Lipidostasis involves lipid synthesis, quality control, membrane assembly as well as sequestration of excess lipids or degradation of damaged lipids. Proteostasis and lipidostasis are maintained by interconnected pathways within the cellular reticular network, which includes the ER and Ca2+ signaling. Importantly, lipidostasis is important in the maintenance of membranes and luminal environment that enable optimal protein processing. Accumulating evidence suggest that the loss of coordinate regulation of proteostasis and lipidostasis has a direct and negative impact on the health of the nervous system.Neurodegenerative diseases often have multifactorial causes and are progressive diseases. Some are inherited while others are acquired, and both vary greatly in onset and severity. Impaired endoplasmic reticulum (ER) proteostasis, involving Ca In response to cellular stress, cells most frequently turn to the coping mechanisms such as the unfolded protein response , are exposed to a wide variety of internal and external factors that induce cellular stress. These factors include gene variations that alter protein structure and function, inducers of oxidative stress, viral infection, environmental toxins, drugs, extremes in temperature, extremes in pH, inflammatory cytokines, lipotoxicity, Cade novo synthesis since lipoproteins are unable to cross the blood-brain barrier , are the core components of the ER protein quality control system  interacting protein 1 (SGIP1), a neuronal regulator of endocytosis, supporting a role for calnexin in the recycling of synaptic membrane proteins and maintaining synaptic homeostasis  and/or ryanodine receptor Ca2+ channels and relies on ER luminal Ca2+ sensors (STIM proteins), a plasma membrane Ca2+ channel (ORAI), and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA; Soboloff et al., 2+ to function, the sustained depletion of ER Ca2+ leads to the accumulation of misfolded proteins which subsequently activates UPR and other corrective strategies (Groenendyk et al., 2+ signaling is especially important as it controls additional processes that do not occur in other tissues, such as synaptic signaling and neurotransmission. Neuronal Ca2+ signaling also plays an important role in learning, memory and neuronal plasticity (Brini et al., 2+ homeostasis is commonly observed in severe neurodegenerative diseases (Mattson et al., 2+ homeostasis might allow neuronal cells to effectively maintain both proteostasis and lipidostasis, and thereby prevent neuronal pathology. Overload of Ca2+ in the ER is also harmful hence ensuring constant supply without regulated release could lead to disease. Increased abundance of STIM1 and ORAI1 in HEK cells resulted in reduced formation and secretion of Aβ peptides (Zeiger et al., 2+ in the ER might allow neuronal cells to effectively maintain both proteostasis and lipidostasis, and thereby prevent neuronal pathology.SOCE is initiated by CaThe BBB is a physical structure that separates the CNS from the rest of the body, and selectively controls the flow of molecules in and out of the brain. Dysfunction of the brain endothelial cells, essential component of the BBB, is involved in the pathology of many CNS disorders (Deane et al., 2+ homeostasis. A detailed knowledge of the regulatory and metabolic pathways involved in proteostasis and lipidostasis in cells that make up the nervous system, will provide better insights into the heterogeneity of neurological disorders and uncover new opportunities for therapeutic development.We propose that disrupted proteostasis and lipidostasis underlie many neurological disorders. Recent studies suggest that molecular chaperones are intimately involved in coordinating the cellular proteostasis and lipidostasis in the nervous system, including the cells that make up the BBB, by ensuring the quality of key proteins and lipid components of the membranes. Importantly, the activity of ER chaperones depends on ER CaAll authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.This work was supported by Canadian Institutes of Health Research grants MOP-15291, MOP-15415, MOP-53050 to MM; MOP-15291 and MOP-86750 to LA; and by a Natural Sciences and Engineering Research Council of Canada Discovery grant to LA.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The lack of commercially-available pediatric drug products and dosage forms is well-known. A group of clinicians and scientists with a common interest in pediatric drug development and medicines-use systems developed a practical framework for identifying a list of active pharmaceutical ingredients (APIs) with the greatest market potential for development to use in pediatric patients. Reliable and reproducible evidence-based drug formulations designed for use in pediatric patients are needed vitally, otherwise safe and consistent clinical practices and outcomes assessments will continue to be difficult to ascertain. Identification of a prioritized list of candidate APIs for oral formulation using the described algorithm provides a broader integrated clinical, scientific, regulatory, and market basis to allow for more reliable dosage forms and safer, effective medicines use in children of all ages. Group members derived a list of candidate API molecules by factoring in a number of pharmacotherapeutic, scientific, manufacturing, and regulatory variables into the selection algorithm that were absent in other rubrics. These additions will assist in identifying and categorizing prime API candidates suitable for oral formulation development. Moreover, the developed algorithm aids in prioritizing useful APIs with finished oral liquid dosage forms available from other countries with direct importation opportunities to North America and beyond. Childhood illnesses often require the use of medications under the premise of “off-label” use. In February 2014, the American Academy of Pediatrics (AAP) released a policy statement from its Committee on Drugs regarding the off-label use of drugs (medications) in children [The issue of “off-label” use of drugs in neonates, infants and children has prevailed for many decades. Federal legislation to address this issue was first proposed in 1998 and reauthorized in 2012. Since that time, various government agencies, including US-FDA and the National Institute of Child Health and Human Development (NICHD), have worked together to develop product labeling for pediatric patients for existing and new drug molecules coming to the market, if the drug has been or could be used in children.According to a recent study published in JAMA-Pediatrics, the legislation has produced 406 pediatric labeling changes; out of those only 24 include data on neonatal drug dosing . IdentifEffective delivery and viable manufacturing are essential to improve the clinical and commercial value of a pharmaceutical product. A reliable formulation will not only ensure optimal clinical outcomes, but also assure reproducibility in manufacturing and increased stability. This gap between commercial availability and clinical utility is bridged daily primarily by the efforts of compounding pharmacists, especially in the hospital setting, where APIs are extemporaneously compounded from adult solid oral dosage forms to provide medications that otherwise are not available to vulnerable pediatric populations, such as children with cardiovascular disease, cancer, cystic fibrosis, organ transplants, and other life threatening conditions.It has been noted that these compounding practices, despite best efforts and intentions, do not incorporate the necessary manufacturing controls to assure reproducible product potency, stability, and purity. Formal efforts to assist pharmacists and other practitioners to compound the best products possible include methods and guidelines found in the United States Pharmacopeia, US-FDA regulations and guidance documents, professional working groups, and elsewhere . WorkingLack of specifications required for component development by compounding pharmacies.No onsite testing of active ingredients and excipients for purity, potency, content and stability.No onsite specifications or testing of product containers and closures.Site-to-site variations in compounding procedures, equipment, and the degree of product handling/manipulation.Lack of environmental control, which might lead to unintentional contamination and generation of degradation products due to inconsistent exposure to light, temperature and processing controls.Lack of testing of finished products for purity, potency, content or stability.Stability data for establishing expiry dates of compounded products are derived from published data, where preparation methods likely vary from local methods, or are simply default expiry periods defined by regional pharmacy regulations and “best practices”.Published preparation methods provide only a portion of the information needed to consistently prepare a stable potent final product.Limited options available to mask bad-tasting active ingredients.etc., vary between sites and between prescription fills.The dose administration technologies used such as droppers, syringes, scoops, spoons, Weak regulatory oversight.When compared to Good Manufacturing Practices (GMPs), the manufacturing standards required by FDA for commercial products, there are multiple recognized deficiencies inherent in extemporaneous formulation-compounding suitable for pediatric patients, which include the following:Unfortunately, there are a number of barriers to the development of pediatric drug formulations under GMPs, not the least of which are economic in nature . The firIn the following sections, we present an algorithm that incorporates clinical and market-oriented variables in relation to existing APIs commonly used in pediatric practice that lack mass-produced formulations suitable for younger patients. Further, we overlay an array of scientific factors that support the selection of these APIs for mass-production, including Biopharmaceutical Classification System (BCS) and hot-melt extrusion (HME) as a flexible production technique for low solubility APIs.