Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the term given to any thromboembolic event (blocking of a blood vessel by a blood clot) occurring in the venous system. The current treatment recommended for VTE is anticoagulation (reduction of the blood's ability to clot). The aim of this review is to summarize results from randomized controlled trials (RCTs) for the effectiveness of anticoagulants (heparins, including low molecular weight heparins and vitamin K antagonists) in the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs) or placebo. OBJECTIVES: To examine the randomized controlled evidence for the effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli (PE) and the recurrence or extension of deep vein thrombosis (DVT). SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005). In addition, DKC also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: All randomized trials of anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or PE or both). DATA COLLECTION AND ANALYSIS: DKC and JM independently assessed trial quality and extracted data. JCP (biostatistician) analyzed the design elements and feasibility of a future randomized controlled trial to determine definitively efficacy and safety of anticoagulants in VTE treatment. MAIN RESULTS: Two RCTs were included. Data were not pooled because of heterogeneity between the studies. The two RCTs were too small to determine any difference in mortality, occurrence of pulmonary emboli, progression or return of DVT between patients treated with anticoagulation and those receiving no anticoagulation. AUTHORS' CONCLUSIONS: The limited evidence from RCTs of anticoagulants versus NSAIDs or placebo is inconclusive regarding the efficacy and safety of anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in clinical practice, so a further RCT comparing anticoagulants to placebo could not ethically be carried out.

Anti-inflammatory treatment for carditis in acute rheumatic fever.

BACKGROUND: Rheumatic heart disease remains the most important cause of acquired heart disease in developing countries. Although the prevention of rheumatic fever and the management of recurrences is well established the optimal management of active rheumatic carditis is still unclear. OBJECTIVES: To assess the effects of anti-inflammatory agents such as aspirin, corticosteroids and immunoglobulin for preventing or reducing further heart valve damage in patients with acute rheumatic fever. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Issue 4, 2000), MEDLINE (1966 to April 2002), EMBASE (1998 to November 2002), LILACS (1998 to November 2002), Index Medicus (1950 to December 2000) and references lists of identified studies. SELECTION CRITERIA: Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins) with placebo or controls, or comparing any of the anti-inflammatory agents with one another, in patients with acute rheumatic fever diagnosed according to the Jones, or modified Jones criteria. The presence of cardiac disease one year after treatment was the major outcome criteria selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Eight randomised controlled trials involving 996 people were included. Several steroidal agents viz. ACTH, cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous immunoglobulin were compared to aspirin, placebo or no treatment in the various studies. Six of the trials were conducted between 1950 and 1965, whilst the remaining two were done in the last 10 years. Overall there was no significant difference in the risk of cardiac disease at one year between the corticosteroid-treated and aspirin-treated groups (relative risk 0.87, 95% confidence interval 0.66 to 1.15). Similarly use of prednisone (relative risk 1.78, 95% confidence interval 0.98 to 3.34) or intravenous immunoglobulins (relative risk 0.87, 95%confidence interval 0.55 to 1.39) when compared to placebo did not reduce the risk of developing heart valve lesions at one year. REVIEWER'S CONCLUSIONS: There is no benefit in using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessment of cardiac outcomes.

Penicillin for secondary prevention of rheumatic fever.

BACKGROUND: People with a history of rheumatic fever are at high risk of recurrent attacks of rheumatic fever and developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of rheumatic fever and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. OBJECTIVES: To assess the effects of penicillin compared to placebo and the effects of different penicillin regimens and formulations for preventing streptococcal infection and rheumatic fever recurrence. SEARCH STRATEGY: We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (1997 to July 2000), EMBASE (1998 to July 2000), reference lists of articles and we contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing (i) penicillin with control, (ii) oral with intramuscular penicillin (iii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous rheumatic fever. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Nine studies were included (n=3008). Data were not pooled because of heterogeneity. Overall, the methodological quality of included studies was poor. Three trials (n= 1301) compared penicillin with control. Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97). Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. One trial (n= 360) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every two-weeks was better at reducing rheumatic fever recurrence (RR 0.52, 95% CI 0.33 to 0.83) and streptococcal throat infections (RR 0.60, 95% CI 0.42 to 0.85). One trial (n= 249) showed 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI 0.48 to 0.92) compared to 4-weekly intramuscular penicillin. REVIEWER'S CONCLUSIONS: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials.

