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Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association.Design Cohort study and self controlled case series.Setting Clinical Practice Research Datalink (1990 to 2013) in UK.Participants Adult patients with a new prescription for a PPI individually matched with controls.Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription.Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99).Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors.

Background Chest radiographs are generally used for diagnostic purposes. They also have potential to quantify disease severity. This analysis tested the hypothesis that there was an association between chest radiograph opacification and measures of respiratory physiological status and systemic inflammation in patients with Covid‐19 infection. Methods Data on chest radiograph opacification were compared with concurrent measures of oxygen requirements and saturation and serum C‐reactive protein. Results Data were available from 628 individuals. The median opacification on chest radiographs was 20% (interquartile range 5–45). This was associated both SFR (oxygen saturation/supplementary oxygen) with an r value of −0.38 (95% confidence intervals CI: −0.45 to −31, Pearson's correlation coefficient) and CRP (+0.33; 95% CI: +0.24 to +0.41, Pearson's correlation coefficient). Conclusion Chest radiograph opacification scores are associated with both respiratory physiology status and systemic inflammation levels in patients with Covid‐19 infection. Chest radiograph opacification scores are associated with both respiratory physiology status and systemic inflammation levels in patients with Covid‐19 infection.

Few studies have quantified the incidence and prevalence of celiac disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time and age groups. Understanding this epidemiology is crucial for hypothesizing about causes and quantifying the burden of disease. Patients with CD or DH were identified in the Clinical Practice Research Datalink between 1990 and 2011. Incidence rates and prevalence were calculated by age, sex, year, and region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and region were calculated with Poisson regression. A total of 9,087 incident cases of CD and 809 incident cases of DH were identified. Between 1990 and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence interval (CI), 3.8-6.8) to 19.1 per 100,000 person-years (95% CI, 17.8-20.5; IRR, 3.6; 95% CI, 2.7-4.8). The incidence of DH decreased over the same time period from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96; 95% CI, 0.94-0.97). The absolute incidence of CD per 100,000 person-years ranged from 22.3 in Northern Ireland to 10 in London. There were large regional variations in prevalence for CD but not DH. We found a fourfold increase in the incidence of CD in the United Kingdom over 22 years, with large regional variations in prevalence. This contrasted with a 4% annual decrease in the incidence of DH, with minimal regional variations in prevalence. These contrasts could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation) or the possibility that diagnosing and treating CD prevents the development of DH.

There is a need for unbiased estimates of cause-specific mortality by etiology in patients with liver cirrhosis. The aim of this study is to use nationwide linked electronic routine healthcare data from primary and secondary care alongside the national death registry data to report such estimates. We identified from the linked Clinical Practice Research Datalink (CPRD) and English Hospital Episode Statistics adults with an incident diagnosis of liver cirrhosis linked to the Office for National Statistics between 1998 and 2009. Age-matched controls from the CPRD general population were selected. We calculated the cumulative incidence (adjusting for competing risks) and excess risk of death by 5 years from diagnosis for different causes of death, stratified by etiology and stage of disease. Five thousand one hundred and eighteen patients with cirrhosis were matched to 152,903 controls. Among compensated patients, the 5-year excess risk of liver-related death was higher than that of any other cause of death for all patients, except those of unspecified etiology. For example, those of alcohol etiology had 30.8% excess risk of liver-related death (95% confidence interval (CI): 27.9%, 33.1%) compared with 9.9% excess risk of non-liver-related death. However, patients of unspecified etiology had a higher excess risk of non-liver-related compared with liver-related death (10.7% vs. 6.7%). This was due to a high excess risk of non-liver neoplasm death (7.7%, 95% CI: 5.9%, 9.5%). All decompensated patients had a higher excess of liver-related mortality than any other cause. In order to reduce associated mortality among people with liver cirrhosis, patients' care pathways need to be tailored depending on the etiology and stage of the disease.

Faecal Immunochemical Testing (FIT) is recommended for patients presenting to primary care with symptoms suggestive of colorectal cancer. This study quantified variations in use across England. Retrospective cohort of English patients (≥18 years) with a FIT result reported in routinely collected primary care records, 2019-2023. Rates of FIT testing by age, sex, year and region were adjusted using Poisson regression. Multivariate logistic regression compared the effect of factors on the proportion of results exceeding the recommended referral threshold (10µgHb/g). Between 01/01/2019 and 05/06/2023 there were 531,735 FIT results among 495,121 patients. Rates of testing increased from 0.69 per thousand person-years in 2019 (95% CI 0.68-0.71) to 27.70 in 2023 (95% CI 27.56-27.85). There were large variations in testing between regions, with rates >3-fold higher in the Northeast than the West Midlands: 17.05 (95% CI 16.87-17.23) versus 4.72 (95% CI 4.67-4.76) per thousand person-years. About 20.4% of FIT results were ≥10µgHb/g. Despite increased testing, this did not change over time. The proportion of FIT ≥10µgHb/g was lower in regions with higher rates of testing, from 16.7% (Southwest) to 25.3% (Southeast; rates of testing 14.62 and 8.00 per thousand person-years respectively). This difference in proportion of FIT ≥10µgHb/g persisted after adjusting for year, sex and age (OR 0.57, 95% CI 0.55-0.58). Rapid increases in FIT testing in primary care show large, persistent variations between English regions, which correlate with the proportion of results meeting the criteria for onward referral. Differences in the population tested and FIT's implementation between regions are likely to explain these variations.

There is no routine registration of the occurrence of newly diagnosed cases of cirrhosis in the United Kingdom. This study seeks to determine precise estimates and trends of the incidence of cirrhosis in England, and directly compare these figures with those for the 20 most commonly diagnosed cancers in the United Kingdom. We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to perform a population-based cohort study. Adult incident cases with a diagnosis of cirrhosis between January 1998 and December 2009 were identified. We described trends in incidence by sex and etiology. We performed a direct standardization to estimate the number of people being newly diagnosed with cirrhosis in 2009, and calculated the change in incidence between 1998 and 2009. A total of 5,118 incident cases of cirrhosis were identified, 57.9% were male. Over the 12-year period, crude incidence increased by 50.6%. Incidence increased for both men and women and all etiology types. We estimated approximately 17,000 people were newly diagnosed with cirrhosis in 2009 in the United Kingdom, greater than that of the fifth most common cancer non-Hodgkin's lymphoma. The percentage change in incidence of cirrhosis between 1998 and 2009 for both men (52.4%) and women (38.3%) was greater than that seen for the top four most commonly diagnosed cancers in the United Kingdom (breast, lung, bowel, and prostate). The occurrence of cirrhosis increased more than that of the top four cancers during 1998 to 2009 in England. Strategies to monitor and reduce the incidence of this disease are urgently needed.

We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell's C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88-0.88) in the first year of follow up, to 0.85 (0.85-0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C = 0.85, 0.83-0.87) compared to the Charlson (C = 0.79, 0.77-0.82) or Elixhauser index (C = 0.81, 0.79-0.83). The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores.

Respiratory rate(RR) is the only vital sign that is currently measured by direct observation in many high-income countries in many healthcare settings. However, when relying on direct observation by humans, values may be susceptible to measurement error. In particular, a continuous variable like RR may be inadvertently semicategorised due to rounding and/or multiplying up counts from shorter periods to give estimated counts for a full minute.

Parental drinking can cause harm to the offspring. A parent's diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent's educational level and diagnosis of ALD. We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent's ALD diagnosis. The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent's ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent's ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact. Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent's diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent's hospitalization with ALD.