Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251.

Characteristics of children requiring admission to neonatal care and paediatric intensive care before the age of 2 years in England and Wales: a data linkage study.

OBJECTIVE: To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. DESIGN: A data linkage study of routinely collected data. SETTING: National Health Service NNUs and PICUs in England and Wales PATIENTS: Children born from 2013 to 2018. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Admission to PICU before the age of 2 years. RESULTS: A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU.The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks' gestational age, n=3550). A third of children admitted to PICU had more than one admission. CONCLUSIONS: Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams.

Service implications of the revised 2022 National Institute for Health and Care Excellence (NICE) follow-up guidelines for stage IA-IIC melanoma.

BACKGROUND: The 2022 National Institute for Health and Care Excellence melanoma guideline update made significant changes to follow-up. The aim of this study was to assess the impact these changes will have on a national melanoma cohort over a 5-year follow-up interval. METHODS: Anonymized, individual-level, population-scale, linkable primary and secondary care National Health Service data for an 18-year interval (2000-2018) in Wales, UK were analysed. These data were used to predict the number of patients over a 10-year interval (2020-2030) that would be diagnosed with melanoma. Follow-up schedules for the 2015 and 2022 National Institute for Health and Care Excellence melanoma guidelines were then used to calculate the number of clinician-led appointments, the number of radiological investigations, and the total healthcare cost between 2025 and 2030, corresponding to a 5-year patient follow-up interval, for those with stage IA-IIC melanoma. RESULTS: Between 2025 and 2030 it is predicted that implementation of the 2022 guidelines would lead to 21 122 (range 19 194-23 083) fewer clinician-led appointments for patients with stage IA-IIC melanoma. However, there would be a significant increase in the number of radiological investigations (7812; range 7444-8189). These changes would lead to a €2.74 million (€1.87 million-€3.61 million) reduction in the total cost of follow-up over the interval 2025-2030. CONCLUSION: Melanoma follow-up guideline changes will result in a substantial reduction in the number of clinical follow-up appointments, but a significant additional burden to radiological services. The overall cost of follow-up at a national level will be reduced.

Identifying the public health needs of a UK probation cohort: a cross-sectional analysis.

BACKGROUND: The health needs of those under probation are likely high, but they have received very little public health attention. Limited evidence exists on the public health needs and interventions to support this cohort. METHODS: Surveys were completed by 257 people on probation as part of a local health needs assessment. Results were compared with the general population responses from the National Survey for Wales (2021-22). RESULTS: People on probation were 4.2 times more likely to self-report not-good general health (fair, bad or very bad) than the general population (adjusted Odds Ratio [aOR] 4.2, 95% Confidence Intervals [CI] 3.2-5.4). The odds of having a mental health condition were over eight times higher than the general population (aOR 8.8, 95% CI 6.8-11.4). Prevalence of smoking (52%), drug use (60%), attention-deficit hyperactivity disorder (21%), autism (4%) and dyslexia (15%) were all higher than the general population. General Practitioner usage and hospital stays were higher, but dentist or optician usage lower than the general population (P < 0.05). Emergency departments were accessed by 35%, with 9% frequenting them three or more times. CONCLUSIONS: People on probation have poorer self-reported health, higher prevalence of unhealthy behaviours and higher accessing of reactive health services than the general population.

Hinge prostheses in the revision of unicompartmental knee replacement: a descriptive analysis of data from the national joint registry for England, Wales and Northern Ireland.

INTRODUCTION: Unicompartmental knee replacement (UKR) is an effective surgical strategy in patients with isolated medial or lateral compartment osteoarthritis. Study aims were to (1) describe the epidemiology of patients undergoing revision of UKR to a hinge knee replacement (HKR); (2) identify factors influencing time to revision; (3) evaluate HKR survival. MATERIALS AND METHODS: An analysis of National Joint Registry data was undertaken, exploring revision of UKR to HKR between 2007 and April 2021. Descriptive analysis of eligible patients and Cox Regression to identify key determinants of time to revision were performed. Failure of HKR post-revision was assessed using survival analysis. RESULTS: 111 patients underwent revision of UKR to HKR. Median age at revision was 70 years and most common indications were instability (n = 42) and infection (n = 22). The most common implant was a rotating HKR. Significant independent factors associated with earlier revision were periprosthetic fracture (p = 0.03) and malalignment (p = 0.03). Progressive osteoarthritis (p = 0.01) and higher ASA grades (3: p = 0.01, 4: p < 0.01) delayed time to revision; patient sex and age were not significant factors. Ten patients required subsequent re-revision; median age at re-revision was 61 years. HKR revised from UKR had an 89.3% revision-free risk at 5 years. Male sex (p < 0.01) and younger age (p < 0.01) were associated with re-revision. CONCLUSIONS: Factors associated with time to revision may be used to counsel patients prior to UKR. The survivorship of the HKR of 89.3% at 5 years is concerning and careful consideration should be given when using this level of constraint when revising UKR in younger or male patients.

