Epidemiology of diabetic retinopathy and maculopathy in Africa: a systematic review.

AIM: To summarize findings from studies reporting the prevalence and incidence of diabetic retinopathy and diabetic maculopathy in African countries in light of the rising prevalence of diabetes mellitus. METHODS: Using a predefined search strategy, we systematically searched MEDLINE, EMBASE, Science Citation index and Conference Proceedings Citation index, African Index Medicus and the grey literature database 'OpenSIGLE' for studies published between January 1990 and February 2011. Included studies reported prevalence or incidence of diabetic retinopathy or diabetic maculopathy of subjects with diabetes resident in African countries. RESULTS: Sixty-two studies from 21 countries were included: three population-based surveys; two cohort studies; five case-control studies; 32 diabetes clinic-based, nine eye clinic-based and 11 other hospital-based surveys. Included studies varied considerably in terms of patient selection, method of assessing the eye and retinopathy classification. In population-based studies, the reported prevalence range in patients with diabetes for diabetic retinopathy was 30.2 to 31.6%, proliferative diabetic retinopathy 0.9 to 1.3%, and any maculopathy 1.2 to 4.5%. In diabetes clinic-based surveys, the reported prevalence range for diabetic retinopathy was 7.0 to 62.4%, proliferative diabetic retinopathy 0 to 6.9%, and any maculopathy 1.2 to 31.1%. No obvious association between prevalence and income level of the country was detected. CONCLUSIONS: Large, community-based cross-sectional and cohort studies are needed to investigate rates and determinants of prevalence of diabetic retinopathy, incidence and progression in Africa. Consensus is needed on the most appropriate methods of identification and classification of retinopathy for research and clinical practice. Estimates of prevalence of diabetic retinopathy, proliferative diabetic retinopathy and maculopathy are comparable with recent European and American studies.

Treatment of urinary schistosomiasis: methodological issues and research needs identified through a Cochrane systematic review.

Guidelines recommend praziquantel (PZQ) for the treatment and control of schistosomiasis, with no real alternative. Metrifonate was still widely used against Schistosoma haematobium in the 1990s, and then withdrawn. Experimental studies and clinical trials suggest that artemisinin compounds are active against S. haematobium. In a Cochrane systematic review assessing the efficacy and safety of drugs for treating urinary schistosomiasis, 24 randomized controlled trials (n=6315 individuals) met our inclusion criteria. These trials compared a variety of single agent and combination regimens with PZQ, metrifonate or artemisinin derivatives. The review confirmed that both the standard recommended doses of PZQ (single 40 mg/kg oral dose) and metrifonate (3x7.5-10 mg/kg oral doses administered fortnightly) are efficacious and safe in treating urinary schistosomiasis, but there is no study comparing these two regimens head-to-head. There is currently not enough evidence to evaluate artemisinin compounds. Most of the studies included in the Cochrane systematic review were insufficiently powered, lacked standardization in assessing and reporting outcomes, and had a number of methodological limitations. In this paper we discuss the implications of these findings with respect to public health and research methodology and propose priority research needs.

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population.

OBJECTIVE: To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population. STUDY DESIGN: Historical cohort study. RESULT: A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy. CONCLUSION: About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

WITHDRAWN: Mefloquine for preventing malaria in non-immune adult travellers.

