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A systematic review of intravenous gamma globulin for therapy of acute myocarditis.

BACKGROUND: Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. METHODS: We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. RESULTS: Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. CONCLUSION: There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG.

Acute Disease↗

Reporting quality of randomized trials in the diet and exercise literature for weight loss.

BACKGROUND: To adequately assess individual studies and synthesize quantitative research on weight loss studies, transparent reporting of data is required. The authors examined the reporting quality of randomized trials in the weight loss literature, focusing exclusively on subject characteristics as they relate to enrollment, allocation, and follow-up. METHODS: An extensive literature review, which included a computerized search of the MEDLINE database, manual searches of bibliographic references, and cross-referencing of 92 review articles was conducted. A checklist, based on CONSORT recommendations, was used to collect information on whether or not authors reported age, gender, co-morbid disease, medication use, race/ethnicity, and postmenopausal status. Also tracked was whether or not initial and final sample size was reported and stratified by gender. RESULTS: Of 604 possible articles, 231 articles met eligibility criteria. Important subject characteristics were not reported as the following breakdown indicates: age (11%), gender (4%), race/ethnicity (86%), co-morbid disease states (34%), and medication use (92%). Additionally, 21% of articles failed to report initial sample size by gender while 69% neglected to report final sample size by gender. CONCLUSION: Inadequate reporting can create difficulties with interpretation and can lead to biased results receiving false credibility. The quality of reporting for weight loss studies needs considerable improvement.

Demography↗

Diffusion and dissemination of evidence-based dietary strategies for the prevention of cancer.

OBJECTIVE: The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? METHODS: A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. RESULTS: One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. CONCLUSIONS AND IMPLICATIONS: Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences.

Congresses as Topic↗

Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials.

INTRODUCTION: The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of ICU-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity. METHODS: We searched the PubMed database (1/1950 to 9/2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes. RESULTS: 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials) polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients were included in our meta-analysis. Our primary analysis that included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (OR = 0.49, 95% CI 0.32-0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55-1.32). There were limited data to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis by adding the 3 non-randomized comparative trials did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with Pseudomonas aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30-0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis. CONCLUSIONS: The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia is warranted, including a more systematic evaluation of issues related to the emergence of resistance.

Administration, Inhalation↗

Exposure to obstetric complications and subsequent development of bipolar disorder: Systematic review.

BACKGROUND: Research has suggested an association between obstetric complications and bipolar disorder. However, no quantitative evaluation has been made of the pooled data from existing studies. AIMS: To systematically review studies comparing exposure to obstetric complications in cases of bipolar disorder v. non-psychiatric controls, and in cases of bipolar disorder v. cases of other mental disorders. METHOD: Publications were identified by computer searches of seven databases, by hand searches of reference lists and from raw data received from researchers. RESULTS: Forty-six studies were identified, of which 22 met the inclusion criteria. The pooled odds ratio for exposure to obstetric complications and subsequent development of bipolar disorder was 1.01 (95% CI 0.76-1.35) compared with healthy controls, 1.13 (95% CI 0.64-1.99) compared with cases of unipolar disorder and 0.61 (95% CI 0.39-0.95) compared with those who developed schizophrenia. CONCLUSIONS: There is no robust evidence that exposure to obstetric complications increases the risk of developing bipolar disorder. However, the range of events regarded as obstetric complications and methodological inadequacies make definitive conclusions difficult.

Bipolar Disorder↗

The effects of ambulance diversion: a comprehensive review.

OBJECTIVES: To review the current literature on the effects of ambulance diversion (AD). METHODS: The authors performed a systematic review of AD and its effects. PubMed, EMBASE, the Cochrane database, societal meeting abstracts, and references from relevant articles were searched. All articles were screened for relevance to AD. RESULTS: The authors examined 600 citations and reviewed the 107 articles relevant to AD. AD is a common occurrence that is increasing in frequency. AD is associated with periods of emergency department (ED) crowding (Mondays, mid-afternoon to early evening, influenza season, and when hospitals are at capacity). Interventions that redesign the AD process or that provide additional hospital or ED resources reduce diversion frequency. AD is associated with increased patient transport times and time to thrombolytics but not with mortality. AD is associated with loss of estimated hospital revenues. Short of anecdotal or case reports, no studies measured the effect of AD on ED crowding, morbidity, patient and provider satisfaction, or EMS resource utilization. CONCLUSIONS: Despite its common use, there is a relative paucity of studies on the effects of AD. Further research into these effects should be performed so that we may understand the role of AD in the health system.

