Interventions for improving coverage of childhood immunisation in low- and middle-income countries.

BACKGROUND: Immunisation plays a major role in reducing childhood morbidity and mortality. Getting children immunised against potentially fatal and debilitating vaccine-preventable diseases remains a challenge despite the availability of efficacious vaccines, particularly in low- and middle-income countries. With the introduction of new vaccines, this becomes increasingly difficult. There is therefore a current need to synthesise the available evidence on the strategies used to bridge this gap. This is a second update of the Cochrane Review first published in 2011 and updated in 2016, and it focuses on interventions for improving childhood immunisation coverage in low- and middle-income countries. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost demand and supply of childhood vaccines, and sustain high childhood immunisation coverage in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and Global Index Medicus (11 July 2022). We searched Embase, LILACS, and Sociological Abstracts (2 September 2014). We searched WHO ICTRP and ClinicalTrials.gov (11 July 2022). In addition, we screened reference lists of relevant systematic reviews for potentially eligible studies, and carried out a citation search for 14 of the included studies (19 February 2020). SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs), non-randomised RCTs (nRCTs), controlled before-after studies, and interrupted time series conducted in low- and middle-income countries involving children that were under five years of age, caregivers, and healthcare providers. DATA COLLECTION AND ANALYSIS: We independently screened the search output, reviewed full texts of potentially eligible articles, assessed the risk of bias, and extracted data in duplicate, resolving discrepancies by consensus. We conducted random-effects meta-analyses and used GRADE to assess the certainty of the evidence. MAIN RESULTS: Forty-one studies involving 100,747 participants are included in the review. Twenty studies were cluster-randomised and 15 studies were individually randomised controlled trials. Six studies were quasi-randomised. The studies were conducted in four upper-middle-income countries (China, Georgia, Mexico, Guatemala), 11 lower-middle-income countries (Côte d'Ivoire, Ghana, Honduras, India, Indonesia, Kenya, Nigeria, Nepal, Nicaragua, Pakistan, Zimbabwe), and three lower-income countries (Afghanistan, Mali, Rwanda). The interventions evaluated in the studies were health education (seven studies), patient reminders (13 studies), digital register (two studies), household incentives (three studies), regular immunisation outreach sessions (two studies), home visits (one study), supportive supervision (two studies), integration of immunisation services with intermittent preventive treatment of malaria (one study), payment for performance (two studies), engagement of community leaders (one study), training on interpersonal communication skills (one study), and logistic support to health facilities (one study). We judged nine of the included studies to have low risk of bias; the risk of bias in eight studies was unclear and 24 studies had high risk of bias. We found low-certainty evidence that health education (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.15 to 1.62; 6 studies, 4375 participants) and home-based records (RR 1.36, 95% CI 1.06 to 1.75; 3 studies, 4019 participants) may improve coverage with DTP3/Penta 3 vaccine. Phone calls/short messages may have little or no effect on DTP3/Penta 3 vaccine uptake (RR 1.12, 95% CI 1.00 to 1.25; 6 studies, 3869 participants; low-certainty evidence); wearable reminders probably have little or no effect on DTP3/Penta 3 uptake (RR 1.02, 95% CI 0.97 to 1.07; 2 studies, 1567 participants; moderate-certainty evidence). Use of community leaders in combination with provider intervention probably increases the uptake of DTP3/Penta 3 vaccine (RR 1.37, 95% CI 1.11 to 1.69; 1 study, 2020 participants; moderate-certainty evidence). We are uncertain about the effect of immunisation outreach on DTP3/Penta 3 vaccine uptake in children under two years of age (RR 1.32, 95% CI 1.11 to 1.56; 1 study, 541 participants; very low-certainty evidence). We are also uncertain about the following interventions improving full vaccination of children under two years of age: training of health providers on interpersonal communication skills (RR 5.65, 95% CI 3.62 to 8.83; 1 study, 420 participants; very low-certainty evidence), and home visits (RR 1.29, 95% CI 1.15 to 1.45; 1 study, 419 participants; very low-certainty evidence). The same applies to the effect of training of health providers on interpersonal communication skills on the uptake of DTP3/Penta 3 by one year of age (very low-certainty evidence). The integration of immunisation with other services may, however, improve full vaccination (RR 1.29, 95% CI 1.16 to 1.44; 1 study, 1700 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Health education, home-based records, a combination of involvement of community leaders with health provider intervention, and integration of immunisation services may improve vaccine uptake. The certainty of the evidence for the included interventions ranged from moderate to very low. Low certainty of the evidence implies that the true effect of the interventions might be markedly different from the estimated effect. Further, more rigorous RCTs are, therefore, required to generate high-certainty evidence to inform policy and practice.

