Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

The economics of a national anterior cruciate ligament injury prevention program for amateur football players: a Markov model analysis.

OBJECTIVES: To estimate the long term cost savings, return on investment, and gain in quality-adjusted life years (QALYs) that could be achieved by a national anterior cruciate ligament (ACL) injury prevention program for amateur football (soccer) players in Australia. STUDY DESIGN: Markov model decision analysis. SETTING, PARTICIPANTS: Two hypothetical scenarios including all amateur football players in Australia (340 253 players): no intervention, and a national ACL injury prevention program. Transitions between health states, including ACL rupture, meniscal injury, knee osteoarthritis, and total knee replacement were made in one-year cycles over 35 years from a societal perspective. MAIN OUTCOME MEASURES: Cost savings, return on investment, and QALY gain achieved in the prevention program scenario relative to control scenario, by age group (10-17, 18-34, 35 years or older) and gender. SECONDARY OUTCOMES: incidence of ACL rupture, knee osteoarthritis, total knee replacement, and total knee replacement revision. RESULTS: The total mean cost of an ACL injury was estimated to be $30 665. The national injury prevention program was projected to save $52 539 751 in medical and societal costs caused by ACL ruptures in amateur footballers over 35 years; the estimated return on each dollar invested in the program was $3.51. Over this period, the number of players with ruptured ACLs could be reduced by 4385 (9%), the number of knee osteoarthritis cases by 780 (8.1%), and the number of total knee replacements by 121 (8.1%); 445 QALYs were gained. CONCLUSION: Our findings support investing in a national, evidence-based program for the primary prevention of ACL injuries in amateur football players.

Managing giant omphalocele: A systematic review of surgical techniques and outcomes.

AIM: We analysed closure techniques in the treatment of giant omphalocele. A challenging pathology where there lacks consensus. METHODS: Cochrane, MEDLINE and EMBASE were searched between 1 January 1992 and 31 December 2022 using terms and variations: omphalocele, exomphalos, giant, closure and outcome. Papers were selected using Preferred Reporting Items for Systematic review and Meta-Analyses 2020 criteria. Data collected included demographics, timing and technique of surgical repair, morbidity and mortality. RESULTS: We identified 342 papers; 34 met inclusion criteria with a total 356 neonates. Initial non-operative management was described in 26 papers (14 dressings, eight silo, four serial sac-ligation). Operative techniques by paper were as follows: Early closure: nine primary suture closure without patch, two primary closure with patch and four mixed methods. Delayed closure: five simple, four-component separation technique, four tissue expanders, one Botox/pneumoperitoneum and two with patch. Median number of procedures was two (1-6) in the early group versus three (1-4) in the delayed. The most favourable was early primary closure with biological patch. The most unfavourable was delayed closure with patch. Cumulative reported mortality remained high, mostly due to non-surgical causes. CONCLUSION: Definitions of giant omphalocele in the literature were heterogeneous with a variety of management approaches described.

Community service rehabilitation therapists' understanding of social accountability.

BACKGROUND:  Social accountability is the obligation of health care providers to address the priority health concerns of the community they serve and of universities to ensure that graduates understand these social responsibilities. Although social accountability can combat systemic health inefficiencies, it is not well-understood or practised. AIM:  The study aimed to explore community service rehabilitation therapists' understanding of social accountability. SETTING:  The study was conducted in KwaZulu-Natal, South Africa. METHODS:  This study used an interpretive exploratory design and purposively recruited 27 community service rehabilitation therapists namely, audiologists, speech-language therapists, occupational therapists, and physiotherapists working in public sector health facilities in rural and peri-urban areas. Four focus group discussions and four free attitude interviews were conducted, the results being thematically analysed. RESULTS:  Despite most of the participants not being instructed in social accountability as part of their formal training or institutional induction, three themes emerged based on their experiences. These themes include describing social accountability, values of social accountability, and values of community-based rehabilitation applicable to social accountability. CONCLUSION:  Inclusion of instruction on social accountability as part of their formal training and health facility induction would contribute to rehabilitation therapists' understanding of social accountability.Contribution: The study contributes to data on rehabilitation education and community service training regarding social accountability within a South African context and has captured how experiences gained during community service contribute to the rehabilitation therapists' understanding of social accountability.

Social accountability challenges and recommendations by community service rehabilitation therapists.

