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Background and Objectives: Advance directives (ADs) are based on state-specific statutes that vary in structure, terminology, and options. This variability leads to inconsistent end-of-life (EOL) care for patients who have executed an AD in 1 state but fall ill in another state. This study revisits a 2002 article that identified considerable differences in ADs to determine whether ADs have become more uniform., Research Design and Methods: ADs from all 50 states and the District of Columbia were examined to determine the frequency of document types and seven key issues. The results were compared to the 2002 study using nonparametric approaches. Mean numbers of key issues were compared using t-tests and 1-way analysis of variance., Results: Consistent with 2002, 3 states in 2023 provide statutes for a healthcare power of attorney (HCPOA). However, states offering a combined HCPOA, and living will (LW), deemed an advance directive for healthcare (ADHC), increased from 13 to 30. Between both studies, Long-Term Care increased significantly in LW and ADHC, whereas Artificial Sustenance significantly increased in LW. Despite the rising prevalence of Alzheimer's in the United States, only 10% of states included this issue in 2023., Discussion and Implications: Despite evolving healthcare trends, minimal revisions have been made to ADs since 2002. This lack of uniformity can cause confusion regarding the proper understanding of EOL wishes. The authors recommend that the Uniform Act for Advance Directives be revisited to promote greater uniformity in ADs and ensure that individuals' preferences are understood and respected across different states., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments., Objectives: To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids., Methods: A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted., Results: All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28-1.58 (P < 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08-1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15-1.54; P < 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77-0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding., Conclusions: Pending validation in prospective studies, where feasible - and despite the heightened risk of relapse - topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: We evaluated whether plasma Alzheimer disease (AD)-related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors., Methods: We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant., Results: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008)., Conclusion: The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively-measured physical activity, cognition, and inflammation in older breast cancer survivors., Methods: Older (≥60 yrs) breast cancer survivors (n = 216) and frequency-matched non-cancer controls (n = 216) were assessed at baseline (pre-systemic therapy for survivors) and annually for up to five years. Assessments included hip-worn ActiGraphs worn for seven days, neuropsychological tests, the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) subscale, and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Data were analyzed using linear mixed-effect, random-effect contemporaneous fluctuation, and multi-level mediation models, considering covariates; p < .05 (two-sided) was considered significant., Results: Survivors had fewer minutes of moderate-to-vigorous physical activity (MVPA) than controls at 36-, 48-, and 60-month time points (p < .03). Fewer survivors met Aerobic Physical Activity Guidelines at 36 months than controls (17.7% vs 33.0%, p = .030). When Guidelines were met (vs not), FACT-Cog PCI scores were 2.1 ± 1.0 (p = .034) points higher. Higher MVPA and meeting Aerobic Guidelines were not related to objective neuropsychological performance. MVPA was inversely associated with CRP and IL-6 (p < .001), but inflammation did not mediate physical activity effects on perceived cognition., Conclusions: Older breast cancer survivors were less physically active than older non-cancer controls, especially farther from baseline. Meeting Aerobic Guidelines was associated with better perceived cognition in survivors. Survivorship care should consider physical activity monitoring and referral to rehabilitation and supervised exercise programs to promote physical activity and improve recovery in older survivors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur., (Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution 2024.)

Objective: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39)., Method: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups., Results: A total of 8 items were differentially difficult between languages in the 32-item version of the MINT. EA scored significantly higher than HA, but the difference was not significant when removing those 8 items (controlling for Education). The Receiver Operating Characteristics showed that the MINT had poor accuracy when identifying CN participants and was acceptable in identifying dementia participants but unacceptable in classifying MCI participants. Finally, we tested the association between MINT scores and magnetic resonance imaging volumetric measures of language-related areas in the temporal and frontal lobes. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral middle temporal gyrus. The left fusiform gyrus correlated with MINT scores regardless of language and MINT version. We also found differential correlations depending on the language of administration., Conclusions: Our results highlight the importance of analyzing cross-cultural samples when implementing clinical neuropsychological tests such as the MINT., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Human landing catches (HLCs) are required to collect blackflies for entomological evaluation to verify onchocerciasis elimination. However, there are ethical concerns regarding exposure of vector collectors to infectious blackflies and safer alternative methods are needed. This study evaluated a modified HLC technique where collectors wore coloured trousers (blue, black or blue-black), protecting them from bites during fly collection, and their performance was compared with the standard., Methods: The study was conducted in Makouopsap, Cameroon, in the Massangam health district for 4 months. Four collector pairs-one 'standard' (bare-legged) and three modified-were placed 50 m apart along known breeding sites on the Mbam and Nja Rivers. Collections were performed from 07:00 to 17:00 h, 4 d/month. Hourly rates of flies caught were analysed using a negative binomial generalised linear model to explore associations between flies caught and collection techniques and seasons., Results: Overall, 17 246 blackflies were caught. There was no significant statistical difference in the number of blackflies and parous flies caught between black trousers and the standard. Thus there is a strong indication that wearing black trousers is a viable non-inferior alternative to the standard HLC., Conclusions: Further studies are needed to confirm generalisability in different ecozones and transmission environments and among different blackfly species., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge., Methods: We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t -tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC., Results: A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p  < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P  = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P  = .003) was noted to be the only independent predictor for rehospitalization with ASUC., Conclusions: This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes., Competing Interests: The authors declare that they have no competing conflict of interest. There was no external funding used in preparing our manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option., Objectives: To assess the clinical efficacy of IA in addition to best medical treatment (BMT)., Methods: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods., Results: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients)., Conclusions: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits., Competing Interests: Conflicts of interest N.v.B. has a joint project and a patent pending with Euroimmun and received honoraria from Fresenius Medical Care. E.S. has a scientific cooperation arrangement with Fresenius Medical Care and received honoraria from this company. M.H. and R.E. have received honoraria from Fresenius Medical Care., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Motivation: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH., Results: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches., Availability and Implementation: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH., (© The Author(s) 2024. Published by Oxford University Press.)

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described., Objectives: Characterization of serum reactivities in DH., Methods: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X)., Results: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%)., Conclusions: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA., Competing Interests: Conflicts of interest C.D. and K.F. are employees of Euroimmun. D.Z. and E.S. have a scientific cooperation with Euroimmun not related to this project. The other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest M.A.L. has served on the advisory boards for AbbVie, InflaRx, Janssen and Viela Bio; consulted for Almirall, BSN Medical, Incyte, Janssen, Kymera, Phoenicis and XBiotech; and is on the medical board of the Hidradenitis Suppurativa Foundation. J.S.K. has received honoraria as a consultant for AbbVie, ChemoCentryx, Incyte, InflaRx, Janssen, Moonlake, Novartis and UCB; and is a speaker for AbbVie, Janssen and UCB. A.A. is a consultant for AbbVie, Boehringer Ingelheim, InflaRx, Novartis and UCB; and an investigator for Boehringer Ingelheim and Processa. N.G. has served on advisory boards for Novartis; consulted for Boehringer Ingelheim; and has participated in clinical trials with AbbVie, ChemoCentryx and Pfizer.

Reduction or complete loss of traits is a common occurrence throughout evolutionary history. In spite of this, numerous questions remain about why and how trait loss has occurred. Cave animals are an excellent system in which these questions can be answered, as multiple traits, including eyes and pigmentation, have been repeatedly reduced or lost across populations of cave species. This review focuses on how the blind Mexican cavefish, Astyanax mexicanus, has been used as a model system for examining the developmental, genetic, and evolutionary mechanisms that underlie eye regression in cave animals. We focus on multiple aspects of how eye regression evolved in A. mexicanus, including the developmental and genetic pathways that contribute to eye regression, the effects of the evolution of eye regression on other traits that have also evolved in A. mexicanus, and the evolutionary forces contributing to eye regression. We also discuss what is known about the repeated evolution of eye regression, both across populations of A. mexicanus cavefish and across cave animals more generally. Finally, we offer perspectives on how cavefish can be used in the future to further elucidate mechanisms underlying trait loss using tools and resources that have recently become available., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Competing Interests: Conflicts of interest: M.A.L. has served on the advisory boards for AbbVie, InflaRx, Janssen and Viela Bio, and consulted for Almirall, BSN medical, Incyte, Janssen, Kymera, Phoenicis and XBiotech. M.A.L. is on the medical board of the Hidradenitis Suppurativa Foundation (HSF). J.S.K. is a consultant for AbbVie, ChemoCentryx, Incyte, InflaRx, Janssen, Moonlake, Novartis and UCB, and receives honoraria. J.S.K. is a speaker for AbbVie, Janssen and UCB. A.A. is a consultant for AbbVie, Boehringer Ingelheim, InflaRx, UCB and Novartis, and an investigator for Boehringer Ingelheim and Processa. N.G. has served on advisory boards for Novartis, consulted for Boehringer Ingelheim, and has participated in clinical trials with AbbVie, Pfizer and Chemocentryx.

