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.

Intermittent preventive treatment for malaria in infants.

BACKGROUND: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited. OBJECTIVES: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas. SEARCH METHODS: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.78, 0.69 to 0.88; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence). AUTHORS' CONCLUSIONS: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi.

Hematopoietic stem cell transplantation for people with sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review. OBJECTIVES: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of the Cochrane Library) and quarterly searches of MEDLINE. We also searched trial registries for ongoing trials up to April 2020. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 December 2019. SELECTION CRITERIA: Randomized controlled and quasi-randomized trials that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. DATA COLLECTION AND ANALYSIS: No trials were eligible for inclusion in the review. MAIN RESULTS: We identified 12 potentially-eligible trials by the searches; we excluded 11 of these and the remaining trial is an ongoing trial that may be eligible for inclusion in a future version of the review. AUTHORS' CONCLUSIONS: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. We did not find any eligible randomized controlled trials assessing the benefit or risk of hematopoietic stem cell transplantations. However, there is an ongoing quasi-randomized trial comparing hematopoietic stem cell transplantation with standard care, Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.

Intermittent preventive treatment for malaria in infants.

BACKGROUND: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited. OBJECTIVES: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas. SEARCH METHODS: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 27% reduction (rate ratio 0.73, 0.65 to 0.82; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.79, 0.74 to 0.85; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence). AUTHORS' CONCLUSIONS: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi. 2 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (3 Dec, 2018) were included.

Hematopoietic stem cell transplantation for people with sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review. OBJECTIVES: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 06 October 2015. SELECTION CRITERIA: Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: Ten trials were identified by the initial search and none for the update. None of these trials were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. No randomized controlled trial assessing the benefit or risk of hematopoietic stem cell transplantations was found. Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.

Interventions for preventing unintended pregnancies among adolescents.

BACKGROUND: Unintended pregnancy among adolescents represents an important public health challenge in high-income countries, as well as middle- and low-income countries. Numerous prevention strategies such as health education, skills-building and improving accessibility to contraceptives have been employed by countries across the world, in an effort to address this problem. However, there is uncertainty regarding the effects of these interventions, hence the need to review the evidence-base. OBJECTIVES: To assess the effects of primary prevention interventions (school-based, community/home-based, clinic-based, and faith-based) on unintended pregnancies among adolescents. SEARCH METHODS: We searched all relevant studies regardless of language or publication status up to November 2015. We searched the Cochrane Fertility Regulation Group Specialised trial register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015 Issue 11), MEDLINE, EMBASE, LILACS, Social Science Citation Index and Science Citation Index, Dissertations Abstracts Online, The Gray Literature Network, HealthStar, PsycINFO, CINAHL and POPLINE and the reference lists of articles. SELECTION CRITERIA: We included both individual and cluster randomised controlled trials (RCTs) evaluating any interventions that aimed to increase knowledge and attitudes relating to risk of unintended pregnancies, promote delay in the initiation of sexual intercourse and encourage consistent use of birth control methods to reduce unintended pregnancies in adolescents aged 10 years to 19 years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias, and extracted data. Where appropriate, binary outcomes were pooled using a random-effects model with a 95% confidence interval (Cl). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 53 RCTs that enrolled 105,368 adolescents. Participants were ethnically diverse. Eighteen studies randomised individuals, 32 randomised clusters (schools (20), classrooms (6), and communities/neighbourhoods (6). Three studies were mixed (individually and cluster randomised). The length of follow up varied from three months to seven years with more than 12 months being the most common duration. Four trials were conducted in low- and middle- income countries, and all others were conducted in high-income countries. Multiple interventionsResults showed that multiple interventions (combination of educational and contraceptive-promoting interventions) lowered the risk of unintended pregnancy among adolescents significantly (RR 0.66, 95% CI 0.50 to 0.87; 4 individual RCTs, 1905 participants, moderate quality evidence. However, this reduction was not statistically significant from cluster RCTs. Evidence on the possible effects of interventions on secondary outcomes (initiation of sexual intercourse, use of birth control methods, abortion, childbirth, sexually transmitted diseases) was not conclusive.Methodological strengths included a relatively large sample size and statistical control for baseline differences, while limitations included lack of biological outcomes, possible self-report bias, analysis neglecting clustered randomisation and the use of different statistical tests in reporting outcomes. Educational interventionsEducational interventions were unlikely to significantly delay the initiation of sexual intercourse among adolescents compared to controls (RR 0.95, 95% CI 0.71 to 1.27; 2 studies, 672 participants, low quality evidence).Educational interventions significantly increased reported condom use at last sex in adolescents compared to controls who did not receive the intervention (RR 1.18, 95% CI 1.06 to 1.32; 2 studies, 1431 participants, moderate quality evidence).However, it is not clear if the educational interventions had any effect on unintended pregnancy as this was not reported by any of the included studies. Contraceptive-promoting interventionsFor adolescents who received contraceptive-promoting interventions, there was little or no difference in the risk of unintended first pregnancy compared to controls (RR 1.01, 95% CI 0.81 to 1.26; 2 studies, 3,440 participants, moderate quality evidence).The use of hormonal contraceptives was significantly higher in adolescents in the intervention group compared to those in the control group (RR 2.22, 95% CI 1.07 to 4.62; 2 studies, 3,091 participants, high quality evidence) AUTHORS' CONCLUSIONS: A combination of educational and contraceptive-promoting interventions appears to reduce unintended pregnancy among adolescents.  Evidence for programme effects on biological measures is limited. The variability in study populations, interventions and outcomes of included trials, and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective.

