Márcio Machado

Sensitivity of Patient Outcomes to Pharmacist Interventions. Part I: Systematic Review and Meta-Analysis in Diabetes Management

Background: Hypertension is a major health concern worldwide due to its deleterio us impact. Few studies have quantitatively assessed pharmacists’ interventions in hypertensive patients. Objectives: To identify and quantify outcomes sensitive to pharmacists’ interventions. Methods: International Pharmaceutical Abstracts, MEDLINE, Cochrane Central, and EMBASE were searched from inception through December 2006. Two independent reviewers identified articles; results were compared and resolved through consensus. Data extracted included intervention type, patient numbers, demographics, study characteristics, instruments used, data compared, and outcomes reported. A random effects meta-analysis was used to combine data. Study quality was assessed using the Downs–Black scale. Results: Of 203 potential articles identified, 98 were selected and their abstracts were read. Nine of these were reviewed full-text and 19 more were identified from references, resulting in a total of 28 articles. Research designs included 18 randomized controlled trials, 6 single-arm clinical trials, 3 nonrandomized comparative trials, and 1 database study. Average quality score was 66% ± 12% (fair). Medication management (82%) and hypertension education (68%) were the interventions most used. Thirty-nine study results (57% of all outcomes evaluated) were sensitive to pharmacists’ interventions. Meta-analysis of 2246 patients in 13 studies found that pharmacists’ interventions significantly reduced systolic blood pressure (10.7 ± 11.6 mm Hg; p = 0.002), while controls remained unchanged (3.2 ± 12.1 mm Hg; p = 0.361). Pharmacists’ interventions further reduced systolic blood pressure (6.9 ± 12.1 mm Hg;p = 0.047) over controls. Nonsensitive results included further reduction in diastolic blood pressure (3.6 ± 3.7 mm Hg; p = 0.06), quality of life (1 of 8 significant), and adherence (5 of 13 significant). Conclusions: Systolic blood pressure is sensitive to pharmacists’ interventions. Other outcomes may also be sensitive; however, more high-quality studies are needed for a comprehensive quantitative assessment

Association of temporal trends in risk factors and treatment uptake with coronary heart disease mortality, 1994-2005.

CONTEXT Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. OBJECTIVE To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. DESIGN, SETTING, AND PATIENTS Prospective analytic study of the Ontario, Canada, population aged 25 to 84 years between 1994 and 2005, using an updated version of the validated IMPACT model, which integrates data on population size, CHD mortality, risk factors, and treatment uptake changes. Relative risks and regression coefficients from the published literature quantified the relationship between CHD mortality and (1) evidence-based therapies in 8 distinct CHD subpopulations (acute myocardial infarction [AMI], acute coronary syndromes, secondary prevention post-AMI, chronic coronary artery disease, heart failure in the hospital vs in the community, and primary prevention for hyperlipidemia or hypertension) and (2) population trends in 6 risk factors (smoking, diabetes mellitus, systolic blood pressure, plasma cholesterol level, exercise, and obesity). MAIN OUTCOME MEASURES The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. RESULTS Between 1994 and 2005, the age-adjusted CHD mortality rate in Ontario decreased by 35% from 191 to 125 deaths per 100,000 inhabitants, translating to an estimated 7585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range, 11% to 124%) of the total mortality decrease, most notably in AMI (8%; range, -5% to 40%), chronic stable coronary artery disease (17%; range, 7% to 35%), and heart failure occurring while in the community (10%; range, 6% to 31%). Trends in risk factors accounted for 3660 fewer CHD deaths prevented or delayed (48% of total; range, 28% to 64%), specifically, reductions in total cholesterol (23%; range, 10% to 33%) and systolic blood pressure (20%; range, 13% to 26%). Increasing diabetes prevalence and body mass index had an inverse relationship associated with higher CHD mortality of 6% (range, 4% to 8%) and 2% (range, 1% to 4%), respectively. CONCLUSION Between 1994 and 2005, there was a decrease in CHD mortality rates in Ontario that was associated primarily with trends in risk factors and improvements in medical treatments, each explaining about half of the decrease.

