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Patient harm due to unsafe healthcare is widespread, potentially devastating, and often preventable. Hoping to eliminate avoidable harms, the World Health Organization (WHO) published the Global Patient Safety Action Plan in July 2021. The UK’s National Health Service relies on several measures, including “never events”, “serious incidents”, patient safety events, and coroners’ prevention of future death reports (PFDs) to monitor healthcare quality and safety. We conducted a systematic narrative review of PubMed and medRxiv on 19 February 2023 to explore the strengths and limitations of coroners’ PFDs and whether they could be a safety metric to help meet the WHO’s Global Patient Safety Action Plan. We identified 17 studies that investigated a range of PFDs, including preventable deaths involving medicines and an assessment during the COVID-19 pandemic. We found that PFDs offered important information that could support hospitals to improve patient safety and prevent deaths. However, inconsistent reporting, low response rates to PFDs, and difficulty in accessing, analysing, and monitoring PFDs limited their use and adoption as a patient safety metric for hospitals. To fulfil the potential of PFDs, a national system is required that develops guidelines, sanctions failed responses, and embeds technology to encourage the prevention of future deaths.

Objectives To audit the transparent and open science standards of health and medical sciences journal policies and explore the impact of the COVID-19 pandemic. Design Repeat cross-sectional study. Setting 19 journals listed in Google Scholar's Top Publications for health and medical sciences. Participants Blood, Cell, Circulation, European Heart Journal, Gastroenterology, Journal of Clinical Oncology, Journal of the American College of Cardiology, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, PLoS ONE, Proceedings of the National Academy of Sciences, Science Translational Medicine, The British Medical Journal, The Journal of the American Medical Association, The Lancet, The Lancet Oncology, and The New England Journal of Medicine. Main outcome measures We used the Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) to evaluate journals standards. Results TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2–12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4–12) in May 2021, but overall, scores were very low at both time points. Journal policies scored highest for their adherence to data transparency and scored lowest for preregistration of study protocols and analysis plans and the submission of replication studies. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n = 16) and during (95%; n = 18) the COVID-19 pandemic. Conclusions The COVID-19 pandemic has highlighted the importance of practising open science. However, requirements for open science practices in audited policies were overall low, which may impede progress in health and medical research. As key stakeholders in disseminating research, journals should promote a research culture of greater transparency and more robust open science practices.

IntroductionOpioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown.ObjectiveWe aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over six years.MethodsWe conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, The Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units per 1000 of the population) and public expenditure (GBP, £ per 1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold.Results31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing £2.55 billion (adjusted: £3.68 billion), were sold over-the-counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (£263/1000 in 2013 to £451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n=569) and formulations (n=12) sold varied.ConclusionIn many parts of the world, substantial numbers of people may be purchasing and consuming codeine from over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products.Study protocol pre-registrationhttps://osf.io/ay4mcThe pre-print version of this work is available on medRxiv:https://doi.org/10.1101/2021.04.21.21255888Key pointsCodeine is one of the most accessible pain medicines available worldwide, yet data on its use as an over-the-counter drug has been limited.We found that total sales and expenditure of over-the-counter products containing codeine increased from April 2013 to March 2019, but there was substantial variation in mean sales between countries and the coverage of data reported by IQVIA, with South Africa, France, Japan, the UK, and Poland accounting for 90% of all sales data.In countries with access to over-the-counter codeine products, sales data should be collected, made available, and reviewed to inform regulatory decisions and public health measures to ensure safety.

BackgroundTrends of opioid prescribing in the NHS has been well published, yet trends for the same in private prescribing have not been widely established.AimTo assess trends and geographical variation of controlled opioids prescribed by private prescribers in England.Design and settingA retrospective observational study in English primary healthcare.MethodsData on Schedule 2 and 3 controlled opioids (“controlled opioids”) was obtained from the NHS Business Services Authority (BSA) using freedom of information (FOI) requests between 01 January 2014 and 30 November 2021. Absolute counts and rates of the number of items dispensed per cumulative number of registered private prescribers were calculated and stratified over time, by opioid type, and geographical region.Results128,341 items controlled opioids were prescribed by private prescribers in England between January 2014 and November 2021, which decreased by 50% from 23,339 items (4.09 items/prescriber) in 2014 to 11,573 items (1.49 items/prescriber) in 2020. Methadone (36%) was the most common controlled opioid prescribed privately, followed by morphine (18%), buprenorphine (16%), and oxycodone (12%). Prescriptions were highest in London (74%), followed by the South-East of England (7%). A proportion of items (n=462, 0.35%) were prescribed by “unidentified doctors” where the prescription is not readily attributable to an individual prescriber by the BSA.ConclusionsControlled opioids prescribed by private prescribers in England decreased and were primarily prescribed in London. To ensure patient safety, the monitoring and surveillance of controlled opioids dispensed privately should continue and items linked to “unidentified doctors” should be addressed further.How this fits inThere are concerns over the long-term, high-dose use of opioids in people with chronic pain – trends for which have been described using English NHS prescription data. However, opioids can also be acquired from outside of NHS services, including private prescribers, over-the-counter (e.g. co-codamol), and through online healthcare services and pharmacies or the “dark web”. Without exploring non-NHS data, the full picture of opioid use in England cannot be understood. This study sought to fill this gap by investigating opioids in the private sector. We found that the number of controlled opioid items prescribed by private prescribers in England halved between January 2014 and November 2021, and that most prescribing occurred from prescribers in London. There were also controlled opioid items dispensed by “unidentified doctors”, which must be addressed to ensure patient safety. While there is monitoring of controlled drug prescribing by NHS England Controlled Drug Accountable Officers, expanding access to such data to allow for a greater visibility and wider analysis of non-NHS data, including the private prescribing of controlled opioids, will allow policymakers and clinicians to further assess the implementation of pain guidelines and identify harms that can be addressed to improve patient safety.

ObjectivesTo examine coroners’ Prevention of Future Deaths reports (PFDs) to identify deaths involving SARS-CoV-2 that coroners deemed preventable.DesignConsecutive case series.SettingEngland and Wales.ParticipantsPatients reported in 510 PFDs dated between 01 January 2020 and 28 June 2021, collected from the UK’s Courts and Tribunals Judiciary website using web scraping to create an openly available database,https://preventabledeathstracker.net/.Main outcome measuresConcerns reported by coroners.Public and Patient InvolvementPatients and members of the public were not involved in this study.ResultsSARS-CoV-2 was involved in 23 deaths reported by coroners in PFDs. Twelve deaths were indirectly related to the COVID-19 pandemic, defined as those that were not medically caused by SARS-CoV-2, but were associated with mitigation measures. In 11 cases the coroner explicitly reported that COVID-19 had directly caused death. There was geographical variation in the reporting of PFDs; most (39%) were written by coroners in the North-West of England. The coroners raised 56 concerns, problems in communication being the most common (30%), followed by failure to follow protocols (23%). Organizations in the National Health Service (NHS) were sent the most PFDs (51%), followed by the Government (26%), but responses to PFDs by these organizations were poor.ConclusionsPFDs contain a rich source of information on preventable deaths that has previously been difficult to examine systematically. Our openly available tool (https://preventabledeathstracker.net/) streamlines this process and has identified many concerns raised by coroners that should be addressed during the Government’s inquiry into the handling of the COVID-19 pandemic, so that mistakes made are less likely to be repeated.Study protocol pre-registrationhttps://osf.io/bfypc/Summary boxWhat is already known about this subject?The UK Government has stated that there will be a public inquiry into the handling of the COVID-19 pandemic, to learn lessons for future pandemics.Coroners in England and Wales have a duty to report and communicate information about the deaths they investigate when the coroner believes that action should be taken to prevent future deaths.These reports, called Prevention of Future Death reports (PFDs), had not yet been systematically analysed to identify deaths that occurred during the COVID-19 pandemic.What are the new findings?We created the Preventable Deaths Database (https://preventabledeathstracker.net/) using web scraping to systematically assess PFDs published on the Courts and Tribunal Judiciary website.Between 01 January 2020 and 28 June 2021, one in 20 (4.5%, n=23) PFDs that were published by coroners involved SARS-CoV-2.Coroners raised many concerns about the care of patients in hospitals, care homes, and people in the community during the COVID-19 pandemic, which require action to prevent future deaths.How might it affect clinical practice in the foreseeable future?Preventable deaths that occurred during the COVID-19 pandemic should be referred to the coroner so that an inquest can be performed and a PFD issued, highlightng actions that could be avoided in improving the handling of future pandemics in both the UK and elsewhere.Our tool,https://preventabledeathstracker.net/, can be used by others to examine preventable deaths in England and Wales, and to identify signals for quality improvement to reduce avoidable harms in clinical practice.