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

BACKGROUND: Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT), non-RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers. DATA COLLECTION AND ANALYSIS: We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence. MAIN RESULTS: Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study).We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility-based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non-vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59). AUTHORS' CONCLUSIONS: Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs.

The effects of radiofrequency electromagnetic fields exposure on tinnitus, migraine and non-specific symptoms in the general and working population: A systematic review and meta-analysis on human observational studies.

BACKGROUND: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). OBJECTIVES: The objective is to systematically review the effects of longer-term or repeated local and whole human body radiofrequency electromagnetic field (RF-EMF) exposure on the occurrence of symptoms. Primary hypotheses were tinnitus, migraine and headaches in relation to RF-EMF exposure of the brain, sleep disturbances and composite symptom scores in relation to whole-body RF-EMF exposure. METHODS: Eligibility criteria: We included case-control and prospective cohort studies in the general population or workers estimating local or whole-body RF-EMF exposure for at least one week. INFORMATION SOURCES: We conducted a systematic literature search in various databases including Web of Science and Medline. Risk of bias: We used the Risk of Bias (RoB) tool developed by OHAT adapted to the topic of this review. SYNTHESIS OF RESULTS: We synthesized studies using random effects meta-analysis. RESULTS: Included studies: We included 13 papers from eight distinct cohort and one case-control studies with a total of 486,558 participants conducted exclusively in Europe. Tinnitus is addressed in three papers, migraine in one, headaches in six, sleep disturbances in five, and composite symptom scores in five papers. Only one study addressed occupational exposure. SYNTHESIS OF RESULTS: For all five priority hypotheses, available research suggests that RF-EMF exposure below guideline values does not cause symptoms, but the evidence is very uncertain. The very low certainty evidence is due the low number of studies, possible risk of bias in some studies, inconsistencies, indirectness, and imprecision. In terms of non-priority hypotheses numerous exposure-outcome combinations were addressed in the 13 eligible papers without indication for an association related to a specific symptom or exposure source. DISCUSSION: Limitations of evidence: This review topic includes various challenges related to confounding control and exposure assessment. Many of these aspects are inherently present and not easy to be solved in future research. Since near-field exposure from wireless communication devices is related to lifestyle, a particular challenge is to differentiate between potential biophysical effects and other potential effects from extensive use of wireless communication devices that may compete with healthy behaviour such as sleeping or physical activity. Future research needs novel and innovative methods to differentiate between these two hypothetical mechanisms. INTERPRETATION: This is currently the best available evidence to underpin safety of RF-EMF. There is no indication that RF-EMF below guideline values causes symptoms. However, inherent limitations of the research results in substantial uncertainty. OTHER: Funding: This review was partially funded by the WHO radioprotection programme. REGISTRATION: The protocol for this review has been registered in Prospero (reg no CRD42021239432) and published in Environment International (Röösli et al., 2021).

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A systematic review of human experimental studies.