Cost‐effectiveness of biologic response modifiers compared to disease‐modifying antirheumatic drugs for rheumatoid arthritis: A systematic review

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects approximately 1% of the population (1,2). The course of RA varies, but for a substantial proportion of patients it is characterized by persistent pain and stiffness, progressive joint destruction, functional disability, and premature mortality (3). RA also presents a serious socioeconomic burden in terms of direct medical costs (associated with resources consumed to research, detect, and treat RA) and indirect costs (associated with lost productivity, early mortality, and time contributed by caregivers) (4–9). The pharmacologic management of RA has been transformed with the introduction of disease-modifying antirheumatic drugs (DMARDs), a large class of drugs that includes hydroxychloroquine, leflunomide, methotrexate, and sulfasalazine. Whereas drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) and corticosteroids control symptoms, DMARDs slow the progression of joint damage that leads to loss of function (10,11). Guidelines advocate treatment with DMARDs as soon as RA is diagnosed to control symptoms and delay disease progression (12). Newly developed biologic response modifiers (biologics) offer even more hope, having a greater potential to suppress disease activity, improve quality of life, and inhibit joint destruction (13–15). But while biologics may have the greatest potential to slow the course of RA, these drugs cost substantially more than DMARDs. Consequently, current guidelines recommend biologics for patients with inadequate responses to DMARDs largely because higher costs preclude their widespread early use (12,16–18). Therefore, at the core of the debate is whether the superior clinical outcomes achieved with biologics are worth their higher costs. Should earlier treatment with biologics be considered, given their potential to slow disease progression and extend productivity, thereby reducing downstream direct costs associated with health care utilization and indirect costs associated with lost productivity? Since the introduction of cyclooxygenase 2–inhibiting NSAIDs and DMARDs, RA drug costs have more than doubled, and now with the recent introduction of biologics, these costs are expected to increase (19). Not surprisingly, many agencies (including the National Institutes of Health in the US) have identified the cost-effectiveness of biologics as one of the highest-priority research topics in the pharmacologic treatment of RA. Decision makers in public and private health care systems need a synopsis of current economic evidence upon which to base funding decisions. An understanding of the existing literature is also essential to identify gaps in the current evidence and to inform the development of future economic evaluations. We therefore undertook a review of the literature to identify and critically appraise existing economic evaluations of biologics versus DMARDs for adults with RA and to determine whether the incremental cost-effectiveness is within the range of generally accepted medical interventions. Gabrielle van der Velde, DC, PhD, Claire Bombardier, MD, FRCPC: Toronto Health Economics and Technology Assessment Collaborative and Institute for Work and Health, Toronto, Ontario, Canada; Ba’ Pham, PhD (Candidate), Márcio Machado, PharmD, PhD (current address: GlaxoSmithKline, Rio de Janeiro, Brazil), Luciano Ieraci, MSc, William Witteman, MIS, Murray Krahn, MD, MSc: Toronto Health Economics and Technology Assessment Collaborative, Toronto, Ontario, Canada. Dr. Bombardier has received consultant fees, speaking fees, and/or honoraria (less than

Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp

10,000 each) from AstraZeneca, Pfizer, Biogen Idec, PESI Healthcare, and Roche, and (more than

Systematic Review and Meta-analysis of the Effect of Warming Local Anesthetics on Injection Pain

10,000 each) from Abbott Canada and Abbott International, Wyeth (Merck), and Schering (Merck). Address correspondence to Gabrielle van der Velde, DC, PhD, THETA Collaborative, Leslie L. Dan Pharmacy Building, University of Toronto, 6th Floor, Room 658, 144 College Street, Toronto, Ontario, M5S 3M2 Canada. E-mail: gabrielle. vandervelde@theta.utoronto.ca. Submitted for publication January 29, 2010; accepted in revised form August 19, 2010. Arthritis Care & Research Vol. 63, No. 1, January 2011, pp 65–78 DOI 10.1002/acr.20338

Systematic review and quality assessment of economic evaluations and quality-of-life studies related to generalized anxiety disorder

Our objective in this study was to review systematically the evidence for safety of Lactobacillus, Bifidobacterium and Saccharomyces spp. during pregnancy and to conduct a meta-analysis of randomized controlled trials (RCTs). Eleven databases were searched from inception to September 2007 for RCTs of probiotic use during pregnancy. Two independent reviewers searched databases. Random-effects models combined data. Eleven studies on Lactobacillus and/or Bifidobacterium examined 1505 patients for four outcomes with no data heterogeneity; no miscarriage data were reported. Five studies reported Caesarean section outcomes (OR 0.88; 95% CI 0.65 to 1.19). Six studies reported birth weight (weighted difference 45 g; 95% CI -181 to 271). Three studies reported gestational age (weighted difference 0.4 weeks; 95%CI -0.4 to 1.2). No malformations were reported in the probiotic group. No RCTs were available for Saccharomyces during pregnancy. Lactobacillus and Bifidobacterium had no effect on the incidence of Caesarean section, birth weight, or gestational age. The safety of Saccharomyces during pregnancy is unknown.

