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A scoping review of stroke services within the Philippines
No full textBACKGROUND: Stroke is a leading cause of mortality and disability. In higher-income countries, mortality and disability have been reduced with advances in stroke care and early access to rehabilitation services. However, access to such services and the subsequent impact on stroke outcomes in the Philippines, which is a lower- and middle-income countries (LMIC), is unclear. Understanding gaps in service delivery and underpinning research from acute to chronic stages post-stroke will allow future targeting of resources. AIMS: This scoping review aimed to map available literature on stroke services in the Philippines, based on Arksey and O'Malley's five-stage-process. A targeted strategy was used to search relevant databases (Focused: MEDLINE (ovid), EMBASE (ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO (ebsco); broad-based: Scopus; review-based: Cochrane Library, International Prospective Register of Systematic Reviews (PROSPERO), JBI (formerly Joanna Briggs Institute) as well as grey literature (Open Grey, Google scholar). The searches were conducted between 12/2022-01/2023 and repeated 12/2023. Literature describing adults with stroke in the Philippines and stroke services that aimed to maximize well-being, participation and function were searched. Studies were selected if they included one or more of: (a) patient numbers and stroke characteristics (b) staff numbers, qualifications and role (c) service resources (e.g., access to a rehabilitation unit) (d) cost of services and methods of payment) (e) content of stroke care (f) duration of stroke care/rehabilitation and interventions undertaken (g) outcome measures used in clinical practice. A total of 70 papers were included. Articles were assessed, data extracted and classified according to structure, process, or outcome related information. Advances in stroke services, including stroke ready hospitals providing early access to acute care such as thrombectomy and thrombolysis and early referral to rehabilitation coupled with rehabilitation guidelines have been developed. Gaps exist in stroke services structure (e.g., low number of neurologists and neuroimaging, lack of stroke protocols and pathways, inequity of stroke care across urban and rural locations), processes (e.g., delayed arrival to hospital, lack of stroke training among health workers, low awareness of stroke among public and non-stroke care workers, inequitable access to rehabilitation both hospital and community) and outcomes (e.g., low government insurance coverage resulting in high out-of-pocket expenses, limited data on caregiver burden, absence of unified national stroke registry to determine prevalence, incidence and burden of stroke). Potential solutions such as increasing stroke knowledge and awareness, use of mobile stroke units, TeleMedicine, TeleRehab, improving access to rehabilitation, upgrading PhilHealth and a unified national long-term stroke registry representing the real situation across urban and rural were identified. CONCLUSION: This scoping review describes the existing evidence-base relating to structure, processes and outcomes of stroke services for adults within the Philippines. Developments in stroke services have been identified however, a wide gap exists between the availability of stroke services and the high burden of stroke in the Philippines. Strategies are critical to address the identified gaps as a precursor to improving stroke outcomes and reducing burden. Potential solutions identified within the review will require healthcare government and policymakers to focus on stroke awareness programs, primary and secondary stroke prevention, establishing and monitoring of stroke protocols and pathways, sustainable national stroke registry, and improve access to and availability of rehabilitation both hospital and community. WHAT IS ALREADY KNOWN?: Stroke services in the Philippines are inequitable, for example, urban versus rural due to the geography of the Philippines, location of acute stroke ready hospitals and stroke rehabilitation units, limited transport options, and low government healthcare insurance coverage resulting in high out-of-pocket costs for stroke survivors and their families. WHAT ARE THE NEW FINDINGS?: The Philippines have a higher incidence of stroke in younger adults than other LMICs, which impacts the available workforce and the country's economy. There is a lack of data on community stroke rehabilitation provision, the content and intensity of stroke rehabilitation being delivered and the role and knowledge/skills of those delivering stroke rehabilitation, unmet needs of stroke survivors and caregiver burden and strain, WHAT DO THE NEW FINDINGS IMPLY?: A wide gap exists between the availability of stroke services and the high burden of stroke. The impact of this is unclear due to the lack of a compulsory national stroke registry as well as published data on community or home-based stroke services that are not captured/published. WHAT DOES THIS REVIEW OFFER?: This review provides a broad overview of existing evidence-base of stroke services in the Philippines. It provides a catalyst for a) healthcare government to address stroke inequities and burden; b) development of future evidence-based interventions such as community-based rehabilitation; c) task-shifting e.g., training non-neurologists, barangay workers and caregivers; d) use of digital technologies and innovations e.g., stroke TeleRehab, TeleMedicine, mobile stroke units.Published vesionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery
No full textBACKGROUND: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. METHODS: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. RESULTS: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. CONCLUSIONS: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation."Published version, accepted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals
No full textINTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.Published version, accepted version, submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome
No full textAround 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes(1). Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome(2). We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.Accepted version (6 month embargo), submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Practical considerations for continuous glucose monitoring in elite athletes with type 1 diabetes mellitus: A narrative review
