Trajectories of self-reported fatigue following initiation of multiple sclerosis disease-modifying therapy.

BACKGROUND: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of fatigue and their association with physical disability following start of disease-modifying therapy (DMT). METHODS: Using a group-modelling approach, we assessed trajectories of fatigue with the Fatigue Scale for Motor and Cognitive Functions and physical disability with Expanded Disability Status Scale among 1587 and 1818 individuals who initiated a first DMT and had a first DMT switch, respectively, followed during 2011-2022. We investigated predictors of fatigue trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories. RESULTS: We identified five trajectories of fatigue in participants who initiated their first DMT: no fatigue (mean starting values=23.7; 18.2% of population), low (35.5; 23.9%), mild (49.0; 21.6%), moderate (61.3; 20.1%) and severe (78.7; 16.1%). While no, low, mild and severe fatigue trajectories remained stable, the moderate trajectory increased to severe fatigue. Similarly, we identified six fatigue trajectories among participants who did a DMT switch, all indicating stable values over time. Women initiating a first DMT were more likely than men to display a severe fatigue trajectory, relative to the no fatigue one. There was a strong association between fatigue and physical disability trajectories. CONCLUSIONS: In this cohort of people with actively treated RRMS, self-reported fatigue remained stable or increased over the years following DMT start. There was a strong association between fatigue and disability after DMT start.

Long-Term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-Based Study.

INTRODUCTION: Healthcare costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease, are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and preexisting (PE) MG in Sweden. METHODS: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥24-month follow-up during the period January 1, 2010, to December 31, 2017, were included. RESULTS: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years, and 52.3% were female. In the first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs. 83.9%), corticosteroids (59.6% vs. 45.8%), thymectomy (12.1% vs. 0.7%), and plasma exchange (3.8% vs. 0.6%); had higher all-cause (70.9% vs. 35.8%) and MG-related (62.5% vs. 18.4%) hospitalization rates with 11 more hospitalization days (all p < 0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred EUR 7,302 (p < 0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p < 0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ∼55% for ND MG from year 1 and were comparable with PE MG. CONCLUSION: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies, and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial.

BACKGROUND: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. OBJECTIVE: To evaluate the efficacy and safety of ritlecitinib, an oral JAK3 (Janus kinase)/TEC (tyrosine kinase expressed in hepatocelluar carcinoma) inhibitor, in patients with active nonsegmental vitiligo in a phase 2b trial (NCT03715829). METHODS: Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50 mg, 100/50 mg, 30 mg, or 10 mg) or placebo for 24 weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50 mg daily in a 24-week extension period. The primary efficacy endpoint was percent change from baseline in Facial-Vitiligo Area Scoring Index at week 24. RESULTS: A total of 364 patients were treated in the dose-ranging period. Significant differences from placebo in percent change from baseline in Facial-Vitiligo Area Scoring Index were observed for the ritlecitinib 50 mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30 mg group (-14.6 vs 2.1; P = .01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period (n = 187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment. LIMITATIONS: Patients with stable vitiligo only were excluded. CONCLUSIONS: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.

Prevalence of Vitiligo among Children and Adolescents in the United States.

BACKGROUND: Vitiligo is an autoimmune disorder that causes patchy loss of skin pigmentation. Up to 2.16% of pediatric patients may have vitiligo. This study estimated vitiligo point prevalence in children and adolescents (ages: 4-11 and 12-17 years) in the United States (US). METHODS: An online, population-based survey of a nationally representative sample of individuals based on 2017 US Census Bureau estimates for age, race, Hispanic origin, income, and geographic region was conducted from December 2019 to March 2020. Parent/legal guardian proxies responded on behalf of their children or adolescents to vitiligo screening questions. Proxy-reported vitiligo status was adjudicated by expert dermatologists who reviewed photographs of vitiligo lesions uploaded by proxies using a teledermatology application. Estimated point prevalence (including diagnosed and undiagnosed vitiligo and its subtypes) was calculated for proxy-reported and clinician-adjudicated vitiligo. RESULTS: There were 9,118 eligible proxy responses (5,209 children, mean age 7.7 years; 3,909 adolescents, mean age 14.4 years). The proxy-reported vitiligo prevalence (95% confidence interval) for children and adolescents was 1.52% (1.11-1.93) and 2.16% (1.66-2.65), respectively. The clinician-adjudicated prevalence (sensitivity analysis bounds) was 0.84% (0.83-1.23) and 1.19% (1.18-1.74), respectively. Approximately 69% of children and 65% of adolescents had nonsegmental vitiligo (clinician adjudicated) and up to 50% may be undiagnosed. CONCLUSION: Based on the clinician-adjudicated prevalence estimates, there were more than 591,000 cases of vitiligo in children and adolescents in the US in 2020. More than two-thirds had nonsegmental vitiligo and nearly half may be undiagnosed. Future studies should confirm these findings.

