Effectiveness of the female condom in preventing HIV and sexually transmitted infections: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of female condoms for preventing HIV and sexually transmitted infections (STIs) remains inconclusive. We examined the effects of female condoms on the acquisition of HIV and STIs. METHODS: We searched four databases, two trial registries, and reference lists of relevant publications in October 2018 and updated our search in February 2020. We screened search output, evaluated study eligibility, and extracted data in duplicate; resolving differences through discussion. We calculated the effective sample size of cluster randomised trials using an intra-cluster correlation coefficient of 0·03. Data from similar studies were combined in a meta-analysis. We performed a non-inferiority analysis of new condoms relative to marketed ones using a non-inferiority margin of 3%. We assessed the certainty of evidence using GRADE. RESULTS: We included fifteen studies of 6921 women. We found that polyurethane female condoms (FC1) plus male condoms may be as effective as male condoms only in reducing HIV acquisition (1 trial, n = 149 women, RR 0.07, 95%CI 0.00-1.38; low-certainty evidence). However, the use of FC1 plus male condoms is superior to male condoms alone in reducing the acquisition of gonorrhoea (2 trials, n = 790, RR 0.59, 95%CI 0.41-0.86; high-certainty evidence) and chlamydia (2 trials, n = 790, RR 0.67, 95%CI 0.47-0.94; high-certainty evidence). Adverse events and failure rates of FC1 were very low and decreased during follow up. Although the functionality of newer female condoms (Woman's, Cupid, Pheonurse, Velvet, and Reddy) may be non-inferior to FC2, there were no available studies assessing their efficacy in preventing HIV and STIs. CONCLUSION: The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV. There is a need for well conducted studies assessing the effects of newer female condoms on HIV and STIs. PROSPERO REGISTRATION NUMBER: CRD42018090710.

Vitamin A supplements for reducing mother-to-child HIV transmission.

BACKGROUND: Strategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section delivery, and avoiding giving children chewed food. In some settings, these interventions may not be practical, feasible, or affordable. Simple, inexpensive, and effective interventions (that could potentially be implemented even in the absence of prenatal HIV testing programmes) would be valuable. Vitamin A, which plays a role in immune function, is one low-cost intervention that has been suggested in such settings. OBJECTIVES: To summarize the effects of giving vitamin A supplements to HIV-positive women during pregnancy and after delivery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 25 August 2017, and checked the reference lists of relevant articles for eligible studies. SELECTION CRITERIA: We included randomized controlled trials conducted in any setting that compared vitamin A supplements to placebo or no intervention among HIV-positive women during pregnancy or after delivery, or both. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility and extracted data. We expressed study results as risk ratios (RR) or mean differences (MD) as appropriate, with their 95% confidence intervals (CI), and conducted random-effects meta-analyses. This is an update of a review last published in 2011. MAIN RESULTS: Five trials met the inclusion criteria. These were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005 and none of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses (daily during pregnancy; a single dose immediately after delivery, or daily doses during pregnancy plus a single dose after delivery). Women allocated to comparison arms received identical placebo (6601 women, 4 trials) or no intervention (697 women, 1 trial). Four trials (with 6995 women) had low risk of bias and one trial (with 303 women) had high risk of attrition bias.The trials show that giving vitamin A supplements to HIV-positive women during pregnancy, the immediate postpartum period, or both, probably has little or no effect on mother-to-child transmission of HIV (RR 1.07, 95% CI 0.91 to 1.26; 4428 women, 5 trials, moderate certainty evidence) and may have little or no effect on child death by two years of age (RR 1.06, 95% CI 0.92 to 1.22; 3883 women, 3 trials, low certainty evidence). However, giving vitamin A supplements during pregnancy may increase the mean birthweight (MD 34.12 g, 95% CI -12.79 to 81.02; 2181 women, 3 trials, low certainty evidence) and probably reduces the incidence of low birthweight (RR 0.78, 95% CI 0.63 to 0.97; 1819 women, 3 trials, moderate certainty evidence); but we do not know whether vitamin A supplements affect the risk of preterm delivery (1577 women, 2 trials), stillbirth (2335 women, 3 trials), or maternal death (1267 women, 2 trials). AUTHORS' CONCLUSIONS: Antepartum or postpartum vitamin A supplementation, or both, probably has little or no effect on mother-to-child transmission of HIV in women living with HIV infection and not on antiretroviral drugs. The intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission.

Interventions to reduce haemorrhage during myomectomy for fibroids.

BACKGROUND: Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11). OBJECTIVES: To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy. SEARCH METHODS: In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods. MAIN RESULTS: Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.Blood lossWe found significant reductions in blood loss with the following interventions: vaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate-quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to -43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD -243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI -502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to -255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD -26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However, pooling data from these peri-cervical tourniquet RCTs revealed significant heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI -2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.Need for blood transfusion We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs, 121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low-quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.There were insufficient data on the adverse effects and costs of the different interventions. AUTHORS' CONCLUSIONS: At present there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation and a fibrin sealant patch may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy.

Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS.

BACKGROUND: UNAIDS estimates that 34 million people are currently living with the human immunodeficiency virus (HIV) worldwide. Currently recommended regimens for initiating HIV treatment consist of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir-boosted protease inhibitor (PI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs). However, there may be some patients for whom NNRTIs and PIs may not be appropriate. This is an update of the review published in the Cochrane Library Issue 3, 2009. OBJECTIVES: To evaluate the effects of any fixed-dose combination of three NRTIs (co-formulated abacavir-lamivudine-zidovudine) for initial treatment of HIV infection. SEARCH METHODS: Between December 2010 and July 2011, we used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language or publication status. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) with a minimum follow-up time of six months which compared co-formulated abacavir-lamivudine-zidovudine with either PI-based or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at least 13 years. DATA COLLECTION AND ANALYSIS: Three authors independently selected eligible studies, assessed risk of bias, and extracted data; resolving discrepancies by consensus. We calculated the risk ratio (RR) or mean difference (MD), as appropriate, with its 95% confidence interval (CI) and conducted meta-analysis using the random-effects method because of significant statistical heterogeneity (P<0.1). MAIN RESULTS: We identified 15 potentially eligible RCTs, four of which met our inclusion criteria. The four included RCTs were conducted in the United States of America (USA); USA, Puerto Rico, Guatemala, Dominican Republic, and Panama; USA and Mexico; and Botswana, respectively. The RCTs compared co-formulated abacavir-lamivudine-zidovudine to treatment based on efavirenz (NNRTI), nelfinavir (PI), atazanavir (PI), and co-formulated lopinavir-ritonavir (PI), respectively. Overall, there was no significant difference in virological suppression between co-formulated abacavir-lamivudine-zidovudine and NNRTI- or PI-based therapy (4 trials; 2247 participants: RR 0.73, 95% CI 0.39 to 1.36). However, the results showed significant heterogeneity (I(2)=79%); with co-formulated abacavir-lamivudine-zidovudine inferior to NNRTI (1 trial, 1147 participants: RR 0.35, 95%CI 0.26 to 0.49) but with a trend towards co-formulated abacavir-lamivudine-zidovudine being superior to PI (3 trials, 1110 participants: RR 1.07, 95%CI 1.00 to 1.16; I(2)=0%). We found no significant differences between co-formulated abacavir-lamivudine-zidovudine and either PI or NNRTI on CD4+ cell counts (3 trials, 1687 participants: MD -0.01, 95%CI -0.11 to 0.09; I(2)=0%), severe adverse events (4 trials: RR 1.22, 95%CI 0.78 to 1.92; I(2)=62%) and hypersensitivity reactions (4 trials: RR 4.04, 95% CI 0.41 to 40.02; I(2)=72%). Only two studies involving PIs reported data on the lipid profile. One study found that the mean increase in total cholesterol from baseline to 96 weeks was significantly lower with co-formulated abacavir-lamivudine-zidovudine than with nelfinavir, but there were no differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both co-formulated abacavir-lamivudine-zidovudine and atazanavir arms at 48 weeks.The significant heterogeneity of effects for most outcomes evaluated was largely due to differences in the control therapy used in the included trials (i.e. NNRTIs or PIs). Using the GRADE approach, we rated the overall quality of the evidence on the relative effects of co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection as moderate. The main reason for downgrading the quality of the evidence was imprecision of the findings. The estimate of the treatment effect for each outcome has wide confidence intervals, which extend from the fixed-dose NRTI combination regimen being appreciably better to the regimen being appreciably worse than PI- or NNRTI-based regimens. AUTHORS' CONCLUSIONS: This review provides evidence that co-formulated abacavir-lamivudine-zidovudine remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia. The varied geographical locations of the included trials augment the external validity of these findings. We are moderately confident in our estimate of the treatment effects of the triple NRTI regimen as initial therapy for HIV infection. In the context of the GRADE approach, such moderate quality of evidence implies that the true effects of the regimen are likely to be close to the estimate of effects found in this review; but there is a possibility that they could be substantially different.  Further research should be geared towards defining the subgroup of HIV patients for whom this regimen will be most beneficial.

Optimal timing for antiretroviral therapy initiation in patients with HIV infection and concurrent cryptococcal meningitis.

