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Misophonia is a common condition that causes significant distress and impairment for patients and families. Despite the growing body of literature, most treatment descriptions do not incorporate objective assessment measures or detail techniques to involve family members in addressing misophonia. This case report provides a step-by-step family-based cognitive-behavioral approach to treat youth with misophonia, uses objective rating scales to monitor therapeutic improvement, and elicits feedback on the therapeutic skills used between therapy sessions. It also provides guidance on implementing inhibitory learning exposures for youth with misophonia.

Ammonium persulfate (APS), an oxidizing agent used in hair products, manufacturing, and pool/spa water, can cause skin reactions, including allergic contact dermatitis.To characterize positive patch test reactions to APS (2.5% petrolatum).Retrospective analysis of patients tested to the North American Contact Dermatitis Group screening series from 2015 to 2018.Of 10,526 patients, 193 (1.8%) had positive patch test reactions to APS. Compared with APS-negative patients, APS-positive patients were significantly more likely to be male (43.2% vs 28.0%; P .0001); have primary hand dermatitis (30.2% vs 22.0%; P = .0064), scattered generalized dermatitis (25.5% vs 17.9%; P = .0064), or trunk dermatitis (8.9% vs 4.9%; P = .0123); and have dermatitis that is occupationally related (22.2% vs 10.9%; P .0001). More than half of the APS-positive reactions were currently relevant (57.0%); 19 (9.8%) were related to occupation, especially hairdressers (68.4%). Swimming pools/spas (23.3%) and hair care products (19.2%) were the most common sources of APS.Immediate reactions and follow-up testing were not captured.The proportion of patients positive to APS was 1.8%. APS positivity was significantly associated with male sex and hand dermatitis. Swimming pool/spa chemicals were important sources of APS exposure.

Background Limited data exist on the incidence and prevalence of psoriatic arthritis (PsA) among US patients with psoriasis (PsO) based on disease severity. Objective To assess the incidence, prevalence, and predictors of PsA among patients with PsO stratified by PsO severity using treatment type. Methods From the Optum electronic health records database, incidence of PsA per 100 PsO patient-years (PY) and prevalence was assessed. Incidence was assessed from PsO diagnosis and 1 year after PsO diagnosis overall and stratified by mutually exclusive treatment classes as a severity surrogate. Results The overall incidence of PsA was 2.9 (95% CI, 2.9-3.0) events per 100 PY. The incidence (95% CI) by severity surrogate was 2.1 (2.1-2.1), 9.9 (9.5-10.4), and 17.6 (16.9-18.3) events per 100 PY for patients with mild, moderate, and severe PsO as determined by receiving nonsystemics, nonbiologic systemic therapy, and biologics, respectively. When excluding patients diagnosed with PsA 1 year after PsO diagnosis, overall incidence was lower (1.7 [95% CI, 1.6-1.7] events per 100 PY), with similar trends for treatment-severity surrogates. Limitations Results may not be generalizable to a wider population. Conclusion The risk of developing PsA increased with disease severity and was highest in patients with the most severe PsO.

Background Despite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF). Methods and Results This randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%–80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η2 = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η2 = 0.09, medium effect), clinical summary (η2 = 0.16, large effect), and total symptom (η2 = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group. Conclusions A multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population. Clinical Trial Registration : URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus–temporal (SLFt) diffusivity (Cohen's f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression. IMPACT STATEMENT: Diffusion tensor imaging outperforms conventional imaging of subcortical small vessel disease as a potential marker of future disease progression. Here we identified the left superior longitudinal temporal fasciculus as a critical white matter fiber bundle, of which worse diffusivity can link presence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mutations to greater severity of small vessel disease and worse executive functioning in asymptomatic stages of the disease. This tract may hold promise and deserves further examination as an early indicator of disease progression.

Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs) and renal scarring. Gut microbiota are associated with disease phenotypes, but there has been no study that associates urinary microbiota (uMB) and metabolic profiles with VUR pathology. To identify dominant uMB genera and metabolites associated with UTIs in VUR, urine samples collected under sterile conditions underwent 16S ribosomal RNA sequencing (n = 49) and metabolomic analysis by mass spectrometry (n = 96). Alterations in uMB and metabolomic profiles in VUR patients suggest remodeling of urinary bacterial communities after UTIs: Dorea- and Escherichia-dominant uMB profiles were more frequently identified in participants with VUR. Prevotella- and Lactobacillus-dominant uMB profiles were more prevalent in controls (p 0.001). Microbial composition varied based on recurrent febrile UTI status (p = 0.001). A total of 243 urinary metabolites involved in energy, amino acid, nucleotide, and lipid metabolism were altered in VUR patients with UTIs (p 0.05). Importantly, VUR specimens revealed changes in the bacteria-associated metabolic pathways such as glutamate degradation, methyl-citrate cycle, and bile acid metabolism. PATIENT SUMMARY: Differences in urinary commensal bacteria and metabolites exist between children with and without vesicoureteral reflux (VUR). These changes may be utilized to identify patients at risk of VUR-associated kidney damage.

Background The EXCEL trial reported similar five-year rates of the primary composite outcome of death, myocardial infarction (MI), or stroke after percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) for treatment of obstructive left main coronary artery disease (LMCAD). Aims We sought to determine whether these outcomes remained consistent regardless of geography of enrolment. Methods We performed a pre-specified subgroup analysis based on regional enrolment. Results Among 1,905 patients randomised to PCI (n=948) or CABG (n=957), 1,075 (56.4%) were recruited at 52 European Union (EU) centres, and 752 (39.5%) were recruited at 67 North American (NA) centres. EU versus NA patients varied according to numerous baseline demographics, anatomy, pharmacotherapy and procedural characteristics. Nonetheless, the relative rates of the primary endpoint after PCI versus CABG were consistent across EU versus NA centres at 30 days and 5 years. However, NA participants had substantially higher late rates of ischaemia-driven revascularisation (IDR) after PCI, driven predominantly by the need for greater target vessel and lesion revascularisation. This culminated in a significant difference in the relative risk of the secondary composite outcome of death, MI, stroke, or IDR at 5 years (pinteraction=0.02). Conclusions In the EXCEL trial, the relative risks for the 30-day and five-year primary composite outcome of death, MI or stroke after PCI versus CABG were consistent irrespective of geography. However, five-year rates of IDR after PCI were significantly higher in NA centres, a finding the Heart Team and patients should consider when making treatment decisions. ClinicalTrials.gov identifier: NCT01205776.

Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/ LUMA). The study aimed to investigate biological roles of TMEM43 through genetic regulation, gene pathways and gene networks, candidate interacting genes, and up- or downstream regulators. Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) were applied for genetic correlation, functional enrichment, and coexpression network analysis using systems genetics approach. The results were validated in a newly created knock-in Tmem43-S358L mutation mouse model (Tmem43S358L) that displayed signs of cardiac dysfunction, resembling ARVC5 phenotype seen in humans. We found high Tmem43 levels among BXDs with broad variability in expression. Expression of Tmem43 highly negatively correlated with heart mass and heart rate among BXDs, whereas levels of Tmem43 highly positively correlated with plasma high-density lipoproteins (HDL). Through finding differentially expressed genes (DEGs) between Tmem43S358L mutant and wild-type (Tmem43WT) lines, 18 pathways (out of 42 found in BXDs GRP) that are involved in ARVC, hypertrophic cardiomyopathy, dilated cardiomyopathy, nonalcoholic fatty liver disease, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease were verified. We further constructed Tmem43-mediated gene network, in which Ctnna1, Adcy6, Gnas, Ndufs6, and Uqcrc2 were significantly altered in Tmem43S358L mice versus Tmem43WT controls. Our study defined the importance of Tmem43 for cardiac- and metabolism-related pathways, suggesting that cardiovascular disease-relevant risk factors may also increase risk of metabolic and neurodegenerative diseases via TMEM43-mediated pathways.

Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no cure. Exercise-based programs are customarily suggested to address motor and non-motor impairments. Dance has been used to supplement ongoing therapies for people with PD, usually on a weekly or biweekly basis proving to be a feasible option for neurorehabilitation. A daily dose of dance, however, may also be feasible -as indicated by previous studies- suggesting to provide careful attention to the question of dose in efficacy. Objectives This study examines the dose effect of daily dance for people with PD on motor and non-motor functions directly within a movement disorders clinic. Design Within-subject, pre-post-intervention, mixed-methods evaluation including the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III). Methods Eight people with mild and moderate severity idiopathic Parkinson’s disease participated in the study consisting in ten dance lessons, each 90-minutes daily within a two-week period. All subjects were paired with expert tango dancers. The Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III was used for pre- and post-motor assessment. A Likert Scale and Exit Interviews were conducted to assess the impact of the dance intervention on participants’ experience. Results Our study found a significant 18% amelioration in motor symptoms as measured by the MDS-UPDRS III in the pre and post-dance intervention (P Conclusions A high dose short-term tango intervention for people with PD improved motor and non-motor aspects of PD with high levels of adherence (97.5%). The frequency or dosage of dance in neurorehabilitation suggests that a high dose (5 times per week) can ameliorate motor symptoms of PD and could be used as a short-term intervention.

Objectives To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship. Methods Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence. Results Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho‐oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and described the role of key clinicians in survivorship including surgical, medical and radiation oncologists; dentists; primary care physicians; psychotherapists; as well as physical, occupational, speech, and respiratory therapists. Conclusion Head and neck cancer survivorship is complex and requires a multidisciplinary approach centered around patients and their caregivers. As survival related to head and neck cancer treatment improves, addressing post‐treatment concerns appropriately is critically important to our patient's quality of life. There continues to be a need to define effective and efficient programs that can coordinate this multidisciplinary effort toward survivorship.

Introduction Guselkumab is approved for the treatment of both moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA) in the USA. However, little is known about patients initiating guselkumab in a real-world setting. The objective of this study was to describe baseline characteristics among patients with plaque psoriasis who initiated guselkumab at or after enrollment in CorEvitas’ Psoriasis Registry. Methods Adult patients who initiated guselkumab in the Psoriasis Registry between July 18, 2017 and November 6, 2018 were included. Demographics, disease characteristics, and patient-reported outcome measures (PROMs) were assessed at the time of guselkumab initiation (baseline). Patients with psoriasis were stratified according to the number of previously received biologics (0 to 4+) for comparison. A subset of patients with psoriasis and concomitant dermatologist-diagnosed PsA were stratified into biologic-naïve and biologic-experienced groups. Results Among 687 patients with psoriasis who initiated guselkumab, biologic-naïve patients and those with four or more prior biologics had the most severe disease and the worst PROM scores at baseline. Among 251 patients with concomitant dermatologist-diagnosed PsA, biologic-naïve patients had more severe disease and worse PROM scores than biologic-experienced patients. Conclusions These findings highlight important differences in baseline characteristics according to biologic experience among patients with plaque psoriasis with or without concomitant PsA initiating guselkumab in a real-world setting. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00637-2.

OBJECTIVE: Alexithymia is common among people who abuse alcohol, yet the mechanisms by which alexithymia exerts its influence remain unclear. This analysis tested a model whereby the three subscales of the Toronto Alexithymia Scale exert an indirect effect on alcohol problems through difficulties with emotion regulation and psychological distress. METHOD: Men and women (n=141) seeking alcohol use disorder (AUD) treatment completed the Toronto Alexithymia Scale, the Difficulties with Emotion Regulation Scale, the Brief Symptom Inventory, the Short Inventory of Problems, and the Alcohol Dependence Scale. RESULTS: The Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale was positively associated with alcohol problems through emotion dysregulation and psychological distress. The other two subscales, Difficulty Describing Feelings and Externally-oriented Thinking, were not associated with any other variables. CONCLUSION: People with alexithymia may consume alcohol to help regulate undifferentiated states of emotional arousal. Given the prevalence of alexithymia among people who abuse alcohol, treatment supplements that enhance the identification of emotions are needed.

BACKGROUND Few studies explored the relationship between stasis dermatitis (SD) and allergic contact dermatitis (ACD). OBJECTIVE To examine trends, associations, and clinical relevance of ACD in patients referred for patch testing who had a final SD diagnosis. METHODS Retrospective analysis from 2001 to 2016 of 38,723 patients from the North American Contact Dermatitis Group. RESULTS After patch testing, 303 (0.7%) patients were diagnosed with SD; 46.7% had a concomitant diagnosis of ACD. Patients with vs. without a final SD diagnosis had similar proportions of ≥ 1 positive allergic reaction (59.7% vs. 64.7%; Chi-square, P = 0.0724) but higher odds of allergic reactions to fragrance mix I, bacitracin, quaternium-15, Myroxylon pereirae, benzalkonium chloride, ethyleneurea melamine formaldehyde, diazolidinyl urea, and propylene glycol. The most commonly relevant allergens in patients with final SD diagnosis were fragrance mix I, Myroxylon pereirae, bacitracin, quaternium-15, and formaldehyde. The most common allergen sources were personal care products, topical medications and other health aid products. CONCLUSION Nearly half of patients with a final SD diagnosis were also diagnosed with ACD, supporting the role of patch testing in select SD patients.