Emerging environmental contaminants: A global perspective on policies and regulations.

Emerging contaminants include many synthetic or natural substances, such as pharmaceuticals and personal care products, hormones, and flame retardants that are not often controlled or monitored in the environment. The consumption or use of these substances is on an ever-rising trend, which dangerously increases their prevalence in practically all environmental matrices. These contaminants are present in low environmental concentrations and cause severe effects on human health and the biota. The present review analyzed 2012-2022 years papers via PubChem, science direct, National Center for Biotechnology Information, web of science on the legislations and policies of emerging contaminants globally. A state-of-the-art review of several studies in the literature focus on examining and evaluating the emerging contaminants and the frameworks adopted by developed and developing countries to combat the release of emerging contaminants and form footprints towards water sustainability which includes water availability, usage patterns, generation and pollution management, the health of aquatic systems, and societal vulnerability. The paper aims to provide a comprehensive view of current global policies and framework regarding evaluating and assessing the chemicals, in light of being a threat to the environment and biota. The review also highlights the future global prospects, including current governmental activities and emerging contaminant policy measures. The review concludes with suggestions and way forward to control the inventory and disposal of emerging contaminants in the environment.

A holistic review on trend, occurrence, factors affecting pesticide concentration, and ecological risk assessment.

Demographic outbursts and increased food demands invoke excessive use of pesticides in the agricultural field for increasing productivity which leads to the relentless decline of riverine health and its tributaries. These tributaries are connected to a plethora of point and non-point sources that transport pollutants including pesticides into the Ganga river's mainstream. Simultaneous climate change and lack of rainfall significantly increase pesticide concentration in the soil and water matrix of the river basin. This paper is intended to review the paradigm shift of pesticide pollution in the last few decades in the river Ganga and its tributaries. Along with this, a comprehensive review suggests the ecological risk assessment method which facilitates policy development, sustainable riverine ecosystem management, and decision-making. Before 2011, the total mixture of Hexachlorocyclohexane was found at 0.004-0.026 ng/mL in Hooghly, but now, the concentration has increased up to 0.465-4.132 ng/mL. Aftermath of critical review, we observed maximum residual commodities and pesticide contamination reported in Uttar Pradesh > West Bengal > Bihar > Uttara Khand possibly because of agricultural load, increasing settlement, and incompetency of sewage treatment plant in the reclamation of pesticide contamination.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Lung Ultrasound Findings in Patients Hospitalized With COVID-19.

OBJECTIVES: Lung ultrasound (LUS) can accurately diagnose several pulmonary diseases, including pneumothorax, effusion, and pneumonia. LUS may be useful in the diagnosis and management of COVID-19. METHODS: This study was conducted at two United States hospitals from 3/21/2020 to 6/01/2020. Our inclusion criteria included hospitalized adults with COVID-19 (based on symptomatology and a confirmatory RT-PCR for SARS-CoV-2) who received a LUS. Providers used a 12-zone LUS scanning protocol. The images were interpreted by the researchers based on a pre-developed consensus document. Patients were stratified by clinical deterioration (defined as either ICU admission, invasive mechanical ventilation, or death within 28 days from the initial symptom onset) and time from symptom onset to their scan. RESULTS: N = 22 patients (N = 36 scans) were included. Eleven (50%) patients experienced clinical deterioration. Among N = 36 scans, only 3 (8%) were classified as normal. The remaining scans demonstrated B-lines (89%), consolidations (56%), pleural thickening (47%), and pleural effusion (11%). Scans from patients with clinical deterioration demonstrated higher percentages of bilateral consolidations (50 versus 15%; P = .033), anterior consolidations (47 versus 11%; P = .047), lateral consolidations (71 versus 29%; P = .030), pleural thickening (69 versus 30%; P = .045), but not B-lines (100 versus 80%; P = .11). Abnormal findings had similar prevalences between scans collected 0-6 days and 14-28 days from symptom onset. DISCUSSION: Certain LUS findings may be common in hospitalized COVID-19 patients, especially for those that experience clinical deterioration. These findings may occur anytime throughout the first 28 days of illness. Future efforts should investigate the predictive utility of these findings on clinical outcomes.

