M Machado

University of Toronto, Toronto, Ontario, Canada

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Publications (63)163.8 Total impact

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    ABSTRACT: Objective: To quantify the rates of clinical outcomes of Canadian Psychiatric Association (CPA) guideline-recommended pharmacotherapies for generalized anxiety disorder (GAD) by drug classification within each treatment line. Methods: Evidence from original research cited by the CPA was included. Pooled analyses, duplicates, and studies with nonextractable data were excluded. Response, remission, and baseline-endpoint or mean reductions scores of the Hamilton Anxiety Rating Scale (HARS) were extracted. The Cochrane Collaboration's computer program, Review Manager, version 5, with a random effects model, was used to pool results. Results: A total of 50 articles were cited as evidence for managing GAD by the CPA. There was sufficient evidence of remission with first- or third-line agents to pool reported rates, and with agents from all 3 treatment lines to pool response rates and reduction in HARS scores. The mean range of effect size varied considerably from study to study within each treatment line. Comparison of pooled remission rates between first- and second-line agents was not possible. While the range of values by drug and drug class overlapped, the summary results for the probability of response and reduction in HARS scores was greater for first-line, compared with second-line, treatments. Drug components for third-line treatments were heterogeneous and produced mixed results. Conclusion: Despite the abundance of evidence in its totality presented in the CPA guidelines, there is inadequate evidence to formulate recommendations based on the pooled results from this study alone. However, such analysis provides an additional resource for clinicians to make more effective treatment decisions for individual patients with GAD.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie 08/2012; 57(8):470-8. · 2.48 Impact Factor
  • Marcio Machado, Thomas R Einarson
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    ABSTRACT: To evaluate, from the perspective of the Brazilian public health care system, the cost-effectiveness of lapatinib plus capecitabine (LAP/CAP) versus capecitabine alone (CAP) or trastuzumab plus capecitabine (TRAST/CAP) in the treatment of women with human epidermal growth factor receptor-2-positive metastatic breast cancer previously treated with trastuzumab. An economic model was developed to compare costs and clinical outcomes over a 5-year time horizon. Both costs and outcomes were discounted at a 5% rate, in accordance with Brazilian pharmacoeconomic guidelines. Clinical inputs were determined using indirect treatment comparisons. Costs were derived from public reimbursement databases and reported in 2010 Brazilian real (R$1 = USD$0.52). Clinical outcomes included progression-free survival years (PFYs), life-years (LYs) and quality-adjusted life-years (QALYs). The economic outcome was the incremental cost per LY, PFY, or QALY gained. The impact of variations in individual inputs (eg, drug cost, drug effectiveness) was examined using one-way sensitivity analyses. Overall model robustness was tested using probabilistic sensitivity analyses, varying the ranges of all input parameters within their standard distributions. Expected cost per patient was R$41,195 for CAP, R$95,256 for LAP/CAP, and R$113,686 for TRAST/CAP. Respective LYs were 1.406, 1.695, and 1.465; PFYs were 0.473, 0.711, and 0.612; and QALYS were 0.769, 0.958, and 0.827. LAP/CAP dominated TRAST/CAP for all outcomes. Incremental cost-effectiveness ratios of LAP/CAP over CAP were R$186,563 for LYs, R$226,403 for PFYs, and R$284,864 for QALYs. Results remained unchanged in one-way sensitivity analyses. In probabilistic analyses, LAP/CAP was dominant over TRAST/CAP in 93.5% of simulations. LAP/CAP increases survival for women with human epidermal growth factor receptor-2-positive metastatic breast cancer. LAP/CAP is cost-effective against TRAST/CAP (ie, produces more benefits at a lower cost) and can be considered cost-effective over CAP at a willingness-to-pay of about R$290,000 (US$151,000) per QALY gained.
    Breast Cancer: Targets and Therapy 01/2012; 4:173-82.
