Explore the vast range of titles available.

Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76–2·12; p<0·0001), hypothyroidism (2·31, 2·05–2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21–1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96–1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88–1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. None.

OBJECTIVE: Diabetes is increasingly common in cystic fibrosis, but little information describing its influence on mortality exists. Using national U.K. data, in this study we document diabetes-specific mortality rates, estimate the impact of diabetes on survival, and estimate population-attributable fractions. RESEARCH DESIGN AND METHODS: This retrospective cohort study identified 8,029 individuals aged 0-65 years from the U.K. Cystic Fibrosis Registry (1996-2005). A total of 5,892 patients were included in analyses of mortality rates, and 4,234 were included in analyses of risk factors. We calculated age-adjusted mortality rates using Poisson regression, standardized mortality ratios using the population of England and Wales, and relative risks using proportional hazards modeling. RESULTS: During 17,672 person-years of follow-up, 393 subjects died. The age-adjusted mortality rate was 1.8 per 100 person-years (95% CI 1.6-2.0). The age-adjusted mortality rates per 100 person-years were 2.0 (1.8-2.4) in female subjects and 1.6 (1.4-1.9) in male subjects, and 4.2 (3.4-5.1) in individuals with diabetes vs. 1.5 (1.3-1.7) in those without diabetes. Independent risk factors for death included diabetes (hazard ratio 1.31 [95% CI 1.03-1.67], female sex (1.71 [1.36-2.14]) plus poorer pulmonary function, lower BMI, Burkholderia cepacia infection, absence of Staphylococcus aureus infection, allergic bronchopulmonary aspergillosis, liver disease, prior organ transplantation, and corticosteroid use. CONCLUSIONS: Individuals with cystic fibrosis die earlier if they have diabetes, which, if delayed or better treated, might reasonably extend survival; this hypothesis merits testing.

The risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods. Electronic searches using the terms \"troponin I\" or \"troponin T\", and \"pregnancy\", \"pregnancy complications\" or \"obstetrics\". cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia. The search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia. TnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology.

OBJECTIVE:--Longer survival of patients with cystic fibrosis has increased the occurrence of cystic fibrosis-related diabetes (CFRD). In this study we documented the incidence of CFRD and evaluated the association between mutations responsible for cystic fibrosis and incident CFRD, while identifying potential risk factors. RESEARCH DESIGN AND METHODS--This was a population-based longitudinal study of 50 cystic fibrosis speciality clinics in the U.K. Subjects included 8,029 individuals aged 0-64 years enrolled in the U.K. Cystic Fibrosis Registry during 1996-2005. Of these, 5,196 with data and without diabetes were included in analyses of incidence, and 3,275 with complete data were included in analyses of risk factors. Diabetes was defined by physician diagnosis, oral glucose tolerance testing, or treatment with hypoglycemic drugs. RESULTS:--A total of 526 individuals developed CFRD over 15,010 person-years. The annual incidence was 3.5%. The incidence was higher in female patients and in patients with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in classes I and II. In a multivariate model of 377 cases of 3,275 patients, CFTR class (relative risk 1.70 [95% CI 1.16-2.49], class I or II versus others), increasing age, female sex, worse pulmonary function, liver dysfunction, pancreatic insufficiency, and corticosteroid use were independently associated with incident diabetes. CONCLUSIONS:--The incidence of CFRD is high in Britain. CFTR class I and II mutations increase the risk of diabetes independent of other risk factors including pancreatic exocrine dysfunction.

Background Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. Methods Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. Results One hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 μg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. Conclusions FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

Background. Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. Methods. From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)—positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. Results. Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%–9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 10 9 neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 10 9 neutrophils/L in EIA-negative controls (P < .0001) and 7.9 × 10 9 neutrophils/L in ST 44 (P = .08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = −0.45), and serum albumin (rho = −0.47). Biomarkers predicted 30%–40% of clade-specific mortality differences. Conclusions. C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential.

Background A faecal immunochemical test (FIT) result ≥ 10 µg/g is recommended in the UK to triage patients with symptoms of colorectal cancer (CRC) in primary care for urgent cancer investigation. The COLOFIT model combining FIT results with demographics and blood tests was developed to reduce the proportion of people referred without CRC. This study aims to externally validate the COLOFIT using data from Oxford University Hospitals (OUH). Methods FITs requested by GPs between January 2017 and February 2024 were extracted from the OUH Clinical Data warehouse. Adults with COLOFIT predictors and 180-day follow-up for CRC were included. External validation of the COLOFIT equation was conducted overall and for six independent time periods. Risk score thresholds where the model captured the same number of cancers as FIT ≥ 10 µg/g were estimated to understand the number of urgent referrals avoided. Results A total of 51,477 individuals (659 CRC) were included; 6194 (12%) had FIT ≥ 10 µg/g. FIT positivity and testing volume increased over time, associated with a gradual change from testing lower-risk patients to including those with higher-risk symptoms. COLOFIT was poorly calibrated overall (observed/expected [O/E] ratio 1.52 with calibration slope 1.05), but calibration improved over time (up to O/E ratio 1.09 with calibration slope 1.05). COLOFIT reduced referrals by 8% overall without missing colorectal cancers compared to FIT ≥ 10 µg/g, but this varied from 23% reduction to 2% increase depending on the period evaluated. Conclusions The potential benefit of COLOFIT varied depending on FIT testing rates, the proportion of FIT ≥ 10 µg/g, and the symptoms in the tested population. Adopting COLOFIT into current clinical practice demands, therefore, FIT positivity of at least 17% and CRC rates within 1.3–1.6%. Further validation in local and different populations would also be of significant value and help to maximise COLOFIT’s ability to improve diagnostic pathways.

Abstract Context Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function. Objective To assess timing and predictors of HPA axis recovery after TSA. Design Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018. Patients Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA. Main outcome measures Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA. Results Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255). Conclusion HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement. After TSA, pre- and postoperative SST cortisol levels can predict 6-week HPA axis recovery. Recovery occurs even 12 months after TSA, demonstrating the need for periodic retesting.

ObjectiveWe examined whether it is cost-effective to measure free thyroxine (FT4) in addition to thyrotropin (thyroid-stimulating hormone (TSH)) on all requests for thyroid function tests from primary care on adult patients.BackgroundHypopituitarism occurs in about 4 people per 100 000 per year. Loss of thyrotropin (TSH) secretion may lead to secondary hypothyroidism with a low TSH and low FT4, and this pattern may help to diagnose hypopituitarism that might otherwise be missed.DesignMarkov model simulation.Primary outcome measureIncremental cost-effectiveness ratio (ICER), the ratio of cost in pounds to benefit in quality-adjusted life years of this strategy.ResultsThe ICER for this strategy was £71 437. Factors with a large influence on the ICER were the utilities of the treated hypopituitary state, the likelihood of going to the general practitioner (GP) and of the GP recognising a hypopituitary patient. The ICER would be below £20 000 at a cost to the user of an FT4 measurement of £0.61.ConclusionWith FT4 measurements at their present cost to the user, routine inclusion of FT4 in a thyroid hormone profile is not cost-effective.

Background Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA—the IDIOM score. The aim of this retrospective observational study was to validate the IDIOM model using two independent external datasets. Methods The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets. Results The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups’ calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than ‘investigate all’ and ‘investigate no-one’ strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets. Conclusion This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings.