The impact of user fees on health services utilization and infectious disease diagnoses in Neno District, Malawi: a longitudinal, quasi-experimental study.

BACKGROUND: User fees have generally fallen out of favor across Africa, and they have been associated with reductions in access to healthcare. We examined the effects of the introduction and removal of user fees on outpatient attendances and new diagnoses of HIV, malaria, and tuberculosis in Neno District, Malawi where user fees were re-instated at three of 13 health centres in 2013 and subsequently removed at one of these in 2015. METHODS: We conducted two analyses. Firstly, an unadjusted comparison of outpatient visits and new diagnoses over three periods between July 2012 and October 2015: during the period with no user fees, at the re-introduction of user fees at four centres, and after the removal of user fees at one centre. Secondly, we estimated a linear model of the effect of user fees on the outcome of interest that controlled for unobserved health centre effects, monthly effects, and a linear time trend. RESULTS: The introduction of user fees was associated with a change in total attendances of -68 % [95 % CI: -89 %, -12 %], similar reductions were observed for new malaria and HIV diagnoses. The removal of user fees was associated with an increase in total attendances of 352 % [213 %, 554 %] with similar increases for malaria diagnoses. The results were not sensitive to control group or model specification. CONCLUSIONS: User fees for outpatient healthcare services present a barrier to patients accessing healthcare and reduce detection of serious infectious diseases.

Global women's health: current clinical trials in low- and middle-income countries.

BACKGROUND: Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. OBJECTIVES: To provide an overview of active women's health trials in LMICs. SEARCH STRATEGY: The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. SELECTION CRITERIA: Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. MAIN RESULTS: Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. AUTHORS' CONCLUSIONS: Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international prioritisation of maternal health.

A qualitative exploration of the motives behind the decision to order a liver function test in primary care.

BACKGROUND: The number of tests ordered in primary care continues to increase influenced by a number of factors not all of which are concerned with diagnosis and management of disease. Liver function tests (LFTs) are a good example of inexpensive tests that are frequently ordered in patients with non-specific symptoms. They remain among the most frequently ordered tests despite their lack of specificity yet the full range of motives behind the decision to order an LFT remains unexplored. AIMS: To gain an understanding of the family practitioner's (FP) medical and non-medical motives for ordering an LFT and the influence of various social and technical factors on this decision. METHODS: We interviewed FPs across six practices who were participating in a prospective study of the efficacy of an abnormal LFT to indicate the development of a serious liver disease. Following content analysis of the data from the semi-structured interviews we used the 'attitude-social influence-efficacy' model to categorise the determinants of test ordering behaviour. RESULTS: Factors influencing an FP's decision to order a test were grouped into two broad categories; the first is 'internal' including expectation of efficacy and general attitude towards LFTs. The second group is 'external' and consists of themes of social influence, tests characteristics and defensive medicine. CONCLUSIONS: Whilst our sample acknowledged the clinical use of LFTs such as the routine monitoring of medication and liver-specific diagnostic purposes we also found that social and behavioural reasons are strong motivators to order an LFT and may take precedence over clinical factors.

Protocol-based assessment and management of first episode psychosis: Comparison of short and medium-term outcomes in psychopathology, quality of life, functioning and family burden across two sites in India.

BACKGROUND: Standard assessment and management protocols exist for first episode psychosis (FEP) in high income countries. Due to cultural and resource differences, these need to be modified for application in low-and middle-income countries. AIMS: To assess the applicability of standard assessment and management protocols across two cohorts of FEP patients in North and South India by examining trajectories of psychopathology, functioning, quality of life and family burden in both. METHOD: FEP patients at two sites (108 at AIIMS, North India, and 115 at SCARF, South India) were assessed using structured instruments at baseline, 3, 6 and 12 months. Standard management protocols consisted of treatment with antipsychotics and psychoeducation for patients and their families. Generalised estimating equation (GEE) modelling was carried out to test for changes in outcomes both across and between sites at follow-up. RESULTS: There was an overall significant improvement in both cohorts for psychopathology and other outcome measures. The trajectories of improvement differed between the two sites with steeper improvement in non-affective psychosis in the first three months at SCARF, and affective symptoms in the first three months at AIIMS. The reduction in family burden and improvement in quality of life were greater at AIIMS than at SCARF during the first three months. CONCLUSIONS: Despite variations in cultural contexts and norms, it is possible to implement FEP standard assessment and management protocols in North and South India. Preliminary findings indicate that FEP services lead to significant improvements in psychopathology, functioning, quality of life, and family burden within these contexts.

