Corticosteroids for tuberculous pleurisy.

BACKGROUND: Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent, raising doubt as to whether such treatment is worthwhile. Concern also exists regarding the potential adverse effects of corticosteroids, especially in HIV-positive people. OBJECTIVES: To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, Current Controlled Trials, and reference lists of articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing any corticosteroid with no treatment, placebo, or other active treatment (both groups should receive the same antituberculous drug regimen) in people diagnosed with tuberculous pleurisy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial methodological quality and extracted data. Data were analysed using relative risks (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI). The fixed-effect model was applied in the absence of statistically significant heterogeneity. MAIN RESULTS: Six trials with 633 participants met the inclusion criteria; one trial included only HIV-positive people. Compared to control, corticosteroid use was associated with less residual pleural fluid at four weeks (RR 0.76, 95% CI 0.62 to 0.94; 394 participants, 3 trials) and reduced pleural thickening (RR 0.69, 95% CI 0.51 to 0.94; 309 participants, 4 trials). We found no evidence of an effect of corticosteroids on death from any cause (194 participants, 1 trial), respiratory function (191 participants, 2 trials), residual pleural fluid at eight weeks (399 participants, 4 trials), or pleural adhesions (123 participants, 2 trials). Although discontinuation of treatment due to adverse events was more frequent in participants receiving corticosteroids than placebo (RR 2.80, 95% CI 1.12 to 6.98; 586 participants, 6 trials), the effects were generally mild. The risk of Kaposi sarcoma may be increased in HIV-positive people receiving corticosteroids (RR 13.00, 95% CI 0.74 to 227.63; 194 participants, 1 trial). AUTHORS' CONCLUSIONS: There are insufficient data to support evidence-based recommendations regarding the use of adjunctive corticosteroids in people with tuberculous pleurisy. Randomized controlled trials that are sufficiently powered to evaluate the effects of corticosteroids on both morbidity and mortality are needed. The effects of corticosteroids on HIV-related complications, such as Kaposi sarcoma, should be assessed in people co-infected with HIV.

Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib.

BACKGROUND: Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs is lacking in patients at high cardiovascular risk who are taking aspirin. OBJECTIVE: To determine the cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. METHODS: The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) of 18 325 patients with osteoarthritis comprised two parallel substudies, comparing lumiracoxib (COX-2 inhibitor) with either ibuprofen or naproxen. A post hoc analysis by baseline cardiovascular risk, treatment assignment, and low-dose aspirin use was performed. The primary composite end point was cardiovascular mortality, non-fatal myocardial infarction, and stroke at 1 year; a secondary end point was the development of congestive heart failure (CHF). RESULTS: In high risk patients among aspirin users, patients in the ibuprofen substudy had more primary events with ibuprofen than lumiracoxib (2.14% vs 0.25%, p = 0.038), whereas in the naproxen substudy rates were similar for naproxen and lumiracoxib (1.58% vs 1.48%, p = 0.899). High risk patients not taking aspirin had fewer primary events with naproxen than with lumiracoxib (0% vs 1.57%, p = 0.027), but not for ibuprofen versus lumiracoxib (0.92% vs 0.80%, p = 0.920). Overall, CHF developed more often with ibuprofen than lumiracoxib (1.28% vs 0.14%; p = 0.031), whereas no difference existed between naproxen and lumiracoxib. CONCLUSIONS: These data suggest that ibuprofen may confer an increased risk of thrombotic and CHF events relative to lumiracoxib among aspirin users at high cardiovascular risk. The study indicates that naproxen may be associated with lower risk relative to lumiracoxib among non-aspirin users. This study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study.

Corticosteroids for HELLP syndrome in pregnancy.

BACKGROUND: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a severe form of pre-eclampsia. Pre-eclampsia is a multi-system disease of pregnancy associated with an increase in blood pressure and increased perinatal and maternal morbidity and mortality. Eighty per cent of women with HELLP syndrome present before term. There are suggestions from observational studies that steroid treatment in HELLP syndrome may improve disordered maternal hematological and biochemical features and perhaps perinatal mortality and morbidity. OBJECTIVES: To summarise the evidence on the effects of corticosteroids on maternal and neonatal mortality and morbidity in women with HELLP syndrome. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2003). We scanned lists of references from review articles and primary studies. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effects of adjunctive corticosteroids in patients diagnosed with HELLP syndrome were sought. DATA COLLECTION AND ANALYSIS: The two authors independently applied inclusion criteria, assessed trial quality and extracted relevant data. MAIN RESULTS: Of the five studies reviewed (n = 170), three were conducted antepartum and two postpartum. Four of the studies randomised participants to standard therapy or dexamethasone. One study compared dexamethasone with betamethasone. DEXAMETHASONE VERSUS CONTROL: There were no significant differences in the primary outcomes of maternal mortality and morbidity due to placental abruption, pulmonary oedema and liver hematoma or rupture. Of the secondary maternal outcomes, there was a tendency to a greater platelet count increase over 48 hours, statistically significantly less mean number of hospital stay days (weighted mean difference (WMD) -4.50, 95% confidence interval (CI) -7.13 to -1.87), mean interval (hours) to delivery (41 +/- 15) versus (15 +/- 4.5) (p = 0.0068) in favour of women allocated to dexamethasone. There were no significant differences in perinatal mortality or morbidity due to respiratory distress syndrome, need for ventilatory support, intracerebral hemorrhage, necrotizing enterocolitis and a five minute Apgar less than seven. The mean birthweight was significantly greater in the group allocated to dexamethasone (WMD 247.00, 95% CI 65.41 to 428.59). DEXAMETHASONE VERSUS BETAMETHASONE: There were no significant differences in all the maternal and perinatal mortality and in primary morbidity outcomes. Women randomised to dexamethasone fared significantly better for: oliguria, mean arterial pressure, mean increase in platelet count, mean increase in urinary output and liver enzyme elevations. REVIEWER'S CONCLUSIONS: There is insufficient evidence to determine whether adjunctive steroid use in HELLP syndrome decreases maternal and perinatal mortality, major maternal and perinatal morbidity.