Ambulances↗

A critical evaluation of the therapeutic range of indinavir.

OBJECTIVE: To provide a summary of the patient population, study characteristics, and important findings of the key studies in the literature evaluating concentration-effect relationships and the therapeutic range for indinavir. DATA SOURCES: Literature search strategy involved using MEDLINE (1966-July 2001) and AIDSLINE (MEDSCAPE) databases (up to July 2001). Reference lists from primary literature and review articles were also examined, and conference abstracts were obtained. STUDY SELECTION: English-language articles were considered suitable for review if the clinical trials in HIV patients reported on concentration-effect relationships and/or pharmacokinetic breakpoints or threshold concentrations. A search of the literature identified 20 peer-reviewed references from 18 separate studies including journal articles and conference abstracts. DATA EXTRACTION: The targeted pharmacokinetic parameters and breakpoint values, the rationale for their selection or method of identification, and other study details and limitations were summarized. DISCUSSION: This article highlights the heterogeneity of studies evaluating the therapeutic range of indinavir and provides a summary of important findings of the key studies in the literature evaluating concentration-effect relationships and therapeutic range. Tables are provided to enable clinicians to make use of currently available information on the therapeutic range of indinavir. CONCLUSIONS: There is insufficient evidence to recommend a general therapeutic range for indinavir. Future investigations should incorporate both pharmacokinetics and pharmacodynamics in order to define a broadly applicable therapeutic range.

Adult↗

Cost-effectiveness of IV-to-oral switch therapy: azithromycin vs cefuroxime with or without erythromycin for the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To conduct a cost-effectiveness analysis of IV-to-oral regimens of azithromycin vs cefuroxime with or without erythromycin in the treatment of patients hospitalized with community-acquired pneumonia (CAP). PATIENTS: Of the 268 evaluable patients enrolled into a randomized, multicenter clinical trial of adults, 266 patients had sufficient data to be included in this cost-effectiveness analysis. One hundred thirty-six patients received azithromycin, and 130 patients received cefuroxime with or without erythromycin. METHODS: A pharmacoeconomic analysis from the hospital provider perspective was conducted. Health-care resource utilization was extracted from the clinical database and converted to national reference costs. Decision analysis was used to structure and characterize outcomes. Sensitivity analyses were performed, and statistics were applied to the cost-effectiveness ratios. RESULTS: The clinical success and adverse event rates and antibiotic-related length of stay were 78%, 11.8%, and 5.8 days for the azithromycin group and 75%, 20.7%, and 6.4 days for the group receiving cefuroxime with or without erythromycin, respectively. Geometric mean treatment costs were 4,104 US dollars (95% confidence interval [CI], 3,874 to 4,334 US dollars) for the azithromycin group, and 4,578 US dollars (95% CI, 4,319 to 4,837 US dollars) for the group receiving cefuroxime with or without erythromycin (p = 0.06). The cost-effectiveness ratios were 5,265 US dollars per expected cure for the azithromycin group, and 6,145 US dollars per expected cure for group receiving cefuroxime with or without erythromycin (p = 0.05). CONCLUSIONS: Despite a higher per-dose purchase price, overall costs with azithromycin tended to be lower due to decreased duration of therapy, lower preparation and administration costs, and reduced hospital length of stay. As empiric therapy, azithromycin monotherapy was cost-effective compared to cefuroxime with or without erythromycin for patients hospitalized with CAP who have no underlying cardiopulmonary disease, and no risk factors for either drug-resistant pneumococci or enteric Gram-negative pathogens.

Administration, Oral↗

The role of cardiac pacing: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery.