Global prevalence and trends in hypertension and type 2 diabetes mellitus among slum residents: a systematic review and meta-analysis.

OBJECTIVE: First, to obtain regional estimates of prevalence of hypertension and type 2 diabetes in urban slums; and second, to compare these with those in urban and rural areas. DESIGN: Systematic review and meta-analysis. ELIGIBILITY CRITERIA: Studies that reported hypertension prevalence using the definition of blood pressure ≥140/90 mm Hg and/or prevalence of type 2 diabetes. INFORMATION SOURCES: Ovid MEDLINE, Cochrane CENTRAL and EMBASE from inception to December 2020. RISK OF BIAS: Two authors extracted relevant data and assessed risk of bias independently using the Strengthening the Reporting of Observational Studies in Epidemiology guideline. SYNTHESIS OF RESULTS: We used random-effects meta-analyses to pool prevalence estimates. We examined time trends in the prevalence estimates using meta-regression regression models with the prevalence estimates as the outcome variable and the calendar year of the publication as the predictor. RESULTS: A total of 62 studies involving 108 110 participants met the inclusion criteria. Prevalence of hypertension and type 2 diabetes in slum populations ranged from 4.2% to 52.5% and 0.9% to 25.0%, respectively. In six studies presenting comparator data, all from the Indian subcontinent, slum residents were 35% more likely to be hypertensive than those living in comparator rural areas and 30% less likely to be hypertensive than those from comparator non-slum urban areas. LIMITATIONS OF EVIDENCE: Of the included studies, only few studies from India compared the slum prevalence estimates with those living in non-slum urban and rural areas; this limits the generalisability of the finding. INTERPRETATION: The burden of hypertension and type 2 diabetes varied widely between countries and regions and, to some degree, also within countries. PROSPERO REGISTRATION NUMBER: CRD42017077381.

Is convalescent plasma futile in COVID-19? A Bayesian re-analysis of the RECOVERY randomized controlled trial.

BACKGROUND: Randomized trials are generally performed from a frequentist perspective, which can conflate absence of evidence with evidence of absence. The RECOVERY trial evaluated convalescent plasma for patients hospitalized with coronavirus disease 2019 (COVID-19) and concluded that there was no evidence of an effect. Re-analysis from a Bayesian perspective is warranted. METHODS: Outcome data were extracted from the RECOVERY trial by serostatus and time of presentation. A Bayesian re-analysis with a wide variety of priors (vague, optimistic, sceptical, and pessimistic) was performed, calculating the posterior probability for: any benefit, an absolute risk difference of 0.5% (small benefit, number needed to treat 200), and an absolute risk difference of one percentage point (modest benefit, number needed to treat 100). RESULTS: Across all patients, when analysed with a vague prior, the likelihood of any benefit or a modest benefit with convalescent plasma was estimated to be 64% and 18%, respectively. The estimated chance of any benefit was 95% if presenting within 7 days of symptoms, or 17% if presenting after this. In patients without a detectable antibody response at presentation, the chance of any benefit was 85%. However, it was only 20% in patients with a detectable antibody response at presentation. CONCLUSIONS: Bayesian re-analysis suggests that convalescent plasma reduces mortality by at least one percentage point among the 39% of patients who present within 7 days of symptoms, and that there is a 67% chance of the same mortality reduction in the 38% who are seronegative at the time of presentation. This is in contrast to the results in people who already have antibodies when they present. This biologically plausible finding bears witness to the advantage of Bayesian analyses over misuse of hypothesis tests to inform decisions.

Trends in 30-day readmissions following hospitalisation for heart failure by sex, socioeconomic status and ethnicity.