(1)Listed on BPCA priority document ;(2)Available in an injection (API is stable in solution for at least 18–24 months);(3)Not a federally controlled substance in Canada or the US ;(4)Potential applicability for oral adult market ;(5)Established indication for any age group in the official labeling of the API (immediate marketability through accelerated ANDA mechanism) and(6)Off-patent in both Canada and the US, and available in a pharmaceutical grade powder from a reputable supplier.Between September and December 2013, a North-American group of pharmacists, pediatricians, and pharmaceutical scientists formed Meds4Kids Research Collaborative, LTD (M4KRC). This group of clinicians and scientists with a common interest in pediatric drug development and medicines-use systems developed a framework for developing drugs in dosage forms suitable for use in pediatric patients . The groThe group reviewed the BPCA list and compared it to the list of 50 compounded non-sterile products (CNPs) prepared extemporaneously at St. Christopher’s Hospital for Children, all of which had scientific evidence for stability in a standardized concentration . The cliThe first tier included API molecules that met at least five of the six criteria;The second tier fulfilled four criteria;The third tier included API molecules not listed by name in the BPCA list but met all others except availability in the United Kingdom; andThe fourth tier included those available in the UK that could be imported readily for pharmacokinetic (PK), pharmacodynamics (PD), and/or pharmacogenomics (PG) studies in children.The original list was then segmented into four tiers:Several API molecules were removed from the list because of new market entry , availability of one oral liquid strength (levetiracetam), known pharmaco-chemical problems , or low use potential in children (pravastatin). The final, fourth tier API molecules identified based on criteria of potential viability as candidates ready for PK/PD/PG studies, are listed in The next step for the group was to apply scientific principles of drug delivery and formulation techniques to the clinically-derived list that would enhance the likelihood of the commercial availability of a mass-produced product.et al. in 1995 [in vivo bioequivalence study [The Biopharmaceutical Drug Classification System (BCS) was introduced by Amidon  in 1995 . Solubil in 1995 . If two ce study .To be able to adopt the BCS classification to paediatric drugs, some consideration have to be made: (a) what are the differences in drug metabolism and transport in the GI tract between adults and children in different age groups; (b) age-relevant changes in the physiology of the GI tract which can change the permeability or solubility classification (c) changes in permeability due to transporters in children. Such data could be developed in paediatric physiologic and population-based pharmacokinetic databases. The volume of fluid the drug is taken and paediatric dose strength will also be different in a paediatric BCS classification compared to the current BCS .i.e., the end product of HME) offer greater thermodynamic stability compared to products prepared by alternative processes such as spray drying, solvent evaporation and other hot melt methods.If these considerations are included, a BCS approach can be used in the development of pediatric dosage forms if a suitable strength exists. The knowledge of the BCS class helps pharmaceutical companies in drug development. For example, a class I drug might need much less formulation work compared to a class II drug where solubility must be improved . The BCSConcerning economics, HME can be used to produce small  lots of a formulated product. The final production sizes of these small lot sizes, denoted by contract manufacturers as research and development batches or Clinical Trial Manufacturing (CTM) batches, are within the range of 10,000 to 50,000 units. The flexibility to produce small batches using HME process may provide a sufficient commercial market for a given pediatric population for a year or more. Compared to commercial tableting or capsule manufacturing approaches, which incorporate processes such as milling, mixing, spray drying, pre-compression, compression, tableting/encapsulation, HME is a much more economical process with reduced production time, fewer processing steps, and is suitable for continuous operation .With regards to formulation attributes and taste masking, HME can produce final drug products with sustained, modified, and targeted release properties, and can also coat poor tasting products. So, the finished product can then be milled in a single step to form powders suitable for incorporation into child-friendly dosage forms such as mini-tablets, orally disintegrating tabs, and liquid suspensions. The output of the extrusion process, known as an extrudate, can be optimized to protect the API against changing pH conditions, light, heat, and moisture levels, thus confer good stability properties to the final formulation. While characterization of the pediatric gut awaits a more complete description, HME provides a useful tool for poorly soluble, highly permeable APIs ,23,24.An example of an API suitable for HME process is metoprolol succinate. Metoprolol is one of the most commonly used beta-blocking agents used in children from infancy through adolescence and into adulthood to treat a variety of cardiovascular conditions as an antihypertensive and heart rate modulator . MetoproMetoprolol is an excellent candidate for HME as this process can increase in the dissolution rate of the drug for deriving clinically-appropriate concentrations, hence ease of reconstitution for a given strength. The process will also deliver good content uniformity of the drug and minimize risk for segregation. Overall, the manufacturing process is very simple, and involves only blending and processing using tight process controls. The HME process allows for in-process monitoring of the product quality using process analytical tools  Spectroscopy). Moreover, there is no need for scaling up and down for different batch sizes.In summary, the M4KRC-derived list of candidate API molecules has been derived from selection matrix that factored in a number of pharmacotherapy, scientific, production, and regulatory variables absent in other rubrics. These additions guided the group to identify the prime API candidates suitable for children in mass produced dosage forms. Further, the market-focused algorithm helped to prioritize useful APIs, and to facilitate clinical studies with finished oral liquid dosage forms available from other countries with direct importation potential to North America. Class II molecules are best suited for formulation using HME technologies Incorporating BCS classification and HME application into the final selection of candidate APIs, the following class II molecules are suggested for formulation and development: metoprolol, clopidogrel, spironolactone, and nifedipine. The assessment of these other variables, in addition to clinical and market parameters, is very important to increase the likelihood that a pharmaceutical manufacturer would successfully mass-produce and market these oral liquid dosage forms for children ,27.Successful public private partnerships have moved the science of pediatric clinical pharmacology forward. However, without reliable and reproducible evidence-based drug formulations designed for use in pediatric patients, safe and consistent clinical practices and outcomes assessments will continue to be difficult to ascertain. Identification and prioritization of prime candidate APIs with the algorithm has provided a broader integrated clinical, scientific, regulatory, and market basis, allowing for more reliable oral dosage forms for safe and effective medicines use in children of all ages.The M4KRC group derived a list of candidate API molecules by factoring in a number of these pharmacotherapeutic, scientific, manufacturing, and regulatory variables into the selection algorithm that were absent in other rubrics. These additions have assisted in identifying and categorizing prime API candidates suitable for oral formulation development. Finally, the developed algorithm aids in prioritizing useful APIs with finished oral liquid dosage forms available from other countries with direct importation opportunities to North America and beyond. These finished and standardized oral dosage forms await further clinical testing.