BACKGROUND: Currently, initiation of antiretroviral therapy (ART) in most patients with human immunodeficiency virus (HIV) infection is based on the CD4-positive-t-lymphocyte count. However, the point during the course of HIV infection at which ART should be initiated in patients with concurrent cryptococcal meningitis remains unclear. The aim of this systematic review was to summarise the evidence on the optimal timing of ART initiation in patients with cryptococcal meningitis for use in clinical practice and guideline development. OBJECTIVES: To compare the clinical and immunologic outcomes for early initiation ART (less than four weeks after starting antifungal treatment) versus later initiation of HAART (four weeks or more after starting antifungal treatment) in HIV-positive patients with concurrent cryptococcal meningitis. SEARCH METHODS: We searched the following databases from January 1980 to February 2011: PubMed, EMBASE, and WHO International Clinical Trials Registry Platform, AEGIS database for conference abstracts, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A total of 35 full text articles were identified and supplemented by a bibliographic search. We contacted researchers and relevant organizations and checked reference lists of all included studies. SELECTION CRITERIA: Randomized controlled trials that compared the effect of ART (consisting of three drug combinations) initiated early or delayed in HIV patients with cryptococcal meningitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Where clinically meaningful, we performed a meta-analysis of dichotomous outcomes using the relative risk (RR) and report the 95% confidence intervals (95% CIs). MAIN RESULTS: Two eligible randomized controlled trials were included (N = 89). In our pooled analysis, we combined the clinical data for both trials comparing early initiation ART versus delayed initiation of ART. There was no statistically significant difference in mortality (RR=1.40, 95% CI [0.42, 4.68]) in the group with early initiation of ART compared to the group with delayed initiation of ART. AUTHORS' CONCLUSIONS: This systematic review shows that there is insufficient evidence in support of either early or late initiation of ART. For the moment, because of the high risk of immune reconstitution syndrome in patients with cryptococcal meningitis, we recommend that ART initiation should be delayed until there is evidence of a sustained clinical response to antifungal therapy. However, large studies with appropriate comparison groups, and adequate follow-up are warranted to provide the evidence base for effective decision making.

Interventions to reduce haemorrhage during myomectomy for fibroids.

BACKGROUND: Uterine myomas (fibroids) are benign tumours of the uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding and prolonged postoperative stay. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library Issue 3, 2009. OBJECTIVES: To assess the effectiveness, safety, tolerability, and costs of interventions to reduce blood loss during myomectomy. SEARCH STRATEGY: Electronic searches were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982 to February 2011), and PsycINFO (1801 to February 2011). SELECTION CRITERIA: Only randomised controlled trials (RCTs) that compared the use of interventions to reduce blood loss during myomectomy to placebo or no treatment were included. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the methodological quality of trials, and extracted data. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). MAIN RESULTS: Twelve RCTs with 674 participants met our inclusion criteria. The interventions were intramyometrial vasopressin (two RCTs), intravenous oxytocin (two RCTs), peri-cervical tourniquet (two RCTs), and one RCT each for vaginal misoprostol, gelatin thrombin matrix, chemical dissection with sodium-2-mercaptoethane sulfonate (mesna), intramyometrial bupivacaine plus epinephrine, tranexamic acid, and myoma enucleation by morcellation. We found significant reductions in blood loss with misoprostol (MD -149.00 ml, 95% CI -229.24 to -68.76), vasopressin (MD -298.72 ml, 95% CI -593.10 to -4.34; I(2) = 99%), bupivacaine plus epinephrine (MD -68.60 ml, 95% CI -93.69 to - 43.51), tranexamic acid (MD -243 ml, 95% CI -460 to -25.98), peri-cervical tourniquet (MD -289.44, 95% CI -406.55 to -172.32; I(2) = 95%), and gelatin-thrombin matrix (MD -545.00 ml, 95% CI -593.26 to -496.74). There was no evidence of an effect on blood loss with oxytocin or morcellation. None of the interventions significantly increased myomectomy-related complications. The trials did not assess the costs of the different interventions. AUTHORS' CONCLUSIONS: There is limited evidence that misoprostol, vasopressin, bupivacaine plus epinephrine, tranexamic acid, gelatin thrombin matrix, peri-cervical tourniquet, and mesna may reduce bleeding during myomectomy. Bupivacaine plus epinephrine has limited clinical importance compared with other interventions as the clinical impact was small. There is no evidence that oxytocin and morcellation reduce blood loss. Further well designed studies are required to establish effectiveness, safety and the costs of different interventions for reducing blood loss during myomectomy.

Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.

