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Stan Shapiro

Publications and source records attributed to Stan Shapiro.

11 recordsLinked to original sources
PubMed2006

Use of antidepressants and risk of colorectal cancer: a nested case-control study.

BACKGROUND: Animal studies suggest that selective serotonin reuptake inhibitors (SSRI) retard the growth of colorectal tumours, whereas tricyclic antidepressants increase the risk of colorectal cancer. We aimed to assess whether SSRI use was associated with a decreased risk of colorectal cancer, and tricyclic-antidepressant use with an increased risk of colorectal cancer. METHODS: We did a population-based nested case-control study from Jan 1, 1981, to Dec 31, 2000, of people aged 5-85 years who were registered with Saskatchewan Health and eligible for prescription-drug benefit. Between Jan 1, 1981, and Dec 31, 2000, 6544 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for use of tricyclic antidepressants; between Jan 1, 1991, and Dec 31, 2000, 3367 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for SSRI use. For every case, four eligible controls matched for age, sex, and calendar time (ie, free of any cancer in calendar month of case diagnosis) were selected randomly by a statistician who used incidence density sampling. By use of conditional logistic regression, we assessed incidence-rate ratios of having colorectal cancer in association with use of antidepressants, analysing dose and time of use. FINDINGS: A decreased risk of colorectal cancer was associated with high (ie, >6.0x10(-6) mol per day) daily SSRI dose during 0-5 years before diagnosis (incidence-rate ratio 0.70 [95% CI 0.50-0.96], p for trend=0.0172), adjusted for age, sex, use of non-steroidal anti-inflammatory drugs in the same period, and SSRI use during 6-10 years before index date (ie, date of diagnosis for a case and the same date for matched controls). No consistent relation was recorded for risk of colorectal cancer and use of tricyclic antidepressants. INTERPRETATION: SSRI use might inhibit the growth of colorectal tumours through an antipromoter effect or direct cytotoxic effect. Further investigation is needed, with more complete assessment of confounders such as lifestyle factors (eg, diet), use of drugs, and comorbidity (eg, diabetes or inflammatory bowel disease) that might affect the occurrence of colorectal cancer.

Adolescent↗
PubMed2005

Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials.

OBJECTIVE: To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group. SELECTION OF STUDIES: Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week. RESULTS: Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42). DISCUSSION: Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.

Adult↗
PubMed2005

Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding?

BACKGROUND: Aprotinin is a serine protease inhibitor used to limit perioperative bleeding and reduce the need for donated blood transfusions during cardiac surgery. Randomized controlled trials of aprotinin evaluating its effect on the outcome of perioperative transfusion have been published since 1987, and systematic reviews were conducted in 1992 and 1997. METHODS: A systematic search was conducted for all RCTs of aprotinin that used placebo controls or were open-label with no active control treatment. Data collected included the primary outcome, objective of each study, whether a systematic review was cited or conducted as part of the background and/or rationale for the study and the number of previously published RCTs cited. Cumulative meta-analyses were performed. RESULTS: Sixty-four randomized, controlled trials of aprotinin were found, conducted between 1987 and 2002, reporting an endpoint of perioperative transfusion. Median trial size was 64 subjects, with a range of 20 to 1784. A cumulative meta-analysis indicated that aprotinin greatly decreased the need for perioperative transfusion, stabilizing at an odds ratio of 0.25 (p < 10 - 6) by the 12th study, published in June of 1992. The upper limit of the confidence interval never exceeded 0.65 and results were similar in all subgroups. Citation of previous RCTs was extremely low, with a median of 20% of prior trials cited. Only 7 of 44 (15%) of subsequent reports referenced the largest trial (N = 1784), which was 28 times larger than the median trial size. CONCLUSIONS: This study demonstrates that investigators evaluating aprotinin were not adequately citing previous research, resulting in a large number of RCTs being conducted to address efficacy questions that prior trials had already definitively answered. Institutional review boards and journals could reduce the number of redundant trials by requiring investigators to conduct adequate searches for prior evidence and conducting systematic reviews.

