Pain management in hidradenitis suppurativa and a proposed treatment algorithm.

Pain contributes substantially to reduced quality of life in individuals living with hidradenitis suppurativa (HS). Although improved understanding of HS pathogenesis and treatment has resulted in improved evidence-based HS management guidelines, comprehensive pain management guidelines have yet to be developed. Few HS-specific data exist to guide pharmacologic analgesia; however, recognizing HS pain as either acute or chronic and predominantly nociceptive (aching and gnawing pain due to tissue damage) versus neuropathic (burning-type pain due to somatosensory nervous system dysfunction) provides a conceptual framework for applying outside pain management practices to HS management. This article incorporates the best available evidence from the HS and pain literature to propose an HS pain algorithm that integrates psychological, pharmacologic, and complementary and alternative treatment modalities.

Proceeding report of the Second Symposium on Hidradenitis Suppurativa Advances (SHSA) 2017.

The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03-05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease.

When Mom Has Migraine: An Observational Study of the Impact of Parental Migraine on Adolescent Children.

OBJECTIVE: The current study aimed to describe the impact of parental migraine on adolescent children (aged 11-17) living at home with a parent with migraine. BACKGROUND: Emerging evidence suggests that migraine impacts the family members of people with migraine. However, there has been little research to evaluate the perspective of the child of a parent with migraine. METHODS: This cross-sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11-17-year-old children currently living with the parent with migraine recruited from neurologist offices and online. Parents completed measures of demographics, a diagnostic migraine criteria screener, parental illness impact (Parental Illness Impact Survey - Revised; subscales = Burden of Daily Help, Emotional Impact, Social Impact, Communication and Understanding, Impact on Personal Future, Friends Reactions, Parent/Child Relationship, and Global Well-Being), migraine-related disability (MIDAS), headache attack frequency, and headache attack pain intensity. Children completed measures of demographics, parental illness impact, and a migraine diagnostic screener if applicable. RESULTS: Children (n = 40) reported the greatest impact of their parent's migraine on the Global Well-Being (M = 3.3, SD = 0.9) and Parent/Child Relationship (M = 3.5, SD = 0.6) subscales. There were no significant differences between the average child and parent rating of parental migraine impact on children. Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale (ρ = 0.55, P < .001), and non-significant for the Parent/Child Relationship (ρ = 0.13, P = .416) and Friends Reactions (ρ = 0.18, P = .257) subscales. Higher attack frequency and endorsing severe disability on the MIDAS were associated with higher child-rated impact (eg, lower scores) on Global Well-Being (frequency ρ = -0.35, P = .028; MIDAS t(38) = 2.74, P = .009) and Impact on Personal Future (frequency ρ = -0.41, P = .009; MIDAS t(35.7) = 2.49, P = .017) subscales. Higher attack pain intensity was associated with higher child-rated impact (eg, lower scores) on Burden of Daily Help (r = -0.34, P = .031) and Emotional Impact (r = -0.40, P = .010). Over half of children (23/40, 57.5%) reported some kind of service or intervention to help them manage the impact of their parent's migraine on their lives would be helpful. CONCLUSIONS: Parental migraine impacts children aged 11-17 living in the home, particularly in the domains of global well-being and the parent/child relationship. Parent and child reports are not strongly correlated across all domains of parental impact.

Does Mindfulness-Based Cognitive Therapy for Migraine Reduce Migraine-Related Disability in People with Episodic and Chronic Migraine? A Phase 2b Pilot Randomized Clinical Trial.

