increased cost of hospital care. The associations of CISDs and HZ were significant even below the recommended ages (<60 and <50 years) for vaccination with live and recombinant HZ vaccine, respectively. Additional studies are needed to confirm these findings and determine the mechanisms of VZV reactivation. Patients with CISDs constitute a significant, previously under-recognized group that is high-risk for hospitalization for HZ. Dermatologists are the primary physicians who manage the vulnerable population of CISDs. They should be on the forefront of screening, intervention, and most importantly, vaccination for their patients. Future studies should explore implementation of outpatient HZ vaccination by dermatologists and revised disease-specific guidelines to cover the spectrum of CISDs.

Up next: Buyer Beware or You Might Get Burned...→

Buyer Beware or You Might Get Burned: Unregulated Photosensitizing Agents Available Without Prescription From Major Online Retailers 

Kimberly Huerth, MD, MEd, Department of Dermatology, Howard University Hospital, Washington, DC; Olivia Ware, BA, Howard University College of Medicine, Washington, DC; Ginette A. Okoye, MD, Department of Dermatology, Howard University Hospital, Washington, DC; Sharon Bridgeman-Shah, MD, Department of Dermatology, Howard University Hospital, Washington, DC
Disclosures: None.

Background
According to the World Health Organization, the vast majority of the world’s population relies on plant-derived medicine as their primary form of healthcare. Closer to home, these alternative therapies are growing in popularity among American healthcare consumers, in concert with increasing access to such products by means of globalization and the growth of Internet retail. There are numerous reasons why an individual might eschew Western medicine in favor of a more naturopathic approach, including perceived health benefits, cost, prior failure of physician guided treatment, a lack of awareness about the risks these products carry, cultural norms, and desperation born of the psychosocial burden of one’s disease. 

A 73-year-old Eritrean man presented to our outpatient dermatology clinic with a severe, acute, phototoxic reaction following the ingestion of Athamanta decoction for the self-directed treatment of vitiligo. The genus Athamanta is in the Apiaceae family and consists of 6 species of flowering plants native to Europe and North Africa. Furanocoumarins are the phototoxic compounds present in these plants, among which psoralen is perhaps the most notorious. The desiccated Athamanta leaves, sought in the absence of medical consultation, had been obtained from a mail order vendor in Egypt which had advertised them as a “miracle effect for curing vitiligo.” 

Objective
To determine the extent to which unregulated photosensitizing agents for the treatment of vitiligo are available to consumers from online retailers, including major ones such as Amazon and eBay. 

Methods
An online product search of eBay and Amazon, as well as an Internet pharmacy by the name of Cheap Generic, was conducted using search terms “vitiligo treatment,” “psoralen for vitiligo,” “furanocoumarin treatment,” “Athamanta vitiligo,” “Apiaceae vitiligo,” and “leukoderma.” Products generated by the search terms were examined for their route of delivery (topical vs systemic), key photosensitizing ingredient, parent plant, cost to consumer, and country of manufacture. Products that did not identify a known photosensitizing compound, or a plant known to contain a photosensitizing compound, on the list of ingredients were excluded from the analysis. 

Results
We identified a total of 11 products—6 listed on Amazon, 3 listed on eBay, and 2 listed by Cheap Generic pharmacy—that had either a photosensitizing compound, or a plant known to contain a photosensitizing compound, on its list of ingredients. 27.3% of products were available in formulations intended for ingestion, such as tablets or powders. 90.9% of products listed psoralen, or a plant known to contain psoralen, as a major ingredient. Of the products that identified the main photosensitizing plant ingredient (72.7%), Psoralea corylifolia was the most common (75%). Products ranged in cost from $3 to $28. The terms “herbal” (54.5%) and “natural” (36.3%) were used most frequently on the packaging and/or website for promotional purposes. While 45.4% of products did not identify a country of origin, of those that did, 66.7% were manufactured in India, while the remainder were prepared in China. 

Conclusion
Topically and systemically administered psoralen-containing products for the treatment of vitiligo are widely available without a prescription from several online vendors. These products are affordable and utilize suggestive packaging to tout the benefits of the products, without mention of their risks.

Up next: Collagen VII: A Link Between the Skin and Bone Marrow...→

Collagen VII: A Link Between the Skin and Bone Marrow Via Extracellular Vesicles

Jeffrey D. McBride, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida
Disclosures: Dr. McBride has been a consultant with Aegle Therapeutics.

Extracellular vesicles—exosomes, microvesicles, and apoptotic bodies—are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell of origin. Specifically, we have discovered that these extracellular vesicles from the bone marrow–derived mesenchymal stem cells stimulate production of basement membrane components by cells that genetically lacked the ability to do so before (ie, collagen VII from fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa). In other words, our work shows that the bone marrow can replenish collagen VII by directly delivering protein but also by transferring messenger RNA, coding for collagen VII, to the epidermolysis bullosa fibroblasts, allowing them to make collagen VII for the first time. Extracellular vesicles, including exosomes, have immediate potential for serving as therapeutics in dermatology over the next decade.

Up next: Genetic Variations in Non-coding Regulatory Regions in Linear Morphea...→

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea
Dawn Zhang Eichenfield, MD, PhD, University of California, San Diego, Medical Center, La Jolla, California
Disclosures: This research was funded by the Women’s Dermatologic Society and the Pediatric Dermatology Research Alliance.

Linear morphea is a chronic inflammatory and pro-fibrotic disease that can be debilitating and disfiguring. It generally presents at an earlier age of onset than other subtypes of morphea. Like other autoimmune diseases, linear morphea presents predominantly in females, has a familial contribution, and has been associated with particular environmental triggers. Beyond this, however, the full pathogenesis of this disease remains unknown. A more thorough understanding of the causes of linear morphea—genetic and environmental—is the first step toward improved diagnosis and treatment.

Lesions of linear morphea predominantly follow Blaschko’s lines, a pattern of lines on the skin thought to represent pathways of epidermal cell migration and proliferation during fetal development. This presentation suggests that genetic mosaicism may be at play, although studies utilizing whole exome sequencing have not found causative somatic genetic mutations in protein-coding regions.^1,2 Recent studies, however, have increasingly shown that genetic diseases, including autoimmune disorders, can be caused by mutations in non-protein coding regions. For example, Castellanos-Rubio et al³ recently identified a long non-coding RNA that plays an essential role in the maintenance of intestinal mucosal immune homeostasis and its genetic polymorphisms contribute to inflammation in celiac disease. New sequencing technologies further highlight the complexities of gene regulation. Recent studies of the ENCODE project estimate hundreds of thousands of non-promoter genomic elements that are regulated in a cell-specific and signal-dependent manner through different transcription factors, non-coding RNAs, as well as other transcriptional regulatory elements.⁴ Taken together, this data suggests that genetic mutations in non-coding regulatory regions have the potential to initiate and perpetuate autoimmune disease.

Our hypothesis is that key somatic genetic mutations in non-coding regulatory regions result in altered transcription factor binding and downstream changes in gene expression, which produce a predisposition to development of linear morphea. To test this hypothesis, we are utilizing whole genome sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) on normal and lesional skin in a cohort of patients with linear morphea to identify disease-specific regulatory variants. If initial experiments yield candidate genes or regulatory regions, we will validate these loci through functional assays to identify variants that stimulate a pro-fibrotic response.

Altogether, these studies will help identify new insights into key genetic contributions to the pathogenesis and transcriptional regulation of linear morphea. Understanding the molecular and genetic basis of linear morphea is significant as it is the first step toward improved pharmacological treatments and preventive strategies for linear morphea.

References

1. Higgins R, Smith A, Walchli R, et al. Absence of somatic mutations in linear localized scleroderma. J Investig Dermatol. 2017;137:S271.
2. Higgins R, Theiler M, Smith A, et al. Genetic architecture of linear localized scleroderma. J Investig Dermatol. 2018;138:S138.
3. Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, et al. A long noncoding RNA associated with susceptibility to celiac disease. Science. 2016;352:91-95.
4. Hoffman MM, Ernst J, Wilder SP, et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2013;41:827-841.

Up next: Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid→

Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid

Sarah Lonowski, MD, MBA, Division of Dermatology, University of California Los Angeles, Los Angeles, California
Disclosures: None.