Across the 10 countries, 77% of 921,918 women left with a contraceptive method after receiving abortion care. While contraceptive uptake was high among all age groups, adolescents ages 15–19 were less likely to choose a method than women 25 years or older. Across the 10 countries, 77% of 921,918 women left with a contraceptive method after receiving abortion care. While contraceptive uptake was high among all age groups, adolescents ages 15–19 were less likely to choose a method than women 25 years or older. Unintended pregnancy disproportionately affects young women and adolescents in developing countries. The abortion care setting offers a unique opportunity for adolescents and young women to access a full range of contraceptive services. This evaluation assesses the factors that influence contraceptive uptake among adolescents and young women seeking abortion care in health facilities.Following provider training, we analyzed client log book data from 921,918 abortion care cases in 4,881 health facilities in 10 countries from July 2011 through June 2015. Log book data included client characteristics such as age, pregnancy gestation, type of service provided, and contraceptive method provision. Health facility characteristics were obtained through administration of a site baseline form prior to initiation of programmatic support by Ipas, an international NGO. Programmatic support included integration of postabortion contraceptive services with abortion care, improvements in commodities logistics, health worker training, upgraded recordkeeping, and post-training follow-up with providers and sites to solve problems and improve performance. We analyzed abortion cases by 3 age categories, ≤19 years, 20–24 years, and ≥25 years, and conducted unadjusted and adjusted analyses for the primary outcomes of interest: receipt of a contraceptive method at the time of care; type of contraceptive method selected; and the client, clinical care, and facility characteristics associated with contraceptive uptake.Overall, 77% of women left the facility with a contraceptive method. The majority (84%) of contraceptive acceptors selected a short-acting method, especially oral contraceptives. In the adjusted model, women ≤19 were less likely to choose a method than women 25 years or older . Adolescents and young women were also significantly less likely to choose a long-acting, reversible contraceptive than those ages 25 or older . Women treated by an Ipas-trained provider were significantly more likely to select postabortion contraception than women treated by non-Ipas-trained providers .Programmatic support to health systems, including provider training in contraceptive counseling and provision, was associated with women's higher acceptance of postabortion contraception. However, gaps remained for young women, especially adolescents, who were significantly less likely than older women to accept postabortion contraception. Health systems and facilities should pay increased attention to meeting the contraceptive needs of young women and adolescents. Between 2010 and 2014, almost 25.1 million unsafe abortions occurred globally each year, most in developing countries.Unsafe abortion disproportionately affects adolescents and young women in developing countries.Underlying these findings are low and/or inconsistent use of contraception among adolescents and young women leading to unintended pregnancies. An estimated 38 million adolescents 15–19 years of age in developing countries are married or unmarried and sexually active and do not wish to have a child within the next 2 years, yet only 40% are using a modern method of contraception.,Abortion care services include provision of induced abortion as well as treatment of incomplete abortion resulting from complications of unsafe abortion or spontaneous abortion; the latter is referred to as postabortion care (PAC). Abortion care services also include postabortion contraceptive counseling and method provision. The terms “induced abortion” and “PAC treatment” are used in this article if a particular setting or finding refers to one or the other type of service. The abortion care setting offers a unique opportunity for adolescents and women to access contraceptive information and methods, if they wish to use one. They are present in a health facility and may not return for subsequent care. Ovulation returns quickly after an abortion and contraception can enable women to avert an unintended pregnancy.The abortion care setting offers a unique opportunity for adolescents and women to access contraceptive information and methods, if they wish to use one.––Multiple studies have demonstrated the effectiveness of interventions to provide contraceptive counseling and methods to abortion clients prior to discharge from health facilities.,,Only a few studies have assessed the client, clinical care, and institutional factors that affect women's acceptance of postabortion contraception.This article examines the factors associated with postabortion contraceptive uptake among young women and adolescents.We report results of programmatic support to health facilities in 10 countries that aimed to improve provision of contraception to women seeking induced abortion or PAC treatment. Support was provided by Ipas, an international NGO, and its network partner, the Ipas Development Foundation, a local NGO in India, in collaboration with ministries of health and other local entities. The countries in our analysis were Ghana, Nigeria, Sierra Leone, Uganda, and Zambia in sub-Saharan Africa, and Bangladesh, India, Myanmar, Nepal, and Pakistan in Asia.Objectives of this article are to: (1) describe an intervention aimed at improving postabortion contraceptive counseling and method provision; (2) assess the factors that influence contraceptive uptake among clients at the time of abortion care, by age; and (3) recommend steps to improve the quality of postabortion contraceptive services in health facilities for young women and adolescents.The type of abortion care provided in facilities varied by the legal, policy, and cultural contexts of the 10 countries. In Nepal, for example, most clients sought an induced abortion, while in Pakistan, Sierra Leone, and Uganda, most women sought PAC treatment of incomplete abortion. In other countries, such as Bangladesh and India, both induced abortion and PAC cases were included in the analysis. Postabortion contraceptive counseling and methods were incorporated into both types of abortion care.Development of technical standards, guidelines, and protocols for provision of care to all women, regardless of age, marital status, or other barriers, based on World Health Organization (WHO) guidancePhysical upgrades in facilities to facilitate contraceptive availability at the time of abortion careImprovements in logistics processes for commoditiesTraining-of-trainers and in-service training of physicians, midwives, clinical officers, and other cadres in clinical care, including contraceptive counseling and provisionValues-clarification training for service providers and staff to reduce stigma toward women and adolescents who need reproductive health servicesProvision of contraceptive counseling and methods at the same location and time as abortion careSeparate, specialized training of providers in counseling and provision of available LARC methods in selected countries, including on medical eligibility, method side effects, counseling approaches at the time of abortion care and afterward, and method insertionImprovements in abortion case recordkeeping and regular use of data to monitor service availability and qualityRoutine follow-up of facilities and trained providers to identify and resolve barriers to care.Postabortion contraceptive support to health systems and facilities fell into 9 domains:In most countries, providers received periodic in-person visits and phone check-ins from Ipas clinical mentors, program staff, and/or health systems supervisors following training, along with a review of their individual summary monitoring data, which underscored contraception as a routine component of comprehensive care.Clinical training courses for providers usually lasted 5 days, but in some countries were held for 10–12 days. The courses were led by clinical master trainers who had previously completed training-of-trainers courses in abortion care. Training participants included obstetrics and gynecology specialists, general physicians, midwives, clinical officers, nurses, and other cadres, depending on the country setting. Follow-up contacts with trained providers usually occurred within 3–4 weeks post-training, either by phone or in-person at their facility. During the check-ins, the mentor/program support specialist assessed the newly trained provider, identified and resolved clinical or programmatic concerns, reviewed log book records (if in-person), and agreed to a follow-up contact time. Subsequent support visits from the program support team member also included review of individualized performance data with the provider. Frequently addressed issues included stock-outs of commodities, need for additional clinical practice, reinforcement of infection prevention practices, insufficient support of upgraded care by facility management, and low caseloads. Examples of strategies to resolve these problems included making contacts with supply chain officials at the facility or higher level; discussions with department heads, facility administrators, and district supervisors on the importance of the service; use of clinical practice job aids; and expanded outreach to inform the community about the service.In-person support to trained providers occurred at their health facility, as noted, but often included interactions and refresher sessions with providers who did not participate in the training but were part of the larger team of caregivers. Technical assistance to and monitoring of health facilities was also carried out, recognizing that providers require a supportive environment in which to practice.,While programmatic support in all countries encompassed core training curricula, standard log book formats, and monitoring tools, each program was designed and implemented to reflect local service delivery contexts, including compliance with Ministry of Health standards and guidelines. Women selected from the abortion methods available in the facility and for which they were medically eligible. Contraceptive commodities included only those methods currently approved and available in each country's health system. The timing of contraceptive counseling, prior to or after the abortion procedure, also varied by the client's clinical condition, type of contraceptive methods available in the setting, and other factors. Ipas does not recommend the inclusion of clients' marital status in abortion care log books since this information can be used to deny women care. However, the Ministries of Health of some countries required this information to be recorded. Client exit interviews were conducted annually in selected facilities in many of the countries to gather women's perspectives on the quality of information that providers shared during their visit, provision of women's preferred contraceptive methods, and source of referral to the facility. Despite these programmatic differences between countries and changes over time, implementation of the core Ipas training curriculum for development of providers' clinical and counseling skills was relatively standardized but updated as new, published evidence became available.Programmatic support for reaching young women and adolescents was carried out in all countries but varied by the specific context. Program components included assessments of existing youth-focused services in health facilities to assist in program planning, upgrades to sites to improve client privacy and confidentiality, provider training on clinical and counseling issues relevant to young clients, sensitization of facility managers and health officials to the needs of young women, and an array of community outreach activities for young women and adolescents. Counseling training focused on a woman-centered approach to identify and address clients' individual needs and preferences in preventing pregnancy and providing voluntary, informed consent. Trainers in India, Nepal, Nigeria, and Zambia also received in-depth skills training on rights-based approaches to contraception. Some programs began as pilot projects in a few health facilities and were subsequently expanded in several countries to broader health systems efforts. Ipas resources such as a training toolkit for abortion care for young women helped guide the design and implementation of programmatic support.Data were collected from abortion care log books in public- and private-sector facilities in the 10 countries. Intervention sites were selected by Ipas and collaborating partners, based on geographic priorities for coverage, Ministry of Health strategies, weak reproductive health indicators, potential for integration of a new/upgraded service, and other criteria. Individual case information on abortion care clients was recorded by providers over a 4-year period from July 2011 through June 2015, and collected by Ipas during monitoring visits to the sites; frequency of the visits varied by country but usually occurred monthly, quarterly, or every 6 months. Collection of monitoring data began after provider training due to the poor quality of log books prior to start-up of the intervention. Client names, their record numbers, or other identifying data were not collected.Abortion care log books were part of the routine health recordkeeping system and included client characteristics such as age, pregnancy gestation (in weeks), and type of service ; the treatment regimen such as the method used for the abortion , pain management, and contraceptive method provided at the time of care, by method type; adverse events; and provider signature or identification. While Ipas recommends that providers indicate women's desire for contraception, in addition to whether they received a method at the time of care, most health systems did not include this information in log books. Many abortion care providers had participated in an Ipas-supported in-service clinical training and were assigned a unique provider ID. During training, providers were instructed on how to complete the log book and asked to add their signature to cases they treated. Log book cases with a signed entry were assumed to have been attended by a provider who had participated in an Ipas-supported training. Information about clients treated in the facility by providers not trained by Ipas were also included in the dataset. Information about facility type, level, and other characteristics was obtained on a site baseline form completed by Ipas before initiation of programmatic support.All log book and site data were entered into Ipas's programmatic monitoring database and cleaned and analyzed using Stata version 11.0. The protocol was approved by the Allendale Institutional Review Board (US).We analyzed abortion cases by 3 age categories: ≤19 years, 20–24 years, and ≥25 years. Primary outcomes of interest included: receipt of a contraceptive method at the time of care; type of contraceptive method selected; and the client, clinical care, and facility characteristics associated with contraceptive uptake within and across each age category.Rates of missing data on age were low, 2% overall; these cases were removed from the dataset. We treated data conservatively, classifying those cases without contraceptive information in the log books as not having received a method. The abortion care delivery setting for each client age category was described by region, health sector (public or private facility), level of the facility , and whether the health care worker who offered the abortion participated in an Ipas-supported training. Additional client data included gestational age, type of abortion (induced abortion or PAC treatment), and the abortion method used.We conducted unadjusted and adjusted analyses for the outcomes of interest. For each age group, we describe overall contraceptive uptake; type of contraceptive method such as condoms, oral contraceptives, or intrauterine devices (IUDs); and method category (short-acting or LARC). Short-acting methods consisted of condoms, oral contraceptives, and injectables. LARC methods were implants and IUDs. The percentage of clients receiving a sterilization procedure was low across all age groups (7%) and not included in our analysis. Percentages are reported for non-missing data.Bivariate analysis of overall contraceptive uptake and by method category was carried out with facility and clinical characteristics. Chi-square tests were applied to determine statistical significance. Adjusted analysis was conducted using logistic regression, controlling for facility clustering and country-level variations. We conducted tests of collinearity and model fit to select the most parsimonious model. Significance levels were set at 0.05.Findings are based on 921,918 abortion cases treated in 4,881 health facilities: India ; Nigeria (464); Nepal (383); Ghana (278); Pakistan (200); Bangladesh (175); Zambia (104); Uganda (48); Myanmar (37); and Sierra Leone (14). A large majority of cases, 67%, occurred in sites in Asia . ClientsThe women served in Africa were younger than those in Asia. Almost two-thirds (64%) of women 19 years and under were from Africa while 36% were from Asia. Most (95%) women sought care during the first trimester of pregnancy, but 9% of clients age 19 or younger obtained care at 13 weeks of pregnancy or later compared with 5% each of women ages 20–24 and those ages 25 and older. In addition, a higher percentage of adolescents ages 15–19 received PAC treatment (45%) than women ages 25 or older (40%). Service delivery characteristics varied little by age. Most (89%) clients were seen in primary- or secondary-level public facilities, and Ipas-trained providers attended 60% of the clients. Almost three-quarters of cases were performed with vacuum aspiration (MVA or EVA).Overall contraceptive uptake was high for all age categories in the unadjusted analysis, with 77% of women leaving the health facility with a contraceptive method. Highest uptake was among women ≥25 years of age (78%), and lowest among women under age 20 (71%) .77% of women left the health facility with a contraceptive method.Of those clients who chose contraception, 84% received a short-acting method. This did not vary markedly across age groups: a slightly higher percentage of women 25 and older (18%) selected a LARC method compared with those under 25 (14%) . The speOral contraceptive pills were the most commonly selected method for each age group, followed by condoms and injectables.Factors positively associated with postabortion contraceptive uptake among women of all ages included obtaining services in a private facility, receiving care from a provider trained as part of an Ipas-supported intervention, being ages 25 years or older, first-trimester gestational age, seeking an induced abortion (compared with receiving PAC services), and choosing a medical abortion. In the adjusted analysis, facility sector was not significantly associated with postabortion contraceptive acceptance, and women under age 20 were less likely to choose a contraceptive method than women 25 years or older  . All othWomen under age 20 were less likely to choose a method than women 25 years or older.In the adjusted model, acceptance of a LARC method was more likely if a client received care in a public facility, was 25 years of age or older, sought an induced abortion (compared with those who sought PAC services), or had a vacuum aspiration abortion (MVA or EVA) compared with medical abortion . AdolescAdolescents and young women were significantly less likely to select a LARC than women 25 years or older.Overall, in the nearly 1,000,000 abortion cases treated in 10 countries of sub-Saharan Africa and Asia, we found high rates of postabortion contraception acceptance among the clients, but adolescents were significantly less likely than women 20 years of age or older to choose to use contraception. Women 15–19 years old and those 20–24 years old had similar uptake of LARC methods, and women 25 or older had significantly higher odds of receiving a LARC method than these younger women. Women cared for by a provider who participated in an