New-onset atrial fibrillation (AF) occurs frequently after cardiac surgery. The utility of prophylactic atrial pacing to prevent AF following cardiac surgery has been investigated in a number of trials, but clinical guidelines for its use are lacking. Trials of prophylactic atrial pacing to prevent AF following cardiac surgery were identified by searching PubMed, the Cochrane database, selected medical journals, and references in selected articles. Nine randomized controlled trials were identified that addressed prophylactic atrial pacing after cardiac surgery to prevent AF. Prophylactic right atrial pacing and prophylactic left atrial pacing have yielded inconclusive results. Prophylactic biatrial pacing (BAP) reduced the incidence of AF significantly in four studies, reduced it nonsignificantly in one study, and had no effect in one study. On the basis of the literature that was reviewed and graded for quality, it was concluded that prophylactic atrial pacing to prevent AF after cardiac surgery is safe. We recommend that BAP be considered, particularly in patients who are at high risk for the development of postoperative AF.

Atrial Fibrillation↗

Prescription drug use among elderly and nonelderly families.

OBJECTIVE: This study augments existing literature by examining characteristics associated with prescription drug utilization and makes an in-depth assessment of family prescription drug economic burden within the United States. The objective of this study was to examine differences in prescription drug use and prescription drug characteristics among elderly and nonelderly families. METHODS: A measure of out-of-pocket prescription drug burden associated with family prescription drug utilization was constructed using data from the 1996 Medical Expenditure Panel Survey (MEPS). Families were designated as the unit of analysis and further divided by age (<65 and e 65 years) of the reference person. The 1996 MEPS database provides medical expenditure data on a national sample of 8,917 families (22,601 individuals) and 147,308 drug episodes, i.e., prescription procurement. The ratio of family prescription out-of-pocket expenditures to family income was used to assign families to economic burden rank-ordered quintiles, each representing 20% of U.S. families in 1996. RESULTS: Prescription size, price, and drug use were higher among elderly families. Their proportion of generic use was higher compared to nonelderly families. Additionally, out-of-pocket prescription expenditures represented 23.7% and 45.6% of the total out-of-pocket medical care burden for nonelderly and elderly families, respectively. The average prescription drug burden (total prescription out-of-pocket costs/family income) was 0.4% for nonelderly and 1.9% for elderly households. CONCLUSION: The study results demonstrate an ability to identify populations with high economic burden for prescription medications. The presumption is that persons age 65 or older, lacking purchasing leverage, are more likely to pay full retail price and, consequently, higher prices. Our findings suggest that high prescription drug burden was a function of prescription size and cost per prescription, with prescription size showing more drastic differences between the high and low prescription drug burden subgroups. Future studies should continue to assess factors influencing families. prescription drug economic burden, and the information derived from these studies should be used by benefit planners in designing drug benefits within health insurance plans.

Age Distribution↗

The use of silymarin in the treatment of liver diseases.

The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.

Alcoholism↗

Intravenous chemotherapy for resected gastric cancer: meta-analysis of randomized controlled trials.