BackgroundDeaths from opioids have increased in England and Wales, despite recognition of their harms. Coroners’ Prevention of Future Death reports (PFDs) provide important insights that may enable safer use and avert harms, yet these reports involving opioids have not been synthesised. We therefore aimed to identify opioid-related PFDs and explore concerns expressed by coroners to prevent future deaths.MethodsIn this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022. These were obtained by web scraping the UK’s Courts and Tribunals Judiciary website to create an openly available database:https://preventabledeathstracker.net/. 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 and responses to such concerns.FindingsOpioids were involved in 219 deaths reported by coroners in PFDs (5·6% of all 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 NHS organisations (51%), but response rates were low overall (47%).InterpretationOpioids could be used more safely and appropriately if coroners’ concerns in PFDs were addressed by national organisations such as NHS bodies, government agencies, and policymakers, as well as individual prescribing clinicians.FundingNo funding was obtained for this study. The National Institute for Health Research (NIHR) School for Primary Care Research (SCPR) provided funding to establish the Preventable Deaths Tracker website:https://preventabledeathstracker.net/Research in contextEvidence before this studyWe conducted a systematic search of PubMed and Google Scholar to identify studies of deaths involving opioids in England and Wales and analyses of coroners’ Prevention of Future Death reports (PFDs). We found that deaths from opioids had increased in England and Wales. We also identified studies that have used PFDs to assess preventable deaths during the COVID-19 pandemic and deaths involving anticoagulants, medicines purchased online, medication errors and adverse drug reactions. However, no study to date has examined opioid-related PFDs.Added value of this studyWe analysed coroners’ concerns in opioid-related deaths for which they issued PFDs and found that on average three decades of life are lost per individual. We found that most opioid-related PFDs involved males (64%) and were caused by prescribed opioids (52%). Deaths involving illicit opioids (24%) were more likely to occur in younger males than deaths from prescribed opioids. Failures in systems and processes were most commonly found to have contributed to preventable opioid-related deaths, but more than half of such concerns remain unaddressed.Implications of all the available evidenceCoroners’ PFDs offer important real-world insights into opioid-related deaths and can inform public health strategies that aim to improve the safe use of opioids. Future work should focus on disseminating these findings more widely and engaging with key stakeholders such as NHS organisations and government agencies, so that findings from PFDs can inform guidelines and be implemented in clinical practice.

ObjectivesTo identify medicines-related deaths in coroners’ reports and to explore concerns to prevent future deaths.DesignRetrospective case series of coroners’ Prevention of Future Deaths reports (PFDs).SettingEngland and Wales.ParticipantsIndividuals identified in 3897 PFDs dated between 1 July 2013 and 23 February 2022, collected from the UK’s Courts and Tribunals Judiciary website using web scraping, and populated into an openly available database:https://preventabledeathstracker.net/Main outcome measuresProportion of PFDs in which coroners reported that a therapeutic medicine or drug of abuse caused or contributed to a death; characteristics of the included PFDs; coroners’ concerns; recipients of PFDs and the timeliness of their responses.Results704 PFDs (18%; 716 deaths) 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 related to patient safety (29%) and communication (26%), including failures of monitoring (10%) and poor communication between organisations (7.5%). NHS England (6%), the Department of Health and Social Care (5%) and the Medicines and Healthcare products Regulatory Agency (2%) received the most medicines-related PFDs. However, most expected responses to PFDs (51%; 615/1245) were not reported on the UK’s Courts and Tribunals Judiciary website.ConclusionsOne in five deaths deemed preventable by coroners involved medicines. Taking actions to address coroners’ concerns, including improving patient safety and poor communication, should increase the safety of medicines. Many concerns were raised repeatedly, but half of 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.Trial registrationhttps://doi.org/10.17605/OSF.IO/TX3CSSummary boxWhat is already known on this topic?Medicines are essential to the provision of healthcare, but if used inappropriately, have the potential to cause significant harms, including death. When an unnatural death occurs, these deaths are often reported to the coroner, which can result in a report to highlight concerns to prevent future deaths. Samples of coroners’ reports have been analysed to identify concerns relating to preventable deaths involving medicines, which found that anticoagulants contributed the most. However, an investigation of all available reports has not been conducted to determine the overall impact of medicines.What this study adds?One in five preventable deaths in England and Wales involved a medicine or drug of misuse, costing nearly 20,000 years of life lost. Opioids, antidepressants, and hypnotics were the most common medicines involved in preventable deaths. Coroners repeatedly raised similar concerns, primarily relating to patient safety and communication. However, it is unclear whether these reports are being used in clinical practice to guide actions to prevent similar deaths.

BackgroundOpioids are strong pain medications that can be essential for acute pain. However, opioids are also commonly used for chronic conditions and illicitly where there are well recognised concerns about the balance of their benefits and harms. Technologies using artificial intelligence (AI) are being developed to examine and optimise the use of opioids. Yet, this research has not been synthesised to determine the types of AI models being developed and the application of these models.MethodsWe aimed to synthesise studies exploring the use of AI in people taking opioids. We searched three databases: the Cochrane Database of Systematic Reviews, EMBASE, and Medline on 4 January 2021. Studies were included if they were published after 2010, conducted in a real-life community setting involving humans, and used AI to understand opioid use. Data on the types and applications of AI models were extracted and descriptively analysed.ResultsEighty-one articles were included in our review, representing over 5.3 million participants and 14.6 million social media posts. Most (93%) studies were conducted in the USA. The types of AI technologies included natural language processing (46%) and a range of machine learning algorithms, the most common being random forest algorithms (36%). AI was predominately applied for the surveillance and monitoring of opioids (46%), followed by risk prediction (42%), pain management (10%), and patient support (2%). Few of the AI models were ready for adoption, with most (62%) being in preliminary stages.ConclusionsMany AI models are being developed and applied to understand opioid use. However, there is a need for these AI technologies to be externally validated and robustly evaluated to determine whether they can improve the use and safety of opioids.SUMMARY BOXKey PointsAcross the landscape of opioid research, natural language processing models (46%) and ensemble algorithms, particularly random forest algorithms (36%), were the most common types of AI technologies studied.There were four domains to which AI was applied to assess the use of opioids, including surveillance and monitoring (46%), risk prediction (42%), pain management (10%), and patient support (2%).The AI technologies were at various stages of development, validation, and deployment, with most (62%) models in preliminary stages, 11% required external validation, and few models were openly available to access (6%).

