Predicting hepatic encephalopathy in patients with cirrhosis: A UK population-based study and validation of risk scores.

BACKGROUND: HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort. Here, we evaluated the performance of the HE risk scores in a UK cohort study. METHODS: Health care records from Clinical Practice Research Datalink and linked Hospital Episode Statistics were used to select patients with cirrhosis who were diagnosed with HE, confirmed by a diagnosis code for HE or a rifaximin-α prescription. The index date was the date of incident cirrhosis. The study period was from January 2003 to June 2019. RESULTS: A total of 40,809 patients with cirrhosis were selected in the UK cohort, of whom 59% were male. A total of 1561 patients were diagnosed with HE. Applying the UK cohort to the baseline sensitivity risk cutoff (≥-11) from the US cohort provided a sensitivity of 92% and a negative predictive value of 99%. Within a longitudinal model, applying a sensitivity cutoff of ≥-3 to this cohort gave a sensitivity of 89% and a negative predictive value of 99%. CONCLUSIONS: Using data from the UK, the previously developed HE risk scores were found to be reliable for selecting those most likely to progress to HE in patients with liver cirrhosis. Despite the HE risk scores originally being estimated using the data from a predominately male US cohort, the scores were validated and found to be generalizable to female patients.

Real-world evidence from the first online healthcare analytics platform-Livingstone. Validation of its descriptive epidemiology module.

Incidence and prevalence are key epidemiological determinants characterizing the quantum of a disease. We compared incidence and prevalence estimates derived automatically from the first ever online, essentially real-time, healthcare analytics platform-Livingstone-against findings from comparable peer-reviewed studies in order to validate the descriptive epidemiology module. The source of routine NHS data for Livingstone was the Clinical Practice Research Datalink (CPRD). After applying a general search strategy looking for any disease or condition, 76 relevant studies were first retrieved, of which 10 met pre-specified inclusion and exclusion criteria. Findings reported in these studies were compared with estimates produced automatically by Livingstone. The published reports described elements of the epidemiology of 14 diseases or conditions. Lin's concordance correlation coefficient (CCC) was used to evaluate the concordance between findings from Livingstone and those detailed in the published studies. The concordance of incidence values in the final year reported by each study versus Livingstone was 0.96 (95% CI: 0.89-0.98), whilst for all annual incidence values the concordance was 0.93 (0.91-0.94). For prevalence, concordance for the final annual prevalence reported in each study versus Livingstone was 1.00 (0.99-1.00) and for all reported annual prevalence values, the concordance was 0.93 (0.90-0.95). The concordance between Livingstone and the latest published findings was near perfect for prevalence and substantial for incidence. For the first time, it is now possible to automatically generate reliable descriptive epidemiology from routine health records, and in near-real time. Livingstone provides the first mechanism to rapidly generate standardised, descriptive epidemiology for all clinical events from real world data.

The absolute risk of incident type 2 diabetes following exposure to systemic corticosteroids in selected steroid-related and phenotypic groups.

AIMS: Exposure to corticosteroids is known to increase the risk of developing type 2 diabetes. We estimated the risk of incident type 2 diabetes in selected patient groups exposed to systemic corticosteroids. MATERIALS AND METHODS: In a retrospective, observational cohort study, using real-world data from UK primary care, patients were selected who had at least one episode of exposure to oral or intravenous corticosteroids for any indication. Corticosteroid-exposed patients were matched with non-exposed patients. Relative dosage was estimated as a weight-based, prednisolone-equivalent dose. Crude rates of progression to type 2 diabetes were determined for patient groups defined by relevant steroid-related and phenotypic characteristics present at corticosteroid exposure. RESULTS: Overall, rates of incidence of type 2 diabetes were 12.5 and 6.7 events per thousand person-years' (pkpy) exposure, respectively, in those who received at least one dose of corticosteroids versus those never exposed. This represented a rate ratio of 1.85 (95% CI 1.74-1.97). The incidence of type 2 diabetes was found to be associated with several of the selected characteristics, both individually and multi-dimensionally. The highest rate of incident type 2 diabetes was observed in very severely obese men aged 46-55 years having had the longest corticosteroid exposure and highest corticosteroid dose (190 incident events pkpy exposure). CONCLUSIONS: Corticosteroid exposure increased the risk of incident type 2 diabetes, and there was evidence of both a dose-response and a duration response. The impact of corticosteroid exposure upon the rate of incident type 2 diabetes appeared, however, to involve a complex, multi-dimensional interaction between the selected characteristics, some of which might be impacted by reverse causality.

