BACKGROUND: Universal Health Coverage is widely endorsed as the pivotal goal in global health, however substantial barriers to accessing health services for children in low and middle-income countries (LMIC) exist. Failure to access healthcare is an important contributor to child mortality in these settings. Barriers to access have been widely studied, however effective interventions to overcome barriers and increase access to services for children are less well documented.
METHODS: We conducted a systematic review of effectiveness of interventions aimed at increasing access to health services for children aged 5 years and below in LMIC. Four databases (EMBASE, Global Health, MEDLINE, and PSYCINFO) were searched in January 2016. Studies were included if they evaluated interventions that aimed to increase: health care utilisation; immunisation uptake; and compliance with medication or referral. Randomised controlled trials and non-randomised controlled study designs were included in the review. A narrative approach was used to synthesise results.
RESULTS: Fifty seven studies were included in the review. Approximately half of studies (49%) were conducted in sub-Saharan Africa. Most studies were randomised controlled trials (n = 44; 77%) with the remaining studies employing non-randomised designs. Very few studies were judged as high quality. Studies evaluated a diverse range of interventions and various outcomes. Supply side interventions included: delivery of services at or closer to home and service level improvements (eg. integration of services). Demand side interventions included: educational programmes, text messages, and financial or other incentives. Interventions that delivered services at or closer to home and text messages were in general associated with a significant improvement in relevant outcomes. A consistent pattern was not noted for the remaining studies.
CONCLUSIONS: This review fills a gap in the literature by providing evidence of the range and effectiveness of interventions that can be used to increase access for children aged ≤5 years in LMIC. It highlights some intervention areas that seem to show encouraging trends including text message reminders and delivery of services at or close to home. However, given the methodological limitations found in existing studies, the results of this review must be interpreted with caution.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420160334200.
BACKGROUND: Many interventions have been implemented to improve maternal health outcomes in sub-Saharan Africa (SSA). Currently, however, systematic information on the effectiveness of these interventions remains scarce. We conducted a systematic review of published evidence on non-drug interventions that reported effectiveness in improving outcomes and quality of care in maternal health in SSA.
METHODS: African Journals Online, Bioline, MEDLINE, Ovid, Science Direct, and Scopus databases were searched for studies published in English between 2000 and 2015 and reporting on the effectiveness of interventions to improve quality and outcomes of maternal health care in SSA. Articles focusing on interventions that involved drug treatments, medications, or therapies were excluded. We present a narrative synthesis of the reported impact of these interventions on maternal morbidity and mortality outcomes as well as on other dimensions of the quality of maternal health care (as defined by the Institute of Medicine 2001 to comprise safety, effectiveness, efficiency, timeliness, patient centeredness, and equitability).
RESULTS: Seventy-three studies were included in this review. Non-drug interventions that directly or indirectly improved quality of maternal health and morbidity and mortality outcomes in SSA assumed a variety of forms including mobile and electronic health, financial incentives on the demand and supply side, facility-based clinical audits and maternal death reviews, health systems strengthening interventions, community mobilization and/or peer-based programs, home-based visits, counseling and health educational and promotional programs conducted by health care providers, transportation and/or communication and referrals for emergency obstetric care, prevention of mother-to-child transmission of HIV, and task shifting interventions. There was a preponderance of single facility and community-based studies whose effectiveness was difficult to assess.
CONCLUSIONS: Many non-drug interventions have been implemented to improve maternal health care in SSA. These interventions have largely been health facility and/or community based. While the evidence on the effectiveness of interventions to improve maternal health is varied, study findings underscore the importance of implementing comprehensive interventions that strengthen different components of the health care systems, both in the community and at the health facilities, coupled with a supportive policy environment.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023750.
AIM: To update a previous systematic review and meta-analyses about the effect of breastfeeding promotion interventions on child growth.
METHODS: Studies evaluating the effect of any type of breastfeeding promotion intervention on child weight, length (or height) and weight/height (or BMI) were screened. Papers published between 2006 and 2014 were checked using the following databases: PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Lilacs and SciELO.
RESULTS: Sixteen studies were added to 19 other studies identified in the previous review, resulting in 35 studies. Meta-analyses of studies reporting on mean weight, length, weight/length or BMI showed that the interventions had no impact on weight or length/height z scores [pooled effect: 0.03 (95% confidence interval: -0.06;0.12) and 0.03 (95% confidence interval: -0.02;0.08), respectively] and had a modest, but significant, reduction in body mass index/weight-for-height z scores [z score mean difference: -0.06 (95% confidence interval: -0.12;0.00)], which was limited to studies from low- and high-incomes settings. For all three outcomes, there was important heterogeneity among studies, which should be taken into account when interpreting the results.
