Background: Agriculture contributes a third of Rwanda’s GDP and is the main source of income for rural households, with 80% of the total population involved in crop and/or livestock production. The Government of Rwanda established the Muvumba rice project in 2011 amidst a policy shift towards rice as a national staple crop. However, the indiscriminate use of pesticides by local, low-income rice growers has raised concerns about potential human, animal and ecosystem health impacts as pesticide distribution and application are not strictly regulated. Although pesticide use can directly influence farmer health and ecosystems, little is known about small-scale farmers’ pesticide application practices and knowledge. We aimed to assess local application practices and understanding of pesticides to identify gaps in farmers’ knowledge on safe pesticide use and deviations from established standards and recommended practices. Methods: We conducted a cross-sectional study consisting of observations of pesticide practices and interviews with 206 small-scale rice growers in Nyagatare District, Rwanda, in March 2017. Descriptive statistical analyses  were performed, and we evaluated the association between farmers’ personal protective equipment (PPE) use and their education level and literacy status. Results: Over 95% of observed farmers did not comply with minimum standards for safe pesticide use, and 80% of respondents reported that they stored pesticides in their homes without personal protection measures. Education and literacy level were not significantly associated with PPE use. Additionally, 90% of respondents had experienced adverse health effects after using pesticides including intense headache, dizziness, stomach cramps, skin pain and itching, and respiratory distress. All respondents also reported animals in and around the rice scheme  behaving abnormally or with signs consistent with pesticide exposure in the six months preceding the study, which may be linked to pesticide-contaminated water. Conclusions: Our study demonstrates potential for high exposure to pesticides for farmers, their families, and animals sharing rice-growing or downstream environments and points to the need for training on safe and effective pesticide use. Agriculture plays a vital role in sustainable development and poverty reduction, especially in many low- and middle-income countries . HoweverOryza spp.) is being promoted by the government as one of the main staple crops across Rwanda, and the Muvumba rice scheme was created in 2011 as an alternative to ancestral livestock-keeping activities in Nyagatare District. Approximately 700 hectares were reserved for Indian rice production investors (Nyagatare Agrovenger Rwanda [NAVR] Ltd) and 1000 hectares were distributed among individual Rwandan farmers and a community cooperative named Cooperative des Producteurs de Riz de Muvumba (COPRIMU) . Butachlor and carbendazim are classified as unlikely to cause acute hazard in normal use (Class U), and propinil and pendimenthalin fall into a moderately hazardous class (Class III) . HoweverIn March, 2017, we conducted a cross-sectional study consisting of observations of pesticide practices and interviews with farmers involved in rice production in Eastern Rwanda. Using a random sampling approach, we selected 206 study participants from 600 rice farmers in Rwempasha sector along the Muvumba Valley marshland . The sitThe Muvumba Valley marshland is located in Nyagatare District in the Eastern Province of Rwanda  [Trained enumerators conducted interviews in Kinyarwanda with rice farmers working in the Muvumba Valley marshland. The study participants were 18 years of age or older, with at least one year of experience working in a rice scheme. Farmers working outside of the study area and those who were unable to give informed consent were not included in the study. A pre-study consultation meeting was organized with different stakeholders involved in the Muvumba rice farming project to discuss local collaboration and possible benefits of the research.The study participants were observed using pesticides for five days before being engaged for interviews. We gathered information on farmer pesticide application practices using an observation sheet, which included eight international standards of good pesticide practices. Farmer behaviors observed included mixing pesticides (powder and liquid) before spraying, cleaning materials after spray/use, storage and disposal of empty containers, and use of personal protective equipment (PPE). The observation sheet was developed from a literature review and international guidelines on the proper use of pesticides . The sheFollowing the observation session, a structured questionnaire on farmer knowledge and perception of pesticide use, handling, and application was administered based on published literature and local context. We divided the questionnaire into three sections: (1) social and demographic information about the subjects, (2) participant knowledge about pesticides and their application, and (3) participant knowledge of the potential impacts of pesticide use on human, animal and environmental health. Questionnaires were tested for clarity, completeness, and participant understanding with 10 rice farmers in a sector outside of the study area.α = 0.05 was used for all statistical tests.Questionnaires, observation sheets, and interview guides were approved by the University of Global Health Equity Institutional Review Board . Permission was granted by district authorities and cooperative leadership to conduct the surveys and observational visits in the Muvumba rice scheme. The study participants were given informational handouts about the proper use, handling, and health effects associated with pesticides following the interviews. Following translation from Kinyarwanda to English, field questionnaire and observation data were entered into Microsoft Excel for data management and cleaning. Descriptive statistical analyses  and range) were performed using STATA software . Chi-square tests were used to evaluate factors  associated with good pesticide practices. A significance level of This study was reviewed by University of Global Health Equity—IRB #0001, and all study participants consented before the interviews.p-values > 0.05; Observed and self-reported pesticide practices showed limited farmer use of recommended methods for safe spraying, mixing and storage . All stuDuring household observational visits, we observed that all study participants stored pesticide in powder or liquid form in their homes. Similarly, all study participants reported storing pesticides or empty pesticide cans in their premises (house/kitchen). The empty cans were used for fetching water, serving water to calves, and as containers for drinking water for children.Farmers relied upon different primary sources of information about safe pesticide mixing, storage, and application . The majOverall, we observed poor compliance with the international standards of good pesticide practices established by FAO and the WHO ,16 acrosA greater proportion of the farmers  was compliant with the 6th standard , followed by standard 4 (avoiding unnecessary and poorly timed application of pesticides) with . The 7th standard (establishing buffer zones where pesticide is not applied a safe distance (minimum of 20 to 30 meters recommended) from wells and surface water) was the least practiced . Only nine study participants (4.4%) were compliant with at least half of the standards of good practice.All of the study participants reported that they sprayed pesticides more than twice (the recommended spaying frequency) per growing cycle. The study participants attributed the need for additional spraying to the ineffectiveness of the pesticides, increased resistance of pests towards the pesticides, and abundance of diseases. Moreover, some farmers  also reported experimentally increasing the pesticide dosage during the mixing stage in order to observe the effect of pesticides used on the control of pests and diseases.The majority of the study participants  believe PPE and regular pesticide safety trainings can protect them from adverse health effects of pesticides. However, only 28% (58 farmers) had previously received any information on pesticide use from various agriculture-related stakeholders . Farmers participated in general pesticide training from the Rwanda Agricultural Board , sector agronomists , or non-governmental organizations . Only four farmers (1.9%) received specific training on human health and safety of pesticides, including safe disposal of pesticides. No trainings were delivered on effects of pesticides on animal and environmental health or on strategies for reducing pesticide use such as Integrated Pest Management (IPM).All study participants reported adverse health effects during or after pesticide spraying in the field. Farmers reported experiencing one or more of the following symptoms: itchy skin, headaches, difficulty breathing, and nausea or stomach upset. Only three farmers (1.5%) could explain the connections between pesticide use and negative impacts on aquatic life and the environment. However, all participants directly observed or had heard reports of cows, birds or fish showing signs of pesticide intoxication  within 30 minutes to six hours after consumption of pesticide or presence in recently sprayed areas. Almost half of study participants  also reported seeing small fish die a few minutes after applying the pesticides, especially during plot preparations before planting rice.Poor pesticide handling, application, and storage can negatively impact the health of humans, animals, and ecosystems . Our stuThe limited use of personal protective equipment (PPE) reported and observed among a majority of small-scale rice farmers likely poses a risk to individual and family health. Although few participants in our study were formally trained on health impacts of pesticides, all participants recognized acute changes in their health after starting to use pesticides including skin, eyes and nasal passage irritations, headache and stomach cramps. Some farmers may therefore understand health risks but ignore PPE recommendations due to practical and financial challenges. Farmers participating in our study commonly reported that they did not follow PPE recommendations because (1) the