mHealth guideline training for non-communicable diseases in primary care facilities in Nigeria: a mixed methods pilot study.

OBJECTIVE: To pilot the use of a scalable innovative mobile health (mHealth) non-communicable diseases (NCDs) training application for nurses at the primary care level. DESIGN: Mixed methods pilot of mHealth training on NCD care for nurses at primary healthcare (PHC) facilities. We provide a descriptive analysis of mHealth training test scores, with trend analysis of blood pressure (BP) control using paired t-test for quantitative data and thematic analysis for qualitative data. SETTING: PHC facilities in rural and urban communities in Cross River State, south eastern Nigeria. NCDs were not part of routine training previously. As in most low-and-middle-income settings, funding for scale-up using conventional classroom in-service training for NCDs is not available in Nigeria, and onsite supervision poses challenges. PARTICIPANTS: Twenty-four health workers in 19 PHC facilities. INTERVENTION: A self-paced mHealth training module on an NCD desk guide was adapted to be applicable within the Nigerian context in collaboration with the Federal Ministry of Health. The training which focused on hypertension, diabetes and sickle cell disease was delivered via Android tablet devices, supplemented by quarterly onsite supervision and group support via WhatsApp. The training was evaluated with pre/post-course tests, structured observations and focus group discussions. This was an implementation pilot assessing the feasibility and potential effectiveness of mHealth training on NCD in primary care delivery. RESULTS: Nurses who received mHealth training recorded a statistically significant difference (p<0.001) in average pretest and post-test training scores of 65.2 (±12.2) and 86.5 (±7.9), respectively. Recordings on treatment cards indicated appropriate diagnosis and follow-up of patients with hypertension with significant improvements in systolic BP (t=5.09, p<0.001) and diastolic BP (t=5.07, p<0.001). The mHealth nurse training and WhatsApp support groups were perceived as valuable experiences and obviated the need for face-to-face training. Increased workload, non-availability of medications, facility-level conflicts and poor task shifting were identified challenges. CONCLUSIONS: This initiative provides evidence of the feasibility of implementing an NCD care package supported by mHealth training for health workers in PHCs and the strong possibility of successful scale-up nationally.

Association of Genetic Polymorphisms of TGF-ß1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV.

RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor ß1 (TGF-ß1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-ß1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-ß1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-ß1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.

Artemeter para tratar la malaria grave / Artemether for severe malaria

No disponible

Survey on available treatment for acute kidney injury in the Southern African Development Community and Nigeria: are we ready for zero deaths by 2025 in sub-Saharan Africa?

