Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial.

OBJECTIVE: To investigate the effects of compliance and periodic telephone counselling by a pharmacist on mortality in patients receiving polypharmacy. DESIGN: Two year randomised controlled trial. SETTING: Hospital medical clinic. PARTICIPANTS: 502 of 1011 patients receiving five or more drugs for chronic disease found to be non-compliant at the screening visit were invited for randomisation to either the telephone counselling group (n = 219) or control group (n = 223) at enrollment 12-16 weeks later. MAIN OUTCOME MEASURES: Primary outcome was all cause mortality in randomised patients. Associations between compliance and mortality in the entire cohort of 1011 patients were also examined. Patients were defined as compliant with a drug if they took 80-120% of the prescribed daily dose. To calculate a compliance score for the whole treatment regimen, the number of drugs that the patient was fully compliant with was divided by the total number of prescribed drugs and expressed as a percentage. Only patients who complied with all recommended drugs were considered compliant (100% score). RESULTS: 60 of the 502 eligible patients defaulted and only 442 patients were randomised. After two years, 31 (52%) of the defaulters had died, 38 (17%) of the control group had died, and 25 (11%) of the intervention group had died. After adjustment for confounders, telephone counselling was associated with a 41% reduction in the risk of death (relative risk 0.59, 95% confidence interval 0.35 to 0.97; P = 0.039). The number needed to treat to prevent one death at two years was 16. Other predictors included old age, living alone, rate of admission to hospital, compliance score, number of drugs for chronic disease, and non-treatment with lipid lowering drugs at screening visit. In the cohort of 1011 patients, the adjusted relative risk for death was 1.61 (1.05 to 2.48; P = 0.029) and 2.87 (1.80 to 2.57; P < 0.001) in patients with compliance scores of 34-66% and 0-33%, respectively, compared with those who had a compliance score of 67% or more. CONCLUSION: In patients receiving polypharmacy, poor compliance was associated with increased mortality. Periodic telephone counselling by a pharmacist improved compliance and reduced mortality. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register: SRCTN48076318.

Effects of structured care by a pharmacist-diabetes specialist team in patients with type 2 diabetic nephropathy.

PURPOSE: We developed a disease management program for patients with Type 2 diabetic nephropathy and evaluated its effects on the time to onset of end-stage renal disease or all-cause death compared with usual care. METHODS: In a 2-year, prospective cohort study, we compared the clinical outcomes of patients managed by a structured care protocol (n = 80) to a group receiving usual care (n=80) in the same hospital. Patients aged < or =80 years with type 2 diabetes, serum creatinine 150-400 micromol/L, and micro- or macroalbuminuria were recruited. The structured care protocol was implemented by a pharmacist-diabetes specialist team with particular emphasis on periodic laboratory assessments, patient adherence, risk factors control, and use of renin-angiotensin system inhibitor. The primary endpoint was the composite of end-stage renal disease or all-cause death. Other endpoints were the rate of renal decline, processes-of-care measures, and control of risk factors. RESULTS: During 22.8+/-7.9 months of follow-up, the primary endpoint developed in 24 and 40 patients in the structured care and usual care groups, respectively (adjusted risk reduction, 60%, P< .001). Structured care (hazard ratio [95% confidence interval (CI)], 0.40 [0.23-0.68]), age (0.95 [0.93-0.98]), baseline systolic blood pressure (BP) (1.014 [1.003-1.026]), logarithm (base 10) of baseline serum creatinine (34 441 [2290-517915]), and macroalbuminuria (8.95 [1.22-65.38]) were independent predictors for the primary endpoint. Structured care slowed the rate of renal decline (P=.032). More intensive laboratory measurements, increased use of renin-angiotensin system inhibitor, and greater reductions in BP and low-density lipoprotein (LDL) cholesterol were reported by patients receiving structured care. CONCLUSIONS: Structured care delivered by a pharmacist-diabetes specialist team reduced the incidence of end-stage renal disease or death compared with usual care in patients with type 2 diabetic nephropathy.

The renoprotective effects of structured care in a clinical trial setting in type 2 diabetic patients with nephropathy.

BACKGROUND: The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors. METHODS: We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study. RESULTS: Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9+/-2.4 years) and after (3.3+/-0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from -11.4 x 10(-5) l micro mol(-1) month(-1) before entry into the trial to -4.7 x 10(-5) l micro mol(-1) month(-1) following entry (P = 0.001). The respective figures were -9.1 x 10(-5) and -5.0 x 10(-5) l micro mol(-1) month(-1) (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled. CONCLUSIONS: The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.

The metabolic effects of insulin and rosiglitazone combination therapy in Chinese type 2 diabetic patients with nephropathy.

BACKGROUND: Few studies have examined the efficacy and safety of thiazolidinedione use in patients with diabetic nephropathy. Our goal was to examine the metabolic effects and tolerability of combination therapy with rosiglitazone and insulin in type 2 diabetic patients with nephropathy and renal failure. MATERIAL/METHODS: We evaluated the metabolic effects and tolerability of rosiglitazone as an add-on therapy to insulin in 12 Chinese type 2 diabetic patients (5 males and 7 females) with nephropathy and renal impairment. The mean age of these patients was 65+/-8.3 years, and the mean duration of disease was 16.5+/-8.6 years. The initial daily dosage of rosiglitazone, 2 mg daily, was increased to 4 mg if their fasting plasma glucose concentrations were above 10 mmol/L after 4 weeks. RESULTS: Over a mean period of 15.5 months, HbA1c improved significantly following the addition of rosiglitazone, from 8.57+/-1.42% to 7.48+/-1.3% (p=0.01). There was a trend towards improved lipid profile with this combination therapy, but it was not statistically significant. There was no major adverse events except for minimal weight gain (71.7+/-13.6 kg vs 73.9+/-13.1 kg, p=0.08). CONCLUSIONS: Combination therapy with rosiglitazone and insulin has beneficial metabolic effects and is generally well tolerated in type 2 diabetic patients with nephropathy and mild to moderate renal failure.