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    ABSTRACT: Metastatic bone disease (MBD) is responsible for >99% of malignant tumors that affect the bone. MBD patients have increased risk of skeletal complications that are often dramatic and result in loss of function or disability, leading to rapid deterioration of quality of life. Bisphosphonates have become the standard therapy for the treatment and prevention of skeletal-related events (SREs). The objective of this study was to evaluate the cost-effectiveness of zoledronate and clodronate in the prevention of SREs in patients with MBD. A pharmacoeconomic analysis was performed for a hypothetical cohort of patients with MBD to compare the costs and consequences of the use of clodronate and zoledronate for treatment and prevention of SREs in MBD in Brazil. The model was constructed using decision analysis techniques. Costs were described in 5 categories-drugs, physician visits, hospitalizations, surgical/medical care, and laboratory tests-and were reported in 2008 Brazilian reais (1 BRL = 0.54 US dollar). Quality-adjusted life years gained was considered as an outcome. Sensitivity analyses tested model robustness. The total cost of treatment of MBD in Brazil for a 5-year time-horizon was R$46,313 with clodronate and R$50,319 with zoledronate. The estimated number of quality-adjusted life years was 2.00 and 1.90 for clodronate and zoledronate, respectively. Cost-effectiveness ranking was unchanged when model time-horizon was changed to 1 or 10 years. Univariate analysis revealed the incidence of osteonecrosis as a sensitive parameter in the model. Multivariate analysis confirmed base-case results, in which >60% of model iterations favored clodronate over zoledronate. The present pharmacoeconomic evaluation, under the premises presented, found that clodronate was dominant over zoledronate from both the public and the private health care perspectives in Brazil.
    Clinical Therapeutics 11/2011; 33(11):1769-1780.e2. · 2.23 Impact Factor
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    ABSTRACT: A 1999 meta-analysis described the relationship between blood glucose and subsequent cardiovascular events (MI, stroke, cardiovascular mortality). More studies have been published; therefore, we updated and refined estimates of this relationship in people without diabetes. ACCEPTABILITY CRITERIA: We accepted prospective studies that reported screening results for blood glucose levels (either fasting, 2-hour postprandial, 1-hour postprandial, or casual) divided into ≥3 quantiles. Required data within each quantile were numbers exposed plus study duration or person-years at risk, and numbers of cardiovascular outcomes (myocardial infarction, stroke, death). No restrictions were placed on language or publication date. Two reviewers searched Medline, Embase, Scopus, and Cochrane databases from inception until December 2009. Consensus settled discrepancies. Poisson regression quantified the relationship between glucose quantile and outcomes. Beta values were combined with inverse variance weightings using a random effects meta-analytic model. We found 36 articles with 141 datasets examining the relationship between blood glucose (32 fasting, 52 2-hour postprandial, 37 1-hour postprandial, 20 casual) in 191,249 patients without diabetes (73% male) for 3 million person-years. There were 12,537 (6.6%) cardiovascular deaths, 14,445 (7.6%) cardiovascular events, 6862 (3.6%) cardiac and 3412 (1.7%) stroke deaths. Relative risks/unit increase in blood glucose were all significant for total cardiovascular events (RRs ranged from 1.09-1.51, all p-values < 0.005) and cardiovascular deaths (RR = 1.05-1.24, p < 0.007), and all for cardiac deaths (p < 0.05) except casual glucose; stroke mortality was less clear. The two strongest relationships were found between fasting levels and all events (RR = 1.51, CI: 1.20-1.89) and with cardiovascular mortality (RR = 1.40, CI: 1.18-1.60). With 2-hour postprandial levels, the respective RRs were 1.22 (1.17-1.28) and 1.24 (1.19-1.30). A limitation is the assumption of a continuous relationship between variables. We have provided refined estimates confirming the association between elevated blood glucose and subsequent cardiovascular events.
    Current Medical Research and Opinion 11/2011; 27(11):2155-63. · 2.26 Impact Factor
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    ABSTRACT: Pressure ulcers are common in many care settings, with adverse health outcomes and high treatment costs. We evaluated the cost-effectiveness of evidence-based strategies to improve current prevention practice in long-term care facilities. We used a validated Markov model to compare current prevention practice with the following 4 quality improvement strategies: (1) pressure redistribution mattresses for all residents, (2) oral nutritional supplements for high-risk residents with recent weight loss, (3) skin emollients for high-risk residents with dry skin, and (4) foam cleansing for high-risk residents requiring incontinence care. Primary outcomes included lifetime risk of stage 2 to 4 pressure ulcers, quality-adjusted life-years (QALYs), and lifetime costs, calculated according to a single health care payer's perspective and expressed in 2009 Canadian dollars (Can$1 = US$0.84). Strategies cost on average $11.66 per resident per week. They reduced lifetime risk; the associated number needed to treat was 45 (strategy 1), 63 (strategy 4), 158 (strategy 3), and 333 (strategy 2). Strategy 1 and 4 minimally improved QALYs and reduced the mean lifetime cost by $115 and $179 per resident, respectively. The cost per QALY gained was approximately $78 000 for strategy 3 and $7.8 million for strategy 2. If decision makers are willing to pay up to $50 000 for 1 QALY gained, the probability that improving prevention is cost-effective is 94% (strategy 4), 82% (strategy 1), 43% (strategy 3), and 1% (strategy 2). The clinical and economic evidence supports pressure redistribution mattresses for all long-term care residents. Improving prevention with perineal foam cleansers and dry skin emollients appears to be cost-effective, but firm conclusions are limited by the available clinical evidence.
    Archives of internal medicine 09/2011; 171(20):1839-47. · 11.46 Impact Factor
  • Ralph Santos-Oliveira, Márcio Machado
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    ABSTRACT: There is a considerable body of evidence describing that the pharmacokinetics and pharmacodynamics of radiopharmaceuticals may be changed by a variety of drugs, disease states and in some cases, surgical procedures. : To systematically search the medical literature and review the published evidence on adverse reactions to radiopharmaceuticals. MEDLINE, EMBASE, International Pharmaceutical Abstracts and Science Citation Index were searched for studies reporting adverse reactions to radiopharmaceuticals. Controlled trials, cohort studies, case-control studies and case series published in major Western languages were considered for the review. Each study included in the present review was described in a narrative way, and major components of each study were reported (ie, research design, patient characteristics, types of drugs and radiopharmaceuticals, dosing information and adverse reactions). The majority of adverse reactions to radiopharmaceuticals described in the literature required little or no treatment, and their negative effects were generally mild and self-limited. Large longitudinal greater than 5-year studies reported prevalence rates of adverse reactions due to radiopharmaceuticals ranging from 0 to 25 cases per 100,000 administrations. Case studies on the use of technetium reported mild adverse reactions; however, some led to potentially harmful complications. Similarly, studies involving fluorodeoxyglucose reported more severe adverse reactions. The literature on radiopharmaceuticals adverse effects is scarce, and just a few studies were conducted to investigate the association between radiopharmaceuticals and adverse reactions. Despite relatively mild and self-limited symptoms, the current widespread use of radiopharmaceuticals requires constant monitoring for adverse reactions.
    The American Journal of the Medical Sciences 07/2011; 342(1):50-3. · 1.33 Impact Factor
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    M. Machado, E. Fonseca, M. Fonseca
    Value in Health 05/2011; 14(3):A17–A18. · 2.19 Impact Factor
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    ABSTRACT: The aim of this meta-analysis was to determine the relationship between HbA(1c) levels and subsequent cardiovascular outcomes in individuals without diabetes. We searched Medline, Embase and Scopus from initiation of the study until the end of 2009. One reviewer searched and another verified findings. Data were extracted by one reviewer and verified by another. We accepted prospective studies in any language reporting three or more quartiles for HbA(1c) levels. Within quartiles, authors must have presented both numbers of patient-years at risk and cardiovascular outcomes. Outcomes per person-time at risk were regressed on average HbA(1c) values using Poisson regression. We pooled β coefficients using Cochran's semi-weighted (inverse variance) random-effects model. Study quality was assessed using the Downs-Black scale. We investigated 16 datasets (nine for total cardiovascular events and seven for death) from five papers with 44,158 patients (44% men) over 404,899 patient-years of follow-up. There were 1,366 cardiovascular deaths (3.1%; 3.37/1,000 person-years) and 2,142 cardiovascular events (4.9%; 5.29/1,000 person-years). The overall meta-analytic β coefficients were 0.720 (95% CI 0.307-1.133) and 0.757 (95% CI 0.382-1.132) for cardiac death and events, respectively. Compared with the baseline value of 0.0427, an HbA(1c) level of 0.05 was associated with a relative risk for cardiovascular death of 1.13 (95% CI 1.05-1.21), a 0.06 value with 1.34 (95% CI 1.13-1.58), and a 0.07 HbA(1c) with relative risk 1.58 (95% CI 1.22-2.06). Results for total cardiovascular events were similar. The average study quality was 0.7 (70%). We conclude that HbA(1c) was significantly associated with cardiovascular events and deaths in persons without diabetes.
    Diabetologia 02/2011; 54(6):1327-34. · 6.49 Impact Factor
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    ABSTRACT: 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. 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. 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). Warming local anesthetics leads to less pain during injection and therefore should be done before administration.
    Annals of emergency medicine 02/2011; 58(1):86-98.e1. · 4.23 Impact Factor
  • Arthritis care & research. 01/2011; 63(1):65-78.
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    ABSTRACT: To quantitatively summarize results (i.e., prices and affordability) reported from international drug price comparison studies and assess their methodological quality. A systematic search of the most relevant databases-Medline, Embase, International Pharmaceutical Abstracts (IPA), and Scopus, from their inception to May 2009-was conducted to identify original research comparing international drug prices. International drug price information was extracted and recorded from accepted papers. Affordability was reported as drug prices adjusted for income. Study quality was assessed using six criteria: use of similar countries, use of a representative sample of drugs, selection of specific types of prices, identification of drug packaging, different weights on price indices, and the type of currency conversion used. Of the 1 828 studies identified, 21 were included. Only one study adequately addressed all quality issues. A large variation in study quality was observed due to the many methods used to conduct the drug price comparisons, such as different indices, economic parameters, price types, basket of drugs, and more. Thus, the quality of published studies was considered poor. Results varied across studies, but generally, higher income countries had higher drug prices. However, after adjusting drug prices for affordability, higher income countries had more affordable prices than lower income countries. Differences between drug prices and affordability in different countries were found. Low income countries reported less affordability of drugs, leaving room for potential problems with drug access, and consequently, a negative impact on health. The quality of the literature on this topic needs improvement.
    Revista Panamericana de Salud Pública 01/2011; 29(1):46-51. · 0.85 Impact Factor
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    ABSTRACT: Specialized multidisciplinary clinics have been shown to reduce mortality in heart failure (HF). Our objective was to evaluate the cost-effectiveness of this model of care delivery. We performed a cost-effectiveness analysis, with a 12-year time horizon, from the perspective of the Ontario Ministry of Health and Long-term Care, comparing a standard care cohort, consisting of all patients admitted to hospital with HF in 2005, to a hypothetical cohort treated in HF clinics. Survival curves describing the natural history of HF were constructed using mortality estimates from the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study. Survival benefits and resource uptake associated with HF clinics were estimated from a meta-analysis of published trials. HF clinics costs were obtained by costing a representative clinic in Ontario. Health-related costs were determined through linkage to administrative databases. Outcome measures included life expectancy (years), costs (in 2008 Canadian dollars) and the incremental cost-effectiveness ratio (ICER). HF clinics were associated with a 29% reduction in all-cause mortality (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.56-0.91) but a 12% increase in hospitalizations (RR 1.12; 95% CI 0.92-1.135). The cost of care in HF clinics was $52 per 30 patient-days. Projected life-expectancy of HF clinic patients was 3.91 years, compared to 3.21 years for standard care. The 12-year cumulative cost per patient in the HF clinic group was $66,532 versus $53,638 in the standard care group. The ICER was $18,259/life-year gained. HF clinics appear to be a cost effective way of delivering ambulatory care to HF patients.
    Value in Health 12/2010; 13(8):915-21. · 2.19 Impact Factor
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    ABSTRACT: Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. 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). The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. 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. 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.
    JAMA The Journal of the American Medical Association 05/2010; 303(18):1841-7. · 29.98 Impact Factor
  • M Machado, T R Einarson
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    ABSTRACT: Controversy exists whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs). To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure. Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. Included studies were those head-to-head randomized trials comparing remission (HAMD-17 <or=7-8, MADRS <or=10-12) after 8-12 weeks of therapeutic doses of SSRIs or SNRIs in patients diagnosed with MDD were targeted for analysis. Reviews, letters, commentaries, economic studies, etc. were excluded. Studies were reviewed by two independent researchers. Where disagreements occurred in study selection, a consensus approach was used. Targeted outcome data included number of patients achieving remission, withdrawing from therapy due to lack of efficacy (LoE) and/or adverse drug reactions (ADRs), and total patients in trial. A random effects model combined intent-to-treat (ITT) and per-protocol (PP) odds ratio (OR), and remission and dropout rates. Chi-square assessed heterogeneity. Quality assessment was done using Downs-Black checklist. Thirty-three studies were identified; 18 were rejected (patients had co-morbidities in 7, outcomes differed in 5, different follow-up in 3, and three reviews). Fifteen head-to-head trials of 3094 patients, average age was 41.9 +/- 11.9 years (for SNRIs) and 41.6 +/- 12.1 years (for SSRIs), P = 0.941. All analyses displayed non-heterogeneity (P > 0.05). The OR (under ITT) was 1.27 (1.06-1.52 95% CI) favoring SNRIs. Meta-analytic remission rates were 48.5 +/- 3.2% and 41.9 +/- 4.2% for SNRIs and SSRIs, respectively. The meta-analytic difference in remission rates between drugs was 5.7% (P = 0.007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3.2% difference, P < 0.001). Dropout rates due to LoE were non-significant between studied groups (P > 0.05). Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.