Mutations in the NOTCH3 gene can lead to small-vessel disease in humans, including the well-characterized cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a condition caused by NOTCH3 mutations altering the number of cysteine residues in the extracellular domain of Notch3. Growing evidence indicates that other types of mutations in NOTCH3, including cysteine-sparing missense mutations or frameshift and premature stop codons, can lead to small-vessel disease phenotypes of variable severity or penetrance. There are currently no disease-modifying therapies for small-vessel disease, including those associated with NOTCH3 mutations. A deeper understanding of underlying molecular mechanisms and clearly defined targets are needed to promote the development of therapies. This review discusses two key pathophysiological mechanisms believed to contribute to the emergence and progression of small-vessel disease associated with NOTCH3 mutations: abnormal Notch3 aggregation and aberrant Notch3 signaling. This review offers a summary of the literature supporting and challenging the relevance of these mechanisms, together with an overview of available preclinical experiments derived from these mechanisms. It highlights knowledge gaps and future research directions. In view of recent evidence demonstrating the relatively high frequency of NOTCH3 mutations in the population, and their potential role in promoting small-vessel disease, progress in the development of therapies for NOTCH3-associated small-vessel disease is urgently needed.

Differences in consumer product availability, distribution, and use may lead to national differences in contact sensitization frequencies. Objective The aim of the study was to describe the differences in contact allergy between the United States (US) and Canada. Methods This is a retrospective cross-sectional analysis of the North American Contact Dermatitis Group data from 2005 to 2016. Frequencies of demographics, clinical characteristics, positive reactions, trends, and occupations were calculated. Results A total of 28,640 patients underwent patch testing. At least 1 positive patch test was observed in 18,599 patients (US, 11,641 [66.5%]; Canada, 6958 [62.5%]). When comparing the 2 groups, US positive reactions were more likely to occur in male patients (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.31-1.49), older than 40 years (OR = 1.30, 95% CI = 1.22-1.38), Black (OR = 2.67, 95% CI = 2.24-3.19) or Hispanic race (OR = 3.53, 95% CI = 2.61-4.78), and/or patients with scattered generalized dermatitis (OR = 1.96, 95% CI = 1.80-2.13). They were less likely to occur in patients with eczema (OR = 0.61, 95% CI = 0.57-0.65) and Asian race (OR = 0.50, 95% CI = 0.44-0.56). Nickel (US, 16.0%; Canada, 22.4%) and methylisothiazolinone (US, 13.4%; Canada, 11.0%) were the top allergens. The third most frequent was neomycin (US, 11.7%) and fragrance mix I (Canada, 10.2%). Conclusions National differences in allergen prevalence and trends exist in North America.

Objectives The aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality). Background Clinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated. Methods A cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD. Results The presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P Conclusions This large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.

Photoallergic contact dermatitis (PACD) is an unusual but not rare form of photosensitivity with an etiology similar to that of allergic contact dermatitis (ACD), with the added requirement of concomitant exposure to ultraviolet (UV) light.1 Photopatch testing (PPT) is a critical tool for diagnosing PACD. There are only a few large studies of photoallergens from North America.2-4 We present a retrospective analysis of North American Contact Dermatitis Group (NACDG) PPT results from 1999-2009.

BACKGROUND Mohs micrographic surgery (MMS) for cutaneous melanoma is becoming more prevalent, but surgical technique varies. OBJECTIVE To define variations in published techniques for MMS for melanoma. METHODS AND MATERIALS A systematic review was performed of PubMed, EMBASE, and Scopus databases to identify all articles describing surgical techniques for MMS for melanoma. Technical details were recorded for the preoperative, intraoperative, and postoperative phases of MMS. RESULTS Twenty-four articles were included. Mohs surgeons vary in how they assess clinical margins, how wide a margin they excise on the first MMS layer, and how they process tissue to determine tumor stage and margin clearance during MMS for melanoma. CONCLUSION Mohs micrographic surgery for melanoma is performed with varied surgical techniques. To establish best practices, additional research is necessary to determine how different techniques affect outcomes.

ObjectivesPalivizumab is a monoclonal antibody which can prevent infection with respiratory syncytial virus (RSV). Due to its high cost, it is recommended for high-risk infants only. We aimed to determine the proportion of infants eligible for palivizumab treatment in England who receive at least one dose.MethodsWe used the Hospital Treatment Insights database containing hospital admission records linked to hospital pharmacy dispensing data for 43/153 hospitals in England. Infants born between 2010 and 2016 were considered eligible for palivizumab if their medical records indicated chronic lung disease (CLD), congenital heart disease (CHD), or severe immunodeficiency (SCID), and they met additional criteria based on gestational age at birth and age at start of the RSV season (beginning of October). We calculated the proportion of infants who received at least one dose of palivizumab in their first RSV season, and modelled the odds of treatment according to multiple child characteristics using logistic regression models.ResultsWe identified 3,712 eligible children, of whom 2,479 (67%) had complete information on all risk factors. Palivizumab was prescribed to 832 of eligible children (34%). Being born at ConclusionIn England, palivizumab is not prescribed to the majority of children who are eligible to receive it. Doctors managing these infants might be unfamiliar with the eligibility criteria or are constrained by other considerations, such as cost.