OBJECTIVES: The International Society of Nephrology (ISN) has called for zero deaths by 2025. This survey aimed to determine the preparedness of Southern African Development Community (SADC) countries and Nigeria to heed this call. SETTING: A questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved. PARTICIPANTS: Clinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire. RESULTS: Completed questionnaires were received from 12 of the 15 SADC countries and Nigeria, covering 48 service providers. The government provided partial funding for dialysis in 41.7% of services. There was no funding for acute dialysis in two countries. Interdisciplinary teams in 72.9% of hospitals covered the intensive care units (ICUs), which included at least one nephrologist in 75%. Only 77% were able to provide dialysis in ICU. Intermittent haemodialysis was the most common modality available (91.7% of facilities), sustained low-efficiency dialysis in 50%, continuous therapies in 35% and peritoneal dialysis in 33.3%. Almost half (47.9%) of the sites were limited to one mode of dialysis and unable to care for severely ill patients. The clinical status was used to initiate and monitor dialysis, with very few sites having clear written standard operating procedures. CONCLUSION: In the 16 countries surveyed, the majority had limited ability to provide comprehensive dialysis programmes for patients with AKI due to lack of facilities and government funding. Additionally, nephrologists are scarce; modes of dialysis are limited; as is the care for severely ill patients and lack of standard operating procedures. Resources, training and funding need to be made available to create universal coverage of dialysis for AKI. The ISN goal of providing renal replacement therapy to all by 2025 is unlikely to be achieved in SADC and Nigeria.

Priority setting for new systematic reviews: processes and lessons learned in three regions in Africa.

Priority setting to identify topical and context relevant questions for systematic reviews involves an explicit, iterative and inclusive process. In resource-constrained settings of low-income and middle-income countries, priority setting for health related research activities ensures efficient use of resources. In this paper, we critically reflect on the approaches and specific processes adopted across three regions of Africa, present some of the outcomes and share the lessons learnt while carrying out these activities. Priority setting for new systematic reviews was conducted between 2016 and 2018 across three regions in Africa. Different approaches were used: Multimodal approach (Central Africa), Modified Delphi approach (West Africa) and Multilevel stakeholder discussion (Southern-Eastern Africa). Several questions that can feed into systematic reviews have emerged from these activities. We have learnt that collaborative subregional efforts using an integrative approach can effectively lead to the identification of region specific priorities. Systematic review workshops including discussion about the role and value of reviews to inform policy and research agendas were a useful part of the engagements. This may also enable relevant stakeholders to contribute towards the priority setting process in meaningful ways. However, certain shared challenges were identified, including that emerging priorities may be overlooked due to differences in burden of disease data and differences in language can hinder effective participation by stakeholders. We found that face-to-face contact is crucial for success and follow-up engagement with stakeholders is critical in driving acceptance of the findings and planning future progress.

Artemether for severe malaria.

BACKGROUND: In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This Cochrane Review evaluates intramuscular artemether compared with both quinine and artesunate. OBJECTIVES: To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in the treatment of severe malaria in adults and children. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, and LILACS, ISI Web of Science, conference proceedings, and reference lists of articles. We also searched the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 7 September 2018. We checked the reference lists of all studies identified by the search. We examined references listed in review articles and previously compiled bibliographies to look for eligible studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous/intramuscular quinine or artesunate for treating severe malaria. DATA COLLECTION AND ANALYSIS: The primary outcome was all-cause death. Two review authors independently screened each article by title and abstract, and examined potentially relevant studies for inclusion using an eligibility form. Two review authors independently extracted data and assessed risk of bias of included studies. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and have presented both measures with 95% confidence intervals (CIs). Where appropriate, we combined data in meta-analyses and used the GRADE approach to summarize the certainty of the evidence. MAIN RESULTS: We included 19 RCTs, enrolling 2874 adults and children with severe malaria, carried out in Africa (12 trials) and in Asia (7 trials).Artemether versus quinineFor children, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.97, 95% CI 0.77 to 1.21; 13 trials, 1659 participants, moderate-certainty evidence). Coma resolution time may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low-certainty evidence). Artemether may make little difference to neurological sequelae (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low-certainty evidence). Compared to quinine, artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate-certainty evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low-certainty evidence).For adults, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate-certainty evidence).Artemether versus artesunateArtemether and artesunate have not been directly compared in randomized trials in children.For adults, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97; two trials, 494 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Artemether appears to be more effective than quinine in children and adults. Artemether compared to artesunate has not been extensively studied, but in adults it appears inferior. These findings are consistent with the WHO recommendations that artesunate is the drug of choice, but artemether is acceptable when artesunate is not available.