Primary eye care (PEC) is a vital component of primary healthcare (PHC) and is the cornerstone for the progress towards universal eye health coverage. While the concept of PEC is not new, with the increased focus of the global eye-health agenda on equity and people-centred care, it is critical to review experiences of delivering PEC in low- and middle-income countries and to identify common lessons learnt. This commentary builds on the available evidence and focuses specifically on three recently published evaluations of PEC in Sightsavers-supported programmes in Tanzania, Sierra Leone and Pakistan. It argues that systems thinking is critical in the delivery of PEC interventions, as only this approach can ensure that the integration of PEC into PHC is delivered in a comprehensive, coherent and sustainable way., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

In 2014, Sightsavers developed the first evidence gap map (EGM) to assess the extent and quality of review-level evidence on cataract relevant to low-and middle-income countries. The EGM identified 52 studies across five broad themes. This paper reports the update of the EGM conducted in 2021 and changes to the extent and quality of the evidence base. We updated the EGM using the exact process conducted to develop the original. Searches were run to 14 September 2021, and two independent reviewers selected eligible studies, critically appraised them and extracted data using the Supporting the Use of Research Evidence checklist. A summary quality assessment was shared with the authors for comments. Forty-six new reviews were identified, and the EGM now includes 98 reviews. The new reviews predominantly focus on treatment and risk factors. The overall methodological quality was found to be improved, with 13/46 reporting high confidence in findings. EGMs remain a useful tool for policy-makers to make informed decisions and periodic updates are important to assess changes and to refine the focus for future research. The EGM highlights significant disparity in the topics addressed by reviews, with health system interventions particularly neglected., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Cataract is a major cause of visual impairment globally, affecting 15.2 million people who are blind, and another 78.8 million who have moderate or severe visual impairment. This study was designed to explore factors that influence the uptake of surgery offered to patients with operable cataract in a free-of-charge, community-based eye health programme., Methods: Focus group discussions and in-depth interviews were conducted with patients and healthcare providers in rural Zambia, Kenya and Uganda during 2018-2019. We identified participants using purposive sampling. Thematic analysis was conducted using a combination of an inductive and deductive team-based approach., Results: Participants consisted of 131 healthcare providers and 294 patients. Two-thirds of patients had been operated on for cataract. Two major themes emerged: (1) surgery enablers, including a desire to regain control of their lives, the positive testimonies of others, family support, as well as free surgery, medication and food; and (2) barriers to surgery, including cultural and social factors, as well as the inadequacies of the healthcare delivery system., Conclusions: Cultural, social and health system realities impact decisions made by patients about cataract surgery uptake. This study highlights the importance of demand segmentation and improving the quality of services, based on patients' expectations and needs, as strategies for increasing cataract surgery uptake., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Aims: Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease., Methods and Results: A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200-500 mg/dL (2.26-5.65 mmol/L). Patients received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6-12 months. The primary endpoint was the percent change in fasting triglyceride levels from baseline to Month 6 of exposure. Baseline median (interquartile range) fasting triglyceride levels were 262 (222-329) mg/dL [2.96 (2.51-3.71) mmol/L]. Treatment with olezarsen resulted in mean percent triglyceride reductions of 23% with 10 mg every 4 weeks, 56% with 15 mg every 2 weeks, 60% with 10 mg every week, and 60% with 50 mg every 4 weeks, compared with increase by 6% for the pooled placebo group (P-values ranged from 0.0042 to <0.0001 compared with placebo). Significant decreases in apoC-III, very low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were also observed. There were no platelet count, liver, or renal function changes in any of the olezarsen groups. The most common adverse event was mild erythema at the injection site., Conclusion: Olezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at high risk for or with established cardiovascular disease., Trial Registration Number: NCT03385239., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Evidence indicates that school-based vision screening by trained teachers is an effective way of identifying and addressing potential vision problems in schoolchildren. However, inconsistencies have been reported in both the testing methods and accuracy of the screeners. This study assessed the prevalence of refractive errors and accuracy of screening by teachers in Grand Kru County, Liberia., Methods: We conducted a retrospective analysis of data from four schools where, in February 2019, children were screened for refractive errors by trained teachers and then re-examined by ophthalmic technicians. One row of five optotypes of the Snellen 6/9 (0.2 logMar) scale (tumbling E chart) was used at a distance of 3 m. The prevalence of visual impairment and associations with sex, age and school were explored. Sensitivity, specificity and predictive values were calculated., Results: Data were available for 823 of 1095 eligible children with a mean age of 13.7 y (range 5-18) and male:female ratio of 1:0.8. Poor vision was identified in 24 (2.9%) children with no differences by either sex or age but small differences by school. Screening by teachers had a sensitivity of 0.25 (95% confidence interval [CI] 0.077 to 0.423) and a specificity of 0.996 (95% CI 0.992 to 1.000). Positive and negative predictive values were 0.667 (95% CI 0.359 to 0.975) and 0.978 (95% CI 0.968 to 0.988), respectively. The results were influenced by a high number of misclassifications in one of the four schools., Conclusions: Teachers can be trained to conduct vision screening tests on schoolchildren to an acceptable level of accuracy, but strong monitoring and quality assurance systems should be built into screening programmes from the onset. In settings like Liberia, where many children do not attend school regularly, screening programmes should extend to community platforms to reach children out of school., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: The number of patients with visual impairment and blindness from glaucoma is rapidly increasing with wide-ranging impacts for individuals and societies. However, the disease often goes undiagnosed for a long time, especially in low- and middle-income countries where healthcare services are limited. This paper presents the results of a pilot programme, which integrated targeted glaucoma screenings of people aged ≥40 y in community-based eye care services in the Ganjam district of Odisha state, India., Methods: Using routine programme data, descriptive statistics were produced for the characteristics of patients participating in the screening programme and the rate and uptake of glaucoma referrals. Bivariate analysis was used to examine associations between patient characteristics, clinical risk factors and glaucoma diagnosis., Results: Out of 23 356 individuals aged ≥40 y screened for glaucoma over a period of 18 mo, 2219 (9.5%) were referred and 2031 presented for further examination. Among them, almost half (n=968, 48%) were diagnosed with glaucoma, representing a screening to diagnosis conversion rate of 4.14% (95% CI 3.9 to 4.4%). A positive diagnosis of glaucoma among suspects was associated with female sex, age >60 y, visual impairment, vertical cap-to-disc ratio ≥0.6:1, intraocular pressure ≥30 mmHg and shallow anterior chamber (p<0.001)., Conclusions: The importance of targeted screening for glaucoma using simple referral criteria to identify patients at high risk of vision loss who can benefit from treatment is critical to slow the progression of the disease and the prevention of blindness. Further studies assessing costs of the targeted screening, the role of technology in improving programme effectiveness and efficiency and the longer term compliance with treatment are needed to support glaucoma policy frameworks, guidelines and clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: More than 2 billion people are thought to be living with some form of vision impairment worldwide. Yet relatively little is known about the wider impacts of vision loss on individual health and well-being, particularly in low- and middle-income countries (LMICs). This study estimated the associations between all-cause vision impairment and self-reported symptoms of anxiety and depression among older adults in Kogi State, Nigeria., Methods: Individual eyes were examined according to the standard Rapid Assessment of Avoidable Blindness methodology, and anxiety and depression were assessed using the Washington Group Short Set on Functioning-Enhanced. The associations were estimated using multivariable logistic regression models, adding two- and three-way interaction terms to test whether these differed for gender subgroups and with age., Results: Overall, symptoms of either anxiety or depression, or both, were worse among people with severe visual impairment or blindness compared with those with no impairment (OR=2.72, 95% CI 1.86 to 3.99). Higher levels of anxiety and/or depression were observed among men with severe visual impairment and blindness compared with women, and this gender gap appeared to widen as people got older., Conclusions: These findings suggest a substantial mental health burden among people with vision impairment in LMICs, particularly older men, underscoring the importance of targeted policies and programmes addressing the preventable causes of vision impairment and blindness., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

In this article, the authors describe the 1-stage surgical technique that has been used by the senior author since 1990 for all his primary grade 2 and grade 3 augmentation-mastopexies. The article provides a safe, simple, and reproducible approach to a challenging procedure, one that tends to be the most litigious in aesthetic breast surgery. The key points of this technique are simple preoperative markings; the augmentation is performed with a true submuscular placement of smooth implants; and the mastopexy is performed with an inferior pedicle technique with unlimited skin flap undermining and no limitation of nipple elevation. Seventy-eight consecutive cases of augmentation mastopexy performed since 1999 by a single surgeon (V.S.) using the same technique were reviewed. The age range was 26-62 years old; the range of implant volume was 150-375 cc; and the follow-up time period was from 1 year to 22 years. After an extensive patient case review, the authors enforce true extended submuscular augmentation (TESMA) as a reliable augmentation technique that can be used as the first procedure in any grades 2 and 3 ptosis, 1-stage augmentation-mastopexies including bariatric cases. The authors believe that the split inferior pedicle for the mastopexy in combination with the TESMA is a breakthrough approach that eliminates the second stage for any augmentation mastopexy procedure. No major complications such as nipple necrosis, implant bottoming, malpositioning, or extrusions were observed. It is a safe, simple, and reproducible procedure., (© 2022 The Aesthetic Society.)