Ipas-supported training were significantly more likely to choose a postabortion contraceptive method, but differences by age remained. While contraceptive uptake was high in our analysis , our findings underscore that young women, especially adolescents, may not have access to the full range of contraceptive methods for which they are medically eligible,Young women, especially adolescents, may not have access to the full range of contraceptive methods for which they are medically eligible.,Abortion care clients of providers who participated in an Ipas-supported training were significantly more likely to select a postabortion contraceptive method, but no differences in LARC acceptance by clients of Ipas-trained versus non-Ipas-trained providers were observed. While we do not have data on providers who did not directly participate in the trainings or who did not receive post-training follow-up, non-Ipas-trained providers may not have prioritized postabortion contraception, or they may have perceived their counseling or clinical skills as insufficient. Another possibility is that they may have held misconceptions about contraceptive methods during the postabortion period. For example, non-Ipas-trained providers may have been unaware that women who select medical abortion and also wish to use a hormonal method of contraception  may start the method on day 1 of the abortion medication regimen, per WHO guidelines.Women with gestations of 13 weeks or more were significantly less likely to choose a contraceptive method than women presenting at 12 weeks or less, a troubling finding since adolescents and young women were disproportionately represented among clients seeking care in later stages of pregnancy.Women with gestations of 13 weeks or more were significantly less likely to choose a contraceptive method than women presenting at 12 weeks or less.,Abortion care clients in later pregnancy gestations are more likely to obtain services in hospital settings than primary-level sites. Hospital environments present special challenges for postabortion contraception, with several studies reporting that women obtaining abortion care in hospitals are less likely to receive any contraception than those in primary health centers or clinics.However, in our study, clients who received contraception were more likely to obtain a LARC method in public facilities than private sites. Larger, public hospitals may be more likely to have had trained and experienced providers with access to LARC supplies and commodities than smaller, private facilities; many primary-level providers who participated in training were new to abortion care and may not have had experience in LARC provision. These findings underscore the importance of access to an array of contraceptive methods and a trained provider across facility sectors and levels for all women seeking abortion care.,,PAC clients include women who require treatment of abortion complications from induced abortions obtained elsewhere; women who have used medical abortion outside of a health facility and present with bleeding; those presenting for miscarriage management of wanted pregnancies and who wish to have another pregnancy soon; and other miscarriage patients who want to delay a subsequent pregnancy. In the adjusted model, women seeking induced abortion were much more likely to choose a contraceptive method than those obtaining PAC services. This finding could partly be due to provider bias if they assumed that most PAC clients had had a miscarriage and wanted to become pregnant again soon. In addition, providers treating patients with severe abortion complications such as septic abortion and shock often prioritize immediate medical needs. While a significant amount of research has been conducted on the uptake of postabortion contraception by PAC clients, a better understanding of women's needs and preferences at the time of care and competing provider constraints could contribute to improved quality.These diverse circumstances underscore the importance of counseling that incorporates clients' fertility preferences and offers adolescents and women their choice of contraceptive methods. Induced abortion clients who accepted contraception were highly significantly more likely to choose a LARC method than PAC clients accepting contraception. Our data do not allow us to determine precise reasons for this finding, but they suggest that PAC clients who want to use contraception may prefer short-acting methods until they recover from the incomplete abortion and are ready to make decisions about pregnancy. Furthermore, PAC clients with septic abortion are not medically eligible for IUD insertion at the time of the abortion, which may also contribute to the finding.,Differences in contraceptive uptake by abortion technology have also been found in other studies using monitoring data from Ipas-supported facilities, with similar or higher acceptance of any contraceptive method with medical abortion compared with MVA/EVA but lower LARC uptake.,Provision of LARC methods to adolescents has received increasing attention in recent years. In the United States, both the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists have issued statements on the safety and appropriateness of IUDs and implants for adolescents who desire these methods.,The Ipas training curriculum, clinical guidelines, and post-training technical support to providers and facilities are consistent with WHO's guidance on abortion care and postabortion contraception and more recent published evidence. These state that all contraceptive methods may be provided to women at the time of an uncomplicated first- or second-trimester abortion procedure performed with vacuum aspiration or medical abortion, according to their medical eligibility.,The provision of LARCs to adolescents, especially those who have not given birth, remains a relatively new concept in many countries in Africa, Asia, and Latin America.Our analysis had the advantages of including a large number of abortion care cases in a variety of service delivery environments in 10 countries. Recordkeeping on client information was of good quality with generally low rates of missing data, and data were available on individual clients. Literature focused specifically on increasing use of LARCs among adolescents in developing countries is quite limited.Limitations of our analysis and findings include the fact that data were not available before Ipas began programmatic support due to the initial poor quality of abortion care log books in most settings. Resource limitations did not permit data collection in comparison facilities that had not received specialized abortion training for providers nor site upgrades. Furthermore, log book data were recorded by providers themselves and therefore had the potential for error or underreporting, especially given the stigma associated with abortion care.Abortion care log book entries rarely include women's fertility desires, and even if noted, the data are unreliable. Women's preferences about if and when they wish to become pregnant again can be collected through other methodologies such as client exit interviews or observation of provider-client interactions during service delivery. Ideally, log book data on contraceptive uptake would be paired with clients' responses on the quality of services, contraceptive method preferences, appropriateness of information offered, and their fertility plans.Our data did not include an important group, women who use medical abortion on their own or with the help of individuals outside a clinical setting. Very little is known of their postabortion contraceptive patterns; the methodological challenges of reaching these women are daunting.–Although this study found relatively high rates of postabortion contraceptive acceptance, gaps remain, especially for adolescents. Any programmatic recommendations to improve postabortion contraception as part of facility-based abortion care for adolescents and young women must maximize the available evidence from other sexual and reproductive health interventions. “Youth-friendly” sexual and reproductive health services are common but often suffer from fragmentation and spotty implementation.Although postabortion contraceptive uptake was relatively high among the population studied, gaps remain, especially for adolescents.Update policies and protocols to eliminate barriers such as requirements that women and adolescents have to be married or have parental or spousal consent for contraceptive services, and ensure that hormonal methods are indicated as appropriate on the same day of medical abortionImplement provision of a wide choice of contraceptive methods for adolescents and young women to select from, including LARC methodsEnsure that contraceptive methods are available in all locations within a facility where induced abortion services and PAC are offeredTrain providers, clinic managers, and facility staff to improve counseling and client interactions, upgrade clinical skills on postabortion contraceptive methods, and implement efforts to reduce stigmaConsider post-training follow-up support of providers and facilities to reinforce new skills and resolve obstacles to careUpgrade facilities to ensure privacy, especially for adolescents, and ensure confidentiality of client interactions and recordsReduce or eliminate out-of-pocket costs of all contraceptive methods, especially for adolescent clientsInclude frequent client and community interviews to determine the preferences of young women and adolescents, and assess the quality of postabortion contraceptive care they receiveOur recommendations to improve postabortion contraception for adolescents and young people receiving health facility care include the following:While our study finds that important progress has been achieved in improving postabortion contraceptive care in Ipas-supported facilities, many health facilities in developing countries still do not offer comprehensive services. This gap is especially tragic for young women and adolescents who are most vulnerable to unintended pregnancy and unsafe abortion. Increased contraceptive use, including after abortion, is critical to their improved sexual and reproductive health and well-being.