BACKGROUND Vitamin E (tocopherol) a naturally occurring mixture of antioxidants commonly used in topical skin care products, may cause allergic contact dermatitis. OBJECTIVE The aim of this study was to characterize positive patch test reactions to tocopherol and tocopherol acetate. METHODS This is a retrospective analysis of North American Contact Dermatitis Group patch test data to tocopherols (dl-α-tocopherol 100% and/or dl-α-tocopherol acetate 100%) from 2001 to 2016. RESULTS Of the 38,699 patients patch tested to tocopherol and/or tocopherol acetate, 349 (0.9%) had positive reactions; of these, 87.6% were currently relevant. Most (51.4%) were weak (+) and/or not related to occupation (99.1%). Compared with tocopherol-negative patients, tocopherol-positive individuals were more likely to be female (72.5% vs 67.2%, P = 0.0355), have a final primary diagnosis of allergic contact dermatitis (74.2% vs 52.6%, P < 0.0001), and have dermatitis in a scattered generalized distribution (23.8% vs 18.2%, P = 0.0072); they were also less likely to have hand involvement (16.6% vs 22.3%, P = 0.0064). The most common source of tocopherol was personal care products, especially moisturizers. CONCLUSIONS Positive patch test reactions to tocopherols were relatively rare given their widespread use. When positive, current clinical relevance was high. Tocopherol-positive patients were more likely to be female and presented with dermatitis on the face or in a scattered generalized pattern.

This subanalysis of the Randomized On-Off Bypass (ROOBY) trial examined transit time flow measurement (TTFM) use and its impact on graft patency and long-term clinical outcomes after coronary artery bypass graft surgery.Use of TTFM for ROOBY centers and surgeons was assessed. Comparative patient outcomes based on TTFM use included 1-year graft patency and 1-year and 5-year major adverse cardiac events: all-cause mortality, nonfatal myocardial infarction, and revascularization (percutaneous coronary intervention or repeat coronary artery bypass graft surgery).Transit time flow measurement was used in 1067 patients (TTFM group) and not used in 501 patients (non-TTFM group); of the TTFM group, median percentage TTFM use was 79% (interquartile range, 41% to 98%) among 18 Veterans Affairs Medical Centers, and 74% (interquartile range, 13% to 98%) among 48 surgeons. Patients were comparable in age (63 ± 8.5 years TTFM vs 62 ± 8 years non-TTFM, P = .30) and estimated 30-day mortality risk (1.8 ± 1.7 TTFM vs 1.9 non-TTFM, P = .53). One-year FitzGibbon A patency was 83% (1600 of 1988 grafts) for TTFM assessed grafts and 78% (629 of 803) for non-TTFM assessed grafts (P.01). Fewer TTFM patients had an occluded graft (29%, vs 38% non-TTFM; P = .01). Comparing TTFM patients with non-TTFM patients, 5-year major adverse cardiac event rates were 30% vs 25% (P = .06). Individual component rates were 14% vs 11% for death (P = .06), 12% vs 8.8% for myocardial infarction (P = .07), and 13% vs 12% for revascularization (P = .62).The association of TTFM use with graft patency and clinical outcome is uncertain. Future randomized studies that account for patient risk factors and practice variation would help address this knowledge gap.

OBJECTIVE: Research has identified several potential mechanisms of behavior change (MOBCs) in cognitive–behavioral therapy for alcohol use disorder, including alcohol abstinence self-efficacy (AASE), negative affect (NA), and positive affect (PA). However, little is known about when MOBCs affect clinical outcomes during alcohol use disorder treatment. Such information could advance MOBC research by identifying relationships between specific treatment content and variations in MOBCs. This study examined three MOBCs simultaneously to determine their timing and relative influence on percent days abstinent (PDA) and drinks per day (DPD). METHOD: Data were derived from a parent study assessing pretreatment change in drinking. Participants (n = 205) received 12 sessions of cognitive–behavioral therapy for alcohol use disorder. AASE, NA, and PA were measured at each treatment session, and time-varying effect models (TVEM) were used to examine their association with PDA and DPD. RESULTS: All three MOBCs were associated with PDA and DPD but varied with regard to time course, strength, and direction. For PDA, AASE was positively associated throughout treatment, NA was negatively associated from Sessions 1 to 10, and PA was positively associated from Sessions 1 to 3 and 11 to 12. For DPD, AASE was positively associated from Session 5 to the end of treatment, NA was positively associated throughout treatment although the strength of the association varied and was strongest at the beginning of treatment, and PA was positively associated from Sessions 5 to 12. CONCLUSIONS: Results show that MOBCs exert their effects at different times during treatment. In addition to replicating these results, future research should attempt to manipulate MOBCs directly and examine their influence on alcohol outcomes.

Patients undergoing heart transplant are at high risk for vasodilatory shock in the postoperative period, due to a combination of vascular dysfunction from end-stage heart failure and inflammatory response to cardiopulmonary bypass and, increasingly, long-term exposure to nonpulsatile blood flow in those who have received a left ventricular assist device as a bridge to transplant. Patients who have this vasoplegic syndrome, which may be refractory to traditional agents used in the treatment of shock, are vulnerable to organ dysfunction and death. Angiotensin II (ANG-2) is of increasing interest as an adjunct to traditional therapy, both for improvement in blood pressure and for sparing the use of high-dose catecholamine vasopressors. This case series describes the use of ANG-2 in 4 clinical scenarios for the treatment of shock due to heart transplant surgery, supporting its use in this role and justifying further prospective studies to clarify the appropriate place for ANG-2 in the hierarchy of adjunctive therapies.

This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve.A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal component analysis followed by logistic regression allowed the development of a predictive model of aortic surgery by combining biomechanical descriptors and biomarkers.The protein activity of MMP-1, TIMP-1, and MMP-2 was positively correlated to the systolic WSS and TAWSS observed in the proximal ascending aorta (eg, R = 0.52, P.001, for MMP-1 with TAWSS) where local maxima of WSS were found. For bicuspid patients, aortic wall strain was associated with miR-26a (R = 0.55, P = .041) and miR-320a (R = 0.69, P.001), which shows a significant difference between bicuspid and tricuspid patients. Receiver-operating characteristics curves revealed that the combination of WSS, MMP-1, TIMP-1, and MMP-12 is predictive of aortic surgery (area under the curve 0.898).Increased flow-based and structural descriptors of ascending aortic aneurysms are associated with high levels of circulating biomarkers, implicating adverse vascular remodeling in the dilated aorta by mechanotransduction. A combination of shear stress and circulating biomarkers has the potential to improve the decision-making process for ascending aortic aneurysms to a highly individualized level.