recommended rubber boots  frequently get stuck in mud when moving across the field during spraying, and (2) they had no financial capacity to purchase PPE. Similarly, low levels of PPE usage were reported in Uganda and Kenya ,19, wherOur study revealed no significant association of education  with PPE use. In contrast, links between increased education and safe pesticide practices have been observed in other low and middle-income countries. In Egypt, farmers with school education used gloves more frequently than those with no school education, but no significant differences were observed in the use of protective clothing or masks . The useImproper pesticide storage practices may be an additional important source of exposure for humans and animals in the study area. All study participants stored full, partially full, or empty cans of pesticides in their kitchen or other areas of their homes and were observed using empty pesticide cans for fetching water for domestic purposes such as washing clothes, cooking and drinking. The proportion of surveyed farmers storing pesticides at home was higher than those reported in Tanzania (68%)  and EthiThe Muvumba River serves as an important water source for irrigation and domestic purposes  as well as for local domestic and wild animal populations. The reported pesticide use behaviors pose potential health risks to the communities in and around the Muvumba River as well as communities downstream, which may be exposed to water contaminated by pesticide runoff. Human environmental contact with pesticides is most likely to occur through occupational exposure  but can This cross-sectional study was based on field observations of farmer practices and self-reported information. There are chances of observer (enumerator) and recall (by farmers) bias. However, the good relationships among the University of Rwanda (UR) and University of Global Health Equity (UGHE) with the study communities, the sample size of over 200 farmers, and our ability to compare observations with self-reported information suggest that our findings on risky pesticide management practices reflect the behavior of the majority of rice farmers in the Muvumba River area. Given the health risks associated with current pesticide practices, there’s an urgent need for regular trainings on pesticide handling, application and management, practical approaches to using PPE in local conditions , and strategies such as Integrated Pest Management (IPM) to decrease pesticide use among rice farmers in Rwanda. Increased PPE accessibility and availability at agricultural shops and affordable prices for farmers are needed. In addition, laws and regulations of pesticide selling, application and monitoring the use should be reinforced by relevant authorities.Our study suggests high potential for exposure to pesticides due to limited basic pesticide safety practices and potentially dangerous health shortfalls in and around the Muvumba Valley rice scheme of Nyagatare District, Rwanda. Specifically, the knowledge and skills of farmers appeared to be inadequate to prevent potential hazards and risks  associated with the use and management of pesticides. Urgent comprehensive intervention measures are needed to reduce major health risks to small-scale rice farmers, their families, and surrounding animals and ecosystems. Such measures could include access to personal protective equipment (PPE), pesticide application and storage training before use, pesticide and health inclusion in the formal education curriculum, adequate warning descriptions in local languages, and measures to reduce cost barriers to the adoption of safe behaviors.


About 5.8 million maternal deaths, neonatal deaths and stillbirths occur every year with 99% of them taking place in low- and middle-income countries. Two thirds of them could be prevented through cost-effective interventions during pregnancy, intrapartum and postpartum periods. Despite the availability of standards and guidelines for the care of mother and newborn, challenges remain in translating these standards into practice in health facilities. Although several quality improvement (QI) interventions have been systematically reviewed by the Cochrane Effective Practice and Organization of Care (EPOC) group, evidence lack on QI interventions for improving perinatal outcomes in health facilities. This systematic review will identify QI interventions implemented for maternal and neonatal care in health facilities and their impact on perinatal outcomes.This review will look at studies of mothers, newborn and both who received inpatient care at health facilities. QI interventions targeted at health system level (macro), at healthcare organization (meso) and at health workers practice (micro) will be reviewed. Mortality of mothers and newborn and relevant health worker practices will be assessed. The MEDLINE, Embase, World Health Organization Global Health Library, Cochrane Library and trial registries electronic databases will be searched for relevant studies from the year 2000 onwards. Data will be extracted from the identified relevant literature using Epi review software. Risk of bias will be assessed in the studies using the Cochrane risk of bias tool for randomized and observational studies. Standard data synthesis and analysis will be used for the review, and the data will be analysed using EPPI Reviewer 4.This review will inform the global agenda for evidence-based health care by (1) providing a basis for operational guidelines for implementing clinical standards of perinatal care, (2) identify research priorities for generating evidence for QI interventions and (3) QI intervention options with lessons learnt for implementation based on the level of needed resources.PROSPERO registration number CRD42018106075The online version of this article (10.1186/s13643-019-1110-9) contains supplementary material, which is available to authorized users. The call under the Sustainable Development Goals (SDGs) to reduce maternal mortality to 70 deaths per 100,000 live births, the global neonatal mortality rate to 9 per 1000 live births and global stillbirth rate to 9 per 1000 births by 2030 has led to widespread attention on increasing the coverage of live-saving interventions for mothers and babies .If the current annual rates of reduction continue, by 2030, 116 million more mothers and babies will die with 99 million having lost development potential (including 31 million disabled), and the targets set for 2030 will be missed [The availability of standard guidelines for the care of mother during pregnancy, intrapartum and postpartum period is very important to accelerate the rate of reduction in deaths , 8. The A strategic pillar of the global Every Newborn Action Plan (ENAP) is to ensure the quality of care for mothers and newborn through quality improvement interventions , 12. HowOptimal health care requires much more than providing infrastructure, drugs, supplies and health care providers . It needThe Millennium Development Goal (MDG) period 2000–2015) saw accelerated progress on achieving global health goals . Materna00–2015 sPoor health worker performance is a fundamental cause of poor-quality care. A host of factors are associated with poor health worker performance , 24. MacThere have been several systematic reviews on QI interventions for improving health worker performance , 11. TheMore than 100 systematic reviews conducted by Cochrane Effective Practice and Organisation of Care (EPOC) group on QI interventions for improving health worker performance –35. ThesIn 2018, to guide countries on how to better implement standards of care to achieve the health-related SDGs, the World Bank, WHO and the Organisation for Economic Co-operation and Development (OECD) identified four types of quality improvement interventions by the level of governance .The availability of evidence at meso and micro levels mostly exists on tailor-made interventions, such as for diabetic care, and general health service delivery. The evidence of which QI interventions work at which level of governance for improving maternal and neonatal care is, however, limited. A 2017 systematic review on QI interventions for a small and sick newborn in low- and middle-income settings identified a number of QI interventions for improving care in sick newborn care units .This systematic review will identify interventions implemented for maternal and neonatal care in health facilities and their impact on perinatal outcomes.This systematic review will use the reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guideline for reporting  and EPOCThe review will search the Medline, Embase, WHO Global Health Library and Cochrane Library electronic databases from 2000 onwards to identify relevant studies. The review will also search the trial registries of WHO, WHO’s International Clinical Trials Registry Platform (ICTRP), the International Standard Randomised Controlled Trial Number (ISRCTN) and ClinicalTrials.gov for completed and ongoing studies. The searches of peer-reviewed publications will be supplemented by scanning the reference lists of relevant studies and systematic reviews. The grey literature will be searched using the databases of WHO technical reports on quality of care, UNICEF field implementation and evaluation reports and Department for International Development (DFID) technical reports. Articles with either abstracts or full text in English, Spanish, French and Chinese and published from 2000 onwards will be searched. The detailed search strategy is provided in Additional file The eligible population groups are systems or organizations or providers who care for mothers or newborns in inpatient settings.Quality improvement is defined as the implementation of measures either together or standalone to improve the quality of care provided to mothers and/or newborn. As per the EPOC and WHO-OECD-World Bank frameworks, the QI interventions will be categorized into macro, meso and micro levels. See details in Table The comparison group will either be no QI intervention or an intervention that has not improved the quality of care for mothers and newborn.Maternal mortality refers to deaths due to complications from pregnancy or childbirthA stillbirth is a baby born with no signs of life at or after 28 weeks of gestationAn antepartum stillbirth refers to where a baby dies in the womb