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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
When I use a word . . . Medicines regulation-diethylene glycol.
In 1937, when diethylene glycol was used as a solvent in the preparation of a medicinal product, an elixir of sulfanilamide, resulting in deaths, public outcry hastened the promulgation of an act that had been in preparation in the USA for several years, but which had met with opposition from pharmaceutical companies. The 1938 Food, Drug, and Cosmetics Act, as it was known, gave greater powers to the then recently formed Food and Drug Administration (FDA) in regulating the contents of medicinal formulations. Nevertheless, although similar regulatory systems have since been established around the world, episodes of poisoning with diethylene glycol in pharmaceutical formulations, whether deliberately included adulteration or as a contaminant, continue to be reported, generally in developing countries, usually affecting children, and often causing deaths.
Parliamentary reaction to the announcement and implementation of the UK Soft Drinks Industry Levy: applied thematic analysis of 2016-2020 parliamentary debates.
Objective: The UK Soft Drinks Industry Levy (SDIL) (announced March 2016; implemented April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order understand how health policy can become established and resilient to opposition. Design: Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus. Setting: The United Kingdom Parliament Participants: N/A Results: Between the announcement (16/03/2016) - royal assent (26/04/2017) two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent - implementation (5/04/2018) one theme was identified 3: The SDIL worked - what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL. Conclusions: After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.
Managing recurrent vulvovaginal thrush from patient and healthcare professional perspectives: A systematic review and thematic synthesis
Objective: This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising published findings. Methods: Five databases were searched for studies on patient and healthcare professional experiences managing recurrent thrush. Two reviewers independently screened and quality assessed qualitative, quantitative, and mixed-methods studies. Findings from eligible studies were thematically synthesised. Results: 720 papers were identified, and 29 were included. Four descriptive themes were developed to depict the repeated management of recurrent thrush. These themes were: (re)experiencing impacts, (re)identifying recurrent thrush, (re)considering consultations, and (re)trying treatments. An analytic high-order frame of ‘interwoven and reoccurring uncertainties’ was used to understand these themes. Conclusions: Patients and healthcare providers face uncertainties when managing recurrent thrush. The inconsistencies raised across papers suggests an unaddressed gap in knowledge about patient experiences and their informational and support needs; this includes insights about this condition's diagnosis, management, treatment, impacts, and meaning. Practice implications: This review has implications for patient education, health promotion, and communication between patients and providers. Our interpretations suggest the need for more research and resources to help support patients and clinicians in managing this condition to promote more understanding, communication, and collaborative care.
Not just surveys and indicators: narratives capture what really matters for health system strengthening
Health system strengthening remains elusive and challenging. Health systems in many countries in sub-Saharan Africa are frequently characterised as weak, with inadequate management and accountability mechanisms, and poor human and financial resources. Putting patients and staff at the heart of health systems is an essential step towards strengthening them. As one of the three pillars of quality in health care, understanding patient experiences is key to moving towards people-centred care. Yet patient experiences are not a singular concept. Patient narratives can convey individual experiences of illness and health care, which complement and augment epidemiological and public health evidence. These narratives, gathered with rigorous, interview-based research and shared with digital tools (audio and video), can generate persuasive evidence. This evidence has important potential for influencing policy and practice, and for supporting people-centred care, but has not been tested systematically in low-income countries. In the Kenyan context of newborn health, work under way is generating evidence to show the transformative potential of patient narratives.
Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study
Background: The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. Methods: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). Findings: Of 6,670,829 adults, we identified 516,491 (7.7%) with CKD, including 32.8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26.8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of people with CKD and co-existing T2D were indicated for treatment, compared to those without T2D (62.8% [n = 106,468] vs. 9.1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17.0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22.0% (n = 23,464) in those with T2D, and <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67–0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77–0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68–0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor, compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45–60 mL/min/1.73 m2 OR 0.65, 95% CI 0.62–0.68, p <0.0001, eGFR 30–45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69–0.78, p <0.0001, eGFR 15–30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46–0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00–0.23, p = 0.0037, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3–30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0.78, 95% CI 0.75–0.82, p <0.0001). Interpretation: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D. Funding: None.
