Strabismus Surgery for Psychosocial Reasons-A Literature Review.

Introduction: Strabismus surgery may be undertaken for visual benefit, to improve or eliminate diplopia symptoms, or to restore or improve binocular single vision (BSV). In patients without visual symptoms or expected visual benefit, strabismus surgery may still be undertaken if the presence of strabismus causes the patient psychosocial symptoms. To evaluate strabismus surgery undertaken for psychosocial reasons, evidence of postoperative outcomes in this specific cohort is needed. Methods: A systematic search of the literature was conducted (1946-2023) to identify evidence where postoperative outcomes were reported for adult patients (age 18 years and above) who had undergone strabismus surgery for psychosocial reasons. Results: Sixty-nine papers were included in the literature review. Most sources of evidence included patients within heterogeneous cohorts of strabismus surgery outcomes, with a range of symptoms and differing surgical aims. Discussion: In adults who underwent strabismus surgery for psychosocial reasons, improved postoperative ocular alignment and/or improved health related quality of life (HRQoL) were common. Strabismus surgery outcomes appeared to be measured satisfactorily at three months postoperatively. Additional surgical outcomes, including an expanded field of vision, unexpected BSV, improved binocular summation, improved task performance and improved eye movements have been reported, but not fully investigated. There was a lack of consensus on how postoperative success should be defined and measured. A core outcome set for strabismus has been suggested and there is potential to add to the available evidence by investigating which outcome measures are most relevant to those with strabismus and psychosocial symptoms. There is a growing need for robust evidence in this specific subgroup of patients due to a lack of evidence specifically reporting postoperative outcomes in adults with strabismus and psychosocial symptoms.

Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study.

BACKGROUND: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). METHODS: An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered. RESULTS: In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320). CONCLUSIONS: Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876.

Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.

INTRODUCTION: One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes. METHODS: The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation. ETHICS AND DISSEMINATION: Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.

Community health workers in clinical research at the example of a phase IIIb/ IV antimalarial drug trial conducted in five African countries.

Global health, particularly in underserved settings can benefit immensely from well-trained community health workers (CHWs) supporting primary healthcare interventions. They can reduce morbidity and mortality of infectious diseases like malaria. Disease control programs can particularly benefit from a tight link between CHWs and communities and several studies have shown the benefit of the participation of non-facility-based CHWs in malaria control program activities for reducing malaria-related mortality in children. Because CHWs are often part of and trusted by served communities, they can also be an important resource to address challenges faced by their communities. Where post-marketing surveillance systems are underserved, they can relay important information about suspected safety signals and factors affecting therapeutic effectiveness in their communities. The CANTAM-Pyramax® trial was a phase IIIb/ IV cohort event monitoring study conducted at six centers in five African countries. To assess real-world effectiveness and safety of the anti-malarial pyronaridine-artesunate in 8560 malaria episodes, follow-up was not primarily conducted by medical staff but by specifically trained CHWs. This perspective paper discusses how the participation of a CHW workforce can be of benefit for effectiveness trials in limited-resource settings, using the example of the CANTAM-Pyramax trial.

Community-based management of a five-arm randomised clinical trial in COVID-19 outpatients in South Africa: challenges and opportunities.

BACKGROUND: Repeated COVID-19 waves and corresponding mitigation measures have impacted health systems globally with exceptional challenges. In response to the pandemic, researchers, regulators, and funders rapidly pivoted to COVID-19 research activities. However, many clinical drug studies were not completed, due to often complex and rapidly evolving research conditions. METHODS: We outline our experience of planning and managing a randomised, adaptive, open-label, phase 2 clinical trial to evaluate the safety and efficacy of four repurposed drug regimens versus standard-of-care (SOC) in outpatients with 'mild to moderate' COVID-19 in Johannesburg, South Africa, in the context of a partnership with multiple stakeholders. The study was conducted between 3 September 2020 and 23 August 2021 during changing COVID-19 restrictions, significant morbidity and mortality waves, and allied supply line, economic, and political instability. RESULTS: Our clinical study design was pragmatic, including low-risk patients who were treated open label. There was built-in flexibility, including provision for some sample size adjustment and a range of secondary efficacy outcomes. Barriers to recruitment included the timing of waves, staff shortages due to illness, late presentation of patients, COVID-19 misinformation, and political unrest. Mitigations were the use of community health workers, deployment of mobile clinical units, and simplification of screening. Trial management required a radical reorganisation of logistics and processes to accommodate COVID-19 restrictions. These included the delivery of staff training and monitoring remotely, electronic consent, patient training and support to collect samples and report data at home, and the introduction of tele-medicine. These measures were successful for data collection, safe, and well received by patients. CONCLUSION: Completing a COVID-19 trial in outpatients during the height of the pandemic required multiple innovations in nearly every aspect of clinical trial management, a high commitment level from study staff and patients, and support from study sponsors. Our experience has generated a more robust clinical research infrastructure, building in efficiencies to clinical trial management beyond the pandemic.