Epidemiology of prurigo nodularis in England: a retrospective database analysis.

BACKGROUND: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England. OBJECTIVES: We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service. METHODS: The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of 4 or 10 years of the midpoint prevalence date. RESULTS: Overall, 11 656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria, 2743 patients formed the point prevalent cohort; the estimated prevalence was 3·27 patients per 10 000 population [95% confidence interval (CI) 3·15-3·40]. In sensitivity analyses the estimated prevalence ranged from 2·24 (95% CI 2·14-2·34) to 6·98 (95% CI 6·80-7·16). Incidence over the study period was 2·88 per 100 000 patient-years. Comorbidity was relatively high in this population, notably for atopic dermatitis (52·2%), depression (41·1%) and anxiety (35·4%). CONCLUSIONS: This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3·27 patients per 10 000 population, which equates to 18 471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management.

Comorbid diseases and conditions in people with HIV in the UK.

OBJECTIVES: This study aimed to characterize the risk of people living with HIV (PLHIV) in the UK progressing to pre-specified HIV-associated comorbidities, compared with matched, HIV-negative controls. METHODS: Primary and secondary care records from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) were used to identify PLHIV, and a matched cohort from the HIV-negative population. Kaplan Meier curves and Cox proportional hazard models were used to evaluate the risk of developing comorbidities including central nervous system (CNS) disorders, end-stage renal disease, osteoporosis, diabetes, cardiovascular disease (CVD), hypertension, stroke and cancer. RESULTS: A total of 2945 PLHIV were matched to a cohort of 5890 HIV-negative controls. PLHIV demonstrated an increased hazard ratio (HR) for time to development of incident sleep disorders, depression, osteoporosis, stroke, cancer and renal disease when compared with their matched HIV-negative control. The HRs for anxiety, hypertension, diabetes and CVD were not significantly increased. CONCLUSIONS: PLHIV in the UK were at a higher risk of developing a number of comorbid conditions, highlighting the need for regular attendance of health reviews such as the annual health reviews recommended by the British HIV Associations (BHIVA) quality standard for care, which are currently not uniformly conducted.

The financial burden of treating patients presenting with acute and chronic cough.

OBJECTIVE: Coughing is a common symptom and responsible for a large number of healthcare visits. This study aimed to characterize healthcare resource use and associated financial costs in people with acute or chronic cough. METHODS: A retrospective cohort study using routine data from the UK National Health Service. Adults (≥18 years) were selected if they had a cough record between 1 March 2014 and 28 February 2015 and were classified by duration. RESULTS: A cohort of 150,231 patients was identified, of whom 12,513 (8.3%) had chronic cough, 38,599 (25.7%) had an acute cough with more than one cough event, and 99,119 (66.0%) had acute cough with one event in the study year. Resource use and combined costs of all healthcare contacts differed between cough groups. The healthcare cost per person-year in patients with a single record of acute cough was £739; for those with chronic cough, the cost was £3,663. CONCLUSIONS: Patients with cough represented a substantial financial burden to the NHS. It was difficult to discern the specific portion of treatment associated with cough itself. However, people with chronic cough were associated with substantially increased healthcare use and costs than were those with acute cough.

Insulin-like growth factor-1, growth hormone and disease outcomes in acromegaly: A population study.

