Maribel Salas

Anemia as an independent prognostic factor for survival in patients with cancer

Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease.

Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials

BACKGROUND The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.

Impaired cognitive function and compliance with antihypertensive drugs in elderly: The Rotterdam Study

To our knowledge, there are no epidemiologic studies on the association between cognitive impairment and noncompliance with antihypertensive therapy. We studied compliance with antihypertensive treatment in elderly patients with cognitive impairment.

Economic Analysis of Galantamine, a Cholinesterase Inhibitor, in the Treatment of Patients with Mild to Moderate Alzheimer’s Disease in The Netherlands

Background: The economic impact of dementia on the Dutch health and social services is substantial. Objective: To predict the long-term economic impact of galantamine, a cholinesterase inhibitor, in the treatment of Dutch patients with mild to moderate Alzheimer’s disease. Method: A pharmacoeconomic model was used to predict long-term outcomes. It has two components: an initial module based on clinical trials of galantamine and a subsequent module that predicts when a patient will deteriorate to a level where full time care (FTC) is needed. The analyses take a broad perspective that includes all formal (paid) care, not just those covered by the Dutch health care system. Direct cost estimates were based on resource use profiles of patients with Alzheimer’s disease in the Netherlands. Key inputs were tested in sensitivity analyses. Results: After 10.5 years all patients are predicted to require FTC. For every hundred patients starting treatment on galantamine at the mild to moderate stage, it is predicted that 18 person-years of FTC will be avoided (14.4 discounted) and about 5 quality-adjusted years of life will be gained (3.9 discounted). Net savings for those starting treatment with galantamine are estimated at NLG 3,050 (1,676 UDS). The cost of galantamine accounts for only about 5.0% of the total cost of care for treated Alzheimer’s patients. The direction of these results remained unchanged when input values and assumptions were tested in sensitivity analyses. Conclusions: The cholinesterase inhibitor galantamine is expected to bring savings in the direct cost of caring for patients with Alzheimer’s disease in the Netherlands.

Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials

BackgroundGastric ulcers are a frequent problem in the United States. Proton pump inhibitors have been shown to increase healing rates and improve clinical symptoms. The objective of this study is to compare gastric ulcer healing rates for patients treated with a proton pump inhibitor (PPI) (omeprazole, rabeprazole, pantoprazole, or lansoprazole), an histamine 2- receptor antagonist (ranitidine) or placebo.MethodsA literature search was conducted to identify randomized, controlled clinical trials that included a PPI in at least one treatment arm and assessed the gastric ulcer healing rates endoscopically. The healing rates were estimated for each treatment at specific time points, and Rate Ratios (RR) and 95% confidence intervals (CI) were estimated for each trial.ResultsSixteen trials met the inclusion criteria: four compared a PPI versus placebo, nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the inclusion criteria), and three compared a newer PPI (lansoprazole, pantoprazole or rabeprazole) versus omeprazole. In relation to ranitidine, the pooled RR of PPIs (lansoprazole, omeprazole and pantoprazole) was 1.33 (95% CI 1.24 to 1.42) at four weeks. In each trial, greater improvement in the studied clinical symptoms was found with the newer PPIs (rabeprazole, pantoprazole and lansoprazole) when compared to omeprazole.ConclusionIn this study treatment with PPIs resulted in higher healing rates than ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer treatment for the greater relief of symptoms is one of the newer PPIs.

Assessing the Health and Economic Impact of Galantamine Treatment in Patients with Alzheimer’s Disease in the Health Care Systems of Different Countries

IntroductionCholinesterase inhibitors have been shown to improve cognitive function and improve or maintain global function.ObjectiveTo estimate the long-term economic impact of treating patients with Alzheimer’s disease with galantamine in seven healthcare systems: Australia, Canada, Finland, New Zealand, Sweden, the Netherlands and the UK.MethodsThe time until patients require full-time care (FTC), defined as the consistent requirement for a significant amount of care giving and supervision each day, and the associated costs were evaluated using the ‘Assessment of Health Economics in Alzheimer’s Disease (AHEAD)’ model. Efficacy data were obtained from three clinical trials comparing galantamine with placebo and local cost and resource use data were determined for each country. Forecast costs reported in Euros (2001 value), were made for up to 10 years in each healthcare system. All costs were determined from a perspective somewhat broader than that of a comprehensive payer, including social services. Both benefits and costs were discounted at 3%.ResultsGalantamine (16 mg/day) is predicted to delay the need for FTC by 6.8%, thus the cumulative cost of care over 10 years is expected to be reduced, and this offsets much or all of the cost of galantamine. Approximately five patients need to be treated to avoid 1 year of FTC. In each healthcare system, FTC was estimated to account for 61–92% of the cost. Savings were estimated for most of the countries. For those countries with an expected expense, there were reasonable costs per FTC month avoided (<€553, discounted) and costs per quality-adjusted life year gained (<€25 000).ConclusionIn addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying FTC may offset the treatment costs.

Are hypoglycaemia and other adverse effects similar among sulphonylureas

This review provides an updated overview of the adverse effects of sulphonylureas and identifies factors associated with variation in adverse effect rates among sulphonylureas published by different studies. A search of Medline, Embase, Current Contents and Cochrane Library was conducted to identify all papers related to sulphonylureas and adverse effects published from 1950–2001. The reference lists of all relevant papers were also searched for additional articles.The frequency of sulphonylurea-induced hypoglycaemia varied from 1.8–59%. Severe hypoglycaemia due to sulphonylurea use has been reported from 1.9–3.5%. Variation in hypoglycaemia rates may be due to differences in definitions, methods to detect and to collect information, patient characteristics, patient knowledge of the condition, threshold for symptoms, and activity level during hypoglycaemia. Other adverse effects associated with sulphonylurea use include bodyweight gain, gastrointestinal distress, disulphiram-like syndrome, dermatological reactions, haematological changes, ocular problems, and the syndrome of inappropriate secretion of antidiuretic hormone. Bodyweight gain has been reported to vary from 1.7–4.8kg, according to the United Kingdom Prospective Diabetes Study (UKPDS-33). Controversy exists regarding cardiovascular adverse effects, but the consensus is to exercise caution in the use of these drugs as first-line therapy for patients with diabetes mellitus and coronary artery disease. The benefits of sulphonylurea treatment should be weighed against the risks associated with them. More work in this area is needed to homogenise the definition of hypoglycaemia, to get consensus on the methods for detection and data collection, as well as to further patient and physician education.

Health and economic impact of combining metformin with nateglinide to achieve glycemic control: Comparison of the lifetime costs of complications in the U.K

BackgroundTo reduce the likelihood of complications in persons with type 2 diabetes, it is critical to control hyperglycaemia. Monotherapy with metformin or insulin secretagogues may fail to sustain control after an initial reduction in glycemic levels. Thus, combining metformin with other agents is frequently necessary. These analyses model the potential long-term economic and health impact of using combination therapy to improve glycemic control.MethodsAn existing model that simulates the long-term course of type 2 diabetes in relation to glycosylated haemoglobin (HbA1c) and post-prandial glucose (PPG) was used to compare the combination of nateglinide with metformin to monotherapy with metformin. Complication rates were estimated for major diabetes-related complications (macrovascular and microvascular) based on existing epidemiologic studies and clinical trial data. Utilities and costs were estimated using data collected in the United Kingdom Prospective Diabetes Study (UKPDS). Survival, life years gained (LYG), quality-adjusted life years (QALY), complication rates and associated costs were estimated. Costs were discounted at 6% and benefits at 1.5% per year.ResultsCombination therapy was predicted to reduce complication rates and associated costs compared with metformin. Survival increased by 0.39 (0.32 discounted) and QALY by 0.46 years (0.37 discounted) implying costs of £6,772 per discounted LYG and £5,609 per discounted QALY. Sensitivity analyses showed the results to be consistent over broad ranges.ConclusionAlthough drug treatment costs are increased by combination therapy, this cost is expected to be partially offset by a reduction in the costs of treating long-term diabetes complications.

Quality of clinical documentation and anticoagulation control in patients with chronic nonvalvular atrial fibrillation in routine medical care.

Objective . Anticoagulation quality and record documentation were retrospectively assessed in patients with chronic nonvalvular atrial fibrillation (CNVAF) managed in a routine care setting. Methods. Medical record data extraction from physician practices in 4 regions of the United States. Results. Of 686 patients, 59% had an electrocardiogram confirming CNVAF, 84% listed at least 1 stroke risk factor, and 60% indicated the goal target international normalized ratio (INR). Two thirds of INRs >3.0 or <2.0 had no recorded dose change, nor did 45% of INRs >5.0. Vitamin K was given (3%) or anticoagulation was temporarily discontinued (9%) for INRs >5.0. The median interval of INR testing was 21 days, which decreased to 7 days for INRs > 4.60. Patients spent 58% of the time in therapeutic range. Conclusion. Serious deficiencies in quality and documentation of routine medical care of anticoagulation for patients with CNVAF continue to exist. (Am J Med Qual 2007;22:327-333)

Health and Economic Effects of Adding Nateglinide to Metformin to Achieve Dual Control of Glycosylated Hemoglobin and Postprandial Glucose Levels in a Model of Type 2 Diabetes Mellitus

BACKGROUND Type 2 diabetes mellitus is a common disease whose complications have great costs, both in quality of life and expense of treatment. Improving glycemic control, as measured by monitoring glycosylated hemoglobin (HbA1c) levels, can reduce the rate of such complications. OBJECTIVES The aims of this study were to estimate the lifetime costs associated with diabetes-related complications in a theoretical population receiving metformin monotherapy and to predict the health and economic effect of improving glycemic control in this theoretical population by combining metformin with nateglinide. METHODS A pharmacoeconomic model was developed to simulate the long-term (30 years) complication rates (microvascular and macrovascular) of a cohort of patients with type 2 diabetes mellitus. The model simulated each year of life for each patient in a theoretical cohort of 10,000 patients until diabetes-related complications were present or death occurred. The mean accumulated costs (direct medical costs for acute care and subsequent care for diabetes-related complications), mean survival time, and the frequency of each type of complication were estimated. Both effectiveness and cost data were discounted at 3%. Sensitivity analyses were conducted on key model input parameters. RESULTS Average costs of treating complications in theoretical patients undergoing metformin monotherapy were estimated at