The long-term impact of vaginal surgical mesh devices on pain clinic and psychological service referrals, anti-inflammatory testing and pelvic scans in UK primary care: A cohort study with the Clinical Practice Research Datalink.

OBJECTIVE: To examine long-term complications in women with stress urinary incontinence (SUI) and pelvic organ prolapse (POP), with and without surgical mesh implants. DESIGN: Longitudinal open cohort study from 1 April 2006 (or 1 April 2012) to 30 November 2018. SETTING: The Clinical Practice Research Datalink (CPRD) Gold database, which is linked to Hospital Episodes Statistics (HES) inpatient data, the HES Diagnostic Imaging Dataset (DID), Office for National Statistics mortality data and Index of Multiple Deprivation socio-economic status data. SAMPLE: Women aged ≥18 years with a diagnostic SUI/POP Read code. METHODS: Rates are estimated using negative binomial regression. MAIN OUTCOME MEASURES: Rates of referrals for: psychological and pain services; urinalysis, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) testing; and pelvic ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) scans. RESULTS: A cohort of 220 544 women were eligible for inclusion; 74% (n = 162 687) had SUI, 37% (n = 82 123) had POP and 11% (n = 24 266) had both. Rates of psychological referrals and CT scans were lower in women with SUI mesh surgery, but this was offset by higher rates of CRP testing in women with SUI or POP mesh, MRI scans in women with SUI mesh, and urinalysis testing and referrals to pain clinics for women with POP mesh. CONCLUSIONS: Our results suggest a higher burden of morbidity in women with SUI/POP mesh surgery, and that these women may require ongoing follow-up in the primary care setting.

GPs' perspectives on diagnostic tests for children: a qualitative interview study.

BACKGROUND: Most healthcare contacts for children in the UK occur in general practice. Diagnostic tests can be beneficial in narrowing differential diagnoses; however, there is substantial variation in the use of tests for children in general practice. Unwarranted variation in testing can lead to variation in quality of care and may exacerbate health inequities. To our knowledge, no previous study has tried to understand why variation in testing exists for children in general practice. AIM: To explore GPs' perspectives on using diagnostic tests for children in primary care and the underlying drivers of variation. DESIGN AND SETTING: Qualitative study in which semi-structured interviews were conducted with GPs and trainee GPs in England. METHOD: Interviews were conducted with 18 GPs and two trainee GPs between April and June 2023. The interviews were transcribed and analysed using reflexive thematic analysis. RESULTS: GPs reflected that their approach to testing in children differed from their approach to testing in adults: their threshold to test was higher, and their threshold to refer to specialists was lower. GPs' perceptions of test utility varied, including objective testing for asthma. Perceived drivers of variation in testing were intrinsic (clinician-specific) factors relating to their risk tolerance and experience; and extrinsic factors, including disease prevalence, parental concern and expectations of health care, workforce changes leading to fragmentation in care, time constraints, and differences in guidelines. CONCLUSION: The findings of this study identify actionable issues for clinicians, researchers, and policymakers to address gaps in education, evidence, and guidance, reduce unwarranted differences in test use, and improve the quality of health care delivered to children in general practice.

An overview of childhood cancer care and outcomes in Egypt: a narrative review.

Childhood cancer is an urgent priority in Egypt, owing to a large number of children with cancer, the great need and demand for paediatric oncology services, limited resources/funds and inferior survival outcomes. Therefore, an overview of the status of childhood cancer care in Egypt and an evidence-based approach towards optimal utilisation of resources/funds to improve this care are needed. This paper summarises key evidence about childhood cancer care and outcomes in Egypt. We conducted a narrative literature review using a structured search strategy of the MEDLINE database through the PubMed interface. All relevant evidence was summarised under five main sub-topics: (1) burden of childhood cancer in Egypt; (2) treatment approaches; (3) health outcomes; (4) costs and cost-effectiveness of treatment; and (5) barriers and facilitators to optimal childhood cancer care. We found high estimates of disease burden of childhood cancer in Egypt. Furthermore, childhood cancer treatment in Egypt is based on either implementing intensity-regulated protocols or adopting international protocols with or without adaptations to local contexts, leading to varying standards of care among the different treating centres. Limited data about the survival outcomes, costs and cost-effectiveness of treatment exist, although high-quality data from retrospective cohort studies were published from a large paediatric oncology centre (Children's Cancer Hospital Egypt-57357). As Egypt joins the WHO Global Initiative for Childhood Cancers as a focus country, it is prepared to move towards streamlining national efforts to implement a national childhood cancer plan to advance care, improve health outcomes and optimise resource use. Through these efforts, Egypt could become a beacon of hope and a role model to other low- and middle-income countries seeking to improve their childhood cancer care.