BACKGROUND: Observational studies of pregnant women in sub-Saharan Africa have shown that low serum vitamin A levels are associated with an increased risk of mother-to-child transmission (MTCT) of HIV. Vitamin A is cheap and easily provided through existing health services in low-income settings. It is thus important to determine the effect of routine supplementation of HIV positive pregnant or breastfeeding women with this vitamin on the risk of MTCT of HIV, which currently results in more than 1000 new HIV infections each day world-wide. OBJECTIVES: We aimed to assess the effect of antenatal and or postpartum vitamin A supplementation on the risk of MTCT of HIV as well as infant and maternal mortality and morbidity. SEARCH STRATEGY: In June 2010 we searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, AIDS Education Global Information System, and WHO International Clinical Trials Registry Platform; and checked reference lists of identified articles for any studies published after the earlier version of this review was updated in 2008. SELECTION CRITERIA: We selected randomised controlled trials conducted in any setting that compared vitamin A supplementation with placebo in known HIV-infected pregnant or breastfeeding women. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed trial eligibility and quality and extracted data. We calculated relative risks (RR) or mean differences (MD), with their 95% confidence intervals (CI) for each study. We conducted meta-analysis using a fixed-effects method (when there was no significant heterogeneity between study results, i.e. P>0.1) or the random-effects method (when there was significant heterogeneity), and report the Higgins' statistic for all pooled effect measures. MAIN RESULTS: Five randomised controlled trials which enrolled 7,528 HIV-infected women (either during pregnancy or the immediate postpartum period) met our inclusion criteria. These trials were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005. We combined the results of these trials and found no evidence that vitamin A supplementation has an effect on the risk of MTCT of HIV (4 trials, 6517 women: RR 1.04, 95% CI 0.87 to 1.24; I(2)=68%). However, antenatal vitamin A supplementation significantly improved birth weight (3 trials, 1809 women: MD 89.78, 95%CI 84.73 to 94.83; I(2)=33.0%), but there was no evidence of an effect on preterm births (3 trials, 2110 women: RR 0.88, 95%CI 0.65 to 1.19; I(2)=58.1%), stillbirths (4 trials, 2855 women: RR 0.99, 95%CI 0.68 to 1.43; I(2)=0%), deaths by 24 months (2 trials, 1635 women: RR 1.03, 95%CI 0.88 to 1.20; I(2)=0%), postpartum CD4 levels (1 trial, 727 women: MD -4.00, 95% CI -51.06 to 43.06), and maternal death ( 1 trial, 728 women: RR 0.49, 95%CI 0.04 to 5.37). AUTHORS' CONCLUSIONS: Current best evidence shows that antenatal or postpartum vitamin A supplementation probably has little or no effect on mother-to-child transmission of HIV. According to the GRADE classification, the quality of this evidence is moderate; implying that the true effect of vitamin A supplementation on the risk of mother-to-child transmission of HIV is likely to be close to the findings of this review, but that there is also a possibility that it is substantially different.

Male circumcision for prevention of homosexual acquisition of HIV in men.

BACKGROUND: Previous systematic reviews found inconsistent effects of male circumcision on HIV acquisition in men who have sex with men (MSM). However, a number of new studies have become available in the three years since the last systematic review. OBJECTIVES: To assess the effects of male circumcision for preventing HIV acquisition by men through sex with men. SEARCH STRATEGY: In June 2010 we electronically searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, AIDS Education Global Information System, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform; hand-searched reference lists of relevant articles; and contacted relevant organisations and experts. We updated the search in March 2011. SELECTION CRITERIA: We looked for randomised controlled trials (RCTs) and observational studies that assessed the effects of male circumcision on HIV acquisition in MSM. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and methodological quality, and extracted data. We expressed study results as odds ratios (OR) with 95% confidence intervals (CI), and conducted random-effects meta-analysis. MAIN RESULTS: We found no completed RCT and included 21 observational studies with 71,693 participants. The only eligible RCT is currently ongoing among MSM in China. The pooled effect estimate for HIV acquisition was not statistically significant (20 studies; 65,784 participants; OR 0.86, 95% CI 0.70 to 1.06) and showed significant heterogeneity (I²=53%). In a subgroup analysis, the results were statistically significant in studies of men reporting an insertive role (7 studies, 3465 participants; OR 0.27, 95% CI 0.17 to 0.44; I²=0%) but not in studies of men reporting a receptive role (3 studies, 1792 participants; OR 1.20, 95% CI 0.63 to 2.29; I² = 0%). There was no significant association between male circumcision and syphilis (8 studies; 34,999 participants: OR 0.96, 95% CI 0.82 to 1.13; I² = 0%), herpes simplex virus 1 (2 studies, 2740 participants; OR 0.90, 95% CI 0.53 to 1.52; I²=0%), or herpes simplex virus 2 (5 studies;10,285 participants; OR 0.86, 95% CI 0.62 to 1.21; I²=0%). The overall GRADE quality of evidence was low. None of the included studies assessed adverse effects associated with male circumcision. AUTHORS' CONCLUSIONS: Current evidence suggests that male circumcision may be protective among MSM who practice primarily insertive anal sex, but the role of male circumcision overall in the prevention of HIV and other sexually transmitted infections among MSM remains to be determined. Therefore, there is not enough evidence to recommend male circumcision for HIV prevention among MSM at present. Further research should be of high quality and further explore interaction with the predominant sexual role.

Facility-based maternal death review in three districts in the central region of Malawi: an analysis of causes and characteristics of maternal deaths.