CONTEXT: A lack of consensus remains about the relative importance of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in predicting adverse outcomes in patients with acromegaly. OBJECTIVE: To describe the differing association between IGF-1 and GH and major disease outcomes in acromegaly. DESIGN: Retrospective cohort study. PATIENTS: United Kingdom National Health Service patients with acromegaly who had an IGF-1 and/or a GH measurement recorded following diagnosis, prior to December 2019. MEASUREMENTS: A composite endpoint including all-cause mortality (ACM), type 2 diabetes (DM), major adverse cardiovascular events (MACE) or cancer was the primary outcome. These outcomes were also analysed individually. Follow-up period was capped at 5 years. RESULTS: A maximum of 417 cases and 332 cases were eligible for the IGF-1 and GH analyses, respectively, comprising 1041.5 and 938.9 years of follow-up. There was a direct association between increased IGF-1 concentration and adjusted event risk for the composite endpoint (hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 1.02-1.5); in GH, the HR was 1.1 (1.0-1.2). For the individual endpoints in relation to IGF-1 level, the HRs were ACM (1.2; 0.93-1.5), MACE (1.2; 0.64-2.1), DM (1.53; 1.09-2.2) and cancer (1.3; 0.95-1.7). For GH, the HRs were ACM (1.1; 0.97-1.2), MACE (0.99; 0.73-1.3), DM (1.1; 0.99-1.2) and cancer (0.90; 0.66-1.2). CONCLUSIONS: In this contemporary data set with extended follow-up, IGF-1 and GH concentrations showed an association with major adverse outcomes from acromegaly.

Scientific independence and objectivity: many questions linger about treatment of type 2 diabetes, such as scientific study design, optimal glucose control and the safety of injecting exogenous insulin.

Whilst clinical guidelines exist for the treatment of people with type 2 diabetes, many underlying assumptions are still not qualified by convincing evidence. In this commentary, it is argued that fundamental issues still cloud clinical practice, such as biases in the design of clinical studies, the association between glucose control & clinical outcomes, and the safety of exposure to exogenous insulin and other glucose-lowering drugs. Relevant scientific evidence and alternative opinions about important issues continue to be largely ignored, and no effort has been made to resolve these questions. This may have had serious consequences, such as stifling innovation because there are no further benefits to be achieved in relation to glucose control.

Retinal thickness fluctuations in patients receiving fluocinolone acetonide implant for diabetic macular edema.

Objectives: To evaluate central foveal thickness (CFT) variability and accompanying changes in visual acuity (VA) 12 months before and after treatment with the 190 mcg fluocinolone acetonide (FAc) intravitreal implant for diabetic macular edema (DME).Methods: The Iluvien Clinical Evidence cohort study in the United Kingdom (ICE-UK) investigated the effectiveness of the FAc implant in people treated at 13 hospitals from April 2013 to April 2015. The following parameters were calculated for CFT for each patient: mean, standard deviation (SD), retinal thickness amplitude (RTA, the difference between maximum and minimum values), and coefficient of variation (CV).Results: In 149 eyes with ≥2 CFT observations both before and after FAc implantation, the median VA was 50 ETDRS letters at implantation. Mean CFT was 487 µm at implantation and 135 µm at 12 months post-implant. Before implantation, the mean CV and mean SD for CFT were 24.6% and 112 µm, respectively; the mean RTA was 254 µm. A statistically significant (p < .001) decrease in all three parameters was observed after implantation (18.3%, 68.2 µm and 146 µm, respectively). There was an association between CFT change between extremes and the corresponding change in VA (Pearson's correlation coefficient, r = -0.292, p < .001, prior to the implant; r = -0.379, p < .001, post-implant).Conclusions: After accounting for the reduction in CFT, retinal thickness stabilized following FAc implantation. There might be VA benefits in reducing variability in CFT over time. This merits further exploration but would require more frequent CFT observations in order to properly determine patterns of retinal thickness variability.

Cough presentation in primary care and the identification of chronic cough: a need for diagnostic clarity?