BACKGROUND:  Social accountability entails providing equitable and accessible services that are tailor-made for the community's healthcare needs and enable rehabilitation therapists to improve the efficiency and efficacy of healthcare delivery and their response. Enabling them to provide optimal care during their community service year requires understanding the gaps in their knowledge, experience and the support they provide to the communities they service. METHODS:  Four in-depth individual interviews and four focus group discussions were conducted via Zoom. The qualitative responses to the questions related to the challenges and recommendations associated with social accountability in clinical settings were analysed using an inductive thematic approach via NVIVO. RESULTS:  Four sub-themes emerged for each of the two areas of interest: the challenges relating to (1) budget and equipment constraints, (2) staff shortages, (3) cultural and language barriers and (4) scope of practice limitations. The recommendations related to (5) collaboration with community caregivers, (6) service inclusion in primary health care clinics, (7) improved executive management support and (8) continuing professional development. CONCLUSION:  Equipping graduates with the knowledge, skills and support needed to work in an under-resourced setting is essential for community service rehabilitation therapists to ensure social accountability, given that they often work alone, specifically in rural settings.Contribution: Being aware of the challenges that face community service rehabilitation therapists, having the necessary tools and health facility management support will enable ongoing improvements in their ability to provide socially accountable services.

Steady states and kinetic modelling of the acid-catalysed ethanolysis of glucose, cellulose, and corn cob to ethyl levulinate.

Ethyl levulinate is a promising advanced biofuel and platform chemical that can be derived from lignocellulosic biomass by ethanolysis processes. It can be blended with both diesel and gasoline and, thus, used in conventional engines and infrastructure. Previously, it has been shown that alkyl levulinate/alcohol/alkyl ether mixtures exhibit significantly enhanced fuel properties relative to any of the individual fuel components, particularly when blended with conventional hydrocarbon liquid fuels. Consequently, this study specifically quantifies the three primary components of the alcoholysis reaction mixture: ethyl levulinate, diethyl ether, and ethanol. The steady state and kinetic phase fractions of ethyl levulinate and diethyl ether produced from glucose, cellulose, and corn cob with 0.5-2 mass% sulphuric acid in ethanol are determined for 5, 10, and 20 mass% of feedstock at 150 °C. Knowledge of the steady state equilibrium mixture fraction is specifically targeted due to its importance in assessing commercial-scale production and in modelling analysis as: (i) it defines the maximum yield possible at a given condition, and (ii) it is equitable to the minimum free energy state. Maximum steady state yields (mass%) of ethyl levulinate of (46.6 ± 3.7), (50.2 ± 5.4), and (27.0 ± 1.9)% are determined for glucose, cellulose, and corn cob, respectively. The conversion of glucose and cellulose to ethyl levulinate in the presence of ethanol and sulphuric acid is shown to be a catalytic process, where the ethyl levulinate yield is not dependent on the acid concentration. For corn-cob biomass, in a new and contrasting finding, the ethyl levulinate yield is shown to strongly depend on the acid concentration. This effect is also observed in the fractions of diethyl ether formed, providing strong evidence that the hydrogen cation is not being replenished in the ethanolysis process and the overall reaction with corncob is not wholly catalytic. Thus, for the acid catalysed alcoholysis of lignocellulosic biomass, acid concentration must be scaled with feedstock concentration. The critical corn cob-to-acid ratio that maximises ethyl levulinate yields while minimizing the formation of undesired co-products (diethyl ether) is in the range 10-20 : 1 at 150 °C. A detailed, hierarchical, mass-conserved chemical kinetic model capable of accurately predicting the relative abundance of the three primary components of the ethanolysis reaction: ethyl levulinate, diethyl ether, and ethanol, from the biochemical composition of the feedstock, is elucidated and validated.

Mastering your fellowship: Part 4, 2024.

The 'Mastering your Fellowship' series provides examples of the question format encountered in the written and clinical examinations for the Fellowship of the College of Family Physicians of South Africa (FCFP [SA]) examination. The series is aimed at helping family medicine registrars prepare for this examination. Model answers are available online.

Heading in football: a systematic review of descriptors, definitions, and reporting methods used in heading incidence studies.

The primary objective of this systematic review was to describe the number and type of heading descriptors used in all published studies which report on heading incidence in football. The secondary objective was to detail the data collection and reporting methods used in the included studies to present heading incidence data. Eligible studies were identified through searches of five electronic databases: Ovid MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science, using a combination of free-text keywords (inception to 12th September 2023). Manual searching of reference lists and retrieved systematic reviews was also performed. A descriptive overview and synthesis of the results is presented. From 1620 potentially eligible studies, 71 studies were included, with the following key findings: 1) only 61% of studies defined a header with even fewer (23%) providing an operational definition of a header within the methods; 2) important study and player demographic data including year and country were often not reported; 3) reported heading descriptors and their coding options varied greatly; 4) visual identification of headers was essential when inertial measurement units were used to collect heading incidence data; and 5) there was a lack of standardisation in the reporting methods used in heading incidence studies making comparison between studies challenging. To address these findings, the development of a standardised, internationally supported, operational definition of a header and related heading descriptors should be prioritised. Further recommendations include the development of minimum reporting criteria for heading incidence research.