Demystifying treatment disposition patterns for psychiatrically high-risk youth referred for intensive outpatient psychiatric services: The role of demographics and telehealth.

Intensive outpatient (IOP) psychiatric treatment is increasingly deployed to meet the needs of psychiatrically high-risk youth; however, documentation of treatment disposition for in-person and/or telehealth modalities following treatment referral is largely unknown. The current study examined psychiatrically high-risk youth baseline treatment disposition patterns and explored variations according to treatment modality (telehealth vs. in-person). Using archival records of 744 adolescents (Mage = 14.91, SD = 1.60) admitted to a psychiatric IOP, multinomial logistic regressions revealed that commercially insured youth fared better than non-commercially insured youth with respect to treatment completion. When treatment modality was accounted for, youth treated on telehealth were no more likely to be psychiatrically hospitalized compared to youth treated with in-person services. However, youth treated on telehealth dropped out due to excessive absences or withdrawal/refusal to a greater extent than those treated in person. Future studies should examine clinical outcomes in addition to treatment disposition patterns to further understand youth's course of treatment at intermediate level of care settings (e.g., IOP).

Structural insights into RNA cleavage by a novel family of bacterial RNases.

Processing of RNA is a key regulatory mechanism for all living systems. We recently discovered a novel family of endoribonucleases that is conserved across all bacteria. Here, using crystallography, cryo-EM microscopy, biochemical, biophysical, and mass spectrometry techniques, we are able to shed light on a novel RNA cleavage mechanism in bacteria. We show that YicC, the prototypical member of this family, forms a hexameric channel that closes down on a 26-mer RNA substrate, and find that it cleaves across an RNA hairpin to generate several short fragments.

Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial.

BACKGROUND: This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19. METHODS: This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18-65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population. FINDINGS: The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ). INTERPRETATION: There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated. FUNDING: Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard.

Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.

BACKGROUND: High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa. METHODS: This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set. FINDINGS: Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections. INTERPRETATION: This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting. FUNDING: Medicines for Malaria Venture.

Ship Segmentation and Georeferencing from Static Oblique View Images.

Camera systems support the rapid assessment of ship traffic at ports, allowing for a better perspective of the maritime situation. However, optimal ship monitoring requires a level of automation that allows personnel to keep track of relevant variables in the maritime situation in an understandable and visualisable format. It therefore becomes important to have real-time recognition of ships present at the infrastructure, with their class and geographic position presented to the maritime situational awareness operator. This work presents a novel dataset, ShipSG, for the segmentation and georeferencing of ships in maritime monitoring scenes with a static oblique view. Moreover, an exploration of four instance segmentation methods, with a focus on robust (Mask-RCNN, DetectoRS) and real-time performances (YOLACT, Centermask-Lite) and their generalisation to other existing maritime datasets, is shown. Lastly, a method for georeferencing ship masks is proposed. This includes an automatic calculation of the pixel of the segmented ship to be georeferenced and the use of a homography to transform this pixel to geographic coordinates. DetectoRS provided the highest ship segmentation mAP of 0.747. The fastest segmentation method was Centermask-Lite, with 40.96 FPS. The accuracy of our georeferencing method was (22 ± 10) m for ships detected within a 400 m range, and (53 ± 24) m for ships over 400 m away from the camera.

Efficacy, Safety and Tolerability of Pyronaridine-artesunate in Asymptomatic Malaria-infected Individuals: a Randomized Controlled Trial.

