UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). METHODS: This was a nationwide observational cohort study conducted from August 2017 until June 2021. RESULTS: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P < .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P < .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P < .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. CONCLUSION: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.

Examining organisational responses to performance-based financial incentive systems: a case study using NHS staff influenza vaccination rates from 2012/2013 to 2019/2020.

OBJECTIVE: Financial incentives are often applied to motivate desirable performance across organisations in healthcare systems. In the 2016/2017 financial year, the National Health Service (NHS) in England set a national performance-based incentive to increase uptake of the influenza vaccination among frontline staff. Since then, the threshold levels needed for hospital trusts to achieve the incentive (ie, the targets) have ranged from 70% to 80%. The present study examines the impact of this financial incentive across eight vaccination seasons. DESIGN: A retrospective observational study examining routinely recorded rates of influenza vaccination among staff in all acute NHS hospital trusts across eight vaccination seasons (2012/2013-2019/2020). The number of trusts included varied per year, from 127 to 137, due to organisational changes. McCrary's density test is conducted to determine if the number of hospital trusts narrowly achieving the target by the end of each season is higher than would be expected in the absence of any responsiveness to the target. We refer to this bunching above the target threshold as a 'threshold effect'. RESULTS: In the years before a national incentive was set, 9%-31% of NHS Trusts reported achieving the target, compared with 43%-74% in the 4 years after. Threshold effects did not emerge before the national incentive for payment was set; however, since then, threshold effects have appeared every year. Some trusts report narrowly achieving the target each year, both as the target rises and falls. Threshold effects were not apparent at targets for partial payments. CONCLUSIONS: We provide compelling evidence that performance-based financial incentives produced threshold effects. Policymakers who set such incentives are encouraged to track threshold effects since they contain information on how organisations are responding to an incentive, what enquiries they may wish to make, how the incentive may be improved and what unintended effects it may be having.

Outcomes for surgical procedures funded by the English health service but carried out in public versus independent hospitals: a database study.

BACKGROUND: The outcomes of elective surgery in public versus Independent Sector Healthcare Providers (ISHPs) are a matter of policy relevance and theoretical interest. METHODS: Retrospective study of all National Health Service (NHS) hospitals and ISHPs in England that provided NHS-funded elective surgery. We used data from the England-wide Hospital Episode Statistics to study 18 common surgical procedures performed between 2006 and 2019. In-hospital outcomes included length of stay, emergency transfers to another hospital or death. Posthospital outcomes included readmission or death within 28 days. Outcomes were compared for each operation type by propensity score matching and survival analysis. RESULTS: The data set included 3 203 331 operations in 734 NHS hospitals and 468 259 operations in 274 ISHPs.In-hospital outcomes: Across all 18 included operation types, length of stay was significantly longer for patients treated in NHS hospitals compared with ISHPs. Effect sizes ranged from a hazard ratio (HR) of 2.15 (95% CI 1.72 to 2.68) for total hip replacement to 1.07 (95% CI 1.05 to 1.09) for wisdom tooth removal; a mean difference of 2.49 and 0.02 days, respectively.Postdischarge outcomes: Treatment at an ISHP was associated with a lower risk of emergency readmission compared with NHS treatment. HRs ranged from 0.36 (95% CI 0.28 to 0.46) for lumbar decompression to 0.75 (95% CI 0.67 to 0.85) for cholecystectomy; absolute risk differences of 1.5 and 1.3 percentage points. There was no difference in mortality. CONCLUSION: Elective surgery in an ISHP is associated with shorter lengths of stay and lower readmission rates than treatment in NHS hospitals across 18 operation types. The data were matched on observable covariates, but we cannot exclude selection bias due to unobserved confounders.

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area.

BACKGROUND: Studies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients. METHODS: Patients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching. RESULTS: All patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6). CONCLUSIONS: Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.

Effects of Primary Sclerosing Cholangitis on Risks of Cancer and Death in People With Inflammatory Bowel Disease, Based on Sex, Race, and Age.

BACKGROUND & AIMS: There are insufficient population-level data on the effects of primary sclerosing cholangitis (PSC) in patients with inflammatory bowel disease (IBD). METHODS: We identified incident cases of IBD, with PSC (PSC-IBD) and without, from April 2006 to April 2016 and collected data on outcomes through April 2019. We linked data from national health care registries maintained for all adults in England on hospital attendances, imaging and endoscopic evaluations, surgical procedures, cancer, and deaths. Our primary aim was to quantify the effects of developing PSC in patients with all subtypes of IBD and evaluate its effects on hepatopancreatobiliary disease, IBD-related outcomes, and all-cause mortality, according to sex, race, and age. RESULTS: Over 10 years, we identified 284,560 incident cases of IBD nationwide; of these, 2588 patients developed PSC. In all, we captured 31,587 colectomies, 5608 colorectal cancers (CRCs) 6608 cholecystectomies, and 41,055 patient deaths. Development of PSC was associated with increased risk of death and CRC (hazard ratios [HRs], 3.20 and 2.43, respectively; P < .001) and a lower median age at CRC diagnosis (59 y vs 69 y without PSC; P < .001). Compared to patients with IBD alone, patients with PSC-IBD had a 4-fold higher risk of CRC if they received a diagnosis of IBD at an age younger than 40 years; there was no difference between groups for patients diagnosed with IBD at an age older than 60 years. Development of PSC also increased risks of cholangiocarcinoma (HR, 28.46), hepatocellular carcinoma (HR, 21.00), pancreatic cancer (HR, 5.26), and gallbladder cancer (HR, 9.19) (P < .001 for all). Risk of hepatopancreatobiliary cancer-related death was lower among patients with PSC-IBD who received annual imaging evaluations before their cancer diagnosis, compared to those who did not undergo imaging (HR, 0.43; P = .037). The greatest difference in mortality between the PSC-IBD alone group vs the IBD alone group was for patients younger than 40 years (incidence rate ratio >7), in contrast to those who received a diagnosis of IBD when older than 60 years (incidence rate ratio, <1.5). Among patients with PSC-IBD we observed 173 first liver transplants. Liver transplantation and PSC-related events accounted for approximately 75% of clinical events when patients received a diagnosis of PSC at an age younger than 40 years vs 31% of patients who received a diagnosis when older than 60 years (P < .001). African Caribbean heritage was associated with increased risks of liver transplantation or PSC-related death compared with white race (HR, 2.05; P < .001), whereas female sex was associated with reduced risk (HR, 0.74; P = .025). CONCLUSIONS: In a 10-year, nationwide study, we confirmed that patients with PSC-IBD have increased risks of CRC, hepatopancreatobiliary cancers, and death compared to patients with IBD alone. In the PSC-IBD group, diagnosis of IBD at age younger than 40 years was associated with greater risks of CRC and all-cause mortality compared with diagnosis of IBD at older ages. Patients who receive a diagnosis of PSC at an age younger than 40 years, men, and patients of African Caribbean heritage have an increased incidence of PSC-related events.