Introduction
Bullous pemphigoid (BP) is a common, debilitating autoimmune blistering disease which is often managed with prednisone and other systemic immunosuppressive medications. Here, we present the largest case series to date evaluating the use of omalizumab for the treatment of BP, providing novel insight and further support for use of this well-tolerated, minimally immunosuppressive agent.

Objective
To review and analyze the experience of patients with BP treated with omalizumab at a single academic institution.

Methods
Retrospective chart analysis of eleven patients with BP treated at a single academic institution over a 32-month period (April 2016–December 2018). Data was obtained through comprehensive review of pathology reports, laboratory data, and physician documentation. Standard descriptive statistics were performed on the data.

Results
Eleven patients were included in the analysis, 5 females (45.5%) and 6 males (54.5%) with a mean age of 78 years (range, 57-95 years). Patients had failed a mean of 2.3 systemic agents prior to initiation of omalizumab. Seven of 11 patients (63.6%) had experienced adverse effects related to prednisone prior to initiation of omalizumab. Six patients (54.5%) had complete clearance of skin lesions after a median duration of 4.4 months on omalizumab, 3 patients (27.3%) had partial response, and 2 patients (18.2%) did not respond to treatment. The median duration of treatment in all patients at the time of analysis was 12.6 months. All 10 patients on prednisone at the time of omalizumab initiation were able to reduce the dose of prednisone, and 5 of 10 patients (50%) were able to discontinue systemic steroids completely. Baseline serum immunoglobulin E (IgE) and eosinophil levels did not predict treatment response. There were no serious treatment-related adverse effects during the treatment period. 

Conclusions/Relevance
Omalizumab is a well-tolerated, steroid-sparing agent which has a significant disease-modifying effect in the majority of patients. Baseline serum IgE and eosinophil levels do not appear to predict treatment response, therefore patient selection should not hinge on these lab values. Omalizumab should be considered as a treatment option for any patient requiring systemic treatment for BP, but especially for those who have experienced or are at risk for experiencing adverse effects from systemic steroids.

Gov. Gavin Newsom (D-CA) signed into law three bills intended to lower drug prices and increase access to prescription drugs as part of a continuing health care initiative intended to benefit the residents of California.

doomu/Thinkstock

AB 824, the Pay for Delay bill, bans pharmaceutical companies from keeping cheaper generic drugs off the market. The bill prohibits agreements between brand name and generic drug manufacturers to delay the release of generic drugs, defining them as presumptively anticompetitive. A Federal Trade Commission study found that “these anticompetitive deals cost consumers and taxpayers $3.5 billion in higher drug costs every year,” according to a statement from the governor’s office.

The second bill, SB 464, is intended to improve black maternal health care. The bill is designed to reduce preventable maternal mortality among black women by requiring all perinatal health care providers to undergo implicit bias training to curb the effects of bias on maternal health and by improving data collection at the California Department of Public Health to better understand pregnancy-related deaths. “We know that black women have been dying at alarming rates during and after giving birth. The disproportionate effect of the maternal mortality rate on this community is a public health crisis and a major health equity issue. We must do everything in our power to take implicit bias out of the medical system – it is literally a matter of life and death,” said Gov. Newsom.

The third bill, SB 159, aims to facilitate the use of pre-exposure prophylaxis and postexposure prophylaxis against HIV infection. The bill allows pharmacists in the state to dispense PrEP and PEP without a physician’s prescription and prohibits insurance companies from requiring prior authorization for patients to obtain PrEP coverage. “All Californians deserve access to PrEP and PEP, two treatments that have transformed our fight against HIV and AIDS,” Gov. Newsom said in a statement.

[email protected]

Gov. Gavin Newsom (D-CA) signed into law three bills intended to lower drug prices and increase access to prescription drugs as part of a continuing health care initiative intended to benefit the residents of California.

doomu/Thinkstock

AB 824, the Pay for Delay bill, bans pharmaceutical companies from keeping cheaper generic drugs off the market. The bill prohibits agreements between brand name and generic drug manufacturers to delay the release of generic drugs, defining them as presumptively anticompetitive. A Federal Trade Commission study found that “these anticompetitive deals cost consumers and taxpayers $3.5 billion in higher drug costs every year,” according to a statement from the governor’s office.