Prevalence and correlates of chronic kidney disease (CKD) among ART-naive HIV patients in the Niger-Delta region of Nigeria.

Widespread use of antiretroviral therapy (ART) in human immunodeficiency virus (HIV) patients has led to improved longevity with the attendant increase in noncommunicable disease prevalence including chronic kidney disease (CKD). This study documents the prevalence of CKD in a large HIV population in Southern Nigeria.This is a single center, 15-year analysis in ART-naïve patients. CKD was defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m on 2 consecutive occasions 3 to 12 months apart using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. The Cochran-Armitage and Cuzick tests were employed to assess for trend across the years for CKD prevalence and CD4 count, respectively. Multivariable logistic regression models were used to identify independent associations with CKD.In all, 1317 patients (62.2% females) with mean age of 34.5 years and median CD4 count of 194 cells/µL were included. CKD prevalence was 13.4% (95%CI 11.6%-15.4%) using the CKD-EPI equation (without the race factor). Multivariable analysis identified increasing age and CD4 count <200 cells/µL as being independently associated with CKD occurrence.This study reports a high prevalence of CKD in ART-naïve HIV-infected patients. Measures to improve diagnosis of kidney disease and ensure early initiation of treatment should be integrated in HIV treatment programmes in this setting.

Chronic kidney disease in the global adult HIV-infected population: A systematic review and meta-analysis.

INTRODUCTION: The widespread use of antiretroviral therapies (ART) has increased life expectancy in HIV patients, predisposing them to chronic non-communicable diseases including Chronic Kidney Disease (CKD). We performed a systematic review and meta-analysis (PROSPERO registration number CRD42016036246) to determine the global and regional prevalence of CKD in HIV patients. METHODS: We searched PubMed, Web of Science, EBSCO and AJOL for articles published between January 1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR) <60ml/min using the MDRD, Cockcroft-Gault or CKD-EPI equations. Random effects model was used to combine prevalence estimates from across studies after variance stabilization via Freeman-Tukey transformation. RESULT: Sixty-one eligible articles (n = 209,078 HIV patients) in 60 countries were selected. The overall CKD prevalence was 6.4% (95%CI 5.2-7.7%) with MDRD, 4.8% (95%CI 2.9-7.1%) with CKD-EPI and 12.3% (95%CI 8.4-16.7%) with Cockcroft-Gault; p = 0.003 for difference across estimators. Sub-group analysis identified differences in prevalence by WHO region with Africa having the highest MDRD-based prevalence at 7.9% (95%CI 5.2-11.1%). Within Africa, the pooled MDRD-based prevalence was highest in West Africa [14.6% (95%CI 9.9-20.0%)] and lowest in Southern Africa (3.2%, 95%CI 3.0-3.4%). The heterogeneity observed could be explained by WHO region, comorbid hypertension and diabetes mellitus, but not by gender, hepatitis B or C coinfection, CD4 count or antiretroviral status. CONCLUSION: CKD is common in HIV-infected people, particularly in Africa. HIV treatment programs need to intensify screening for CKD with added need to introduce global guidelines for CKD identification and treatment in HIV positive patients.