© 2020, The Royal Society of Medicine. In recent years there has been increasing awareness of problems that have undermined trust in medical research. This review outlines some of the most important issues including research culture, reporting biases, and statistical and methodological issues. It examines measures that have been instituted to address these problems and explores the success and limitations of these measures. The paper concludes by proposing three achievable actions which could be implemented to deliver significantly improved transparency and mitigation of bias. These measures are as follows: (1) mandatory registration of interests by those involved in research; (2) that journals support the ‘registered reports’ publication format; and (3) that comprehensive study documentation for all publicly funded research be made available on a World Health Organization research repository. We suggest that achieving such measures requires a broad-based campaign which mobilises public opinion. We invite readers to feedback on the proposed actions and to join us in calling for their implementation.

Background The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. Methods We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. Results We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. Conclusions High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. Study registration PROSPERO, CRD42018088057

Introduction: The consumption of opioids has increased globally since the 1990s. Previous studies of global opioid consumption have concentrated on morphine alone or a subset of opioids, with a focus on cancer pain and palliative care. In this study, we have determined the global, regional, and national consumption of all controlled opioids, including anaesthetics, analgesics, antidiarrheals, opioid substitution therapies, and cough suppressants. Methods: We conducted a cross-sectional study using data from the International Narcotics Control Board (INCB). We calculated mean opioid consumption (mg/person) globally, regionally, and nationally for 2015–2017, where consumption refers to the total amount of controlled opioids distributed for medical purposes and excludes recreational use. We ranked countries by total consumption and quantified the types of opioids consumed globally. Results: Between 2015 and 2017, 90% of the world’s population consumed only 11% of controlled opioids. An average of 32 mg/person was consumed annually, but this was not equally distributed across the world. Consumption was the highest in Germany (480 mg/person), followed by Iceland (428 mg/person), the United States (398 mg/person) and Canada (333 mg/person). Oxycodone (35%) was the most heavily consumed controlled opioid globally, followed by morphine (15.9%), methadone (15.8%) and tilidine (14%). Conclusion: Large disparities persist in most of the world in accessing essential opioid medicines. Consumption patterns should continue to be monitored, and collaborative strategies should be developed to promote access and the appropriate prescribing of opioids in all countries and non-metropolitan territories.

Cross-disciplinary openness and transparency of research plays an important role in scientific progress. We evaluated open-science related policies of 19 high ranking health and medical journals before (February 2020) and during (May 2021) the COVID-19 pandemic. The Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) were used to audit journal policies. TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n=16) and during (95%; n=18) the COVID-19 pandemic. The COVID-19 pandemic has highlighted the importance of practising open science, however adherence to open science standards in audited policies was low overall, which may reduce progress in health and medical research.

Background: Low-dose codeine products can be purchased without a prescription in most of Canada. We explored trends in the purchasing of these products across the Canadian provinces from 2014 to 2019, evaluating the impact of Health Canada’s 2016 announcement of a proposed regulatory change and the 2017 opening of a 60-day public comment period, as well as the impact of Manitoba’s 2016 policy change requiring a prescription for the purchase of all codeine products in that province. Methods: We evaluated population-adjusted monthly purchasing of codeine products from January 2014 to October 2019 using the IQVIA Canadian Drug Store and Hospital Purchases Audit database, stratified by province and over-the-counter (OTC) status. The primary outcomes were change in the monthly volume of low-dose codeine purchased after the 2016 federal regulatory proposal and the 2017 period of public comment across the provinces. Our secondary analysis was the impact of Manitoba’s policy change in February 2016 requiring a prescription for low-dose codeine. We conducted a time-series analysis using interventional autoregressive integrated moving average models. Results: Over the study period, 24 120 kg of codeine (3.025 billion units) and 937 867 kg of acetaminophen were sold as OTC, low-dose codeine products across the Canadian provinces. Health Canada’s 2016 announcement did not significantly affect OTC codeine purchasing (p = 0.57). The initiation of a 60-day public comment period was associated with a roughly 44% decrease in OTC codeine purchasing (p = 0.03). In Manitoba, purchasing of the same codeine formulations decreased after rescheduling in February 2016 (p < 0.001). We observed no significant change in the rate of purchasing of higher dose codeine formulations in response to scheduling changes in Manitoba (p = 0.22). Interpretation: Although Health Canada’s 2016 announcement of a proposed regulatory change did not appear to have an effect on OTC codeine purchasing nationally, the 60-day comment period was associated with a decrease in purchasing. Further, Manitoba’s 2016 policy change was associated with a significant and sustained decrease in the overall volume of codeine purchased. Given the potential risks of codeine dependence and acetaminophen toxicity with these products, a national rescheduling strategy should be considered.

The opioid crisis in the United States (US) is one of the most high-profile public health scandals of the 21st century with millions of people unknowingly becoming dependent on opioids. The United Kingdom (UK) had the world’s highest rate of opioid consumption in 2019, and opiate-related drug poisoning deaths have increased by 388% since 1993 in England and Wales. This article explores the epidemiological definitions of public health emergencies and epidemics in the context of opioid use, misuse, and mortality in England, to establish whether England is facing an opioid crisis.

In England and Wales, coroners are required to write Prevention of Future Deaths reports (PFDs) when a death is deemed preventable so that action is taken to avert similar deaths. Since July 2013, PFDs have been openly available via the Courts and Tribunals Judiciary website (https://www.judiciary.uk/subject/prevention-of-future-deaths/). However, their presentation has been insufficient to identify trends and learn lessons. We designed a web scraper to create the Preventable Deaths Tracker (https://preventabledeathstracker.net/). On 22 June 2022, 4001 PFDs were scraped, analysed, and compared to the Office of National Statistics (ONS) preventable mortality statistics. This commentary summarises the key findings and offers recommendations to improve the PFD system so lessons can be learnt to avert preventable deaths.

Registration of health and medical research is an effective way of improving the transparency and credibility of evidence. Registration involves pre-specifying the research objectives, design, methods and analytic plan on a publicly accessible repository before conducting the study. Registration can reduce bias and improve the transparency and credibility of research findings. Registration is mandated for clinical trials, but it is also relevant to systematic reviews, observational and preclinical experimental research. This paper describes how researchers can register their research and outlines possible barriers and challenges in doing so. Widespread adoption of research registration can reduce research waste and improve evidence-informed clinical and policy decision making.

Aim Three million cases of paediatric traumatic brain injury (pTBI) occur annually, the majority of which occur in low-and-middle-income countries (LMICs). However, there is a paucity of data on the outcomes of pTBI available. We aimed to systematically review and synthesise the reported morbidity and mortality from pTBI in the published literature about LMICs. Method A systematic review and meta-analysis were conducted. MEDLINE, EMBASE, Global Health, and Global Index Medicus were searched for relevant articles from January 2000 to May 2020. Observational or experimental studies on pTBI (individuals between the ages of 0 to 16 years) in LMICs were included. Morbidity data were descriptively analysed, and a random-effects model was used to pool mortality rates. PROSPERO ID: CRD42020171276. Results We included 145 studies from 38 countries representing 174073 patients with pTBI. Males were twice (95% CI: 1.6 – 2.4) as likely to have a pTBI than females. Where available, mild TBI represented ≥ 60% of all pTBI cases in most reports (n = 24/43, 56%). The commonest cited cause of pTBI was road traffic accidents (n = 16643/43083, 39%), followed by falls (n = 10927/43083, 25%). 4385 patients (n = 4385/18092, 24%) had a reduction from normal function on discharge. On average, there were 6.7 deaths per 100 cases of pTBI. Conclusions Only 38 LMICs have published data on the volume and burden of pTBI in their country. Limited data available suggests that young male children are at a high-risk of pTBIs in LMICs, particularly from road traffic accidents.

