Developing a National-Level Concept Dictionary for EHR Implementations in Kenya

The increasing adoption of Electronic Health Records (EHR) by developing countries comes with the need to develop common terminology standards to assure semantic interoperability. In Kenya, where the Ministry of Health has rolled out an EHR at 646 sites, several challenges have emerged including variable dictionaries across implementations, inability to easily share data across systems, lack of expertise in dictionary management, lack of central coordination and custody of a terminology service, inadequately defined policies and processes, insufficient infrastructure, among others. A Concept Working Group was constituted to address these challenges. The country settled on a common Kenya data dictionary, initially derived as a subset of the Columbia International eHealth Laboratory (CIEL) / Millennium Villages Project (MVP) dictionary. The initial dictionary scope largely focuses on clinical needs. Processes and policies around dictionary management are being guided by the framework developed by Bakhshi-Raiez et al. Technical and infrastructure-based approaches are also underway to streamline workflow for dictionary management and distribution across implementations. Kenya's approach on comprehensive common dictionary can serve as a model for other countries in similar settings

Automatic identification of informative regions with epigenomic changes associated to hematopoiesis

Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify 42 human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis. The analysis of the orthogonal dimension of the chromatin space identify 32,662 chromatin determinant regions (CDRs), genomic regions with different epigenetic characteristics between the cell types. Functional analysis revealed that these regions are linked with cell identities. The inclusion of leukemia epigenomes in the healthy hematological chromatin sample space gives us insights on the healthy cell types that are more epigenetically similar to the disease samples. Further analysis of tumoral epigenetic alterations in hematopoietic CDRs points to sets of genes that are tightly regulated in leukemic transformations and commonly mutated in other tumors. Our method provides an analytical approach to study the relationship between epigenomic changes and cell lineage differentiation. Method availability: https://github.com/david-juan/ChromDet.European Union’s Seventh Framework Programme [FP7/2007–2013, 282510 (BLUEPRINT)]; Spanish Ministry of Economy, Industry and Competitiveness and European Regional Development Fund [Project Retos BFU2015–71241-R]. Funding for open access charge: Project Retos BFU2015–71241-R (to A.V.).Peer ReviewedPostprint (published version

Increased condom use among key populations using oral PrEP in Kenya: results from large scale programmatic surveillance

Background: Female sex workers (FSW) and men having sex with men (MSM) in Kenya have high rates of HIV infection. Following a 2015 WHO recommendation, Kenya initiated national scale-up of pre-exposure prophylaxis (PrEP) for all persons at high-risk. Concerns have been raised about PrEP users’ potential changes in sexual behaviors such adopting condomless sex and multiple partners as a result of perceived reduction in HIV risk, a phenomenon known as risk compensation. Increased condomless sex may lead to unintended pregnancies and sexually transmitted infections and has been described in research contexts but not in the programmatic setting. This study looks at changes in condom use among FSW and MSM on PrEP through a national a scale-up program. Methods: Routine program data collected between February 2017 and December 2019 were used to assess changes in condom use during the frst three months of PrEP in 80 health facilities supported by a scale-up project, Jilinde. The primary outcome was self-reported condom use. Analyses were conducted separately for FSW and for MSM. Log-Binomial Regression with Generalized Estimating Equations was used to compare the incidence proportion (“risk”) of consistent condom use at the month 1, and month 3 visits relative to the initiation visit. Results: At initiation, 69% of FSW and 65% of MSM reported consistent condom use. At month 3, this rose to 87% for FSW and 91% for MSM. MSM were 24% more likely to report consistent condom use at month 1 (Relative Risk [RR], 1.24, 95% Confidence Interval [CI], 1.18–1.30) and 40% more likely at month 3 (RR, 1.40, 95% CI, 1.33–1.47) compared to at initiation. FSW were 15% more likely to report consistent condom use at the month one visit (RR, 1.15, 95% CI, 1.13–1.17) and 27% more likely to report condom use on the month 3 visit (RR 1.27, 95% CI, 1.24–1.29). Conclusion: Condom use increased substantially among both FSW and MSM. This may be because oral PrEP was provided as part of a combination prevention strategy that included counseling and condoms but could also be due to the low retention rates among those who initiated

Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

Estimating the costs and perceived benefits of oral pre-exposure prophylaxis (PrEP) delivery in ten counties of Kenya: a costing and a contingent valuation study