BACKGROUND: Mefloquine is commonly prescribed to prevent malaria in travellers, and has replaced other drugs because Plasmodium falciparum is commonly resistant to them. However, mefloquine may be associated with neuropsychiatric harmful effects. OBJECTIVES: To assess the effects of mefloquine in adult travellers compared to other regimens in relation to episodes of malaria, withdrawal from prophylaxis, and adverse events. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (September 2002), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), LILACS (September 2002), Science Citation Index (1981 to September 2002), and bibliographies in retrieved papers and standard textbooks. We contacted researchers in the subject of malaria chemoprophylaxis, and pharmaceutical companies. SELECTION CRITERIA: Randomised trials comparing mefloquine with other standard prophylaxis or placebo in non-immune adult travellers, and in non-travelling volunteers. For adverse events, any published case reports were collected. DATA COLLECTION AND ANALYSIS: We independently assessed trial quality and extracted data. Adverse events from observational studies were categorised by the study type. We also contacted study authors. MAIN RESULTS: We included 10 trials involving 2750 non-immune adult participants. Five of these were field trials, and of these all were in mainly male soldiers. One trial comparing mefloquine with placebo showed mefloquine prevented malaria episodes in an area of drug resistance (Peto odds ratio 0.04, 95% confidence interval 0.02 to 0.08). Withdrawals in the mefloquine group were consistently higher in four placebo controlled trials (odds ratio 3.56, 95% confidence interval 1.67 to 7.60). In five trials comparing mefloquine with other chemoprophylaxis, no difference in tolerability was detected. We found 516 published case reports of mefloquine adverse effects. 63 per cent of these published reports involved tourists and business travellers. There were four fatalities attributed to mefloquine. AUTHORS' CONCLUSIONS: Mefloquine prevents malaria, but has adverse effects that limit its acceptability . There is evidence from non-randomised studies that mefloquine has potentially harmful effects in tourists and business travellers, and its use needs to be carefully balanced against this. Trials of comparative effects of antimalarial prophylaxis should include episodes of malaria and withdrawal from prophylaxis as outcomes.

Deworming drugs for treating soil-transmitted intestinal worms in children: effects on growth and school performance.

BACKGROUND: In areas where intestinal worm infections occur, the World Health Organization recommends treating all school children at regular intervals with deworming drugs to improve growth and school performance. The evidence base for this policy needs to be established for countries to commit resources to implement these programmes. OBJECTIVES: To summarize the effects of deworming drugs used to treat soil-transmitted intestinal worms (nematode geohelminths) on growth and school performance in children. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, mRCT, and reference lists. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on growth, nutritional status, school performance, or cognition tests. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trials and evaluated methodological quality; one author extracted data, and another checked a sample. Continuous data were analysed using the weighted mean difference (WMD) with 95% confidence intervals (CI). The random-effects model (RE model) was used in the presence of statistically significant heterogeneity. MAIN RESULTS: Thirty-four RCTs, including six cluster-RCTs, met the inclusion criteria. Four trials had adequate allocation concealment, and three cluster-RCTs failed to take design effects into account in their analysis. Weight increased after one dose of a deworming drug (WMD 0.34 kg, 95% CI 0.05 to 0.64, RE model; 2448 children, 9 trials); however, there was considerable heterogeneity between trials that was not explained by background intestinal worm infection or intensity. A meta-analysis of multiple dose trials reporting on outcomes within a year of starting treatment showed no significant difference in weight gain (1714 children, 6 trials); however, one cluster-RCT did show effects on weight at one year in a subgroup analysis. In the seven multiple dose trials with follow up beyond 12 months, only one showed a significant increase in weight. Six of seven trials reported clear data on cognitive tests and school performance: five reported no significant effects, and one showed some improvements in three out of 10 cognitive tests. AUTHORS' CONCLUSIONS: Deworming drugs used in targeted community programmes may be effective in relation to weight gain in some circumstances but not in others. No effect on cognition or school performance has been demonstrated.

Open general medical wards versus specialist psychiatric units for acute psychoses.

BACKGROUND: As international healthcare policy has moved away from treating people with severe mental illness in large inpatient psychiatric institutions, beds for people with acute psychiatric disorders are being established in specialised psychiatric units in general hospitals. In developing countries, however, limited resources mean that it is not always possible to provide discrete psychiatric units, either in general hospitals or in the community. An alternative model of admission, used in the Caribbean, is to treat the person with acute psychosis in a general hospital ward. OBJECTIVES: To compare the outcomes for people with acute psychosis who have been admitted to open medical wards with those admitted to conventional psychiatric units. SEARCH STRATEGY: We searched The Cochrane Schizophrenia Group's study-based register (April 2007). This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library, EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference proceedings. SELECTION CRITERIA: We would have included all relevant randomised or quasi-randomised trials, allocating anyone thought to be suffering from an acute psychotic episode to either acute management on general medical wards, or acute management in a specialist psychiatric unit. The primary outcomes of interest were length of stay in hospital and relapse. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we would have calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based using a fixed effects model. MAIN RESULTS: We didnt identify any relevant randomised trials. AUTHORS' CONCLUSIONS: The Caribbean practice of treating people with severe mental illness on general medical wards has been influenced by socio-economic factors rather than evidence from randomised trials. This practice affords an opportunity for a well designed, well conducted and reported randomised trial, now impossible in many other settings.