Magnesium sulphate for eclampsia: putting the evidence into clinical practice.

Eclampsia is the third commonest cause of maternal mortality after haemorrhage and infection. The morbidity and mortality in eclampsia is related to the number of convulsions. The control of convulsions is, therefore, important in reducing maternal morbidity and mortality. Teaching hospitals in Southern Africa contributed to the multicentre Collaborative Eclampsia Trial, which provided the overwhelming evidence for the superiority of magnesium sulphate as the drug of choice for eclampsia. While other parts of the world have put this evidence into practice, this trend has not yet become uniform in Africa. This paper seeks to encourage African governments, teaching hospitals, the pharmaceutical industry and the regional Cochrane Collaboration Centre in South Africa to co-operate in order to facilitate the practice of evidence-based medicine in this aspect of maternal health in the region.

Cardiac disease distribution among patients referred for echocardiography in Harare, Zimbabwe.

OBJECTIVE: To determine the distribution of cardiac diseases seen in a tertiary referral hospital. DESIGN: Cross sectional survey. SETTING: Harare Central Hospital, Harare, Zimbabwe. SUBJECTS: 1,507 patients referred for echocardiographic evaluation. MAIN OUTCOME MEASURE: Cardiac diagnosis. RESULTS: 1,153 (76.5%) echocardiographic studies were abnormal, while 354 were normal. Rheumatic heart disease was the predominant diagnosis (25.1%) with 208 (74.3%) of cases being females. The main valvular lesion in females was mitral stenosis (48.1%), while in males it was mitral regurgitation (61.1%). Other diagnoses were: pericardial disease 250 (22.4%), dilated cardiomyopathy 245 (22.0%), hypertensive heart disease 148 (13.3%) and others (17.4%). There were 65 cases of peripartum cardiomyopathy among the cases of dilated cardiomyopathy and 34 cases of acute myocarditis among "others". CONCLUSION: A detailed clinical, radiological and echocardiographic assessment at the time of echocardiography enabled a credible diagnosis to be assigned to the majority of patients. Echocardiography is appropriate technology in this setting given the range of "echo-friendly" cardiac lesions found.

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease.

OBJECTIVE: To elucidate the relationship between HIV, CD4+ count and pleural TB. METHOD: In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. RESULTS: Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4+ count (191 vs 1106 x 10(6)/l respectively, P = 0.004). A CD4+ count of <200 x 10(6)/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4+ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. CONCLUSION: In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4+ count.

A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension.

OBJECTIVE: To compare the effectiveness of the combination of hydrochlorothiazide (HCT) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering high blood pressure (BP) unresponsive to HCT monotherapy. DESIGN: An open, randomised crossover drug trial. SETTING: Outpatients' clinic in Parirenyatwa Hospital, Harare, a tertiary referral centre. SUBJECTS: 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied. INTERVENTION: Patients were kept on HCT 25 mg daily and were randomised to receive either reserpine 0.25 mg daily or nifedipine (Adalat Retard) 20 mg bd for four weeks. This was followed by a two week washout period during which patients received HCT 25 mg daily only. After the washout period patients were crossed over to the alternative treatment for four weeks. Patients were kept on HCT 25 mg daily throughout the trial. MAIN OUTCOME MEASURES: The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. RESULTS: Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them. Nifedipine reduced SBP by 18.9 mmHg (95% CI 12.1 to 25.7) and DBP by 9.6 mmHg (95% CI 7.2 to 12.0). Reserpine reduced SBP by 15.9 mmHg (95% CI 8.4 to 23.4) and DBP by 11.1 mmHg (95% CI 7.5 to 14.6). However, only two patients attained the target DBP of < or = 90 mmHg after each active treatment period. CONCLUSION AND RECOMMENDATIONS: Since both agents were equally effective in reducing both SBP and DBP and reserpine is much cheaper than nifedipine, it is recommended that for a developing country like Zimbabwe, the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage. However, further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs.

A case of gram negative pericarditis in a patient with the Acquired Immunodeficiency Syndrome.

A diagnosis of pericarditis due to Escherichia coli was made in a 38 year old male patient with AIDS. The source of infection in this patient was not established. This case highlights the need to carry out a diagnostic pericardiocentesis in immunocompromised patients presenting with pericardial effusions and the importance of adequate antibiotic cover when treating such patients prior to microbiological confirmation of the causative organism.