The costs in provision of haemodialysis in a developing country: A multi-centered study

<p>Abstract</p> <p>Background</p> <p>Chronic Kidney Disease is a major public health problem worldwide with enormous cost burdens on health care systems in developing countries. We aimed to provide a detailed analysis of the processes and costs of haemodialysis in Sri Lanka and provide a framework for modeling similar financial audits.</p> <p>Methods</p> <p>This prospective study was conducted at haemodialysis units of three public and two private hospitals in Sri Lanka for two months in June and July 2010. Cost of drugs and consumables for the three public hospitals were obtained from the price list issued by the Medical Supplies Division of the Department of Health Services, while for the two private hospitals they were obtained from financial departments of the respective hospitals. Staff wages were obtained from the hospital chief accountant/chief financial officers. The cost of electricity and water per month was calculated directly with the assistance of expert engineers. An apportion was done from the total hospital costs of administration, cleaning services, security, waste disposal and, laundry and sterilization for each unit.</p> <p>Results</p> <p>The total number of dialysis sessions (hours) at the five hospitals for June and July were 3341 (12959) and 3386 (13301) respectively. Drug and consumables costs accounted for 70.4-84.9% of the total costs, followed by the wages of the nursing staff at each unit (7.8-19.7%). The mean cost of a dialysis session in Sri Lanka was LKR 6,377 (US$56). The annual cost of haemodialysis for a patient with chronic renal failure undergoing 2-3 dialysis session of four hours duration per week was LKR 663,208-994,812 (US$ 5,869-8,804). At one hospital where facilities are available for the re-use of dialyzers (although not done during study period) the cost of consumables would have come down from LKR 5,940,705 to LKR 3,368,785 (43% reduction) if the method was adopted, reducing costs of haemodialysis per hour from LKR 1,327 at present to LKR 892 (33% reduction).</p> <p>Conclusions</p> <p>This multi-centered study demonstrated that the costs of haemodialysis in a developing country remained significantly lower compared to developed countries. However, it still places a significant burden on the health care sector, whilst possibility of further cost reduction exists.</p

Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs

Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients.This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30 kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy.Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Buprenorphine &ndash; an attractive opioid with underutilized potential in treatment of chronic pain

Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about &ldquo;ceiling effect&rdquo; or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed &micro;-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other &micro;-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pai

Tolerability of oral sorafenib in pet dogs with a diagnosis of cancer

Amanda Foskett,&nbsp;Christina Manley,&nbsp;Rebecca Naramore,&nbsp;Ira K Gordon,&nbsp;Bridget M Stewart,&nbsp;Chand Khanna The Oncology Service, LLC, Leesburg, VA, USA Abstract: Sorafenib is a multi-target small molecule inhibitor of the RAF kinase family and VEGFR-2/PDGFR. The US Food and Drug Administration approved sorafenib in human patients&nbsp;with liver, thyroid, or renal carcinoma. The aim of this study was to help guide future pharmacokinetic (PK) studies of sorafenib in dogs with a cancer diagnosis. Client-owned dogs were eligible if they had a cytologic or histologic diagnosis of cancer. Patients were enrolled at escalating doses of sorafenib. Patients were evaluable for the study if they received at least one dose of sorafenib and presented 1 week later for a follow-up examination, blood work, and assessment of drug tolerability. The goal of this study was not to define a maximum tolerated dose as may be reasonable in conventional cytotoxic chemotherapy drugs, but rather to describe the tolerability of this drug in dogs with a cancer diagnosis, as a prequel to future sorafenib PK studies. No patients in the study had any evidence of adverse events that were attributable to sorafenib. Doses of 3&nbsp;mg/kg were well tolerated and associated with a suggestion of clinical activity, supportive of future PK, and pharmacodynamic analysis. Such future studies are recommended at this dose to define the associated exposure achieved and determine a reasonable schedule for sorafenib administration. Keywords: sorafenib, cancer, tolerability study, developmental therapeutics&nbsp