BACKGROUND: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s exposing large proportions of the population. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF. OBJECTIVES: To systematically assess the effects of exposure to RF-EMF on self-reported non-specific symptoms in human subjects and to assess the accuracy of perceptions of presence or absence of RF-EMF exposure. METHODS: Eligibility criteria: experimental studies carried out in the general population and in individuals with idiopathic environmental intolerance attributed to EMF (IEI-EMF), in any language. INFORMATION SOURCES: Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos, Embase and EMF portal, searched till April 2022. Risk of Bias (ROB): we used the RoB tool developed by OHAT adapted to the topic of this review. SYNTHESIS OF RESULTS: we synthesized studies using random effects meta-analysis and sensitivity analyses, where appropriate. RESULTS: Included studies: 41 studies were included, mostly cross over trials and from Europe, with a total of 2,874 participants. SYNTHESIS OF RESULTS: considering the primary outcomes, we carried out meta-analyses of 10 exposure-outcomes pairs. All evidence suggested no or small non-significant effects of exposure on symptoms with high (three comparisons), moderate (four comparisons), low (one comparison) and very low (two comparisons) certainty of evidence. The effects (standard mean difference, where positive values indicate presence of symptom being exposed) in the general population for head exposure were (95% confidence intervals) 0.08 (-0.07 to 0.22) for headache, -0.01 (-0.22 to 0.20) for sleeping disturbances and 0.13 (-0.51 to 0.76) for composite symptoms; and for whole-body exposure: 0.09 (-0.35 to 0.54), 0.00 (-0.15 to 0.15) for sleeping disturbances and -0.05 (-0.17 to 0.07) for composite symptoms. For IEI-EMF individuals SMD ranged from -0.19 to 0.11, all of them with confidence intervals crossing the value of zero. Further, the available evidence suggested that study volunteers could not perceive the EMF exposure status better than what is expected by chance and that IEI-EMF individuals could not determine EMF conditions better than the general population. DISCUSSION: Limitations of evidence: experimental conditions are substantially different from real-life situations in the duration, frequency, distance and position of the exposure. Most studies were conducted in young, healthy volunteers, who might be more resilient to RF-EMF than the general population. The outcomes of interest in this systematic review were symptoms, which are self-reported. The available information did not allow to assess the potential effects of exposures beyond acute exposure and in elderly or in chronically ill people. It cannot be ruled out that a real EMF effect in IEI-EMF groups is masked by a mix with insensitive subjects. However, studies on symptoms reporting and/or field perceptions did not find any evidence that there were particularly vulnerable individuals in the IEI-EMF group, although in open provocation studies, when volunteers were informed about the presence or absence of EMF exposure, such differences were consistently observed. INTERPRETATION: available evidence suggests that acute RF-EMF below regulatory limits does not cause symptoms and corresponding claims in the everyday life are related to perceived and not to real EMF exposure status.

Hematopoietic stem cell transplantation for people with sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. OBJECTIVES: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 16 August 2012. SELECTION CRITERIA: Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: Ten trials were identified by the initial search and none for the update. None of these trials were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. No randomized controlled trial assessing the benefit or risk of hematopoietic stem cell transplantations was found. Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.

Open-label trial of three dosage regimens of fixed-dose combination of artemisinin and naphthoquine for treating uncomplicated falciparum malaria in Calabar, Nigeria.

BACKGROUND: The use of anti-malarial drug combinations with artemisinin, or with one of its derivatives, is now widely recommended to overcome drug resistance in falciparum malaria. Fixed-dose combination of artemisinin and naphthoquine is a new generation artemisinin combination therapy (ACT) offered as a single dose therapy. The aim of the study was to assess the therapeutic efficacy, safety and tolerability of three dosage schedules of fixed-dose combination of artemisinin (125 mg) and naphthoquine (50 mg) for treating uncomplicated Plasmodium falciparum malaria among adolescents and adults in Calabar, South-east Nigeria. METHOD: A total of 121 patients aged ≥15 years with uncomplicated P. falciparum malaria were enrolled and randomly assigned to three dosage schedules: (A) 700 mg (four tablets) single dose; (B) 700 mg 12-hourly x two doses; and (C) 1,400 mg (eight tablets) single dose. Patients were observed for 28 days, with clinical, parasitological, and haematological assessments. RESULTS: A total of 108 patients completed the study. The overall 28-day cure rate was 88.9%. Day 28-cure rates of the three dosage schedules were 85.3%, 93.1% and 88.9% for Group A, B and C respectively. Adverse events were few and mild, the commonest being weakness and headache; there was no serious adverse event. CONCLUSION: Concerns for emergence of parasite resistance due to the use of artemisinin-naphthoquine as single dose regimen is likely to compromise the usefulness of this potentially important combination treatment. A robust multi-centre trial is recommended to evaluate a three-day regimen with potentials to achieve high cure rates while minimizing the risk of emergence of resistant parasite strains.