Availability of results of clinical trials registered on EU Clinical Trials Register: cross sectional audit study.

Objective: To identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository. Design: Cross sectional audit study. Setting: EUCTR protocols and results sections, data extracted 1-3 December 2020. Population: Random sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018). Main outcome measures: Proportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route. Results: In the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1). Conclusions: EUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.

Trends in diagnostic tests ordered for children: a retrospective analysis of 1.7 million laboratory test requests in Oxfordshire, UK from 2005 to 2019.

OBJECTIVE: To better understand testing patterns in children, we measured temporal trends in paediatric testing from 2005 to 2019 in Oxfordshire, UK. DESIGN: Descriptive study of population-based secondary data. SETTING: Oxfordshire University Hospitals National Health Service Trust laboratories. PARTICIPANTS: Children aged 0-15 years in Oxfordshire who received at least one blood test. MAIN OUTCOME MEASURES: We estimated average annual percentage changes (AAPCs) in test use using joinpoint regression models. Temporal changes in age-adjusted rates in test use were calculated overall and stratified by healthcare setting, sex, and age. RESULTS: Between 2005 and 2019, 1 749 425 tests were performed among 113 607 children. Overall test use declined until 2012, when test rates appeared to increase (AAPC 1.5%, 95% CI -0.8% to 3.9%). Most tests were performed in inpatient settings, where testing rates stayed steady (AAPC -0.6%, 95% CI -2.1% to 0.9%). Increases were highest in females, those aged 6-15 years and in the outpatient setting. The greatest increase in testing was for vitamin D (AAPC 26.5%), followed by parathyroid hormone (9.8%), iron studies (9.3%), folate (8.4%), vitamin B12 (8.4%), HbA1c (8.0%), IgA (7.9%) and coeliac (7.7%). CONCLUSIONS: After an initial decline, laboratory test use by children in Oxfordshire demonstrated an apparent increase since 2012. Test use increased in outpatient and general practice settings, however remained steady in inpatient settings. Further research should examine the root causes and implications for test increases, and whether these increases are warranted. We encourage clinicians to consider the individual and systemic implications of performing blood tests in children.

Conditional versus non-conditional incentives to maximise return of participant completed questionnaires in clinical trials: a cluster randomised study within a trial.

BACKGROUND: High participant retention enhances the validity of clinical trials. A monetary incentive can increase retention, but it is not known if when it is provided and if it is conditional matters. We aimed to determine whether there was a difference in the number of follow-up trial questionnaires returned when a monetary (gift voucher) incentive was given to participants at recruitment (non-conditional), compared to informing participants at recruitment that the incentive would be given only once their 14-day daily diary (questionnaire) had been returned (conditional). METHOD: A cluster randomised study within a trial embedded within the Antivirals for influenza-Like Illness, An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) Trial. Matched site pairs (GP practices) were randomised using computer-generated random numbers, to either a non-conditional or conditional monetary voucher incentive (only once their 14-day daily diary (questionnaire) had been returned. Sites were matched on previous recruitment levels and practice list size. Analyses were conducted according to randomised groups irrespective of compliance with a two-sided 5% level statistical significance level. The main analysis of the primary outcome (site proportion of diaries returned) was linear regression accounting for site pair (using cluster-robust variance). Additional weighted, paired and non-parametric sensitivity analyses were conducted. Secondary outcomes were the site average number of completed pages, time to return diary, and cost related to the incentive (administration and postage). RESULTS: Of the 42 randomised sites (21 for each intervention), only 28 recruited at least one participant with only 10 practice pairs recruiting participants at both constituent sites. Raw diaries return proportions were 0.58 (127/220) and 0.73 (91/125) for non-conditional and conditional incentive groups. Regression analysis adjusted for site pair showed no significant difference in returns, - 0.09, (95% CI, - 0.29, 0.10, p = 0.34); when weighted, there was still no clear difference: 0.15 (95% CI, - 0.02, 0.31, p = 0.07). There was no clear statistical evidence of a difference in time taken to return questionnaires, nor the proportion of pages completed, by the intervention group in the main analyses (all p > 0.05). The conditional incentive was approximately £23 cheaper per diary returned based upon observed data. CONCLUSION: There was no clear evidence of a statistically significant difference in the proportion of participant-completed diaries returned between conditional or non-conditional incentive groups. The time to questionnaire return and completeness of the returned questionnaires were similar in both groups. There was substantial statistical uncertainty in the findings. Some of the sensitivity analyses suggested that a meaningful benefit of a conditional incentive of a magnitude that would be meaningful was plausible. The conditional approach costs less in cash terms.