OBJECTIVE: The current Phase 2b study aimed to evaluate the efficacy of mindfulness-based cognitive therapy for migraine (MBCT-M) to reduce migraine-related disability in people with migraine. BACKGROUND: Mindfulness-based interventions represent a promising avenue to investigate effects in people with migraine. MBCT teaches mindfulness meditation and cognitive-behavioral skills and directly applies these skills to address disease-related cognitions. METHODS: Participants with migraine (6-30 headache days/month) were recruited from neurology office referrals and local and online advertisements in the broader New York City area. During the 30-day baseline period, all participants completed a daily headache diary. Participants who met inclusion and exclusion criteria were randomized in a parallel design, stratified by chronic migraine status, to receive either 8 weekly individual MBCT-M sessions or 8 weeks of waitlist/treatment as usual (WL/TAU). All participants completed surveys including primary outcome evaluations at Months 0, 1, 2, and 4. All participants completed a headache diary during the 30-day posttreatment evaluation period. Primary outcomes were the change from Month 0 to Month 4 in the headache disability inventory (HDI) and the Migraine Disability Assessment (MIDAS) (total score ≥ 21 indicating severe disability); secondary outcomes (headache days/30 days, average headache attack pain intensity, and attack-level migraine-related disability [Migraine Disability Index (MIDI)]) were derived from the daily headache diary. RESULTS: Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%) and Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%) with a graduate degree (n = 35/60; 55.0%) who were working full-time (n = 38/60; 63.3%). At baseline, the average HDI score (51.4, SD = 19.0) indicated a moderate level of disability and the majority of participants (50/60, 83.3%) fell in the "Severe Disability" range in the MIDAS. Participants recorded an average of 16.0 (SD = 5.9) headache days/30 days, with an average headache attack pain intensity of 1.7 on a 4-point scale (SD = 0.3), indicating moderate intensity. Average levels of daily disability reported on the MIDI were 3.1/10 (SD = 1.8). For the HDI, mean scores decreased more from Month 0 to Month 4 in the MBCT-M group (-14.3) than the waitlist/treatment as an usual group (-0.2; P < .001). For the MIDAS, the group*month interaction was not significant when accounting for the divided alpha, P = .027; across all participants in both groups, the estimated proportion of participants falling in the "Severe Disability" category fell significantly from 88.3% at Month 0 to 66.7% at Month 4, P < .001. For diary-reported headache days/30 days an average headache attack pain intensity, neither the group*month interaction (Ps = .773 and .888, respectively) nor the time effect (Ps = .059 and .428, respectively) was significant. Mean MIDI scores decreased in the MBCT-M group (-0.6/10), whereas they increased in the waitlist/treatment as an usual group (+0.3/10), P = .007. CONCLUSIONS: MBCT-M demonstrated efficacy to reduce headache-related disability and attack-level migraine-related disability. MBCT-M is a promising emerging treatment for addressing migraine-related disability.

Correction to: Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa.

The original version of this article contains an error in the spelling of the title. The title should read: Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa.

Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa [corrected].

PURPOSE OF REVIEW: Hidradenitis suppurativa (HS) is a chronic, painful dermatologic disease characterized by recurrent inflammatory nodules and abscesses of intertriginous areas such as the axilla and groin. People with HS suffer from greater pain and associated psychological comorbidities, including depression, anxiety, disability, and impairments in quality of life (QoL), compared to those with other dermatologic conditions. Our review focuses on the occurrence of pain and these relationships. RECENT FINDINGS: The existing literature indicates that acute and chronic pain, depression, anxiety, and disability all contribute to poor quality of life in individuals with HS. Despite the central role of pain and distress in the presentation of HS, few studies have empirically evaluated the impact of pain and gaps remain in the existing psychosocial literature. There are no formal guidelines for treating HS-specific pain or psychological comorbidities. The results of this review show a clear and pressing need to develop treatment recommendations and effective interventions for addressing acute and chronic pain, psychological comorbidities, disability, and impaired quality of life among people with HS. This review outlines a multidisciplinary approach to treating and managing pain and psychological comorbidities.

In vitro and in vivo activities of antibiotic PM181104.

Drug resistance has become a global threat that, if not addressed, may return us to the preantibiotic era. A way to overcome the problem of growing incidence of global antibiotic resistance is to introduce compounds belonging to classes that are new to the clinic. During a screening of the marine microbial extract library for new antibiotics, one of the extracts showed promising antibacterial activity against Gram-positive organisms. Bioactivity-guided isolation and characterization of active metabolites led to the discovery of a novel thiazolyl cyclic-peptide antibiotic, PM181104. It was isolated and characterized from a marine sponge-associated actinobacterium strain of the genus Kocuria (MTCC 5269). The compound exhibited a potent in vitro antibacterial activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The MIC values evaluated for the compound were found to be in the single-digit nanomolar range. In in vivo studies of PM181104 in a BALB/c murine septicemia model, the compound displayed 100% effective dose (ED100) values of 2.5 and 5.0 mg/kg of body weight against MRSA and 10.0 mg/kg against VRE. In this report, in vitro and in vivo studies of PM181104 are described.

Response to Mindfulness-Based Cognitive Therapy Differs Between Chronic and Episodic Migraine.

OBJECTIVE: Evaluate whether the benefits of Mindfulness-Based Cognitive Therapy for Migraine (MBCT-M) on headache disability differs among people with episodic and chronic migraine (CM). METHODS: This is a planned secondary analysis of a randomized clinical trial. After a 30-day baseline, participants were stratified by episodic (6-14 d/mo) and CM (15-30 d/mo) and randomized to 8 weekly individual sessions of MBCT-M or wait list/treatment as usual (WL/TAU). Primary outcomes (Headache Disability Inventory; Severe Migraine Disability Assessment Scale [scores ≥ 21]) were assessed at months 0, 1, 2, and 4. Mixed models for repeated measures tested moderation with fixed effects of treatment, time, CM, and all interactions. Planned subgroup analyses evaluated treatment*time in episodic and CM. RESULTS: Of 60 participants (MBCT-M N = 31, WL/TAU N = 29), 52% had CM. CM moderated the effect of MBCT-M on Severe Migraine Disability Assessment Scale, F(3, 205) = 3.68, p = 0.013; MBCT-M vs WL/TAU reduced the proportion of people reporting severe disability to a greater extent among people with episodic migraine (-40.0% vs -14.3%) than CM (-16.4% vs +8.7%). Subgroup analysis revealed MBCT-M (vs WL/TAU) significantly reduced Headache Disability Inventory for episodic (p = 0.011) but not CM (p = 0.268). CONCLUSIONS: MBCT-M is a promising treatment for reducing headache-related disability, with greater benefits in episodic than CM. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02443519. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that MBCT-M reduces headache disability to a greater extent in people with episodic than CM.

Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea.

PURPOSE: This retrospective study was designed to analyze the FSHR gene variants in subjects with primary and secondary amenorrhea with hypergonadotropic hypogonadism. MATERIALS AND METHODS: Eighty six women with primary or secondary amenorrhea and 100 normally cycling proven fertile women of Indian origin were retrospectively studied. These subjects were systematically screened for entire FSHR gene. RESULTS: The frequency distribution of polymorphism at -29 position of FSHR gene is altered in women with primary and secondary amenorrhea as compared to controls. AA genotype at -29 position of FSHR gene seems to be associated with increased serum FSH levels in the study subjects. We have identified a novel homozygous mutation C(1723)T (Ala(575)Val) in one woman with primary amenorrhea. CONCLUSIONS: Our findings suggest that increased serum FSH levels in subjects with primary amenorrhea correlated to FSHR genotype at position -29. We identified a novel homozygous mutation C(1723)T (Ala(575)Val) in a woman with primary amenorrhea.

CGG repeat sizing in the FMR1 gene in Indian women with premature ovarian failure.

The CGG repeat stretch in the FMR1 gene is polymorphic, ranging from 5 to 50 repeats in the normal population. Expansion of the repeats to the premutation range (50-200) has been associated with premature ovarian failure (POF). This case-control study was conducted to enumerate CGG repeats in the FMR1 gene in 80 Indian women with non-familial, non-syndromic POF, and 70 controls from the same ethnicity. A possible association between CGG repeats and endocrine profile of these cases was investigated. All patients and controls had CGG repeats in the normal polymorphic range. Serum FSH concentrations were significantly raised in both POF cases and controls having CGG repeats in the 31-40 repeats range (P < 0.0001). POF cases and controls had FSH concentrations of 133.7 versus 84.2 mIU/ml and 16.0 versus 6.2 mIU/ml for >30 repeats versus <30 repeats respectively. Inhibin B concentrations were not associated with CGG repeats. The results of this study indicate that FMR1 premutations are rare in sporadic cases of POF with no family history of fragile X syndrome. However, although in the normal polymorphic range, expansion of the CGG repeat tract to beyond 30 repeats was associated with serum FSH concentrations in both POF cases and controls.

Transfer of isoniazid from circulation to breast milk in lactating women on chronic therapy for tuberculosis.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Isoniazid is the most widely used first line antituberculosis drug. It is considered safe during lactation, but limited data are available on the transfer of isoniazid from circulation to milk in lactating women, which can provide an assessment of extent of exposure to the nursling. WHAT THIS STUDY ADDS: The study documents the transfer pattern and milk to plasma (M : P) ratio of isoniazid at a steady state. Peak plasma and milk concentrations of isoniazid were reached within 1 h and the projected exposure of the drug to the infant is much lower than the prophylactic dose, supporting its safety during breast feeding. AIM: To determine milk to plasma (M : P) ratios and infant dose (absolute and relative) for isoniazid in lactating women on antituberculosis therapy. METHODS: Concentrations of isoniazid in plasma and milk were measured in exclusively breast feeding women taking 300 mg day(-1) as treatment for tuberculosis. RESULTS: Peak plasma and milk concentrations of isoniazid were observed at 1 h. A mean M : P(AUC) value of 0.89 (95% CI 0.7, 1.1) was calculated for isoniazid from seven women over 24 h. The mean absolute infant dose was estimated to be 89.9 mug kg day(-1) (95% CI 65.6, 114) and the relative infant dose was 1.2% of the weight adjusted maternal dose. CONCLUSIONS: The mean relative dose of isoniazid (1.2%) transmitted to the infant via breast milk is below the 10% notional level of concern. These data suggest that isoniazid therapy is safe during breastfeeding.