Directly observed therapy for treating tuberculosis.

BACKGROUND: For tuberculosis treatment, policies have been introduced to encourage adherence to treatment regimens. One such policy is directly observed therapy (DOT), which involves people directly observing patients taking their antituberculous drugs. OBJECTIVES: To compare DOT with self administration of treatment or different DOT options for people requiring treatment for clinically active tuberculosis or prevention of active disease. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, and mRCT. We also checked article reference lists and contacted relevant researchers and organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a health worker, family member, or community volunteer routinely observing people taking antituberculous drugs compared with routine self administration of treatment at home. We include people requiring treatment for clinically active tuberculosis or medication for preventing active disease. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial methodological quality and extracted data. Data were analysed using relative risks (RR) with 95% confidence intervals (CI) and the fixed-effect model when there was no statistically significant heterogeneity (chi square P > 0.1). Trials of drug users were analysed separately. MAIN RESULTS: Eleven trials with 5609 participants met the inclusion criteria. No statistically significant difference was detected between DOT and self administration in terms of cure (RR 1.02, 95% CI 0.86 to 1.21, random-effects model; 1603 participants, 4 trials), with similar results for cure plus completion of treatment. When stratified by location, DOT provided at home compared with DOT provided at clinic suggests a possible small advantage with home-based DOT for cure (RR 1.10, 95% CI 1.02 to 1.18; 1365 participants, 3 trials). There was no significant difference detected in clinical outcomes between DOT at a clinic versus by a family member or community health worker (2 trials), or for DOT provided by a family member versus a community health worker (1326 participants, 1 trial). Two small trials of tuberculosis prophylaxis in intravenous drugs users found no statistically significant difference between DOT and self administration (199 participants, 1 trial) or a choice of location for DOT for completion of treatment (108 participants, 1 trial). AUTHORS' CONCLUSIONS: The results of randomized controlled trials conducted in low-, middle-, and high-income countries provide no assurance that DOT compared with self administration of treatment has any quantitatively important effect on cure or treatment completion in people receiving treatment for tuberculosis.

WITHDRAWN: Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being recommended by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (May 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1988 to May 2005), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Six trials (1698 participants) tested a four dose regimen. Failure rates for artemether-lumefantrine tended to be higher (comparisons included sulfadoxine-pyrimethamine, halofantrine, and mefloquine; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. Two trials (419 participants) tested a six dose regimen against mefloquine plus artesunate. Artemether-lumefantrine was associated with higher failure rates but the studies were small. AUTHORS' CONCLUSIONS: The four dose regimen of artemether-lumefantrine seems to be less effective than most other current antimalarial regimens. The six dose regimen is largely untested. The authors are aware that some recently published trials may change the results of this review, and are preparing an update. These trials are referenced in 'Studies awaiting assessment'.

WITHDRAWN: Interventions for promoting adherence to tuberculosis management.