Cardiovascular events and venous thromboembolism after primary malignant or non-malignant brain tumour diagnosis: a population matched cohort study in Wales (United Kingdom).

BACKGROUND: Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the CVD incidences and cardiovascular risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities. METHODS: Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥ 18 years in the primary care database with first diagnosis of malignant or non-malignant brain tumour identified in the cancer registry in 2000-2014 and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any cancer diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable Cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour (malignant or non-malignant) and follow-up period. RESULTS: There were 2869 and 3931 people diagnosed with malignant or non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). After the first year, the risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained higher than controls. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls. CONCLUSIONS: The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.

Profiles of tobacco smokers and ex-smokers in a large-scale random sample survey across Wales: an unsupervised machine-learning cluster analysis.

BACKGROUND: The Welsh government recently set a target to be smoke-free by 2030, which means reducing the prevalence of tobacco smoking in adults to 5% by then. The goal is to improve health and population life expectancy. To support this strategy, we identified profile groups with different sets of socioeconomic and demographic characteristics within the population of smokers. We compared these profiles to those identified in the ex-smoker population to provide a broader understanding of smokers and inform targeting of interventions and policy. METHODS: We did a cross-sectional study using data from the National Survey for Wales. This survey is a random sample telephone survey of individuals aged 16 years and older across Wales carried out from Sept 1, 2021 to Jan 31, 2022, weighted to be representative of the Welsh population. For the smoking subgroup, we did a weighted hierarchical cluster analysis with multiple imputation to impute missing data and repeated it for ex-smokers. In total, 63 survey variables were used in the analysis. These variables included smoking history, e-cigarette use, sociodemographics, lifestyle factors, individual-level deprivation, general health and long-term conditions, mental health, and wellbeing. FINDINGS: Among the 6407 respondents (weighted proportions: 49% male, 51% female; 28% aged 16-34 years, 46% aged 35-44 years, 26% aged ≥65 years; 95% white, 5% other ethnicity), 841 (13%) smoked and 2136 (33%) were ex-smokers. Four distinctive profiles of smokers were identified, the groups were of relatively comparable size and characterised by similarities described as (1) high-risk alcohol drinkers and without children; (2) single, mostly in social housing, and poor health and mental health; (3) mostly single, younger, tried e-cigarettes, and poor mental health; (4) older couples and poor health; when comparing the groups with each other. Cluster quality and validation statistics were considered fair: silhouette coefficient=0·09, Dunn index (Dunn2)=1·06. Generally, ex-smoker clusters differed from smoking clusters because of themes related to increased sickness, better affluence, employment, and older age (≥75 years). INTERPRETATION: This study suggests that not all smokers are the same, and they do not fall into one coherent group. Smoking cessation interventions to improve the health of ageing populations might need a different approach to consider a wider context or motivations to inform targeted quitting. It is acknowledged that smoking might be underreported because of perceived social unacceptability. FUNDING: Public Health Wales.

Mastectomy patterns among older women with early invasive breast cancer in England and Wales: A population-based cohort study.