AIM: To assess the safety and efficacy of different intravenous chemotherapeutic regimens in patients with gastric carcinomas who had undergone gastrectomy. METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Language was restricted to Chinese and English. RCTs were identified from Medline and Embase (1980-2001/4), and Chinese Bio-medicine Database (1990-2001/1). Literature references were checked at the same time. We included randomized and quasi-randomized trials comparing the efficacy of intravenous chemotherapy after gastrectomy with that of surgery alone in patients with confirmed gastric carcinomas who had undergone gastrectomy. Selection criteria were: randomized or quasi-randomized trials with following-up results; Trials could be double-blind, single-blind or not blind; Chemotherapy groups were given intravenous chemotherapy after gastrectomy without neo-adjuvant chemotherapy, intraperitoneal hyperthermic perfusion, radiotherapy or chemoimmunotherapy; Controlled group included those receiving gastrectomy alone. The following data were extracted: the number of survival and death by the end of the follow-up; the different agents and doses of the intravenous chemotherapy; the baseline of the chemotherapy group and the controlled arm; the serious adverse events; the statistical consideration; cost-effectiveness analysis. The statistical analysis was performed by RevMan4.1 software which was provided by the Cochrane Collaboration. A P value of <0.05 was considered statistically significant. Meta-analysis was done with random effects model. Heterogeneity was checked by chi-square test. Sensitivity analysis was performed by excluding the trials in which Jadad-scale was only 1 score. The result was expressed with odds ratio (OR) for the categorical variable. RESULTS: Fourteen trials involving 4543 patients were included. Meta-analysis was done with random effects model. Heterogeneity and sensitivity analysis were performed also. The effect of intravenous chemotherapy after gastrectomy was better than surgery alone (odds ratio 0.56, 95 %CI 0.40-0.79). There was a significant difference between the two groups by u-test (P=0.0008). Sensitivity analysis revealed the same difference (odds ratio 0.81, 95 % CI 0.70-0.94). Of fourteen trials, only three studies were of high quality according to the Jadad-scale (with three score). There was one meta-analysis trial and the others, about ten trials, were of low quality. There was no trial which mentioned sample-size calculation, allocation concealment, intention-to-treat analysis. Most of the trials didn't describe the blind-procedure. There were five trials which detailed the side-effects according to the toxicity grade by WHO standard. The side-effects halting treatment were haematologic and biochemical toxicity, debilitating nausea and vomiting. There were two patients died of chemotherapy toxicity. CONCLUSION: Based on the review, intravenous chemotherapy after gastrectomy may have positive treatment effect on gastric cancer. However, the evidence is not strong because of the general low methodologic quality of the RCTs. Therefore, we can't make the conclusion that intravenous chemotherapy after gastrectomy may have better treatment effect on gastric cancer than that of surgery alone. Rigorously designed, randomised, double-blind, placebo-controlled trials are required.

Antineoplastic Agents↗

Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness and safety of fluoroquinolones with beta-lactams in the treatment of patients with skin and soft tissue infections (SSTIs). METHODS: We searched the PubMed database, Cochrane Database of Controlled Trials, and references of relevant articles for study reports published between January 1980 and February 2006. RESULTS: Twenty randomized controlled trials that enrolled 4817 patients were included in the analysis. Fluoroquinolones as empirical treatment of patients with SSTIs were more effective than beta-lactams for the clinically evaluable patients (90.4% vs 88.2%; odds ratio [OR], 1.29; 95% confidence interval [CI], 1.00-1.66). This was also true in subset analyses of randomized controlled trials that studied ciprofloxacin (OR, 2.49; 95% CI, 1.45-4.26) and for patients with mild to moderate infections (OR, 1.83; 95% CI, 1.13-2.96). In contrast, no difference was found between the compared regimens for patients with moderate to severe infections (OR, 1.12; 95% CI, 0.80-1.55), for patients who did not receive third-generation cephalosporins as the comparator antibiotic (OR, 0.99; 95% CI, 0.73-1.34), or for the microbiologically evaluable patients (OR, 1.19; 95% CI, 0.89-1.59). Fluoroquinolones were also associated with more adverse effects (19.2% vs 15.2%; OR, 1.33; 95% CI, 1.13-1.57). CONCLUSION: The high proportion of successfully treated patients in the compared groups of antibiotics and the development of more adverse effects associated with fluoroquinolone use suggest that these antibiotics do not have substantial advantages compared with beta-lactams for empirical treatment of patients with SSTIs.

Anti-Infective Agents↗

Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature.

