Real-world data of a digitally enabled, time-restricted eating weight management program in public sector workers living with overweight and obesity in the United Kingdom: A service evaluation of the Roczen program.

Introduction: The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time-restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health-related outcomes. Methods: This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low-carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support. Results: A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12-month. At 12-month, members mean actual and percentage weight loss was -9.0 kg (7.0; p < 0.001) and -9.2% (6.7, p < 0.001) respectively and waist circumference reduced by -10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (-11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (-4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006). Conclusion: Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health-related outcomes and eating behaviors that were sustained at 12-month.

Anaemia management with subcutaneous epoetin delta in patients with chronic kidney disease (predialysis, haemodialysis, peritoneal dialysis): results of an open-label, 1-year study.

BACKGROUND: Anaemia is common in patients with chronic kidney disease (CKD) and can be managed by therapy with erythropoiesis-stimulating agents (ESAs). Epoetin delta (DYNEPO, Shire plc) is the only epoetin produced in a human cell line. The aim of this study was to demonstrate the safety and efficacy of subcutaneously administered epoetin delta for the management of anaemia in CKD patients (predialysis, peritoneal dialysis or haemodialysis) METHODS: This was a 1-year, multicentre, open-label study. Patients had previously received epoetin subcutaneously and were switched to epoetin delta at an identical dose to their previous therapy. Dose was titrated to maintain haemoglobin at 10.0-12.0 g/dL. The primary endpoint was mean haemoglobin over Weeks 12-24. Secondary analyses included long-term haemoglobin, haematocrit and dosing levels. Safety was assessed by monitoring adverse events, laboratory parameters and physical examinations. RESULTS: In total 478 patients received epoetin delta, forming the safety-evaluable population. Efficacy analyses were performed on data from 411 of these patients. Mean +/- SD haemoglobin over Weeks 12-24 was 11.3 +/- 1.1 g/dL. Mean +/- SD weekly dose over Weeks 12-24 was 84.4 +/- 72.7 IU/kg. Haemoglobin levels were maintained for the duration of the study. Epoetin delta was well tolerated, with adverse events occurring at rates expected for a CKD patient population; no patient developed anti-erythropoietin antibodies. CONCLUSION: Subcutaneously administered epoetin delta is an effective and well-tolerated agent for the management of anaemia in CKD patients, irrespective of dialysis status. TRIAL REGISTRATION: http://www.controlled-trials.com ISRCTN68321818.

Albumin induces interleukin-6 release from primary human proximal tubule epithelial cells.

BACKGROUND: Proximal tubule epithelial cells (PTECs) release proinflammatory and profibrogenic mediators when exposed to serum albumin that may contribute to progression of kidney disease. Interleukin 6 (IL-6) may influence renal fibrosis by modulating transforming growth factor beta1 (TGFbeta1) signalling. PTECs have been demonstrated to produce IL-6 in response to albumin treatment, but the mechanism has not been investigated. We hypothesized that albumin would induce release of IL-6 from PTECs, which would be sensitive to inhibition of PI3K, ERK1,2, p38 MAPK and NFkB. METHODS: Primary human PTECs were exposed to albumin (0.75-150 micronM) for 8 and 24 hours. IL-6 release was determined using enzyme-linked immunosorbent assay (ELISA). The effects of LY294002 (10 micronM), NH4Cl (10 mM), pyrrolidine dithiocarbamate (PDTC) (20 micronM), CAPE (17.5 micronM), PD098059 (20 micronM), SB202190 (5 micronM) and MG132 (10 micronM) on albumin-mediated IL-6 release were studied. RESULTS: Albumin caused a significant time- and concentration-dependent increase in IL-6 release by PTECs. LY294002, NH4Cl, CAPE, PD098059 and SB202190 all reduced albumin-mediated IL-6 release, but neither PDTC nor MG132 had any effect. CONCLUSIONS: These data demonstrate that albumin induces IL-6 release by primary human PTECs, and support a role for endocytosis, p38 MAPK, ERK1,2 and in this process.

Healthcare resource utilization for anemia management: current practice with erythropoiesis-stimulating agents and the impact of converting to once-monthly C.E.R.A.

UNLABELLED: Background andMethods: A prospective, observational study in 12 German and UK dialysis centers which quantified personnel time for anemia treatment using erythropoiesis-stimulating agents (ESAs). Tasks directly observable were measured through the time-and-motion method; time for non-observable tasks was estimated by healthcare staff. Using activity-based costing methods, time was converted into monetary units. Modeling was used to estimate potential time and cost savings using once-monthly C.E.R.A., a continuous erythropoietin receptor activator. RESULTS: For current ESAs in Germany and the UK, respectively: mean observed time was 1.67 and 2.67 min/patient/administration, corresponding to 31 and 42 days/year/center/100 patients; mean total time/center/100 patients/year was estimated at 79 and 95 days, equivalent to EUR 17,031 and GBP 18,739. Assuming 100% once-monthly C.E.R.A. uptake, the observed time/patient/year may decrease by 79 and 84% in Germany and the UK, respectively, compared with traditional ESAs. CONCLUSION: Conversion to once-monthly C.E.R.A. may offer the potential to reduce time spent on ESA administration in hemodialysis centers.

Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment.

BACKGROUND/AIMS: Lanthanum carbonate (LC, FOSRENOL) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy. METHODS: Patients from four previous trials entered this study. RESULTS: Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium x phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system. CONCLUSIONS: LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.

BMP-7 and proximal tubule epithelial cells: activation of multiple signaling pathways reveals a novel anti-fibrotic mechanism.