ObjectiveStress urinary incontinence (SUI) and pelvic organ prolapse (POP) are treated with surgical mesh devices; evidence of their long-term complications is lacking. To examine long-term complications in women with SUI and/or POP, with and without surgical mesh implants.DesignLongitudinal open cohort study from April 01 2006 to November 30 2018SettingThe Clinical Practice Research Datalink (CPRD) Gold database, linked to Hospital Episodes Statistics (HES) inpatient data, Office for National Statistics mortality data, and Index of Multiple Deprivation socioeconomic status data.ParticipantsWomen aged ≥18 years with a diagnostic SUI/POP code.ExposureMesh surgery coded in HES or CPRD data, compared to no mesh surgery.Main Outcomes measuresRates of diagnoses of depression, anxiety or self-harm (composite measure) and sexual dysfunction, using Cox proportional hazards regression, and rates of prescriptions for antibiotics and opioids, using negative binomial regression.ResultsThere were 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. Women undergoing mesh surgery for SUI or POP had higher rates of antibiotic use (SUI: IRR 1.15 (95% CI 1.13 to 1.18; pConclusionsMesh surgery was associated with poor mental and sexual health outcomes, alongside increased opioid and antibiotic use, in women with no history of these outcomes and improved mental health, and lower opioid use, in women with a previous history of these outcomes. Careful consideration of the benefits and risk of mesh surgery for women with SUI or POP on an individual basis is required.What is known on this topicThere are well publicised concerns about high complication rates and harms associated with surgical mesh, a treatment that has been used in urogynaecological procedures to treat stress urinary incontinence (SUI) and pelvic organ prolapse (POP) for the past 20 years. Yet, there is a consistent lack of long-term evidence over the use of surgical mesh beyond surgical readmission, with NICE, Cochrane, and the FDA all reporting a lack of long-term outcome data. This study reports long-term complications in women with stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP), with and without surgical mesh implants.What this study addsIn this cohort of 162,687 women with SUI and 82,123 women with POP, rates of depression, anxiety, self-harm, sexual dysfunction and opioid prescriptions were higher in women with mesh-surgery who had no previous history of these outcomes. Lower rates of depression, anxiety and self-harm were seen in women with a history of these outcomes and SUI or POP mesh surgery. Opioid prescribing was lower in women with a previous history of prescriptions and POP mesh surgery. Careful consideration of the benefits and risk of mesh surgery for women with SUI or POP on an individual basis is required.

The challenges facing the evidence-based medicine (EBM) movement are well documented.1 2 Yet, the problems facing early-career and mid-career researchers (EMCRs) working in the ecosystem of EBM have not been articulated. The coming together of a cohort of EMCRs from across the globe enabled this articulation.3 The 2019 EBMLive conference (see box 1) provided a space for EMCRs to discuss problems, exchange ideas and create a list of potential solutions. This article outlines four key problems faced by EMCRs and their potential solutions (see box 2). Box 1 ### The EBMLive Conference The EBMLive Conference (www.ebmlive.org) is a joint partnership between the Centre for Evidence-Based Medicine and the BMJ , designed to develop, disseminate, and implement better evidence for better healthcare . Since inception, EBMLive has worked tirelessly to include the voice of students and early-career researchers. Building on previous work, the inaugural Doug Altman Scholarship3 and Building Capacity Bursaries were launched in 2019 to fund the travel and attendance of early-career researchers from across the globe to attend the conference. Box 2 ### Problems facing EMCR and their potential solutions In the lead up to the EBMLive conference, Doug Altman Scholars submitted personal and general problems they have faced as early-career researchers. The responses were synthesised and shared with the Scholars to generate further discussion. During EBMLive, the problems and ideas for potential solutions were discussed and presented during dedicated sessions for early- and mid-career researchers. The key list of problems facing early-career and mid-career researchers and their potential solutions are as follows: 1. Tokenistic training of evidence-based medicine 2. Emphasis of quantity over quality 3. Lack …

Background: Medicine use is considered off-label when used for an indication, at a dose, via a route of administration or in a patient group not included in the approved product information. Off-label use varies according to therapeutic class and patient group, and often occurs in those who are vulnerable. Objective: The aim of this article is to discuss ethical, practice and policy considerations associated with off-label medicine use. Discussion: A number of professional organisations have issued guidance in relation to offlabel medicine use. Prescribers should inform patients and document consent when prescribing off-label, including an open discussion about known and unknown benefits and risks. It is important that the prescriber documents the reason for off-label use in the patient’s record and ensures that patients are aware of the intended duration and relevant monitoring. Australia’s new national health priority of Quality Use of Medicine and Medicine Safety should stimulate all stakeholders including consumers to work together to address off-label medicine use.

BackgroundThe global burden of cardiovascular disease (CVD) is forecast to increase, and anticoagulants will remain important medicines for its management. Coroners’ Prevention of Future Death reports (PFDs) provide valuable insights that may enable safer and more effective use of these agents.AimTo identify CVD-related PFDs involving anticoagulants.Design and SettingRetrospective observational study of coronial case reports in England and Wales between 2013 and 2019.MethodWe screened 3037 PFDs for eligibility and included PFDs where CVD and an anticoagulant caused or contributed to the death. We descriptively analysed included cases and used content analysis to assess concerns raised by coroners and who responded to them.ResultsWe identified 113 cardiovascular disease-related PFDs involving anticoagulants. Warfarin (36%), enoxaparin (11%), and rivaroxaban (11%) were the most common anticoagulants reported. Concerns most frequently raised by coroners included poor systems (31%), poor communication (25%), and failures to keep accurate medical records (25%). These concerns were most often directed to NHS trusts (29%), hospitals (10%), and general practices (8%). Nearly two-thirds (60%) of PFDs had not received responses from such organisations, which are mandatory under regulation 28 of the Coroners’ (Investigations) Regulations 2013. We created a publicly available tool,https://preventabledeathstracker.net/, which displays coroners’ reports in England and Wales to streamline access and identify important lessons to prevent future deaths.ConclusionNational organisations, healthcare professionals, and prescribers should take actions to address the concerns of coroners’ in PFDs to improve the safe use of anticoagulants in patients with cardiovascular disease.How this fits inA previous assessment of 500 PFDs identified anticoagulants as the class of drugs most often involved in fatal medication errors. This study uses innovative methods to automatically collect all available PFDs between 2013 and 2019 to identify deaths from cardiovascular disease when the use of or lack of anticoagulants caused or contributed to the death. Coroners’ raised hundreds of coroners in their reports, including issues with communication, following protocols, education and training, access to resources, and safety. Despite repeat concerns with national relevance being identified, most CVD-anticoagulant PFDs were sent locally to NHS Trusts, hospitals, and general practices, limiting their ability to reduce harms and prevent premature deaths.