during pregnancy and before labour or in utero 12 h before deliveryAn intrapartum stillbirth refers to where a baby dies during labour or in utero within 12 h before deliveryFirst-day mortality refers to neonatal mortality within 24 h of birthFirst seven-day mortality refers to early neonatal mortality or the death of newborn babies within the first 7 days of lifeFirst 28-day mortality refers to late neonatal mortality or the death of newborn babies between 7 and 28 days of being bornPre-discharge mortality refers to where a baby dies before being discharged from health facilitiesThe foetal heart rate during the intrapartum periodInfection prevention practices during labour, delivery and neonatal periodSkin to skin contact between mother and baby in the first hour of lifeNeonatal resuscitationKangaroo mother careEarly breastfeedingThe treatment of in-patient neonatal infectionDuration of hospital dayClient satisfactionRandomized controlled trials (RCT) at cluster and individual levels.Observational studies including cross-sectional studies, cohort studies and interrupted time series design studies.Quasi-experimental studies, including research and evaluation studies in which participants were not randomly assigned to treatment conditions, but in which comparison groups were constructed by statistical means.The review will consider the following types of studies on quality improvement interventions for perinatal care in health facilities :RandomizTwo of the overview authors (AK and JT) will independently screen titles and abstracts found in EPI-Review to identify reviews that may meet the inclusion criteria. Two other authors (AKC and SSB) will screen all titles and abstracts that cannot be confidently included or are excluded after the first screening to identify any additional eligible reviews. One overview author will screen the reference lists.One overview author (AK or JT) will apply the selection criteria to the full texts of potentially eligible reviews and assess the reliability of reviews that meet all other selection criteria. Two other authors (AKC and SSB) will independently check these judgments.The review will use standard forms to extract data from research on the background of the study: interventions, participants, settings, outcomes, key findings, considerations of applicability, equity, economics, and monitoring and evaluation. The review will assess the certainty of the evidence for the main comparisons using the GRADE approach.Study setting—Region, country, location , level of health facility Study design—Randomized control trial, observational study , or quasi-experimental studyMethod of data analysis—Descriptive analysis of frequency, percentage, mean and standard deviation with inferential statistics through chi-squared test and logistic regressionQuality improvement interventions—Facilitation, continuing education events, audit and feedback, reminders, checklists, outreach visits and financial incentivesDuration of interventionParticipants—study population, number of participants in each group and patient characteristicsOutcomes—primary and secondary outcomesA standardized pre-piloted data extraction form will be developed by the team and tested on 20 articles and revised iteratively as needed. Information will be extracted on the following:Risk of bias and the quality of individual studies will be assessed using Cochrane risk of bias (ROB) tool for randomized studies  and RiskInformation on overarching approaches for improving the quality of health care of mothers and newborn.Information on whether and how the approaches for QI relate to specific signal functions for maternal and newborn care.The efficacy and effectiveness of the efforts to improve maternal and newborn care.The process and outcomes used as measures of quality improvement.Where possible, results will be disaggregated according to geography , wealth quintile, rural or urban setting, public or private health facility and type of health facility.It is anticipated that the selected studies will have a variety of research designs that use qualitative and quantitative methods. The results from the studies will be summarized and tabulated according to the following key headings:Research studies can have implementation and design bias, which will be referred to as meta-biases , 47. FunGRADE criteria will be used to assess the quality of studies and reporting done in the studies . GRADE pRandomized trials generally begin as high-quality evidence and observational studies as low-quality evidence. The quality of evidence may be subsequently downgraded as a result of limitations in study design or implementation, imprecision of estimates , variability in results, indirectness of evidence or publication bias. Quality may be upgraded because of a very large magnitude of effect, a dose-response gradient and if all plausible biases would reduce an apparent treatment effect. Quality assessments will be undertaken by two independent researchers. Any discrepancies will be resolved through discussion with a third reviewer.The framework will thus examine the quality of methodology, the relevance of methodology and the relevance of evidence to the issue under review. An average of these weightings will be taken to establish the overall weight of evidence of each study.This systematic review has three implications. First, it will identify evidence on QI interventions implemented to improve the care of mothers and newborn in health facilities and provide further evidence on the impact of QI interventions on quality of care. The evidence on the impact on care on maternal and neonatal care will enable an implementation framework on quality improvement to be developed. This framework can then be used to develop overall operational guidelines for implementing standards of care for mothers and newborn in different health care settings.Second, the types of QI interventions identified will indicate gaps in the evidence base for informing decision-making on QI interventions. The review will identify research gaps on QI interventions for improving care to identify subjects that need researching.Third, the evidence of the impact of QI interventions on improving care will provide guidance to governments and other stakeholders on the resources needed to implement QI interventions for the more effective care of mothers and babies.The QI interventions in this review will discuss the context of implementing the interventions. The Consolidated Framework for Implementation Research (CFIR) , 53 withAdditional file 1:PRISMA-P Checklist: Impact of Quality improvement intervention(s) on perinatal outcome in health facilities: a systematic review. (DOCX 20 kb)Additional file 2:Search strategy. (DOCX 13 kb)


Supplemental Digital Content is available in the text. Craniofacial microsomia (CFM) is a congenital condition associated with malformations of the bone and soft tissue of the face and the facial nerves, all of which have the potential to impair facial expressiveness. We investigated whether CFM-related variation in expressiveness is evident as early as infancy.Participants were 113 ethnically diverse 13-month-old infants (n = 63 cases with CFM and n = 50 unaffected matched controls). They were observed in 2 emotion induction tasks designed to elicit positive and negative effects. Facial and head movement was automatically measured using a computer vision–based approach. Expressiveness was quantified as the displacement, velocity, and acceleration of 49 facial landmarks  and head pitch and yaw.For both cases and controls, all measures of expressiveness strongly differed between tasks. Case–control differences were limited to infants with microtia plus mandibular hypoplasia and other associated CFM features, which were the most common phenotypes and were characterized by decreased expressiveness relative to control infants.Infants with microtia plus mandibular hypoplasia and those with other associated CFM phenotypes were less facially expressive than same-aged peers. Both phenotypes were associated with more severe involvement than microtia alone, suggesting that infants with more severe CFM begin to diverge in expressiveness from controls by age 13 months. Further research is needed to both replicate the current findings and elucidate their developmental implications. Prevalence is approximately 1 in 3,500 live births3 and higher among boys and children from Hispanic and Native American families.4 Children with CFM have myriad health care needs that require multiple, cross-disciplinary evaluations and interventions, including surgeries that help restore facial form and function.5Craniofacial microsomia (CFM) is a complex congenital condition characterized by the underdevelopment of structures arising from the first and second pharyngeal arches.6 and the extent of facial nerve involvement can be difficult to ascertain in infancy due to the patient’s inability to cooperate with a structured facial nerve examination. In older children, facial palsy is evaluated by asking children to imitate specific facial expressions that indicate the responsiveness of different branches of the facial nerve. However, with infants, clinicians must rely on informal observations of spontaneous facial expressions during clinic visits, a process that is potentially unreliable and may under-identify palsy, delaying the recognition of need for relevant treatments . Moreover, facial palsy in early childhood, either alone or in combination with scarring from surgical interventions, may undermine infants’ facial communications of emotions to caregivers. The caregiver’s recognition of and responsiveness to infant facial expressions is a critical developmental process that has been linked to children’s later attainment of emotion regulation and socialization skills.9 If the facial anomalies associated with CFM disrupt this process, psychosocial interventions could be used to minimize or prevent such problems.12 However, such an approach would require a novel, reliable method of assessing facial expressions in very young patients.Facial nerve palsy is one of the many anomalies associated with CFM13 we used human coders and a manual coding system  to compare the facial responses of cases versus controls. Positive and negative emotion induction tasks successfully elicited the intended facial expressions, but overall expressiveness