    Journal of Clinical Pharmacy and Therapeutics 04/2010; 35(2):177-88. · 2.10 Impact Factor
  • Value in Health 01/2010; 13(3). · 2.19 Impact Factor
  • Value in Health 01/2010; 13(3). · 2.19 Impact Factor
  • Value in Health 01/2010; 13(3). · 2.19 Impact Factor
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    ABSTRACT: To assess the efficacy of botulinum toxin type A in lowering the frequency of migraine headaches in patients with episodic migraines. Meta-analysis of eight randomized, double-blind, placebo-controlled trials. A total of 1601 patients with a history of episodic migraine headaches classified as those experiencing headaches fewer than 15 times/month over a 3-month period. PubMed, Google Scholar, and the Cochrane Library were searched from inception to October 2007 in order to locate randomized, double-blind, placebo-controlled trials that compared the efficacy of pericranial botulinum toxin A injections with placebo in the prevention of migraines in patients with a history of episodic migraine headaches. The primary outcome of interest was change from baseline to end point in migraine frequency (number of migraines/month). A random effects model was used to combine study results, and the standardized mean difference (Cohen's d) in migraine frequency between the placebo and botulinum toxin A groups was reported. Effect sizes (d) less than 0.2 were considered small. Quality assessment was performed by using the Downs and Black scale. Eight randomized, double-blind, placebo-controlled clinical trials (1601 patients) presented a quantitative assessment of the efficacy of botulinum toxin A versus placebo. The overall treatment effect size of botulinum toxin A over placebo for 30, 60, and 90 days after injection was d -0.06 (95% confidence interval [CI] - 0.14-0.03, z=1.33, p=0.18), d -0.05 (95% CI -0.14-0.03, z=1.22, p=0.22), and d -0.05 (95% CI -0.13-0.04, z=1.07, p=0.28), respectively. Even after controlling for a high placebo effect, and after dose stratification, no significant effect of botulinum toxin A in reducing migraine frequency/month was seen over placebo. Botulinum toxin A for the prophylactic treatment of episodic migraine headaches was not significantly different from placebo, both from a clinical and statistical perspective.
    Pharmacotherapy 08/2009; 29(7):784-91. · 2.31 Impact Factor
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    ABSTRACT: 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.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 07/2009; 31(6):542-52.
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    ABSTRACT: Complications from skeletal-related events (SREs) constitute a challenge in the care of patients with metastatic bone disease (MBD) that originated from any type of malignancy. The purpose of this article was to compare the efficacy of clodronate, pamidronate, and zoledronate with that of placebo in reducing morbidity and overall mortality in cancer patients with MBD. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (from inception to January 2009) to retrieve randomized clinical trials that evaluated the bisphosphonates of interest. The search included articles published in English, French, Italian, Portugese, and Spanish. Patients with a definite (ie, biopsy-proven) diagnosis of MBD were included in the analysis. We extracted and combined data from studies that reported the number of patients with SREs and mortality data. A random-effects, meta-analytic model was applied in all calculations. The Jadad scale was used to assess the quality of study reporting. The literature search identified 62 potential full-text studies; 44 of these studies were excluded and 18 were evaluated. The mean (SD) quality of reporting of the included studies was 57.8% (22.6%), or 2.89/5 (1.1/5). Each of the 3 drugs was found to be more effective than placebo in preventing all SREs in cancer patients with MBD. The relative risk of developing SREs was 0.70 (95% CI, 0.61-0.81; N = 1211) for zoledronate, 0.81 (95% CI, 0.73-0.91; N = 2251) for pamidronate, and 0.87 (95% CI, 0.75-1.00; N = 681) for clodronate. However, no clear advantage of one drug over the others was observed (CIs overlapped substantially). None of the bisphosphonates was more beneficial than placebo in reducing the number of deaths in the course of the trials (P = NS). Clodronate, pamidronate, and zoled-ronate were associated with reductions in morbidity in cancer patients with MBD with regard to preventing SREs, but were not associated with a reduction in overall mortality.
    Clinical Therapeutics 06/2009; 31(5):962-79. · 2.23 Impact Factor

Publication Stats

553 Citations
163.80 Total Impact Points

Institutions

  • 2007–2012
    • University of Toronto
      • • Leslie L. Dan Faculty of Pharmacy
      • • Toronto Health Economics and Technology Assessment (THETA) Collaborative
      Toronto, Ontario, Canada
    • Pharmideas Research And Consulting Inc.
      Oakville, Ontario, Canada
  • 2011
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2006–2007
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
    • University of Chile
      CiudadSantiago, Santiago, Chile