Steroids for treating tuberculous pleurisy.

BACKGROUND: TB of the pleura is associated with inflammation and fibrosis. Steroids could reduce the effects of the inflammation, but the immunosuppression could make patients vunerable. OBJECTIVES: This review aims to summarise the evidence about the effects of corticosteroids in patients with TB of the pleura, and explores if HIV status is associated with differences in effect estimates. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Library, MEDLINE, and EMBASE. Lists of references from review articles and primary studies were scanned and experts in the field of tuberculosis were contacted. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effects of adjunctive corticosteroids in patients diagnosed with TB pleurisy were sought. Both beneficial and adverse effects were noted. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria, assessed trial quality and extracted the relevant data. MAIN RESULTS: Three small trials met the inclusion criteria( total participants n=236), conducted in only HIV negative patients, and with insufficient power to examine death as an outcome. There was no difference in residual lung function between steroid and control groups at completion of treatment. The point estimates for secondary outcomes tended towards benefit with steroids rather than harm, but none were significant; number with pleural fluid (RR 0.28, 95% CI 0.06 to 1.34), number with pleural thickening (RR 0.76, 95% 0.48 to 1.21), and number with pleural adhesions (RR 0.30, 95% CI 0.03 to 2.66). Adverse effects were few and did not result in treatment being discontinued. REVIEWER'S CONCLUSIONS: There is insufficient evidence to know whether steroids are effective in tuberculous pleural effusion.

Directly observed therapy and treatment adherence.

Direct observation of patients taking their medication is a strategy to improve completion rates for tuberculosis treatment, but the programmes to implement this approach consist of a complex array of inputs aimed at influencing adherence. Policy makers need a clear understanding of these inputs to succeed. We systematically identified and reviewed published reports of direct observation therapy (DOT) programmes and compared inputs with WHO's short-course DOT programme. DOT programmes frequently consist of more than the five elements of WHO's strategy, including incentives, tracing of defaulters, legal sanctions, patient-centred approaches, staff motivation, supervision, and additional external funds. Focusing on direct observation as a key factor in the promotion of adherence seems inappropriate. Multiple components might account for the success of DOT programmes, and WHO should make these explicit.

Intrapartum amnioinfusion for meconium-stained liquor in developing countries.

BACKGROUND: Intrapartum amnioinfusion (AI) has been reported to decrease perinatal mortality and morbidity in women with meconium-stained liquor. Such work has not previously been performed at King Edward VIII Hospital (KEH), in a developing country, where the incidence of meconium-stained liquor is said to be extremely high. OBJECTIVE: To establish whether AI during the intrapartum period for meconium-stained liquor decreases Caesarean section rates for fetal distress and decreases perinatal morbidity. METHOD: Informed consent was obtained from patients in labour who were 3-8 cm dilated, with meconium-staining of the liquor, grades I to III inclusive, and who had a normal cardiotocograph on presentation at term. Sixty patients were included in the trial; 30 had AI. The control group was managed by standard methods. The study group had an amnioinfusion of 0.9% normal saline at 15 ml/min under continuous cardiotocographic monitoring, until a volume of 11 was completed. This was repeated if delivery did not occur within 4 h. RESULTS: The mean pH of umbilical arterial blood was significantly higher in the AI group (7.30 versus 7.23; P = 0.0029). In addition fewer patients in this group developed hypoxic ischaemic encephalopathy (0 versus 2 controls) or meconium aspiration syndrome (1 versus 4 controls). This was not statistically significant. Caesarean section for fetal distress was performed on fewer patients in the AI group (3 versus 7 controls), although this was not statistically significant. CONCLUSION: These results demonstrate that amnioinfusion is an effective technique for improving the perinatal outcome of pregnancies complicated by meconium-stained liquor in labour. The decrease in Caesarean sections for fetal distress, though not statistically significant in this study, has clinical relevance. Furthermore, this study suggests that amnioinfusion is cost effective in a busy, high-risk labour ward unit and consequently should become standard practice in the management of meconium-stained liquor in labour.