To conduct an exploratory examination of dietary patterns and quality during pregnancy in African-American women who were class I, II, or III obese, and those women with normal pre-pregnancy body mass index (pBMI), as well to identify dietary factors associated with GWG, and changes in the distal gut microbiome. African American women represent the largest group affected by pre-pregnancy obesity, a risk factor for several adverse birth outcomes. This prospective study investigated the association between diet, distal gut microbiome, and GWG among African-American women (n = 21) with obesity (n = 15) compared to women with a normal pre-pregnancy body mass index (pBMI) (n = 6) at two time points, 27–29 and 37–39 weeks gestation. Dietary patterns associated with obesity severity and GWG gain were assessed using Welch’s T-test and Mann–Whitney U. The association between the gut microbiome and dietary patterns was assessed using a regression-based kernel association test and the adaptive microbiome-based sum of powered score test. In early pregnancy, dietary intake of Total Fruits and Greens and Beans was significantly different between pBMI and GWG groups; significance was 0.022 and 0.028 respectively. Women with Class II/III obesity and those with GWG above guidelines had Healthy Eating Index (HEI) scores below 50, meeting less than 75% of dietary guidelines, and did not meet recommendations for fruit and vegetable or fiber intake. We found no significant associations between the microbiome composition and diet (HEI Scores). Overall, the results indicate that women with pBMI obesity are not meeting minimum dietary guidelines for nutrient intakes during pregnancy, specifically fruits, vegetables, and fiber, regardless of GWG. Interventions for African-American women with pre-pregnancy obesity, with a focus on increasing consumption of fruits and vegetables, would be beneficial to control GWG and improve birth outcomes.

Objectives To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses. Patients and methods Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function. Results One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients. Conclusions A starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

Sub-Tenon's implantation of the Xen Gel stent resulted in significant intraocular pressure (IOP) lowering along with a low rate of postoperative bleb needling, and a favorable bleb morphology on anterior segment optical coherence tomography (AS-OCT).The aim was to assess clinical outcomes and bleb morphology following sub-Tenon's implantation of the Xen Gel Stent.The medical records of patients who underwent sub-Tenon's Xen Gel Stent implantation with intraoperative mitomycin-C through an open conjunctival approach were reviewed. Postoperative IOP and number of glaucoma medications at 1, 3, 6, 9, and 12 months were assessed. Bleb morphology was analyzed at various timepoints using AS-OCT (Topcon DRI OCT version 1.1.1).Twenty-six eyes were included in the study. Mean age was 69.4±8.0 years. Mean preoperative IOP was 28.1±7.8 mm Hg on an average of 3.5±0.9 glaucoma medications. Mean IOP at postoperative month 12 (n=23 eyes) was 12.9±4.0 mm Hg (P0.01) on an average of 0.3±0.6 (P0.01) glaucoma medications. Three eyes (12%) required postoperative needle revision. Bleb morphology in the early postoperative period (≤3 mo) was characterized by multiple small subconjunctival microcysts on AS-OCT. At the intermediate (6 to 12 mo) and long-term (12 mo) timepoints, reduction in microcysts with multiple internal parallel layers of aqueous flow and a uniform pattern were more frequently noted. All functional blebs were characterized by the presence of a posterior episcleral fluid lake. Failed blebs showed absence of aqueous humor around the distal end of the microshunt.Following an open conjunctival approach, sub-Tenon's placement of the Xen Gel Stent with significant IOP lowering was achieved. In eyes with good shunt function, bleb morphology by AS-OCT showed a posterior episcleral fluid lake similar to findings following trabeculectomy.

Specialty site melanomas on the head and neck, hands and feet, genitalia, and pretibial leg have higher rates of surgical complications after conventional excision with postoperative margin assessment (CE-POMA) compared with trunk and proximal extremity melanomas. The rule of 10s describes complication rates after CE-POMA of specialty site melanomas: ∼10% risk for upstaging, ∼10% risk for positive excision margins, ∼10% risk for local recurrence, and ∼10-fold increased likelihood of reconstruction with a flap or graft. Trunk and proximal extremity melanomas encounter these complications at a lower rate, according to the rule of 2s. Mohs micrographic surgery (MMS) with frozen section melanocytic immunostains (MMS-I) and slow Mohs with paraffin sections decrease complications of surgery of specialty site melanomas by detecting upstaging and confirming complete tumor removal with comprehensive microscopic margin assessment before reconstruction. This article reviews information important for counseling melanoma patients about surgical treatment options and for developing consensus guidelines with clear indications for MMS-I or slow Mohs.

On the basis of high-local recurrence risk features and tissue-rearranging reconstruction, consensus guidelines recommend microscopic margin control for keratinocyte carcinomas (KCs) but not for cutaneous melanoma.To compare high-local recurrence risk features and frequency of tissue-rearranging reconstruction for head and neck KC with those for melanoma.Retrospective cohort study of KC versus melanoma treated at the Hospital of the University of Pennsylvania with Mohs micrographic surgery.A total of 12,189 KCs (8743 basal cell carcinomas and 3343 squamous cell carcinomas) and 1475 melanomas (1065 melanomas in situ and 410 invasive melanomas) were identified from a prospectively updated Mohs micrographic surgery database. Compared with KCs, melanomas were significantly more likely to have high-local recurrence risk features, including larger preoperative size (2.10 cm vs 1.30 cm [P .0001]), recurrent status (5.08% vs 3.91% [P = .031]), and subclinical spread (31.73% vs 26.52% [P .0001]). Tissue-rearranging reconstruction was significantly more common for melanoma than for KCs (44.68% vs 33.02% [P .0001]; odds ratio, 1.98 [P .0001]).This was a retrospective study, and it did not compare outcomes with those of other treatment methods, such as slow Mohs or conventional excision.Melanomas of the head and neck have high-local recurrence risk features and require tissue-rearranging reconstruction more frequently than KCs do.

The diversity and dominant bacterial taxa in the vagina are reported to be influenced by multiple intrinsic and extrinsic factors, including but not limited to pregnancy, contraceptive use, pathogenic states, socioeconomic status, and ancestry. However, the extent to which host genetic factors influence variation in the vaginal microbiota is unclear. We used a biometrical genetic approach to determine whether host genetic factors contribute to inter-individual differences in taxa from a sample of 332 twins who self-identified as being of African (44 pairs) or European ancestry (122 pairs). Lactobacillus crispatus, a major determinant of vaginal health, was identified as heritable among European American women (narrow-sense heritability = 34.7%, P-value = 0.018). Heritability of L. crispatus is consistent with the reduced prevalence of adverse reproductive disorders, including bacterial vaginosis and preterm birth, among women of European ancestry., Wright et al. apply biometric genetic approach to identify the extent to which host genetic factors influence species-level variation in the vaginal microbiota. Their study suggests that Lactobacillus crispatus, a major determinant of vaginal health, is heritable among European American women, consistent with the reduced prevalence of adverse reproductive disorders in them.