The second bill, SB 464, is intended to improve black maternal health care. The bill is designed to reduce preventable maternal mortality among black women by requiring all perinatal health care providers to undergo implicit bias training to curb the effects of bias on maternal health and by improving data collection at the California Department of Public Health to better understand pregnancy-related deaths. “We know that black women have been dying at alarming rates during and after giving birth. The disproportionate effect of the maternal mortality rate on this community is a public health crisis and a major health equity issue. We must do everything in our power to take implicit bias out of the medical system – it is literally a matter of life and death,” said Gov. Newsom.

The third bill, SB 159, aims to facilitate the use of pre-exposure prophylaxis and postexposure prophylaxis against HIV infection. The bill allows pharmacists in the state to dispense PrEP and PEP without a physician’s prescription and prohibits insurance companies from requiring prior authorization for patients to obtain PrEP coverage. “All Californians deserve access to PrEP and PEP, two treatments that have transformed our fight against HIV and AIDS,” Gov. Newsom said in a statement.

[email protected]

Gov. Gavin Newsom (D-CA) signed into law three bills intended to lower drug prices and increase access to prescription drugs as part of a continuing health care initiative intended to benefit the residents of California.

doomu/Thinkstock

AB 824, the Pay for Delay bill, bans pharmaceutical companies from keeping cheaper generic drugs off the market. The bill prohibits agreements between brand name and generic drug manufacturers to delay the release of generic drugs, defining them as presumptively anticompetitive. A Federal Trade Commission study found that “these anticompetitive deals cost consumers and taxpayers $3.5 billion in higher drug costs every year,” according to a statement from the governor’s office.

The second bill, SB 464, is intended to improve black maternal health care. The bill is designed to reduce preventable maternal mortality among black women by requiring all perinatal health care providers to undergo implicit bias training to curb the effects of bias on maternal health and by improving data collection at the California Department of Public Health to better understand pregnancy-related deaths. “We know that black women have been dying at alarming rates during and after giving birth. The disproportionate effect of the maternal mortality rate on this community is a public health crisis and a major health equity issue. We must do everything in our power to take implicit bias out of the medical system – it is literally a matter of life and death,” said Gov. Newsom.

The third bill, SB 159, aims to facilitate the use of pre-exposure prophylaxis and postexposure prophylaxis against HIV infection. The bill allows pharmacists in the state to dispense PrEP and PEP without a physician’s prescription and prohibits insurance companies from requiring prior authorization for patients to obtain PrEP coverage. “All Californians deserve access to PrEP and PEP, two treatments that have transformed our fight against HIV and AIDS,” Gov. Newsom said in a statement.

[email protected]

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

The AGA Center for GI Innovation and Technology supports innovation and the development of new technology in gastroenterology, hepatology, nutrition and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process. To learn more visit www.gastro.org/CIGT. 

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

The AGA Center for GI Innovation and Technology supports innovation and the development of new technology in gastroenterology, hepatology, nutrition and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process. To learn more visit www.gastro.org/CIGT. 

Despite theoretical preferences for either the anterior or the posterior approach to peroral endoscopic myotomy (POEM) in patients with achalasia, a new study has found no significant difference between the two in regard to clinical success or safety.

“Both approaches are equivalently safe when performed by experienced operators,” wrote Mouen A. Khashab, MD, of Johns Hopkins Medicine in Baltimore and coauthors, adding that the most notable difference was “closure was rated as easier during the posterior approach,” and fewer clips were needed. The study was published in Gastrointestinal Endoscopy.

To analyze and compare the efficacy of the two POEM approaches, the researchers conducted a multicenter controlled clinical trial of 150 patients with achalasia. They were randomized into two groups: those receiving POEM with the anterior approach (n = 73) or the posterior approach (n = 77). Of those patients, 148 received POEM and 138 completed 1-year follow-up. At 3, 6, and 12 months’ follow-up by phone call, patients were evaluated via outcomes that included Eckardt and dysphagia scores, quality of life scales, and gastroesophageal reflux disease questionnaire score.