Objective: To investigate patterns of presentation of cough in primary care and develop an algorithm to identify probable and possible chronic cough (CC).Methods: This retrospective observational study used routine English primary care data and linked hospital data. Patients with ≥1 cough event in the study period (March 2014-February 2015) were selected. Index date was that of the earliest cough event in this period. Adults (aged ≥18 years) were classified as having probable CC if they had an explicit CC diagnosis; as having possible CC if they had ≥3 cough events recorded over 8-26 weeks; or, otherwise, as having acute cough. Underlying conditions associated with CC were identified.Results: 198,151 people were identified. 56.5% were female; median age was 47.0 years. The prevalence of cough in the study year was 17.6%. Of the 150,213 identified adults, 1600 (1.1%), 10,913 (7.3%) and 137,718 (91.7%) were classified as having probable CC, possible CC or acute cough, respectively. Compared with probable CC and acute cough, a higher percentage of possible CC cases had a record on or prior to index date indicative of chronic obstructive pulmonary disease (30.6% versus 10.1% and 9.7%), gastro-esophageal reflux disease (32.6% versus 24.9% and 21.1%) or asthma (45.9% versus 27.6% and 27.9%). Prevalences of probable and possible CC were 0.18% and 1.2%, respectively.Conclusions: The prevalence of CC was lower than reported in previous studies. People with possible CC had higher rates of underlying conditions associated with CC. These observations may suggest poor recognition and/or under-recording of CC in primary care.

Evaluation of the epidemiology of peanut allergy in the United Kingdom.

Aims: To describe the epidemiology of peanut allergy (PA) in the UK over the last three decades.Methods: PA patients were identified from the Clinical Practice Research Datalink between 1987 and 2015. Incidence and prevalence of PA were compared between 2000 and 2015. Prevalence and relative risk (RR) of atopic comorbidities, anaphylaxis, adrenaline prescriptions versus matched controls were calculated.Results: Point prevalence of PA in the entire population and those <18 years increased from 31 to 202 and 116 to 635 per 100,000, respectively, between 2000 and 2015. Incidence increased from 8.6 to 18.2 per 100,000. Incidence in 2015 was 105 cases per 100,000 aged 0-4 years versus 13.4 per 100,000 aged 5+ years. Anaphylactic events affected 1.2% of the cases and 0.007% of the controls. The rate of adrenaline prescriptions was 5,910 per 100,000 person-years for PA patients. RRs for asthma, eczema and allergic rhinitis in PA patients versus controls were 4.5 (95% CI 4.2-4.8), 3.2 (3.1-3.4) and 2.6 (2.4-3.0), respectively.Conclusions: The prevalence and incidence of PA increased markedly over the study period. PA was associated with atopic conditions and anaphylaxis. PA patients had increased adrenaline prescriptions.

The Model of Mortality with Incident Cirrhosis (MoMIC) and the model of Long-term Outlook of Mortality in Cirrhosis (LOMiC).

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97-3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47-3.38)), elevated bilirubin levels (aHR = 1.38, 1.26-1.51) and low sodium levels (aHR = 2.26, 1.84-2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists.

Major adverse cardiovascular events in people with chronic kidney disease in relation to disease severity and diabetes status.