No full textType 1 diabetes mellitus (T1DM) refers to a metabolic condition where a lack of insulin impairs the usual homeostatic mechanisms to control blood glucose levels. Historically, participation in competitive sport has posed a challenge for those with T1DM, where the dynamic changes in blood glucose during exercise can result in dangerously high (hyperglycaemia) or low blood glucoses (hypoglycaemia) levels. Over the last decade, research and technological development has enhanced the methods of monitoring and managing blood glucose levels, thus reducing the chances of experiencing hyper- or hypoglycaemia during exercise. The introduction of continuous glucose monitoring (CGM) systems means that glucose can be monitored conveniently, without the need for frequent fingerpick glucose checks. CGM devices include a fine sensor inserted under the skin, measuring levels of glucose in the interstitial fluid. Readings can be synchronized to a reader or mobile phone app as often as every 1-5 min. Use of CGM devices is associated with lower HbA1c and a reduction in hypoglycaemic events, promoting overall health and athletic performance. However, there are limitations to CGM, which must be considered when being used by an athlete with T1DM. These limitations can be addressed by individualized education plans, using protective equipment to prevent sensor dislodgement, as well as further research aiming to: (i) account for disparities between CGM and true blood glucose levels during vigorous exercise; (ii) investigate the effects of temperature and altitude on CGM accuracy, and (iii) explore of the sociological impact of CGM use amongst sportspeople without diabetes on those with T1DM.0RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Predictors of appendicectomy one year after antibiotic treatment for acute appendicitis: Insights from a prospective, multicentre, observational study
No full textBACKGROUND: Surgeons are sometimes reluctant to manage uncomplicated appendicitis non-operatively. Reasons cited include the risk of recurrent appendicitis and the risk of missed appendiceal malignancy. The aim of this study was to address these uncertainties and determine the long-term efficacy of antibiotic versus operative management of appendicitis. METHOD: One-year follow-up of patients enrolled in the multicentre, COVID:HAREM cohort study during March-June 2020 was performed. Initial operative or non-operative management was determined on a case-by-case basis by the responsible surgeon. Outcomes were appendicectomy rate at 1-year, histology of removed appendix and predictors of unsuccessful antibiotic treatment. RESULTS: A total of 625 patients who had non-operative management were included. Emergency appendicectomy had been performed by 1-year in 24% (149/625), with a median time to appendicectomy of 12 days [IQR 1-77] from presentation. Thirty-one patients had elective appendicectomy. Normal histology was reported in 6% of emergency procedures and 58% of elective ones. There were 7 malignancies and 3 neuroendocrine tumors identified at histology. All patients with malignant histology had ≥1 risk factors for malignancy at initial presentation. Faecolithiasis (hazard ratios (HR) 2.3, 95% confidence intervals (CI) 1.51-3.49) and a high Adult Appendicitis Score (AAS >16; HR 2.44, 95% CI 1.52-3.92) were independent risk factors for unsuccessful non-operative management. CONCLUSION: At 1 year, 71% of patients managed non-operatively did not undergo an appendicectomy. Recurrence of appendicitis was associated with faecolithiasis and a high AAS. Patients at higher risk for appendiceal malignancy should have targeted follow-up. These factors should be considered when counseling patients on non-operative management.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
The impact of the COVID-19 pandemic and the changing landscape of CF on the cASPerCF trial: a real-world experience
No full textJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope
No full textThis guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.Published version, accepted version, submitted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
A Hidden Threat: Hydatid Cyst Masked by Bacterial Infection
No full textHydatid cysts are parasitic infections that primarily affect the liver, but complications like secondary bacterial infections can obscure the clinical presentation. Though infections are common in general practice, hepatic abscesses, particularly those associated with hydatid cysts, are rare and often manifest with non-specific symptoms, leading to delayed diagnosis. Given the risk of serious complications such as rupture and sepsis, maintaining a high index of suspicion is critical, especially in patients with risk factors like a history of travel to endemic regions, liver disease, or excessive alcohol consumption. This case report highlights the clinical challenge posed by a hydatid cyst complicated by bacterial infection. The patient's non-specific complaints initially masked the true pathology, resulting in a delayed recognition of the hepatic abscess. Prompt recognition of this condition, despite its rare presentation, is crucial for timely intervention and improved patient outcomes.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
I Live With Lynch. Cancer Worry Ebbs Into the Background, Then Something Brings It to the Fore.' A Qualitative Interview Study Exploring How Lynch Syndrome Carriers Make Sense of Their Cancer Risks and Implications to Support Decision Making
No full textBACKGROUND: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management? METHODS: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK. Semi-structured interviews explored lived experiences of carriers' access to care with a focus on decision support. Themes were constructed using framework analysis. These were developed into a conceptual model with recommendations for codevelopment of improved information and support including a tailored decision aid to complement integrated healthcare. RESULTS: Twenty participants included 12 women and eight men, half with a history of cancer. Six overarching themes were: (1) finding balance with Lynch; (2) living 'on higher alert'; (3) managing uncertainty: 'I've thought about it a lot'; (4) burden of responsibility: 'It's on me'; (5) access to joined-up care and support: 'There's something missing'; and (6) influence/pressure from others. CONCLUSIONS: This qualitative interview study provided in-depth insights from Lynch syndrome carriers about their lived experiences, informed by their values. Recommendations to empower carriers to make sense of genetic cancer risks and support decisions included accessible, trusted information, educated healthcare professionals, shared decision making, and joined-up integrated care pathways complemented by tailored decision aids.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.New Full Text unavailable for 1 year from time of publication. Please click an article to explore additional access options