Background Severe atopic dermatitis (AD) is increasingly treated with systemic immunomodulatory drugs, yet their safety is unclear. Objective We evaluated the comparative risk of serious bacterial and opportunistic infections among patients with severe AD using systemic immunomodulatory medications in routine care. Methods In a population-based claims data study, we identified adult patients with AD who were treated with systemic drugs. The incidence of serious bacterial and opportunistic infections leading to hospitalization was computed by using International Classification of Disease diagnosis codes. Relative risks (RRs) were computed after 1-to-1 propensity score matching. Results Up to 232,611 patients with AD were eligible. The incidence of serious infections was 7.53 (7.18-7.89) risk per 1,000 patients among systemic nonbiologic–treated patients, 7.38 (5.68-9.57) risk per 1,000 patients among phototherapy-treated patients, and 2.6 (0.45-14.3) risk per 1,000 patients among dupilumab users. After matching, cyclosporine had a significantly reduced 6-month risk (RR 0.87) and prednisone (RR 1.78), azathioprine (RR 1.89), and mycophenolate (RR 3.31) showed increased risks compared with methotrexate. A small number of dupilumab users showed no increased risk (RR 0.33, 95% confidence interval 0.03-3.20). Limitations Some comparisons involved small population sizes. Conclusion In this population-based study of adult AD patients, cyclosporine and methotrexate have the lowest 6-month risks of serious infections. Increased risks were observed for prednisone, azathioprine, and mycophenolate relative to methotrexate.

Background Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC. Methods This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes. Results In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69 years (range, 25-101 years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1 mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%). Conclusions Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.

Introduction Warthin’s tumor, also known as papillary cystadenoma lymphomatosum, is one of the most common benign salivary gland neoplasms. The current first-line treatment for Warthin’s tumor is parotidectomy. However, surgical resection has the risk of complications including facial nerve weakness and Frey’s syndrome. Recently, ultrasound-guided ethanol sclerotherapy (UGES) has been found to be efficacious in the treatment of a variety of head and neck lesions. Case report We present a patient with multifocal Warthin’s tumor who was managed with partial parotidectomy and two cycles of ultrasound-guided ethanol sclerotherapy. Discussion Ethanol sclerotherapy has been used as a minimally invasive alternative to surgical excision or observation alone for a variety of head and neck masses. To our knowledge, this is the first case presented in the literature where sclerotherapy was used in conjunction with a partial parotidectomy. Minimizing the extent of surgical resection can reduce the risk of facial nerve weakness and Frey’s syndrome and negate the need for fat grafting for defect reconstruction. Conclusion UGES may serve as a safe and reliable procedure that can be performed in conjunction with partial parotidectomy for patients who wish to achieve definitive diagnosis while also minimizing the risk of complications associated with extensive parotidectomy.

BACKGROUND Secukinumab [an interleukin (IL)-17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL-12/23 inhibitor) in patients with moderate-to-severe plaque psoriasis. OBJECTIVES To report 52-week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate-to-severe plaque psoriasis from the head-to-head EXCEED monotherapy study comparing secukinumab with adalimumab. METHODS Patients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1-4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate-to-severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality-of-life outcomes. Missing data were handled using multiple imputation. RESULTS Of the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate-to-severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints. CONCLUSIONS This prespecified analysis in PsA patients with concomitant moderate-to-severe plaque psoriasis in the EXCEED study provides further evidence that IL-17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

Background & Aims Studies of the effects of direct oral anticoagulants (DOACs) in patients with cirrhosis have been limited by their small sample size, inclusion of patients with well-compensated cirrhosis, short follow-up times, inadequate validation of cirrhosis diagnoses, and non-standard definitions of bleeding. We aimed to systematically determine the characteristics, indications, and outcomes of patients with cirrhosis of all severity classes who received DOACs. Methods We performed a retrospective study of 138 patients with confirmed cirrhosis (93 with Child-Turcotte-Pugh scores of B or C) at a single center who started DOAC therapy (58,984 person-days; median, 181 days per patient) from September 2011 through April 2019. We collected data on clinical characteristics, indications for DOAC use, and outcomes. Standardized and validated definitions for bleeding complications were used. Results Twenty-nine patients (21%) stopped therapy due to a diagnosis of or perceived bleeding. The most common bleeding events were non-variceal upper and lower intestinal bleeding. No pretreatment laboratory parameters were associated with bleeding while patients received treatment, including platelet count (P = .50), international normalized ratio (P = .34), creatinine (P = .27), and model for end-stage liver disease score (P = .22). Frequency of bleeding events related to DOAC did not differ significantly among patients of different Child-Turcotte-Pugh classes (P = .81), DOAC indications (P = .60), or DOAC dosages (P = .10). Higher proportions of patients with hepatocellular carcinoma (P = .01) had major bleeding while receiving. Conclusions Patients with decompensated cirrhosis have significant bleeding and rates of discontinuation of DOACs when they take them long term. Pretreatment laboratory parameters, DOAC dose, and Child-Turcotte-Pugh class were not associated with bleeding; hepatocellular carcinoma was associated with major bleeding.

Purpose: To describe the efficacy and safety of open versus closed conjunctival implantation of the XEN45 Gel Stent (Allergan Inc). Design: Retrospective, multicenter study. Participants: A total of 137 patients with glaucoma who underwent XEN45 implantation via open or closed conjunctival methods. The XEN45 was implanted as a stand-alone procedure or at the time of cataract surgery by 5 surgeons. Methods: Patient demographics, diagnoses, preoperative and postoperative clinical data, outcome measures including intraocular pressure (IOP), use of glaucoma medications, visual acuity, and complications were collected. Statistical analyses were performed with P < 0.05 as significant. Main Outcome Measures: Failure was defined as less than 20% reduction of IOP from medicated baseline or IOP >21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Eyes that had not failed but required glaucoma medications were defined as qualified successes. Results: Complete success was achieved in 31% and 56% of the closed and open groups, respectively (P = 0.01). Qualified success was achieved in 53% and 71% of the closed and open groups, respectively (P = 0.06). At postoperative month 12, the open conjunctiva group was using fewer glaucoma medications than the closed group (0.9 vs. 1.8, respectively; P = 0.02). At postoperative month 12, the open group had a significantly greater percentage of IOP reduction compared with the closed group (43.1% vs. 24.8%, respectively; P = 0.02). Postoperative needling rates were higher in the closed group compared with the open group (36.1% vs. 11.8%, P = 0.001). Conclusions: Implantation of the XEN45 with opening of the conjunctiva is a safe and efficacious procedure to lower IOP with comparable success rate and lower needling rate compared with the closed conjunctiva technique. Prospective evaluation of the various methods for XEN45 implantation will allow for further comparison.