Background: Reducing the high patient and economic burden of early readmissions after hospitalisation for heart failure (HF) has become a health policy priority of recent years. Methods: An observational study linking Hospital Episode Statistics to socioeconomic and death data in England (2002-2018). All first hospitalisations with a primary discharge code for HF were identified. Quasi-poisson models were used to investigate trends in 30-day readmissions by age, sex, socioeconomic status and ethnicity. Findings: There were 698,983 HF admissions, median age 81 years [IQR 14].In-hospital deaths reduced by 0.7% per annum (pa), whilst additional deaths at 30-days remained stable at 5%. Age adjusted 30-day readmissions (21% overall), increased by 1.4% pa (95% CI 1.3-1.5). Readmissions for HF (6%) and 'other cardiovascular disease (CVD)' (3%) remained stable, but readmissions for non-CVD causes (12%) increased at a rate of 2.6% (2.4-2.7) pa. Proportions were similar by sex but trends diverged by ethnicity. Black groups experienced an increase in readmissions for HF (1.8% pa, interaction-p 0.03) and South Asian groups had more rapidly increasing readmission rates for non-CVD causes (interaction-p 0.04). Non-CVD readmissions were also more prominent in the least (15%; 15-15) compared to the most affluent group (12%; 12-12). Strongest predictors for HF readmission were Black ethnicity and chronic kidney disease, whilst cardiac procedures were protective. For non-CVD readmissions, strongest predictors were non-CVD comorbidities, whilst cardiologist care was protective. Interpretation: In HF, despite readmission reduction policies, 30-day readmissions have increased, impacting the least affluent and ethnic minority groups the most. Funding: NIHR.

Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions.

OBJECTIVE: To investigate discrepancies between direct comparison and adjusted indirect comparison in meta-analyses of new versus conventional pharmaceutical interventions. STUDY DESIGN AND SETTING: Results of direct comparison were compared with results of adjusted indirect comparison in three meta-analyses of new versus conventional drugs. The three case studies are (1) bupropion versus nicotine replacement therapy for smoking cessation, (2) risperidone versus haloperidol for schizophrenia, and (3) fluoxetine versus imipramine for depressive disorders. RESULTS: In all the three cases, effects of new drugs estimated by head-to-head trials tend to be greater than that by adjusted indirect comparisons. The observed discrepancies could not be satisfactorily explained by the play of chance or by bias and heterogeneity in adjusted indirect comparison. This observation, along with analysis of possible systematic bias in the direct comparisons, suggested that the indirect method might have produced less biased results. Simulations found that adjusted indirect comparison may counterbalance bias under certain circumstances. CONCLUSION: Adjusted indirect comparison could be used to cross-examine the validity and applicability of results from head-to-head randomized trials. The hypothesis that adjusted indirect comparison may provide less biased results than head-to-head randomized trials needs to be investigated by further research.

Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However, women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming requiring intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified and nine were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live birth or clinical pregnancy rate between LOD and gonadotrophins and the pooled odds ratios (OR) (all studies) were 1.04 (95% CI 0.59 to 1.85) and 1.08 (95% CI 0.69 to 1.71) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% versus 16%; OR 0.13, 95% CI 0.03 to 0.52). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 95% 0.36 to 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long-term effects of LOD on ovarian function.

WITHDRAWN: Androgens versus placebo or no treatment for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. Androgens have been suggested as a treatment because its binding proteins maintain a maintain a high intratesticular level testosterone essential for spermatogenesis and because the epididymis and seminal vesicles affect the seminal constitution and sperm motility and are also androgen-dependent. However exogenous testosterone was found to exert negative feedback on the pituitary-gonadal axis and thereby to suppress FSH and LH secretion. Spermatogenesis was thus adversely affected. Nevertheless androgens are used for the treatment of male infertility either for a putative direct "stimulatory" or "rebound" therapy. The stimulatory androgens used are mesterolone and testosterone undecanoate which, it is postulated, in a form and dosage that does not influence pituitary gonadotrophin secretion, either have a direct stimulatory effect on spermatogenesis or influence sperm transport and maturation though an effect on the epididymis, ductus deferens and seminal vesicles. Other androgens have been used to produce a rebound effect. These androgens are administered to suppress gonadotrophin secretion and spermatogenesis. After androgen therapy is discontinued there is a surge of FSH and LH and spermatogenesis is recommenced. Because of their different proposed mechanisms of action, stimulatory and rebound androgen therapy are analysed separately in the comparisons. This review considers the available evidence of the effect of androgens for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective of this review was to assess the effect of androgen treatment of men among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of mesterolone or testosterone undecanoate versus placebo or no treatment (stimulatory therapy), or testosterone enanthate or testosterone undecanoate versus placebo or no treatment (rebound therapy) in couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. MAIN RESULTS: Eleven trials involving 930 patients were included. For stimulatory therapy, androgens had little effect on endocrinal outcomes and sperm parameters. The rate of pregnancy after androgens with stimulatory effect compared to no treatment or placebo was also similar (odds ratio 1.10, 95% confidence interval 0.75 to 1.61). In rebound therapy, no difference was found in sperm parameters. The pregnancy rate after androgens with rebound effect also showed no difference compared to no treatment or placebo (odds ratio 1.60, 95% confidence interval 0.42 to 6.16). Adverse effects such as headaches and exanthema were reported. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the use of androgens for male subfertility.[This abstract has been prepared centrally.].