CONCLUSION: Breastfeeding promotion interventions were not associated with significant changes in weight or length, but led to a modest, albeit significant, reduction in body mass index/weight-for-height z scores.
BACKGROUND: While maternal, infant and under-five child mortality rates in developing countries have declined significantly in the past two to three decades, newborn mortality rates have reduced much more slowly. While it is recognised that almost half of the newborn deaths can be prevented by scaling up evidence-based available interventions (such as tetanus toxoid immunisation to mothers, clean and skilled care at delivery, newborn resuscitation, exclusive breastfeeding, clean umbilical cord care, and/or management of infections in newborns), many require facility-based and outreach services. It has also been stated that a significant proportion of these mortalities and morbidities could also be potentially addressed by developing community-based packaged interventions which should also be supplemented by developing and strengthening linkages with the local health systems. Some of the recent community-based studies of interventions targeting women of reproductive age have shown variable impacts on maternal outcomes and hence it is uncertain if these strategies have consistent benefit across the continuum of maternal and newborn care.
OBJECTIVES: To assess the effectiveness of community-based intervention packages in reducing maternal and neonatal morbidity and mortality; and improving neonatal outcomes.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 May 2014), World Bank's JOLIS (25 May 2014), BLDS at IDS and IDEAS database of unpublished working papers (25 May 2014), Google and Google Scholar (25 May 2014).
SELECTION CRITERIA: All prospective randomised, cluster-randomised and quasi-randomised trials evaluating the effectiveness of community-based intervention packages in reducing maternal and neonatal mortality and morbidities, and improving neonatal outcomes.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, assessed trial quality and extracted the data. Data were checked for accuracy.
MAIN RESULTS: The review included 26 cluster-randomised/quasi-randomised trials, covering a wide range of interventional packages, including two subsets from three trials. Assessment of risk of bias in these studies suggests concerns regarding insufficient information on sequence generation and regarding failure to adequately address incomplete outcome data, particularly from randomised controlled trials. We incorporated data from these trials using generic inverse variance method in which logarithms of risk ratio (RR) estimates were used along with the standard error of the logarithms of RR estimates.
Our review showed a possible effect in terms of a reduction in maternal mortality (RR 0.80; 95% confidence interval (CI) 0.64 to 1.00, random-effects (11 studies, n = 167,311; random-effects, Tau² = 0.03, I² 20%). However, significant reduction was observed in maternal morbidity (average RR 0.75; 95% CI 0.61 to 0.92; four studies, n = 138,290; random-effects, Tau² = 0.02, I² = 28%); neonatal mortality (average RR 0.75; 95% CI 0.67 to 0.83; 21 studies, n = 302,646; random-effects, Tau² = 0.06, I² = 85%) including both early and late mortality; stillbirths (average RR 0.81; 95% CI 0.73 to 0.91; 15 studies, n = 201,181; random-effects, Tau² = 0.03, I² = 66%); and perinatal mortality (average RR 0.78; 95% CI 0.70 to 0.86; 17 studies, n = 282,327; random-effects Tau² = 0.04, I² = 88%) as a consequence of implementation of community-based interventional care packages.
Community-based intervention packages also increased the uptake of tetanus immunisation by 5% (average RR 1.05; 95% CI 1.02 to 1.09; seven studies, n = 71,622; random-effects Tau² = 0.00, I² = 52%); use of clean delivery kits by 82% (average RR 1.82; 95% CI 1.10 to 3.02; four studies, n = 54,254; random-effects, Tau² = 0.23, I² = 90%); rates of institutional deliveries by 20% (average RR 1.20; 95% CI 1.04 to 1.39; 14 studies, n = 147,890; random-effects, Tau² = 0.05, I² = 80%); rates of early breastfeeding by 93% (average RR 1.93; 95% CI 1.55 to 2.39; 11 studies, n = 72,464; random-effects, Tau² = 0.14, I² = 98%), and healthcare seeking for neonatal morbidities by 42% (average RR 1.42; 95% CI 1.14 to 1.77, nine studies, n = 66,935, random-effects, Tau² = 0.09, I² = 92%). The review also showed a possible effect on increasing the uptake of iron/folic acid supplementation during pregnancy (average RR 1.47; 95% CI 0.99 to 2.17; six studies, n = 71,622; random-effects, Tau² = 0.26; I² = 99%).
It has no impact on improving referrals for maternal morbidities, healthcare seeking for maternal morbidities, iron/folate supplementation, attendance of skilled birth attendance on delivery, and other neonatal care-related outcomes. We did not find studies that reported the impact of community-based intervention package on improving exclusive breastfeeding rates at six months of age. We assessed our primary outcomes for publication bias and observed slight asymmetry on the funnel plot for maternal mortality.