Emollients are readily available in prescription and over-the-counter products, and are commonly used in homes and healthcare facilities. These products are not harmful or flammable in isolation, but if they are combined with flames, such as the light of a cigarette, and fabric, they accelerate fires, resulting in burns and deaths. This article describes a prevent future death case report of a 74-year-old woman who succumbed to burns in the presence of paraffin based emollient creams and a lighted match. We highlight the fire risks of such products and the need for greater awareness among the public and healthcare professionals. > This article is part of the coroners’ concerns to prevent harms series.1 It discusses a prevention of future death report on the fire accelerant properties of emollient products.2 Products containing emollients, from E45 and Vaseline to Cetraben, are widely available over the counter or by prescription. In the past 12 months (October 2019 to September 2020), more than 15 million items containing emollients were dispensed in England, costing more than £93 million.3 They come in various formulations, including liquids, creams and ointments (box 1), and are used to hydrate the skin. Emollients can contain paraffin, an oily liquid composed of saturated hydrocarbons from petroleum,4 to help form a protective film over the skin and trap moisture. Paraffin is cheaper than alternative agents, such as lanolin or olive oil.5 If their residue on fabric is exposed to fire (eg, from the light of a cigarette or stovetop), emollients (both paraffin free and paraffin based) can act as accelerants to the fire, and have devastating consequences. It was previously thought that the risk of fire was posed only by emollients containing more than 50% paraffin, but it has been acknowledged that the fire risk cannot be excluded …

Classes of substances and nomenclature Opioids are naturally occurring or synthetic substances that have morphine-like activity. The term “opiate” refers only to substances that are structurally related to morphine, which was isolated in 1806 [1]. The term “opioid” refers to these drugs and other compounds, not structurally related to morphine, but with similar actions at opioid receptors. These actions exert their effects on metabotropic opioid receptors, including mu (MOP), kappa (KOP), and delta opioid (DOP) receptors, as well as the more recently discovered nociceptin/orphanin (NOP) receptor [2]. All four receptors are G-protein coupled receptors (GPCRs) and exert their effects by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and modifying the permeability of ion channels, causing downstream effects [2]. Substances that bind to opioid receptors but elicit little agonist activity and prevent the effects of opioid agonists are known as opioid receptor antagonists. Some drugs have both agonist and antagonist effects (partial agonists). The opioids and their antagonists can be divided into three groups: (a) opioid receptor agonists (morphine and morphine-like opioids); (b) opioid receptor antagonists (for example, naloxone and naltrexone); (c) opioid receptor partial agonists (for example buprenorphine and nalbuphine). The word “narcotic” is used to describe substances with morphine-like activity in phrases such as “narcotic analgesics” and “narcotic antagonists”. Modifications of the morphine-like alkaloid derivatives led to the production of semi-synthetic opioids. Later fully synthetic opioids were derived from morphinan, dophenylheptane, becomorphan, and phenylpiperidine [1]. The development of opioids is being driven by their analgesic properties. Some opioids are effective in reducing postoperative pain, cancer pain, and labour pain and in palliative care [3,4]. However, there is little evidence to suggest that they are effective in managing chronic non-cancer pain, and no evidence for their use in high doses (>200 mg of oral morphine equivalents, OME) [5,6]. Opioids are also associated with significant adverse reactions such as constipation, nausea, dizziness, drowsiness, fatigue, hot flushes, increased sweating, pruritus, vomiting, respiratory depression, and in some cases death [6–8]. Tolerance, as well as euphoria, can result in abuse and misuse [9]. A typical clinical trajectory begins with the prescription of an opioid for the appropriate reduction of pain. This is initially effective in reducing the pain, but over time higher doses are required to produce the same effect. This can escalate to misuse, dependence, and in some cases opioid addiction. Many parts of the world are now seeing an increase in opioid overdoses; for example, the USA experienced a 120% rise between 2010 and 2018, now referred to as the US opioid crisis [10]. Tougher regulations to reduce access to prescribed opioids and lower prescribing rates in the USA turned those dependent on opioids to ‘street’ or ‘black market’ opioids (e.g. heroin and fentanyl), which pose a much greater risk of overdose [11]. In the UK, deaths from opioids have likewise doubled in the last decade [12], and prescribing of opioids has had a corresponding increase of 127% between 1998 and 2016 in England [13], nearly 4% of those prescribed opioids receiving high doses (>120 mg of OME) [14]. However, the ever-increasing need for analgesia is not reflected in the confidence of prescribers. Studies have shown that primary care providers often report that they have been inadequately trained in opioid prescribing for chronic non-cancer pain [15–17]. This poor knowledge of opioid pharmacology and use may be a driver of increased opioid prescribing. The benefits and adverse effects of opioids differ based on their pharmacological profile. Recent efforts in drug development have tried to find less addictive alternatives, with some success [18]. However, the number of opioids that have been developed is unknown. Efforts have been made to categorize drugs and provide resources of drug information. The British National Formulary (BNF), Martindale’s Extra Pharmacopoeia, and the Merck Index, are leading examples of drug repositories widely used by healthcare professionals, academics, and industry partners, while the WHO’s Anatomical Therapeutic Chemical (ATC) system classifies drugs based on their therapeutic, pharmacological, and chemical properties [19]. However, there is currently no centralized catalogue of opioids containing information about their pharmacology. Narcotic analgesics are among the most commonly prescribed drugs in English primary care [20]. A centralized list of all known opioids and their pharmacology could help increase knowledge of opioids among the public and prescribers. Such a catalogue could contribute to a reduction in the harm associated with opioids by elucidating the heterogeneous nature of opioids, helping comparisons of existing opioids, and providing a single repository of information to develop less addictive opioids. Our objectives are therefore: 1) to determine the number of opioids developed, to create a robust list of opioid drug names; and 2) to catalogue the opioids based on their pharmacological properties.

High doses or prolonged use of diclofenac, a commonly prescribed non-steroidal anti-inflammatory drug (NSAID), may result in gastrointestinal complications, which, if ignored, can be fatal. A preventable death attributed to diclofenac in a 16-year-old girl with complex needs has been identified, and is described in this article. Adverse drug reactions from NSAIDs should be considered and treated in children and adolescents, especially those with complex needs. > This article is part of the Coroners’ Concerns to Prevent Harms series.1 It discusses a Prevention of Future Death (PFD) report related to harm from diclofenac in an adolescent.2 Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that is commonly prescribed for its analgesic, antipyretic and anti-inflammatory effects. About 658 000 prescriptions were dispensed for diclofenac in English primary care in the 12 months from September 2019 to August 2020, costing £8.3 million.3 Diclofenac is thought to exert its action by reducing prostaglandin synthesis through inhibition of the cyclo-oxygenase enzymes (COX-1 and COX-2). It is classified as a non-selective COX inhibitor, though in vitro studies have shown it preferentially inhibits COX-2 more than COX-1.4 Diclofenac is most commonly prescribed for pain relief but the specific indications for its use in children and adolescents vary by age, as recommended in the British National Formulary for Children, see box 1.5 Diclofenac, along with other NSAIDs, is associated with increased risks of bleeding, cardiovascular events, renal impairment and gastrointestinal complications, including peptic ulcer disease.6 These harms are well reported in the elderly, and NSAIDs have been implicated in 30% of all hospital admissions due to preventable adverse drug reactions (ADRs).7 However, the prevalence of such harms is not well studied in children and adolescents. Box 1 ### EBM facts: Information on diclofenac from the British National Formulary for Children #### Formulations #### Indications for use

IntroductionOpioids are deemed essential medicines by the World Health Organization (WHO). However, many countries have inadequate access to them. Whether including opioids in national essential medicines lists (EMLs) influences national opioid consumption has not been evaluated.MethodsWe conducted a cross-sectional study to determine whether the listing of opioids in national EMLs was associated with consumption. We quantified the numbers and types of all opioids included in 137 national EMLs, for comparison with opioids in the WHO’s Model List of Essential Medicines. Using the International Narcotics Control Board (INCB) consumption statistics for 2015–2017, we assessed the relation between annual mean opioid consumption (mg/person) and the numbers of opioids included in EMLs, controlling for region, population, healthcare expenditure, life expectancy, gross domestic product, human development and corruption.ResultsFive opioids were included in the 20th edition of the WHO’s Model List of Essential Medicines: codeine, fentanyl, loperamide, methadone and morphine. On average, countries’ lists included significantly (pConclusionsIncluding opioids in national EMLs was not associated with consumption. National EMLs should be regularly updated to reflect the availability of opioids and the populations’ needs for managing pain.