Draft genome sequence data on Bacillus safensis U41 isolated from soils of Santiniketan, India.

The draft genome sequence of an isolate of Bacillus safensis U41 from the soils of Santiniketan (23040'12″ N and 87039'52″ E) is reported here. Bacillus safensis is a bacterium that produces cellulases, which is essential for the breakdown of plant biomass. As such, it is a valuable source of digestive enzymes from plant biomass, especially cellulases. The genomic DNA was extracted from a single colony using a QIAgen Blood and Tissue kit (QIAgen Inc., Canada). Sequencing was performed via Illumina HiSeq X using 2 × 150 paired-end chemistry, generating 7,352,576 reads with sequence coverage of 509x. The assembly produced 20 contigs over 200 base pairs (bp) in length, with an N50 value of 901304 and an L50 of 2. The genome size was 3,732,407 bp, and the average GC content was 41.43 %. Genome annotation and gene predictions were performed using Prokka v.1.14.6, which identified 3783 coding sequences, 64 tRNA genes, and 3 rRNA genes.

Strengthening caesarean birth: Sub-Saharan Africa health system evaluation: Scoping review.

BACKGROUND:  Promoting safe caesarean birth (CB) is a challenge in sub-Saharan Africa (SSA) where maternal and neonatal mortality rates are high due to inadequate maternal health services. Although the CB rate in SSA is lower than the World Health Organization (WHO) recommendation, it is often associated with high maternal and neonatal mortality. AIM:  The aim of this scoping review was to report on the extent to which SSA health systems deliver safe CB. METHODS:  A systematic search across various databases identified 53 relevant studies, comprising 30 quantitative, 10 qualitative and 16 mixed methods studies. RESULTS:  These studies focused on clinical protocols, training, availability, accreditation, staff credentialing, hospital supervision, support infrastructure, risk factors, surgical interventions and complications related to maternal mortality and stillbirth. CB rates in SSA varied significantly, ranging from less than 1% to a high rate of 29.7%. Both very low as well as high rates contributed to significant maternal and neonatal morbidity. Factors influencing maternal and perinatal mortality include poor referral systems, inadequate healthcare facilities, poor quality of CBs, inequalities in access to maternity care and affordable CB intervention. CONCLUSION:  The inadequate distribution of healthcare facilities, and limited access to emergency obstetric care impacted the quality of CBs. Early access to quality maternity services with skilled providers is recommended to improve CB safety.Contributions: This scoping review contributes to the body of knowledge motivating for the prioritization of maternal service across SSA.

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.

OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.

Accurate automated segmentation of autophagic bodies in yeast vacuoles using cellpose 2.0.

Segmenting autophagic bodies in yeast TEM images is a key technique for measuring changes in autophagosome size and number in order to better understand macroautophagy/autophagy. Manual segmentation of these images can be very time consuming, particularly because hundreds of images are needed for accurate measurements. Here we describe a validated Cellpose 2.0 model that can segment these images with accuracy comparable to that of human experts. This model can be used for fully automated segmentation, eliminating the need for manual body outlining, or for model-assisted segmentation, which allows human oversight but is still five times as fast as the current manual method. The model is specific to segmentation of autophagic bodies in yeast TEM images, but researchers working in other systems can use a similar process to generate their own Cellpose 2.0 models to attempt automated segmentations. Our model and instructions for its use are presented here for the autophagy community.Abbreviations: AB, autophagic body; AvP, average precision; GUI, graphical user interface; IoU, intersection over union; MVB, multivesicular body; ROI, region of interest; TEM, transmission electron microscopy; WT,wild type.

Men's involvement in maternal health in sub-Saharan Africa: A scoping review of enablers and barriers.

