ABSTRACT
BACKGROUND: Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices. RESULTS: Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into "highest score" and "lowest score", and "best response to elamipretide" and "worst response to elamipretide". Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60-93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%). CONCLUSIONS: In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.
Subject(s)
Barth Syndrome , Humans , Time Factors , Cardiolipins , FatigueABSTRACT
Introduction: To combat the COVID-19 pandemic, a mass vaccination campaign was initiated in Italy on December 27, 2020. The vaccine available to immunize Italian healthcare workers (HCWs) was the BNT162b2 mRNA COVID-19 vaccine (Comirnaty). Many studies have shown the high effectiveness of this vaccine in preventing infection and symptomatic disease in the fully immunized.Methods: This study evaluated the effectiveness of the vaccine against documented SARS-CoV-2 infection and symptomatic diseases in the medium- to long-term. HCWs at Bari Policlinico University-Hospital (Italy) who completed the vaccination schedule were matched with HCWs who had refused vaccination; the two groups were followed-up for 5 months (January–May 2021).Findings: Vaccine effectiveness (VE) against infection was 97·7% (95·4–99·0%) at 14–34 days after the first dose, and 94·8% (87·0–97·8%), 83·0% (65·0–92·0%), and 81·0% (42·0-94·0%) at 14–41, 42–69, and >69 days, respectively, after the second dose. The estimated VE for documented symptomatic disease was 99·2% (96·4–99·8%) at 14–34 days after the first dose and 97·2% (90·3–99·2%), 85·0% (63·0–94·2%), and 88·0% (42·0–97·6%) at 14–41, 42–69, and >69 days, respectively, after the second dose.Interpretations: The demonstrated effectiveness and safety of the BNT162b2 mRNA vaccine over the medium- to long-term provides further evidence that it is an essential weapon in ending the COVID-19 pandemic. Efforts to increase vaccination rates should be strengthened, including mandatory vaccination for HCWs and greater incentives to increase vaccine acceptance by the general population.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The research protocol was approved by Apulian Epidemiological Observatory and all human participants gave written informed consent.
Subject(s)
COVID-19 , Barth SyndromeABSTRACT
Background: Unpaid caregivers for adults play critical roles in health care systems by providing care to older adults and those with chronic conditions. The COVID-19 pandemic has heightened the need for care, forcing some into caregiving roles and disrupting others. Research is needed to estimate the prevalence of caregiving and identify factors associated with adverse mental health.Methods: In June 2020, Internet-based surveys with questions about demographics, caregiving responsibilities, and mental health were administered to US adults aged ≥18 years. Demographic quota sampling and survey weighting to improve cross-sectional sample representativeness of age, gender, and race/ethnicity. Prevalence ratios for adverse mental health symptoms were estimated using multivariable Poisson regressions.Findings: Of 9,896 eligible invited adults, 5,412 (54·7%) completed surveys; 5,011 (92·6%) respondents met screening criteria and were analysed, including 1,362 (27·2%) caregivers. Caregivers had higher prevalences of adverse mental health symptoms than non-caregivers, including anxiety or depressive disorder symptoms (57·6% vs 21·5%, respectively, p<0·0001) having recently seriously considered suicide (33·4% vs 3·7%, p<0·0001). Symptoms were more common among caregivers who were young vs older adults (eg, aged 18–24 vs ≥65 years, aPR 2·75, 95% CI 1·95–3·88, p<0·0001), Hispanic or Latino vs non-Hispanic White (1·14, 1·04–1·25, p=0·0044), living with vs without disabilities (1·18, 1·10–1·26, p<0·0001), and with moderate and high vs low Caregiver Intensity Index scores (2·31, 1·65–3·23; 2·81, 2·00–3·94; both p<0·0001). Suicidal ideation was more prevalent among non-Hispanic Black vs non-Hispanic White caregivers (1·48, 1·15–1·90, p=0·0022).Interpretation: Caregivers, who accounted for one in four US adult respondents in this nationally representative sample, more commonly reported adverse mental health symptoms than non-caregivers. Increased visibility of and access to mental health care resources are urgently needed to address mental health challenges of caregiving.Funding Statement: Monash University; Austin Health; Phillips Respironics; Whoop Inc; Alexandra DraneDeclaration of Interests: All authors report grants from Whoop, Inc., which supported in part administration of the survey in June 2020, and other support from ARCHANGELS, which permitted the investigators to use the proprietary ARCHANGELS Caregiver Intensity Index for this study without cost. Mr Czeisler reports grants from Australian-American Fulbright Commission administered through a 2020 Fulbright Future Scholarship funded by The Kinghorn Foundation, and personal fees from Vanda Pharmaceuticals, outside the submitted work. Ms Drane is co-founder of and employed by ARCHANGELS and receives salary and has equity. Ms Drane reports grants from Ralph C Wilson Junior Foundation; personal fees from Prudential Financial Services and Walmart; and other from RAND Health, Rosalynn Carter Institute for Caregivers, United States of Care - Entrepreneurs Council, Open Notes, Executive Council for Division of Sleep Medicine – Harvard Medical School, Massachusetts Technology Collaborative, C-TAC, EndWell, Beth Israel Deaconess Medical Center, MassChallenge Health Tech, Boston Children's Hospital, Health Evolution, Edenbridge Health, WHOOP, and HPT Development/Drane Associates, outside the submitted work. Ms Stephens Winnay reports a grant from Ralph C Wilson Junior Foundation (RCWJF), outside the submitted work. In addition, Ms Drane and Ms Winnay have a patent ARCHANGELS - Planned pending on the ARCHANGELS Caregiver Intensity Index, and a patent ARCHANGELS CII - Trademark pending on the ARCHANGELS Caregiver Intensity Index. Ms Capodilupo is employed by WHOOP, Inc., from which she receives salary and is a company shareholder, and is on the board of advisors at ARCHANGELS, and is a company shareholder. Dr Czeisler reports institutional education and research support from Cephalon, Inc. and from Philips Respironics Inc.; institutional grants from National Institute of Occupational Safety and Health R01-OH-011773; personal fees from and equity interest in Vanda Pharmaceuticals Inc; personal fees from Teva Pharmaceuticals Industries Ltd, Teva Pharma Australia, outside the submitted work. In addition, Dr Czeisler has a patent for the Actiwatch-2 and Actiwatch-Spectrum devices, with royalties paid from Philips Respironics Inc. Dr Czeisler's interests were reviewed and managed by Brigham and Women's Hospital and Mass General Brigham in accordance with their conflict of interest policies. Dr Czeisler served as a voluntary board member for the Institute for Experimental Psychiatry Research Foundation, Inc. Dr Shantha Rajaratnam reports grants from Turner Institute for Brain and Mental Health, Monash University; grants and personal fees from Cooperative Research Centre for Alertness, Safety and Productivity; grants and institutional consulting fees from Vanda Pharmaceuticals, and Teva Pharmaceuticals; and institutional consulting fees from BHP Billiton, Circadian Therapeutics, and Herbert Smith Freehills, outside the submitted work. Dr Mark Howard reports a grant from the Institute for Breathing and Sleep, Austin Health. No other potential competing interests were declared.Ethics Approval Statement: The Monash University Human Research Ethics Committee reviewed and approved the study protocol on human subjects research (ID #24036). This activity was also reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (45 CFR part 46, 21 CFR part 56; 42 USC Sect 241(d); 5 USC Sect 552a; 44 USC Sect 3501 et seq).