Diabetes plays an important role in the complex relationship between chronic kidney disease (CKD) and cardiovascular disease. This retrospective observational study compared the influence of estimated glomerular filtration rate (eGFR) and proteinuria on the risk of major adverse cardiovascular event (MACE; myocardial infarction or stroke) in CKD patients with and without diabetes. Data were from a linked database of UK electronic health records. Individuals with CKD and no prior MACE were classified as type 1 diabetes (T1DM; n = 164), type 2 diabetes (T2DM; n = 9,711), and non-diabetes (non-DM; n = 75,789). Monthly updated time-dependent Cox proportional hazard models were constructed to calculate adjusted hazard ratios (aHRs) for progression to MACE from first record of abnormal eGFR or proteinuria (index date). In non-DM, aHRs (95% CIs) by baseline eGFR category (referent G2) were G1: 0.70 (0.55-0.90), G3a: 1.28 (1.20-1.35), G3b: 1.64 (1.52-1.76), G4: 2.19 (1.98-2.43), and G5: 3.12 (2.44-3.99), and by proteinuria category (referent A1) were A2: 1.13 (1.00-1.28), A2/3 (severity indeterminable): 1.58 (1.28-1.95), and A3: 1.64 (1.38-1.95). In T2DM, aHRs were G1: 0.98 (0.72-1.32), G3a: 1.18 (1.03-1.34), G3b: 1.31 (1.12-1.54), G4: 1.87 (1.53-2.29), G5: 2.87 (1.82-4.52), A2: 1.22 (1.04-1.42), A2/3: 1.45 (1.17-1.79), and A3: 1.82 (1.53-2.16). Low numbers in T1DM precluded analysis. Modelling T2DM and non-DM together, aHRs were, respectively, G1: 3.23 (2.38-4.40) and 0.70 (0.55-0.89); G2: 3.18 (2.73-3.70) and 1.00 (referent); G3a: 3.65 (3.13-4.25) and 1.28 (1.21-1.36); G3b: 4.01 (3.40-4.74) and 1.65 (1.54-1.77); G4: 5.78 (4.70-7.10) and 2.21 (2.00-2.45); G5: 9.00 (5.71-14.18) and 3.14 (2.46-4.00). In conclusion, reduced eGFR and proteinuria were independently associated with increased risk of MACE regardless of diabetes status. However, the risk of MACE in the same eGFR state was 4.6-2.4 times higher in T2DM than in non-DM.

Evaluation of the healthcare resource use and the related financial costs of managing peanut allergy in the United Kingdom.

Aims: We aimed to estimate the resource use and associated costs for patients with peanut allergy (PA) compared to matched controls. Methods: This was a retrospective cohort study using data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. PA patients were matched to two control cohorts: the first (simple-matched) were matched 1:1 on year of birth, general practice, gender and registration year. The second (atopy-matched) were matched on the same characteristics plus presence/absence of an atopic condition. Prescriptions and primary and secondary care contacts were compared between cases and controls. Results: 15,483 peanut-allergic patients were identified: 13,609 (87.9%) were simple-matched and 9,320 (60.2%) atopy-matched. The total per person annual incremental health-care costs associated with PA were £253 (atopy-matched) and £333 (simple-matched). For those with PA and a prior anaphylaxis incremental costs were £662, for those prescribed an epinephrine autoinjector incremental costs were £392. Extrapolated to the U.K. population, total excess costs of PA were between £33 and 44 million in 2015. Conclusions: Patients with PA had increased health-care contacts and consequently increased associated costs compared to controls. Observation bias should be considered in interpretation, but this study suggests that PA presents significant burden to health-care systems.

Comparison of data characterizing the clinical effectiveness of the fluocinolone intravitreal implant (ILUVIEN) in patients with diabetic macular edema from the real world, non-interventional ICE-UK study and the FAME randomized controlled trials.

Objective: To compare the effectiveness and safety of the fluocinolone acetonide (FAc) intravitreal implant between the observational Iluvien Clinical Evidence study in the United Kingdom (ICE-UK) and the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) randomized controlled trials (RCTs) in people with diabetic macular edema (DME). Clinical Trials Registration: NCT00344968. Methods: This study selected patients randomized to receive 0.2 µg/day FAc insert (FAc treated eyes) or sham injection (control eyes) from the FAME RCTs, and patients' first FAc treated eye and non-FAc treated fellow (control) eye from the ICE-UK study. Outcomes included change in visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP). Results: After 12 months follow-up, mean change in VA was 5.0 letters improvement (p < .001) and 1.6 letters improvement (p = .003) in FAME FAc treated and control eyes, and 3.8 letters (p = .012) and -2.1 letters (p = .056) in ICE-UK FAc treated and control eyes, respectively. Mean change in CFT was -144 µm (p < .001) vs -72 µm (p < .001) in FAME FAc treated and control eyes and -113 µm (p < .001) vs -13 µm (p < .001) in ICE-UK FAc treated and control eyes. For eyes with a follow-up of 12 months, 77 (22.3%) and 15 (8.6%) FAME FAc treated and control eyes and 25 (18.7%) and six (4.3%) ICE-UK FAc treated and control eyes required emergent IOP-lowering therapy. Conclusions: Statistically significant improvements in VA 12 months after FAc implantation were observed in both the real-world study and in the RCTs. The improvement in VA and CFT in the RCTs was marginally greater than in the real-world study; however, recruits in the real-world study had more severe visual morbidity at baseline. Whilst there were many changes in the care of people with DME over this time, these data all support the value of treatment with FAc intravitreal implant.