Purpose To study the effect of phacoemulsification on intraocular pressure (IOP) control in patients with preexisting glaucoma drainage implants (GDIs). Design Retrospective, observational case series. Participants A total of 45 patients (51 eyes) with previously placed GDIs who underwent phacoemulsification between January 2013 and March 2018. Methods The list of patients was obtained from billing records. Clinical data were retrieved from the corresponding electronic medical records. Main Outcome Measures Intraocular pressure, number of glaucoma medications before and after phacoemulsification (postoperative day 1, week 1, months 1, 3, 6, 12, 18, and 24), rate of failure (failure defined as IOP >18 mmHg and IOP increase >20% at 2 consecutive visits after month 1, need for additional glaucoma surgery, or loss of light perception vision), and postoperative complications. Results Mean follow-up was 23.0 ± 11.1 months. The average interval between GDI surgery and phacoemulsification was 9.4 ± 6.7 months. An Ahmed glaucoma valve (AGV; New World Medical) was implanted in 12 eyes, a Baerveldt glaucoma implant (BGI; Johnson & Johnson Surgical Vision) was implanted in 36 eyes, and a Molteno (Molteno Ophthalmic Limited) glaucoma implant was implanted in 3 eyes. Before phacoemulsification, the mean IOP was 14.4 ± 4.4 mmHg on 2.1 ± 1.3 glaucoma medications. At postoperative month 24, the mean IOP was 12.6 ± 4.4 mmHg (n = 29, P = 0.519) on 2.0 ± 1.6 (P = 0.457) glaucoma medications. The reduction in IOP was significant only at postoperative week 1 (P = 0.031). The cumulative failure rate was 3.9% at 1 year and 11.8% at 2 years. The AGV group had a significantly higher mean IOP before phacoemulsification than the BGI group (P = 0.016). Analysis of covariance, taking the baseline IOP as a covariate, revealed no differences in postoperative IOP and number of glaucoma medications between groups, except for month 18 (1 patient in the BGI group had uncontrolled IOP requiring surgery). Postoperative complications included cystoid macular edema (10%), corneal decompensation (6%), and choroidal effusion (4%). Conclusions Phacoemulsification after GDI surgery resulted in a transient reduction in IOP at postoperative week 1. Patients with previously placed AGVs had similar postoperative outcomes compared with those with BGIs.

Psoriasis is a chronic, immune-mediated disease that includes a broad spectrum of systemic manifestations, complications, and comorbidities. Approximately 20%-30% of patients with psoriasis eventually develop psoriatic arthritis, and up to half of those without psoriatic arthritis experience subclinical musculoskeletal abnormalities. Recognition of early musculoskeletal inflammatory signs in patients with psoriasis is important to understand the extent and severity of this systemic disease, assess the risk of structural joint damage, and ensure timely and effective treatment of the complete spectrum of psoriatic disease. Delayed or ineffective treatment can lead to decreased quality of life, irreversible musculoskeletal damage, and loss of function. In this review, we highlight features of subclinical or early psoriatic arthritis among patients with psoriasis of which dermatologists should be aware. Recent knowledge of features of preclinical psoriatic arthritis in patients with psoriasis is presented. We briefly discuss important risk factors, clinical features, and other characteristics of patients likely to progress from psoriasis to psoriatic arthritis that should be known by dermatologists. Screening tools commonly used in the dermatology clinic to detect psoriatic arthritis are also critically reviewed. Finally, we provide expert commentary for dermatologists concerning the treatment of patients with psoriasis and subclinical signs of early psoriatic arthritis.

Psoriatic arthritis is an inflammatory condition affecting up to 30% of patients with psoriasis. Patients may experience irreversible joint damage if not treated early, and diagnostic delays of even 6 months are associated with radiographic progression and impaired function. Therefore, early detection and intervention are of critical importance in patients with psoriatic arthritis. Given that psoriasis often precedes symptoms of psoriatic arthritis, dermatologists are uniquely positioned to identify patients with psoriatic arthritis early in their disease course, before permanent damage has occurred. Several screening tools have been developed to help dermatologists identify patients who may have psoriatic arthritis, but these tools may not capture patients with subclinical disease or quantify the type and severity of the underlying tissue insult, which is often the presenting sign of psoriatic arthritis. In these cases, a combination of clinical assessment and musculoskeletal imaging (e.g., ultrasound) is required. This review summarizes three common musculoskeletal imaging techniques used in the diagnosis and management of patients with psoriatic arthritis: conventional radiography, ultrasound, and magnetic resonance imaging. Further understanding of musculoskeletal imaging will assist dermatologists in making treatment decisions and allow them to have a more active role in the detection of psoriatic arthritis.

BACKGROUND: Sleep disturbance is common among individuals with Tourette’s Disorder (TD). Given that sleep is influenced by the circadian system, this study examined circadian rhythms and sleep in adults with TD, and explored the possible benefit of short-wavelength wearable morning light therapy. METHODS: Participants were 34 adults with TD (n=14) and age- and sex-matched healthy controls (HC; n=20). Participants were screened using clinician-rated diagnostic and tic severity interviews, and procedures lasted 3 consecutive weeks. Participants completed a baseline week of actigraphy. Adults with TD completed two weeks of Re-Timer(™) morning light therapy and continued actigraphy monitoring. Dim light melatonin onset (DLMO) phase assessment, tic severity interview, and measures of chronotype, sleep disturbance, daytime sleepiness, disability, depression, anxiety, and stress were completed at baseline and post-intervention. RESULTS: Adults with TD reported significantly greater eveningness and sleep disturbance relative to controls. Per wrist actigraphy, adults with TD exhibited significantly longer sleep onset latency, lower sleep efficiency, and greater sleep fragmentation than HC. Following morning light therapy there was significant advances in DLMO phase, but not self-report or actigraphy sleep variables. There were small, statistically significant decreases in tic severity and impairment. There were also significant reductions in daytime sleepiness, and self-reported anxiety, but not depression, stress, or disability. Participants reported minimal side effects and rated light therapy as acceptable and comfortable. CONCLUSIONS: Findings showed some benefits following brief light therapy in TD; further exploration of the impact of spectral tuning the photic environment as part of treatment for TD subjects is warranted.