Intermittent preventive treatment for malaria in children living in areas with seasonal transmission.

BACKGROUND: In malaria endemic areas, pre-school children are at high risk of severe and repeated malaria illness. One possible public health strategy, known as Intermittent Preventive Treatment in children (IPTc), is to treat all children for malaria at regular intervals during the transmission season, regardless of whether they are infected or not. OBJECTIVES: To evaluate the effects of IPTc to prevent malaria in preschool children living in endemic areas with seasonal malaria transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (July 2011), CENTRAL (The Cochrane Library 2011, Issue 6), MEDLINE (1966 to July 2011), EMBASE (1974 to July 2011), LILACS (1982 to July 2011), mRCT (July 2011), and reference lists of identified trials. We also contacted researchers working in the field for unpublished and ongoing trials. SELECTION CRITERIA: Individually randomized and cluster-randomized controlled trials of full therapeutic dose of antimalarial or antimalarial drug combinations given at regular intervals compared with placebo or no preventive treatment in children aged six years or less living in an area with seasonal malaria transmission. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, extracted data and assessed the risk of bias in the trials. Data were meta-analysed and measures of effects (ie rate ratio, risk ratio and mean difference) are presented with 95% confidence intervals (CIs). The quality of evidence was assessed using the GRADE methods. MAIN RESULTS: Seven trials (12,589 participants), including one cluster-randomized trial, met the inclusion criteria. All were conducted in West Africa, and six of seven trials were restricted to children aged less than 5 years.IPTc prevents approximately three quarters of all clinical malaria episodes (rate ratio 0.26; 95% CI 0.17 to 0.38; 9321 participants, six trials, high quality evidence), and a similar proportion of severe malaria episodes (rate ratio 0.27, 95% CI 0.10 to 0.76; 5964 participants, two trials, high quality evidence). These effects remain present even where insecticide treated net (ITN) usage is high (two trials, 5964 participants, high quality evidence).IPTc probably produces a small reduction in all-cause mortality consistent with the effect on severe malaria, but the trials were underpowered to reach statistical significance (risk ratio 0.66, 95% CI 0.31 to 1.39, moderate quality evidence).The effect on anaemia varied between studies, but the risk of moderately severe anaemia is probably lower with IPTc (risk ratio 0.71, 95% CI 0.52 to 0.98; 8805 participants, five trials, moderate quality evidence).Serious drug-related adverse events, if they occur, are probably rare, with none reported in the six trials (9533 participants, six trials, moderate quality evidence). Amodiaquine plus sulphadoxine-pyrimethamine is the most studied drug combination for seasonal chemoprevention. Although effective, it causes increased vomiting in this age-group (risk ratio 2.78, 95% CI 2.31 to 3.35; two trials, 3544 participants, high quality evidence).When antimalarial IPTc was stopped, no rebound increase in malaria was observed in the three trials which continued follow-up for one season after IPTc. AUTHORS' CONCLUSIONS: In areas with seasonal malaria transmission, giving antimalarial drugs to preschool children (age < 6 years) as IPTc during the malaria transmission season markedly reduces episodes of clinical malaria, including severe malaria. This benefit occurs even in areas where insecticide treated net usage is high.

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A protocol for a systematic review of human experimental studies.

BACKGROUND: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s across multiple sectors exposing large proportions of the population. This fact has raised concerns related to the potential consequences to people's health. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF and has carried out an international survey amongst experts, who have identified six priority topics to be further addressed through systematic reviews, whereof the effects on symptoms is one of them. We report here the systematic review protocol of experimental studies in humans assessing the effects of RF-EMF on symptoms. OBJECTIVE: Our objectives are to assess the effects of exposure to electromagnetic fields (compared to no or lower exposure levels) on symptoms in human subjects. We will also assess the accuracy of perception of presence of exposure in volunteers with and without idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF). ELIGIBILITY CRITERIA: We will search relevant literature sources (e.g. the Web of Science, Medline, Embase, Epistemonikos) for randomized trials (comparing at least two arms) and randomised crossover trials of RF-EMF exposure that have assessed the effects on symptoms. We will also include studies that have measured the accuracy of the perception of the presence or absence of exposure. We will include studies in any language. STUDY APPRAISAL AND SYNTHESIS: Studies will be assessed against inclusion criteria by two independent reviewers. Data on study characteristics, participants, exposure, comparators and effects will be extracted using a specific template for this review, by two independent reviewers. Discrepancies will be solved by consensus. Risk of bias (ROB) will be assessed using the ROB Rating Tool for Human and Animal Studies and the level of confidence in the evidence of the exposure-outcome relations will be assessed using the GRADE approach. For the perception studies, we will use adapted versions of the ROB tool and GRADE assessment. Where appropriate, data will be combined using meta-analytical techniques.