did not differ between the 2 groups of infants, and only modestly distinguished the phenotypic variants associated with CFM . These null findings may be related to the fact that this study relied upon manually coded observations of facial movement, and small and subtle, but important, movements may have been missed by the coders. These include the displacement, velocity, and acceleration of not only facial movements but also movements of the head as well. Head movement is potentially important because face and head movement are inseparable in emotion communication and are strongly coupled, together influencing how facial expressions of emotion are communicated and perceived.16 Second, this study relied upon manually coded observations of facial movement, and small and subtle, but important, movements may have been missed by the codersWe are developing such a method, using standardized emotion induction tasks to elicit positive and negative facial expressions in 12- to 14-month-old infants with CFM (“cases”) and demographically similar infants without CFM (“controls”). In a previous study,17 has enabled the use of automatic facial analysis (AFA), which tracks and quantifies facial and head movements directly from digital video data.18 AFA has made possible the reliable and efficient measurement of displacement, velocity, and acceleration of facial and head movement. In previous research, AFA has revealed strong associations between effects and the dynamics of facial and head movement.21In recent years, machine learning24 Expressiveness was operationalized as the displacement, velocity, and acceleration of automatically tracked facial landmarks and head pitch and yaw. We addressed 2 specific questions: Do infants with CFM differ from controls in terms of head and facial expressiveness? Are these group differences specific to phenotypic anomalies associated with CFM? Secondary analyses involving all participants examined the potential moderating influence of infant sex, ethnicity, and type of emotion induction (positive versus negative).In the current study, we used AFA to investigate whether infants with and without CFM differ in the dynamics of facial and head movement during tasks designed to elicit positive and negative effects. Face and head movements were tracked from 2D video using a well-validated generic approach made possible by training the algorithm with high-resolution 3D face-scans.25 , epibulbar dermoid, macrostomia); (2) Be diagnosed by a regional craniofacial team; (3) Be between the ages of 12 and 24 months (or corrected age if born between 34 and 36 weeks’ gestation); (4) Have a legal guardian able to provide informed written consent and willing to comply with all study procedures; and (5) Be available for the duration of the study. Exclusion criteria were (1) Diagnosis of a known syndrome ; (2) Presence of an abnormal karyotype or major medical or neurological condition ; (3) Premature birth (less than 34 weeks’ gestation); (4) Any circumstance that would preclude the family’s ability to participate fully in the research; (5) A sibling already participating in the Craniofacial Microsomia: Longitudinal Outcomes for Children Pre-Kindergarten (CLOCK) study; and (6) consenting parent unable to speak English or Spanish. Because the dynamics of facial movement can vary as children age, participants more than 15 months of age were excluded.Participants were 113 ethnically diverse 13-month-old infants. Cases (n = 63) were recruited from hospital-based craniofacial centers at Children’s Hospital of Los-Angeles, Children’s Hospital of Philadelphia, Seattle Children’s Hospital, University of Illinois-Chicago, and University of North-Carolina-Chapel Hill. Inclusion criteria were (1) Have at least one of the CFM indicators developed by the Facial Asymmetry Collaborative for Interdisciplinary Analysis and Learning (FACIAL) networkControls (n = 50) were recruited through pediatric practices located near the hospitals from which cases were recruited. These sources were supplemented by flyers posted in pediatric practices and from available infant studies participant pools. Inclusion criteria were demographic characteristics that met frequency-matching criteria for the case cohort with respect to infant age and sex, socioeconomic status, and language spoken in the home (English or Spanish).Exclusion criteria included (1) meeting one or more of the exclusionary criteria for cases; (2) diagnosis or history of any disorder, condition, or injury that would affect facial features; and age older than 15 months.26 The photographic protocol and classification method27 generated 3 phenotypic subgroups: Microtia only ; Microtia plus mandibular hypoplasia (n = 38); and Other combinations of CFM- associated malformations (n = 9).We classified the participant’s phenotype with a case-by-case integration of standardized photographic ratings of facial features and data taken from a medical history interview and medical charts.28 For each task, infants were seated in a highchair in front of an experimenter and their mother to the side .Infants’ expressiveness was observed in response to 2 standardized emotion inductions, one intended to elicit positive affect and the other negative affect.see figure, Supplemental Digital Content 2, which displays examples of Negative Emotion Task (left) and Positive Emotion Task (right), http://links.lww.com/PRSGO/A955).The experimenter engaged the infant by blowing soap bubbles toward them and using her voice to build suspense and elicit surprise, amusement, or interest . The NegET was terminated if the infant became too upset or at the mother’s request.The examiner first allowed the infant to play with an attractive toy and then covered the toy with a clear plastic bin just out of the infant’s reach, which typically elicited frustration, anger, or distress  were each repeated 1–3 times unless the infant became too distressed to continue. Both tasks were recorded using a Sony DXC190 compact-camera.see figure, Supplemental Digital Content 3, which displays examples of AFA tracking results (head orientation pitch (green), yaw (blue), and roll (red), and the 49 fiducial points). http://links.lww.com/PRSGO/A956]. Tracking results were overlaid on the source videos and manually reviewed. Frames that could not be tracked or failed visual review were not analyzed.A person-independent 3D face tracker  was used to track the 3D coordinates of 49 fiduciary points and head pitch  and yaw  in each video frame [The movement of the 49 detected 3D fiduciary points corresponds to the movement (without rigid head movements) of the corresponding facial features  and was used to measure expressiveness from facial movement. The displacement, velocity, and acceleration of each one of the 49 detected fiduciary points was computed. The root mean square (RMS) was then used to measure the magnitude of variation of the fiduciary points’ displacement, velocity, and acceleration, respectively. The RMSs of the fiduciary points displacement, fiduciary points velocity, and fiduciary points acceleration are referred to as facial displacement, velocity, and acceleration, respectively. Because the movements of individual points are highly correlated, principal components analysis was used to reduce the number of parameters. The first principal components of displacement, velocity, and acceleration accounted for 63%, 76%, and 75% of the respective variance and were used as measurements of facial expressiveness.Head angles in the horizontal  and vertical  directions were used. Head angles were converted into angular displacement by subtracting the overall mean head angle from each observed head angle within each valid segment . Angular velocity and angular acceleration for pitch and yaw were computed as the derivative of angular displacement and angular velocity, respectively. Similar to facial movement, the RMS was used to measure the magnitude of variation of the angular displacement, the angular velocity, and angular acceleration for pitch and yaw, respectively. RMSs of the angular displacement, angular velocity, and angular acceleration for pitch and yaw were used as measurement of head expressiveness.Expressiveness was the primary outcome and was operationalized using the dynamics of facial and head movement during both the PosET and NegET. Facial expressiveness was operationalized as the displacement, velocity, and acceleration of the automatically tracked 49 landmarks. Head expressiveness was operationalized as the angular displacement, angular velocity, and angular acceleration of pitch and yaw, respectively.To confirm that the induction tasks elicited the targeted affects, general estimating equations using an independent correlation matrix was used to compare expressiveness between PosET and NegET after adjustment for case status, sex, and ethnicity (Hispanic or Latino versus non-Hispanic/non-Latino). Linear regression with robust standard error estimates was used to estimate differences in expressiveness between cases and controls, as well as differences across phenotype, after adjustment for sex and ethnicity.P values were unadjusted for multiple comparisons and they did not serve as the sole basis for estimating the strength of the findings. Instead, we assessed the magnitude of observed effect sizes, their precision, and the consistency of these estimates across multiple measures and the 2 emotion induction tasks.29 Standardized mean difference effect sizes were calculated using a modification of Cohen’s d30 that divides the estimated mean difference by the RMS error of the model.Due to the exploratory nature of this research, Average age at the time of the assessment was 13.2 months . Head and face displacement, velocity, and acceleration were consistently greater during the NegET than PosET .After adjustment for case status and sex, Hispanic/Latino infants had lower levels of expressiveness in facial velocity and acceleration, pitch velocity and acceleration, and yaw velocity and acceleration. Effect sizes ranged from −0.7 to −0.1 with the strongest effects observed for the NegET . The latter subgroup had lower displacement head pitch during both positive and negative tasks, lower displacement head yaw  during the negative task, and marginally lower head yaw displacement in the positive task. No differences were found for the less severe, microtia only group. Nonetheless, we must acknowledge that adjustment for multiple comparisons  would require a 13 the current findings more strongly suggest that CFM, and in particular individuals with microtia plus mandibular hypoplasia and other associated CFM features, is associated with a reduction in expressiveness as early as 13 months of age. Several factors may account for the increased sensitivity of our approach. First, the holistic measures were continuous, whereas Hammal et al13 used summed, binary measures (occurrence versus not occurrence), which emphasized the density of actions  rather than their intensity. Measurement of intensity was central to our approach and we sampled a far larger number of facial movements. In the prior study, they attended to 9 facial action units, whereas in the present study, we sampled 49 points across the face plus head pitch and yaw. Second, the temporal envelope of expressiveness was explicitly quantified in the current study , whereas the action unit approach was insensitive to intensity change over time. Previous work in both infants and adults suggests that variation in displacement, velocity, and acceleration over time is strongly related to affect and interpersonal communication. Third, Hammal et al. used manual coding whereas our approach was fully automatic. Recent breakthroughs in computer vision and machine learning have made possible reliable automatic coding of action units that is consistent with experts’ manual coding.31 Although both human experts and algorithms now can code action units comparably, face and head movement dynamics can only be measured reliably by automatic algorithms. Reliable, automated measurement of face and head movement dynamics was necessary to further investigate expressiveness of infants with CFM.In comparison with the findings of Hammal et al.,32 Cross-cultural difference in expressiveness between Hispanic and non-Hispanic American infants have not previously been documented to our knowledge. For clinical purposes in evaluating expressiveness in Hispanic infants, it would be important to have use of separate norms for Hispanic and Euro-American non-Hispanic infants, as well as for East Asian infants.An unexpected finding was that Hispanic infants were less expressive than non-Hispanic infants, regardless of cases status and phenotype. Previous research has found that Chinese infants are less expressive than Euro-American infants, with Japanese infants either comparable with Euro- American infants or between them and Chinese infants.Clinically, the present findings suggest that infants with only microtia have minimal risk for alterations in facial expressiveness. Elevated risk is suggested for infants with more severe phenotypic presentations of CFM. Increased monitoring and surgical or behavioral intervention may be indicated for these subgroups of patients.Two limitations of the current study may be noted. One is that Hispanic infants were over-represented among cases relative to controls. As a consequence, ethnicity was included as a covariate in the analyses. Because ethnicity was related to expressiveness, controlling for ethnicity may have reduced sensitivity to detect CFM-related differences in expressiveness. We may have under-estimated CFM effects. The other limitation is the relatively small number of facial landmarks we quantified relative to what is possible. We sampled 49 landmarks. To provide denser sampling of facial movement, future work should consider using a larger number of landmarks.In this study, we have demonstrated the initial application of a novel, machine learning approach to the measurement of facial expressiveness in infants with a congenital condition that carries an elevated risk of facial palsy. Infants with CFM phenotypes beyond isolated microtia were less expressive than control infants. This finding, which requires replication, suggests that infants with more severe CFM begin to diverge in expressiveness from controls by 13 months of age. Longitudinal studies will be needed to learn whether these differences are stable or increase through early childhood, whether similar effects emerge for the less severe phenotype of microtia only and whether individual variation in facial expressiveness among infants with CFM predicts their psychosocial status in the preschool years.The authors thank our colleagues Drs. Kathy Kapp-Simon (University of Illinois-Chicago), Amelia Drake (University of North Carolina-Chapel Hill), Alexis Johns , and Leanne Magee  at the participating craniofacial centers and the families who so generously volunteered their time to participate in this research.


Tailoring communicable disease preparedness and response strategies to unique population movement patterns between an outbreak area and neighboring countries can help limit the international spread of disease. Global recognition of the value of addressing community connectivity in preparedness and response, through field work and visualizing the identified movement patterns, is reflected in the World Health Organization’s declaration on July 17, 2019, that the 10th Ebola virus disease (Ebola) outbreak in the Democratic Republic of the Congo (DRC) was a Public Health Emergency of International Concern  toolkit,The IDI-CDC team conducted 12 data collection events with 52 participants, including border public health volunteers, health care providers, security officials, transportation officials, community leaders, army officers, and informal traders . ParticiFive of the 12 events (three focus group discussions and two key informant interviews) described cross-border movements principally between DRC and Uganda, directly and through Rwanda. A main travel pathway linking the three countries was a bus route from DRC  through Rwanda (Gisenyi) and then into Uganda via the Cyanika ground crossing to Kisoro district . This buNo seasonality was associated with general population movement, which was almost uniformly described as constant. However, increases in refugee movement were associated with more insecurity in DRC, and increases in trader movements were associated with agricultural cycles for a range of products.The Uganda MOH National Task Force, which has led Ebola preparedness activities since DRC declared the Ebola outbreak on August 1, 2018, along with district leadership, used these findings to prioritize health facilities, points of entry, and villages for enhanced preparedness activities. These measures included public health screening of travelers, enhanced community-based surveillance procedures, targeted risk communication, and Ebola vaccination of frontline workers at facilities that were more likely to receive patients from outbreak-affected areas of DRC.This population connectivity mapping exercise in two high-priority districts of southwestern Uganda helped national and district leadership identify locations and population groups to prioritize for preparedness efforts to avert or contain importation of Ebola from DRC. District-level stakeholders identified numerous locations within Uganda with high connectivity to the outbreak area in DRC. Additional locations within Uganda, such as the Kisoro bus park, were highlighted because of their risk for onward transmission to urban areas within southwestern Uganda and more distant locations, including the capital city of Kampala. The results illustrated the impact of border system interventions on population movement patterns, as evidenced by the major shifts in movement following border closures.Goma, a large urban area in DRC, first reported an Ebola case on July 30, 2019, which led to a cluster with four confirmed cases (When adapting preparedness and response initiatives to the range of locations identified through this initiative, national and district leaders considered the unique characteristics of each location. Preparing workers in a marketplace to better identify persons with suspected Ebola cases follows a different process from that of preparing workers in points of entry or health care facilities. Market vendors who typically lack medical or public health training, require sensitization and training suitable to their backgrounds. Of note, the observed markets had multiple, nonuniform entry points, posing challenges to screening all market visitors. To increase the likelihood of identifying persons with possible Ebola at such busy locations or on inbound or outbound routes, preparedness efforts might require sensitizing not only stakeholders at the venues but also communities connected with them by proximity or travel patterns. National border health interventions must evolve to accommodate those implemented in neighboring countries as demonstrated by the highlighted shift in movement between countries caused by the Cyanika ground crossing closure.The findings in this report are subject to at least one limitation regarding potential biases among the purposive participant sampling during the PopCAB implementation. To reduce the risk for bias, the team invited participants who represented multiple sectors and facilitated events in a range of locations across Kanungu and Kisoro districts.This multisectoral, community-level engagement in southwestern Uganda helped to characterize the complexity of population movement and connectivity among DRC, Rwanda, and Uganda. National and district leadership in Uganda used the results to guide comprehensive border health strategies including identifying ground crossings for enhanced traveler screening and health facilities for surveillance, both along the border and within Uganda (Understanding cross-border population movement patterns can help countries tailor public health interventions to limit international spread of communicable disease.Land-based travel routes among the Democratic Republic of the Congo, Rwanda, and Uganda shifted as a result of formal border closures. Uganda assessed population movement patterns to tailor its surveillance, infection prevention and control, and communication strategies to address the risk for importation of Ebola virus disease from neighboring countries.Strategies to forecast, identify, and rapidly respond to the international spread of disease require adapting to complex, dynamic, multisectoral cross-border population movement, which can be influenced by border control and public health measures used by neighboring countries.