This review examined 83 articles using neuroimaging modalities to investigate the neural correlates underlying static and dynamic human balance control, with aims to support future mobile neuroimaging research in the balance control domain. Furthermore, this review analyzed the mobility of the neuroimaging hardware and research paradigms as well as the analytical methodology to identify and remove movement artifact in the acquired brain signal. We found that the majority of static balance control tasks utilized mechanical perturbations to invoke feet-in-place responses (27 out of 38 studies), while cognitive dual-task conditions were commonly used to challenge balance in dynamic balance control tasks (20 out of 32 studies). While frequency analysis and event related potential characteristics supported enhanced brain activation during static balance control, that in dynamic balance control studies was supported by spatial and frequency analysis. Twenty-three of the 50 studies utilizing EEG utilized independent component analysis to remove movement artifacts from the acquired brain signals. Lastly, only eight studies used truly mobile neuroimaging hardware systems. This review provides evidence to support an increase in brain activation in balance control tasks, regardless of mechanical, cognitive, or sensory challenges. Furthermore, the current body of literature demonstrates the use of advanced signal processing methodologies to analyze brain activity during movement. However, the static nature of neuroimaging hardware and conventional balance control paradigms prevent full mobility and limit our knowledge of neural mechanisms underlying balance control. Approximately 30% of adults aged 65 years or older experience one or more falls annually, a third of which result in a moderate to severe injury  and foot placement from step to step , single-photon emission computed tomography (SPECT), and positron emission tomography (PET), leading to the identification of a supraspinal locomotor network  have allowed for acquisition of brain activity during upright stance and with some degree of subject mobility. Using fNIRS, differential activation of the sensorimotor cortices, supplementary motor areas, and prefrontal cortex have been observed during gait initiation  and steady-state walking  1: What are the spatial and temporal dynamics of brain activity when mechanical perturbations, cognitive tasks, and modulation of sensory inputs challenge static balance control?Evaluation of human balance control uses a variety of paradigms to challenge motor, cognitive, and sensory components of balance  2: What are the spatial and temporal dynamics of brain activity when mechanical challenges, cognitive tasks, and modulation of sensory inputs test dynamic balance control?While brain activity during walking has been recently reviewed  3: What methods have been used to identify and remove movement artifact from brain signals acquired during balance control tasks?Understanding the neural underpinnings of human balance control is an essential next step in addressing slip and fall risks in the general population. While spatial brain activation during steady-state walking has been reviewed by Hamacher et al. , to our Neuroimaging modalities are sensitive to head and body movement, which introduces movement artifact into the acquired brain signal. The characteristics of movement artifact are related to both the neuroimaging modality and the research paradigm, with minimal artifact when subjects are completely still. However, it is reasonable to expect sudden movements to maintain static balance control or rhythmic walking during dynamic balance control to introduce variable movement artifact. In order to identify neural mechanisms involved in balance control, movement artifact must be correctly identified and removed. Therefore, it is important to identify the artifact removal methods used in static and dynamic balance control studies.This systematic review utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses  IEEExplore and (2) Compendex, both to provide an engineering perspective, (3) ACM Library, to provide a computing and signal processing perspective, (4) PubMed, to provide a clinical perspective, and (5) Web of Science, to provide a cross disciplinary perspective. The database search included search terms found in the article title, abstracts, and keywords. The results from each database were added to Mendeley and checked for any duplicate results.Search inclusion and exclusion were based on the characteristics and goals of the balance control tasks and the use and application of neuroimaging modalities. Literature included in this review aimed to investigate human balance control. Studies were included if they incorporated balance challenges . Only articles in English were considered. We excluded literature from this review when either the balance control paradigm or the neuroimaging paradigm did not align with the goals of this study. Studies that evaluate the effects of a therapy or intervention, including drug or hormone trials, rehabilitation, training, robotic-assisted walking, or development (in children and adolescents) were excluded. Studies that did not include active subject movement, such as those using motor imagery, brain volume correlation, or passive walking paradigms were excluded. Passive walking paradigms are those where the experimenter or specially designed equipment assisted the subject in moving their legs  brain activity during static balance control tasks and (2) brain activity during dynamic balance control tasks. Studies in both groups that included methodologies for movement artifact identification and removal were pooled to address research question three. The subsequent data were then extracted from each article: Authors, year of publication, static or dynamic balance task, type of balance challenge , treadmill or overground walking (for dynamic studies), subject characteristics, modality of brain imaging, and brain activity . As well as extraction of pre-processing, spatial filtering, and artifact removal methods.Literature searches included relevant studies published on or before September 1, 2016, and resulted in 1,462 results, with 1,444 studies remaining after duplicate removal. After initial screening of the abstract, 117 studies were evaluated for inclusion in the static balance control or dynamic balance control category. The full-text articles for each of the studies was reviewed, a total of 38 studies were eligible for inclusion in the static balance control group and 47 for the dynamic group, with two studies including both static and dynamic balance control tasks. All 83 studies included in the static and dynamic groups were evaluated for inclusion in addressing research question three regarding identification and removal of movement artifact. Figure 4, respectively.This review covered 38 studies investigating neural correlates of static balance control. The balance challenge paradigms include mechanical perturbations, cognitive, dual-task paradigms and sensory degradation, or impairment, which can be found in Tables Twenty-seven studies used mechanical perturbations to elicit a balance control response, 15 of which focused on the evoked cortical potentials , which is known to be evoked when an error is committed and to originate in the anterior cingulate cortex (ACC). Marlin et al.  investigAlthough there has been research in the early cortical response following perturbations, the role of later potentials is still unclear. In the auditory domain, for example, the event related potential (ERP) component around 200 ms post-stimulus (P200), represents a shift in attention toward the initial audio cue. Quant et al.  used horThirteen EEG studies performed frequency analysis. As task difficulty increased , alpha power in healthy controls decreased, indicating increased cortical activation  is another method to challenge balance control. Eleven studies used a form of sensory removal or augmentation, including eyes closed conditions and the use of virtual reality  >1,000 μV, kurtosis >5 SD from mean, or poor correlation (r < 0.4) with neighboring channels for >1% of time samples. Ten additional studies used these criteria for removing noisy channels prior to further analysis. Twenty-five studies used spatial filtering techniques, including Laplacian estimation (3), referencing to a common average (21), and bi-lateral referencing (1).Table The literature reports a multitude of techniques to identify and remove ocular, muscular, and/or movement artifact during dynamic balance tasks, ranging from visual inspection (10) to sophisticated computational techniques. Petrofsky and Khowailed  and Tse However, approximately half the studies  used conventional ICA or adaptive mixture ICA (AMICA) to identify and remove artifacts from EEG data collected during walking. Hülsdünker et al.  and HülsThis study reviewed 83 articles using neuroimaging modalities to investigate the neural correlates underlying static and dynamic human balance control, with aims to support future mobile neuroimaging research in the balance control domain. Images demonstrating the use of mobile neuroimaging modalities integrated with a dynamic balance control tasks can be found in Kline et al. . LikewisThis review found that static balance control was largely examined with sensory or mechanical balance paradigms. There were relatively few static paradigms that utilized cognitive challenges to study the neural components of balance. Additionally, all but one static balance study using sensory challenges, such as using open and closed eye conditions, were performed on healthy, young adults. Analysis of brain activity during standing balance control included perturbation evoked ERPs and frequency analysis, with findings of increased activation during balance challenges, regardless of challenge type . Activation of the prefrontal cortex (PFC), supplementary motor area (SMA), and Premotor cortex (PMC) frequently occurred in response to the static balance challenges. Although more common in dynamic balance control studies, seven of the static balance control studies invoking mechanical perturbations used advanced signal processing methodologies such as ICA to reduce movement artifacts  put forward in this review provide a foundation for future investigation of neuroimaging within the balance control domain. The relatively recent breakthroughs in mobile neuroimaging paradigms have allowed researchers to investigate brain activity during natural human movement (Gramann et al., All authors contributed equally to this work by conducting the review and drafting the initial manuscript. EW and JT were responsible for writing and editing the current manuscript under supervision of CN and JF who oversaw the project and guided it to completion. All authors discussed the results and implications and commented on the manuscript at all stages.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