Clinical profile and outcome of patients with biopsy-proven acute interstitial nephritis in Cape Town: a 10-year review
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BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury that has not been adequately characterized in Sub-Saharan Africa (SSA) despite an increasing use of potentially inciting agents for the treatment of human immunodeficiency virus (HIV) and tuberculosis in the region. METHODS: A retrospective audit of records of patients with biopsy-proven AIN diagnosed at Groote Schuur Hospital, Cape Town from the 1st of January, 2006, to the 31st of December, 2015. RESULTS: 54 patients with biopsy-proven AIN were reviewed. The majority were of black African origin (59.2%), with HIV (42.8%) and HIV-tuberculosis coinfection (30.5%) as the most common comorbidities. Drug-related AIN was seen in 38 (67.9%) patients, with rifampicin as the most often implicated medication. Probable drug-related AIN was seen in 3 (5.4%) patients, infection-related AIN in 8 (14.3%), and unspecified causes in 4 (7.4%). AIN was suspected in 44.6% of patients before biopsy. 18 patients (34%) received hemodialysis, while 19 (35.2%) were treated with corticosteroids. Complete renal recovery at 30 and 90 days was seen in 23 (42.6%) patients and 24 (45.3%) patients, respectively, with the majority seen among those with drug-induced AIN. Six (11.1%) patients died; 4 (10.5%) of the patients were in the drug-related group. There was no correlation between degree of interstitial inflammation and severity of renal failure (p = 0.10). On multivariate logistic regression, drug-related causes of AIN were predictive of complete recovery at day 30 (OR 16.63; 95% CI: 1.71 - 161.6, p = 0.02), and presence of interstitial fibrosis reduced likelihood of recovery (OR 0.03; 95% CI 0.002 - 0.46, p = 0.012). Steroid use did not influence partial recovery (OR 0.59, 95% CI 0.17 - 1.77; p = 0.32) or complete recovery (OR 3.38, 95% CI 0.38 - 30.39, p = 0.28). CONCLUSIONS: AIN is common in patients with HIV or those on treatment for tuberculosis. Drug-related AIN is often associated with improved outcomes. This is particularly reassuring in the SSA region where the use of potentially-inciting medications is rife from a high burden of HIV and tuberculosis.
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Antibiotics for treating septic abortion.

BACKGROUND: A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. OBJECTIVES: To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. MAIN RESULTS: We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1). The evidence for this was of moderate quality. "Response to treatment was evaluated by the patient's 'fever index' expressed in degree-hour and defined as the total quantity of fever under the daily temperature curve with 99°F (37.2°C) as the baseline".There was no difference in duration of hospitalisation between clindamycin and penicillin plus chloramphenicol. The mean duration of hospital stay for women in each group was 5 days (MD 0.00, 95% CI -0.54 to 0.54; women = 77; studies = 1).One study evaluated the effect of penicillin plus chloramphenicol versus cephalothin plus kanamycin before and after D&C. Response to therapy was evaluated by "the time from start of antibiotics until fever lysis and time from D&C until patients become afebrile". Low-quality evidence suggested that the effect of penicillin plus chloramphenicol on fever did not differ from that of cephalothin plus kanamycin (MD -2.30, 95% CI -17.31 to 12.71; women = 56; studies = 1). There was no significant difference between penicillin plus chloramphenicol versus cephalothin plus kanamycin when D&C was performed during antibiotic therapy (MD -1.00, 95% CI -13.84 to 11.84; women = 56; studies = 1). The quality of evidence was low.A study with unclear risk of bias showed that the time for fever resolution (MD -5.03, 95% CI -5.77 to -4.29; women = 100; studies = 1) as well as time for resolution of leukocytosis (MD -4.88, 95% CI -5.98 to -3.78; women = 100; studies = 1) was significantly lower with tetracycline plus enzymes compared with intravenous penicillin G.Treatment failure and adverse events occurred infrequently, and the difference between groups was not statistically significant. AUTHORS' CONCLUSIONS: We found no strong evidence that intravenous clindamycin alone was better than penicillin plus chloramphenicol for treating women with septic abortion. Similarly, available evidence did not suggest that penicillin plus chloramphenicol was better than cephalothin plus kanamycin for the treatment of women with septic abortion. Tetracyline enzyme antibiotic appeared to be more effective than intravenous penicillin G in reducing the time to fever defervescence, but this evidence was provided by only one study at low risk of bias.There is a need for high-quality RCTs providing reliable evidence for treatments of septic abortion with antibiotics that are currently in use. The three included studies were carried out over 30 years ago. There is also a need to include institutions in low-resource settings, such as sub-Saharan Africa, Latin America and the Caribbean, and South Asia, with a high burden of abortion and health systems challenges.

Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF)-containing regimens in the treatment of HIV-infected children have safety concerns with respect to renal and bone toxicity. OBJECTIVE: The aim of this study was to systematically review and critically appraise the literature relating to the reported renal and bone adverse effects of TDF-based regimens in the treatment of HIV-infected children from 2 to 19 years old. METHODS: Searches were performed using the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, OvidSP, ScienceDirect and Web of Science databases and platforms. All primary studies involving tenofovir use in HIV-infected children were sought. Studies that involved the use of TDF for pre- and post-exposure prophylaxis, and treatment of chronic hepatitis B virus infection were excluded. Data on study characteristics, participant's characteristics, therapeutic intervention and adverse effects were extracted using a piloted tool. In addition, pharmacovigilance data from the WHO Adverse Reaction database were included. RESULTS: We identified 19 studies that reported the presence of renal and bone adverse effects of TDF and these included a total of 1100 study participants. The reports were in distinctly heterogeneous participant groups. A total of 287 renal and bone adverse effects were reported (250 renal and 37 bone adverse effects). Approximately 238 (21.6 %) participants were affected by these adverse effects. Of these, 15 participants stopped their TDF-containing regimen due to these adverse effects. In addition, the pharmacovigilance data from the WHO Adverse Reaction database reported 101 renal and bone adverse effects for patients whose indication was HIV/AIDS. CONCLUSION: This systematic review summarises the reports of renal and bone adverse effects of a TDF-containing regimen in the treatment of HIV-infected children. Our findings suggest that the benefits of using TDF in children need to be balanced against the potential risk of toxicity.

Artemether for severe malaria.

BACKGROUND: In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation, many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This review evaluates intramuscular artemether compared with both quinine and artesunate. OBJECTIVES: To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in treating severe malaria in adults and children. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and LILACS, ISI Web of Science, conference proceedings and reference lists of articles. We also searched the WHO clinical trial registry platform, ClinicalTrials.gov and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 9 April 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous or intramuscular antimalarial for treating severe malaria. DATA COLLECTION AND ANALYSIS: The primary outcome was all-cause death.Two authors independently assessed trial eligibility, risk of bias and extracted data. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD), and presented both measures with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 18 RCTs, enrolling 2662 adults and children with severe malaria, carried out in Africa (11) and in Asia (7). Artemether versus quinine For children in Africa, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.96, 95% CI 0.76 to 1.20; 12 trials, 1447 participants, moderate quality evidence). Coma recovery may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low quality evidence), and artemether may result in fewer neurological sequelae, but larger trials would be needed to confirm this (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low quality evidence). Artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate quality evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low quality evidence).For adults in Asia, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate quality evidence). Artemether versus artesunate Artemether and artesunate have not been directly compared in randomized trials in African children.For adults in Asia, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97, two trials,494 participants, moderate quality evidence). AUTHORS' CONCLUSIONS: Although there is a lack of direct evidence comparing artemether with artesunate, artemether is probably less effective than artesunate at preventing deaths from severe malaria. In circumstances where artesunate is not available, artemether is an alternative to quinine.

Immediate postabortal insertion of intrauterine devices.

Background The use of an effective contraceptive may be necessary after an abortion. Insertion of an intrauterine device (IUD) may be done the same day or later. Immediate IUD insertion is an option since the woman is not pregnant, pain of insertion is less because the cervical os is open, and her motivation to use contraception may be high. However, insertion of an IUD immediately after a pregnancy ends carries risks, such as spontaneous expulsion.Objectives To assess the safety and efficacy of IUD insertion immediately after spontaneous or induced abortion.Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov,and ICTRP in January 27, 2014. We also contacted investigators to identify other trials.Selection criteria We sought all randomised controlled trials (RCTs) with at least one treatment arm that involved IUD insertion immediately after an induced abortion or after curettage for spontaneous abortion.Data collection and analysis We evaluated the methodological quality of each report and abstracted the data. We focused on discontinuation rates for accidental pregnancy, perforation, expulsion, and pelvic inflammatory disease.We computed the weighted average of the rate ratios.We compute drisk ratios (RRs) with 95% Confidence Intervals (CIs).We performed an intention-to-treat (ITT) analysis by including all randomised participants in the analysis according to the Cochrane Handbook for Systematic Reviews of Interventions.Main results We identified 12 trials most of which are of moderate risk of bias involving 7,119 participants which described random assignment.Five trials randomised to either immediate or delayed insertion of IUD. One of them randomised to immediate versus delayed insertion of Copper 7 showed immediate insertion of the Copper 7 was associated with a higher risk of expulsion than was delayed insertion(RR 11.98, 95% CI 1.61 to 89.35,1 study, 259 participants); the quality of evidence was moderate. Moderate quality of evidence also suggests that use and expulsion of levonorgestrel-releasing intrauterine system or CuT380A was more likely for immediate compared to delayed insertion risk ratio (RR) 1.40 (95% CI 1.24 to 1.58; 3 studies; 878 participants) and RR 2.64 ( 95% CI 1.16 to 6.00; 3 studies; 878 participants) respectively. Another trial randomised to the levonorgestrel IUD or Nova T showed discontinuation rates due to pregnancy were likely to be higher for women in the Nova T group. (MD 8.70, 95% CI 3.92 to 13.48;1 study; 438 participants);moderate quality evidence.Seven trials examined immediate insertion of IUD only. From meta-analysis of two multicentre trials, pregnancy was less likely for the TCu 220C versus the Lippes Loop (RR 0.43, 95% CI 0.24 to 0.75; 2 studies; 2257 participants ) as was expulsion (RR 0.61, 95% CI0.46 to 0.81; 2 studies; 2257 participants). Estimates for the TCu 220 versus the Copper 7 were RR 0.42 ( 95% CI 0.23 to 0.77; 2 studies, 2,274 participants) and RR 0.68, (95% CI 0.51 to 0.91); 2 studies, 2,274 participants), respectively. In other work, adding copper sleeves to the Lippes Loop improved efficacy (RR 3.40, 95% CI 1.28 to 9.04, 1 study, 400 participants) and reduced expulsion(RR 3.00, 95% CI 1.51 to 5.97; 1 study, 400 participants).Authors' conclusions Moderate quality evidence shows that insertion of an IUD immediately after abortion is safe and practical. IUD expulsion rates appear higher immediately after abortions compared to delayed insertions. However, at six months postabortion, IUD use is higher following immediate insertion compared to delayed insertion.

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Typhoid and paratyphoid are febrile illnesses, due to a bacterial infection, which remain common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends the fluoroquinolone antibiotics in areas with known resistance to the older first-line antibiotics. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating children and adults with enteric fever. SEARCH STRATEGY: We searched The Cochrane Infectious Disease Group Specialized Register (February 2011); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 2); MEDLINE (1966 to February 2011); EMBASE (1974 to February 2011); and LILACS (1982 to February 2011). We also searched the metaRegister of Controlled Trials (mRCT) in February 2011. SELECTION CRITERIA: Randomized controlled trials examining fluoroquinolone antibiotics, in people with blood, stool or bone marrow culture-confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial's methodological quality and extracted data. We calculated risk ratios (RR) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI).Comparative effectiveness has been interpreted in the context of; length of treatment, dose, year of study, known levels of antibiotic resistance, or proxy measures of resistance such as the failure rate in the comparator arm. MAIN RESULTS: Twenty-six studies, involving 3033 patients, are included in this review.Fluoroquinolones versus older antibiotics (chloramphenicol, co-trimoxazole, amoxicillin and ampicillin)In one study from Pakistan in 2003-04, high clinical failure rates were seen with both chloramphenicol and co-trimoxazole, although resistance was not confirmed microbiologically. A seven-day course of either ciprofloxacin or ofloxacin were found to be superior. Older studies of these comparisons failed to show a difference (six trials, 361 participants).In small studies conducted almost two decades ago, the fluoroquinolones were demonstrated to have fewer clinical failures than ampicillin and amoxicillin (two trials, 90 participants, RR 0.11, 95% CI 0.02 to 0.57).Fluoroquinolones versus current second-line options (ceftriaxone, cefalexin, and azithromycin)The two studies comparing a seven day course of oral fluoroquinolones with three days of intravenous ceftriaxone were too small to detect important differences between antibiotics should they exist (two trials, 89 participants).In Pakistan in 2003-04, no clinical or microbiological failures were seen with seven days of either ciprofloxacin, ofloxacin or cefixime (one trial, 139 participants). In Nepal in 2005, gatifloxacin reduced clinical failure and relapse compared to cefixime, despite a high prevalence of NaR in the study population (one trial, 158 participants, RR 0.04, 95% CI 0.01 to 0.31).Compared to a seven day course of azithromycin, a seven day course of ofloxacin had a higher rate of clinical failures in populations with both multi-drug resistance (MDR) and nalidixic acid resistance (NaR) enteric fever in Vietnam in 1998-2002 (two trials, 213 participants, RR 2.20, 95% CI 1.23 to 3.94). However, a more recent study from Vietnam in 2004-05, detected no difference between gatifloxacin and azithromycin with both drugs performing well (one trial, 287 participants). AUTHORS' CONCLUSIONS: Generally, fluoroquinolones performed well in treating typhoid, and maybe superior to alternatives in some settings. However, we were unable to draw firm general conclusions on comparative contemporary effectiveness given that resistance changes over time, and many studies were small. Policy makers and clinicians need to consider local resistance patterns in choosing a fluoroquinolone or alternative.There is some evidence that the newest fluoroquinolone, gatifloxacin, remains effective in some regions where resistance to older fluoroquinolones has developed. However, the different fluoroquinolones have not been compared directly in trials in these settings.

WITHDRAWN: Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Review status: Current question - no update intended. Azithromycin treatments are included in the review: Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). (Thaver D, Zaidi AKM, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD004530. DOI: 10.1002/14651858.CD004530.pub3.)   This latter review is being updated, and will be published in late 2011.Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease. OBJECTIVES: To compare azithromycin with other antibiotics for treating uncomplicated enteric fever. SEARCH STRATEGY: In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI). MAIN RESULTS: Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug-resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting. AUTHORS' CONCLUSIONS: Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone.

Haemodialysis in an emerging centre in a developing country: a two year review and predictors of mortality.

BACKGROUND: Haemodialysis is the most common form of renal replacement therapy in Nigeria. The high cost of haemodialysis has made optimal therapy of end-stage renal disease difficult in Nigeria. This paper is a review of data collected over two years of provision of dialysis services in a new tertiary hospital in Southern Nigeria. METHODS: This retrospective analysis is done on data obtained from the patient case files and dialysis records in the first two years of provision of dialysis services in our centre. A gender comparison of the patients' baseline sociodemographic, clinical and biochemical was performed and a logistic regression model used to assess the predictors of mortality. RESULTS: A total of 98 patients had 471 sessions in the two years under review. Males and females had similar characteristics at baseline except for a higher median serum urea in the males. The commonest causes of end-stage renal disease were chronic glomerulonephritis (34.5%), hypertension (32.1%) and diabetes mellitus (17.9%). The main predictor of mortality was under treatment with haemodialysis due to inability to pay for more than a few dialysis sessions. CONCLUSIONS: This study has highlighted the unchanging demographics of our advanced kidney failure patients. Efforts should be aimed at subsidizing the cost of dialysis for our teeming population of dialysis dependent chronic kidney disease patients.

Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease. OBJECTIVES: To compare azithromycin with other antibiotics for treating uncomplicated enteric fever. SEARCH STRATEGY: In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI). MAIN RESULTS: Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug-resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting. AUTHORS' CONCLUSIONS: Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone.