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Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort.TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups.A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%).The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus.

Rationale & Objective Since the change in erythropoiesis-stimulating agent (ESA) labeling and bundling of dialysis services in the United States, few studies have addressed the clinical importance of ESA hyporesponsiveness and none have considered health care resource use in this population. We aimed to further explore ESA hyporesponsiveness and its consequences. Study Design Retrospective observational cohort study. Setting & Participants US Renal Data System Medicare participants receiving dialysis with a minimum 6 months of continuous ESA use from 2012 to 2014. Predictors Erythropoietin resistance index (≥2.0 U/kg/wk/g/L) and ESA dose were used to identify ESA hyporesponders and hyporesponsive subgroups: isolated, intermittent, and chronic. Outcomes Associations between ESA responsiveness and mortality, cardiovascular hospitalization rates, and health care resource use were evaluated and compared across subgroups. Analytical Approach Baseline characteristics were compared using Wilcoxon rank sum tests for continuous variables and χ2 tests for categorical variables. Incidence rates of health care resource use were modeled using an unadjusted and adjusted generalized linear model. Results Of 834,115 dialysis patients in the CROWNWeb database, 38,891 ESA hyporesponders and 59,412 normoresponders met all inclusion criteria. Compared with normoresponders, hyporesponders were younger women, weighed less, and had longer durations of dialysis (all P < 0.001). Hyporesponders received 3.8-fold higher ESA doses (mean, 94,831 U/mo) and erythropoietin resistance index was almost 5 times higher than in normoresponders. Hyporesponders had lower hemoglobin levels and parathyroid hormone levels > 800 pg/mL, and iron deficiency was present in 26.5% versus 10.9% in normoresponders. One-year mortality was higher among hypo- compared with normoresponders (25.3% vs 22.6%). Hyporesponders also had significantly higher rates of hospitalization for cardiovascular events, emergency department visits, inpatient stays, home health agency visits, skilled nursing facility, and hospice days. Limitations Only US Medicare patients were included and different hyporesponder definitions may have influenced the results. Conclusions This study explored ESA hyporesponsiveness using new definitions and incorporated clinical and economic outcomes. It established that ESA-hyporesponsive dialysis patients had higher mortality, cardiovascular hospitalization rates, and health care costs as compared with ESA-normoresponsive patients., Graphical abstract

Long-term levodopa therapy and related fluctuating plasma concentrations are associated with between-dose periods of ‘off time’ resulting in substantial variation in symptoms and functioning throughout the day in people with Parkinson’s (PwP). PwP across UK, France, Spain and Italy completed an online survey to explore: the impact of ‘off time’ on (1) health-related quality of life (HRQL) and (2) on functioning and ability to undertake usual activities; (3) the value of ‘off time’ relative to other factors associated with Parkinson’s through a stated preference discrete choice experiment (SPDCE). In total, 305 PwP completed the online survey. Overall mean HRQL (utility) score was significantly lower for ‘off time’ (0.37) than for ‘on time’ (0.60). All attributes within the SPDCE were significant predictors of treatment choice, although increased duration of ‘on time’ (per hour per day: odds ratio (OR) = 1.40) and predictability of ‘off time’ to within 30 min (OR = 1.42) were valued most highly. ‘On time’ and predictability of ‘off time’ are highly valued by PwP. Due to substantial diurnal variation of Parkinson’s symptoms, standard patient-reported outcome (PRO) assessments may not adequately capture the impact of ‘off time’ on HRQL and participation in daily activities.

Resumen Antecedentes y objetivo El estudio INSTIGATE tuvo como objetivo evaluar los costes directos sanitarios incurridos por pacientes con diabetes mellitus tipo-2 (DM2) que inician insulinoterapia en Espana. Es un estudio observacional, no intervencionista, prospectivo y multicentrico. Material y metodos Se valoraron los costes directos por paciente, segun la practica clinica habitual, durante un periodo de 6 meses antes y despues del inicio de la insulinoterapia. En total se evaluaron 188 pacientes (42,6% mujeres) con una edad media de 65,3 anos, un indice de masa corporal medio de 29,7 kg/m 2 y una duracion media de la enfermedad de 10,7 anos. Resultados Antes de iniciar la insulinoterapia, la media (desviacion estandar) de las variables clinicas fueron: % de hemoglobina-A 1c 9,22 (1,58); glucosa plasmatica en ayunas (mmol/L) 12,03 (3,62), y colesterol total (mmol/L) 4,90 (1,1). La media del total de los costes directos sanitarios por paciente 6 meses antes y despues de iniciar el tratamiento con insulina fue de 639€ y 1.110€ respectivamente. Los costes medios totales a los 6 meses del inicio de la insulinoterapia comprendieron: costes de ingresos hospitalarios (30,5%; 339€), insulina (16,2%; 180€), asistencia en servicios de atencion primaria (14,3%; 159€), monitorizacion de glucosa en sangre (13,8%; 153€), asistencia por parte de especialistas (13,3%; 148€), antidiabeticos orales (7,8%; 87€) y otros tratamientos relacionados con la diabetes (3,9%; 43€). Conclusiones Los resultados clinicos de este grupo de pacientes con DM2 mejoraron tras iniciar terapia con insulina. Esta mejoria se acompano de aumentos en la utilizacion de recursos y de costes directos sanitarios durante los 6 primeros meses de insulinoterapia.