OBJECTIVE: The rapid intraoperative parathyroid hormone assay is transforming the parathyroidectomy procedure. We present a review of the literature on the use of the assay as an adjunct to surgery. To our knowledge, this is the first review of the literature to encompass and compare all known primary studies of this assay in parathyroidectomy patients. DATA SOURCES: Articles were collected by searching MEDLINE databases using relevant terminology. The references of these articles were reviewed for additional studies. Supplementary articles pertinent to the parathyroidectomy procedure, preoperative parathyroid localization studies, and intraoperative parathyroid hormone assay development also were examined. STUDY SELECTION AND DATA EXTRACTION: One hundred sixty-five references were analyzed and categorized separately into groups. DATA SYNTHESIS: The primary studies of intraoperative data on patients undergoing parathyroidectomy were compared when possible. Studies were analyzed by type of assay used, where performed, turnaround time, and efficiency of use. Reviews of the types of parathyroid surgery and preoperative localization were included for educational purposes.Conclusions.-The intraoperative parathyroid hormone assay is a useful adjunct to preoperative imaging and parathyroid surgery because of its unique ability to detect an occult residuum of hyperfunctioning parathyroid tissue. Use of this assay will obviate the need for frozen section in most routine cases. The test facilitates minimally invasive parathyroidectomy for single parathyroid adenomas, which, in turn, improves cost-effectiveness and cosmetic outcome. Its use in patients with known preoperative multiglandular disease is promising but requires further study.

Humans↗

Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND: Subclinical thyroid dysfunction is a risk factor for developing symptomatic thyroid disease. Advocates of screening argue that early treatment can prevent serious morbidity in individuals who are found to have laboratory evidence of subclinical thyroid dysfunction. PURPOSE: This article focuses on whether it is useful to order a thyroid function test for patients who have no history of thyroid disease and have few or no signs or symptoms of thyroid dysfunction. DATA SOURCES: A MEDLINE search, supplemented by searches of EMBASE and the Cochrane Library, reference lists, and a local database of thyroid-related articles. STUDY SELECTION: Controlled treatment studies that used thyroid-stimulating hormone (TSH) levels as an inclusion criterion and reported quality of life, symptoms, or lipid level outcomes were selected. Observational studies of the prevalence, progression, and consequences of subclinical thyroid dysfunction were also reviewed. DATA EXTRACTION: The quality of each trial was assessed by using preset criteria, and information about setting, patients, interventions, and outcomes was abstracted. DATA SYNTHESIS: The prevalence of unsuspected thyroid disease is lowest in men and highest in older women. Evidence regarding the efficacy of treatment in patients found by screening to have subclinical thyroid dysfunction is inconclusive. No trials of treatment of subclinical hyperthyroidism have been done. Several small, randomized trials of treatment of subclinical hypothyroidism have been done, but the results are inconclusive except in patients who have a history of treatment of Graves disease, a subgroup that is not a target of screening in the general population. Data on the adverse effects of broader use of L-thyroxine are sparse. CONCLUSION: It is uncertain whether treatment will improve quality of life in otherwise healthy patients who have abnormal TSH levels and normal free thyroxine levels.

Adult↗

St. John's wort: a new alternative for depression?

OBJECTIVE: The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. METHODS: Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. RESULTS: A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. CONCLUSIONS: From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Antidepressive Agents↗

Elevated systolic blood pressure as a risk factor for cardiovascular and renal disease.

AIM: To review published literature on the relationship between systolic blood pressure and risk of cardiovascular and renal disease. DATA: identification Studies were retrieved using the MEDLINE database, bibliographies, and the authors' reference files. STUDY SELECTION: Prospective cohort studies and randomized controlled trials which were published in English-language journals. DATA EXTRACTION: All retrieved publications were reviewed by the two authors. Information on sample size, duration, study design, antihypertensive medication, participant characteristics and outcomes was abstracted for randomized controlled trials which reported reductions in systolic blood pressure during intervention. DATA SYNTHESIS: Results from several prospective cohort studies indicate that the association between systolic blood pressure and risk of coronary heart disease, stroke and end-stage renal disease is continuous, graded, and independent. Furthermore, they suggest that the association of systolic blood pressure with these outcomes is stronger than that of diastolic blood pressure. Pooling of the data available from randomized controlled trials indicates that an average reduction of 12-13 mmHg in systolic blood pressure over 4 years of follow-up is associated with a 21% reduction in coronary heart disease, a 37% reduction in stroke, a 25% reduction in total cardiovascular mortality, and a 13% reduction in all-cause mortality. CONCLUSION: Observational epidemiologic studies and randomized controlled trials have demonstrated that systolic blood pressure is an independent and strong predictor of risk of cardiovascular and renal disease.

Adult↗