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

Consistent with international reports,1 this group of Tourette syndrome (TS) experts has noticed a recent increase in adolescents presenting with tic-like symptoms that show a markedly atypical onset and course. These sudden-onset motor movements and vocalizations are often associated with significant impairment and disability, resulting in emergency department visits and hospitalizations for some affected youths.

Introduction: Parkinson's disease (PD) is associated with a range of cognitive deficits. Few studies have carefully examined the subtle impacts of PD on cognition among patients who do not meet formal criteria for MCI or dementia. The aim of the current study was thus to describe the impact of PD on cognition in those without cognitive impairment in a well-characterized cohort.Methods: Non-cognitively impaired participants (122 with PD, 122 age- and sex-matched healthy volunteers) underwent extensive cognitive testing. Linear regression analyses compared diagnostic group performance across cognitive measures. For cognitive tasks that were significantly different between groups, additional analyses examined group differences restricting the group inclusion to PD participants with mild motor symptoms or disease duration less than 10years.Results: Processing speed and semantic verbal fluency were significantly lower in the PD group (B =-3.77, 95% CIs [-5.76 to -1.77], p

There is little data regarding the relationship in children and how it may change with aging. The aim of this radiographic study was to define the relationship between pelvic incidence (PI) and segmental vertebral body lordosis through childhood. In 150 children, CT scans of the lumbar spine and pelvis were analyzed measuring PI, sacral table angle (STA), sacral kyphosis (SK), and segmental lordosis (SL) individually L1-L5. Children were grouped by age: (1) 0-60 months; (2) 61-120 months; (3) 121-185 months. Mean PI for the entire cohort was 40.4, mean SL for L1-0.6, L2 0.0, L3 1.8, L4, 4.7, and L5 11.4. There were 40 children in Group 1, 63 in Group 2 and 37 in Group 3. SL differed between age groups at all levels except at L2. L1 and L2 became more kyphotic with increasing age; L3, L4, and L5 became more lordotic with increasing age. The correlation between PI and SL at each level became stronger with increasing age. Similarly, the correlation between PI and STA and between PI and SK also became stronger with increasing age. As children mature, the relationship between PI and segmental lordosis at each level of the lumbar spine becomes stronger-the relationship between PI and lordosis trends toward that seen in the adult. Future work should aim to define when the adult PI-LL relationship is realized.

Potent synthetic opioids are an important cause of death in the United States' opioid epidemic, and a breathing stimulant may have utility in treating opioid overdose. We hypothesized that sufentanil-induced respiratory depression may be reversed by breathing stimulant administration. METHODS : Using nose-only plethysmography and arterial blood analysis, we compared effects of several breathing stimulants in reversing sufentanil-induced respiratory depression in conscious rats. We studied taltirelin (1 mg/kg IV), PKTHPP (5 mg/kg IV), CX717 (30 mg/kg IV), BIMU8 (1 mg/kg IV), A85380 (30 mcg/kg IV), 8-OH-DPAT (150 mcg/kg IV/IM), and used sufentanil (10 mcg/kg IV). RESULTS : By plethysmography (in % baseline, mean{plus minus}SEM), taltirelin restored ventilation in sufentanil-treated rats (from 50{plus minus}5 to 102{plus minus}8%) by increased breathing rates (from 80{plus minus}4 to 160{plus minus}12%). By arterial blood analysis, however, taltirelin did not correct hypoxia, decreased hypercarbia only after 45 min, and worsened metabolic acidosis (base excess from +0{plus minus}1 to -7{plus minus}1 mEq/L). Additionally, taltirelin increased exhaled carbon dioxide, an estimate of oxygen consumption, by up to 64%. PKTHPP, CX717, BIMU8, and A85380 failed to significantly change ventilation or arterial blood values in sufentanil-treated rats. 8-OH-DPAT, however, improved ventilation (from 54{plus minus}8 to 92{plus minus}10%), reversed hypercarbia (from 64{plus minus}6 to 47{plus minus}2 mmHg) and shortened time-to-righting from 43{plus minus}4 to 15{plus minus}1 min in sufentanil-treated rats placed supine. CONCLUSION : Taltirelin has limited therapeutic potential as its ventilatory effects are offset by metabolic acidosis, possibly from increased oxygen consumption. At the doses studied, PKTHPP, CX717, BIMU8, and A85380 have limited effects in reversing sufentanil-induce respiratory depression; 8-OH-DPAT, however, warrants further study. Significance Statement Respiratory depression is an important cause of death following potent synthetic opioid overdose. 8-OH-DPAT or related compounds may be useful in treating respiratory depression as caused by potent synthetic opioids.

Background Little is known about the relationship between psoriasis and allergic contact dermatitis (ACD). Objective To examine the associations with ACD, related clinical characteristics, and common positive and clinically relevant allergens of patients with a final diagnosis of psoriasis who were referred for patch testing. Methods Retrospective analysis of 38,723 patients from the North American Contact Dermatitis Group. Results Patients with a final diagnosis of psoriasis had lower proportions of ACD than those without psoriasis (32.7% vs 57.8%). In multivariable logistic regression models, psoriasis was inversely associated with female sex, black or Asian race, history of atopic dermatitis and hay fever. Patients with a final diagnosis of psoriasis were less likely to have one or more positive allergic patch test reactions or to have a current clinically relevant patch test reaction to the majority of the most commonly positive and/or relevant allergens. The most clinically relevant allergens included nickel sulfate, methylisothiazolinone, and fragrance mix I. Conclusion Approximately one-third of patients who were referred for patch testing with a final diagnosis of psoriasis were also diagnosed with ACD. In select patients with suspected psoriasis who also have a clinical presentation suggestive of ACD, patch testing may be helpful. This article is protected by copyright. All rights reserved.