The impact of vaginal surgical mesh devices on consultation rates by type and health care provider in UK primary care: A cohort study in the Clinical Practice Research Datalink.

OBJECTIVES: To examine consultation rates by type of consultation and health care provider in women with stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP), with and without surgical mesh implants. STUDY DESIGN: Longitudinal open cohort study from April 2006 to November 2018 in the Clinical Practice Research Datalink (CPRD). MAIN OUTCOME MEASURES: Rates of consultations with general practitioners (GPs), nurses, other clinicians and administrators by consultation type (face-to-face, telephone or administrative), and types of administrative consultations, estimated using negative binomial regression. RESULTS: Of 220,544 women eligible for inclusion, 74 % (n = 162,687) had SUI, 37 % (n = 82,123) had POP, and 11 % (n = 24,266) had both. Face-to-face consultation rates were stable over time, at about 9 per year. Administrative consultations with GPs and administrators increased between 2006 and 2018, but averaged 31 per year. After adjustment, for both SUI and POP mesh surgery, there were lower rates of face-to-face consultations with GPs, higher rates of face-to-face consultations with other clinicians, higher rates of telephone consultations with GPs and other clinicians, and higher rates of administrative consultations with GPs, nurses and administrators. The higher rate of consultations with GPs coded as administrative consisted of results recording and administrative codes, and the higher rates of consultations with administrators were coded as repeat issue, other, administration and third-party consultations. CONCLUSIONS: Caring for women with mesh places a higher administrative burden on GPs and administrators. There may be potential to reduce this workload through a more streamlined care pathway.

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners' reports.

BACKGROUND: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. METHODS: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. RESULTS: Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). CONCLUSIONS: Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.

Recognition of Coroners' Concerns to Prevent Future Deaths from Medicines: A Systematic Review.

BACKGROUND: Coroners, who hold inquests to determine the causes of unnatural deaths in England and Wales, having recognised factors that could cause other deaths, are legally obliged to signal concerns by sending 'Reports to Prevent Future Deaths' (PFDs) to interested persons. We aimed to establish whether Coroners' concerns about medications are widely recognised. METHODS: We searched MEDLINE, Embase and Web of Science up to 30 November, 2022 for publications linking PFDs and medications using a combination of search terms "coroner*", "inquest*", "medicine*", "medication*" and "prevent*". We also searched the BMJ, a UK journal that carries news items; and the databases Nexis Advance and News On the Web for reports in national newspapers between 2013 and 2022, using the search terms ("regulation 28" OR "prevent future deaths" OR "prevention of future deaths") AND "coroner". We recorded the number of publications, as well as their citations in Google Scholar at 23 May, 2023. RESULTS: Only 11 published papers on medicines referenced UK PFDs, nine of which were from our group. The BMJ carried 23 articles mentioning PFDs, five related to medicines. Of 139 PFDs (out of over 4000) mentioned in national newspapers, only nine related to medicines. CONCLUSIONS: The PFDs related to medicines are not widely referred to in medical journals or UK national newspapers. By contrast, the Australian and New Zealand National Coronial Information System has contributed cases to 206 publications cited in PubMed, of which 139 are related to medicines. Our search suggests that information from English and Welsh Coroners' PFDs is under-recognised, even though it should inform public health. The results of inquiries by Coroners and medical examiners worldwide into potentially preventable deaths involving medicines should be used to strengthen the safety of medicines.

Drug shortages. Part 1. Definitions and harms.