A genetic programming approach to development of clinical prediction models: A case study in symptomatic cardiovascular disease.

BACKGROUND: Genetic programming (GP) is an evolutionary computing methodology capable of identifying complex, non-linear patterns in large data sets. Despite the potential advantages of GP over more typical, frequentist statistical approach methods, its applications to survival analyses are rare, at best. The aim of this study was to determine the utility of GP for the automatic development of clinical prediction models. METHODS: We compared GP against the commonly used Cox regression technique in terms of the development and performance of a cardiovascular risk score using data from the SMART study, a prospective cohort study of patients with symptomatic cardiovascular disease. The composite endpoint was cardiovascular death, non-fatal stroke, and myocardial infarction. A total of 3,873 patients aged 19-82 years were enrolled in the study 1996-2006. The cohort was split 70:30 into derivation and validation sets. The derivation set was used for development of both GP and Cox regression models. These models were then used to predict the discrete hazards at t = 1, 3, and 5 years. The predictive ability of both models was evaluated in terms of their risk discrimination and calibration using the validation set. RESULTS: The discrimination of both models was comparable. At time points t = 1, 3, and 5 years the C-index was 0.59, 0.69, 0.64 and 0.66, 0.70, 0.70 for the GP and Cox regression models respectively. At the same time points, the calibration of both models, which was assessed using calibration plots and the generalization of the Hosmer-Lemeshow test statistic, was also comparable, but with the Cox model being better calibrated to the validation data. CONCLUSION: Using empirical data, we demonstrated that a prediction model developed automatically by GP has predictive ability comparable to that of manually tuned Cox regression. The GP model was more complex, but it was developed in a fully automated way and comprised fewer covariates. Furthermore, it did not require the expertise normally needed for its derivation, thereby alleviating the knowledge elicitation bottleneck. Overall, GP demonstrated considerable potential as a method for the automated development of clinical prediction models for diagnostic and prognostic purposes.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom.

OBJECTIVE: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE. METHOD: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years. RESULTS: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay. CONCLUSION: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Impact of treatment with pioglitazone on stroke outcomes: A real-world database analysis.

AIMS: Randomized controlled trials have reported an association between pioglitazone and reduced incidence of stroke in type 2 diabetic (T2DM) and insulin-resistant populations. We investigated this association within a real-world database. MATERIALS AND METHODS: T2DM patients who initiated pioglitazone between 2000 and 2012 were extracted from the Clinical Practice Research Datalink (CPRD), a UK routine data source. Two non-exposed control cohorts were matched according to age, gender, HbA1c, diabetes duration, stroke history, co-morbidities and prior T2DM regimen. Control cohort-1 comprised patients initiating a new T2DM therapy as their respective case initiated pioglitazone. Control cohort-2 maintained the same T2DM regimen as their respective case prior to the case initiating pioglitazone. Primary outcome was incident stroke; other outcomes included mortality, length of hospital stay and stroke recurrence. RESULTS: A total of 4234 patients initiating pioglitazone were matched to controls in cohort-1 and 3604 in cohort-2. For the primary outcome there were significantly reduced hazard ratios (HRs) for cases: controls. For cohort 1, the HR was 0.666 (95% CI, 0.466-0.952) during the therapy period and was 0.750 (0.612-0.919) over the entire observation period; for cohort 2, respective HRs were 0.516 (0.336-0.794) and 0.773 (0.611-0.978). There was no significant difference in 30-day mortality rate or rate of recurrent stroke. For stroke events that required hospitalization, there was a significant difference in length of stay for patients discharged to usual residence (median, 3.0 days vs 7.0 days; P = .008) for control cohort-2 while undergoing treatment. CONCLUSIONS: In support of evidence from 2 large randomized trials, these observational data show that pioglitazone has a potent effect in reducing stroke events in patients with type 2 diabetes.