Aprotinin↗
PubMed2004

Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials.

OBJECTIVE: To examine the reporting and success of double blinding in a sample of randomised, placebo controlled trials from leading general medicine and psychiatry journals. METHODS: Identification of placebo controlled, randomised controlled trials from prespecified general medical and psychiatric journals indexed on Medline between 1 January 1998 and 1 October 2001, from which a random sample of 200 randomised clinical trials was chosen, of which 191 trials were evaluated. RESULTS: Only seven of the 97 (7%) general medicine trials provided evidence on the success of blinding, with five reporting that the success of blinding was imperfect. In trials from psychiatric journals, the success of blinding was reported in eight of the 94 trials, with four reporting that the blinding was imperfect. Overall, only four of the 191 (2%) trials assessed blinding in the participants and either the outcome assessors or the investigators. CONCLUSIONS: The current lack of reporting on the success of blinding provides little evidence that success of blinding is maintained in placebo controlled trials. Trialists and editors should make a concerted effort to incorporate, report, and publish such information and its potential effect on study results.

Double-Blind Method↗
PubMed2003

Clinical outcomes following institution of universal leukoreduction of blood transfusions for premature infants.

CONTEXT: Leukocytes present in stored blood products can have a variety of biological effects, including depression of immune function, thereby increasing nosocomial infections and possibly resulting in organ failure and death. Premature infants, given their immature immune state, may be uniquely predisposed to the effects of transfused leukocytes. OBJECTIVE: To evaluate the clinical outcomes following implementation of a universal prestorage red blood cell (RBC) leukoreduction program in premature infants admitted to neonatal intensive care units (NICUs). DESIGN AND SETTING: Retrospective before-and-after study conducted in 3 Canadian tertiary care NICUs from January 1998 to December 2000. PATIENTS: A total of 515 premature infants weighing less than 1250 g who were admitted to the NICU, received at least 1 RBC transfusion, and survived at least 48 hours were enrolled. The intervention group consisted of infants admitted in the 18-month period following the introduction of universal leukoreduction (n = 247) and the control group consisted of infants admitted during the 18 months prior to the introduction of universal leukoreduction (n = 268). MAIN OUTCOME MEASURES: Primary outcomes were nosocomial bacteremia and NICU mortality, compared before and after implementation of universal leukoreduction using multivariate regression. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. RESULTS: The proportion of infants who acquired bacteremia after an RBC transfusion was 79/267 (29.6%) in the nonleukoreduction period and 63/246 (25.6%) in the leukoreduction period. For NICU mortality, there were 45 deaths (16.8%) in the nonleukoreduction period and 44 deaths (17.8%) in the leukoreduction period. The adjusted odds ratio (OR) for bacteremia was 0.59 (95% confidence interval [CI], 0.34-1.01) and for mortality was 1.22 (95% CI, 0.59-2.50). The adjusted ORs for bronchopulmonary dysplasia and retinopathy of prematurity were 0.42 (95% CI, 0.25-0.70) and 0.56 (95% CI, 0.33-0.93), respectively. The adjusted ORs for necrotizing enterocolitis and grade 3 or 4 intraventricular hemorrhage were 0.39 (95% CI, 0.17-0.90) and 0.65 (95% CI, 0.35-1.19), respectively. The adjusted OR for a composite measure of any major neonatal morbidity was 0.31 (95% CI, 0.17-0.56). Crude and adjusted rates for all secondary outcomes suggest that leukoreduction was associated with improved outcomes. CONCLUSION: Implementation of universal prestorage leukoreduction was not associated with significant reductions in NICU mortality or bacteremia but was associated with improvement in several clinical outcomes in premature infants requiring RBC transfusions.

Bacteremia↗
PubMed2003

Absence of association between infectious agents and endothelial function in healthy young men.