External Quality Assessment (EQA) surveys performed by the World Health Organization Regional Office for Africa (WHO AFRO) revealed the need for the strengthening of public health microbiology laboratories, particularly for testing of epidemic-prone diseases in the African Region. These surveys revealed common issues such as supply chain management, skilled personnel, logistical support and overall lack of quality standards. For sustainable improvements to health systems as well as global health security, deficiencies identified need to be actively corrected through robust quality assurance programmes and implementation of laboratory quality management systems.Given all the pathogens of public health importance, an external quality assessment programme with a focus on vaccine-preventable diseases and emerging and re-emerging dangerous pathogens is important, and should not be stand-alone, but integrated within laboratory networks as seen in polio, measles, yellow fever and rubella.In 2015, WHO AFRO collaborated with the US Centers for Disease Control and Prevention, the London School of Hygiene & Tropical Medicine and partners in a series of consultations with countries and national and regional EQA providers for the development of quality assurance models to support HIV point-of-care testing and monitoring. These consultations revealed similar challenges as seen in the WHO AFRO surveys. WHO AFRO brought forth its experience in implementing quality standards for health programmes, and also opened discussions on how lessons learned through such established programmes can be utilised to supporting and strengthening the introduction of early infant diagnosis of HIV and viral load point-of-care testing.An optimised external quality assessment programme will impact the ability of countries to meet core capacities, providing improved quality management systems, improving the confidence of diagnostic network services in Africa, and including capacities to detect events of international public health importance. The EQAP encompasses: (1) investments in building human capacity; (2) investments in building laboratory management systems, infrastructure and management of quality systems; (3) well-written policies and procedures; (4) a quality control system, quality improvement (QI) and external quality assessment (EQA); and (5) accreditation standardsLaboratory professionals should routinely perform quality control testing to guarantee that test methods and equipment perform according to established standards. Laboratory professionals must participate in EQA/proficiency testing programmes in order to demonstrate that acceptable systems are in place and that specimens are collected and processed appropriately.The objectives of the World Health Organization Regional Office for Africa (WHO AFRO) EQAP are:To support countries in their efforts to improve their laboratory quality management systems, including accreditation.To collect, analyse, and report laboratory EQA feedback data and use this information for corrective action and laboratory capacity strengthening.To establish recognised, accurate, and sustainable diagnostic practices using appropriate algorithms.WHO AFRO has established and monitored several national/regional laboratory networks linked by EQA programmes, including polio, measles and rubella, yellow fever, rotavirus and influenza laboratories, the Emerging and Dangerous Pathogens Laboratory Network, and the epidemic-prone bacterial diseases laboratory network, including tuberculosis. The Polio Laboratory Surveillance Network was established in Africa in 1993 to support the Global Polio Eradication Initiative. This laboratory network is made up of 16 laboratories in 15 countries, with each laboratory supporting at least one other country. Of these, 12 polio laboratories have integrated functions supporting measles, yellow fever and rotavirus programmes .The Emerging and Dangerous Pathogens Laboratory Network has been established for the confirmation of viral haemorrhagic fevers in the WHO African region. The network consists of laboratories in 17 countries, categorised based on their capacity, as described in The laboratory capacity to diagnose influenza infections by real-time PCR in the African Region has grown since the 2009 pandemic. Presently, the regional influenza laboratory network comprises 30 national influenza reference laboratories in 30 countries. Currently, 14 countries are registered as National Influenza Centres and are members of the WHO Global Influenza Surveillance Network in the African Region . Since 22 The WHO/NICD microbiology EQAP was started in May 2002 and currently, over 90 laboratories in 45 African countries participate in this programme at a cost of USD 150 000/year  in South Africa as the EQA provider.000/year .3 The NICD has the capacity to produce, perform quality control of and distribute samples for the EQAP. The resulting data goes to both NICD and WHO AFRO, belonging to the WHO AFRO EQAP programme.Its objective is to assess laboratory capacity to detect epidemic-prone diseases (enteric and meningitis pathogens and plague). In addition, this programme assesses laboratory capacity to diagnose malaria and tuberculosis.The EQAP conducts three surveys (shipments) per calendar year, with 2 to 4 disease components per survey:Bacteriology discipline: six simulated specimens containing organisms isolated from enteric, meningeal and routine clinical samples for microscopy, culture, identification and/or antimicrobial susceptibility testing.Yersinia pestis, including microscopy.Plague discipline: two simulated samples for diagnostic tests for Tuberculosis microscopy: 10 slides per panel for reporting on the presence of acid-fast bacilli using the International Union for Tuberculosis and Lung Disease smear-grading system.Malaria microscopy: 20 slides per panel to assess ability to diagnose malaria species and to count parasites.Laboratories for enteric and meningitis pathogens were graded based on a score depending on their capacity to do the following:Microscopy: clinically important, basic skill, relevant.Culture and identification.Serotyping/serogrouping: important to evaluate disease prevention and control strategies.Antimicrobial agents selected for testing.Antimicrobial susceptibility testing.4 These surveys reflect common issues, such as shortages of supplies and human resources, as well as the critical need for national standards and quality assessments.5In the region, it was observed that errors in antimicrobial resistance testing included inappropriate selection of antibiotics, guideline availability, no adherence to guidelines, no control/reference strains, and incorrect results and interpretation.®.6As shown in As part of EQA, laboratories with low performance in the EQAP receive feedback, training and technical support aimed at instituting corrective action. In a joint collaboration, the EQAP and NICD provide feedback and corrective action to all participating laboratories in the three official working languages in the WHO African Region . On-site and regional training sessions are also provided. As part of technical support, standard operating procedures and guidelines are made available. Specifically, guidelines and standard operating procedures for laboratories performing antimicrobial susceptibility testing are made available in addition to laboratory bench training workshops.In 2015, WHO AFRO collaborated with the US Centers for Disease Control and Prevention, the London School of Hygiene & Tropical Medicine and partners in a series of consultations with countries and international, national and regional EQA providers for the development of quality assurance models to support HIV point-of-care testing. Participants consulted revealed similar challenges with supply chain management, skilled personnel, logistical support and overall lack of quality standards. WHO AFRO provided experiential oversight in implementing quality standards for health programmes, as well as facilitating discussions on how lessons learned through such established programmes should be utilised in supporting and strengthening the introduction of HIV early infant diagnosis and viral load point-of-care testing.The EQAP has provided a clearer understanding of the capacities of participating laboratories to produce accurate results. This international EQAP provides a unique opportunity for African national public health laboratories to continuously assess and improve their laboratory performance, identifying their strengths, limitations and on-going challenges. The EQAP facilitates an improvement in the confidence of test results from diagnostic networks that impacts on treatment capacities by the requesting treatment centres.Given all the pathogens of public health importance, the EQAP should not be stand-alone, but rather integrated within laboratory networks, as seen with polio, measles, yellow fever and rubella. Grouping them together provides economy of scale for cost-effectiveness and efficiencies for ease of training and reporting. The EQAP needs to emphasise the utility of such programmes in improving services for both vaccine-preventable diseases and emerging and re-emerging dangerous pathogens.Finally, an optimised EQAP will impact the ability of countries to meet International Health Regulations (2005) core capacities, including the capacity to detect events of international public health importance. This programme has allowed WHO AFRO to identify the capacities and resources needed by countries for sustainable improvement and competency of diagnostic services throughout Africa. Improved quality of laboratory networks produces highly-accurate surveillance data which is required to estimate disease burden in countries, identify outbreaks and inform strategies for disease control and prevention.