A strong challenge is posed for patients and their caretakers by the growing need for promoting oral healthcare for this population, as research substantiates the connection between oral health and systemic health. This study identified the major barriers to providing optimal oral care to the older population. Fifty patients aged 60 and over visiting the Columbia University College of Dental Medicine Clinic were administered a questionnaire which reflected possible barriers to oral health care. Statistical analysis of data revealed that the top three barriers in order of relevance were the (1) cost of treatment, (2) anxiety, and (3) transportation. The youngest old (60-69) indicated that the lack of time and conflict with work schedules were additional barriers, while the older sample (70+) experienced obstacles due to disability and illness. When gender differences were analyzed, transportation was the most significant as a barrier among males, and fear/anxiety was most significant for females. Ethnically, non-Hispanics indicated that (1) shortage of time, (2) anxiety, and (3) lack of social/physical support were significant barriers. Findings indicated that even those with Medicaid insurance coverage believed that the cost of dental treatment and caregiving responsibilitieswere major barriers to seeking care. Conversely, even those without dental insurance indicated that disability and illness were barriers to seeking care. This pilot study highlighted various barriers to oral health care and highlighted the need for intervention to address barriers, such as social services, expanded Medicaid coverage, and transportation assistance, to ultimately improve access to optimal oral health care.


People who inject drugs (PWID) in Kazakhstan face many barriers to HIV testing as well as to accessing HIV care, to retention in HIV care, and to initiating and adhering to anti-retroviral treatment (ART). Needle and syringe programs (NSPs) are an opportune setting for integrated interventions to link PWID to HIV care.This Hybrid Type II study employs a stepped-wedge design to evaluate both effectiveness and implementation outcomes of Bridge, an intervention to identify, test, and link HIV-positive PWID to HIV care. The study is conducted at 24 NSPs in three different regions of Kazakhstan, to assess outcomes on the individual, organizational, and policy levels.This trial responds to an identified need for new models of HIV service delivery for PWID through harm reduction settings.NCT02796027 on June 10, 2016. Contributions to the literatureThis paper describes the Bridge study, an implementation study to improve access to HIV testing and linkage to care among people who inject drugs (PWID) in Kazakhstan. This is the first HIV implementation study among PWID conducted in Central Asia.Provides an example of a stepped-wedge design and robust multi-level assessments to evaluate effectiveness and implementation outcomes of Bridge.Can serve as a model of a differentiation of care approach that utilizes harm reduction settings for HIV testing, linkage, and retention in care.Injection drug use remains a large contributor to the HIV epidemic in Kazakhstan, a country with an estimated 127,800 people who inject drugs (PWID) . FurtherLarge gaps in the continuum of HIV care for PWID have intensified the epidemic among this community, as indicated in Fig. Communities and medical providers often believe that PWID will not adhere to treatment and therefore are at higher risk of developing drug resistance , 12. HowWorldwide, needle and syringe programs (NSPs) have played a pivotal role in curbing the HIV epidemic by providing prevention information along with syringes and condoms and referring clients to testing and treatment. A recent meta-analyses of 12 studies found that exposure to NSPs reduced the likelihood of HIV transmission . Across In Central Asia and globally, many barriers prevent PWID from regularly accessing NSPs, including criminalization of drug use, arrest and policing, negative provider attitudes towards PWID, and lack of staff training and knowledge regarding their needs , 18–21. Despite these challenges, Kazakhstan’s NSPs, with community-based locations, outreach staff with strong connections to PWID communities, and ready access to primary care clinics and NGO services, may be an optimal setting to close the gaps in the HIV care continuum for PWID. A differentiation of care approach advocates for shifting HIV services from traditional medical institutions into peer networks and community-based organizations such as NSPs . This maEngaging vulnerable groups such as PWID requires outreach and intensive coordination of care on the part of drug treatment and harm reduction programs , 26. EviFinally, there is little implementation research on NSP service delivery in Kazakhstan and Central Asia, with existing reports limited to examining the characteristics of their clients, and their role as stand-alone harm reduction interventions . As HIV This paper describes the study protocols for evaluating the effectiveness and implementation of Bridge, a three-component HIV intervention, which integrates peer network-based recruitment of PWID to NSPs, rapid testing in NSPs, and linkage from NSPs to treatment and other services through an enhanced Antiretroviral Treatment and Access to Services (ARTAS) case management program . The stuBridge is a Hybrid Type II study , which tPrimary study aims include:Aim 1: To evaluate the effectiveness of Bridge on (1) increasing the number of PWID who attend NSPs, (2) increasing the number of PWID who receive a rapid test for HIV at the NSP, and (3) linking HIV-positive PWID at NSPs (including both new cases and those who have not attended HIV care in the past 6 months) to HIV care at the AIDS Center (Effectiveness).Aim 2: To assess how the Bridge intervention’s package of four implementation strategies  impacts intervention uptake and fidelity and the intervention effectiveness as described in Aim 1 (Implementation).Secondary study aims include:Aim 3: To evaluate the effectiveness of Bridge on (1) increasing retention in HIV care, (2) increasing retention in NSPs, (3) initiating ART, and (4) increasing adherence to HIV treatment regimens and viral suppression (Effectiveness).Aim 4: To assess how multi-level theory-driven factors  influence the implementation and effectiveness of Bridge on primary and secondary effectiveness aims using mixed methods (Implementation).Aim 5: To estimate the cost of the Bridge intervention and assess implications for feasibility of program expansion and sustainability (Implementation).We utilize a stepped-wedge, cluster trial in three cities containing eight NSPs each, 24 NSPs in total see Fig. . After 6Due to their high prevalence of PWID, sufficient numbers of NSPs and estimated numbers of HIV-positive PWID who remained unlinked to care, we selected the cities of Almaty, Shymkent, and Karaganda/Temirtau (considered as a single city given their geographic proximity and shared administrative oversight). To select eight sites within each city, we carried out a selection via multiple steps depicted in Fig. The study team includes US and Kazakhstan researchers, and program staff based in the 24 NSPs. The study is conducted in close collaboration with NSP leadership, including local and national AIDS Centers and Departments of Health. A Community Advisory Board (CAB) was assembled in each study city, consisting of NSP and AIDS Center leaders, drug treatment clinic leaders, local NGOs, international organizations, and representatives from local associations of people living with HIV. CAB meetings take place twice a year to elicit feedback on study design and implementation challenges and to share findings with these key stakeholders.The primary implementers of the Bridge intervention are 24 nurses or social workers (one per NSP) and 48 outreach workers (two per NSP). Organizational leadership selected which staff members would work part-time as implementers of Bridge and receive a supplemental salary for time spent on intervention activities. All Bridge program staff receive training in human subject protection as well as intervention protocols. Bridge staff are both implementers of the intervention as well as research subjects, as described below.We collect data on existing clients of NSPs and AIDS Centers. While we introduce an enhanced recruitment technique  as part of the Bridge intervention, the study does not utilize its own cohort of participants, and instead relies on data collected on existing clients. NSP nurses and social workers obtain verbal informed consent from clients before data collection begins.All research activities involving human subjects received approval from the Institutional Research Board at Columbia University and the ethics committee of the Kazakhstan School of Public Health.Bridge is an integrated intervention which combines (1) Social Network Strategy (SNS), a peer-driven recruitment approach based on social network theory , 34, whiThe following four implementation strategies for Bridge are standard across all three cities:Nurses, social workers, and outreach workers from each study NSP receive intensive training on Bridge protocols in the month prior to implementation in their city. All Bridge program staff complete a 7-day group training led by the study team. Using an adult learning design guided by social learning theory, staff are trained on how to conduct the program protocols specific to their role. Training includes review of HIV facts, pre- and post-test rapid HIV counseling, how to conduct referrals to the AIDS Center, drug treatment clinics, and medication-assisted treatment and other services. Nurses and social workers are trained in communication skills grounded in Motivational Interviewing  