Point-of-Care Ultrasound Predicts Clinical Outcomes in Patients With COVID-19.

OBJECTIVES: Point-of-care ultrasound (POCUS) detects the pulmonary manifestations of COVID-19 and may predict patient outcomes. METHODS: We conducted a prospective cohort study at four hospitals from March 2020 to January 2021 to evaluate lung POCUS and clinical outcomes of COVID-19. Inclusion criteria included adult patients hospitalized for COVID-19 who received lung POCUS with a 12-zone protocol. Each image was interpreted by two reviewers blinded to clinical outcomes. Our primary outcome was the need for intensive care unit (ICU) admission versus no ICU admission. Secondary outcomes included intubation and supplemental oxygen usage. RESULTS: N = 160 patients were included. Among critically ill patients, B-lines (94 vs 76%; P < .01) and consolidations (70 vs 46%; P < .01) were more common. For scans collected within 24 hours of admission (N = 101 patients), early B-lines (odds ratio [OR] 4.41 [95% confidence interval, CI: 1.71-14.30]; P < .01) or consolidations (OR 2.49 [95% CI: 1.35-4.86]; P < .01) were predictive of ICU admission. Early consolidations were associated with oxygen usage after discharge (OR 2.16 [95% CI: 1.01-4.70]; P = .047). Patients with a normal scan within 24 hours of admission were less likely to require ICU admission (OR 0.28 [95% CI: 0.09-0.75]; P < .01) or supplemental oxygen (OR 0.26 [95% CI: 0.11-0.61]; P < .01). Ultrasound findings did not dynamically change over a 28-day scanning window after symptom onset. CONCLUSIONS: Lung POCUS findings detected within 24 hours of admission may provide expedient risk stratification for important COVID-19 clinical outcomes, including future ICU admission or need for supplemental oxygen. Conversely, a normal scan within 24 hours of admission appears protective. POCUS findings appeared stable over a 28-day scanning window, suggesting that these findings, regardless of their timing, may have clinical implications.

Interobserver Agreement of Lung Ultrasound Findings of COVID-19.

BACKGROUND: Lung ultrasound (LUS) has received considerable interest in the clinical evaluation of patients with COVID-19. Previously described LUS manifestations for COVID-19 include B-lines, consolidations, and pleural thickening. The interrater reliability (IRR) of these findings for COVID-19 is unknown. METHODS: This study was conducted between March and June 2020. Nine physicians (hospitalists: n = 4; emergency medicine: n = 5) from 3 medical centers independently evaluated n = 20 LUS scans (n = 180 independent observations) collected from patients with COVID-19, diagnosed via RT-PCR. These studies were randomly selected from an image database consisting of COVID-19 patients evaluated in the emergency department with portable ultrasound devices. Physicians were blinded to any patient information or previous LUS interpretation. Kappa values (κ) were used to calculate IRR. RESULTS: There was substantial IRR on the following items: normal LUS scan (κ = 0.79 [95% CI: 0.72-0.87]), presence of B-lines (κ = 0.79 [95% CI: 0.72-0.87]), ≥3 B-lines observed (κ = 0.72 [95% CI: 0.64-0.79]). Moderate IRR was observed for the presence of any consolidation (κ = 0.57 [95% CI: 0.50-0.64]), subpleural consolidation (κ = 0.49 [95% CI: 0.42-0.56]), and presence of effusion (κ = 0.49 [95% CI: 0.41-0.56]). Fair IRR was observed for pleural thickening (κ = 0.23 [95% CI: 0.15-0.30]). DISCUSSION: Many LUS manifestations for COVID-19 appear to have moderate to substantial IRR across providers from multiple specialties utilizing differing portable devices. The most reliable LUS findings with COVID-19 may include the presence/count of B-lines or determining if a scan is normal. Clinical protocols for LUS with COVID-19 may require additional observers for the confirmation of less reliable findings such as consolidations.

