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Mitchell Levine

Publications and source records attributed to Mitchell Levine.

17 recordsLinked to original sources
PubMed2006

Exploring design-related bias in clinical studies on receptor genetic polymorphism of hypertension.

BACKGROUND AND OBJECTIVES: Although several candidate genes of Renin-Angiotensin-Aldosterone System (RAAS) have been investigated, the gene-drug relationship remains unclear. The objective was to appraise the elements of research methodology and explore potential biases, which may be contributing to discordant results in the gene-drug interaction assessment for RAAS. METHODS: Systematic review of studies involving candidate polymorphisms, searching PubMed, and EMBASE. RESULTS: Sixteen studies were identified. Nine studies had a genomic evaluation as the primary question. Six studies investigated more than one gene. A gene-drug interaction was evaluated in two studies and only one of the studies had a placebo arm for accurately exploring the interaction. Almost, 90% of the studies had sample sizes of less than 500 patients. Four studies combined the allele frequencies of the heterozygotes group with one of the homozygotes groups. Almost one quarter of the studies combined different therapeutics in one group. Five studies included patients in one group from previous studies in which selection criteria were not quite similar. CONCLUSION: Most studies contain several methodological limitations. Also biases driven from patient selection, combining different alleles, combining different therapeutics, and combining end points may have occurred in these studies. These limitations and biases may contribute to inconsistency of the results of these studies.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Community-based evaluation of etanercept in patients with rheumatoid arthritis.

OBJECTIVES: Etanercept is one of a new subgroup of biological disease modifying antirheumatic drugs (DMARD) to treat patients with rheumatoid arthritis (RA) who are non-responsive or intolerant to conventional DMARD. We evaluated the effects of etanercept (Enbrel) therapy in patients with RA in community-based clinical practice in Canada. METHODS: Using a cohort design, patients requesting etanercept therapy were stratified into treatment and control arms based upon their individual accessibility to obtain the drug. Patients were interviewed serially during a 12-month period of monitoring. The study measured painful or tender joint count, morning stiffness, pain severity, quality of life measures, medication utilization, health services utilization, and presence of adverse events. RESULTS: The baseline demographic and clinical variables for the treatment group (n = 223) and the control group (n = 208) were similar, except for education, income, and drug plan coverage. In followup, there was greater improvement in most clinical variables in the treatment arm compared to the control arm during the first 6 months, but the magnitude of difference between the 2 groups for some clinical variables decreased or became non-significant during the second 6 months. During the 12 month followup period there were 40 (18%) patient dropouts in the treatment group. CONCLUSION: In a community based setting for the treatment of RA, etanercept can effectively improve the disease state, functional class, work disability, and quality of life during the first 6 months of use. To determine the longterm sustainability of these effects studies with more than 12 months' duration will be required.

Antirheumatic Agents↗
PubMed2006

Sex differences in hospital admissions from emergency departments in asthmatic adults: a population-based study.

BACKGROUND: Women represent the majority of adult patients hospitalized for asthma. Analyzing the course of emergency department (ED) visits before hospital admission can help understanding of the mechanisms behind the excess of hospitalizations in women. OBJECTIVE: To investigate sex differences in hospital admission rates in adult patients with asthma visiting EDs in Ontario. METHODS: Asthmatic patients 18 to 55 years old who visited Ontario EDs between April 1, 2003, and March 31, 2004, were identified using the Canadian Institute for Health Information's National Ambulatory Care Reporting System. The generalized estimating equations for binary outcome were used to model rates of hospital admission with sex, age, and triage (severity) score as covariates. Analysis was further stratified by the ED volume. RESULTS: Women represented 62.2% of all ED visits. They were on average older than men, but both groups had similar distributions of triage scores. Female patients accounted for more hospital admissions than male patients (7.4% vs 4.5%). After adjusting for age and triage score, women were more likely to be admitted than men (odds ratio, 1.64; 95% confidence interval, 1.41-1.90). The interaction found between sex and triage level indicates that hospitalized women may have less severe asthma than hospitalized men. Analysis by ED volume did not significantly alter the results. CONCLUSION: The higher admission rates in women may be related to sex differences in the subjective perception of dyspnea, management of asthma by ED physician, or inadequate ambulatory care strategies in women and thus merit further investigation.

Adolescent↗
PubMed2006

Is fetal gender associated with emergency department visits for asthma during pregnancy?