BackgroundKenya included oral PrEP in the national guidelines as part of combination HIV prevention, and subsequently began providing PrEP to individuals who are at elevated risk of HIV infection in 2017. However, as scale-up continued, there was a recognized gap in knowledge on the cost of delivering oral PrEP. This gap limited the ability of the Government of Kenya to budget for its PrEP scale-up and to evaluate PrEP relative to other HIV prevention strategies. The following study calculated the actual costs of oral PrEP scale-up as it was being delivered in ten counties in Kenya. This costing also allowed for a comparison of various models of service delivery in different geographic regions from the perspective of service providers in Kenya. In addition, the analysis was also conducted to understand factors that indicate why some individuals place a greater value on PrEP than others, using a contingent valuation technique.MethodsData collection was completed between November 2017 and September 2018. Costing data was collected from 44 Kenyan health facilities, consisting of 23 public facilities, 5 private facilities and 16 drop-in centers (DICEs) through a cross-sectional survey in ten counties. Financial and programmatic data were collected from financial and asset records and through interviewer administered questionnaires. The costs associated with PrEP provision were calculated using an ingredients-based costing approach which involved identification and costing of all the economic inputs (both direct and indirect) used in PrEP service delivery. In addition, a contingent valuation study was conducted at the same 44 facilities to understand factors that reveal why some individuals place a greater value on PrEP than others. Interviews were conducted with 2,258 individuals (1,940 current PrEP clients and 318 non-PrEP clients). A contingent valuation method using a “payment card approach” was used to determine the maximum willingness to pay (WTP) of respondents regarding obtaining access to oral PrEP services.ResultsThe weighted cost of providing PrEP was $253 per person year, ranging from$217 at health centers to $283 at dispensaries. Drop-in centers (DICEs), which served about two-thirds of the client volume at surveyed facilities, had a unit cost of$276. The unit cost was highest for facilities targeting MSM ($355), while it was lowest for those targeting FSW ($248). The unit cost for facilities targeting AGYW was $323 per person year. The largest percentage of costs were attributable to personnel (58.5$2 per month (mean was $4.07 per month). This covers only one-third of the monthly cost of the medication (approximately$6 per month) and less than 10% of the full cost of delivering PrEP ($21 per month). A sizable proportion of current clients (27%) were unwilling to pay anything for PrEP. Certain populations put a higher value on PrEP services, including: FSW and MSM, Muslims, individuals with higher education, persons between the ages of 20 and 35, and households with a higher income and expenditures.DiscussionThis is the most recent and comprehensive study on the cost of PrEP delivery in Kenya. These results will be used in determining resource requirements and for resource mobilization to facilitate sustainable PrEP scale-up in Kenya and beyond. This contingent valuation study does have important implications for Kenya's PrEP program. First, it indicates that some populations are more motivated to adopt oral PrEP, as indicated by their higher WTP for the service. MSM and FSW, for example, placed a higher value on PrEP than AGYW. Higher educated individuals, in turn, put a much higher value on PrEP than those with less education (which may also reflect the higher “ability to pay” among those with more education). This suggests that any attempt to increase demand or improve PrEP continuation should consider these differences in client populations. Cost recovery from existing PrEP clients would have potentially negative consequences for uptake and continuation

RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression

Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.This work was supported by a HFSP fellowship to M.C-A. (LT000110/2015-L/1), grants from the Spanish Ministerio de Ciencia e Innovación (MCI) (SAF2015-64287R, SAF2017-90604-REDT-NurCaMein, RTI2018-095928-B100), La Marató de TV3 Foundation (201605-32) and Comunidad de Madrid (MOIR-B2017/BMD-3684) to M.R, and the Formación de Profesorado Universitario (FPU17/01731) programme (MCI) to J.P. The CNIC is supported by the MCI and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Initial evidence of reduction of malaria cases and deaths in Rwanda and Ethiopia due to rapid scale-up of malaria prevention and treatment

<p>Abstract</p> <p>Background</p> <p>An increasing number of malaria-endemic African countries are rapidly scaling up malaria prevention and treatment. To have an initial estimate of the impact of these efforts, time trends in health facility records were evaluated in selected districts in Ethiopia and Rwanda, where long-lasting insecticidal nets (LLIN) and artemisinin-based combination therapy (ACT) had been distributed nationwide by 2007.</p> <p>Methods</p> <p>In Ethiopia, a stratified convenience sample covered four major regions where (moderately) endemic malaria occurs. In Rwanda, two districts were sampled in all five provinces, with one rural health centre and one rural hospital selected in each district. The main impact indicator was percentage change in number of in-patient malaria cases and deaths in children < 5 years old prior to (2001–2005/6) and after (2007) nationwide implementation of LLIN and ACT.</p> <p>Results</p> <p>In-patient malaria cases and deaths in children < 5 years old in Rwanda fell by 55% and 67%, respectively, and in Ethiopia by 73% and 62%. Over this same time period, non-malaria cases and deaths generally remained stable or increased.</p> <p>Conclusion</p> <p>Initial evidence indicated that the combination of mass distribution of LLIN to all children < 5 years or all households and nationwide distribution of ACT in the public sector was associated with substantial declines of in-patient malaria cases and deaths in Rwanda and Ethiopia. Clinic-based data was a useful tool for local monitoring of the impact of malaria programmes.</p

Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma?:Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies

γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.S