Point-of-care ultrasound for the evaluation of non-traumatic visual disturbances in the emergency department: The VIGMO protocol.

OBJECTIVES: To establish a standardized approach for the rapid and accurate identification of non-traumatic, ophthalmologic pathology in patients with eye complaints in the emergency department. METHODS: In this detailed protocol we offer an easy, reproducible method for the use of ocular point-of-care ultrasound (POCUS) in helping practitioners identify and distinguish between common eye pathology encountered in the emergency setting: retinal detachment, vitreous detachment, vitreous hemorrhage, optic nerve pathology, and syneresis. CONCLUSIONS: This protocol can help identify patients that may need urgent ophthalmology consultation those that can follow-up on an outpatient, and those that may need additional emergent testing.

Health care Resource Utilization and Migraine Disability Along the Migraine Continuum Among Patients Treated for Migraine.

OBJECTIVE: To examine the disability, health care resource utilization, and direct annual costs among patients with migraine, categorized according to the number of headache days experienced in the past month. BACKGROUND: Migraine exists on a continuum of different attack frequencies and associated levels of disability. People with migraine have increased health care utilization and incur substantially more direct costs than those without the disease. While the broad implications of migraine are evident, there is a need to comprehensively describe the impact of headache frequency on the burden of illness. DESIGN/METHODS: Data from a cross-sectional, self-administered, Internet-based survey of respondents recruited from the US National Health and Wellness Survey panel were assessed. Adults who had self-reported migraine diagnosis or migraine symptoms in the past 3 months were grouped by their frequency of headache days in the past month: low-frequency episodic migraine (LFEM, <4 days), moderate-frequency episodic migraine (MFEM, 4-9 days), high-frequency episodic migraine (HFEM, 10-14 days), and chronic migraine (CM, ≥15 days). Headache-related disability was determined from the Headache Impact Test (HIT-6) scores, and health care resource utilization was assessed by the number of ER visits, hospitalizations, and visits to health care practitioners (HCPs) in the past 12 months. The estimated annual direct costs were calculated from the number of each type of visit and all-cause cost data from the 2014 Medical Expenditure Panel Survey. RESULTS: A total of 1347 patients (LFEM, n = 813; MFEM, n = 301; HFEM, n = 105; CM, n = 128) were included. Patient groups differed significantly by comorbidity index, education and income level, alcohol consumption, and insurance type. Overall, patients with LFEM had the least disability and lowest health care utilization and direct costs. Patients with CM scored 3.7 points (adjusted mean score [95% confidence interval, CI] 68.2 [67.3, 69.0] points) higher on HIT-6 compared with those in the LFEM group (64.5 points [64.1, 64.8]), while those with HFEM and MFEM scored 2.4 (66.8 points [65.9, 67.8]) and 2.3 (66.7 points [66.2, 67.3]) points higher, respectively (all, P < .001). The CM and MFEM groups reported significantly more HCP visits ([mean ± standard error] CM: 7.03 ± 0.83; MFEM: 5.34 ± 0.42; vs LFEM: 3.48 ± 0.18; both, P < .001) and migraine-related hospitalizations (CM: 0.06 ± 0.03; MFEM: 0.05 ± 0.02; vs LFEM: 0.02 ± 0.01; both, P < .05) than the LFEM group. There were significant differences in the total direct costs between the CM and MFEM groups compared with the LFEM group (CM: $3155 ± $609; MFEM: $2721 ± $342; vs LFEM: $1560 ± $118; both, P < .001), with differences largely driven by costs of HCP visits. CONCLUSIONS: In patients with migraine, as the number of headache days increased, so did the burden of disease (disability, health care utilization, and direct costs). Elucidating the burden associated with EM and CM has implications for guiding treatment decisions and management of patients with migraine.