Combined KIT and CTLA-4 Blockade in Patients with Refractory GIST and Other Advanced Sarcomas: A Phase Ib Study of Dasatinib plus Ipilimumab.

Purpose: A phase Ib study of dasatinib plus ipilimumab in patients with gastrointestinal stromal tumor (GIST) and other sarcomas was performed on the basis of preclinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic.Experimental Design: A standard 3 + 3 design was used to evaluate the safety, efficacy, and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks, followed by maintenance every 12 weeks with escalating doses of dasatinib (70 mg daily, 100 mg daily, or 70 mg twice daily). Response was assessed by RECIST 1.1, Choi, and immune-related RECIST criteria (irRC).Results: A total of 28 patients (17 male) were enrolled. Histologic subtypes included GISTs (n = 20) and other sarcomas (n = 8.) Dasatinib 70 mg/day with ipilimumab 10 mg/kg or dasatinib 140 mg/day with ipilimumab 3 mg/kg can be safely administered. Dose-limiting toxicities included grade 3 gastric hemorrhage and anemia. No partial or complete responses were noted by RECIST or irRC. There were 7 of 13 partial responses in the GIST patients by Choi criteria, and 3 of 13 patients each had stable and progressive disease, respectively.Conclusions: Dasatinib and ipilimumab can be safely administered to GIST and sarcoma patients. However, dasatinib was not synergistic with ipilimumab, as there was limited clinical efficacy with the combination. This limited cohort provides prospective data that indoleamine-2,3-dioxygenase (IDO) suppression may potentially correlate with antitumor efficacy in GIST. Given the small cohort, it is only hypothesis generating and additional data would be required. In the era of more modern and effective checkpoint inhibitors, next steps could be consideration of tyrosine kinase inhibitors or IDO inhibitors in combination with anti-PD-1 therapy. Clin Cancer Res; 23(12); 2972-80. ©2016 AACR.

Screening for FOXL2 gene mutations in women with premature ovarian failure: an Indian experience.

Premature ovarian failure (POF) occurs in 1% of the general population and affects approximately 10% of non-ovulating women, resulting in infertility and sex steroid deficiency. The forkhead domain transcription factor (FOXL2) gene is one of the candidate genes associated with POF. This case-control study was designed for mutational analysis of the coding region of the FOXL2 gene in 80 cases of POF patients, 50 controls and 17 family members of 11 index cases using restriction fragment length polymorphism, single-stranded conformational polymorphism, heteroduplex analysis and direct DNA sequencing. A 738C-->T transition and a 773C-->G transversion were detected in two of the 80 patients and a family member of one index case, but in none of the 50 controls screened. No other alterations in the coding region of FOXL2 gene were detected. These data suggest that FOXL2 gene mutations are a rare occurrence in isolated POF cases and may not be involved in the pathogenesis of POF.

Development and validation of an ELISA for hemoglobin-A2: a novel method for beta-thalassemia screening in developing countries.

Hemoglobin-A2 (HbA2) measurement in human hemolysates has great significance, since its level can indicate beta-thalassemia carrier status in otherwise healthy individuals. An ELISA for HbA2 using antiserum monospecific to the delta chain of HbA2 and affinity purified antirabbit gamma globulins (ARGG) conjugated to horseradish peroxidase (HRP) have been developed. The monospecific antiserum used does not cross react with other hemoglobins. Hemolysates from volunteers are used for measurement of HbA2. In a limited trial for beta-thalassemia carrier screening (n = 350), the results obtained with the developed ELISA are comparable with those obtained with a micro-column chromatography method (r > or = 0.89). The developed ELISA is simple, accurate, precise, inexpensive, and several samples can be processed simultaneously with ease, making this system a suitable candidate for transforming into a user friendly kit.