Glucose Control and Weight Change Associated with Treatment with Exenatide Compared with Basal Insulin: A Retrospective Study.

INTRODUCTION: The aim of the study was to compare glycemic and weight change outcomes for type 2 diabetes patients treated with either exenatide once-weekly (EQW) or exenatide twice-daily (EBID) with those patients treated with basal insulin (BI). METHODS: Retrospective data (2010-2014) were extracted from the Clinical Practice Research Datalink, a UK primary care database. Patients previously naïve to injectable therapy initiating EQW, EBID, or BI were extracted and matched by propensity score within two analyses (EQW vs BI and EBID vs BI). Absolute and relative change in HbA1c and weight from baseline and the proportion of patients achieving HbA1c ≤ 7.0% (53 mmol/mol) combined with weight reduction targets of (1) any weight loss or (2) ≥ 5.0% from baseline were compared at 6 and 12-24 months. RESULTS: A total of 485 patients initiated EQW, 3573 EBID, and 13,503 BI. In the propensity matched EQW versus BI analysis, mean HbA1c decreased with changes of - 1.33% (- 14.5 mmol/mol) and - 1.24% (- 13.5 mmol/mol) at 6 months and - 1.19% (- 13.0 mmol/mol) and - 1.17% (- 12.8 mmol/mol) at 12-24 months, respectively. Respective weight change was - 3.7 kg versus + 1.2 kg (p < 0.001) and - 3.2 kg versus + 2.5 kg (p < 0.001). Significantly more EQW patients achieved the combined HbA1c ≤ 7.0% (53 mmol/mol) and weight loss target (22.4% versus 9.9% at 6 months and 18.2% versus 8.0% at 12-24 months, respectively) and HbA1c ≤ 7.0% (53 mmol/mol) and minimum 5% weight loss (11.8% versus 3.7% at 6 months, and 8.0% versus 0.0% at 12-24 months). For EBID versus BI, similar results were found. CONCLUSION: In this real-world data analysis, exenatide QW and exenatide BID were associated with similar glycemic control and greater weight reduction compared with basal insulin.

Poor compliance and increased mortality, depression and healthcare costs in patients with congenital adrenal hyperplasia.

OBJECTIVES: To evaluate the risks of depression and all-cause mortality, healthcare utilisation costs and treatment adherence in congenital adrenal hyperplasia (CAH) in the United Kingdom. DESIGN AND METHODS: A retrospective, matched-cohort study using UK primary-care data from the Clinical Practice Research Datalink linked to hospital and death certification data. Patients diagnosed with CAH and having ≥1 corticosteroid prescription were matched 1:10 to reference subjects. Risk of death and lifetime prevalence of depression were compared using Cox regression models. Direct financial costs were estimated for healthcare contacts. Treatment adherence was measured by medical possession ratio (MPR). RESULTS: 605 patients with CAH were identified; 562 were matched. 270 CAH patients (2700 controls) were linkable to death-certificate data, with adjusted hazard ratio for all-cause mortality 5.17 (95% CI 2.81-9.50). Mean (s.d.) age at death in CAH patients was 54.8 (23.9) vs 72.8 (18.0) years in control patients. The prevalence ratio of depression in CAH vs control patients was 1.28 (95% CI 1.13-1.45). Mean (s.d.) annual healthcare costs were higher in CAH than controls: at age 0-6 years, £7038 (£14 846) vs £2879 (£13 972, P < 0.001); 7-17 years, £3766 (£7494) vs £1232 (£2451, P < 0.001); 18-40 years, £1539 (£872) vs £1344 (£1620, P = 0.007) and ≥41 years, £4204 (£4863) vs £1651 (£2303, P < 0.001). Treatment adherence was lowest in adults, with 141 (36%) of 396 eligible patients having an MPR <80%. CONCLUSIONS: This first analysis of CAH in routine UK healthcare suggests that patients with CAH have increased mortality, depression and healthcare utilisation and low treatment adherence.