Effects of protocol-driven care versus usual outpatient clinic care on survival rates in patients with type 2 diabetes.

OBJECTIVE: To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care. STUDY DESIGN: Descriptive analysis of a prospective cohort. PATIENTS AND METHODS: During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records. RESULTS: Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%). CONCLUSION: Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.

Weight management and current options in pharmacotherapy: orlistat and sibutramine.

BACKGROUND: Chronic obesity is associated with various cardiovascular disorders, including diabetes, dyslipidemia, and hypertension. Pharmacotherapy with antiobesity agents is an important management strategy in conjunction with lifestyle interventions. OBJECTIVE: This article describes the pharmacologic management of obesity, concentrating on orlistat and sibutramine. METHODS: Relevant articles were identified through a MEDLINE search (1966-February 2002) using the terms obesity, overweight, weight loss, antiobesity drugs, orlistat, and sibutramine. The search for efficacy trials was limited to randomized controlled studies of >6 months' duration. Also included in the review were relevant references cited in the bibliographies of identified articles, news reports, and the authors' own data. RESULTS: Orlistat reduces fat absorption by inhibiting gastrointestinal lipases. In randomized, controlled trials of up to 2 years' duration, orlistat plus a hypocaloric diet produced significantly greater weight loss than placebo (P < 0.001). In the maintenance phase, patients taking orlistat had less weight regain than did placebo recipients. The weight reduction with orlistat was also associated with a significant improvement in control of cardiovascular risk factors (P < 0.05). Unlike orlistat, sibutramine works by suppressing appetite; its efficacy, however, was similar to that of orlistat in the identified clinical trials. Orlistat was associated primarily with gastrointestinal side effects. Use of orlistat was associated with minimal drug interactions, except with cyclosporine, with which it should not be taken. Sibutramine was also well tolerated, although it may cause dry mouth, anorexia, and insomnia, and should be used with caution in patients at risk for cardiovascular disease. CONCLUSIONS: Orlistat and sibutramine demonstrated a favorable efficacy and safety profile in randomized controlled trials. Current evidence supports their use as adjuncts to lifestyle modifications in the treatment of obesity.

Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer.

BACKGROUND: Intravenous administration of proton pump inhibitors after endoscopic treatment of bleeding peptic ulcers has been shown to decrease the rate of recurrent bleeding and the need for subsequent surgery. Yet there is a relative lack of formal assessment of this practice. The aim of this study was to examine the cost-effectiveness of this therapy by using standard pharmacoeconomic methods. METHODS: The present study was performed in conjunction with a randomized controlled clinical trial that included 232 patients who received either omeprazole (80 mg intravenous bolus followed by infusion at 8 mg/hour for 72 hours) or placebo after hemostasis was achieved endoscopically. A cost-effectiveness analysis was performed to evaluate the different outcomes of the trial. All related direct medical costs were identified from patient records. Cost-effectiveness ratios were calculated. RESULTS: Analysis by the Kolmogorov-Smirnov test showed that the direct medical cost in the omeprazole group was lower than that for the placebo group. Cost-effectiveness ratios for omeprazole and placebo groups were, respectively, HK$ 28,764 (US$ 3688) and HK$ 36,992 (US$ 4743) in averting one episode of recurrent bleeding in one patient after initial hemostasis was achieved endoscopically. CONCLUSIONS: Intravenous administration of high-dose omeprazole appears to be a cost-effective therapy in reducing the recurrence of bleeding and need for surgery in patients with active bleeding ulcer after initial hemostasis is obtained endoscopically.

Relationship between obesity and cardiovascular risk factors in elderly Chinese subjects.

OBJECTIVE: To investigate the relative effects of degree and distribution of body fat with several cardiovascular disease (CVD) risk factors in elderly Chinese subjects. METHODS: One hundred and thirty-five elderly Chinese individuals (age range, 60-65 y) without any history of significant renal, hepatic or cardiac disease were recruited. Seated blood pressure, anthropometric and fasting plasma biochemical parameters were measured. Student's t-test was used to compare the differences in biochemical and anthropometric markers between cohorts. RESULTS: Males were heavier (64.6 +/- 8.6, 57.2 +/- 8.2kg, P < 0.001), taller (1.65 +/- 0.06, 1.51 +/- 0.05 m, P < 0.001) and their greater body fat was predominantly deposited centrally (Waist-to- hip ratio, 0.91 +/- 0.06, 0.88 +/- 0.07, P < 0.05). Females were more generally obese with increased body mass index (BMI, 23.8 +/- 4.6, 25.0 +/- 3.5 kg/m2, P < 0.05) and percentage body fat [26.3% (24.5%-28.1%) vs 37.2% (36.0%-38.9%), P < 0.001] than the males. However, despite an 11% higher proportion of body fat in females, no significant differences were identified in blood pressure, lipid profile, indices of insulin resistance or albumin-to-creatinine ratios. CONCLUSION: It is likely that central adiposity contributes disproportionately to these metabolic disorders in males even though they are much leaner than elderly Chinese females.