Rate of neuropathic progression in hereditary transthyretin amyloidosis with polyneuropathy and other peripheral neuropathies: a systematic review and meta-analysis.

BACKGROUND: We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT). METHODS: Literature searches identified studies reporting neuropathic progression, measured by Neuropathy Impairment Score (NIS) or NIS-Lower Limbs (NIS-LL). Our study also included unpublished data from a clinical registry of patients who were diagnosed with different peripheral neuropathies and seen at the Oregon Health & Science University (OHSU) during 2016-2020. Meta-analysis and meta-regression models examined and compared annual progression rates, calculated from extracted data, between studies of ATTRv-PN and other peripheral neuropathies. RESULTS: Data were synthesized from 15 studies in which NIS and/or NIS-LL total scores were assessed at least twice, with ≥12 weeks between assessments, among untreated patients with ATTRv-PN or other peripheral neuropathies. Meta-analysis models yielded that the annual progression rate in NIS total scores was significantly different from zero for studies in ATTRv-PN and CMT (11.77 and 1.41; both P < 0.001), but not DPN (- 1.96; P = 0.147). Meta-regression models showed significantly faster annual progression in studies in ATTRv-PN, which statistically exceeded that in other peripheral neuropathies by 12.45 points/year for NIS, and 6.96 for NIS-LL (both P < 0.001). CONCLUSIONS: Peripheral nervous function deteriorates more rapidly in patients with ATTRv-PN than for other peripheral neuropathies. These findings may improve understanding of the natural history of neuropathy in ATTRv-PN, facilitate early diagnosis, and guide the development of assessment tools and therapies specifically targeting neuropathic progression in this debilitating disease.

Antipsychotic treatment experiences of people with bipolar I disorder: patient perspectives from an online survey.

BACKGROUND: Oral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use. METHODS: Adults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive. RESULTS: The survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as "very" or "extremely bothersome." Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects - most commonly anxiety and lack of emotion - negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included "feeling like a 'zombie'" (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and "feeling like a 'zombie'" (47%). CONCLUSIONS: Side effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles.

Mental health impact on healthcare workers due to the COVID-19 pandemic: a U.S. cross-sectional survey study.

BACKGROUND: The COVID-19 pandemic has impacted the mental health and well-being of health care workers (HCWs). This study examined mental health outcomes and COVID-related stress impacts among a diverse sample of ambulatory HCWs, including clinicians and support staff, as well as the associations between mental health outcomes and work impairments in this population. Detailing these results can help in designing interventions to alleviate this burden. METHODS: "The Health Care Worker Stress Survey" was administered to ambulatory care providers and support staff at three multispecialty care delivery organizations as part of an online, cross-sectional study conducted between June 8, 2020, and July 13, 2020. RESULTS: The greatest stress impact reported by HCWs was the uncertainty regarding when the COVID-19 outbreak would be under control, while the least reported concern was about self-dying from COVID-19. Differences in COVID-19 stress impacts were observed by age, gender, and occupational risk factors. Approximately 50% of participants reported more than a minimal level of anxiety, including 22.5% who indicated moderate to severe levels of anxiety. Higher levels of anxiety were observed with younger ages and female gender, while occupational roles with increased exposure risk did not report higher levels of anxiety. Roughly two-thirds of the sample reported less than good sleep quality and one-third to one-half of the sample reported other sleep related problems that differed by age and gender. Role limitations due to emotional health correlated with COVID-19 related stress, anxiety and sleep problems. CONCLUSIONS: Using established, validated measures, we quantified mental health outcomes within a diverse sample of ambulatory care HCWs during the pandemic. Younger and female HCWs reported greater anxiety burden; HCWs with higher occupational risk of COVID exposure did not report higher levels of anxiety. Notable proportions of HCWs reported sleep and work impairments. Due to the cross-sectional nature of the study, it is difficult to attribute these patterns to the pandemic. These results underscore the depth and extent of mental health outcomes in HCWs in ambulatory settings and raise important questions on new interventions to relieve that burden. Further research is needed to study specific interventions to support the mental health and wellbeing of HCWs.

Psychometric properties of FACIT-Fatigue in systemic lupus erythematosus: a pooled analysis of three phase 3 randomised, double-blind, parallel-group controlled studies (BLISS-SC, BLISS-52, BLISS-76).

BACKGROUND: Fatigue is a key symptom in patients with systemic lupus erythematosus (SLE), and regulatory bodies recommend its assessment in clinical trials of SLE therapies. METHODS: This post hoc pooled analysis of the three BeLimumab In Subjects with Systemic lupus erythematosus (BLISS) Phase 3 randomised, double-blind, parallel-group controlled trials evaluated the measurement properties of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Patients (N = 2520) completed the FACIT-Fatigue every 4 weeks from baseline until the end of each study period. Internal consistency, test-retest reliability, convergent validity, and ability to detect changes in SLE were evaluated for the FACIT-Fatigue. RESULTS: The FACIT-Fatigue showed good internal consistency reliability (Cronbach's alpha > 0.90), very good test-retest reliability (0.76 ≤ intraclass correlation coefficient ≤ 0.92), and moderate-strong convergent validity (0.49 ≤ |r| ≤ 0.86) against scale and summary measure scores from the Short Form 36 Health Survey Version 2. Correlations between FACIT-Fatigue and British Isles Lupus Assessment Group (BILAG) General/Musculoskeletal scores (0.24 ≤ |r| ≤ 0.43) supported convergent validity. Correlations between FACIT-Fatigue and the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and SLE annualised flare rate were weak but in the expected direction (ranging from - 0.02 to - 0.25). Known-groups validity testing showed that the FACIT-Fatigue can significantly discriminate between patient groups with differing scores for SELENA-SLEDAI, BILAG (General and Musculoskeletal) ratings, and Physician's Global Assessment (PGA). Patients showing improvement in PGA and meeting the BILAG responder criteria had significantly higher mean improvement in FACIT-Fatigue scores than those without improvements in either measure (Week 52 mean score difference [95% confidence interval]: - 4.0 [- 5.0, - 3.0] and -2.2 [-3.1, -1.2], respectively; both p < 0.0001). The range of important (i.e. meaningful) change in FACIT-Fatigue, based on multiple anchors, was 3-6 points. CONCLUSIONS: The FACIT-Fatigue demonstrated adequate psychometric properties in patients with SLE. The body of evidence from the three BLISS trials (both pooled and individually) supports the FACIT-Fatigue as a reliable and valid measure of SLE-related fatigue in clinical trials. CLINICAL TRIAL IDENTIFIERS: BLISS-SC (NCT01484496), BLISS-52 (NCT00424476), and BLISS-76 (NCT00410384).