INTRODUCTION: Older women with early invasive breast cancer (EIBC) are more likely to receive a mastectomy compared with younger women. This study assessed factors associated with receiving a mastectomy among older women with EIBC, with a particular focus on comorbidity and frailty. MATERIALS AND METHODS: Women diagnosed with EIBC (stages I-IIIa) aged ≥50 years from 2014 to 2019 in English and Welsh NHS organisations who received breast surgery were identified from cancer registration datasets linked to routine hospital data. Separate multivariable logistic regression models explored factors associated with mastectomy use, within each tumour stage (T1-T3). For each tumour stage, risk-adjusted rates of mastectomy were calculated for each NHS organisation and displayed using funnel plots. RESULTS: We included 106,952 women with EIBC: 23.4% received a mastectomy as their first breast cancer surgery. Receipt of mastectomy was more common among patients with a higher tumour stage (T1: 12.3%; T2: 37.6%; T3: 77.5%), and mastectomy use increased with age within each tumour stage category (50-59 vs 80 + years: 11.8% vs 26.3% for T1; 31.5% vs 56.9% for T2; 73.4% vs 90.3% for T3). Results from a multivariable regression model showed that more severe frailty was associated with mastectomy use for women with T1 (p = 0.002) or T2 (p = 0.003) tumours, but may not be for women with T3 tumours (p = 0.041). There was no association between comorbidity and mastectomy use after accounting for frailty (all p > 0.1). Adjusting for clinical and patient factors only slightly reduced the association between age and mastectomy use. Variation in mastectomy use between NHS organisations was greatest for women with T2 EIBC (unadjusted range: 17.7% to 68.4%). DISCUSSION: Older women with EIBC are more commonly treated with mastectomy. This could not be explained by tumour characteristics or physical fitness, raising questions about whether surgical decision-making inconsistently incorporates information on patient fitness and functional age.

A Comparison of the Periprosthetic Fracture Rate of Unicompartmental and Total Knee Replacements: An Analysis of Data of >100,000 Knee Replacements from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man and Hospital Episode Statistics.

BACKGROUND: Periprosthetic fractures are rare but devastating complications of knee replacement, often requiring complex surgery with substantial morbidity and mortality. It is not known how the fracture rates after total knee replacement (TKR) and unicompartmental knee replacement (UKR) compare. We performed the first matched study comparing TKR and UKR periprosthetic fracture rates. METHODS: This study involved 54,215 UKRs and 54,215 TKRs, identified in the National Joint Registry and Hospital Episodes Statistics database, which were propensity score-matched on patient and surgical factors. The International Classification of Diseases, Tenth Revision, (ICD-10) code M96.6 was used to identify periprosthetic fractures at ≤3 and >3 months postoperatively, as well as estimate rates at up to 10 years. Subgroup analyses were performed in different age groups (<55, 55 to 64, 65 to 74, and ≥75 years), body mass index (BMI) categories (normal, 18.5 to <25 kg/m 2 ; overweight, 25 to <30 kg/m 2 ; obese, 30 to <40 kg/m 2 ; and morbidly obese, ≥40 kg/m 2 ), and sexes. RESULTS: The 3-month fracture rate was 0.09% (n = 50) in the UKR group and 0.05% (n = 25) in the TKR group, with this difference being significant (odds ratio [OR], 2.0; p = 0.004). The rate of fractures occurring at >3 months was 0.32% (n = 171) in the UKR group and 0.61% (n = 329) in the TKR group (OR, 0.51; p < 0.001). At 10 years, the cumulative incidence of fractures was 0.6% after UKR versus 1% after TKR (OR, 0.68; p < 0.001). Fracture rates increased with increasing age, decreasing BMI, and female sex for both UKRs and TKRs. CONCLUSIONS: The fracture risk was small after both UKR and TKR, with small absolute differences between implant types. During the first 3 postoperative months, the fracture rate after UKR was 0.1% and was about twice as high as that after TKR. However, over the first 10 years, the cumulative fracture rate after TKR was 1% and was almost twice as high as that after UKR. Fracture rates after both UKR and TKR were higher in women, patients ≥75 years of age, and patients with normal weight. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

COVID-19 vaccination in pregnancy: the impact of multimorbidity and smoking status on vaccine hesitancy, a cohort study of 25,111 women in Wales, UK.

BACKGROUND: Multimorbidity, smoking status, and pregnancy are identified as three risk factors associated with more severe outcomes following a SARS-CoV-2 infection, thus vaccination uptake is crucial for pregnant women living with multimorbidity and a history of smoking. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. METHODS: This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was employed to examine and compare the length of time to vaccination uptake in pregnancy by considering multimorbidity, smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. The study also assessed the variation in uptake by multimorbidity, smoking status, and demographics, both jointly and separately for the independent conditions, using hazard ratios (HR) derived from the Cox regression model. RESULTS: Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.002). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). CONCLUSION: Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Pregnant individuals living with multimorbidity exhibit a slight but statistically significant reduction in vaccine hesitancy towards COVID-19 during pregnancy.