Immigration and health outcomes: A study on native health perception and limitations in Europe
This study examines the impact of immigration on the self-perceived health of natives in 16 European countries from 2006 to 2018. Utilizing data from the European Union Statistics on Income and Living Conditions (EU-SILC) and the European Union Labor Force Survey (EU-LFS), we focus on two health outcomes: natives’ self-perceived health and health-related limitations in daily activities. Contrary to concerns, our findings indicate a positive influence of immigration on natives’ health perception and a reduction in health-related limitations. Noteworthy variations by gender and age emerge, with more pronounced benefits in countries with lower human capital. These results underscore the potential health advantages of immigration, emphasizing the necessity for nuanced immigration policies that consider societal impact and call for a comprehensive evaluation of immigration's effects.
Infection, delirium, and risk of dementia in patients with and without white matter disease on previous brain imaging: a population-based study.
BACKGROUND: The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. METHODS: We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94 567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. FINDINGS: From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86-1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47-4·74; p=0·0013 vs 3·41, 1·91-6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23-7·19 vs 3·94, 1·95-7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04-2·94 vs 0·68, 0·39-1·20; pdiff=0·023). INTERPRETATION: The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. FUNDING: National Institute for Health and Care Research and Wellcome Trust.
Disparities in COVID-19 Mortality Amongst the Immunosuppressed: A Systematic Review and Meta-analysis for Enhanced Disease Surveillance.
BACKGROUND: Effective disease surveillance, including that for COVID-19, is compromised without a standardised method for categorising the immunosuppressed as a clinical risk group. METHODS: We conducted a systematic review and meta-analysis to evaluate whether excess COVID-associated mortality compared to the immunocompetent could meaningfully subdivide the immunosuppressed. Our study adhered to UK Immunisation against infectious disease (Green Book) criteria for defining and categorising immunosuppression. Using OVID (EMBASE, MEDLINE, Transplant Library, and Global Health), PubMed, and Google Scholar, we examined relevant literature between the entirety of 2020 and 2022. We selected for cohort studies that provided mortality data for immunosuppressed subgroups and immunocompetent controls. Meta-analyses, grey literature and any original works that failed to provide comparator data or reported all-cause or paediatric outcomes were excluded. Odds Ratios (OR) and 95% confidence intervals (CI) of COVID-19 mortality were meta-analysed by immunosuppressed category and subcategory. Subgroup analyses differentiated estimates by effect measure, country income, study setting, level of adjustment, use of matching and publication year. Study screening, extraction and bias assessment were performed blinded and independently by two researchers; conflicts were resolved with the oversight of a third researcher. PROSPERO registration number is CRD42022360755. FINDINGS: We identified 99 unique studies, incorporating data from 1,542,097 and 56,248,181 unique immunosuppressed and immunocompetent patients with COVID-19 infection, respectively. Compared to immunocompetent people (pooled OR, 95%CI), solid organ transplants (2.12, 1.50-2.99) and malignancy (2.02, 1.69-2.42) patients had a very high risk of COVID-19 mortality. Patients with rheumatological conditions (1.28, 1.13-1.45) and HIV (1.20, 1.05-1.36) had just slightly higher risks than the immunocompetent baseline. Case type, setting income and mortality data matching and adjustment were significant modifiers of excess immunosuppressed mortality for some immunosuppressed subgroups. INTERPRETATION: Excess COVID-associated mortality among the immunosuppressed compared to immunocompetent was seen to vary significantly across subgroups. This novel means of subdivision has prospective benefit for targeting patient triage, shielding and vaccination policies during periods of high disease transmission. FUNDING: Supported by EMIS Health and the UK Medical Research Council. Grant number: MR/R015708/1.
Predicting the risk of acute kidney injury in primary care:
Background Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks. Aim To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment. Design and setting Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England. Method People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n = 1 772 618), using a Fine–Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n = 3 805 322). Results The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk. Conclusion This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.
The diagnostic Accuracy of Visual versus automated dipstick proteinuria testing in Pregnancy: A systematic review and Meta-Analysis
Objective: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. Design: Systematic review and meta-analysis. Data Sources: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. Eligibility Criteria and Data Analysis: Included studies measured the sensitivity and specificity of POC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determined heterogeneity. Main Outcome Measures: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within the subgroups test brand, reference standard, and hypertension status. Results: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. Conclusion: Visual dipsticks have comparable accuracy to automated readers, yet are not adequate as a rule-out test for proteinuria. Proteinuria POC testing may be beneficial in antenatal care when repeat follow-up tests are performed. PROSPERO Registration Number: CRD42021231914.