WITHDRAWN: Clomiphene or tamoxifen for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility.The administration of anti-oestrogens is a common treatment because anti oestrogens interfere with the normal negative feedback of sex steroids at hypothalamic and pituitary levels in order to increase endogenous gonadotropin-releasing hormone secretion from the hypothalamus and FSH and LH secretion directly from the pituitary. In turn, FSH and LH stimulate Leydig cells in the testes, and this has been claimed to lead to increased local testosterone production, thereby boosting spermatogenesis with a possible improvement in fertility. There may also be a direct effect of anti-oestrogens on testicular spermatogenesis or steroidogenesis. This review considers the available evidence of the effect of both Clomiphene citrate and tamoxifen, both of which have a predominant anti-oestrogenic effect, for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective was to assess the effects of treating subfertile men with anti-oestrogens (clomiphene or tamoxifen) on pregnancy rates among couples where subfertility has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of anti-oestrogen therapy for 3 months or more compared to placebo or no placebo for subfertile males among couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Any differences were resolved with a third reviewer. MAIN RESULTS: Ten studies involving 738 men were included. Five of the trials did not specify method of randomisation. Anti-oestrogens had a positive effect on endocrinal outcomes, such as serum testosterone levels. In trials with secure randomisation there was no difference in the pregnancy rate between the anti-oestrogen groups and the control groups (odds ratio 1.26, 95% confidence interval 0.99 to 1.56). The overall pregnancy rate for these five trials was 15.4% compared to the spontaneous rate of 12.5% in the control groups. These odds increased to 1.56 (95% confidence interval 0.99 to 2.19) when all 10 trials were included, but this result is likely to be artificially inflated. AUTHORS' CONCLUSIONS: Anti-oestrogens appear to have a beneficial effect on endocrinal outcomes, but there is not enough evidence to evaluate the use of anti-oestrogens for increasing the fertility of males with idiopathic oligo-asthenospermia.[This abstract was prepared centrally.].

WITHDRAWN: Bromocriptine for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology)of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility.Whilst bromocriptine treatment for reducing prolactin levels in hyperprolactinaemic males (as in females), and, in the treatment of hypogonadotropic hypogonadism with hyperprolactinaemia, is beneficial, it has also been used for oligospermic men in the absence of any endocrinopathy. Prolactin may play a direct role in spermatogenesis and hormone production. It has also been claimed that in oligospermic men with normal gonadotrophins mean prolactin levels are higher and that hyperprolactinaemia is more common compared to fertile men. It has been proposed that the administration of bromocriptine under these circumstances might counteract a prolactin-induced block on the action of gonadotrophins on the testicles and, subsequently, that the reduction in prolactin levels might lead to an improvement in semen parameters and fertility. Although it is not licensed for use in male infertility, bromocriptine has been used for normogonadotrophic individuals with oligospermia and normal or slightly elevated prolactin levels. This review considers the available evidence of the effect of bromocriptine therapy for normoprolactinaemic males with idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective of this review was to assess the effects of bromocriptine on pregnancy rates among couples where subfertility has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of oral bromocriptine versus placebo or no treatment for couples with subfertility attributed to male factor. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and any disagreements were resolved by discussion with other reviewers. MAIN RESULTS: Four studies were included. The method of randomisation was not specified in any of the trials, which were all of crossover design. Compared with placebo, bromocriptine was associated with a significant reduction in serum prolactin levels (weighted mean difference -195.3 micro international units per litre, 95% confidence interval -276.5 to -114). No effects on sperm parameters were seen. There was also no effect on pregnancy rates observed between bromocriptine and placebo (0.70 odds ratio, 95% confidence interval 0.15 to 3.24). AUTHORS' CONCLUSIONS: Bromocriptine appears to reduce prolactin levels in subfertile men with normal gonadotrophic function. There is not enough evidence to show that bromocriptine is helpful in improving fertility.[This abstract was prepared centrally.].

WITHDRAWN: Oil-soluble versus water-soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women.

BACKGROUND: There has been debate in the literature for more than 40 years as to whether flushing of the Fallopian tubes enhances fertility and whether this presumed therapeutic effect is greater with oil-soluble media than with water-soluble media. A meta-analysis of the therapeutic role of oil-soluble contrast media at hysterosalpingography was published in March 1994 (Watson 1994). This Cochrane Review is an expansion and update of that overview. OBJECTIVES: To evaluate the effect of flushing the Fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy rates in infertility patients. SEARCH STRATEGY: 1. For randomised controlled trials (RCTs): we searched the Cochrane Subfertility Review Group specialised register of controlled trials. 2. For non-randomised controlled studies: Medline and manual search of eight relevant journals. SELECTION CRITERIA: Six RCTs and six non-randomised controlled studies. In two studies tubal flushing was compared with no treatment-controls. Eleven studies, comprising a total of 2635 subjects, compared oil- with water-soluble media. DATA COLLECTION AND ANALYSIS: Independently by first 2 authors for: 1. Methodological trial characteristics 2. Characteristics of participants 3. OUTCOMES: the main studied outcome was pregnancy rate per patient MAIN RESULTS: In comparison with no treatment, a significant benefit on pregnancy rates was seen by flushing the tubes with oil-soluble media (OR 1.80, 95% CI 1.29-2.50) but not with water-soluble media (OR 0.87, 95% CI 0.50-1.52). In the direct comparison of oil- and water-soluble media the former lead to significantly higher pregnancy rates (OR 1.92, 95% CI 1.60-2.29). The treatment effect appeared similar in RCTs and non-RCTs. Subgroup analysis suggested the therapeutic benefit was greatest for patients suffering from unexplained infertility and least for those with tubal factor infertility. REVIEWER'S CONCLUSIONS: Flushing of the tubes with oil-soluble media increases subsequent pregnancy rates in infertility patients. The hypothesis that tubal "plugs" are a cause of proximal tubal occlusion and that oil-soluble media may flush them out, is supported by new techniques such as falloposcopy. Clinicians should consider flushing the tubes with OSCM before contemplating more invasive therapies.

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent fertility outcomes in couples with infertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 31 January 2007), MEDLINE, EMBASE, Biological Abstract and reference lists of articles. SELECTION CRITERIA: All randomised trials comparing tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media or with no treatment in women with subfertility. DATA COLLECTION AND ANALYSIS: Four authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: Twelve trials involving 2079 participants were included. Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of live birth (Peto OR 2.98, 95% CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95% CI 2.00 to 5.43). For the comparison of tubal flushing with oil-soluble media versus tubal flushing with water-soluble media, the increase in the odds of live birth for tubal flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95% CI 1.05 to 2.11) was based on two trials where statistical heterogeneity was present and the higher quality trial showed no significant difference; there was no evidence of a significant difference in the odds of pregnancy (Peto OR 1.21, 95% CI 0.95 to 1.54). The addition of oil-soluble media to flushing with water-soluble media showed no evidence of a significant difference in the odds of pregnancy (Peto OR 1.28, 95% CI 0.92 to 1.79) or live birth (Peto OR 1.06, 95% CI 0.64 to 1.77). There were no serious adverse event reported. AUTHORS' CONCLUSIONS: There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. Future robust randomised trials, comparing oil-soluble versus water-soluble media, water-soluble media versus no intervention and tubal flushing versus established treatments for infertility would be a useful further guide to clinical practice.

Techniques for pelvic surgery in subfertility.

BACKGROUND: Since the introduction of in-vitro fertilisation (IVF) tubal surgery has been less frequently undertaken as a technique to improve fertility in women with damaged fallopian tubes. There are various surgical techniques that can be used to repair blocked or damaged fallopian tubes. OBJECTIVES: To evaluate the role of tubal surgery in the management of tubal infertility and to evaluate surgical techniques for the treatment of tubal infertility. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. We identified relevant trials from the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (searched up to July 2005) and Cochrane Central Register of Controlled Trials (CENTRAL). The following databases were searched using the OVID platform: 1. MEDLINE (1966 to July 2005); 2. EMBASE (1980 to July 2005). SELECTION CRITERIA: All randomised controlled trials investigating the following topics on infertility surgery technique as follows were included.1) The role of infertility surgery versus no treatment.2) The role of infertility surgery versus alternative treatments.3) The role of magnification.4) The role of the CO2 laser at infertility surgery. 5) The role of operative laparoscopy to perform infertility surgery. 6) Any other intervention regarding surgical technique investigated by RCT. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the first two authors. Differences of opinion were recognised and resolved by consensus. Two by two tables were generated for each trial for the dichotomous outcome of pregnancy and the effects on pregnancy rate of each study is expressed as an odds ratio with 95% confidence intervals. MAIN RESULTS: Seven randomised control trials were identified. No RCTs comparing infertility surgery versus no treatment or alternative treatments were found. There was no RCT found investigating the use of magnification for tubal surgery. There was no evidence for or against the use of a CO2 laser compared with standard techniques for adhesiolysis (OR for pregnancy 1.07, 95% CI 0.40 to 2.87) or salpingostomy (OR for pregnancy 1.38, 95% CI 0.47 to 4.05) from two RCTs. One RCT randomised women for salpingostomatolysis by laparotomy and laparoscopy using the classic approach or the one suture technique. There was no evidence of benefit or disadvantage when laparoscopy was compared to laparotomy. The OR for bilateral tubal patency was 1.32 (95% CI 0.55 to 3.22) and unilateral tubal patency OR was 0.82 (95% CI 0.29 to 2.29). The pregnancy rate was not reported. There was no evidence of benefit or disadvantage from two RCTs assessing the use of a prosthesis at salpingostomy compared with non-use (combined odds of pregnancy (term) in group using the prosthesis as compared to the control (OR for pregnancy at term 1.17, 95% CI 0.47 to 2.93). There was no evidence of benefit or disadvantage difference in one RCT comparing Cuff versus Bruhat technique for salpingostomy One RCT compared two methods of salpingostomy (OR for pregnancy rate ( intrauterine) 1.02, 95% CI 0.22 to 4.61). One RCT showed no evidence of benefit or disadvantage for the use of thermocoagulation or electrocoagulation at adhesiolysis, odds for pregnancy rate between the two groups OR 0.87 (95% CI 0.51 to 1.46). AUTHORS' CONCLUSIONS: From these limited data there is no evidence of benefit or disadvantage of tubal surgery versus no treatment or alternative treatments. Likewise there is no evidence of advantage or disadvantage of using microsurgery over standard techniques; laparoscopic approach over laparotomy; the use of CO2 laser; or electrocoagulation over thermocoagulation. Randomised controlled trials should be undertaken to determine the role of tubal surgery versus no treatment or alternative treatments. Randomised controlled trials should be undertaken to determine the role at tubal surgery of magnification, laparoscopic approach, the use of lasers or electrocoagulation.

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Steroids, antihistamines and heparin were amongst the first substances to be advocated for adhesion prevention. More recently icodextrin 4%, hyaluronic acid agents and SprayGel have been used. This review aims to evaluate the role of fluid and pharmacological agents in the prevention of adhesions in fertility-conserving gynaecological surgery. OBJECTIVES: To investigate fluid and pharmacological agents for adhesion prevention when used as adjuvants during pelvic surgery. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesion formation after fertility-conserving gynaecological surgery. DATA COLLECTION AND ANALYSIS: Data extraction and analysis was performed independently by two authors (Metwally M and Watson A). Two-by-two tables were generated for dichotomous outcomes and expressed as odds ratios (OR) with 95% confidence intervals (CI). For continuous outcomes a standardised mean difference was used. MAIN RESULTS: There is no evidence of benefit from the use of steroids, dextran or other pharmacological agents in any of the outcomes. The use of hyaluronic acid agents may decrease adhesion formation (OR 0.31, 95% CI 0.19 to 0.51) and prevent the deterioration of pre-existing adhesions (OR 0.28 (95% CI 0.12 to 0.66). There is insufficient evidence for the use of icodextrin 4% or SprayGel as adhesion-preventing agents. None of the studied agents has been shown to improve the pregnancy rate when used as an adjunct during pelvic surgery. AUTHORS' CONCLUSIONS: The current evidence for the use of fluid and pharmacological agents for the prevention of adhesions is limited. There is no evidence on any benefit for improving pregnancy outcomes when pharmacological and fluid agents are used as an adjunct during pelvic surgery. There is insufficient evidence for the use of the following agents: steroids, icodextrin 4%, SprayGel and dextran in improving adhesions following surgery. There is some evidence that hyaluronic acid agents may decrease the proportion of adhesions and prevent the deterioration of pre existing adhesions. However, due to the limited number of studies available, this evidence should be interpreted with caution and further studies are needed.

Review article: Population screening for colorectal cancer.

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

OBJECTIVES: To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. DESIGN: Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. SETTING: Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. PARTICIPANTS: Healthy adults with a wide range of educational backgrounds and ages. INVESTIGATIONS: Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. MAIN OUTCOME MEASURES: Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. RESULTS: Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. CONCLUSIONS: This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.