Contrasting socio-economic influences on colorectal cancer incidence and survival in England and Wales.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world and second most common cause of cancer death. The relationship between socio-economic deprivation and CRC incidence is unclear and previous findings have been inconsistent. There is stronger evidence of an association between area-level deprivation and CRC survival; however, few studies have investigated the association between individual-level socio-economic status (SES) and CRC survival. Data from the Office for National Statistics Longitudinal Study (LS) in England and Wales was used. LS members aged 50+ were stratified by individual-level educational attainment, social class, housing tenure and area deprivation quintile, measured at the 2001 Census. Time-to-event analysis examined associations between indicators of SES and CRC incidence and survival (all-cause and CRC death), over a 15-year follow-up period. Among 178116 LS members, incidence of CRC was lower among those with a degree, compared to those with no degree and higher among those employed in manual occupations compared to non-manual occupations. No clear relationship was observed between CRC incidence and the area-based measure of deprivation. Disparities were greater for survival. Among 5016 patients diagnosed with CRC aged 50+, probability of death from all-causes was lower among those with a degree, compared to no degree and higher among those employed in manual occupations, compared to non-manual occupations and among those living in social-rented housing, compared to owner-occupiers. Individual indicators of SES were also associated with probability of death from CRC. Those living in the most deprived areas had a higher probability of death (from all-causes and CRC) compared to those in the least deprived areas. Both individual and area-based indicators of SES were associated with CRC survival, and the relationships were stronger than those observed for CRC incidence. These findings could help inform more effective targeting of public health interventions for CRC.

The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.

PURPOSE: Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care. METHODS: A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds. RESULTS: We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision. CONCLUSIONS: We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.

Patients' recovery of mobility and return to original residence after hip fracture are associated with multiple modifiable components of hospital service organisation: the REDUCE record-linkage cohort study in England and Wales.

BACKGROUND: Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture. METHODS: A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture. RESULTS: Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17-43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8-13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4-42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8-30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]). CONCLUSIONS: Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence.

Cardiovascular morbidity and mortality in patients in Wales, UK with resistance to thyroid hormone ß (RTHß): a linked-record cohort study.

BACKGROUND: Individuals with resistance to thyroid hormone owing to mutations in the thyroid hormone receptor ß gene (RTHß) exhibit impaired tissue sensitivity to thyroid hormones, but retain sensitivity in cardiac tissue. Long-term health and survival outcomes in this rare disorder have not been evaluated. We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTHß, followed-up in UK endocrine clinics. METHODS: In a retrospective cohort design, we linked genetically confirmed patients with RTHß and age-matched and sex-matched population controls to outcomes in datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank. Kaplan-Meier and Cox regression models analysed associations of RTHß with all-cause mortality and cardiovascular events. FINDINGS: We identified 61 patients with a genetic diagnosis of RTHß between Jan 1, 1997, and Dec 31, 2019, and matched them with 2750 controls. Compared with controls, patients exhibited increased risks for all-cause mortality (hazard ratio [HR] 2·84, 95% CI 1·59-5·08), atrial fibrillation (10·56, 4·72-23·63), heart failure (HR 6·35, 95% CI 2·26-17·86), and major adverse cardiovascular events (MACE), comprising cardiovascular death, acute myocardial infarction, heart failure, or strokes (HR 3·49, 95% CI 2·04-5·99). The median age of first occurrence of any adverse event was 11 years earlier in patients (56 years, 95% CI 44-65) compared with controls (67 years, 65-70). Cubic spline analyses showed positive associations between FT4 concentrations at diagnosis and mortality or MACE, with FT4 concentration of 30 pmol/L or greater conferring increased risk. Compared with no intervention, treatment with antithyroid drugs, surgery or radioiodine gland ablation, or thyroxine did not control thyroid hormone excess. INTERPRETATION: We have documented reduced survival and increased cardiovascular morbidity in a cohort of patients with RTHß for the first time. These outcomes might be driven by lifelong cardiac exposure to thyroid hormone excess; and effective therapies, targeting hormone resistant pathways, could potentially curtail this risk. FUNDING: Royal College of Physicians, Wellcome Trust Investigator Award, and NIHR Cambridge Biomedical Research Centre.

