No abstract

BackgroundWe conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian cancer, lymphoma, myeloma or sarcoma.MethodsRandomized controlled trials were sought using comprehensive searches of electronic databases in June 2008. Reference lists of retrieved articles were also scanned for additional articles. Outcomes investigated were early or late clinical and sub-clinical cardiotoxicity. Trial quality was assessed, and data were pooled through meta-analysis where appropriate.ResultsFifty-five published RCTs were included; the majority were on women with advanced breast cancer. A significantly greater risk of clinical cardiotoxicity was found with anthracycline compared with non-anthracycline regimens (OR 5.43 95% confidence interval: 2.34, 12.62), anthracycline versus mitoxantrone (OR 2.88 95% confidence interval: 1.29, 6.44), and bolus versus continuous anthracycline infusions (OR 4.13 95% confidence interval: 1.75, 9.72). Risk of clinical cardiotoxicity was significantly lower with epirubicin versus doxorubicin (OR 0.39 95% confidence interval: 0.20, 0.78), liposomal versus non-liposomal doxorubicin (OR 0.18 95% confidence interval: 0.08, 0.38) and with a concomitant cardioprotective agent (OR 0.21 95% confidence interval: 0.13, 0.33). No statistical heterogeneity was found for these pooled analyses. A similar pattern of results were found for subclinical cardiotoxicity; with risk significantly greater with anthracycline containing regimens and bolus administration; and significantly lower risk with epirubicin, liposomal doxorubicin versus doxorubicin but not epirubicin, and with concomitant use of a cardioprotective agent. Low to moderate statistical heterogeneity was found for two of the five pooled analyses, perhaps due to the different criteria used for reduction in Left Ventricular Ejection Fraction. Meta-analyses of any cardiotoxicity (clinical and subclinical) showed moderate to high statistical heterogeneity for four of five pooled analyses; criteria for any cardiotoxic event differed between studies. Nonetheless the pattern of results was similar to those for clinical or subclinical cardiotoxicity described above.ConclusionsEvidence is not sufficiently robust to support clear evidence-based recommendations on different anthracycline treatment regimens, or for routine use of cardiac protective agents or liposomal formulations. There is a need to improve cardiac monitoring in oncology trials.

Background: The effect of alcohol portrayals and advertising on the drinking behaviour of young people is a matter of much debate. We evaluated the relationship between exposure to alcohol advertising, marketing and portrayal on subsequent drinking behaviour in young people by systematic review of cohort (longitudinal) studies.

BackgroundOur aim was to describe the range of perineal trauma in women with a singleton vaginal birth and estimate the effect of maternal and obstetric characteristics on the incidence of perineal tears.MethodsWe conducted a prospective observational study on all women with a planned singleton vaginal delivery between May and September 2006 in one obstetric unit, three freestanding midwifery-led units and home settings in South East England. Data on maternal and obstetric characteristics were collected prospectively and analysed using univariable and multivariable logistic regression. The outcome measures were incidence of perineal trauma, type of perineal trauma and whether it was sutured or not.ResultsThe proportion of women with an intact perineum at delivery was 9.6% (125/1,302) in nulliparae, and 31.2% (453/1,452) in multiparae, with a higher incidence in the community (freestanding midwifery-led units and home settings). Multivariable analysis showed multiparity (OR 0.52; 95% CI: 0.30–0.90) was associated with reduced odds of obstetric anal sphincter injuries (OASIS), whilst forceps (OR 4.43; 95% CI: 2.02–9.71), longer duration of second stage of labour (OR 1.49; 95% CI: 1.13–1.98), and heavier birthweight (OR 1.001; 95% CI: 1.001–1.001), were associated with increased odds. Adjusted ORs for spontaneous perineal truama were: multiparity (OR 0.42; 95% CI: 0.32–0.56); hospital delivery (OR 1.48; 95% CI: 1.01–2.17); forceps delivery (OR 2.61; 95% CI: 1.22–5.56); longer duration of second stage labour (OR 1.45; 95% CI: 1.28–1.63); and heavier birthweight (OR 1.001; 95% CI: 1.000–1.001).ConclusionsThis large prospective study found no evidence for an association between many factors related to midwifery practice such as use of a birthing pool, digital perineal stretching in the second stage, hands off delivery technique, or maternal birth position with incidence of OASIS or spontaneous perineal trauma. We also found a low overall incidence of OASIS, and fewer second degree tears were sutured in the community than in the hospital settings. This study confirms previous findings of overall high incidence of perineal trauma following vaginal delivery, and a strong association between forceps delivery and perineal trauma.

Objective To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis. Design Systematic review of randomised trials that compared at least 12 weeks' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis. Participants 15 187 patients with osteoarthritis or rheumatoid arthritis. Main outcome measures Efficacy: Western Ontario and McMaster universities osteoarthritis index; American College of Rheumatology responder index and joint scores for rheumatoid arthritis. Tolerability: withdrawal rates for adverse effects. Gastrointestinal safety: incidence of ulcers, bleeds, perforations, and obstructions. Results Nine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin. Conclusion Celecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.