PURPOSE: We sought to determine the causes and characteristics maternal deaths that occur in health facilities in Malawi. METHODS: Forty-three maternal deaths were reviewed in 9 hospitals in 3 districts in Central Malawi over a 1-year period. Causes and avoidable factors of maternal deaths were identified during the review, and recommendations made and implemented. MAIN FINDINGS: There were 28 (65.1%) direct obstetric deaths and 15 (34.9%) indirect obstetric deaths. The major causes of maternal deaths were postpartum hemorrhage (25.6%), postpartum sepsis (16.3%), HIV/AIDS (16.3%), ruptured uterus (7.0%), complications of abortion (7.0%), anemia (7.0%), antepartum hemorrhage (4.7), and eclampsia (4.7). Two thirds of the women were referred either from another health facility (51.2%) or by a traditional birth attendant (TBA; 11.6%), and up to 79.1% were critically ill on admission. Four groups of factors that contributed to maternal deaths were identified: 1) health worker factors, 2) administrative factors, 3) patient/family factors, and 4) TBA factors. The major health worker factors were inadequate resuscitation (69.8%), lack of obstetric life-saving skills (60.5%), inadequate monitoring (55.8%), initial assessment incomplete (46.5%), and delay in starting treatment (46.5%). The most common administrative factor was lack of blood for transfusion (20.9%). The major problems encountered include shortage of staff and other resources, difficulty in maintaining anonymity, poor quality of data, and difficulty in implementing recommendations. CONCLUSION: Adequate training on obstetric life-saving skills, addressing HIV/AIDS, and raising community awareness could be important factors for reducing maternal mortality in Malawi and countries with similar socioeconomic profiles.

Interventions to reduce haemorrhage during myomectomy for fibroids.

BACKGROUND: Uterine myomas (fibroids) are benign tumours of the uterus. Myomectomy, the surgical removal of myomas, is an important treatment option especially for women who wish to preserve their uteri. The major problem with myomectomy is excessive bleeding, which can be life-threatening and prolong postoperative stay. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. OBJECTIVES: To assess the effectiveness, safety, tolerability, and costs of interventions to reduce blood loss during myomectomy. SEARCH STRATEGY: Electronic searches were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to September 2008), EMBASE (1980 to September 2008), CINAHL (1982 to September 2008), and PsycINFO (up to September 2008). SELECTION CRITERIA: Only randomised controlled trials (RCTs) that compared the use of interventions to reduce blood loss during myomectomy to placebo or no treatment were included. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the methodological quality of trials, and extracted data. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). MAIN RESULTS: Ten RCTs with 531 participants met our inclusion criteria: intramyometrial vasopressin and analogues (two trials), intravenous oxytocin (two trials), and one RCT for each of the interventions vaginal misoprostol, peri-cervical tourniquet, chemical dissection with sodium-2-mercaptoethane sulfonate (mesna), intramyometrial bupivacaine plus epinephrine, tranexamic acid and the enucleation of myoma by morcellation while it is attached to the uterus. We found significant reductions in blood loss with misoprostol (MD -149.00 ml, 95% CI -229.24 to -68.76), vasopressin and analogues (MD -298.72 ml, 95% CI -593.10 to -4.34), bupivacaine plus epinephrine (MD -68.60 ml, 95% CI -93.69 to - 43.51), tranexamic acid (MD -243 ml, 95% CI -460 to -25.98), and peri-cervical tourniquet (MD -1870.00 ml, 95% CI -2547.16 to -1192.84). There was no evidence of effect on blood loss with myoma enucleation by morcellation or oxytocin. The trials did not assess the tolerability and costs of the different interventions. AUTHORS' CONCLUSIONS: Evidence is limited from a few RCTs that misoprostol, vasopressin, bupivacaine plus epinephrine, tranexamic acid, tourniquet, and mesna may reduce bleeding during myomectomy. There is no evidence that oxytocin and morcellation have an effect on intraoperative blood loss. There is a need for adequately powered RCTs to shed more light on the effectiveness, safety, and costs of different interventions in reducing blood loss during myomectomy.

A combination drug of abacavir-lamivudine-zidovudine (Trizivir) for treating HIV infection and AIDS.

BACKGROUND: The human immunodeficiency virus (HIV) has become one of the greatest challenges to global public health. In 2007 UNAIDS estimated that 33.2 million people were living with HIV. Currently recommended regimens for initiating HIV treatment consist of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonvair-boosted protease inhibitor (PI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs); however, there may be some patients for whom NNRTIs and PIs may not be appropriate. OBJECTIVES: The aim of this review was to evaluate the effects of Trizivir, a fixed-dose combination of three NRTIs (abacavir-lamivudine-zidovudine) for initial treatment of HIV infection. SEARCH STRATEGY: In February 2008, we searched the Cochrane Library, PubMed, EMBASE, AIDSearch and GATEWAY and checked reference lists of identified articles. In May 2009, we repeated the search in PubMed and the Cochrane Library. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) with a minimum follow-up time of six months which compared Trizivir with either a PI- or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at least 13 years. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data. We calculated the relative risk (RR) or mean difference (as appropriate) for each outcome with its 95% confidence interval (CI) and conducted meta-analysis using the random-effects method because of significant statistical heterogeneity (P<0.1). MAIN RESULTS: We identified nine potentially eligible RCTs, three of which met our inclusion criteria. One trial compared Trizivir to efavirenz (an NNRTI) plus two or three NRTIs; the second trial compared Trizivir to a treatment based on the PI nelfinavir; and the third compared Trizivir to atazanavir (a PI) plus two NRTIs. Overall, there was no significant difference in the incidence of virological failure between participants on Trizivir and those on PI-based or NNRTI-based therapy (three trials, N=1687; RR 1.14, 95% CI 0.56 to 2.32). However, there was significant heterogeneity between the results of the three trials (heterogeneity P=0.009, I(2)=79%), with a significant increase in virological failure for Trizivir compared to efavirenz (N=1147; RR 1.93, 95% CI 1.46 to 2.55) but no difference between Trizivir and PIs (two trials, N=540; RR 0.82, 95% CI 0.50 to 1.36). We found no significant differences between Trizivir and either the PI or NNRTI on CD4+ cell counts (standardized mean difference -0.01, 95% CI -0.11 to 0.09, heterogeneity P=0.59, I(2)=0%), severe adverse events (RR 1.41, 95% CI 0.61 to 3.25, heterogeneity P=0.03, I(2)=73%) and hypersensitivity reactions (RR 4.04, 95% CI 0.41 to 40.02, heterogeneity P=0.03, I(2)=72%). Only the studies involving PIs reported the effect of the treatment regimens on the lipid profile. One study found that at 96 weeks, the mean increase in total cholesterol from baseline was significantly lower with Trizivir than with nelfinavir, but there were no significant differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both the Trizivir and atazanavir arms at 48 weeks. AUTHORS' CONCLUSIONS: Our findings indicate that Trizivir remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir.

Acceptability of intrapartum HIV counselling and testing in Cameroon.

BACKGROUND: To assess the acceptability of intrapartum HIV testing and determine the prevalence of HIV among labouring women with unknown HIV status in Cameroon. METHOD: The study was conducted in four hospitals (two referral and two districts hospitals) in Cameroon. Labouring women with unknown HIV status were counselled and those who accepted were tested for HIV. RESULTS: A total of 2413 women were counselled and 2130 (88.3%) accepted to be tested for HIV. Of the 2130 women tested, 214 (10.1%) were HIV positive. Acceptability of HIV testing during labour was negatively associated with maternal age, parity and number of antenatal visits, but positively associated with level of education. HIV sero-status was positively associated with maternal age, parity, number of antenatal visits and level education. CONCLUSION: Acceptability of intrapartum HIV testing is high and the prevalence of HIV is also high among women with unknown HIV sero-status in Cameroon. We recommend an opt-out approach (where women are informed that HIV testing will be routine during labour if HIV status is unknown but each person may decline to be tested) for Cameroon and countries with similar social profiles.

Using criteria-based audit to improve the management of postpartum haemorrhage in resource limited countries: a case study of Malawi.

OBJECTIVE: The goal of this study was to assess and improve the management of postpartum haemorrhage (PPH) in maternity units in Malawi. The main objective was to determine whether criteria-based audit can improve adherence to standards for the management of PPH. METHODS: We used a before-and-after design and univariate statistics for data analysis. A retrospective review of 40 consecutive cases of PPH was conducted in eight hospitals and the results compared with standards for PPH, established based on World Health Organisation manuals. RESULTS: of the audit were presented to healthcare providers who made and implemented recommendations for improvement. A re-audit (45 cases) was conducted 3 months later. RESULTS: There was a significant improvement in adherence to three standards: typing and cross-match carried out (65.0% vs. 84.4%; P = 0.034), patient's hematocrit or haemoglobin established (67.5% vs. 86.7%; P = 0.029), and fluid intake/output chart maintained (0.0% vs 33.3%; P < 0.001). There was no significant change in close monitoring of vital signs (32.5% vs. 53.3%, P = 0.065) and case fatality rate (10.0% vs. 6.7%, P = 0.702), intravenous access achieved and intravenous fluids administered (100.0% vs. 97.8%; P = 0.735), and oxytocic drugs administered (100.0% vs. 95.6%; P = 0.357). CONCLUSION: Introduction of criteria-based audit can improve the management of postpartum haemorrhage in countries with limited resources. Future studies should consider using larger sample size to evaluate the effect of criteria-based audit on mortality.

Availability, utilisation and quality of basic and comprehensive emergency obstetric care services in Malawi.

OBJECTIVE: To establish a baseline for the availability, utilisation and quality of maternal and neonatal health care services for monitoring and evaluation of a maternal and neonatal morbidity/mortality reduction programme in three districts in the Central Region of Malawi. METHODS: Survey of all the 73 health facilities (13 hospitals and 60 health centres) that provide maternity services in the three districts (population, 2,812,183). RESULTS: There were 1.6 comprehensive emergency obstetric care (CEmOC) facilities per 500,000 population and 0.8 basic emergency obstetric care (BEmOC) facilities per 125,000 population. About 23% of deliveries were conducted in emergency obstetric care (EmOC) facilities and the met need for emergency obstetric complications was 20.7%. The case fatality rate for emergency obstetric complications treated in health facilities was 2.0%. Up to 86.7% of pregnant women attended antenatal clinic at least once and only 12.0% of them attend postnatal clinic at least once. There is a shortage of qualified staff and unequal distribution with more staff in hospitals leaving health centres severely understaffed. CONCLUSIONS: The total number of CEmOC facilities is adequate but the distribution is unequal, leaving some rural areas with poor access to CEmOC services. There are no functional BEmOC facilities in the three districts. In order to reduce maternal mortality in Malawi and countries with similar socio-economic profile, there is a need to upgrade some health facilities to at least BEmOC level by training staff and providing equipment and supplies.