BackgroundCardiovascular disease (CVD) such as ischemic heart disease and stroke is the leading causes of death and disability globally with a growing burden in low and middle-income countries. A credible way of managing the incidence and prevalence of cardiovascular diseases is by reducing risk factors. This understanding has led to the development and recommendation for the clinical use of cardiovascular risk stratification tools. These tools enhance clinical decision-making. However, there is a lag in the implementation of these tools in most countries. This systematic review seeks to synthesise the current knowledge of the factors influencing the implementation of cardiovascular risk scoring in primary care settings.MethodsWe searched bibliographic databases and grey literature for studies of any design relating to the topic. Titles, abstracts and full texts were independently assessed for eligibility by two reviewers. This was followed by quality assessment and data extraction. We analysed data using an integrated and best fit framework synthesis approach to identify these factors. Quantitative and qualitative forms of data were combined into a single mixed-methods synthesis. The Consolidated Framework for Implementation Research was used as the guiding tool and template for this analysis.ResultsTwenty-five studies (cross-sectionaln= 12, qualitativen= 9 and mixed-methodsn= 4) were included in this review. Twenty (80%) of these were conducted in high-income countries. Only four studies (16%) included patients as participants. This review reports on a total of eleven cardiovascular risk stratification tools. The factors influencing the implementation of cardiovascular risk scoring are related to clinical setting and healthcare system (resources, priorities, practice culture and organisation), users (attributes and interactions between users) and the specific cardiovascular risk tool (characteristics, perceived role and effectiveness).ConclusionsWhile these findings bolster the understanding of implementation complexity, there exists limited research in the context of low and middle-income countries. Notwithstanding the need to direct resources in bridging this gap, it is also crucial that these efforts are in concert with providing high-quality evidence on the clinical effectiveness of using cardiovascular risk scoring to improve cardiovascular disease outcomes of mortality and morbidity.Trial registrationPROSPERO registration number: CRD42018092679.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Scientific progress requires transparency and openness. The ability to critique, replicate and implement scientific findings depends on the transparency of the study design and methods, and the open availability of study materials, data and code. Journals are key stakeholders in supporting transparency and openness. This study aimed to evaluate 10 highest ranked pain journals' authorship policies with respect to their support for transparent and open research practices. Two independent authors evaluated the journal policies (as at 27 May 2019) using three tools: the self-developed Transparency and Openness Evaluation Tool, the Centre for Open Science (COS) Transparency Factor and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosure of conflicts of interest. We found that the journal policies had an overall low level of engagement with research transparency and openness standards. The median COS Transparency Factor score was 3.5 (IQR 2.8) of 29 possible points, and only 7 of 10 journals' stated requirements for disclosure of conflicts of interest aligned fully with the ICMJE recommendations. Improved transparency and openness of pain research has the potential to benefit all that are involved in generating and using research findings. Journal policies that endorse and facilitate transparent and open research practices will ultimately improve the evidence base that informs the care provided for people with pain.

Background The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is unknown. To fill this gap, we conducted a review that aimed to characterize the causes of pTBI in LMICs, and their reported associated mortality and morbidity. Methods A systematic review was conducted. MEDLINE, Embase, Global Health, and Global Index Medicus were searched from January 2000 to May 2020. Observational or experimental studies on pTBI of individuals aged between 0 and 16 years in LMICs were included. The causes of pTBI and morbidity data were descriptively analyzed, and case fatality rates were calculated. PROSPERO ID: CRD42020171276. Results A total of 136 studies were included. Fifty-seven studies were at high risk of bias. Of the remaining studies, 170,224 cases of pTBI were reported in 32 LMICs. The odds of having a pTBI were 1.8 times higher (95% confidence interval, 1.6–2.0) in males. The odds of a pTBI being mild were 4.4 times higher (95% confidence interval, 1.9–6.8) than a pTBI being moderate or severe. Road traffic accidents were the most common cause (n = 16,275/41,979; 39%) of pTBIs. On discharge, 24% of patients (n = 4385/17,930) had a reduction in their normal mental or physical function. The median case fatality rate was 7.3 (interquartile range, 2.1–7.7). Conclusions Less than a quarter (n = 32) of all LMICs have published high-quality data on the volume and burden of pTBI. From the limited data available, young male children are at a high risk of pTBIs in LMICs, particularly after road traffic accidents.

Understanding the causes of deaths and how they can be prevented is critical for improving healthcare outcomes. At a population level, over-reporting or under-reporting of deaths can have a profound impact on policy decisions, which in turn affect global economies and the day-to-day lives of citizens. At the individual level, understanding how and why deaths occur may prevent similar deaths or serious harms from occurring in the future. One in 20 people are exposed to preventable harms in medical settings globally, and 12% of preventable harms result in disability or death.1 Coroners’ reports hold a wealth of information on the circumstances of individual deaths. In England and Wales, the law requires coroners to report and communicate a death when the coroner believes that action should be taken to prevent deaths.2 These reports, named Prevent Future Deaths (PFDs), are mandated under paragraph 7 of schedule 5 of the Coroners and Justice Act 2009, and regulations 28 and 29 of the Coroners (Investigations) Regulations 2013.3 4 Under these regulations, individuals or organisations that receive a PFD report are required under statue to respond to the coroner within 56 days of receiving the report, to outline actions proposed or taken to address the coroner’s concerns. The Courts and Tribunals Judiciary website hosts the PFD reports and responses to the reports.5 As these reports contain valuable lessons, concerns have been raised regarding …

For Nicholas DeVito, Georgia Richards and Peter Inglesby, custom webscrapers have driven their research — and their collaborations. For Nicholas DeVito, Georgia Richards and Peter Inglesby, custom webscrapers have driven their research — and their collaborations.

