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Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice
No full textInfertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. ?y bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility.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
Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder
No full textSequence variants in the HERC2 gene are associated with a significant reduction in HERC2 protein levels and cause a neurodevelopmental disorder known as the HERC2-related disorder, which shares clinical features with Angelman syndrome, including global developmental delay, intellectual disability, autism, and movement disorders. Remarkably, the HERC2 gene is commonly deleted in individuals with Angelman syndrome, suggesting a potential contribution of HERC2 to the pathophysiology of this disease. Given the known critical role of autophagy in brain development and its implication in neurodevelopmental diseases, we undertook different experimental approaches to monitor autophagy in fibroblasts derived from individuals affected by the HERC2-related disorder. Our findings reveal alterations in the levels of the autophagy-related protein LC3. Furthermore, experiments with lysosomal inhibitors provide confirmation of an upregulation of the autophagy pathway in these patient-derived cells. Mechanistically, we corroborate an interaction between HERC2 and the deubiquitylating enzyme USP20; and demonstrate that HERC2 deficiency leads to increased USP20 protein levels. Notably, USP20 upregulation correlates with enhanced stability of the autophagy initiating kinase ULK1, highlighting the role of HERC2 as an autophagy regulator factor through the USP20-ULK1 axis. Moreover, we show that p38 acts as a modulator of this pathway, since p38 activation disrupts HERC2-USP20 interaction, leading to increased USP20 and LC3-II protein levels. Together, these findings uncover a previously unknown role for HERC2 in autophagy regulation and provide insights into the pathomolecular mechanisms underlying the HERC2-related disorder and Angelman syndrome.Published versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embarg
Hypophosphatemia attenuates improvements in vitality after intravenous iron treatment in patients with inflammatory bowel disease
No full textPURPOSE: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. METHODS: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. RESULTS: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). CONCLUSIONS: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.Published 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 (12 month embargo)
Age-related disparities in complications among women with peripartum cardiomyopathy
No full textINTRODUCTION: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age. METHODS: Records from the 2016-2020 National Inpatient Sample were used for our study. The sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in in-hospital complications between the two groups using multivariable regression. RESULTS: The analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, of whom 57.3 % were in the 30-40 years cohort and 42.7 % in the 15-29 years group. The prevalence of cardiovascular risk factors such as smoking, obesity, hypertension, diabetes and lipid disorder was higher among women aged 30-40 years (p < 0.01). These patients also demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95 % CI 1.038-1.767, p = 0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95 % CI 0.688-0.901, p < 0.01) as compared to those aged 15-29 years during their hospitalisation with PPCM. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95 % CI 0.976-1.182, p = 0.143), acute pulmonary oedema (aOR 1.147, 95 % CI 0.988-1.332, p = 0.071) or in-hospital mortality (aOR 0.978, 95 % CI 0.742-1.290, p = 0.877). CONCLUSION: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock.Published version, accepted version (12 month embargo), submitted versionNot hel
Not all knees are the same
No full textThe aim of mechanical alignment in total knee arthroplasty is to align all knees into a fixed neutral position, even though not all knees are the same. As a result, mechanical alignment often alters a patient's constitutional alignment and joint line obliquity, resulting in soft-tissue imbalance. This annotation provides an overview of how the Coronal Plane Alignment of the Knee (CPAK) classification can be used to predict imbalance with mechanical alignment, and then offers practical guidance for bone balancing, minimizing the need for soft-tissue releases.unknownNot hel
The Getting It right First Time (GIRFT) programme in urology; rationale and methodology
No full textThe Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.Published version, accepted version (12 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
Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study
No full textContemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030.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 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
Switching to reusable cartridge insulin pens can reduce National Health Service costs while delivering environmental benefits
No full textPublished version, accepted version (12 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