BACKGROUND: To investigate if fetal gender (1) affects the risk of having an emergency department (ED) visit for asthma; and (2) is associated with adverse pregnancy outcomes among women who had at least one visit to the ED for asthma during pregnancy. METHODS: We linked two provincial administrative databases containing records on in-patient deliveries and ED visits. The study sample included women who delivered a live singleton baby between April 2003 and March 2004. Pregnant women who made at least one ED visit for asthma were counted as cases and the rest of the women as control subjects. We performed a multivariable analysis using logistic regression to model the risk of having an ED visit for asthma, with fetal gender being one of the predictors. In addition, a series of multivariable logistic regressions were also constructed separately for cases and controls for the following adverse delivery outcomes: low birth weight baby, preterm delivery, and delivery via Caesarian section. RESULTS: Among 109,173 live singleton deliveries, 530 women had visited ED due to asthma during pregnancy. While having an ED visit for asthma was positively associated with teenage pregnancy, low income, and presence of pregnancy-induced hypertension, it was not associated with fetal gender (OR 1.01, 95% CI 0.85-1.19). Fetal gender was not a significant predictor of adverse pregnancy outcomes among women who had an asthma ED visit during pregnancy. CONCLUSION: Fetal gender does not affect the risk of having an ED visit for asthma during pregnancy, and it is not associated with adverse pregnancy outcomes among women who had an asthma-related ED during pregnancy.

Adolescent↗
PubMed2006

Patient characteristics associated with nocturnal emergency department visits for asthma.

STUDY OBJECTIVES: To identify patient characteristics associated with nocturnal emergency department (ED) visits for asthma. METHODS: Asthmatic patients 18 to 55 years of age who visited Ontario EDs between April 1, 2003 and March 31, 2004, were identified through an administrative clinical database. Patients' time of ED presentation was analyzed for circadian pattern using histogram and polynomial regression. Risk of nocturnal visit (presentation at the ED between midnight and 8 AM) was modeled through generalized estimating equations with patient age, gender, and asthma severity level as covariates. The effect of nocturnal visit on return rate to the ED within 14 days after the initial visit was determined through Cox regression. RESULTS: During study period there were 31,490 ED visits for asthma made by 23,253 patients. Their time of ED visits displayed a distinct circadian pattern with peak between 7 and 8 PM, and trough at 5 AM. Approximately 22% of visits (6,868) occurred at night. Men had higher odds of presenting at night than women (OR 1.61; 1.49-1.73). Patients with mild asthma were significantly less likely to visit the ED at night than patients with moderate or severe asthma. Nocturnal presentation was not associated with higher odds of subsequent returns to the ED (HR 1.00; 0.89-1.14). CONCLUSION: Higher odds of nocturnal visits in men suggest the existence of gender-differences in health-seeking behavior in asthmatics. Although nocturnal visits are associated with more severe asthma, they do not lead to higher return rates.

Adolescent↗
PubMed2006

A comparison between integrating clinical practice setting and randomized controlled trial setting into economic evaluation models of therapeutics.

BACKGROUND: Cost-effectiveness analyses generated from randomized controlled trials (RCTs) represent results obtained under ideal experimental conditions (efficacy) and the applicability of these data to real-world settings (effectiveness) may be questionable. OBJECTIVE: To compare cost-effectiveness results obtained from a RCT setting with the results derived from community-based clinical practice. METHODS: Using data from a community-based cohort study and from a RCT, two cost-effectiveness analyses were performed and the incremental cost-effectiveness ratios (ICERs) were calculated for the use of etanercept in the treatment of patients with rheumatoid arthritis. RESULTS: Using an effectiveness-based analysis, the mean quality-adjusted life years (QALYs) gained during the 12-month monitoring period were 0.45 and 0.35 for the treatment and control groups respectively. The ICER for etanercept treatment was 174,200 dollars (CDN) per QALY (95% confidence limits between 119,500 dollars and 285,000 dollars). Incorporating efficacy data obtained from the RCT into the analysis, the mean QALYs gained were 0.56 and 0.35 for the treatment and control groups respectively. This resulted in a substantially lower ICER for etanercept treatment of 82,952 dollars per QALY (95% confidence limits between 66,500 dollars and 103,430 dollars). CONCLUSION: Depending on the type of clinical setting used for the analysis, the resulting ICER for etanercept treatment was very different. These results help to explain the difference in cost-effectiveness reported in previous modeling studies, some based on RCT assumptions and some based on effectiveness setting.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Clinical data gap between phase III clinical trials (pre-marketing) and phase IV (post-marketing) studies: evaluation of etanercept in rheumatoid arthritis.

BACKGROUND: There are fundamental differences in design between phase III clinical trials and phase IV post-marketing studies that involve patient characteristics, the clinical setting (environment) and the manner of drug use. As well, many phase IV studies are extensions of randomized clinical trials (RCTs) and suffer from selection bias. OBJECTIVE: To determine if the data obtained from RCTs of etanercept (Enbrel) in the treatment of rheumatoid arthritis would be representative of the effects attainable in community practice. METHOD: An analysis was conducted comparing data from published RCTs of etanercept use in rheumatoid arthritis patients with data collected in a community based cohort study that was not an extension of an RCT. RESULTS: Baseline clinical data, such as tender or painful joint count, patient's global assessment, the heath assessment questionnaire, physical and mental component summary of the SF-36, and rheumatoid arthritis drug profile were significantly different between the patients receiving etanercept in the phase IV community cohort study and the patients enrolled in the RCTs. Differences in the baseline data for the control patients were also noted amongst the RCT studies. The treatment outcome, American College of Rheumatology (ACR) response rate of 20%, 50% and 70% at 6 month, was the same between the cohort study and the RCTs, but at 12 months the clinical response was less for the community based patients than for the RCT patients. At 6 months there were fewer withdrawals involving community-based patients than RCT patients due to less frequent withdrawals associated with lack of efficacy. At 12 months the withdrawal rate due to either a lack of efficacy or from adverse events was similar between data sets. CONCLUSION: The data from the etanercept phase III RCTs may not reflect the characteristics of patients using etanercept in community practice, nor the clinical outcomes observed by RA patients at 12 months. These discrepancies may be derived from methodological differences in study design and patient selection. On the other hand, outcomes such as withdrawal rates at 12 months appear comparable between the two types of populations.

Antirheumatic Agents↗
PubMed2005

Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.

Journal Article↗
PubMed2005

Effect of gender, age, and severity of asthma attack on patterns of emergency department visits due to asthma by month and day of the week.

OBJECTIVE: To examine the pattern and strength of seasonal fluctuations in emergency department (ED) visits due to asthma, by month and day of the week, by the patient's age, gender, and severity of asthma attack. METHODS: Time series analysis of ED visits was conducted among patients with asthma aged from 18 to 55 years who visited Ontario EDs between April 1, 2001 and March 31, 2004. Autoregressive regression models with months and days of the week as predictors were fitted for (1) all patients; (2) females and males separately; (3) each combination of gender and age group, and (4) each combination of gender and level of severity. The strength of seasonality in each group of patients was estimated from the R2-statistic derived from autoregression models. RESULTS: For all patient groups, the highest number of ED visits occurred in October and December, and on Sundays and Mondays. Month of January and Fridays were associated with a decreased number of visits. The strength of seasonality was similar in men and women (R2 = 0.52), was the highest in young patients and decreased with age, in men more rapidly than in women. Severe cases of asthma attacks exhibited weaker seasonality (R2 = 0.30) compared to mild (R2 = 0.45) or moderate (R2 = 0.53) cases. CONCLUSION: The strength of seasonal patterns of asthma ED visits is influenced by age and the severity of attack, and to a lesser extent, gender. Understanding the significance of seasonal precipitants of asthma in different patients subgroups could lead to better management strategies.

Acute Disease↗
PubMed2004

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma.

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.

Journal Article↗
PubMed2004

The 2004 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I--Blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk and identifiable causes for adults with high blood pressure. OPTIONS: For persons in whom a high blood pressure value is recorded, the assignment of a diagnosis of hypertension is dependent on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases should be assessed to determine the urgency, intensity and type of treatment. For persons diagnosed as having hypertension, defining overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: The identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension. EVIDENCE: Medline searches were conducted from November 2001, one year before the period of the last revision of the Canadian recommendations for the management of hypertension, to October 2003. Reference lists were scanned, experts were polled, and the personal files of subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised using prespecified levels of evidence by content experts and methodological experts. VALUES: A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and persons with identifiable and potentially modifiable causes of hypertension. BENEFITS, HARMS AND COSTS: The identification of persons at higher risk of cardiovascular disease will permit counselling for lifestyle maneuvers and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. For certain subgroups of patients and specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The document contains recommendations for blood pressure measurement, diagnosis of hypertension and assessment of cardiovascular risk for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for diagnosis of hypertension, and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, and the role of echocardiography for those with hypertension. VALIDATION: All recommendations were graded according to strength of evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Only the recommendations that achieved high levels of consensus are reported. These guidelines will be updated annually.