The difficulties of conducting maternal death reviews in Malawi.

BACKGROUND: Maternal death reviews is a tool widely recommended to improve the quality of obstetric care and reduce maternal mortality. Our aim was to explore the challenges encountered in the process of facility-based maternal death review in Malawi, and to suggest sustainable and logically sound solutions to these challenges. METHODS: SWOT (strengths, weaknesses, opportunities and threats) analysis of the process of maternal death review during a workshop in Malawi. RESULTS: Strengths: Availability of data from case notes, support from hospital management, and having maternal death review forms. Weaknesses: fear of blame, lack of knowledge and skills to properly conduct death reviews, inadequate resources and missing documentation. Opportunities: technical assistance from expatriates, support from the Ministry of Health, national protocols and high maternal mortality which serves as motivation factor. Threats: Cultural practices, potential lawsuit, demotivation due to the high maternal mortality and poor planning at the district level. Solutions: proper documentation, conducting maternal death review in a blame-free manner, good leadership, motivation of staff, using guidelines, proper stock inventory and community involvement. CONCLUSION: Challenges encountered during facility-based maternal death review are provider-related, administrative, client related and community related. Countries with similar socioeconomic profiles to Malawi will have similar 'pull-and-push' factors on the process of facility-based maternal death reviews, and therefore we will expect these countries to have similar potential solutions.

Criteria for clinical audit of women friendly care and providers' perception in Malawi.

BACKGROUND: There are two dimensions of quality of maternity care, namely quality of health outcomes and quality as perceived by clients. The feasibility of using clinical audit to assess and improve the quality of maternity care as perceived by women was studied in Malawi. OBJECTIVE: We sought to (a) establish standards for women friendly care and (b) explore attitudinal barriers which could impede the proper implementation of clinical audit. METHODS: We used evidence from Malawi national guidelines and World Health Organisation manuals to establish local standards for women friendly care in three districts. We equally conducted a survey of health care providers to explore their attitudes towards criterion based audit. RESULTS: The standards addressed different aspects of care given to women in maternity units, namely (i) reception, (ii) attitudes towards women, (iii) respect for culture, (iv) respect for women, (v) waiting time, (vi) enabling environment, (vii) provision of information, (viii) individualised care, (ix) provision of skilled attendance at birth and emergency obstetric care, (x) confidentiality, and (xi) proper management of patient information. The health providers in Malawi generally held a favourable attitude towards clinical audit: 100.0% (54/54) agreed that criterion based audit will improve the quality of care and 92.6% believed that clinical audit is a good educational tool. However, there are concerns that criterion based audit would create a feeling of blame among providers (35.2%), and that manager would use clinical audit to identify and punish providers who fail to meet standards (27.8%). CONCLUSION: Developing standards of maternity care that are acceptable to, and valued by, women requires consideration of both the research evidence and cultural values. Clinical audit is acceptable to health professionals in Malawi although there are concerns about its negative implications to the providers.

Hormonal contraception, sexual behaviour and HIV prevalence among women in Cameroon.

BACKGROUND: Data on the effect of contraceptive methods, other than the condom, on HIV acquisition is not clear. The aim of this study was to describe hormonal contraceptive use, sexual behaviour and HIV prevalence among women in Cameroon in order to provide baseline information for future analytical studies. METHODS: This is a cross-sectional descriptive study based a nationally representative sample of 4486 sexually active women aged 15-49 years who participated in the 2004 Cameroon Demographic and Health Survey. RESULTS: The overall HIV prevalence was 7.4% (332/4486). The HIV prevalence was higher in the 25-35 year age group (10.03%), urban residents (9.39%), and formerly married (18.48%), compared to their compatriots. The prevalence was lower in women with five or more living child (3.67%), women in the low wealth index category (3.79%) and women who had no formal education (3.37%). The HIV prevalence was higher among women who had two or more partners in the last 12 months (10.26%) and women who reported to have had four or more partners in their lifetime (12.40%). The prevalence of HIV was higher among current hormonal contraceptive users (6.63%) compared to the current non-users (3.06%), among ever users of hormonal contraception (13.27%) compared to the never users (7.11%). CONCLUSION: We conclude that the prevalence of HIV among sexually active women in Cameroon varies according to sociodemographic characteristics, sexual behaviour and hormonal contraceptive use. Our findings underscore the need to counsel women using hormonal contraception to be aware that hormonal methods do not protect against HIV infection. Given the biologic plausibility of the link between hormonal contraception and HIV infection, future research should focus on carefully designed prospective studies to establish the temporal relationship and estimate the incidence of HIV infection among women using and not using hormonal contraceptive methods.