Drug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two-part review, we discuss definitions of drug shortages and so-called stockouts, which are localized shortages, and the harms that they can cause. Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations, but we lack an adequate definition. The problems are too complicated to be encompassed in a brief intensional dictionary-style definition, and that is reflected in the many different attempts at definition that have been proposed. We therefore propose an extensional operational definition that incorporates the processes by which products are manufactured, the causes of shortages and the contributory factors. A definition of this sort allows one to identify the main causes of a particular drug shortage and therefore the remedies that might prevent, mitigate or manage it. In the second part of the review we discuss the causes and solutions in more detail. Adverse drug reactions and medication errors attributable to shortages occur but are not often reported. Adverse reactions to substitute medicines are possible, and errors can occur because of unfamiliarity or unnecessary treatment with replacement medicines. Other harmful outcomes include withdrawal reactions, undertreatment, treatment delays and cancellations, failure of alternatives and disruption of clinical trials.

Drug shortages. Part 2: Trends, causes and solutions.

Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations. In the first part of this review we proposed an operational definition that incorporates the processes by which products are manufactured, the causes of shortages and stock-outs (local shortages), and the contributory factors. Here we discuss causes and possible solutions. Drug shortages have complex causes, and a single cause cannot always be identified. Reasons include lack or shortage of raw materials, manufacturing difficulties, regulatory and political actions, voluntary recalls, just-in-time inventory systems, halts in production for financial or other business reasons, low demand (eg, orphan products, reduced usage), mergers, market shifts (eg, diversion to home markets) and unexpected increases in demand (eg, improved diagnosis, new trial information, epidemics and pandemics, inappropriate use, off-label use). Potential solutions are as diverse as the potential causes. Prevention is hard, because shortages are not easily predicted. Everyone in the supply chain is involved in anticipating and managing shortages, with responsibilities for preventing them or at least trying to mitigate their effects. This includes manufacturers and suppliers, particularly of generic formulations, pharmacists, prescribers, patients and governments. Solutions can therefore be linked to the causes and classified according to where the responsibility for implementing them lies.

Barriers and Facilitators to Implementing Cost-Effective Evidence-Based Childhood Cancer Treatment in a Resource-Limited Setting in Egypt: A Qualitative Interview Study.

PURPOSE: Childhood cancer treatment is complex, resource-intensive, and expensive, and resource-limited settings would benefit from providing cost-effective treatment approaches on the basis of evidence. Effective implementation of cost-effective evidence-based treatment requires knowledge about factors influencing its use. In this study, we determined the clinicians' perceptions of the barriers and facilitators to implementing cost-effective evidence-based treatment for children with cancer in a resource-limited pediatric oncology setting in Egypt. METHODS: We conducted a qualitative study on the basis of semistructured interviews with senior clinicians who make high-level decisions on treatment protocols and tailored decisions for the atypically complicated group of patients. Purposive sampling was used to recruit the participants. Thematic analysis was conducted semantically to develop themes of barriers and facilitators. RESULTS: Fourteen participants agreed to participate in the study: nine pediatric oncologists; three surgeons; and two radiation oncologists. We identified four main themes of barriers and facilitators: awareness and orientation; knowledge, skills, and attitudes; system, resources, and context; and clinical practice. The main barriers included absence of easily available costs/cost-effectiveness data, limited resources and inability to pay for expensive novel (cost-effective) drugs, and gap between evidence and practice. The main facilitators included adopting standard treatment protocols on the basis of clinical effectiveness, leadership support, availability of patients' clinical and cost data from local context, and existing knowledge and skills in clinical research and health economic evaluation. The interview participants also provided suggestions to promote the implementation of cost-effective evidence-based treatment in priority areas. CONCLUSION: Our study findings provide an understanding of the barriers and facilitators affecting the implementation of cost-effective evidence-based treatment for childhood cancers in Egypt. We provide practical recommendations to address the implementation gaps with implications on practice, policy, and research.

The quality of diagnostic guidelines for children in primary care: A meta-epidemiological study.