Summary Objective: To investigate switching from thiazolidinediones, and predictors for switching treatment, after publication of a meta-analysis reporting an increased risk of myocardial infarction associated with rosiglitazone use. Research design and methods: Using the Health Information Network (THIN) UK primary care database, the number of people with type 2 diabetes prescribed either thiazolidinedione, rosiglitazone (n = 10,062) or pioglitazone (n = 4454), and the rate of switching from thiazolidinediones (n = 3301 and 1106, respectively), were computed for each month, May 2006 to January 2008. The probability of switching post-publication, May 2007 to January 2008, was modelled by logistic regression in a forward stepwise model. Variables included demographics, history of ischaemic heart disease (IHD), heart failure (HF) or stroke, risk factors for IHD, glucose-lowering and cardiovascular drug use, HbA1c and diabetes duration. Results: There was a sharp increase in switching from both thiazolidinediones in summer 2007; rosiglitazone prescription numbers then decreased while pioglitazone prescribing increased. Switching from rosiglitazone was associated with IHD [adjusted odds ratio (OR) 1.72; 95% confidence intervals (CI) 1.47–2.00], insulin treatment (OR 5.10; 95% CI 3.21–8.10), HF (OR 2.26; 95% CI 1.62–3.18), a recent sulphonylurea prescription (OR 1.33; 95% CI 1.17–1.51) gender (OR men vs. women 0.79; 95% CI 0.70, 0.90) and duration of therapy. Switching from pioglitazone was associated with HF (OR 3.05; 95% CI 1.77–5.26), duration of therapy, and number of glucose-lowering treatments. Conclusions: Prescribing habits for both thiazolidinediones changed immediately following the safety warning. IHD was associated with switching from rosiglitazone; otherwise reasons for change appear to be complex, not directly related to the findings of the meta-analysis.

To examine insulin regimens and factors that affect glycaemic control at 6 months after initiation of insulin therapy in patients with type 2 diabetes mellitus.Information on patients requiring insulin initiation as part of usual care was collected in a prospective, observational, open-label study in five European countries. Univariate and multiple regression analyses were used to investigate factors associated with HbA1c achieved at 6 months.Mean HbA1c for all patients at baseline was 9.6 ± 1.8%. Long/intermediate-acting insulin only was most commonly initiated in France and Spain, while long/intermediate or pre-mixed formulations were initiated in Greece and UK. This was consistent with guidelines used in those countries and there was little change in insulin regimen at 6 months in these countries. In Germany, short-acting insulin only was favoured at baseline and there was a shift towards basal/bolus regimens at 6 months, which reflected the local guidelines for insulin initiation in Germany. Mean HbA1c reduction was greatest in Germany (-2.3%), which was the only country to achieve a mean of7% at 6 months. In all countries, HbA1c achieved at 6 months was associated with baseline HbA1c. Differences between countries were seen for influence of factors such as BMI, duration of diabetes, insulin regimen, insulin dose and number of oral anti-diabetes drugs on HbA1c achieved. Explained variability for the factors ranged from 5.6% to 22.9%.Differences in insulin regimen were observed between countries, and appeared to reflect the guidelines and treatment regimens used.