BACKGROUND: Although several studies have reported correlations between infections and coronary artery disease, associations with endothelial dysfunction, its precursor, have not been established. This study assessed whether infection with Chlamydia pneumoniae (CP), cytomegalovirus (CMV), Epstein-Barr virus (EBV), or Helicobacter pylori (HP) is associated with decreased endothelial function. METHODS AND RESULTS: Sixty-five male subjects, aged 20 to 45 years, with no risk factors or known coronary artery disease were enrolled in a seroepidemiological cross-sectional study. Endothelial function was determined by flow-mediated brachial vasodilation. Serum antibodies consisting of anti-CP IgG and IgM, anti-CMV IgG, anti-EBV nuclear antigen, and anti-HP IgG and markers of inflammation including high-sensitivity C-reactive protein were measured. Average age was 29.3+/-5.5 years. Seroprevalence values were 65.1%, 34.9%, 88.9%, and 14.3% for CP, CMV, EBV, and HP, respectively. Average values for endothelium-dependent and -independent vasodilation were 9.4+/-4.5% and 12.6+/-5.0%. Despite adequate statistical power (82% for the primary end point), no association between endothelial function and seropositivity to individual infectious agents, infectious burden, or C-reactive protein was observed in regression analyses controlling for variables including age, blood pressure, and lipid parameters. Moreover, no dose-response trends between serum titers and endothelial function were found. CONCLUSIONS: Lack of association between chronic infection with CP, CMV, EBV, HP, or pathogen burden and endothelial function was observed, suggesting that these agents are not implicated as early etiologic triggers in the genesis of coronary artery disease. These results do not preclude active involvement at later stages of the pathophysiological process, such as acceleration of existing atherosclerosis and acute plaque rupture.

Adult↗
PubMed2003

Does aggressive care following acute myocardial infarction reduce mortality? Analysis with instrumental variables to compare effectiveness in Canadian and United States patient populations.

BACKGROUND: Previous U.S. studies suggest that the incremental ("marginal") use of the aggressive approach to care for acute myocardial infarction (AMI) in patients differing only in their distance to hospitals offering aggressive care may be associated with small mortality benefits. We hypothesized that the marginal benefits should be larger in Canada, as the country is operating on a lower margin because the approach to care is more conservative overall. METHODS: This retrospective study used administrative data of hospital admissions and health services for all patients admitted for a first AMI in Quebec in 1988 (n = 8,674). We used differential distances to hospitals offering aggressive care as instrumental variables when measuring mortality up to four years after AMI. RESULTS: Of the 4,422 subjects who were > or = 65 years old, 11 percent received cardiac catheterization within 90 days after admission. In a previous study that applied similar methodology to the 1987 U.S. Medicare population, 23 percent of subjects received catheterization within 90 days. As in the U.S. study, we found that subjects living closer to hospitals offering aggressive care were more likely to receive aggressive care than subjects living further away (26 percent versus 19 percent received cardiac catheterization within 90 days; 95 percent CI: 5 percent to 9 percent). Unlike the U.S. study, we found no differences in mortality across the "close" versus "far" differential distance groups (unadjusted differences at one year: 1 percent; 95 percent CI: -1 percent to 3 percent). This absence of association held in elderly (> or = 65 years) and younger age groups. Adjusted results also showed no differences between subjects receiving aggressive versus conservative care (at one year: 4 percent; 95 percent CI: -11 percent to 20 percent). CONCLUSIONS: Contrary to our hypothesis, but consistent with results from numerous randomized trials and observational studies, we cannot confirm that, on the margin, the aggressive approach to post-AMI care is associated with mortality benefits in Canada.

Aged↗
PubMed2002

Predictive factors and correlates for pain in postpoliomyelitis syndrome patients.

OBJECTIVE: To identify predictive and associated factors for muscle and joint pain in postpoliomyelitis syndrome (PPS). DESIGN: Cross-sectional study design. SETTING: Postpolio clinics. PARTICIPANTS: Baseline data on 126 PPS patients entered into a multicentered clinical trial. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Adjusted odds ratios were computed by using logistic regression modeling. Patients with or without muscle or joint pain were compared with regard to predictors and associated factors. RESULTS: In multivariate analyses for muscle pain, significant predictive and associated factors were female gender (P=.0006), longer duration of general fatigue (P=.019), and a lower score on the general health scale (P=.009) of the Medical Outcomes Study 36-Item Short-From Health Survey (SF-36). In multivariate analyses for joint pain, significant predictive and associated factors were female gender (P<.003), longer latency (duration of stability after polio; P=.008), younger age at interview (P<.002), greater weakness at acute polio (P<.07), weaker lower-extremity muscle strength (P<.04), and a lower SF-36 general health scale score (P<.02). CONCLUSIONS: Women are more likely to report muscle and joint pain in PPS. Greater initial motor unit involvement and lower-extremity weakness may be additional important factors for determining joint pain. Both muscle and joint pain are associated with reductions in quality of life.

Aged↗
PubMed2002

The before/after study design in transfusion medicine: methodologic considerations.

To ascertain the effectiveness of an intervention, a randomized controlled trial (RCT) is considered the gold standard. An obstacle to conducting an RCT only rarely discussed is the universal implementation of an intervention. Universal implementation clearly precludes the feasibility of conducting an RCT. Thus, the most attractive alternative study design in such instances becomes the before/after study. This article describes important methodologic considerations in undertaking a before/after evaluation. The methodologic considerations to be discussed are (1) threats to internal validity, (2) precision and (3) generalizability. Two before/after studies evaluating the potential effectiveness of universal leukoreduction serve as examples. Because of the universal application of many transfusion interventions, one has to consider carefully the methodologic rigor as to which of these interventions are evaluated. We have outlined the major methodologic issues one must consider when undertaking a before/after study design. When properly conceived, conducted, and analyzed, such a before/after study design can yield informative associations.

Adult↗
PubMedDate not supplied

A Canadian, multicentre, randomized clinical trial of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease: rationale and methods.

BACKGROUND: Pulmonary rehabilitation remains largely underused. Self-monitored, home-based rehabilitation is a promising approach to improving the availability of pulmonary rehabilitation. OBJECTIVE: To report the rationale and methods of a trial comparing the effectiveness of self-monitored, home-based rehabilitation with hospital-based, outpatient rehabilitation in patients with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: A parallel-group, randomized, noninferiority, multicentre trial will be performed with 240 patients with moderate to severe COPD. INTERVENTION: Patients will be randomly assigned to conventional, supervised, hospital-based outpatient rehabilitation or self-monitored, home-based rehabilitation. Both interventions will include a standardized, comprehensive self-management program, in addition to the hospital-based outpatient or home-based exercise program. After the three-month intervention, patients in both groups will be encouraged to continue exercising at home. Patients will be assessed monthly with telephone interviews and in person at enrollment, three months and 12 months. OUTCOMES: The dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) at 12 months is the primary outcome variable. Secondary outcome variables include total and domain-specific CRQ scores; exercise tolerance and activity of daily living; health service use over the one-year study period; and direct and indirect costs of COPD treatment. ANALYSIS: An intent-to-treat approach will be used as the primary analysis. The primary analysis will focus on the change in the CRQ dyspnea score using a two-sided t distribution based on 95% CIs. The same approach will be used for secondary continuous outcome variables. CONCLUSION: The present trial will address two unresolved issues in pulmonary rehabilitation for patients with COPD: the short-term and long-term effectiveness of home-based pulmonary rehabilitation strategies. The authors will also determine if home-based pulmonary rehabilitation can reduce health service use (eg, hospitalizations and emergency visits) and if it can be done at a lower cost than the traditional hospital-based outpatient pulmonary rehabilitation.

Adult↗