AIM: To determine the quality of paediatric guidelines relevant to diagnosis of three of the most common conditions in primary care: fever, gastroenteritis and constipation. METHODS: We undertook a meta-epidemiological study of paediatric guidelines for fever, gastroenteritis and gastroenteritis. We systematically searched MEDLINE, Embase, Trip Database, Guidelines International Network, the National Guideline Clearinghouse and WHO from February 2011 to September 2022 for guidelines from high-income settings containing diagnostic recommendations. We assessed the quality of guideline reporting for included guidelines using the AGREE II tool. RESULTS: We included 16 guidelines: fever (n = 7); constipation (n = 4) and gastroenteritis (n = 5). The overall quality across the three conditions was graded moderate (median AGREE II score 4.5/7, range 2.5-6.5) with constipation guidelines rated the highest (median 6/7), and fever rated the lowest (median 3.8/7). Major methodological weaknesses included consideration of guideline applicability. Half of the guidelines did not report involving parent representatives, and 56% did not adequately declare or address their competing interests. CONCLUSIONS: Substantial variations exist in the quality of paediatric guidelines related to the diagnosis of primary care presentations. Better quality guidance is needed for general practitioners to improve diagnosis for children in primary care.

The quality of paediatric asthma guidelines: evidence underpinning diagnostic test recommendations from a meta-epidemiological study.

BACKGROUND: Asthma is one of the most frequent reasons children visit a general practitioner (GP). The diagnosis of childhood asthma is challenging, and a variety of diagnostic tests for asthma exist. GPs may refer to clinical practice guidelines when deciding which tests, if any, are appropriate, but the quality of these guidelines is unknown. OBJECTIVES: To determine (i) the methodological quality and reporting of paediatric guidelines for the diagnosis of childhood asthma in primary care, and (ii) the strength of evidence supporting diagnostic test recommendations. DESIGN: Meta-epidemiological study of English-language guidelines from the United Kingdom and other high-income countries with comparable primary care systems including diagnostic testing recommendations for childhood asthma in primary care. The AGREE-II tool was used to assess the quality and reporting of the guidelines. The quality of the evidence was assessed using GRADE. RESULTS: Eleven guidelines met the eligibility criteria. The methodology and reporting quality varied across the AGREE II domains (median score 4.5 out of 7, range 2-6). The quality of evidence supporting diagnostic recommendations was generally of very low quality. All guidelines recommended the use of spirometry and reversibility testing for children aged ≥5 years, however, the recommended spirometry thresholds for diagnosis differed across guidelines. There were disagreements in testing recommendations for 3 of the 7 included tests. CONCLUSIONS: The variable quality of guidelines, lack of good quality evidence, and inconsistent recommendations for diagnostic tests may contribute to poor clinician adherence to guidelines and variation in testing for diagnosing childhood asthma.

Coinfection with Strongyloides and SARS-CoV-2: A Systematic Review.

BACKGROUND: Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. METHODS: We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. RESULTS: We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. CONCLUSIONS: Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Preventable Deaths Involving Medicines: A Systematic Case Series of Coroners' Reports 2013-22.

INTRODUCTION: Medicines cause over 1700 preventable deaths annually in England. Coroners' Prevention of Future Death reports (PFDs) are produced in response to preventable deaths to facilitate change. The information in PFDs may help reduce medicine-related preventable deaths. OBJECTIVES: We aimed to identify medicine-related deaths in coroners' reports and to explore concerns to prevent future deaths. METHODS: We carried out a retrospective case series of PFDs across England and Wales, dated between 1 July, 2013 and 23 February, 2022, collected from the UK's Courts and Tribunals Judiciary website using web scraping, generating an openly available database: https://preventabledeathstracker.net/ . We used descriptive techniques and content analysis to assess the main outcome criteria: the proportion of PFDs in which coroners reported that a therapeutic medicine or drug of abuse had caused or contributed to a death; the characteristics of included PFDs; coroners' concerns; the recipients of PFDs; and the timeliness of their responses. RESULTS: There were 704 PFDs (18%; 716 deaths) that involved medicines, representing an estimated 19,740 years of life lost (average of 50 years lost per death). Opioids (22%), antidepressants (9.7%), and hypnotics (9.2%) were the most common drugs involved. Coroners expressed 1249 concerns, primarily around the major themes of patient safety (29%) and communication (26%), including minor themes of failures of monitoring (10%) and poor communication between organizations (7.5%). Most expected responses to PFDs (51%; 630/1245) were not reported on the UK's Courts and Tribunals Judiciary website. CONCLUSIONS: One in five coroner-reported preventable deaths involved medicines. Addressing coroners' concerns, including problems with patient safety and communication, should reduce harms from medicines. Despite concerns being raised repeatedly, half of the PFD recipients failed to respond, suggesting that lessons are not generally learned. The rich information in PFDs should be used to foster a learning environment in clinical practice that may help reduce preventable deaths. CLINICAL TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/TX3CS .