Association between fertility and HIV status: what implications for HIV estimates?

BACKGROUND: Most estimates of HIV prevalence have been based on sentinel surveillance of pregnant women which may either under-estimate or over-estimate the actual prevalence in adult female population. One situation which can lead to either an underestimate or an overestimate of the actual HIV prevalence is where there is a significant difference in fertility rates between HIV-positive and HIV-negative women. Our aim was to compare the fertility rates of HIV-infected and HIV-uninfected women in Cameroon in order to make recommendations on the appropriate adjustments when using antenatal sentinel data to estimate HIV prevalence. METHODS: Cross-sectional, population-based study using data from 4493 sexually active women aged 15 to 49 years who participated in the 2004 Cameroon Demographic and Health Survey. RESULTS: In the rural area, the age-specific fertility rates in both HIV positive and HIV negative women increased from 15-19 years age bracket to a maximum at 20-24 years and then decreased monotonically till 35-49 years. Similar trends were observed in the urban area. The overall fertility rate for HIV positive women was 118.7 births per 1000 woman-years (95% Confidence Interval [CI] 98.4 to 142.0) compared to 171.3 births per 1000 woman-years (95% CI 164.5 to 178.2) for HIV negative women. The ratio of the fertility rate in HIV positive women to the fertility rate of HIV negative women (called the relative inclusion ratio) was 0.69 (95% CI 0.62 to 0.75). CONCLUSION: Fertility rates are lower in HIV-positive than HIV-negative women in Cameroon. The findings of this study support the use of summary RIR for the adjustment of HIV prevalence (among adult female population) obtained from sentinel surveillance in antenatal clinics.

Criteria-based audit to improve a district referral system in Malawi: a pilot study.

BACKGROUND: To study the feasibility of using criteria-based audit to improve a district referral system. METHODS: A criteria-based audit was used to assess the Salima District referral system in Malawi. A retrospective review of 60 obstetric emergencies referred from 12 health centres was conducted and compared with prior established standards for optimal referral of emergencies. Recommendations were made and implemented. Three months later, a re-audit was conducted (62 cases). RESULTS: There were significant improvements in 4 out of 7 standards: adequate resuscitation before referral (33.3% vs 88.7%; p = 0.001); delay of less than 2 hours from the time the ambulance is called to when the ambulance brought the patient to the hospital (42.8% vs 88.3%; p = 0.014); clinician attends to patient within 30 minutes of arrival to hospital (30.8% vs 92.6%; p = 0.001) and feedback given to the referring health centres (1.7% vs 91.9%; p <0.001). The rest of the three standards showed a high level of attainment (>95%) in both the initial audit and the re-audit: referred patients accompanied by a referral form; ambulances are available at all times and the district hospital is informed through short-wave radio by the health centre when a patient is referred. CONCLUSION: Criteria-based audit can improve the ability of a district referral system to handle obstetric emergencies in countries with limited resources.

A multilevel analysis of effect of neighbourhood and individual wealth status on sexual behaviour among women: evidence from Nigeria 2003 Demographic and Health Survey.

BACKGROUND: Nigeria is home to more people living with HIV than any other country in the world, except South Africa and India - where an estimated 2.9 million [1.7 million - 4.2 million] people were living with the virus in 2005. Women bear the greatest burden of frequent high-risk pregnancies, raising large families, and increasingly, the AIDS epidemic. Thus, there is a need for better understanding of the determinants of high risk sexual behaviour among women. In this study, we examined factors associated with extra-marital sex among women in Nigeria and investigated how much variation in reported extra-marital sex can be attributed to individual-, and community-level factors. METHODS: We analyzed data from 6362 sexually active women aged 15 - 49 years who participated in the Nigeria 2003 Demographic and Health Survey using multilevel logistic regression models. Results are presented as odds ratio with 95% confidence interval. RESULTS: Independent of other factors, compared to women aged 15-24 years, those 25 - 34 years (odds ratio [OR] 0.59; 95% CI: 0.44 - 0.79) and 35 years or older (OR 0.36; 95% CI: 0.24 - 0.54) were less likely to have reported multiple concurrent sex partners in the last 12 years. As expected, women currently or formerly married were less likely to have reported multiple concurrent sex partners than women never married. Women who drank alcohol in the last three months were more likely to have reported multiple concurrent sex partners. Compared to women from richest household, women from poorest and middle household were 83% and 51% more likely to multiple concurrent sex partners in the last 12 month respectively. After individual compositional and contextual factors, community wealth status was statistically significant with sexual behaviour. CONCLUSION: The study has demonstrated that individual and community wealth status are independent predictors of women's sexual behaviour, and that there is significant neighbourhood variation in odds of multiple concurrent sex partners, even after controlling for effects of both individual- and community-level characteristics. Scholars trying to understand variation individual high risk sexual behaviour should pay attention to the characteristics of both individuals and places of residence.