BACKGROUND: Globally, there are about 800 maternal deaths every day, with low-to-middle-income countries accounting for most of these deaths. A lack of access to maternal healthcare services is one of the main causes of these deaths. In sub-Saharan Africa (SSA), one of the barriers to accessing maternal healthcare services by women is a lack of their male partners' involvement. This scoping review aimed to assess the enablers and barriers to men's involvement in maternal healthcare services. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist was used as a guide for this review. We searched for peer-reviewed articles published between 2013 and 2023 in the English language from SCOPUS, ScienceDirect, PubMed, Africa Journals Online (AJOL), and Google Scholar databases. Two reviewers independently conducted the data extraction and article selection. All of the authors discussed and decided on the codes and categories for enablers and barriers after using NVivo to generate them. RESULTS: Twenty-seven articles were used in this review. Of these, seventeen were qualitative studies, six were quantitative studies, and four were mixed-methods studies. The enablers of men's involvement in maternal healthcare were grouped into sociodemographic factors, health system factors, and policy factors, while barriers were grouped into sociodemographic, cultural, economic, and health system barriers. The lack of maternal health knowledge, insufficient economic resources, and unfriendly staff at healthcare facilities all contributed to a lack of involvement by men. CONCLUSION: To improve men's involvement in maternal healthcare in SSA, there should be economic empowerment of both men and women, health education, and the provision of adequate infrastructure in healthcare facilities to accommodate men.

Prospective diagnostic accuracy study of history taking and physical examination for adults with vertigo in general practice: study protocol.

INTRODUCTION: Vertigo is a prevalent and burdensome symptom. More than 80% of patients with vertigo are primarily treated by their general practitioner (GP) and are never referred to a medical specialist. Despite this therapeutic responsibility, the GP's diagnostic toolkit has serious limitations. All recommended tests lack empirical evidence, because a diagnostic accuracy study on vestibular disorders ('How well does test x discriminate between patients with or without target condition y?') has never been performed in general practice. The VERtigo DIagnosis study aims to fill this gap. METHODS AND ANALYSIS: We will perform a diagnostic accuracy study on vertigo of primary vestibular origin in general practice to assess the discriminative ability of history taking and physical examination. We will compare all index tests with a respective reference standard. We will focus on five target conditions that account for more than 95% of vertigo diagnoses in general practice: (1) benign paroxysmal positional vertigo, (2) vestibular neuritis, (3) Ménière's disease, (4) vestibular migraine (VM) and (5) central causes other than VM. As these five target conditions have a different pathophysiology and lack one generally accepted gold standard, we will use consensus diagnosis as a construct reference standard. Data for each patient, including history, physical examination and additional tests as recommended by experts in an international Delphi procedure, will be recorded on a standardised form and independently reviewed by a neurologist and otorhinolaryngologist. For each patient, the reviewers have to decide about the presence/absence of each target condition. We will calculate sensitivity, specificity, predictive values, likelihood ratios and diagnostic ORs, followed by decision rules for each target condition. ETHICS AND DISSEMINATION: The study obtained approval from the Vrije Universiteit Medical Center Medical Ethical Review Committee (reference: 2022.0817-NL83111.029.22). We will publish our findings in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ISRCTN97250704.

Mastering your fellowship: Part 2, 2024.

The 'Mastering your Fellowship' series provides examples of the question format encountered in the written and clinical examinations, Part A of the Fellowship of the College of Family Physicians of South Africa (FCFP [SA]) examination. The series is aimed at helping family medicine registrars prepare for this examination.

From the President's Desk: Part 1, 2024.

No abstract available.

Health budget cuts will be paid for by the most vulnerable.

No abstract available.

Turbulence causes kinematic and behavioural adjustments in a flapping flier.

Turbulence is a widespread phenomenon in the natural world, but its influence on flapping fliers remains little studied. We assessed how freestream turbulence affected the kinematics, flight effort and track properties of homing pigeons (Columba livia), using the fine-scale variations in flight height as a proxy for turbulence levels. Birds showed a small increase in their wingbeat amplitude with increasing turbulence (similar to laboratory studies), but this was accompanied by a reduction in mean wingbeat frequency, such that their flapping wing speed remained the same. Mean kinematic responses to turbulence may therefore enable birds to increase their stability without a reduction in propulsive efficiency. Nonetheless, the most marked response to turbulence was an increase in the variability of wingbeat frequency and amplitude. These stroke-to-stroke changes in kinematics provide instantaneous compensation for turbulence. They will also increase flight costs. Yet pigeons only made small adjustments to their flight altitude, likely resulting in little change in exposure to strong convective turbulence. Responses to turbulence were therefore distinct from responses to wind, with the costs of high turbulence being levied through an increase in the variability of their kinematics and airspeed. This highlights the value of investigating the variability in flight parameters in free-living animals.