Aga Khan University Hospital Nairobi

Abstract We herein present an overview of the upcoming 5 th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Sebastien Gagneux and colleagues analyze a global collection of Mycobacterium tuberculosis clinical isolates to classify sublineages by phylogeography. They find globally distributed ‘generalist’ and geographically restricted ‘specialist’ sublineages of lineage 4, indicating that different evolutionary strategies were adopted to succeed in various ecological niches. Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.

BACKGROUND: Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20-30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy. METHODS: We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations. RESULTS: Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence. CONCLUSIONS: WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.

In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Author(s): Bergman, Åke; Heindel, Jerrold J; Kasten, Tim; Kidd, Karen A; Jobling, Susan; Neira, Maria; Zoeller, R Thomas; Becher, Georg; Bjerregaard, Poul; Bornman, Riana; Brandt, Ingvar; Kortenkamp, Andreas; Muir, Derek; Drisse, Marie-Noël Brune; Ochieng, Roseline; Skakkebaek, Niels E; Byléhn, Agneta Sundén; Iguchi, Taisen; Toppari, Jorma; Woodruff, Tracey J

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. CONCLUSIONS: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

BACKGROUND: Pathology and laboratory medicine diagnostics and diagnostic imaging are crucial to achieving universal health coverage. We analysed Service Provision Assessments (SPAs) from ten low-income and middle-income countries to benchmark diagnostic availability. METHODS: Diagnostic availabilities were determined for Bangladesh, Haiti, Malawi, Namibia, Nepal, Kenya, Rwanda, Senegal, Tanzania, and Uganda, with multiple timepoints for Haiti, Kenya, Senegal, and Tanzania. A smaller set of diagnostics were included in the analysis for primary care facilities compared with those expected at hospitals, with 16 evaluated in total. Surveys spanned 2004-18, including 8512 surveyed facilities. Country-specific facility types were mapped to basic primary care, advanced primary care, or hospital tiers. We calculated percentages of facilities offering each diagnostic, accounting for facility weights, stratifying by tier, and for some analyses, region. The tier-level estimate of diagnostic availability was defined as the median of all diagnostic-specific availabilities at each tier, and country-level estimates were the median of all diagnostic-specific availabilities of each of the tiers. Associations of country-level diagnostic availability with country income as well as (within-country) region-level availability with region-specific population densities were determined by multivariable linear regression, controlling for appropriate covariates including tier. FINDINGS: Median availability of diagnostics was 19·1% in basic primary care facilities, 49·2% in advanced primary care facilities, and 68·4% in hospitals. Availability varied considerably between diagnostics, ranging from 1·2% (ultrasound) to 76·7% (malaria) in primary care (basic and advanced) and from 6·1% (CT scan) to 91·6% (malaria) in hospitals. Availability also varied between countries, from 14·9% (Bangladesh) to 89·6% (Namibia). Availability correlated positively with log(income) at both primary care tiers but not the hospital tier, and positively with region-specific population density at the basic primary care tier only. INTERPRETATION: Major gaps in diagnostic availability exist in many low-income and middle-income countries, particularly in primary care facilities. These results can serve as a benchmark to gauge progress towards implementing guidelines such as the WHO Essential Diagnostics List and Priority Medical Devices initiatives. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Many programmes on young people and HIV/AIDS prevention have focused on the in-school and channeled sexual and reproductive health messages through schools with limited activities for the young people's families. The assumption has been that parents in African families do not talk about sexual and reproductive health (SRH) with their children. These approach has had limited success because of failure to factor in the young person's family context, and the influence of parents. This paper explores parent-child communication about SRH in families, content, timing and reasons for their communication with their children aged 14-24 years in rural Tanzania. METHODS: This study employed an ethnographic research design. Data collection involved eight weeks of participant observation, 17 focus group discussions and 46 in-depth interviews conducted with young people aged 14-24 years and parents of young people in this age group. Thematic analysis was conducted with the aid of NVIVO 7 software. RESULTS: Parent-child communication about SRH happened in most families. The communication was mainly on same sex basis (mother-daughter and rarely father-son or father-daughter) and took the form of warnings, threats and physical discipline. Communication was triggered by seeing or hearing something a parent perceived negative and would not like their child to experience (such as a death attributable to HIV and unmarried young person's pregnancy). Although most young people were relaxed with their mothers than fathers, there is lack of trust as to what they can tell their parents for fear of punishment. Parents were limited as to what they could communicate about SRH because of lack of appropriate knowledge and cultural norms that restricted interactions between opposite sex. CONCLUSIONS: Due to the consequences of the HIV pandemic, parents are making attempts to communicate with their children about SRH. They are however, limited by cultural barriers, and lack of appropriate knowledge. With some skills training on communication and SRH, parents may be a natural avenue for channeling and reinforcing HIV/AIDS prevention messages to their children.

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla(NDM-1) carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

The introduction of ultrasound into medical student education is well underway in many locations around the world, but is still in its infancy or has yet to begin in others. Proper incorporation of ultrasound education into medical training requires planning and resources, both capital and human. In this article, we discuss the state of the art of ultrasound in medical education throughout the world, as well as various methodologies utilized to improve student education and to incorporate ultrasound into every facet of training. Experiences from various educational systems and available evidence regarding the impact of ultrasound education are summarized. Representing multiple societies and specialties throughout the world, we discuss established modern as well as novel education structures and different successful approaches.

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

In sub-Saharan Africa, the burden of typhoid fever, caused by Salmonella enterica serovar Typhi, remains largely unknown, in part because of a lack of blood or bone marrow culture facilities. We characterized a total of 323 S. Typhi isolates from outbreaks in Kenya over the period 1988 to 2008 for antimicrobial susceptibilities and phylogenetic relationships using single-nucleotide polymorphism (SNP) analysis. There was a dramatic increase in the number and percentage of multidrug-resistant (MDR) S. Typhi isolates over the study period. Overall, only 54 (16.7%) S. Typhi isolates were fully sensitive, while the majority, 195 (60.4%), were multiply resistant to most commonly available drugs-ampicillin, chloramphenicol, tetracycline, and cotrimoxazole; 74 (22.9%) isolates were resistant to a single antimicrobial, usually ampicillin, cotrimoxazole, or tetracycline. Resistance to these antibiotics was encoded on self-transferrable IncHI1 plasmids of the ST6 sequence type. Of the 94 representative S. Typhi isolates selected for genome-wide haplotype analysis, sensitive isolates fell into several phylogenetically different groups, whereas MDR isolates all belonged to a single haplotype, H58, associated with MDR and decreased ciprofloxacin susceptibility, which is also dominant in many parts of Southeast Asia. Derivatives of the same S. Typhi lineage, H58, are responsible for multidrug resistance in Kenya and parts of Southeast Asia, suggesting intercontinental spread of a single MDR clone. Given the emergence of this aggressive MDR haplotype, careful selection and monitoring of antibiotic usage will be required in Kenya, and potentially other regions of sub-Saharan Africa.

BACKGROUND: The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20-30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics - non-digestible oligosaccharides that stimulate growth of probiotic bacteria - have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy. METHODS: The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy. We performed a systematic review of randomized controlled trials of prebiotics, and reviewed the evidence about patient values and preferences, and resource requirements (up to January 2015, with an update on July 29, 2015). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Based on GRADE evidence to decision frameworks, the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants. Both recommendations are conditional and based on very low certainty of the evidence. We found no experimental or observational study of prebiotic supplementation in pregnant women or in breastfeeding mothers. Thus, the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding, at this time. CONCLUSIONS: WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy, term infants.