to enhanThe Bridge supervision model enhances existing support structures with new methods, resulting in a strength-based team approach for program implementation. To build local capacity and ownership, each local AIDS Center selected a single senior staff member as a program supervisor for all eight sites. The program supervisor is responsible for providing feedback and guidance to NSP nurses and social workers on HIV testing and ARTAS components, and conducting the Community of Practice described below. NSP nurses and social workers supervise outreach workers on the SNS component of Bridge. Supervision protocols promote a collaborative and group learning approach. Staff are encouraged to troubleshoot problems and challenges as a team prior to requesting technical assistance from the research team and to work together to ensure a streamlined experience for new clients.Bridge utilizes shared learning through a Community of Practice in each city. This takes two forms: a monthly in-person meeting for all Bridge study staff within a site, facilitated by the program supervisor, and an ongoing text-messaging group on WhatsApp, a commonly-used smartphone program. Both forms provide a forum for nurses and outreach workers to discuss ongoing challenges and successes with Bridge implementation, and share new experience and lessons learned.The Bridge research team responds to technical assistance requests such as troubleshooting problems with assessment instruments or intervention materials, requests for additional training or information on core elements, or requests for guidance in challenging clinical situations. All technical assistance requests and responses are tracked by the research team to inform implementation aims and cost estimates.In order to capture outcomes related to all the effectiveness and implementation aims described above, the following assessment tools are utilized Table :Table 1BIn order to assess effectiveness aims of the study (Aims 1 and 3), point-of-care data entry is conducted at NSPs and AIDS Centers to record services received at each and linkages between the two. Service providers  in NSPs and AIDS Centers (nurses) use a Google-based application on a tablet computer to create an electronic case record for each PWID client. Clients receive a random identification number encoded in a QR code on a keychain, which then is scanned to log in and identify each client during regular NSP and AIDS Center visits. NSP nurses or social workers conduct informed consent and enroll clients in this system during their regular visits to the NSP, and then enter data on the services received by that client during visits on the application. As NSPs only serve PWID clients, there is no selection process, and all clients who provide consent are enrolled. A complete list of indicators collected during client visits is included in Table In addition to serving as a data source for primary aims related to testing, linkage to and retention in care, this application measures Bridge intervention uptake, by including indicators to show which, if any, Bridge intervention activities were received that day  and provides records on client care that are often not available at the point-of-care data collection, such as test results, which take up to a week to be processed. Chart review for Bridge utilizes data from the Electronic HIV Case Management System, a government-approved computer system for the collection, storage, transfer, and analysis of epidemiological, laboratory, and clinical data on all registered cases of HIV infection in Kazakhstan. Within this system, a file is created for each client who registers at the AIDS Center. Staff from the epidemiology and treatment departments enter all visits, HIV and STI tests, results and treatment information for each client. Each AIDS Center is responsible for assuring the quality of entered data through regular checks by specialists.For this study, a summary of AIDS Center client medical records is conducted every 6 months by an AIDS Center staff member trained by the research team. Staff only extract medical record data on PWID clients and enter it into report format that is transferred to the researchers. The data received are de-identified using a code to which only the AIDS Center staff member has access. Indicators entered into the reports include client’s gender and age, whether client has received services from a NSP over the last 6 months and if so, which one, the number of client visits to the AIDS Center over the past 6 months, any CD4 or Viral Load testing done in the last 6 months and results, any initiation or adjustment in the client’s ART regime during the last 6 months, and any sexually transmitted disease testing done during the last 6 months and results.A number of program materials and reporting forms are used to assess intervention delivery. Nurses and outreach workers fill out monthly reporting forms, which, in addition to being utilized in the supervisory model, provide the primary process measures for the number of Bridge activities completed and a self-assessment of fidelity to the implementation. Reporting forms contain information on the number and category of study activities completed (for SNS and ARTAS), self-reported fidelity to study activities, and narratives on challenges and barriers faced during implementation. Observation of Community of Practice meetings and group text transcript is also used to monitor implementation. Records collected will also inform study aims on assessing feasibility and sustainability.To evaluate the impact of training, nurses and outreach workers complete pre- and post-training assessments as well as an audio-recorded role-play following the training. Research staff complete documentation related to the number of hours of training delivered to each site.Tracking technical assistance requests provides valuable information about the challenges faced during implementation. Measures encompass what technological assistance is needed to support implementation, requests for clinical support, content clarification, skills-building, and additional training. Technical assistance data is collected by Bridge staff, who log each request they receive, including by whom, what, where, and how assistance was requested and provided.Staff and leadership surveys assess our secondary study aim of examining multi-level factors that impede or facilitate implementation and effectiveness of Bridge. The measurements for this study aim were guided by the Consolidated Framework for Implementation Research (CFIR), which is widely used in implementation research . By examSurvey questions contain measures of selected CFIR constructs. This includes questions about organizational culture, opportunities for growth and learning within the organization, leadership and management styles, attitudes towards HIV, PWID and drug treatment (stigma), challenges faced by each organization and, post-implementation, opinions on the Bridge intervention, acceptability, adoption and appropriateness and effectiveness of the implementation strategies. Surveys are conducted using a computer-assisted self-interview (CASI) program. Participants are compensated $15 for each survey.The research team documents contextual changes that are challenging to capture in the staff or leadership surveys, including new protocols or policies regarding HIV, drug use, or other related services, new domestic or international funding sources or HIV-related programming, regularly scheduled activities of the AIDS Center or NSPs that might conflict with Bridge programming, and trends in staff turnover. Research staff in Kazakhstan regularly seek information about such changes and enter this information into a pre-set reporting form. As this data also affects ongoing study activities, it is collected and reviewed weekly by the study team.To assess the cost of the intervention, data is collected regarding staff time , intervention materials, and compensation for participants. This data collection is conducted after 1 year of implementation in each city, after the intervention is well-established and has reached a steady state. Additional data is gathered on time and materials for providing HIV-related services  at the NSPs and AIDS Centers. Unit costs for these services (staff labor rates and costs of tests and medications) are provided by staff at NSPs and AIDS Centers.Bridge includes a number of quality assurance (QA) protocols to ensure intervention quality and data accuracy. While the primary responsibility for intervention quality assurance remains within the supervisory model, the research team also monitors intervention progress and fidelity on an ongoing basis, through review of supervision records. The research team conducts quarterly observations at each NSP to observe the accuracy and the challenges of a tablet data collection system, and each reporting period, 10% of chart review reports from the AIDS Center are checked for accuracy.The research team has convened a data safety and monitoring board (DSMB), which consists of Kazakhstan-based researchers. This DSMB meets annually to review ongoing human subjects and data protocols and events.Aim 1 Hypothesis: Compared to pre-implementation time blocks, time blocks where Bridge is implemented will have increased numbers of PWID clients who (a) attend NSPs, (b) receive a rapid test for HIV at NSPs, and (c) link to HIV care at the AIDS center, when their test is positive for HIV care in the past 6 months).N = 24 NSPs). Hypothesis testing in this manner involves permuting the Bridge implementation status of each time point; since the time period “assignment” (pre-implementation vs. Bridge intervention implementation) is allocated based on city, permutations will account for clustering by city . Not only does this conservatively account for shared variance that might be present due to being located in the same city, statistical efficiency can be improved by clustered permutation testing [p value.Formal hypothesis testing for study aim 1 (the primary effectiveness aim) draws on data from two sources  correlations due to repeated measures with the same NSP and (2) correlations due to NSPs operating in the same city. Hypothesis testing will rely on Generalized Linear Mixed Models (GLMM) and Generalized Estimating Equations (GEE) as described and recommended for stepped-wedge trials . GLMM isα = 0.05 with two-tailed hypothesis testing and designing the study to have at least 80% statistical power. The smallest effect size will occur for the proportion achieving undetectable viral load; we posited a 25% point increase, which would result in achieving a level of coverage frequently posited to achieve significant reductions in HIV prevalence [p values as well as simulated cluster permutation . Results indicate 80% power is achieved with a sample size of 24 NSPs.Sample sizes for effectiveness outcome hypothesis testing (study aims 1 and 3) were determined from power analyses using evalence . Power aAim 2 Hypothesis: NSPs with greater utilization of the implementation strategies will have increased effectiveness within the time periods of Bridge implementation.To evaluate the study’s primary implementation aim (study aim 2), we will generate descriptive statistics on Bridge implementation strategies and study activities conducted, including numbers of staffing and clients served. We will use program documentation and supervision forms to generate measures of intervention fidelity, including the percentage of program activities conducted as planned for SNS peer recruiter coaching sessions and ARTAS sessions. These measures will be synthesized into summary measures that will be examined as mediators of effectiveness outcomes. Specifically, we will examine whether these measures are related to variability in effectiveness outcomes across NSPs in the periods of Bridge implementation by adding them as predictors in these effectiveness analyses using the primary outcome assessment data.We will calculate the estimated net cost of the intervention compared to no intervention and assess implications for feasibility and sustainability by conducting a budget impact analysis. Net cost of the intervention includes the cost of implementing Bridge as well as the cost of providing HIV-related services. Intervention costs will be assessed using micro-costing techniques , 42. A cThis paper describes the protocols for an implementation study to identify hard-to-reach and stigmatized populations of PWID, test them for HIV, and link them to HIV care, all of which is implemented at existing NSPs in Kazakhstan. This paper also describes how the effectiveness and implementation of this intervention will be rigorously evaluated through multiple assessments in a stepped-wedge, cluster design. This clinical trial has a number of strengths, including the innovative Bridge intervention, a multi-faceted and comprehensive data collective system, a bundle of implementation strategies that enhance existing structures, and integration into local HIV and harm reduction systems.The Bridge intervention revolutionizes the role that NSPs play in the existing HIV care system in Kazakhstan, transforming them from ordinary harm reduction programs into a single source of support for all stages of the HIV care continuum. It does this through its unique combination of three evidence-based interventions, targeting multiple stages of the HIV continuum of care through a streamlined approach. This integrated approach is strengthened further by involving multiple levels of staff . Bridge creatively utilizes a team-based approach and role redefinition to ensure that each site has a set of skilled staff to move clients along the continuum of care and even provides an internal supervision and group learning structure designed to increase local investment and ownership. Finally, by providing program services in NSPs, which are accessible, community-based organizations, Bridge responds to calls for differentiated approaches to HIV care. It takes advantage of existing close relations between outreach workers and local communities of PWID to provide them with linkage and retention support as well as enhanced recruitment and testing services. There are no other programs or services in Kazakhstan that currently provide a comprehensive range of services for PWID at a single location.As a research study, Bridge provides a range of innovative data collection procedures. Bridge incorporates biological, behavioral, interpersonal, organizational, community and structural level-assessments, allowing for evaluation of intervention effectiveness on multiple levels. Not only are these data collection systems comprehensive, they are also unique and carefully adapted to the context. The tablet-based data collection program is the only system currently being used in Kazakhstan to collect point-of-care data on services and linkages. Finally, Bridge’s comprehensive use of the CFIR framework responds to calls in the literature for a thorough application of CFIR constructs.By integrating Bridge into existing services in Kazakhstan, this study ensures high external validity, sustainability, and reproducibility to inform the scale up of Bridge in a range of low-threshold settings in Kazakhstan and in other low- and middle-income countries in the future. Bridge was designed specifically for the context of NSPs in Kazakhstan, based off the investigators’ past studies of PWID .As an implementation study, Bridge is subject to a unique set of challenges. Because Bridge is deeply integrated into local organizations, it is highly subject to influence from external factors. Unlike a randomized controlled trial, we cannot control changes in funding and staffing in the NSPs, organizational structure in the NSPs or AIDS Center, changes in test systems used, nor can we control for these differences across study sites. The large geographic scale and the long implementation period heighten these risks. Though we cannot control many of these elements, we will rely on staff and leadership surveys and our policy and environment monitoring tools to account for disruptions and control for their influence on the intervention.Another challenge is the differentiation between the activities related to Bridge and the Bridge study assessments. Some data collection elements, such as the tablet-based data entry system, require a great deal of effort on the part of the NSP staff, and we suspect that our outcomes of feasibility and acceptability of Bridge components might be contaminated by staff reactions to study data collection systems. We have tried to minimize these effects by initiating this data collection system during the pre-implementation period see Fig. . FurtherTo our knowledge, this is the only HIV implementation research study conducted with PWID or in harm reduction settings in the Central Asian region to address the full continuum of HIV services from diagnosis of new cases, linkage to HIV care to retention, and adherence to HIV care for viral load suppression. If successful, it may suggest that NSPs and other community-based harm reduction services have a crucial role to play in all stages of the HIV care continuum. Furthermore, our comprehensive implementation measures will show what organizational environments, staff characteristics, and types of implementation strategies and support for NSP staff are necessary for successful implementation an intervention. Moreover, this study informs the scale-up of Bridge intervention to other NSPs in Kazakhstan, as well as in other Central Asian countries and globally to curb the steep rise in HIV rates among PWID. Bridge rigorously examines barriers and facilitators to achieving these goals among the key populations that are so crucial to their success.


In southern California, most of the N air pollution is in oxidized forms as nitrogen oxides (NOx), nitric acid (HNO3), and particulate nitrate (NO3) resulting from fossil fuel combustion and subsequent complex photochemical reactions. In southern California, dry deposition of gases and particles provides most (up to 95%) of the atmospheric N to forests and other ecosystems. In the mixed-conifer forest zone, elevated deposition of N may initially benefit growth of vegetation, but chronic effects may be expressed as deterioration of forest health and sustainability. HNO3 vapor alone has a potential for toxic effects causing damage of foliar surfaces of pines and oaks. In addition, dry deposition of predominantly HNO3 has lead to changes in vegetation composition and contamination of ground- and stream water where terrestrial N loading is high. Long-term, complex interactions between N deposition and other environmental stresses such as elevated ozone (O3), drought, insect infestations, fire suppression, or intensive land management practices may affect water quality and sustainability of California forests and other ecosystems.Atmospheric deposition of nitrogen (N) in California ecosystems is ecologically significant and highly variable, ranging from about 1 to 45 kg/ha/year. The lowest ambient concentrations and deposition values are found in the eastern and northern parts of the Sierra Nevada Mountains and the highest in parts of the San Bernardino and San Gabriel Mountains that are most exposed to the Los Angeles air pollution plume. In the Sierra Nevada Mountains, N is deposited mostly in precipitation, although dry deposition may also provide substantial amounts of N. On the western slopes of the Sierra Nevada, the majority of airborne N is in reduced forms as ammonia (NH