BACKGROUND: Pyronaridine-artesunate (PA) is a registered artemisinin-based combination therapy, potentially useful for mass drug administration campaigns. However, further data are needed to evaluate its efficacy, safety and tolerability as full or incomplete treatment in asymptomatic Plasmodium falciparum-infected individuals. METHODS: This phase II, multi-center, open label, randomized clinical trial was conducted in The Gambia and Zambia. Participants with microscopically confirmed asymptomatic P. falciparum infection were randomly assigned (1:1:1) to receive a 3-day, 2-day, or 1-day treatment regimen of PA (180:60 mg), dosed according to bodyweight. The primary efficacy outcome was polymerase chain reaction (PCR)-adjusted adequate parasitological response (APR) at day 28 in the per-protocol population. RESULTS: A total of 303 participants were randomized. Day 28 PCR-adjusted APR was 100% for both the 3-day (98/98) and 2-day regimens (96/96), and 96.8% (89/94) for the 1-day regimen. Efficacy was maintained at 100% until day 63 for the 3-day and 2-day regimens but declined to 94.4% (84/89) with the 1-day regimen. Adverse event frequency was similar between the 3-day (51.5% [52/101]), 2-day (52.5% [52/99]), and 1-day (54.4% [56/103]) regimens; the majority of adverse events were of grade 1 or 2 severity (85% [136/160]). Asymptomatic, transient increases (>3 times the upper limit of normal) in alanine aminotransferase/aspartate aminotransferase were observed for 6/301 (2.0%) participants. CONCLUSIONS: PA had high efficacy and good tolerability in asymptomatic P. falciparum-infected individuals, with similar efficacy for the full 3-day and incomplete 2-day regimens. Although good adherence to the 3-day regimen should be encouraged, these results support the further investigation of PA for mass drug administration campaigns. CLINICAL TRIALS REGISTRATION: NCT03814616.

Exploring health seeking behaviour among incidentally diagnosed HIV cases in Rawalpindi, Pakistan: A qualitative perspective.

Objective: To identify the determinants of health-seeking behaviour among incidentally diagnosed cases of HIV and to explore the patterns of care seeking behaviour among these HIV infected persons. METHODS: The qualitative study based on the grounded theory was conducted from February to September 2019 at the Armed Forces Institute of Transfusion, Rawalpindi, Pakistan, and comprised incidentally diagnosed new cases of human immunodeficiency virus. Data was collected using in-depth interviews to understand how local environments and settings impact healthcare-seeking behaviour. Data was analysed using the constant comparison method. RESULTS: Of the 12 patients, 10(83.3%) were male, 1(8.3%) female and 1(8.3%) transgender. The mean age of the sample was 31±5 years. Of the total, 10(83.3%) patients were receiving free antiretroviral treatment from government hospitals in Rawalpindi/Islamabad, while 2 (16.7%) opted for some alternative form of healthcare. Ten (80%) were married and were carrying the diagnosis for >6 months. Processing of human immunodeficiency virus status, value placed in one's own health, experiences with healthcare provider and medication-related factors were the main themes that emerged from the data. Better counselling services, free-of-cost medication, positive patient-provider relationship and social support were the key players, while non-disclosure due to fear of stigma and beliefs about the disease were the main stumbling blocks. CONCLUSIONS: Value placed in one's own healthcare and thus the need for healthcare services, regardless of social norms, cultural reservations and personal beliefs, was the most important factor affecting the healthcare-seeking behaviour of human immunodeficiency virus patients.

Brain profiling in murine colitis and human epilepsy reveals neutrophils and TNFα as mediators of neuronal hyperexcitability.