Topical application of recombinant platelet-derived growth factor increases the rate of healing and the level of proteins that regulate this response.

A bipedicle ischaemic rat skin flap model was used to study the effects of daily topical applications of platelet-derived growth factor (PDGF) on the healing of ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1-beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of 72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and ischaemic wounds received either vehicle or 0·01% recombinant PDGF-BB. Additional applications were made on the wounds on a daily basis. Wound areas were measured at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound healing as well as an increase in TNFA, IL1B and both the pro and active forms of MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA concentration in both normal and ischaemic wounds, and the rate of wound healing closely resembled the pattern of TNFA protein expression. PDGF also reduced both the magnitude and duration of the increases in IL1B and both the pro and active forms of MMP2 and MMP9 induced by ischaemia.

Shared Decision-Making in the Treatment of Multiple Sclerosis: Results of a Cross-Sectional, Real-World Survey in Europe and the United States.

Introduction: Multiple sclerosis (MS) is a neurodegenerative disease characterized by progressive deterioration of cognitive and physical functioning, reducing activities of daily living and quality of life (QoL). Several treatments are available that modify the course of the disease and reduce the frequency of relapses. Although effective, all treatment options are accompanied by adverse events, and this study aimed to assess the extent to which patients were involved in the choice of treatment. Methods: Data were drawn from the Adelphi Multiple Sclerosis Disease Specific Program (DSP)™, a cross-sectional survey of healthcare practitioners (HCP) and their patients with MS in real-world clinical settings in Europe and the United States (US) between December 2020 and July 2021. HCPs reported patient demographics, clinical characteristics, current and previous treatment, and treatment outcomes. Patients voluntarily completed questionnaires reporting the physical and psychological impact of their MS and its treatment. Regression analysis with inverse probability of treatment weighting was used to compare treatment outcomes in patients actively involved in their current treatment choice with those who were not. Results: Of a total of 692 patients, median age 40 years and 64% female, mostly diagnosed with relapsing-remitting MS, those who were involved in shared decision-making tended to choose oral therapies such as dimethyl fumarate more often than HCPs. MS had greater impact on physical and psychological functioning in patients whose HCP made treatment decisions solely. Patients involved in decision-making reported greater satisfaction with their treatment and a better QoL. Discussion: Because no single optimal therapy exists for patients with MS, treatments should be individualized with consideration of patients' preferences. Our study shows that shared decision-making is under-utilized in the management of MS and supports the benefits of patient involvement. Conclusion: Patients who have an active role in treatment decision-making show improved wellbeing and QoL, and overall treatment satisfaction.

The occurrence, fate, toxicity, and biodegradation of phthalate esters: An overview.

Phthalate esters (PAEs) are a class of emerging xenobiotic compounds that are extensively used as plasticizers. In recent times, there has been an increasing concern over the risk of this pervasive pollution exposure causing endocrine disruption and carcinogenicity in humans and animals. The widespread use of PAEs in home and industrial applications has resulted in their discharge in aquatic bodies via leaching, volatilization, and precipitation. In this overview, the current state of PAE pollution, its potential origins, its fate, as well as its effects on the aquatic environment are discussed. A state-of-the-art review of several studies in the literature that focus on the biological degradation of PAEs is included in this study. The paper aims to provide a comprehensive view of current research on PAEs in the environment, highlighting its fate and alleviated risks on the aquatic biotas, their challenges, future prospects, and the need for good management and policies for its remediation. PRACTITIONER POINTS: Occurrence of phthalate esters was summarized in various environmental matrices along with its serious ecotoxicological implications on biota. Wastewater is the prime source of PAEs contamination. Lack of species-specific effects on biota due to dose, exposure route, and susceptibility. The predominant route to mineralization in PAEs is biodegradation. A critical analysis of worldwide PAE production and consumption identifies the necessity for global PAE production, consumption, and release policies.

The Association of Alopecia Areata-Related Emotional Symptoms with Work Productivity and Daily Activity Among Patients with Alopecia Areata.

INTRODUCTION: Patients with alopecia areata (AA) experience psychological and psychosocial symptoms including depression, anxiety, anger, social withdrawal, embarrassment, and low self-esteem. While multiple studies have measured the detrimental emotional impact of AA on patient quality of life, evidence of its effect on work productivity loss (WPL) and daily activities is limited. This study aimed to assess the extent of AA-related emotional symptom (ES) burden on work productivity and activity impairment. METHODS: A cross-sectional survey of dermatologists and their adult patients with AA was conducted in the USA in 2019. Dermatologists provided assessments of patients' clinical characteristics, while patients completed sociodemographic questionnaires along with two validated patient-reported outcome measures of the Work Productivity and Activity Impairment (WPAI) and the AA Patient Priority Outcomes (AAPPO) ES subscale. The WPAI assessed AA-related WPL (employed respondents) and activity impairment (all respondents), and the AAPPO-ES assessed AA-related frequency of feeling self-conscious, embarrassed, sad, or frustrated. Multiple linear regression models were fitted to both WPAI scores with the AAPPO ES as an independent variable. RESULTS: A total of 242 patients with a mean (SD) age of 39.2 (13.3) years, treated by 59 dermatologists, were evaluated. Mean (SD) ES score was 2.0 (1.1). Mean (SD) work productivity loss [n = 170] and activity impairment [n = 242] were 12.2% (17.4%) and 13.3% (18.3%), respectively. After adjusting for covariates, WPL increased by 4.1% [95% confidence interval (CI) 1.6-6.7%; p = 0.002] and activity impairment increased by 3.1% (95% CI 0.7-5.4%; p = 0.010) for every 1-point increase in ES. For an average patient, a 1-SD decrease (about 1 point) on the ES scale substantially reduced WPL and activity impairment (by at least 25%). CONCLUSIONS: Patients with AA reported significant increases in WPL and activity impairment associated with worsening AA-related ES. These findings underscore the substantial emotional and psychosocial burden among patients with AA and a need for improved treatment options.

Right-sided weakness in a Rwandan patient with untreated Tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease encountered in pediatrics with surgical repair being the definitive treatment. Long-term survival after surgical repair has improved; however, reported mortality rates in untreated TOF are significant. Associated complications include neurological sequelae such as brain abscess and stroke. In countries without early intervention for congenital heart disease (including TOF), delayed presentations and complications require recognition by healthcare workers. CASE PRESENTATION: A 22-year-old male with a history of untreated TOF presented to Rwanda's tertiary university hospital, University Teaching Hospital of Kigali, with acute right-sided hemiparesis. Diagnostic imaging identified a left-sided brain lesion consistent with brain abscess and cardiac mass, concerning endocardial vegetation. He was managed with intravenous antibiotics but subsequently died due to complications of septicemia. DISCUSSION: In countries where surgical repair of TOF is not available, early recognition and medical management are key in temporizing the development of devastating sequelae. Describing the prevalence of CHD in Rwanda is urgent, requiring further research by which effective prevention and treatment strategies can be developed.

Severity and worsening of fatigue among individuals with multiple sclerosis.

Background: Fatigue is associated with reduced quality of life and social participation, and poor employment outcomes. However, most studies examining fatigue are limited by small sample sizes or short follow-up periods. Objective: To characterize the natural history of fatigue. Methods: The North American Research Committee on Multiple Sclerosis Registry participants with ≥7 years of longitudinal data between 2004 and 2019 and a relapsing disease course were included. A subset of participants enrolled within 5 years of diagnosis was identified. The Fatigue Performance Scale assessed fatigue and ≥1-point increase in Fatigue Performance Scale sustained at the next survey defined fatigue worsening. Results: Of 3057 participants with longitudinal data, 944 were within 5 years of multiple sclerosis diagnosis. Most participants (52%) reported fatigue worsening during follow-up. Median time to fatigue worsening ranged from 3.5 to 5 years at lower levels of index fatigue. Fatigue worsening was associated with lower annual income, increasing disability, lower initial fatigue level, taking injectable disease-modifying therapies and increasing depression levels in the relapsing multiple sclerosis participants. Conclusion: Most multiple sclerosis participants early in their disease suffer from fatigue and at least half reported fatigue worsening over time. Understanding factors associated with fatigue may help to identify populations most at risk of fatigue worsening will be informative for the overall management of patients with multiple sclerosis.