AUTHORS' CONCLUSIONS: Our review offers encouraging evidence that community-based intervention packages reduce morbidity for women, mortality and morbidity for babies, and improves care-related outcomes particularly in low- and middle-income countries. It has highlighted the value of integrating maternal and newborn care in community settings through a range of interventions, which can be packaged effectively for delivery through a range of community health workers and health promotion groups. While the importance of skilled delivery and facility-based services for maternal and newborn care cannot be denied, there is sufficient evidence to scale up community-based care through packages which can be delivered by a range of community-based workers.
BACKGROUND: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy.This review focused on community-based interventions and health systems-related interventions.
OBJECTIVES: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria.
AUTHORS' CONCLUSIONS: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.
BACKGROUND: Each year almost 3 million newborns die within the first 28 days of life, 2.6 million babies are stillborn, and 287,000 women die from complications of pregnancy and childbirth worldwide. Effective and cost-effective interventions and behaviours for mothers and newborns exist, but their coverage remains inadequate in low- and middle-income countries, where the vast majority of deaths occur. Cost-effective strategies are needed to increase the coverage of life-saving maternal and newborn interventions and behaviours in resource-constrained settings.
METHODS: A systematic review was undertaken on the cost-effectiveness of strategies to improve the demand and supply of maternal and newborn health care in low-income and lower-middle-income countries. Peer-reviewed and grey literature published since 1990 was searched using bibliographic databases, websites of selected organizations, and reference lists of relevant studies and reviews. Publications were eligible for inclusion if they report on a behavioural or health systems strategy that sought to improve the utilization or provision of care during pregnancy, childbirth or the neonatal period; report on its cost-effectiveness; and were set in one or more low-income or lower-middle-income countries. The quality of the publications was assessed using the Consolidated Health Economic Evaluation Reporting Standards statement. Incremental cost per life-year saved and per disability-adjusted life-year averted were compared to gross domestic product per capita.
RESULTS: Forty-eight publications were identified, which reported on 43 separate studies. Sixteen were judged to be of high quality. Common themes were identified and the strategies were presented in relation to the continuum of care and the level of the health system. There was reasonably strong evidence for the cost-effectiveness of the use of women's groups, home-based newborn care using community health workers and traditional birth attendants, adding services to routine antenatal care, a facility-based quality improvement initiative to enhance compliance with care standards, and the promotion of breastfeeding in maternity hospitals. Other strategies reported cost-effectiveness measures that had limited comparability.
CONCLUSION: Demand and supply-side strategies to improve maternal and newborn health care can be cost-effective, though the evidence is limited by the paucity of high quality studies and the use of disparate cost-effectiveness measures.
TRIAL REGISTRATION: PROSPERO_ CRD42012003255.
Psychological interventions delivered by non-specialist health workers are effective for the treatment of perinatal depression in low- and middle-income countries. In this systematic review, we describe the content and delivery of such interventions. Nine studies were identified. The interventions shared a number of key features, such as delivery provided within the context of routine maternal and child health care beginning in the antenatal period and extending postnatally; focus of the intervention beyond the mother to include the child and involving other family members; and attention to social problems and a focus on empowerment of women. All the interventions were adapted for contextual and cultural relevance; for example, in domains of language, metaphors and content. Although the competence and quality of non-specialist health workers delivered interventions was expected to be achieved through structured training and ongoing supervision, empirical evaluations of these were scarce. Scalability of these interventions also remains a challenge and needs further attention.
INTRODUCTION: Harmful gender norms and inequalities, including gender-based violence, are important structural barriers to effective HIV programming. We assess current evidence on what forms of gender-responsive intervention may enhance the effectiveness of basic HIV programmes and be cost-effective.
METHODS: Effective intervention models were identified from an existing evidence review ("what works for women"). Based on this, we conducted a systematic review of published and grey literature on the costs and cost-effectiveness of each intervention identified. Where possible, we compared incremental costs and effects.
RESULTS: Our effectiveness search identified 36 publications, reporting on the effectiveness of 22 HIV interventions with a gender focus. Of these, 11 types of interventions had a corresponding/comparable costing or cost-effectiveness study. The findings suggest that couple counselling for the prevention of vertical transmission; gender empowerment, community mobilization, and female condom promotion for female sex workers; expanded female condom distribution for the general population; and post-exposure HIV prophylaxis for rape survivors are cost-effective HIV interventions. Cash transfers for schoolgirls and school support for orphan girls may also be cost-effective in generalized epidemic settings.
CONCLUSIONS: There has been limited research to assess the cost-effectiveness of interventions that seek to address women's needs and transform harmful gender norms. Our review identified several promising, cost-effective interventions that merit consideration as critical enablers in HIV investment approaches, as well as highlight that broader gender and development interventions can have positive HIV impacts. By no means an exhaustive package, these represent a first set of interventions to be included in the investment framework.