Point-of-care ultrasound (POCUS) has become a topical subject and can be applied in a variety of ways with differing outcomes. The cost of all diagnostic procedures including obstetric ultrasound examinations is a major factor in the developing world and POCUS is only useful if it can be equated to good outcomes at a lower cost than a routine obstetric examination. The aim of this study was to assess a number of processes including accuracy of images and reports generated by midwives, performance of a tablet-sized ultrasound scanner, training of midwives to complete ultrasounds, teleradiology solution transmissions of images via internet, review of images by a radiologist, communication between midwife and radiologist, use of this technique to identify high-risk patients and improvement of the education and teleradiology model components. The midwives had no previous experience in ultrasound. They were stationed in rural locations where POCUS was available for the first time. After scanning the patients, an interim report was generated by the midwives and sent electronically together with all images to the main hospital for validation. Unique software was used to send lossless images by mobile phone using a modem. Transmission times were short and quality of images transmitted was excellent. All reports were validated by two experienced radiologists in our department and returned to the centers using the same transmission software. The transmission times, quality of scans, quality of reports and other parameters were recorded and monitored. Analysis showed excellent correlation between provisional and validated reports. Reporting accuracy of scans performed by the midwives was 99.63%. Overall flow turnaround time (from patient presentation to validated report) was initially 35 min but reduced to 25 min. The unique mobile phone transmission was faultless and there was no degradation of image quality. We found excellent correlation between final outcomes of the pregnancies and diagnoses on the basis of reports generated by the midwives. Only 1 discrepancy was found in the midwives' reports. Scan results versus actual outcomes revealed 2 discrepancies in the 20 patients identified as high risk. In conclusion, we found that it is valuable to train midwives in POCUS to use an ultrasound tablet device and transmit images and reports via the internet to radiologists for review of accuracy. This focus on the identification of high-risk patients can be valuable in a remote healthcare facility.

BACKGROUND AND STUDY AIMS: Pill-induced esophageal injury is a common but under-reported problem. The purpose of this study was to explore the clinical and endoscopic features, and the outcome of pill-related esophageal injury. PATIENTS AND METHODS: Endoscopy records for the period from January 1997 to June 2003 were searched for reports of esophageal pathology. The records of patients with pill-induced esophageal injury were evaluated. RESULTS: A total of 92 patients with pill-induced esophageal injury were identified (33 men, 59 women; mean age 59, range 25-87). Common symptoms were odynophagia (n = 69, 75 %), chest pain (n = 55, 60 %), vomiting (n = 53, 58 %), dysphagia (n = 31, 33 %), and hematemesis (n = 14, 15 %). The endoscopic findings in the esophagus were: erythema in 76 patients (83 %), erosions in 53 patients (58 %), ulcers in 24 patients (26 %), seven of which were "kissing" ulcers, esophageal ulcer with bleeding in 17 patients (18 %), and esophageal strictures in seven patients (8 %). The causative pills were nonsteroidal anti-inflammatory drugs in 38 patients (41 %), tetracyclines in 20 patients (22 %), potassium chloride tablets in nine patients (10 %), alendronate in eight patients (9 %), and other drugs in 17 patients (18 %). Underlying diseases included diabetes in 60 patients (65 %), ischemic heart disease in 39 patients (42 %), and hypothyroidism in four patients (4 %). The mean hospital stay was 1.94 days; 14 patients (15 %) required injection of epinephrine 1 : 10,000 to control bleeding; and two patients died. CONCLUSIONS: Pill-induced injury may present as erosions, kissing ulcers, and multiple small areas of ulceration with bleeding, mainly in the middle third of the esophagus. Advanced age, female gender, diabetes, and ischemic heart disease were common associations. The majority of patients made an uneventful recovery.