Background: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance., Objectives: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus., Methods: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg -1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058)., Results: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg -1 and 13 of 15 (87%) patients receiving 25 mg kg -1 , with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg -1 per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2-41 weeks., Conclusions: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus., (© 2021 Argenx - SE. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: European guidelines propose a 0·5 mg kg -1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients., Methods: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg -1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg -1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score., Results: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively., Conclusions: A 0·5 mg kg -1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous., (© 2021 British Association of Dermatologists.)

Background: Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti-Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3., Objectives: To characterize the Ca 2+ flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles., Methods: Immunoprecipitation, Ca 2+ flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used., Results: PV IgG and PF IgG, but neither Dsg3-specific monoclonal antibody (AK23) nor mPV IgG, caused Ca 2+ influx in primary human keratinocytes. Phosphatidylinositol 4-kinase α interacts with Dsg1 but not with Dsg3. Its downstream target - phospholipase-C-γ1 (PLC) - was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5-trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca 2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca 2+ release-activated channels (CRAC)-mediated Ca 2+ influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG-induced Ca 2+ influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG-induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo., Conclusions: Ca 2+ -mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca 2+ signalling may be a promising approach to treat epidermal manifestations of pemphigus., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Patients with aphasia can present a type of acalculia referred to as aphasic acalculia., Aims: To investigate the correlation and to test regression models for one- and two-digit calculation skills using verbal and nonverbal predictors., Methods and Procedures: We selected an aphasia sample of 119 men and 81 women with a mean age of 57.37 years (SD = 15.56) and an average level of education of 13.52 years (SD = 4.08). Spanish versions of the Western Aphasia Battery and Boston Diagnostic Aphasia Examination, plus a Written Calculation test, were individually administered. The calculation section of the Western Aphasia Battery and the Written Calculation tests were used to pinpoint calculation difficulties., Outcomes and Results: Calculation difficulties were more severe in Global and Mixed non-fluent aphasia; they were very similar in Broca, Conduction, and Amnesic Aphasia. All correlations between the two calculation subtests and the other subtests of the Western Aphasia Battery were statistically significant. Calculation subtests correlated negatively with age and positively with schooling. Sex and time post-onset did not show any correlation with the calculation scores. Education, Reading, Block Design, and Raven's Colored Progressive Matrices were significant predictors of Western Aphasia Battery Calculation. Writing was the only significant predictor of the Written Calculation scores., Conclusions: Nonverbal abilities were predictors of calculation tests, whereas agraphia defects were predictors of the Written Calculation test. Therefore, calculation abilities can be regarded both as written language-dependent and verbal language-independent., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The COVID-19 pandemic is impacting communities worldwide, with direct effects of illness and mortality, and indirect effects on economies, workplaces, schools/daycares, and social life. However, we understand very little about the effects of this pandemic on families of young children. We used a risk and resilience model to evaluate the effects of the pandemic on mental health in diverse caregivers (N = 286) with children ages birth to 5. We evaluated the hypotheses that (a) pandemic stress and caregiver-reported child psychosocial concerns correlate with caregivers' mental health symptoms and (b) caregivers' pandemic-related self-efficacy and coping mediate these relationships. Caregivers completed surveys in April-May 2020 assessing pandemic stress (e.g., health, finances, and housing), child psychosocial problems, coping strategies, and self-efficacy to manage family needs. Our primary outcome was caregivers' self-reported changes in mental health symptoms since the outbreak. Path analysis revealed that higher pandemic stress was associated with caregivers' reduced confidence in meeting their family's needs related to COVID-19, which correlated with worse caregiver mental health symptoms. Greater child psychosocial problems also predicted worse caregiver mental health symptoms. Findings suggest that pandemic stress, child psychosocial problems, and caregiver self-efficacy are interrelated in their influence on caregivers' mental health. While further research is needed to examine strategies to foster resilience and buffer the pandemic's effects on caregiver mental health, this is a first step in evaluating the psychosocial effects of this pandemic in families of young children. Clinical implications are discussed for a tiered response to mitigate the pandemic's impacts on family functioning., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)