Variation in Rates of Post-Mastectomy Radiotherapy Among Women with Early Invasive Breast Cancer in England and Wales: A Population-Based Cohort Study.

AIMS: This study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. MATERIALS AND METHODS: The study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I-IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. RESULTS: Among 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3-77.3%), but varied less for the high-risk (range 77.1-91.6%) and low-risk groups (range 4.1-32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. CONCLUSIONS: Rates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.

Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study.

BACKGROUND: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care. METHODS: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites. FINDINGS: 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4-73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5-80·1), negative predictive value of 97·6% (97·1-98·0), sensitivity of 66·3% (61·2-71·1), and specificity of 98·4% (98·1-98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0-34·1) in stage I to 95·3% (88·5-98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 85·2% (95% CI 79·8-89·3) of cases. Sensitivity 80·4% (95% CI 66·1-90·6) and negative predictive value 99·1% (98·2-99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer. INTERPRETATION: This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms. FUNDING: GRAIL Bio UK.

Outcomes from a national screening program for Ukrainian refugees at risk of drug resistant tuberculosis in Wales.

High rates of drug-resistant tuberculosis in Ukraine suggest screening is necessary to mitigate public health hazards for host populations. A pathway was implemented in Wales and data prospectively collected Between 8 April and 21 December 2022. Of 5425 Ukrainian arrivals, notifications were received by TB teams on 2395 (44%) of whom 1955 (82%) were screened. The refugees were young (median age 30, IQR 14-41), and predominantly female (66.1%). Interferon- gamma release assay (IGRA) tests were positive in 112 (6.5%). One Case of active tuberculosis was identified (0.05%). Our data supports European guidelines that routine screening of this population is not recommended, but we remain uncertain as to the risks of this population going forwards.

Repeat operations in patients with anal fistula, a retrospective study across England and Wales.

AIM: This article reports the frequency of repeat operations including waiting times within the National Health Service (NHS) of England and Wales. METHODS: Retrospective study on repeat operations for anal fistula (AF) performed between 1st January 2010 and 31st December 2016. Data were extracted from the national registry of data entered into Hospital Episode Statistics (HES). Patient factors (age, sex, self-declared ethnicity) and geographical location were tested for association with repeat operations and time to the second operation. RESULTS: We analysed 36,223 patients that had an operation for AF within 148 NHS trusts. The median follow-up time was 28 months. The majority of patients (67.4%) had only one operation. Eighty-five per cent of them remained under the care of a single consultant. Six per cent of the repeat surgeries occurred in at least three different treatment sites. Young age and female sex were associated with higher rates of repeat operations. Non-declared and Black or Black British ethnicity were associated with fewer operations. The median waiting time between the first and second operations was 27.4 weeks (IQR: 14.7-55.3); between the second and third 28.0 weeks (IQR: 14.7-57.0); between the third and fourth 29.0 weeks. CONCLUSION: This large real world population-based study shows that the majority of patients with AF undergo only one operation. Patients requiring multiple procedures tend to stay under the care of a small number of consultants but waiting times between operations are long. There is a geographical variation in the number of operations and the time between them.

Excess deaths by cause and place of death in England and Wales during the first year of COVID-19.

Using officially registered weekly mortality data, we estimate a counterfactual death count in the absence of the pandemic and we calculate the number of excess deaths in England and Wales during 2020 after the pandemic onset. We also break down those figures by region, age, gender, place of death, and cause of death. Our results suggest that there were 82,428 (95% Confidence interval [CI]: 78,402 to 86,415) excess deaths, and 88.9% (95% CI: 84.8%-93.5%) of them was due to COVID-19, suggesting that non-COVID-19 excess mortality may have been slightly higher that what has been previously estimated. Regarding deaths not due to COVID-19, persons older than 45 years old who died at their homes, mainly from heart diseases and cancer, were the most affected group. Across all causes of death, there was increased excess mortality from dementia and Alzheimer's disease, diabetes, Parkinson's disease and heart-related disease, while at the same period there was a reduction in deaths from pneumonia and influenza, stroke as well as infectious diseases and accidents. Supported by regional panel event estimates, our results highlight how measures to mitigate the pandemic spread and ease the pressure on healthcare service systems may adversely affect out-of-hospital mortality from other causes.