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

PURPOSE: Coroners' Prevention of Future Death (PFDs) reports are an under-utilized resource to learn about preventable deaths in England and Wales. We aimed to identify sepsis-related PFDs and explore the causes and concerns in this subset of preventable sepsis deaths. METHODS: Four thousand three hundred five reports were acquired from the Courts and Tribunals Judiciary website between July 2013 and November 2022, which were screened for sepsis. Demographic information, coroners concerns and responses to these reports were extracted and analyzed, including a detailed paediatric subgroup analysis. RESULTS: Two hundred sixty-five reports (6% of total PFDs) involved sepsis-related deaths. The most common cause of death in these reports was "sepsis without septic shock" (42%) and the most common site of infection was the respiratory system (18%) followed by gastrointestinal (16%) and skin (13%) infections. Specific pathogens were named in few reports (27%). Many deaths involved multimorbid patients (49%) or those with recent surgery (26%). Coroners named 773 individual concerns, the most frequent were: a failure to keep accurate records or notes (28%), failure in communication or handover (27%) or failure to recognize risk factors or comorbidities (20%). Paediatric cases frequently reported issues with sepsis screening tools (26%). Sepsis PFDs resulted in 421 individual reports being sent, of which 45% received no response. Most organisations who did respond acknowledged concerns and initiated a new change (74%). CONCLUSION: Sepsis-related PFDs provide valuable insights into preventable causes of sepsis and identify important sources of improvement in sepsis care. Wider dissemination of findings is vital to learn from these reports.

Preventable deaths involving falls in England and Wales, 2013-22: a systematic case series of coroners' reports.

BACKGROUND: Falls in older people are common, leading to significant harm including death. Coroners have a duty to report cases where action should be taken to prevent future deaths, but dissemination of their findings remains poor. OBJECTIVE: To identify preventable fall-related deaths, classify coroner concerns and explore organisational responses. DESIGN: A retrospective systematic case series of coroners' Prevention of Future Deaths (PFD) reports, from July 2013 (inception) to November 2022. SETTING: England and Wales. METHODS: Reproducible data collection methods were used to web-scrape and read PFD reports. Demographic information, coroner concerns and responses from organisations were extracted and descriptive statistics used to synthesise data. RESULTS: Five hundred and twenty-seven PFDs (12.5% of PFDs) involved a fall that contributed to death. These deaths predominantly affected older people (median 82 years) in the community (72%), with subsequent death in hospital (70.8%). A high proportion of cases experienced fractures (51.6%), major bleeding (35.9%) or head injury (38.7%). Coroners frequently raised concerns regarding falls risks assessments (20.9%), failures in communication (20.3%) and documentation issues (17.5%). Only 56.7% of PFDs received a response from organisations to whom they were addressed. Organisations tended to produce new protocols (58.5%), improve training (44.6%) and commence audits (34.3%) in response to PFDs. CONCLUSIONS: One in eight preventable deaths in England and Wales involved a fall. Addressing concerns raised by coroners should improve falls prevention and care following falls especially for older adults, but the poor response rate may indicate that lessons are not being learned. Wider dissemination of PFD findings may help reduce preventable fall-related deaths in the future.

Association between ethnic background and COVID-19 morbidity, mortality and vaccination in England: a multistate cohort analysis using the UK Biobank.

OBJECTIVES: Despite growing evidence suggesting increased COVID-19 mortality among people from ethnic minorities, little is known about milder forms of SARS-CoV-2 infection. We sought to explore the association between ethnic background and the probability of testing, testing positive, hospitalisation, COVID-19 mortality and vaccination uptake. DESIGN: A multistate cohort analysis. Participants were followed between 8 April 2020 and 30 September 2021. SETTING: The UK Biobank, which stores medical data on around half a million people who were recruited between 2006 and 2010. PARTICIPANTS: 405 541 subjects were eligible for analysis, limited to UK Biobank participants living in England. 23 891 (6%) of participants were non-white. PRIMARY AND SECONDARY OUTCOME MEASURES: The associations between ethnic background and testing, testing positive, hospitalisation and COVID-19 mortality were studied using multistate survival analyses. The association with single and double-dose vaccination was also modelled. Multistate models adjusted for age, sex and socioeconomic deprivation were fitted to estimate adjusted HRs (aHR) for each of the multistate transitions. RESULTS: 18 172 (4.5%) individuals tested positive, 3285 (0.8%) tested negative and then positive, 1490 (6.9% of those tested positive) were hospitalised, and 129 (0.6%) tested positive at the moment of hospital admission (ie, direct hospitalisation). Finally, 662 (17.4%) died after admission. Compared with white participants, Asian participants had an increased risk of negative to positive transition (aHR 1.24 (95% CI 1.02 to 1.52)), testing positive (95% CI 1.44 (1.33 to 1.55)) and direct hospitalisation (1.61 (95% CI 1.28 to 2.03)). Black participants had an increased risk of hospitalisation following a positive test (1.71 (95% CI 1.29 to 2.27)) and direct hospitalisation (1.90 (95% CI 1.51 to 2.39)). Although not the case for Asians (aHR 1.00 (95% CI 0.98 to 1.02)), black participants had a reduced vaccination probability (0.63 (95% CI 0.62 to 0.65)). In contrast, Chinese participants had a reduced risk of testing negative (aHR 0.64 (95% CI 0.57 to 0.73)), of testing positive (0.40 (95% CI 0.28 to 0.57)) and of vaccination (0.78 (95% CI 0.74 to 0.83)). CONCLUSIONS: We identified inequities in testing, vaccination and COVID-19 outcomes according to ethnicity in England. Compared with whites, Asian participants had increased risks of infection and admission, and black participants had almost double hospitalisation risk, and a 40% lower vaccine uptake.

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.

Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.

OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster. METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards. RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]). CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.

A matter of time: Circadian clocks in osteoarthritis and the potential of chronotherapy.

Osteoarthritis (OA) is a common and debilitating joint disease which develops and progresses with age. Despite extensive research into the disease, potent disease-modifying drugs remain elusive. Changes to the character and function of chondrocytes of the articular cartilage underly the pathogenesis of OA. A recently emerging facet of chondrocyte biology that has been implicated in OA pathogenesis is the role of circadian rhythms, and the cellular clock which governs rhythmic gene transcription. Here, we review the role of the chondrocyte's cellular clock in governing normal homeostasis, and explore the wide range of consequences that contribute to OA development when the clock is dysregulated by aging and other factors. Finally, we explore how harnessing this understanding of clock mechanics in aging and OA can be translated into novel treatment strategies, or 'chronotherapies', for patients.

Mitophagy in Parkinson's disease: From pathogenesis to treatment target.

Healthy mitochondria play an essential role in energy metabolism, but dysfunctional mitochondria can cause perturbations in cellular processes which can ultimately lead to cell death. The process which selectively removes and degrades dysfunctional mitochondria, mitophagy, protects against the accumulation of abnormal mitochondria and hence has a protective role in maintaining cell health. Increasing numbers of studies have linked defective mitophagy to a range of diseases, including Parkinson's disease (PD). Whilst current treatment strategies in PD can improve the classical motor symptoms of the disease, they are also associated with often severe side-effects, and generally do not tackle the underlying progressive neurodegeneration seen in the disease. The identification of novel treatment targets, such as mitophagy, are therefore of increasing interest in PD research. This review will begin by outlining the process of mitophagy, before examining evidence implicating mitophagy in both monogenic and sporadic forms of PD, drawing links between mitophagy and wider pathological processes such as protein accumulation and neuroinflammation. Finally, this review will examine the diverse strategies employed to promote mitophagy so far, discuss considerations arising from these studies, and present a framework for eventual assessment of mitophagy-promoting compounds and their viability as a treatment strategy for PD patients.