BACKGROUND: Patients with chronic inflammatory disorders such as inflammatory bowel disease frequently experience neurological complications including epilepsy, depression, attention deficit disorders, migraines, and dementia. However, the mechanistic basis for these associations is unknown. Given that many patients are unresponsive to existing medications or experience debilitating side effects, novel therapeutics that target the underlying pathophysiology of these conditions are urgently needed. METHODS: Because intestinal disorders such as inflammatory bowel disease are robustly associated with neurological symptoms, we used three different mouse models of colitis to investigate the impact of peripheral inflammatory disease on the brain. We assessed neuronal hyperexcitability, which is associated with many neurological symptoms, by measuring seizure threshold in healthy and colitic mice. We profiled the neuroinflammatory phenotype of colitic mice and used depletion and neutralization assays to identify the specific mediators responsible for colitis-induced neuronal hyperexcitability. To determine whether our findings in murine models overlapped with a human phenotype, we performed gene expression profiling, pathway analysis, and deconvolution on microarray data from hyperexcitable human brain tissue from patients with epilepsy. RESULTS: We observed that murine colitis induces neuroinflammation characterized by increased pro-inflammatory cytokine production, decreased tight junction protein expression, and infiltration of monocytes and neutrophils into the brain. We also observed sustained neuronal hyperexcitability in colitic mice. Colitis-induced neuronal hyperexcitability was ameliorated by neutrophil depletion or TNFα blockade. Gene expression profiling of hyperexcitable brain tissue resected from patients with epilepsy also revealed a remarkably similar pathology to that seen in the brains of colitic mice, including neutrophil infiltration and high TNFα expression. CONCLUSIONS: Our results reveal neutrophils and TNFα as central regulators of neuronal hyperexcitability of diverse etiology. Thus, there is a strong rationale for evaluating anti-inflammatory agents, including clinically approved TNFα inhibitors, for the treatment of neurological and psychiatric symptoms present in, and potentially independent of, a diagnosed inflammatory disorder.

Establishing Clinical Swallowing Assessment Services via Telepractice: A Multisite Implementation Evaluation.

Purpose While research has confirmed the feasibility and validity of delivering clinical swallowing evaluations (CSEs) via telepractice, challenges exist for clinical implementation. Using an implementation framework, strategies that supported implementation of CSE services via telepractice within 18 regional/rural sites across five health services were examined. Method A coordinated implementation strategy involving remote training and support was provided to 18 sites across five health services (five hub and spoke services) that had identified a need to implement CSEs via telepractice. Experiences of all 10 speech-language pathologists involved at the hub sites were examined via interviews 1 year post implementation. Interview content was coded using the Consolidated Framework for Implementation Research (CFIR) and constructs were rated for strength and direction of influence, using published CFIR coding conventions. Results Services were established and are ongoing at all sites. Although there were site-specific differences, 10 CFIR constructs were positive influencing factors at all five sites. The telepractice model was perceived to provide clear advantages for the service, and clinicians were motivated by positive patient response. Strategies used to support implementation, including having a well-organized implementation resource and an external facilitator who worked closely with the local champions, were highly valued. Two CFIR constructs, Structural Characteristics and Available Resources, were challenges for all sites. Conclusions A complex interplay of factors influenced service implementation at each site. A strong local commitment to improving patient care, and the assistance of targeted strategies to support local implementation were viewed as central to enabling implementation.

Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study.

BACKGROUND: In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. METHODS AND FINDINGS: This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. CONCLUSIONS: Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201770.

Mental health and substance use patterns associated with lifetime suicide attempt, incarceration, and homelessness: A latent class analysis of a nationally representative sample of U.S. veterans.

A substantial proportion of U.S. military veterans experience mental health and/or substance use disorders. As public awareness of these difficulties rises, so too does interest in the relation between veteran behavioral health and high-risk events, namely suicide attempts, incarceration, and homelessness. Using latent class analysis and a large, nationally representative sample of community veterans, the current study examined common patterns of veteran behavioral health disorders and the associations between these patterns and high-risk events. Results suggest four classes of veterans, including a "healthy" class (comprising 69% of the total sample), a "substance use disorder" class (16%), a "personality disorder-substance use disorder" class (8%), and a "depressive disorder" class (7%). Veterans in the healthy class had the lowest rates of suicide attempt (2%), incarceration (14%), and homelessness (3%), whereas veterans in the personality disorder-substance use disorder class had the highest rates of these events (27%, 45%, and 22%, respectively). Results attest to the importance of investing clinical resources into addressing the needs of veterans experiencing complex behavioral health patterns, particularly personality and substance use disorders. Implications for the health care of veterans are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Informal carers' experiences of caring for a person with heart failure in a community setting.