PURPOSE: Bone morphogenic protein-7 (BMP-7) is a member of the transforming growth factor beta (TGFbeta) superfamily involved in organogenesis. Recent work suggests that BMP-7 can reverse the fibrotic effects of TGFbeta but the underlying mechanism is unknown. We sought to determine BMP-7 signaling and its modulation of TGFbeta induced fibrotic outcomes in adult human proximal tubule epithelial cells (PTECs). METHODS: The effect of BMP-7 on phospho-p38 was assessed by Western blotting, p38 ELISA and Bio-plex phospho-protein assay. Secreted fibronectin (Fn) was measured by ELISA. RESULTS: BMP-7 had a concentration-dependent effect on intracellular signaling activating Smad 1/5/8 at higher concentrations and p38 mitogen activated protein (MAP) kinase at lower concentrations in both primary and transformed PTECs; BMP-7 caused phosphorylation of p38 at 2.5 ng/ml and Smads at 200 ng/ml. Similarly, nuclear accumulation of phospho-p38 and Smad were observed at these respective concentrations. These results suggested an inverse relationship between activation of Smads and p38 MAP kinase in this context. Consistent, with this BMP7 at 200 ng/ml reduced TGFbeta-induced p38 MAP activation and the p38-dependent TGFbeta-induced Fn secretion by PTECs. CONCLUSION: We have shown novel p38/Smad signaling along a BMP-7 gradient and demonstrated BMP-7 regulation of TGFbeta MAP kinase signaling and fibrotic outcomes.

Epoetin delta, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients.

OBJECTIVE: To demonstrate safety and efficacy of epoetin delta for the management of anaemia in predialysis patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: This was a multicentre, open-label, uncontrolled study with predialysis CKD patients who had previously received subcutaneous epoetin therapy. Patients were switched to epoetin delta from their previous therapy, at an identical dose. Dose was subsequently titrated to maintain haemoglobin at 10.0-12.0 g/dL. Study duration was 52 weeks. MAIN OUTCOME MEASURES: The primary endpoint was average haemoglobin levels over Weeks 12, 16, 20 and 24. Secondary analyses were performed on the proportion of patients with haemoglobin and haematocrit levels over preset target levels, haemoglobin and haematocrit levels through to study end and dosing levels. RESULTS: Haemoglobin levels were maintained at 11.3 +/- 1.2 g/dL over Weeks 12-24. Over 80% of the haemoglobin measurements and 95% of the haematocrit measurements were above the predefined target level (haemoglobin > or = 10 g/dL; haematocrit > or = 30%). Weekly dose levels did not change significantly over the course of the trial. Epoetin delta was well tolerated, with adverse events occurring at frequencies expected for this patient population; no patient developed neutralizing anti-erythropoietin antibodies. CONCLUSIONS: Epoetin delta was an effective and well-tolerated agent for the management of anaemia in a subgroup of predialysis CKD patients.

Is early treatment of anaemia with epoetin-alpha beneficial to pre-dialysis chronic kidney disease patients? Results of a multicentre, open-label, prospective, randomized, comparative group trial.

BACKGROUND: This multicentre, open-label prospective, randomized, comparative-group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis chronic kidney disease (CKD) patients. METHODS: A total of 197 patients were randomized to start subcutaneous epoetin-alpha (SC-EPO; EPREX; 1000 U twice weekly) at an early stage of anaemia to maintain Hb at 11.0 +/- 1.0 g/dl (group A, n = 65), or to allow Hb to fall to < or =9.0 g/dl before starting SC-EPO (group B, n = 132) (2000 U three times weekly); and subsequently maintaining Hb at 11.0 +/- 1.0 g/dl. RESULTS: Of 132 patients randomized to group B, 55 progressed to treatment (-trigger). The study was prematurely terminated due to contraindication of the subcutaneous administration route. Mean weekly EPO doses at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for group A; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass (-12.5 vs -9.7%; P = 0.82). In groups A and B, 48% and 52%, respectively, terminated the study because of dialysis/death, after a median of 36.3 and 27.3 months, respectively. CONCLUSION: Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM, the primary efficacy variable. Time to dialysis/death was not significantly different between groups A and B.

The effects of control of thermal balance on vascular stability in hemodialysis patients: results of the European randomized clinical trial.

BACKGROUND: Many reports note that the use of cool dialysate has a protective effect on blood pressure during hemodialysis (HD) treatments. However, formal clinical trials in which dialysate temperature is tailored to the body temperature of appropriately selected hypotension-prone patients are lacking. METHODS: We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients selected from 27 centers in nine European countries. Patients were eligible for the study if they had symptomatic hypotensive episodes in 25% or more of their HD sessions, assessed during a prospective screening phase over 1 month. The study is designed as a randomized crossover trial with two phases and two treatment arms, each phase lasting 4 weeks. We used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), by which we compared a procedure aimed at preventing any transfer of thermal energy between dialysate and extracorporeal blood (thermoneutral dialysis) with a procedure aimed at keeping body temperature unchanged (isothermic dialysis). RESULTS: One hundred sixteen HD patients were enrolled, and 95 patients completed the study. During thermoneutral dialysis (energy flow rate: DeltaE = -0.22 +/- 0.29 kJ/kg x h), 6 of 12 treatments (median) were complicated by hypotension, whereas during isothermic dialysis (energy flow rate: DeltaE = -0.90 +/- 0.35 kJ/kg x h), the median decreased to 3 of 12 treatments (P < 0.001). Systolic and diastolic blood pressures and heart rate were more stable during the latter procedure. Isothermic dialysis was well tolerated by patients. CONCLUSION: Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.

Pulmonary renal syndrome: a 4-year, single-center experience.

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS.