Citations

Abstract Background Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. Objectives To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. Methods Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients’ self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from ‘very dissatisfied’ to ‘very satisfied’. Results The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62–2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74–3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62–0·99; active vs. never), depression (OR 0·69, 95% CI 0·54–0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81–0·96) and increasing flare frequency. Conclusions There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics.Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

ABSTRACT Background Early‐onset Parkinson's disease (EOPD)/young‐onset Parkinson's disease (YOPD) is defined as Parkinson's disease (PD) with an age at onset (AAO) after age 21 years but before the usual AAO for PD. Consensus is lacking, and the reported maximal age for EOPD/YOPD has varied from 40 to 60 years, leading to a lack of uniformity in published studies and difficulty in harmonization of data. EOPD and YOPD have both been used in the literature, somewhat interchangeably. Objective To define the nomenclature and AAO cutoff for EOPD/YOPD. Methods An extensive review of the literature and task force meetings were conducted. Conclusions were reached by consensus. Results First, the literature has seen a shift from the use of YOPD toward EOPD. This seems motivated by an attempt to avoid age‐related stigmatization of patients. Second, in defining EOPD, 56% of the countries use 50 or 51 years as the cutoff age. Third, the majority of international genetic studies in PD use an age cutoff of younger than 50 years to define EOPD. Fourth, many studies suggest that changes in the estrogen level can affect the predisposition to develop PD, making the average age at menopause of 50 years an important factor to consider when defining EOPD. Fifth, considering the differential impact of the AAO of PD on professional and social life, using 50 years as the upper cutoff for the definition of EOPD seems reasonable. Conclusions This task force recommends the use of EOPD rather than YOPD. It defines EOPD as PD with AAO after 21 years but before 50 years.

AbstractIntroduction/AimsIn this study we investigated COVID‐19 vaccination–related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).MethodsSeven‐day vaccine ADEs were collected in an international patient self‐reported e‐survey. Descriptive statistics were obtained and multivariable regression was performed.ResultsTen thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30‐455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04‐7.3) and minor (OR, 1.5; IQR, 1.1‐2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2‐4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1‐3.3; and OR, 2.2; IQR, 1.1‐4.3, respectively). Overall, ADEs were less frequent in inclusion‐body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients.DiscussionSeven‐day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID‐19 through vaccination likely outweighs the risk of vaccine‐related ADEs. Our results may inform future guidelines regarding COVID‐19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long‐term outcomes and disease flares are needed to shed more light on developing future COVID‐19 vaccination guidelines.

AbstractSummary1H nuclear magnetic resonance (NMR) spectroscopy is an established bioanalytical technology for metabolic profiling of biofluids in both clinical and large-scale population screening applications. Recently, urinary protein quantification has been demonstrated using the same 1D 1H NMR experimental data captured for metabolic profiling. Here, we introduce NMRpQuant, a freely available platform that builds on these findings with both novel and further optimized computational NMR approaches for rigorous, automated protein urine quantification. The results are validated by interlaboratory comparisons, demonstrating agreement with clinical/biochemical methodologies, pointing at a ready-to-use tool for routine protein urinalyses.Availability and implementationNMRpQuant was developed on MATLAB programming environment. Source code and Windows/macOS compiled applications are available at https://github.com/pantakis/NMRpQuant, and working examples are available at https://doi.org/10.6084/m9.figshare.18737189.v1.Supplementary informationSupplementary data are available at Bioinformatics online.

AbstractBackgroundTwo studies that examined the interaction between HLA‐DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.ObjectiveTo perform a large‐scale independent replication of the HLA‐DRB1 × smoking interaction.MethodsWe genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA‐DRB1.ResultsAt the amino acid level, a valine at position 11 (V11) in HLA‐DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking‐induced modifications of α‐synuclein on binding affinity showed findings consistent with this interaction pattern.ConclusionsDespite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Background and objectives C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years. Design, setting, participants, & measurements To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome. Results Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitial fibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores. Conclusions Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

BackgroundWeight gain after a breast cancer diagnosis is common and is associated with inferior outcomes. Young survivors may be especially susceptible to weight changes given the impact of treatment on menopausal status.MethodsThe authors identified women who were diagnosed with stage 0 to III breast cancer at age 40 years or younger between 2006 and 2016 from a multicenter prospective cohort. Self‐reported weight was collected at diagnosis and at 1 year and 3 years postdiagnosis. Tumor and treatment data were obtained from medical records and patient surveys. Multinomial logistic regression was used to identify the factors associated with weight gain (≥5%) or weight loss (≥5%) versus stable weight at 1 year and 3 years postdiagnosis.ResultsThe cohort included 956 women with a median age of 37 years at diagnosis. Mean weight significantly increased over time from 66.54 ± 14.85 kg at baseline to 67.33 ± 15.53 and 67.77 ± 14.65 kg at 1 year and 3 years, respectively (p ≤ .001 for both comparisons). The proportion of women experiencing ≥5% weight gain increased from 24.8% at 1 year to 33.9% at 3 years. At 1 year, less self‐perceived financial comfort, Black race, and stage III disease were significantly associated with weight gain; at 3 years, only less self‐perceived financial comfort remained significant. Baseline overweight or obesity was significantly associated with weight loss at both time points. Chemotherapy, endocrine therapy, and treatment‐related menopause were not associated with weight change.ConclusionsOne third of young breast cancer survivors experienced clinically significant weight gain 3 years after diagnosis; however, treatment‐related associations were not observed. Age‐appropriate lifestyle interventions, including the reduction of financial barriers, are needed to prevent weight gain in this high‐risk population.

Background: Optimal management of cardiac implantable electronic devices (CIEDs) in patients with Ebstein anomaly during tricuspid valve (TV) surgery is unknown. Thus, we aimed to characterize CIED management/outcomes in patients with Ebstein anomaly undergoing TV surgery. Methods: Patients at the Mayo Clinic from 1987 to 2020 with Ebstein anomaly and CIED procedure were reviewed for procedural details, complications, echocardiogram, and lead parameters. Five-year cumulative incidence of CIED complications were estimated using the Kaplan-Meier method. Results: Ninety-three patients were included; 51 were female, and mean age was 40.7±17.5 years. A new CIED was implanted in 45 patients at the time of TV surgery with the majority receiving an epicardial (n=37) CIED. Among 34 patients who had preexisting CIED (11 epicardial, 23 transvenous) at time of TV surgery, 20 had a transvenous right ventricular lead managed by externalizing the lead to the TV (n=15) or extracting the transvenous lead with epicardial lead implantation (n=5). Fourteen patients underwent CIED implantation (4 epicardial, 10 transvenous) without concurrent surgery. Placement of lead across the TV was avoided in 85% of patients. The 5-year cumulative incidence of CIED complications was 24% with no significant difference between epicardial and transvenous CIEDs (26% versus 23%, P =0.96). Performance of lead parameters was similar in epicardial and transvenous leads during median (interquartile range) follow-up of 44.5 (61.1) months. Conclusions: In patients with Ebstein anomaly undergoing TV surgery, the use of epicardial leads and externalization of transvenous leads to the TV can avoid lead placement across the valve leaflets. Lead performance and CIED complications was similar between epicardial and transvenous CIEDs.

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF (p = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.