Stephen Jones,1 Conxa Castell,2 Albert Goday,3 Helen T Smith,4 Claudia Nicolay,5 Alexander Simpson,4 Carole Salaun-Martin61James Cook University Hospital, Middlesborough, UK; 2Department of Health, Barcelona, Spain; 3Hospital Del Mar, Barcelona, Spain; 4Eli Lilly and Company, Erl Wood, UK; 5Lilly Deutschland GmbH, Bad Homburg, Germany; 6Lilly France, Suresnes, FranceBackground: The purpose of this study was to describe the resource use and associated direct costs of diabetes care for patients with type 2 diabetes mellitus in the 6 months before and after initiation of insulin therapy.Methods: INSTIGATE is a prospective, noninterventional, multicenter study of patients with type 2 diabetes who were initiating insulin for the first time as part of their usual care in 2006. The study was conducted in France, Germany, Greece, Spain, and the UK, and observed the course of diabetes therapy for up to 6 months. Direct medical costs were evaluated from the national health care system (third-party payer) perspective at 2006 prices.Results: Of the 1153 patients with type 2 diabetes, 1051 (91.2%) had follow-up visits in the 6 months after insulin initiation and were included in the cost analysis. In all countries in our study, mean total direct costs per patient increased in the 6-month follow-up period, compared with the 6-month period prior to insulin initiation, and ranged from €577 in Greece to €1402 in France. The incremental cost of adding insulin treatment ranged from €81 in France to €471 in Spain.Conclusion: In all countries, the mean total direct cost of care for diabetes increased after starting insulin. The breakdown of total direct costs by expenditure category varied considerably across countries, reflecting differences in resource use patterns, prices of medical resources, and different health care systems.Keywords: type 2 diabetes mellitus, costs, resource use, insulin

Introduction To examine changes in insulin regimens and glycemic control during the 24 months after initiation of insulin in patients with type 2 diabetes mellitus. Methods Data were collected over a 24-month period from patients requiring insulin initiation as part of usual care, in a prospective, observational study. Changes in insulin regimens and hemoglobin A1c (HbA1c) were examined within countries (Germany, Greece, Spain) and overall. Results Prandial insulin only was most commonly initiated in Germany, while basal or premixed formulations were initiated in Greece and Spain. In Germany, compared with Greece or Spain, the patients were slightly younger and had a shorter diabetes duration when initiating insulin. For patients overall, 76.1% did not change their insulin regimen between initiation and 24 months. The most obvious change was a shift from prandial to basal/bolus in Germany, with almost doubling of mean daily insulin dose; in Greece and Spain, more patients stopped using insulin and the trend to more complex regimens was not seen. Overall, mean (SD) HbA1c decreased from baseline (9.4 [1.7]%) to 6 months (7.2 [1.0]%), but with little further change through 24 months (7.2 [1.1]%). HbA1c change with basal/bolus insulin (−2.6 [2.0]%, baseline 10.1%) was greater than with basal only (−2.0 [1.8]%, baseline 9.3%). Mean HbA1c less than 7% was achieved and maintained over 24 months in Germany, but was not achieved at any time in Greece or Spain. Conclusions Within 24 months of insulin initiation, the majority of patients with type 2 diabetes remained on the same insulin regimen initially instigated, despite the well-established progressive loss of prandial and basal endogenous insulin secretion. Adequate glycemic control was best achieved where insulin dosage adjustments and insulin intensification took place.

Background and objectives The INSTIGATE study was designed to assess the direct health care costs incurred by patients with type 2 diabetes mellitus (T2DM) who start insulin therapy in Spain. It was a multicenter, observational, non-interventional, prospective study. Methods Direct costs per patient in standard clinical practice were assessed for 6 months before and after the start of insulin therapy from the perspective of the Spanish health care system. A total of 188 patients (42.6% women) with a mean age of 65.3 years, a mean body mass index of 29.7 kg/m 2 , and a mean disease duration of 10.7 years were assessed. Results Before insulin therapy was started, the mean (standard deviation) values of various clinical parameters were: hemoglobin A1c (%), 9.22 (1.58); fasting plasma glucose (mmol/L), 12.03 (3.62); and total cholesterol (mmol/L), 4.90 (1.1). These values decreased after insulin therapy was started. Mean total direct health care costs per patient 6 months before and after insulin start were €639 and €1,110, respectively. Mean total costs 6 months after insulin was started included hospitalization costs (30.5%, €339), insulin (16.2%, €180), primary care (14.3%, €159), blood glucose monitoring (13.8%, €153), specialized care (13.3%, €148), oral antidiabetics (7.8%, €87), and other diabetes-related treatment (3.9%, €43). Conclusions The clinical outcomes of T2DM patients improved after insulin therapy was started. This improvement was associated with increases in resource utilization and direct health care costs in the first 6 months of insulin therapy.

Juvenile fathead minnows (Pimephales promelas) were stocked in tanks at different densities and different ration levels, in two experiments, to determine effects on final population density, growth and fecundity. Length and weight of fish increased with increased food availability. Egg size was exponentially related to growth and perhaps directly to ration level. High population density appeared to limit growth and gamete development regardless of food abundance. Additionally, water volume appeared to limit numbers (tolerance density) of fish which can be supported in a specific volume of water.