BACKGROUND: Up to half the people with tuberculosis do not complete their treatment. Strategies to improve adherence to diagnostic and treatment regimens are therefore important. OBJECTIVES: To assess the effects of various interventions aimed at promoting adherence to anti-tuberculosis treatment and completion of TB diagnostic protocols. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Infectious Diseases Group trials register, Medline, Embase, Lilacs and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of interventions to promote adherence with curative or preventive chemotherapy and diagnostic protocols for tuberculosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Fourteen trials were included. Reminder cards sent to defaulters, a combination package of a monetary incentive and health education and more supervision of clinic staff increased the number of people completing their tuberculosis treatment. Intensive counselling/education did not help in one study. Direct observation showed better clinical outcomes in one study, and no difference in another. Return to the clinic for reading of a tuberculin skin test was enhanced by monetary incentives, assistance by lay health workers, contracts and telephone prompts but not by health education. AUTHORS' CONCLUSIONS: We have found evidence of benefit for a number of specific interventions to improve adherence to anti-tuberculous therapy and completion of diagnostic protocols. These should be implemented by health care providers where appropriate to local circumstances. Future studies in low income countries are a priority and should measure adherence and clinical outcomes. This review summarises trials up to 2000. It is being replaced by a series of reviews on particular intervention strategies. The details are in the 'Published notes' section.

Contracts between patients and healthcare practitioners for improving patients' adherence to treatment, prevention and health promotion activities.

BACKGROUND: Contracts are a verbal or written agreement that a patient makes with themselves, with healthcare practitioners, or with carers, where participants commit to a set of behaviours related to the care of a patient. Contracts aim to improve the patients' adherence to treatment or health promotion programmes. OBJECTIVES: To assess the effects of contracts between patients and healthcare practitioners on patients' adherence to treatment, prevention and health promotion activities, the stated health or behaviour aims in the contract, patient satisfaction or other relevant outcomes, including health practitioner behaviour and views, health status, reported harms, costs, or denial of treatment as a result of the contract. SEARCH STRATEGY: We searched: the Cochrane Consumers and Communication Review Group's Specialised Register (in May 2004); the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2004, issue 1); MEDLINE 1966 to May 2004); EMBASE (1980 to May 2004); PsycINFO (1966 to May 2004); CINAHL (1982 to May 2004); Dissertation Abstracts. A: Humanities and Social Sciences (1966 to May 2004); Sociological Abstracts (1963 to May 2004); UK National Research Register (2000 to May 2004); and C2-SPECTR, Campbell Collaboration (1950 to May 2004). SELECTION CRITERIA: We included randomised controlled trials comparing the effects of contracts between healthcare practitioners and patients or their carers on patient adherence, applied to diagnostic procedures, therapeutic regimens or any health promotion or illness prevention initiative for patients. Contracts had to specify at least one activity to be observed and a commitment of adherence to it. We included trials comparing contracts with routine care or any other intervention. DATA COLLECTION AND ANALYSIS: Selection and quality assessment of trials were conducted independently by two review authors; single data extraction was checked by a statistician. We present the data as a narrative summary, given the wide range of interventions, participants, settings and outcomes, grouped by the health problem being addressed. MAIN RESULTS: We included thirty trials, all conducted in high income countries, involving 4691 participants. Median sample size per group was 21. We examined the quality of each trial against eight standard criteria, and all trials were inadequate in relation to three or more of these standards. Trials evaluated contracts in addiction (10 trials), hypertension (4 trials), weight control (3 trials) and a variety of other areas (13 trials). Sixteen trials reported at least one outcome that showed statistically significant differences favouring the contracts group, five trials reported at least one outcome that showed differences favouring the control group and 26 trials reported at least one outcome without differences between groups. Effects on adherence were not detected when measured over longer periods. AUTHORS' CONCLUSIONS: There is limited evidence that contracts can potentially contribute to improving adherence, but there is insufficient evidence from large, good quality studies to routinely recommend contracts for improving adherence to treatment or preventive health regimens.

Electronic mosquito repellents for preventing mosquito bites and malaria infection.

BACKGROUND: Electronic mosquito repellents (EMRs) are marketed to prevent mosquitoes biting and to prevent malaria. OBJECTIVES: To assess whether EMRs prevent mosquito bites, and to assess any evidence of an effect on malaria infection. SEARCH STRATEGY: In August 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, Cambridge Scientific Abstracts, and the Science Citation Index. We also checked conference proceedings, contacted international specialist centres and EMR manufacturers, and checked reference lists. SELECTION CRITERIA: Field entomological studies, which controlled for geographic site, time, and attractiveness of human participants, of EMRs for preventing mosquito bites; and randomized and quasi-randomized controlled trials of EMRs to prevent malaria infection. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality, and extracted and analysed the data. MAIN RESULTS: Ten field entomological studies met the inclusion criteria. All 10 studies found that there was no difference in the number of mosquitoes caught from the bare body parts of the human participants with or without an EMR. No randomized or quasi-randomized controlled trials on the efficacy of EMR on malaria infection were found. AUTHORS' CONCLUSIONS: Field entomological studies confirm that EMRs have no effect on preventing mosquito bites. Therefore there is no justification for marketing them to prevent malaria infection.

Drugs for preventing malaria in pregnant women.

BACKGROUND: Malaria contributes to maternal illness and anaemia in pregnancy, especially in first-time mothers, and can harm the mother and the baby. Drugs given routinely to prevent or mitigate the effects of malaria during pregnancy are often recommended. OBJECTIVES: To assess drugs given to prevent malaria infection and its consequences in pregnant women living in malarial areas. This includes prophylaxis and intermittent preventive treatment (IPT). SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers working in the field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing antimalarial drugs given regularly with no antimalarial drugs for preventing malaria in pregnant women living in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: Both authors extracted data and assessed methodological quality. Dichotomous variables were combined using relative risks (RR) and weighted mean differences (WMD) for mean values, both with 95% confidence intervals (CI). MAIN RESULTS: Sixteen trials (12,638 participants) met the inclusion criteria; two used adequate methods to conceal allocation. Antimalarials reduced antenatal parasitaemia when given to all pregnant women (RR 0.53, 95% CI 0.33 to 0.86; 328 participants, 2 trials), placental malaria (RR 0.34, 95% CI 0.26 to 0.45; 1236 participants, 3 trials), but no effect was detected with perinatal deaths (2890 participants, 4 trials). In women in their first or second pregnancy, antimalarial drugs reduced severe antenatal anaemia (RR 0.62, 95% CI 0.50 to 0.78; 2809 participants, 1 prophylaxis and 2 IPT trials), antenatal parasitaemia (RR 0.27, 95% CI 0.17 to 0.44, random-effects model; 2906 participants, 6 trials), and perinatal deaths (RR 0.73, 95% CI 0.53 to 0.99; 1986 participants, 2 prophylaxis and 1 IPT trial; mean birthweight was higher (WMD 126.70 g, 95% CI 88.64 to 164.75 g; 2648 participants, 8 trials), and low birthweight less frequent (RR 0.57, 95% CI 0.46 to 0.72; 2350 participants, 6 trials). Proguanil performed better than chloroquine in one trial of women of all parities in relation to maternal fever episodes. Sulfadoxine-pyrimethamine performed better than chloroquine in two trials of low-parity women. AUTHORS' CONCLUSIONS: Chemoprophylaxis or IPT reduces antenatal parasite prevalence and placental malaria when given to women in all parity groups. They also have positive effects on birthweight and possibly on perinatal death in low-parity women.

Strategies for integrating primary health services in middle- and low-income countries at the point of delivery.

BACKGROUND: Strategies to integrate primary health care aim to bring together inputs, organisation, management and delivery of particular service functions to make them more efficient, and accessible to the service user. In some middle and low income countries, services have been fragmented by separate vertical programmes established to ensure delivery of particular technologies. We examined the effectiveness of integration strategies at the point of delivery. OBJECTIVES: To assess the effects of strategies to integrate primary health care services on producing a more coherent product and improving health care delivery and health status. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (August 2005), MEDLINE (1966 to September 2005), EMBASE (1988 to 2005), Socio Files (1974 to September 2005), Popline (1970 to September 2005), HealthStar (1975 to September 2005), Cinahl (1982 to September 2005); Cab Health (1972 to 1999), International Bibliography of the Social Sciences (1970 to 1999), and reference lists of articles. We also searched the Internet and World Health Organization (WHO) library database, hand searched relevant WHO publications and contacted experts in the field. SELECTION CRITERIA: Randomised trials, controlled before and after studies, and interrupted time series analyses of integration strategies in primary health care services. Health services in high-income countries were excluded. The primary outcomes were indicators of health care delivery, user views on any measure of service coherence, and health status. We also sought information on comparative costs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study quality. MAIN RESULTS: Three cluster randomised trials and two controlled before and after studies were included, with three types of comparison: integration by adding on an additional component to an existing service (family planning); integrated services versus single special services (for sex workers); integrated delivery systems versus a vertical service (for family planning); and packages of enhanced primary child care services (integrated management of childhood illnesses) vs. routine child care. Interventions were complex and in some studies inputs varied substantially between comparison arms. Overall, no consistent pattern emerged. Only one study attempted to assess the user's view of the service provided. AUTHORS' CONCLUSIONS: Few studies of good quality, large and with rigorous study design have been carried out to investigate strategies to promote service integration in low and middle income countries. All describe the service supply side, and none examine or measure aspects of the demand side. Future studies must also assess the client's view, as this will influence uptake of integration strategies and their effectiveness on community health.

Directly observed therapy for treating tuberculosis.

BACKGROUND: People with tuberculosis require treatment for at least six months. As many patients do not complete their treatment, policies have been introduced to encourage adherence to treatment regimens. One such policy is directly observed therapy, which involves people directly observing patients taking their antituberculous drugs. OBJECTIVES: To compare directly observed therapy (DOT) with self administration of treatment in people requiring treatment for clinically active tuberculosis or prevention of active disease. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (November 2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1974 to November 2005), LILACS (1982 to November 2005), and reference lists of articles. We also contacted researchers and organizations working in the field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a health worker, family member, or community volunteer routinely observing people taking antituberculous drugs compared with routine self administration of treatment at home. We include patients requiring treatment for clinically active tuberculosis or medication for preventing active disease. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial methodological quality and extracted data. Data were analysed using relative risks (RR) with 95% confidence intervals (CI) and the fixed-effect model when there was no statistically significant heterogeneity (chi square P > 0.1). Trials of drug users were analysed separately. MAIN RESULTS: Ten trials with 3985 participants met the inclusion criteria. There was no statistically significant difference between DOT and self administration of treatment for the number of people cured (RR 1.02, 95% CI 0.86 to 1.21, random-effects model; 1603 participants, 4 trials) or who were cured or completed treatment (RR 1.06, 95% CI 1.00 to 1.13; 1603 participants, 4 trials). Stratifying the location of the DOT by home or at a clinic suggests a possible small effect with home-based DOT (RR 1.10, 95% CI 1.02 to 1.18; 1365 participants, 3 trials). Two small trials of tuberculosis prophylaxis in intravenous drugs users found no statistically significant difference between DOT and self administration (199 participants, 1 trial), or a choice of location for DOT for completion of treatment (108 participants, 1 trial). AUTHORS' CONCLUSIONS: The results of randomized controlled trials conducted in low-, middle-, and high-income countries provide no assurance that directly observed therapy compared with self-administered treatment has any quantitatively important effect on cure or treatment completion in people receiving treatment for tuberculosis.

Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND: The World Health Organization recommends artemether-lumefantrine, an expensive drug, as a treatment for uncomplicated malaria. We sought evidence of the superiority of the four-dose regimen over existing treatments. OBJECTIVES: To evaluate the four-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (1982 to October 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing four doses of artemether-lumefantrine with standard treatment regimens (single drug or combination), or six doses of artemether-lumefantrine, for treating uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Seven trials (2057 participants) tested a four-dose regimen. More people tended to fail treatment with artemether-lumefantrine than with other drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial), halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1 trial; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two trials (378 participants), but over 50% of the participants treated with chloroquine had total failure by day 28. Fewer people failed treatment with the six-dose regimen compared to the four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial). AUTHORS' CONCLUSIONS: The four-dose regimen of artemether-lumefantrine seems to be less effective than regimens against which it has been tested. The six-dose regimen is superior to four-dose regimen.