Heart failure (HF) is a life-limiting condition with a poor prognosis and unpredictable disease trajectory. HF brings physical and emotional challenges for patients and their carers. Predominantly the informal carer population consists of older females, however, caring is evolving as longevity increases and complex conditions are becoming more commonplace. Consequently, more men and younger people are contributing to daily care. The aim of this study was to explore the positive as well as negative dimensions of caring in HF across a range of carer characteristics. Fourteen semi-structured interviews were conducted with informal carers of people with HF in the UK (median age 71; female 10). Interviews were transcribed verbatim and analysed with the assistance of NVivo10 using Interpretative Phenomenological Analysis. Findings from the study demonstrated that most participants considered caring as integral to their relationships. Dimensions facilitating positivity in caring included compassion, thoughtfulness and understanding. An ability to cope was influenced by a range of attributes including quality of relationships in the carer/patient dyad and with formal social care providers who offered access to tailored and timely information and support. The unpredictable HF disease trajectory influenced the carer experience and enhanced the challenges encountered. The information needs of carers were not always adequately met and younger adult carers expressed particular difficulties with appropriate information and support. Expectations of our informal carer population are increasing and evolving. Health and social care policy requires innovative proposals for the funding and delivery of health and social care that has the contribution made by informal carers at its core.

Implementation of speech pathology telepractice services for clinical swallowing assessment: An evaluation of service outcomes, costs and consumer satisfaction.

INTRODUCTION: Timely assessment of swallowing disorders (dysphagia) by speech pathologists helps minimise patient risk, optimise quality of life, and limit healthcare costs. This study involved a multi-site implementation of a validated model for conducting adult clinical swallowing assessments via telepractice and examined its service outcomes, costs and consumer satisfaction. METHODS: Five hub-spoke telepractice services, encompassing 18 facilities were established across a public health service. Service implementation support, including training of the telepractice speech pathologists (T-SP) and healthcare support workers in each site, was facilitated by an experienced project officer. New referrals from spoke sites were managed by the hub T-SP as per published protocols for dysphagia assessments via telepractice. Data was collected on existing service models prior to implementation, and then patient demographics, referral information, session outcomes, costs and patient and T-SP satisfaction when using telepractice. RESULTS: The first 50 sessions were analysed. Referrals were predominantly for inpatients at spoke sites. Telepractice assessments were completed successfully, with only minor technical issues. Changes to patient management (i.e. food/fluid changes post assessment) to optimise safety or progress oral intake, was required for 64% of patients. Service and cost efficiencies were achieved with an average 2-day reduction in waiting time and an average cost benefit of $218 per session when using the telepractice service over standard care. High clinician and patient satisfaction was reported. CONCLUSION: Telepractice services were successfully introduced across multiple sites, and achieved service and cost benefits with high consumer satisfaction.

Patient Perspectives in Geographic Atrophy (GA): Exploratory Qualitative Research to Understand the Impact of GA for Patients and Their Families.

BACKGROUND: Age-related macular degeneration (AMD) is the major cause of blindness for the older population in the developed world. Geographic atrophy (GA) is an advanced form of AMD. This progressive degenerative disease causes loss of visual function but unlike exudative AMD there are currently no approved therapeutic treatments for GA. Instead management of the condition is through supportive care. The aim of this study was to conduct exploratory qualitative research to develop a further understanding specifically of the impact of geographic atrophy (GA) on the quality of life for both patients and their families and to explore the resources GA patients most frequently access. METHODS: Two focus groups were conducted where participants were assigned to the 'better' or 'worse' group based upon their level of visual acuity. The data were analysed using the principles of thematic analysis. Transcripts were coded using an a priori framework. Emerging themes and subthemes were added, and transcripts recoded to reflect this. Transcripts were coded by one researcher, and the emerging themes and subthemes discussed and agreed prior to transcript recoding. RESULTS: Nine participants were recruited to the study (n = 5 'better group' and n = 4 'worse group'). Six overarching themes were identified. These are: experience of symptoms and understanding of GA; impact on activities; feelings and emotions; relationships and informal support; accessing formal support; and information needs. CONCLUSION: Key findings indicated that: participants had little knowledge of the mechanisms of GA but were aware of their prognosis; activities impacted by GA included management of daily activities and reading; emotions experienced included fear and frustration, and these frequently crossed over into their relationships with others; and access to formal support was mainly practical and information needs were largely unmet, with peer support being identified as important. Management of GA should include signposting to appropriate support agencies, such as low-vision services and charities.