Efficacy of Botulinum Toxin Type A for the Prophylaxis of Episodic Migraine Headaches: A Meta-analysis of Randomized, Double-Blind, Placebo-Controlled Trials

STUDY OBJECTIVE Local anesthetics are the main class of analgesics used for pain management during laceration repair and other minor surgeries; however, they are administered by injection, which is painful. Warming local anesthetics has been proposed as a cost-free intervention that reduces injection pain. A systematic review of the effectiveness of this technique has not yet been undertaken. We determine the effectiveness of warming local anesthetics to reduce pain in adults and children undergoing local anesthetic infiltration into intradermal or subcutaneous tissue. METHODS We used published articles from MEDLINE (1950 to June 2010), EMBASE (1980 to June 2010), CINAHL (1982 to June 2010), the Cochrane Library (second quarter 2010), International Pharmaceutical Abstracts (1970 to June 2010), and ProQuest Dissertations and Theses database (1938 to June 2010). We included studies with randomized or pseudorandomized designs and healthy subjects or patients receiving subcutaneous or intradermal injection of local anesthetics that were warmed (body temperature) or not (room temperature). Studies of regional anesthesia and intraarticular, spinal, or periorbital administration of local anesthetics were excluded. Data were extracted onto predesigned forms and verified by 2 reviewers. Quality was assessed with the Cochrane risk of bias tool. The primary outcome was self-reported pain as assessed by a visual analog or numeric rating scale. Data were combined with mean differences with 95% confidence intervals (CIs) by using a random-effects model. RESULTS Twenty-nine studies were retrieved for close examination and 19 studies met inclusion criteria. A total of 18 studies with 831 patients could be included in a meta-analysis. Seventeen studies had an unclear risk of bias and 1 had a high risk of bias. A mean difference of -11 mm (95% CI -14 to -7 mm) on a 100-mm scale was found in favor of warming local anesthetics. Subgroup analysis of 8 studies investigating the effect of warming on buffered local anesthetics yielded similar results: -7 mm (95% CI -12 to -3 mm). CONCLUSION Warming local anesthetics leads to less pain during injection and therefore should be done before administration.

Efficacy of Clodronate, Pamidronate, and Zoledronate in Reducing Morbidity and Mortality in Cancer Patients With Bone Metastasis: A Meta-Analysis of Randomized Clinical Trials

BACKGROUND The objectives of this article were to systematically review, summarize the results of, and assess the quality of economic evaluations and humanistic studies related to patients with generalized anxiety disorder (GAD). METHODS EMBASE, EBM Reviews, MEDLINE, and HealthSTAR databases were searched (from the time of inception through April 2008). Full-text publications describing full economic evaluations (cost-benefit, cost-minimization, cost-effectiveness, and cost-utility analyses), partial economic evaluations (cost, burden-of-illness, and resource-utilization analyses), and humanistic outcomes (utilities, preferences, and willingness-to-pay analyses) were included. GAD diagnoses per official publications (eg, Diagnostic and Statistical Manual of Mental Disorders) and associated comorbid conditions were included; anxiety-related symptoms without a diagnosis of GAD were excluded. Study quality was assessed with a 38-point checklist of criteria previously developed by the Panel on Cost-Effectiveness in Health and Medicine. RESULTS Thirty-six articles were included. Full economic evaluations (n = 5) were based on conventional decision-making modeling or population-summary data, using time horizons < or =12 months. Cognitive-behavioral therapy by a public-salaried psychologist and evidence-based care generated savings compared with current care. Pharmacotherapy with extended-release venlafaxine treatment was cost-effective compared with diazepam; escitalopram was cost-effective compared with paroxetine because of productivity gains. Full economic evaluations addressed 55.3% to 68.4% of the 38 items on the quality-assessment checklist. Partial evaluations were reported; GAD incurred larger mean marginal health care costs compared with other anxiety disorders (a difference of US

Cost-effectiveness of specialized multidisciplinary heart failure clinics in Ontario, Canada.

2138 in year-1999 values). GAD patients with severe pain interference incurred significantly higher costs than did patients with pain but no GAD. Furthermore, GAD patients used more services from a primary care provider or specialist than did patients with other psychiatric disorders. Comorbidities were associated with greater absenteeism than was having a diagnosis of GAD alone. Mean (SE) utility scores for quality-of-life assessments among patients with GAD (15D, 0.783 [0.019]; EuroQoL EQ-5D, 0.589 [0.038]) were similar to those for patients who were 20 years older and reported somatic conditions such as Parkinsons disease or heart failure. CONCLUSIONS Current evidence suggests that GAD is associated with substantial economic and humanistic impact on patients and health care systems. Future research should address economic evaluations from the private-payer perspective, studies related to the cost of underdiagnosed or untreated GAD, and full economic evaluations that incorporate longer clinical courses of the disorder.

Perfil da mortalidade por intoxicação com medicamentos no Brasil, 1996-2005: retrato de uma década

Study Objective. To assess the efficacy of botulinum toxin type A in lowering the frequency of migraine headaches in patients with episodic migraines.