Albendazole for lymphatic filariasis.

BACKGROUND: Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis. We sought reliable evidence of the effects of albendazole on the disease and the parasite. OBJECTIVES: To summarize the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2005), CENTRAL (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1974 to August 2005), LILACS (1982 to August 2005), and reference lists. We also contacted researchers, the World Health Organization, and GlaxoSmithKline. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of albendazole alone or combined with another antifilarial drug for treating individuals with lymphatic filariasis, or for reducing transmission in endemic communities. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility and trial quality, and extracted data. Authors contacted investigators for missing information or clarification. MAIN RESULTS: Seven trials including 6997 participants (995 with detectable microfilariae) met the criteria. A comparison of albendazole and placebo detected no effect on microfilariae prevalence (920 participants; 3 trials); one trial (499 participants) reported significantly lower microfilariae density at six months. Albendazole performed slightly worse than ivermectin in two trials (436 participants). Compared with diethylcarbamazine (DEC), two small trials (56 participants) found little difference in microfilariae prevalence over an extended follow up. One larger trial (502 participants) found a statistically significant effect for DEC at six months, but none at three months. Microfilariae prevalence and density were statistically significantly lower with the combination of albendazole and ivermectin compared with ivermectin alone in two of three trials (649 participants). Two trials compared albendazole plus DEC with DEC alone and found no statistically significant difference in microfilariae prevalence, though one trial favoured the combination at six months (relative risk 0.62, 95% confidence interval 0.32 to 1.21; 491 participants). This trial also found a statistically significant reduction in microfilariae density. AUTHORS' CONCLUSIONS: There is insufficient evidence to confirm or refute that albendazole co-administered with DEC or ivermectin is more effective than DEC or ivermectin alone in clearing microfilariae or killing adult worms. Albendazole combined with ivermectin appears to have a small effect on microfilaraemia, but this was not consistently demonstrated. The effect of albendazole against adult and larval filarial parasites, alone and in combination with other antifilarial drugs, deserves further rigorous research.

Chemoprophylaxis and intermittent treatment for preventing malaria in children.

BACKGROUND: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children. OBJECTIVES: To evaluate chemoprophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria endemic areas. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), and reference lists of identified trials. We also contacted researchers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in an area where malaria is endemic. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM). MAIN RESULTS: Nineteen trials (14,393 participants) met the inclusion criteria. Children receiving antimalarial drugs as prophylaxis or intermittent treatment had fewer clinical malaria episodes (RR 0.52, 95% CI 0.35 to 0.77, REM; 4051 participants, 8 trials), and severe anaemia was less common (RR 0.54, 95% CI 0.42 to 0.68; 2727 participants, 8 trials). We did not detect a difference in the number of deaths from any cause (RR 0.82, 95% CI 0.65 to 1.04; 7929 participants, 9 trials), but the confidence intervals do not exclude a potentially important difference. None of the trials reported serious adverse events. Three trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small. AUTHORS' CONCLUSIONS: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children. There is insufficient evidence to detect an effect on mortality.

Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND: The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over existing treatment regimens as well as its effectiveness in clinical situations. OBJECTIVES: To evaluate the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing six doses of artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination), or supervised with unsupervised treatment, for uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Nine trials (4547 participants) tested the six-dose regimen. Total failure at day 28 for artemether-lumefantrine was lower when compared with amodiaquine (270 participants, 1 trial), amodiaquine plus sulfadoxine-pyrimethamine (507 participants, 1 trial), but not with chloroquine plus sulfadoxine-pyrimethamine (201 participants, 2 trials). In comparisons with artemisinin derivative combinations, artemether-lumefantrine performed better than amodiaquine plus artesunate (668 participants, 2 trials), worse than mefloquine plus artesunate (270 participants, 4 trials), and no differently to dihydroartemisinin-napthoquine-trimethoprim (89 participants, 1 trial). AUTHORS' CONCLUSIONS: The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.