Accuracy of self-diagnosis in conditions commonly managed in primary care: diagnostic accuracy systematic review and meta-analysis.

OBJECTIVES: To assess the diagnostic accuracy of self-diagnosis compared with a clinical diagnosis for common conditions in primary care. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews and CINAHL from inception to 25 January 2021. STUDY SELECTION: Eligible studies were prospective or retrospective studies comparing the results of self-diagnosis of common conditions in primary care to a relevant clinical diagnosis or laboratory reference standard test performed by a healthcare service provider. Studies that considered self-testing only were excluded. DATA EXTRACTION: Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2. METHODS AND RESULTS: 5047 records identified 18 studies for inclusion covering the self-diagnosis of three common conditions: vaginal infection (five studies), common skin conditions (four studies) and HIV (nine studies). No studies were found for any other condition. For self-diagnosis of vaginal infection and common skin conditions, meta-analysis was not appropriate and data were reported narratively. Nine studies, using point-of-care oral fluid tests, reported on the accuracy of self-diagnosis of HIV and data were pooled using bivariate meta-analysis methods. For these nine studies, the pooled sensitivity was 92.8% (95% CI, 86% to 96.5%) and specificity was 99.8% (95% CI, 99.1% to 99.9%). Post hoc, the robustness of the pooled findings was tested in a sensitivity analysis only including four studies using laboratory testing as the reference standard. The pooled sensitivity reduced to 87.7% (95% CI, 81.4% to 92.2%) and the specificity remained the same. The quality of all 18 included studies was assessed as mixed and overall study methodology was not always well described. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Overall, there was a paucity of evidence. The current evidence does not support routine self-diagnosis for vaginal infections, common skin conditions and HIV in primary care. PROSPERO REGISTRATION NUMBER: CRD42018110288.

Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status. Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality. Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers. Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy. Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Integrating patient values and preferences in healthcare: a systematic review of qualitative evidence.

OBJECTIVES: To identify and thematically analyse how healthcare professionals (HCPs) integrate patient values and preferences ('values integration') in primary care for adults with non-communicable diseases (NCDs). DESIGN: Systematic review and meta-aggregation methods were used for extraction, synthesis and analysis of qualitative evidence. DATA SOURCES: Relevant records were sourced using keywords to search 12 databases (ASSIA, CINAHL, DARE, EMBASE, ERIC, Google Scholar, GreyLit, Ovid-MEDLINE, PsycINFO, PubMed-MEDLINE, Scopus and Web of Science). ELIGIBILITY CRITERIA: Records needed to be published between 2000 and 2020 and report qualitative methods and findings in English involving HCP participants regarding primary care for adult patients. DATA EXTRACTION AND SYNTHESIS: Relevant data including participant quotations, authors' observations, interpretations and conclusions were extracted, synthesised and analysed in a phased approach using a modified version of the Joanna Briggs Institute (JBI) Data Extraction Tool, as well as EPPI Reviewer and NVivo software. The JBI Critical Appraisal Checklist for Qualitative Research was used to assess methodological quality of included records. RESULTS: Thirty-one records involving >1032 HCP participants and 1823 HCP-patient encounters were reviewed. Findings included 143 approaches to values integration in clinical care, thematically analysed and synthesised into four themes: (1) approaches of concern; (2) approaches of competence; (3) approaches of communication and (4) approaches of congruence. Confidence in the quality of included records was deemed high. CONCLUSIONS: HCPs incorporate patient values and preferences in healthcare through a variety of approaches including showing concern for the patient as a person, demonstrating competence at managing diseases, communicating with patients as partners and tailoring, adjusting and balancing overall care. Themes in this review provide a novel framework for understanding and addressing values integration in clinical care and provide useful insights for policymakers, educators and practitioners. PROSPERO REGISTRATION NUMBER: CRD42020166002.