Adult↗
PubMed2004

The 2004 Canadian recommendations for the management of hypertension: Part II--Therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the management of hypertension in adults. OPTIONS AND OUTCOMES: For patients who require pharmacological therapy for hypertension, a number of antihypertensive agents may be used. Randomized trials evaluating first-line therapy with diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, centrally acting agents or angiotensin receptor antagonists were reviewed. Also, randomized trials evaluating other agents, such as statins or acetylsalicylic acid, in patients with hypertension were reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. In addition, other relevant outcomes such as development of end-stage renal disease or changes in blood pressure were examined where appropriate. EVIDENCE: MEDLINE searches were conducted from November 2001 to October 2003 to update the 2001 Recommendations for the management of hypertension. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence by content and methodology experts. RECOMMENDATIONS: This document contains detailed recommendations and supporting evidence on treatment thresholds, target blood pressures and choice of agents for hypertensive patients with or without comorbidities. Lifestyle modifications are a key component of any antiatherosclerotic management strategy and detailed recommendations are contained in a separate document. Key recommendations for pharmacotherapy include the following: treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbidities, with particular attention to systolic blood pressure; blood pressure should be lowered to 140/90 mmHg or less in all patients, and 130/80 mmHg or less in those with diabetes mellitus or renal disease (125/75 mmHg or less in those with nondiabetic renal disease and more than 1 g of proteinuria per day); most adults with hypertension require more than one agent to achieve target blood pressures; for adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), ACE inhibitors (in non-Blacks), long-acting dihydropyridine CCBs or angiotensin receptor antagonists; other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or angiotensin receptor antagonists; certain comorbidities provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or thiazides in patients with diabetes mellitus without albuminuria) are appropriate first-line therapies; and in patients with mild to moderate nondiabetic renal disease, ACE inhibitors are recommended; all hypertensive patients should have their fasting lipids screened and those with dyslipidemia should be treated using the thresholds, targets and agents as per the Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease; and selected patients with hypertension should also receive statin and/or acetylsalicylic acid therapy. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Individuals with irreconcilable competing interests (declared by all members, compiled and circulated before the meeting) relative to any specific recommendation were excluded from voting on that recommendation. Only recommendations achieving at least 70% consensus are reported here. These guidelines will continue to be updated annually.

Adult↗
PubMed2002

The 2001 Canadian recommendations for the management of hypertension: Part one--Assessment for diagnosis, cardiovascular risk, causes and lifestyle modification.

OBJECTIVE: To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure. OPTIONS: For persons in whom a high blood pressure value is recorded, hypertension is diagnosed based on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases must be assessed to determine the urgency, intensity and type of treatment. For persons receiving a diagnosis of hypertension, defining the overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: The outcomes were: the identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension. EVIDENCE: Medline searches were conducted from one year before the period of the last revision of the Canadian recommendations for the management of hypertension (May 1999 to May 2001). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. In addition to an update of the previous year's review, new sections on assessing overall cardiovascular risk and endocrine causes are provided. VALUES: A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and of persons with identifiable causes of hypertension. BENEFITS, HARMS AND COSTS: The identification of persons at higher risk of cardiovascular disease will permit counseling for lifestyle manoeuvres and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. In certain subgroups of patients, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity or mortality. RECOMMENDATIONS: The present document contains recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, the role of echocardiography and lifestyle modifications. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported. These guidelines will be updated annually. ENDORSEMENT: These guidelines are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control, Health Canada.

Antihypertensive Agents↗
PubMed2002

The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.

Antihypertensive Agents↗
PubMedDate not supplied

The steroid-responsive hiccup reflex arc: competitive binding to the corticosteroid-receptor?

Hiccups occurring secondary to high-doses of corticosteroids are a well-recognized problem in the field of neurosurgery. Numerous reports of oral, intravenous and intraarticular corticosteroids inducing hiccups exist in the literature. To date, there is only one case of anabolic steroids inducing hiccups. We now present a case of a patient who underwent a suboccipital craniotomy for resection of a cerebellar pontine angle meningioma. Postoperatively the patient was on high doses of Decadron and Oxandrin, an anabolic-anticatabolic agent used to combat the deleterious effects of corticosteroids. The patient suffered intractable hiccups postoperative day one, resistant to Thorazine. Oxandrin was discontinued to assess the possibility of a anabolic steroid-induced singultus. The hiccups resolved within 24 hours. This report validates the previous report on anabolic steroids inducing hiccups and exemplifies the ability for steroids as a class, due to there backbone structural homology, to induce function even as competitive inhibitors.

Adrenal Cortex Hormones↗