Most weight loss research focuses on weight as the primary outcome, often to the exclusion of other physiological or psychological measures. This study aims to provide a holistic evaluation of the effects from weight loss interventions for individuals with obesity by examining the physiological, psychological and eating disorders outcomes from these interventions.Databases Medline, PsycInfo and Cochrane Library (2011–2016) were searched for randomised controlled trials and systematic reviews of obesity treatments . Data extracted included study features, risk of bias, study outcomes, and an assessment of treatment impacts on physical, psychological or eating disorder outcomes.From 3628 novel records, 134 studies met all inclusion criteria and were evaluated in this review. Lifestyle interventions had the strongest evidence base as a first-line approach, with escalation to pharmacotherapy and bariatric surgery in more severe or complicated cases. Quality of life was the most common psychological outcome measure, and improved in all cases where it was assessed, across all intervention types. Behavioural, psychological and lifestyle interventions for weight loss led to improvements in cognitive restraint, control over eating and binge eating, while bariatric surgery led to improvements in eating behaviour and body image that were not sustained over the long-term.Numerous treatment strategies have been trialled to assist people to lose weight and many of these are effective over the short-term. Quality of life, and to a lesser degree depression, anxiety and psychosocial function, often improve alongside weight loss. Weight loss is also associated with improvements in eating disorder psychopathology and related measures, although overall, eating disorder outcomes are rarely assessed. Further research and between-sector collaboration is required to address the significant overlap in risk factors, diagnoses and treatment outcomes between obesity and eating disorders.The online version of this article (doi:10.1186/s40337-017-0143-5) contains supplementary material, which is available to authorized users. Obesity and eating disorders are often viewed as distinct problems on opposite ends of the weight spectrum, but in actuality, they share a number of risk and protective factors and frequently co-occur. Individuals with binge eating disorder are often overweight, and individuals that are overweight are at an increased risk of developing eating disorders. Despite this, weight loss interventions usually focus on physical factors, such as changes in weight or body composition, to the exclusion of other factors, such as psychological well-being or eating disorders.In this review, we conduct a detailed examination of published literature on the range of available interventions for overweight and obesity, taking physical, psychological and eating disorders outcomes into equal consideration. ‘Lifestyle’ interventions that include exercise, dietary and behavioural components have the strongest evidence as a first-line approach, while obesity (bariatric) surgery is the most effective intervention in terms of the amount of weight lost. Quality of life is not commonly measured, but where reported it tends to improve alongside weight loss. Interventions that included behavioural or psychological components had the most positive impacts on eating disorders psychopathology and related measures, although these outcomes were only reported in a small number of studies.Obesity and eating disorders are significant public health concerns that are associated with a range of adverse physical and psychological outcomes. In Australia, more than 60% of adults and 25% of children and adolescents are overweight or obese , 2, withThe reasons for such a large increase in comorbid obesity and eating disorders in a relatively short period of time are unclear, but media and weight-reduction campaigns have been suggested as precipitating factors . Media eA growing body of evidence highlights the significant shared space between disorders at both ends of the weight spectrum. Obesity and eating disorders share a number of risk factors that apply to a broad range of eating- and weight-related problems –16. ThesOverweight individuals are at increased risk of disordered eating and eating disorders compared with the general population . At the Since the vast majority of weight loss intervention research focuses on weight as the primary outcome, often to the exclusion of other physiological or psychological measures, the potential impact of weight loss interventions on eating disorders and overall wellbeing is unclear. Therefore, this systematic review aims to provide a holistic evaluation of the effects from weight loss interventions for individuals with obesity, assessing physiological, psychological and eating disorders outcomes. Due to the large volume of literature on the topic, we constrained our search to cases of uncomplicated obesity – that is, individuals who were otherwise healthy, and with the exception of BED, had no physical or psychological comorbidities. A synthesis of outcomes is then used to identify gaps in the literature and guide our recommendations for future research and practice that encourages an integrated approach to the prevention and management of obesity and eating disorders.This review was conducted in accordance to the PRISMA guidelines for systematic reviews . SearcheWe considered peer-reviewed systematic reviews (SRs) and randomized controlled trials (RCTs) published in 2011 or more recent, or in the case of SRs, an original or updated search date of 2011 or more recent. These criteria were chosen because of the large volume of available literature, because older RCTs will be evaluated within recent systematic reviews, and because recent systematic reviews eclipse non-recent systematic reviews. We excluded non-English studies, studies reporting primarily qualitative or methodological data, studies focused on preventative interventions and studies in which the outcomes of an overweight or obesity intervention were not the main focus of the study.The target sample included overweight or obese males and females ranging in age from 12–65 years. Adolescents (12–18 years) were assessed separately from adults (18–65 years). Because of prominent differences in treatment strategies, paediatric and elderly patients were excluded from consideration. The primary interventions evaluated in this review were dietary, exercise/physical activity, psychological/behavioural, pharmacological and surgical interventions, while the primary outcome measures were standardized anthropometric measures  and body weight), standardized body composition measures , psychological, eating disorder and quality of life measures, and reports of adverse treatment effects.All included studies were assessed first individually and second collectively  according to treatment intervention. Study assessment included appraisal of study quality, clinical impact and consistency. Each assessment item was scored as high, moderate or low by one of two reviewers, and a subset of studies (10%) was scored by both reviewers to assess accuracy. Disagreements were resolved by discussion.The Overview Quality Assessment Questionnaire (OQAQ)  and the Following the assessment of each individual SR and RCT, the evidence was evaluated for each intervention, taking into account the number, quality, clinical impact and consistency of included studies. Each factor was assigned a rating of poor, satisfactory, good or excellent based on the degree to which relevant criteria (adapted from the NHMRC Body of Evidence Matrix ) see Ad were fulThe search strategy yielded a total of 3628 citations after removal of duplicates. Following exclusion of studies that did not meet inclusion criteria, 134 studies remained, of which 33 were SRs and 101 were RCTs  as well as mood, fatigue and confusion (lipid dietary supplement), although one substance (the anticonvulsant zonisamide) led to a worsening of anxiety, depression, attention, concentration and memory.Pharmacotherapies delivered as an adjunct to behavioural and psychological interventions led to improvements in quality of life  and depEating disorders were evaluated in two RCTs assessed. The first study  prescribNine SRs –132 and Mental health and quality of life were the primary focus of three SRs –129, andImprovements in eating disorder outcomes were reported in two SRs  127]. O. O127]. While lifestyle interventions, pharmacotherapy and surgery remain the primary approaches for treating overweight and obesity, one SR  and 10 rReduced energy consumption and increased physical activity were the basis for obesity interventions for adolescents, as they were for adults. Pharmacological and surgical interventions were considered in more severe or treatment-resistant cases. Four SRs –153 and One SR and 6 RCTs evaluated mental health and eating disorders outcomes. Quality of life improved following adjustable gastric banding  and combNumerous treatment strategies exist to assist people in losing weight. Consistent with the literature , 168, liunhealthy dieting behaviours, which confer a 5- to 18-fold risk for development of eating disorders. It is important that clinicians are aware of the increased risk for harm in individuals engaging in unhealthy dietary practices, and monitor individuals to ensure that healthy diets do not transition into unhealthy diets.Concerns have previously been raised that dieting may precipitate eating disorders in overweight and obese individuals , howeverIn Australia, the use of surgical procedures to treat obesity has risen dramatically in recent years . ConsistA recent Australian study of bariatric surgery candidates reported that 13.5% of individuals met the DSM-IV criteria for BED , while sFuture research should endeavour to evaluate and develop a more comprehensive metric of treatment success than BMI or body composition measures alone. There is presently a lack of consensus on what an ‘ideal’ BMI is, particularly for individuals losing large amounts of weight , 203, anThe limitations in this review should be taken into account when interpreting outcomes. These include: 1) the RCTs included in evaluated SRs were often highly heterogeneous, precluding pooling for meta-analysis in studies that included these ; 2) studThere are a number of evidence-based strategies for weight loss, and many of these have the additional benefit of improving quality of life, depression and unhealthy eating behaviours. The weight loss strategy that is most effective will depend on an individual’s unique needs and the characteristics of their illness. These include the severity of their obesity, their treatment history, their history of disordered eating or psychological comorbidities, as well as their willingness to manage adverse effects from treatment. Bariatric surgeries lead to the greatest and most persistent reductions in weight, but are frequently accompanied by adverse effects that range from mild to severe. In contrast, interventions incorporating behavioural or psychological components are less efficacious for weight loss, overall, but cause no adverse effects while leading to improvements in psychological well-being and eating disorders symptomatology. Given the interconnected nature of obesity, mental health and eating disorders, we suggest that weight-loss interventions focus simultaneously on two targets: an evidence-based component that targets weight loss  alongside an evidence-based behavioural or mental health component that focuses on psychological well-being. This second component should include an ongoing evaluation of disordered eating behaviours and psychopathologies.There is an increased need for prevention and treatment interventions that target the broad spectrum of weight-related disorders. This necessarily requires dialogue and collaboration between professionals in obesity and eating disorders sectors, as well as the involvement of stakeholders at all levels of community and government. Treatment strategies for overweight and obesity should be evidence based and comprehensive, taking into account a broader range of health outcomes than weight or BMI alone . Given tAdditional file 1:Study assessment procedures: Overview Quality Assessment Questionnaire, Jadad Scale and NHMRC Body of Evidence Matrix. (DOCX 47 kb)Additional file 2: Table S1.Study features and assessment of risk of bias within individual systematic reviews –153, 208Additional file 3: Table S2.Study features and assessment of risk of bias within individual randomized controlled trials , 209–213Additional file 4: Table S3.Overview descriptions of interventions included in this review , 214–220