The early era of evidence-based medicine (EBM) saw the emergence of a cohort of leaders who applied the concepts of clinical expertise, best available evidence and patient preferences to healthcare. Yet, with time, these core components of EBM have become distorted, misinterpreted and hijacked.1 The EBM Manifesto provided a roadmap for tackling the core issues related to the practice and application of EBM.2 One of the important items in the manifesto is to ‘ Encourage the next generation of leaders in evidence-based medicine ’.2 Achieving improvements in healthcare globally requires building and sustaining early and mid-career researchers (EMCRs).3 Yet, there are big gaps in both critical appraisal and research capacity, particularly in low-income and middle-income countries (LMICs), and this hinders development in these regions.4 At the 2019 EBMLive conference (see box 1), we wanted to better understand the problems and challenges that EMCRs encounter. In particular, we focused on EMCRs in those LMICs undergoing major health system transformations, such as Brazil and India. We asked the six recipients of the Building Capacity Bursaries (all co-authors of this commentary) to describe the challenges that they have encountered individually and among their peers, along with potential solutions (see box 2). Their responses reflect healthcare professionals who practice in South America, Africa, the Middle East and Asia. While some challenges are specific to certain settings, we tried to identify, highlight and describe broad overarching themes. Box 1 ### The EBMLive Conference

A recent cohort study investigated ‘the risk of transitioning from acute to prolonged use’ of opioid analgesics in patients undergoing elective surgery. Patients given tramadol or long-acting opioids after discharge were at greater risk of prolonged opioid use than those who were given other short-acting opioids. ### EBM verdict EBM Verdict on: Chronic use of tramadol after acute pain episode: cohort study. BMJ 2019 May 14. doi: 10.1136/bmj.l1849. Strong pain-relieving medicines called opioids are commonly prescribed when patients are discharged from hospitals. However, pain after elective surgery is usually short-lived. This cohort study1 addresses an important question regarding the prolonged use of opioid analgesics after elective surgery in light of the opioid crisis in the USA and Canada and increased prescribing of opioids in high-income countries.2 Tramadol is both a weak mu-opioid receptor agonist and a serotonin and norepinephrine reuptake inhibitor. Its active metabolite, O -desmethyltramadol, is longer acting than tramadol itself and is a more potent mu-opioid receptor agonist. Responses to tramadol, therefore, vary according to the genotype of the main metabolising enzyme, CYP2D6.3 Tramadol has been …

Background The value of biomarkers for diagnosing bacterial infections in older outpatients is uncertain and limited official guidance exists for clinicians in this area. The aim of this review is to critically appraise and evaluate biomarkers for diagnosing bacterial infections in older adults (aged 65 years and above). Methods We searched Medline, Embase, Web of Science and the Cochrane Library, from inception to January 2018. We included studies assessing the diagnostic accuracy of blood, urinary, and salivary biomarkers in diagnosing bacterial infections in older adults. The QUADAS-2 tool was used to assess study quality. Results We identified 11 eligible studies of moderate quality (11,034 participants) including 51 biomarkers at varying thresholds for diagnosing bacterial infections. An elevated Procalcitonin (≥ 0.2 ng/mL) may help diagnose bacteraemia in older adults [+ve LR range 1.50 to 2.60]. A CRP ≥ 50 mg/L only raises the probability of bacteraemia by 5%. A positive urine dipstick aids diagnosis of UTI (+ve LR range 1.23 to 54.90), and absence helps rule out UTI (−ve LR range 0.06 to 0.46). An elevated white blood cell count is unhelpful in diagnosing intra-abdominal infections (+ve LR range 0.75 to 2.62), but may aid differentiation of bacterial infection from other acute illness (+ve LR range 2.14 to 7.12). Conclusions The limited available evidence suggests that many diagnostic tests useful in younger patients, do not help to diagnose bacterial infections in older adults. Further evidence from high quality studies is urgently needed to guide clinical practice. Until then, symptoms and signs remain the mainstay of diagnosis in community based populations. Electronic supplementary material The online version of this article (10.1186/s12877-019-1205-0) contains supplementary material, which is available to authorized users.

Objectives This review seeks to synthesise current knowledge on factors that influence the implementation of cardiovascular risk scoring in various primary care settings as reported in primary studies. Primary objective To explore the facilitators and barriers to the implementation of cardiovascular risk scoring in primary care. Secondary objective To examine these factors within different contexts such as a country’s Gross National Income classification and the users of the intervention. Method We searched bibliographic databases and grey literature such as EMBASE, MEDLINE, The Cochrane Library, CINAHL, PsycINFO, Global Health and Web of Science for studies of any design relating to the topic. Titles, abstracts, and full texts were independently assessed for eligibility by two reviewers. This was followed by quality assessment and data extraction. The analysis was done through an integrated and best fit framework synthesis approach. Quantitative and qualitative forms of data were combined into a single mixed methods synthesis. The Consolidated Framework for Implementation Research was used as the guiding tool and template for this analysis. The aggregated data was coded using NVivo 12. Additional analysis was conducted to identify the facilitators and barriers common in high-income countries versus those in low and middle-income countries, those that are patient-related versus those that are healthcare provider-related and those that related to physicians versus those related to non-physicians. Results Twenty-five studies of various designs were included in this review. Most of these studies were conducted in high-income countries. All studies included healthcare professionals as participants and reported on a total of 11 cardiovascular risk scores. The a priori framework (CFIR) used in this review was appropriate in that the extracted data fit the framework’s constructs. However, one new theme emerged from the data – knowledge and belief about disease and risk. This was classified under the characteristics of individuals’ domain. The factors influencing the implementation of cardiovascular risk scoring were broadly conceptualised into factors relating to the cardiovascular risk tool, users, clinical setting and healthcare system. Despite the dearth in research in low and middle-income countries, there were many similarities in the findings across all Gross National Income indices and users. Conclusions The findings from this review show that factors influencing the implementation of cardiovascular risk scoring can be broadly conceptualised into: the healthcare system and clinical settings, the users of cardiovascular risk scoring, and the tools used for cardiovascular risk scoring. Whilst these findings reinforce the understanding that implementation processes are multifaceted and that they involve many components which act synergistically, there is limited research in the context of low and middle-income countries. Notwithstanding the need to direct resources in bridging this gap, it is also crucial that these efforts are in concert with providing high quality evidence on the clinical effectiveness of using cardiovascular risk scoring to improve cardiovascular disease outcomes of mortality and morbidity.Research in the form of effectiveness-implementation hybrid designs which will combine the elements of clinical effectiveness and implementation research to enhance public health impact is crucial.

© 2019 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd. Objective: To identify the barriers and facilitators of achieving continuity of care between health services for patients with chronic conditions living in regional, rural and remote Australia. Design: A systematic literature review of peer-reviewed journal publications between January 1990 and April 2018. Setting: Publications were sourced from medical and scientific databases, including: PubMed; Embase; OvidSP; ProQuest research library; and ScienceDirect. Participants: Studies, involving two groups, were included in the review: (a) Australian adults, residing in non-metropolitan areas with a chronic condition, who accessed health care services; and (b) health care service providers (eg, doctors) who provided care to non-metropolitan patients. Main outcome measures: Facilitators and barriers of continuity of care for non-metropolitan patients with a chronic condition. Results: Initially, 536 studies were included in the review. Of these, 12 studies were found to have met the eligibility criteria and were included in the final analysis. Conclusions: Coordination of health care services for non-metropolitan patients with chronic conditions substantially improves the outcomes for patients. Overall, communication, availability of resources and location are the major barriers and facilitators to continuity of care, depending on how they are managed. Recommendations have been provided to assist practitioners and policy-makers to improve the experience of shared care and health outcomes for non-metropolitan patients.

© 2019 Elsevier Ltd Background: There is a call for greater monitoring of opioid prescribing in the UK, particularly of strong opioids in chronic pain, for which there is little evidence of clinical benefit. We aimed to comprehensively assess trends and variation in opioid prescribing in primary care in England, from 1998 to 2018, and to assess factors associated with high-dose opioid prescribing behaviour in general practices. Methods: We did a retrospective database study using open data sources on prescribing for all general practices in England. For all standard opioids we calculated the number of items prescribed, costs, and oral morphine equivalency to account for variation in strength. We assessed long-term prescribing trends from 1998 to 2017, patterns of geographical variation for 2018, and investigated practice factors associated with higher opioid prescribing. We also analysed prescriptions for long-acting opioids at high doses. Findings: Between 1998 and 2016, opioid prescriptions increased by 34% in England (from 568 per 1000 patients to 761 per 1000). After correcting for total oral morphine equivalency, the increase was 127% (from 190 000 mg to 431 000 mg per 1000 population). There was a decline in prescriptions from 2016 to 2017. If every practice prescribed high-dose opioids at the lowest decile rate, 543 000 fewer high-dose prescriptions could have been issued over a period of 6 months. Larger practice list size, ruralness, and deprivation were associated with greater high-dose prescribing rates. The clinical commissioning group to which a practice belongs accounted for 11·7% of the variation in high-dose prescribing. We have developed a publicly available interactive online tool, OpenPrescribing.net, which displays all primary care opioid prescribing data in England down to the individual practice level. Interpretation: Failing to account for opioid strength would substantially underestimate the true increase in opioid prescribing in the National Health Service (NHS) in England. Our findings support calls for greater action to promote best practice in chronic pain prescribing and to reduce geographical variation. This study provides a model for routine monitoring of opioid prescribing to aid targeting of interventions to reduce high-dose prescribing. Funding: National Institute for Health Research (NIHR) School of Primary Care Research, NIHR Biomedical Research Centre Oxford, NHS England.

Objectives Analgesics are among the most commonly used and accessible drugs in the world. They are generally well tolerated and effective if consumed appropriately. Yet, not all medicines available over-the-counter (OTC) are low risk. Products containing codeine have been associated with dependence, addiction, overdose-related deaths and collateral toxicity from combinations with paracetamol or ibuprofen. Policy surrounding public access to OTC codeine varies across the world. Currently, 15 of the 28 European Union member states do not permit the sale of OTC codeine. More recently, Australia and Manitoba, Canada changed the status of codeine-containing medicines to prescription-only. Access to data and monitoring of OTC medicines is limited. Without access to this data, it is unclear whether policies that restrict OTC medicines are effective in reducing use and associated harms. Codeine-containing products are available OTC in the United Kingdom (UK). Thus, we will explore trends and variation in OTC analgesics in the UK and review current policy across the world. Method We will use a national retail database from a global data analytics company. The data will include value sales (cost), unit sales (number of packs sold) and volume sales (number of tablets sold) of oral analgesics for adults at the national and regional level. The data will be adjusted for population growth using data from the Office of National Statistics. Trends will be plotted over time, aggregated and stacked by class of analgesic (i.e. opioids, paracetamol and non-steroidal anti-inflammatory drugs). Choropleth maps will be created to depict geographical variation aggregated to regions. For each region, we will calculate the value, unit and volume sold per 1000 of the population for each class of analgesic. Descriptive statistics will be used to compare regions and analgesic classes over time. Restrictive review methods will be used to compare and contrast current policy on OTC codeine-containing products globally. Results Over the last five years, sales of OTC medicines increased by 13% (£2.3 billion in 2012 to £2.6 billion in 2017, IRI, 2017). Implementation of this protocol is required to determine what proportion of this increase was for analgesics and codeine-containing medicines. The restricted review with synthesise current policies and restrictions on OTC codeine containing medicines and the evidence-based used for these decisions. Conclusions Examining trends, variation and legislation of OTC codeine sales is important with the current push to promote self-care and change policy on the access of codeine-containing medicines. Previous studies have focused on analysing trends in the prescribed medicines. This focus may be attributed to the difficulty and lack of available data on sales of OTC medicines. Our team is interested in investigating international trends so if your country or region has access to OTC analgesic data please get in contact. Conflicts of interest GCR is receiving funding from the National Health Service (NHS) National Institute of Health Research (NIHR) School of Primary Care Research, Naji Foundation and Rotary Foundation to study for a Doctor of Philosophy at the University of Oxford with no other relevant conflicts of interests.

Supplemental Digital Content is Available in the Text., Introduction: Cognitive performance and inflammation are altered in people with chronic low back pain (CLBP). Yet, the magnitude of these changes has been unclear because of the potential influence of opioid analgesics. Objectives: This cross-sectional pilot study aimed to explore whether patients with CLBP receiving long-term opioid analgesics differed from patients not taking opioids on measures of cognitive performance and plasma cytokine concentrations. Methods: Patients with CLBP who were either taking (N = 18) or not taking (N = 22) opioids daily for 3 or more months were recruited from a tertiary care private hospital and compared with healthy adults (N = 20). All groups were administered validated questionnaires to assess depression, anxiety, and stress; a cognitive test of memory, attention, and executive function; and a peripheral blood draw to measure proinflammatory (IL-1β, IL-2, IL-8, IL-12p70, TNF-α, and IFN-γ), anti-inflammatory (IL-4, IL-10, and IL-13), and pleiotropic (IL-6) cytokine concentrations. Patients also completed pain-specific questionnaires. Results: Patients receiving opioid analgesics performed significantly (P < 0.05) worse in attention and had significantly (P < 0.05) lower pain self-efficacy beliefs than those patients not taking opioids. Patient groups did not differ in mean pain severity or pain interference scores, tests of memory and executive function, and mean plasma cytokine concentrations, despite long-term opioid analgesics. Conclusion: Patients receiving long-term opioid analgesics for CLBP have minor differences when compared with patients not taking opioids. This has important clinical implications when considering long-term treatment for patients with CLBP.

Objectives The prescription of opioid analgesics is rising in communities of high-income countries. Some of this increase may be appropriately addressing the growing number of people living with pain. Yet, the inappropriate prescribing of opioids (i.e. prescribing that deviates from evidence-based guidelines) may be causing more harms than potential benefits. Previous studies have focused disproportionately on demonstrating the increases in opioid prescribing without understanding what is driving the increase in prescribing. Therefore, We aim to systematically review the literature to establish what factors are driving inappropriate opioid prescribing and potential variation in opioid prescribing practices in high-income countries. Method We searched MEDLINE, EMBASE and Web of Science using ‘primary care’, ‘factors’, ‘variation’, ‘opioid’, ‘prescribing’ and derivatives of these. No language, date or additional limits were applied. The search was completed on 12 February 2018 and is registered on PROSPERO [CRD42018088057]. Studies are being reviewed by two authors who will independently select the eligible articles, extract the data, assess the risk of bias using ROBINS-I (Sterne et al. 2016) and quality of the evidence using GRADE. Relevant internet proceedings, reference lists of included studies and review articles will be examined. Inclusion criteria includes: observational studies, adults (aged ≥18) recruited in communities of high-income countries, a measurement of opioid prescribing, factors that explain prescribing and/or a measure of variation in prescribing practices. Inpatients or patients admitted to hospital (unless followed up in the community), patients with a pre-existing opioid-use disorder or addiction and case studies will be excluded. Results We identified 3950 records to be reviewed for inclusion or exclusion after 4421 duplicates were removed. We anticipate a range of patient-, practitioner- and system-level factors to be found that explain inappropriate opioid analgesic prescribing in the community. Variation is expected to be found across countries, on the indication for prescription and type of opioid prescribed. Conclusions The prescription of opioid analgesics is continuing to rise. Identifying potential patient-, prescriber- and system-level factors associated with opioid prescribing will be the first step in understanding the drivers of prescription and address unwarranted variation in the treatment of pain. This study will provide a framework for a primary database study to be designed that will develop our understanding of the growing treatment needs for people living with persistent pain.