BACKGROUND: Attention deficit hyperactivity disorder is the most common childhood neurobehavioral disorder with well documented adverse consequences in adolescence and adulthood, yet 60-80% of cases go undiagnosed. Routine screening is not practiced in most pediatric outpatient services and little information exists on factors associated with the condition in developing countries. METHODS: This was a questionnaire based cross-sectional survey whose primary objective was to determine prevalence of attention deficit hyperactivity disorder (ADHD) symptoms in children aged 6-12 years attending a tertiary care hospital Accidents and Emergency unit. Secondary objectives were to: (i) ascertain if physical injury and poor academic performance were associated with ADHD, (ii) compare diagnostic utility of parent-filled Vanderbilt Assessment Scale (VAS) against Statistical Manual of Mental Disorders-IV (DSM-IV) as the gold reference and (iii) establish if there exists an association between ADHD symptoms cluster and co-morbid conditions. RESULTS: Prevalence of cluster of symptoms consistent with ADHD was 6.3% (95% CI; 3.72-10.33) in 240 children studied. Those affected were more likely to repeat classes than the asymptomatic (OR 20.2; 95% CI 4.02-100.43). Additionally, 67% of the symptomatic had previously experienced burns and 37% post-traumatic open wounds. The odds of having an injury in the symptomatic was 2.9 (95% CI; 1.01-8.42) compared to the asymptomatic. Using DSM-IV as reference, VAS had a sensitivity of 66.7% (95%; CI 39.03-87.12) and specificity of 99.0% (95% CI; 96.1-99.2). Positive predictive value was 83.0% (95% CI; 50.4-97.3) and negative predictive value 98.0% (CI 95.1-99.1). Oppositional defiant disorder symptoms, anxiety, depression and conduct problems were not significantly associated with ADHD cluster of symptoms. CONCLUSION: The study found a relatively high prevalence of symptoms associated with ADHD. Symptomatic children experienced poor school performance. These findings support introduction of a policy on routine screening for ADHD in pediatric outpatient service. Positive history of injury and poor academic performance should trigger further evaluation for ADHD. Vanderbilt assessment scale is easier to administer than DSM-IV but has low sensitivity and high specificity that make it inappropriate for screening. It however provides a suitable alternative confirmatory test to determine who among clinically symptomatic patients requires referral to a psychiatrist.

BACKGROUND: Multiple-micronutrient deficiencies often coexist in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother. Substantive evidence regarding the effectiveness of multiple-micronutrient supplements (MMS) during pregnancy is not available. OBJECTIVES: To evaluate the benefits to mother and infant of multiple-micronutrient supplements in pregnancy and assess the risk of excess supplementation and potential adverse interactions between micronutrients. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 December 2005). SELECTION CRITERIA: All prospective randomised controlled trials evaluating micronutrient supplementation during pregnancy and its effects on the pregnancy outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Nine trials (15,378 women) are included. When compared with supplementation of two or less micronutrients or no supplementation or a placebo, multiple-micronutrient supplementation resulted in a statistically significant decrease in the number of low birthweight babies (relative risk (RR) 0.83; 95% confidence interval (CI) 0.76 to 0.91), small-for-gestational-age babies (RR 0.92; 95% CI 0.86 to 0.99) and in maternal anaemia (RR 0.61; CI 0.52 to 0.71). However, these differences lost statistical significance when multiple-micronutrient supplementation was compared with iron folic acid supplementation alone. No statistically significant differences were shown for the outcomes of preterm births and perinatal mortality in any of the comparisons. A number of prespecified clinically important outcomes could not be assessed due to insufficient or non-available data from the included trials. These include placental abruption, congenital anomalies including neural tube defects, premature rupture of membranes, pre-eclampsia, miscarriage, maternal mortality, neurodevelopmental delay, very preterm births, cost of supplementation, side-effects of supplements, maternal wellbeing or satisfaction and nutritional status of children. AUTHORS' CONCLUSIONS: The evidence provided in this review is insufficient to suggest replacement of iron and folate supplementation with a multiple-micronutrient supplement. A reduction in the number of low birthweight and small-for-gestational-age babies and maternal anaemia has been found with a multiple-micronutrient supplement against supplementation with two or less micronutrients or none or a placebo, but analyses revealed no added benefit of multiple-micronutrient supplements compared with iron folic acid supplementation. These results are limited by the small number of studies available. There is also insufficient evidence to identify adverse effects and to say that excess multiple-micronutrient supplementation during pregnancy is harmful to the mother or the fetus. Further research is needed to find out the beneficial maternal or fetal effects and to assess the risk of excess supplementation and potential adverse interactions between the micronutrients.

BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.