Technical success was achieved in all 77 patients in the posterior group compared with 71 patients (97.3%) in the anterior group (P = .23). Both groups had a median length of hospital stay post procedure of 2 days. Adverse events occurred in seven patients (9%) in the posterior group and in eight patients (11%) in the anterior group (P = .703).

Though no significant differences were found between the two groups in time to perform mucosal incision, submucosal tunneling, myotomy, or closure, the median difficulty of closure in the posterior group was lower than in the anterior group (P = .002). In addition, fewer clips were needed during closure in the posterior approach.

After per-protocol analysis, clinical success at 1 year was achieved in 89% of patients in the posterior group (95% confidence interval, 81%-96%) and 90% of patients in the anterior group (95% CI, 82%-97%). At 1-year follow-up, both groups had an Eckardt score of 0 (P = .994) and their median gastroesophageal reflux disease score was 6 (P = .73). All patients who completed quality of life questionnaires reported improvements, with a median change in pain of 23 in the anterior group and 34 in the posterior group (P = .49). The posterior group also reported a greater median change in social functioning (50 vs. 38; P = .02).

The authors noted their study’s potential limitations, including relying on the Eckardt scoring system – one that was recently questioned in terms of validity – to determine clinical success. However, they also offered an argument in favor of clinical scoring because of “the importance of symptom improvement from the patient perspective.” Also, because of the lack of prestudy data comparing the anterior and posterior approaches, they chose 15% as the noninferiority margin for clinical efficacy, which could be regarded as a limitation as well.

Four of the authors reported potential conflicts of interest, including serving as consultants for various medical companies, serving on medical advisory boards, and receiving research support and personal fees. The other authors reported no conflicts of interest.

SOURCE: Khashab MA et al. Gastrointest Endosc. 2019 Aug 10. doi: 10.1016/j.gie.2019.07.034.

The AGA Center for GI Innovation and Technology supports innovation and the development of new technology in gastroenterology, hepatology, nutrition and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process. To learn more visit www.gastro.org/CIGT. 

One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.

Christoph Burgstedt/iStock/Getty Images Plus

Nationwide, 1,306 infants acquired syphilis from their mother in 2018, a 40% rise over 2017, according to federal data released Oct. 8. Seventy-eight of those babies were stillborn, and 16 died after birth.

In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.

The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.

For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.

“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.

It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.

The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.

The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.

Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.

For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.

Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.

Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.

“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.

The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”

A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”

San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.

In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.

Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.

In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.

Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.

“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”

The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.

Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.

In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
 

This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
 

One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.

Christoph Burgstedt/iStock/Getty Images Plus

Nationwide, 1,306 infants acquired syphilis from their mother in 2018, a 40% rise over 2017, according to federal data released Oct. 8. Seventy-eight of those babies were stillborn, and 16 died after birth.

In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.

The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.

For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.

“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.

It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.

The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.

The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.

Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.

For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.

Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.

Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.

“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.

The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”

A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”

San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.

In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.

Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.

In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.

Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.

“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”

The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.

Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.

In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
 

This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
 

One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.

Christoph Burgstedt/iStock/Getty Images Plus

Nationwide, 1,306 infants acquired syphilis from their mother in 2018, a 40% rise over 2017, according to federal data released Oct. 8. Seventy-eight of those babies were stillborn, and 16 died after birth.

In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.

The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.

For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.

“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.

It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.

The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.

The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.

Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.

For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.

Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.

Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.

“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.

The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”

A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”

San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.

In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.

Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.

In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.

Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.

“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”

The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.

Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.

In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
 

This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
 

A study of dupilumab in adolescents with atopic dermatitis (AD) has provided longer term efficacy and safety data, with no new safety signals and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.

The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.

In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg

The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.

There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.

However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.

By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.

More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.

“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.

Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.

SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.

A study of dupilumab in adolescents with atopic dermatitis (AD) has provided longer term efficacy and safety data, with no new safety signals and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.

The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.

In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg

The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.

There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.

However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.

By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.

More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.

“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.

Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.

SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.

A study of dupilumab in adolescents with atopic dermatitis (AD) has provided longer term efficacy and safety data, with no new safety signals and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.

The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.

In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg

The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.

There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.

However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.

By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.

More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.

“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.

Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.

SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.