BACKGROUND: Birth Preparedness and Complication Readiness (BPCR) interventions are widely promoted by governments and international agencies to reduce maternal and neonatal health risks in developing countries; however, their overall impact is uncertain, and little is known about how best to implement BPCR at a community level. Our primary aim was to evaluate the impact of BPCR interventions involving women, families and communities during the prenatal, postnatal and neonatal periods to reduce maternal and neonatal mortality in developing countries. We also examined intervention impact on a variety of intermediate outcomes important for maternal and child survival.
METHODS: We conducted a systematic review and meta-analysis of randomized trials of BPCR interventions in populations of pregnant women living in developing countries. To identify relevant studies, we searched the scientific literature in the Pubmed, Embase, Cochrane library, Reproductive health library, CINAHL and Popline databases. We also undertook manual searches of article bibliographies and web sites. Study inclusion was based on pre-specified criteria. We synthesised data by computing pooled relative risks (RR) using the Cochrane RevMan software.
RESULTS: Fourteen randomized studies (292 256 live births) met the inclusion criteria. Meta-analyses showed that exposure to BPCR interventions was associated with a statistically significant reduction of 18% in neonatal mortality risk (twelve studies, RR = 0.82; 95% CI: 0.74, 0.91) and a non-significant reduction of 28% in maternal mortality risk (seven studies, RR = 0.72; 95% CI: 0.46, 1.13). Results were highly heterogeneous (I2 = 76%, p < 0.001 and I2 = 72%, p = 0.002 for neonatal and maternal results, respectively). Subgroup analyses of studies in which at least 30% of targeted women participated in interventions showed a 24% significant reduction of neonatal mortality risk (nine studies, RR = 0.76; 95% CI: 0.69, 0.85) and a 53% significant reduction in maternal mortality risk (four studies, RR = 0.47; 95% CI: 0.26, 0.87).Pooled results revealed that BPCR interventions were also associated with increased likelihood of use of care in the event of newborn illness, clean cutting of the umbilical cord and initiation of breastfeeding in the first hour of life.
CONCLUSIONS: With adequate population coverage, BPCR interventions are effective in reducing maternal and neonatal mortality in low-resources settings.
INTRODUCTION: Preconception care includes any intervention to optimize a woman's health before pregnancy with the aim to improve maternal, newborn and child health (MNCH) outcomes. Preconception care bridges the gap in the continuum of care, and addresses pre-pregnancy health risks and health problems that could have negative maternal and fetal consequences. It therefore has potential to further reduce global maternal and child mortality and morbidity, especially in low-income countries where the highest burden of pregnancy-related deaths and disability occurs.
METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture.
RESULTS: Women who received preconception care in either a healthcare center or the community showed improved outcomes, such as smoking cessation; increased use of folic acid; breastfeeding; greater odds of obtaining antenatal care; and lower rates of neonatal mortality.
CONCLUSION: Preconception care is effective in improving pregnancy outcomes. Further studies are needed to evaluate consistency and magnitude of effect in different contexts; develop and assess new preconception interventions; and to establish guidelines for the provision of preconception care.
Universal Health Coverage is widely endorsed as the pivotal goal in global health, however substantial barriers to accessing health services for children in low and middle-income countries (LMIC) exist. Failure to access healthcare is an important contributor to child mortality in these settings. Barriers to access have been widely studied, however effective interventions to overcome barriers and increase access to services for children are less well documented.
METHODS:
We conducted a systematic review of effectiveness of interventions aimed at increasing access to health services for children aged 5 years and below in LMIC. Four databases (EMBASE, Global Health, MEDLINE, and PSYCINFO) were searched in January 2016. Studies were included if they evaluated interventions that aimed to increase: health care utilisation; immunisation uptake; and compliance with medication or referral. Randomised controlled trials and non-randomised controlled study designs were included in the review. A narrative approach was used to synthesise results.
RESULTS:
Fifty seven studies were included in the review. Approximately half of studies (49%) were conducted in sub-Saharan Africa. Most studies were randomised controlled trials (n = 44; 77%) with the remaining studies employing non-randomised designs. Very few studies were judged as high quality. Studies evaluated a diverse range of interventions and various outcomes. Supply side interventions included: delivery of services at or closer to home and service level improvements (eg. integration of services). Demand side interventions included: educational programmes, text messages, and financial or other incentives. Interventions that delivered services at or closer to home and text messages were in general associated with a significant improvement in relevant outcomes. A consistent pattern was not noted for the remaining studies.
CONCLUSIONS:
This review fills a gap in the literature by providing evidence of the range and effectiveness of interventions that can be used to increase access for children aged ≤5 years in LMIC. It highlights some intervention areas that seem to show encouraging trends including text message reminders and delivery of services at or close to home. However, given the methodological limitations found in existing studies, the results of this review must be interpreted with caution.