Interventions for improving coverage of child immunization in low- and middle-income countries.

BACKGROUND: Immunization coverage remains low, particularly in low- and middle-income countries (LMIC), despite its proven effectiveness in reducing the burden of childhood infectious diseases. A Cochrane review has shown that patient reminder recall is effective in improving coverage of immunization but technologies to support this strategy are lacking in LMIC. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunization coverage in LMIC. SEARCH STRATEGY: We searched the following databases for primary studies: Cochrane Central Register of Controlled Trials (CENTRAL) 2010, Issue 1, part of The Cochrane Library. www.thecochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 8 July 2010); MEDLINE, Ovid (1948 to March Week 3 2011) (searched 30 March 2011); EMBASE, Ovid (1980 to 2010 Week 26) (searched 8 July 2010); CINAHL, EBSCO (1981 to present ) (searched 8 July 2010); LILACS, VHL (1982 to present) (searched 8 July 2010); Sociological Abstracts, CSA Illumnia (1952 to current) (searched 8 July 2010). Reference lists of all papers and relevant reviews were identified and searched for additional studies. SELECTION CRITERIA: Included studies were randomized controlled trials (RCTs), non-randomized controlled trials (NRCTs), and interrupted-time-series (ITS) studies. Study participants were children aged 0 to 4 years, caregivers, and health providers. Interventions included patient and community-oriented interventions, provider-oriented interventions, health system interventions, multi-faceted (any combination of the above categories of interventions), and any other single or multifaceted intervention intended to improve childhood immunisation coverage The primary outcome was the proportion of the target population fully immunized with recommended vaccines by age. DATA COLLECTION AND ANALYSIS: Two authors independently screened full articles of selected studies, extracted data, and assessed study quality. MAIN RESULTS: Six studies were included in the review; four were at high risk of bias. There was low quality evidence that: facility based health education may improve the uptake of combined vaccine against diphtheria, pertussis, and tetanus (DPT3) coverage (risk ratio (RR) 1.18; 95% CI 1.05 to 1.33); and also that a combination of facility based health education and redesigned immunization cards may improve DPT3 coverage (RR 1.36; 95% CI 1.22 to 1.51). There was also moderate quality evidence that: evidence-based discussions probably improve DPT3 coverage (RR 2.17; 95% CI 1.80 to 2.61), and that information campaigns probably increase uptake of at least a dose of a vaccine (RR 1.43; 95% CI 1.01 to 2.02). AUTHORS' CONCLUSIONS: Home visits and health education may improve immunization coverage but the quality of evidence is low.

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance.

Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species.

The effects of radiofrequency electromagnetic fields exposure on tinnitus, migraine and non-specific symptoms in the general and working population: A protocol for a systematic review on human observational studies.

BACKGROUND: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). Concern has been raised that RF-EMF exposure affects health related quality of life, because a part of the population reports to experience a variety of symptoms related to low exposure levels below regulatory limits. OBJECTIVES: To systematically review the effects of longer-term or repeated local and whole human body RF-EMF exposure on the occurrence of symptoms evaluating migraine, tinnitus, headaches, sleep disturbances and composite symptom scores as primary outcomes. METHODS: We will follow the WHO handbook for guideline development. For the development of the systematic review protocol we considered handbook for conducting systematic reviews for health effects evaluations from the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT) and COSTER (Recommendations for the conduct of systematic reviews in toxicology and environmental health research). ELIGIBILITY CRITERIA: Peer-reviewed epidemiological studies in the general population or workers aiming to investigate the association between local or whole-body RF-EMF exposure for at least one week and symptoms are eligible for inclusion. Only cohort, case-control and panel studies will be included. INFORMATION SOURCES: We will search the scientific literature databases Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos and Embase, using a predefined search strategy. This search will be supplemented by a search in the EMF-Portal and checks of reference lists of relevant papers and reviews. STUDY APPRAISAL AND SYNTHESIS METHOD: Data from included papers will be extracted according to predefined forms. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidence, complemented with meta-analyses. We will separately review effects of local, far field and occupational exposure. RISK OF BIAS: The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for Human and Animal Studies, elaborated to observational RF-EMF studies. EVIDENCE APPRAISAL: To rate certainty of the evidence, we will use the OHAT GRADE-based approach for epidemiological studies. FRAMEWORK AND FUNDING: This protocol concerns one of the ten different systematic reviews considered in a larger systematic review of the World Health Organization to assess potential health effects of exposure to RF-EMF in the general and working population. REGISTRATION: PROSPERO CRD42021239432.

Patterns of cord, placental and post-delivery maternal malaria parasitemia.

Malaria transmission is high and perennial in south-east Nigeria and is associated with a high burden of morbidity and mortality in children under 5 years and pregnant women. It is associated with maternal anemia, placental infection, intrauterine growth retardation and low birth weight. To evaluate the status of malaria in pregnancy in Cross River State, Nigeria, we assessed the prevalence rates of maternal, cord and placental malaria parasitemia in the dry and rainy seasons for 626 consecutively recruited pregnant women who delivered at two rural and two urban health facilities. Demographic data were obtained at delivery and maternal, placental and cord blood samples were collected and examined for malaria parasites by light microscopy. Of the mother and infant pairs, 120 (19.2%), 69 (14.7%) and 62 (13.5%), respectively, had positive maternal, placental and cord blood parasitemia. Parasitemia rates in the rainy season were higher than in the dry season (p < 0.05). There were no significant differences in maternal, placental and cord parasitemia between urban and rural areas. The prevalence rates of parasitemia at delivery indicate high malaria transmission and poor control during pregnancy.

Hematopoietic stem cell transplantation for children with sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. OBJECTIVES: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (Clinical Trials) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: September 2008. SELECTION CRITERIA: Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in children under 16 years of age irrespective of the type of sickle cell disease, gender and setting. DATA COLLECTION AND ANALYSIS: No relevant trials have been identified. MAIN RESULTS: Ten trials were identified by the initial search of which none were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. No randomized controlled trial has assessed the benefit or risk of different types of hematopoietic stem cell transplantations in children. Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of different types of hematopoietic stem cell transplantations comparing sickle status and severity of disease in children.

Interventions for preventing unintended pregnancies among adolescents.

BACKGROUND: Unintended pregnancy among adolescents represent an important public health challenge in developed and developing countries. Numerous prevention strategies such as health education, skills-building and improving accessibility to contraceptives have been employed by countries across the world, in an effort to address this problem. However, there is uncertainty regarding the effects of these intervention, and hence the need to review their evidence-base OBJECTIVES: To assess the effects of primary prevention interventions (school-based, community/home-based, clinic-based, and faith-based) on unintended pregnancies among adolescents. SEARCH STRATEGY: We searched electronic databases (CENTRAL, PubMed, EMBASE) ending December 2008. Cross-referencing, hand-searching, and contacting experts yielded additional citations. SELECTION CRITERIA: We included both individual and cluster randomized controlled trials (RCTs) evaluating any interventions that aimed to increase knowledge and attitudes relating to risk of unintended pregnancies, promote delay in the initiation of sexual intercourse and encourage consistent use of birth control methods to reduce unintended pregnancies in adolescents aged 10-19 years. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and risk of bias in studies that met the inclusion criteria. Where appropriate, binary outcomes were pooled using random effects model with a 95% confidence interval (Cl). MAIN RESULTS: Forty one RCTs that enrolled 95,662 adolescents were included. Participants were ethnically diverse. Eleven studies randomized individuals, twenty seven randomized clusters (schools (19), classrooms (5), and communities/neighbourhoods (3). Three studies were mixed (individually and cluster randomized). The length of follow up varied from 3 months to 4.5 years. Data could only be pooled for a number of studies (15) because of variations in the reporting of outcomes. Results showed that multiple interventions (combination of educational and contraceptive interventions) lowered the rate of unintended pregnancy among adolescents. Evidence on the possible effects of interventions on secondary outcomes (initiation of sexual intercourse, use of birth control methods, abortion, childbirth, sexually transmitted diseases) is not conclusive.Methodological strengths included a relatively large sample size and statistical control for baseline differences, while limitations included lack of biological outcomes, possible self-report bias, analysis neglecting clustered randomization and the use of different statistical test in reporting outcomes. AUTHORS' CONCLUSIONS: Combination of educational and contraceptive interventions appears to reduce unintended pregnancy among adolescents. Evidence for program effects on biological measures is limited. The variability in study populations, interventions and outcomes of included trials, and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective.