The Influence of HLA Polymorphisms on the Severity of COVID-19 in the Romanian Population.

In this study, we aimed to investigate whether specific HLA alleles found in patients from Romania and the Republic of Moldova were associated with the severity of COVID-19 infection and its associated mortality. We analyzed the HLA alleles at the -A, -B, -C, -DRB1, and -DQB1 loci in a cohort of 130 individuals with severe and extremely severe forms of COVID-19, including 44 individuals who died. We compared these findings to a control group consisting of individuals who had either not been diagnosed with COVID-19 or had experienced mild forms of the disease. Using multivariate logistic regression models, we discovered that the B*27 and B*50 alleles were associated with an increased susceptibility to developing a severe form of COVID-19. The A*33 and C*15 alleles showed potential for offering protection against the disease. Furthermore, we identified two protective alleles (A*03 and DQB1*02) against the development of extremely severe forms of COVID-19. By utilizing score statistics, we established a statistically significant association between haplotypes and disease severity (p = 0.021). In summary, this study provides evidence that HLA genotype plays a role in influencing the clinical outcome of COVID-19 infection.

The impact of the COVID-19 pandemic on primary health care practices and patient management in the Republic of Moldova - results from the PRICOV-19 survey.

BACKGROUND: The COVID-19 pandemic has had an enormous impact on health systems in Europe and has generated unprecedented challenges for tertiary care. Less is known about the effects on the activities of local family doctors (FDs), who have shifted tasks and adapted their practice to accommodate the new services brought by the pandemic. The PRICOV-19 study was a multi-country survey aiming to understand the challenges posed by the pandemic in primary health care (PHC) practices around Europe. Within the framework of this study, we assessed the impact of the pandemic on PHC facilities in urban, rural, and mixed urban/rural areas in the Republic of Moldova. METHODS: We present the results from the PRICOV-19 questionnaire designed at Ghent University (Belgium) and distributed between January and March 2021 to PHC facilities from the 35 districts of the Republic of Moldova. This analysis presents descriptive data on limitations to service delivery, staff role changes, implementation and acceptance of COVID-19 guidelines, and incidents reported on staff and patient safety during the pandemic. RESULTS: Results highlighted the differences between facilities located in urban, rural, and mixed areas in several dimensions of PHC. Nearly half of the surveyed facilities experienced limitations in the building or infrastructure when delivering services during the pandemic. 95% of respondents reported an increase in time spent giving information to patients by phone, and 88% reported an increase in responsibilities. Few practices reported errors in clinical assessments, though a slightly higher number of incidents were reported in urban areas. Half of the respondents reported difficulties delivering routine care to patients with chronic conditions and a delay in treatment-seeking. CONCLUSIONS: During the pandemic, the workload of PHC staff saw a significant increase, and practices met important structural and organizational limitations. Consequently, these limitations may have also affected care delivery for vulnerable patients with chronic conditions. Adjustments and bottlenecks need to be addressed, considering the different needs of PHC facilities in urban, rural, and mixed areas.

Implementing a package of noncommunicable disease interventions in the Republic of Moldova: two-year follow-up data.

Noncommunicable diseases (NCDs) are a growing challenge in the Republic of Moldova. A previously reported pilot cluster randomized controlled trial aimed to determine the feasibility of implementing and evaluating essential interventions for NCDs (e.g. cardiovascular risk scoring, hypertension management, statin treatment, etc.) in primary health care in the Republic of Moldova, with a view toward national scale up. One-year follow-up data (previously published) demonstrated modest improvements in NCD risk factor identification and management could be achieved. Herein, we report the second-year follow-up data and conclude that sustainable improvements in NCD risk factor control (e.g. hypertension control) can be achieved in primary health care in low resource settings by adapting existing resources (e.g. WHO PEN) and conducting focused clinical training and support. If scaled to a national level, these improvements in risk factor control could significantly translate to reductions in premature mortality from NCDs.

Implementing Package of Essential Non-communicable Disease Interventions in the Republic of Moldova-a feasibility study.

BACKGROUND: The aim of this study is to determine the feasibility of implementing and evaluating the World Health Organization Package of Essential Non-communicable Disease Interventions (WHO PEN) approach in primary healthcare in the Republic of Moldova. METHODS: According to our published a priori methods, 20 primary care clinics were randomized to 10 intervention and 10 control clinics. The intervention consisted of implementation of adapted WHO PEN guidelines and structured training for health workers; the control clinics continued with usual care. Data were gathered from paper-based patient records in July 2017 and August 2018 resulting in a total of 1174 and 995 patients in intervention and control clinics at baseline and 1329 and 1256 at follow-up. Pre-defined indicators describing assessment of risk factors and total cardiovascular risk, prescribing medications and treatment outcomes were calculated. Differences between baseline and follow-up as well as between intervention and control clinics were calculated using logistic and linear regression models and by assessing interaction effects. RESULTS: Improvements were seen in recording smoking status, activity to measure HbA1c among diabetes patients and achieving control in hypertension treatment. Improvement was also seen in identification of patients with hypertension or diabetes. Less improvement or even deterioration was seen in assessing total risk or prescribing statins for high-risk patients. CONCLUSIONS: It is feasible to evaluate the quality and management of patients with non-communicable diseases in low-resource settings from routine data. Modest improvements in risk factor identification and management can be achieved in a relatively short period of time.

Mental health system reform in Moldova: Description of the program and reflections on its implementation between 2014 and 2019.

In 2014, the Republic of Moldova started a systematic process of reforming its mental health system, implementing priority actions set out in the National Mental Health Programme. The reform entailed a service delivery re-design, instituting mechanisms for collaboration across health and social sectors, and revision of the policy framework. Outcomes of the first 4 years of the reform included: 1) the establishment of a network of mental health services in 4 pilot districts embedding mental health diagnosis, treatment and referral in primary and specialized mental healthcare; 2) creation of an enabling policy environment at the national and district level; and 3) strengthened community support and acceptance of mental health issues. Objectives of the first Phase were achieved and the reform is now in its second Phase (2018-2022). The implementation strategy in Phase 1 focused efforts on 4 pilot districts, whereas Phase 2 harnesses lessons learned from Phase 1 and facilitates local leaders and actors to scale-up the model to all 32 districts and municipalities in Moldova. Ownership over the reform process shifted from project-led in Phase 1 to national and local government-led in Phase 2. We reflect on the process and contents of the mental health reform, discuss lessons learned and implementation challenges encountered. We conclude with learning points for policymakers and researchers considering mental health reform in other countries.

Protocol for the evaluation of a pilot implementation of essential interventions for the prevention of cardiovascular diseases in primary healthcare in the Republic of Moldova.

INTRODUCTION: Nearly 90% of all deaths in the Republic of Moldova are caused by non-communicable diseases, the majority of which (55%) are caused by cardiovascular diseases (CVD). In addition to reducing premature mortality from CVD, it is estimated that strengthening primary healthcare could cut the number of hypertension-related hospital admissions and diabetes-related hospitalisations in half. The aim of this evaluation is to determine the feasibility of implementing and evaluating essential interventions for the prevention of CVD in primary healthcare in the Republic of Moldova, with a view towards national scale-up. METHODS AND ANALYSIS: A national steering group including international experts will be convened to adapt WHO Package of Essential NCD Intervention from Primary Healthcare in Low Resource Settings protocols 1 and 2 to the health system of the Republic of Moldova, develop and conduct training of primary healthcare workers and test a core set of indicators to monitor the quality of care and change in clinical practice. To evaluate the impact of this pilot implementation, a pragmatic, sequential mixed methods explanatory design, composed of quantitative and qualitative strands of equal weight, will be used. Twenty primary healthcare centres will be selected and randomised to the training and implementation arm (n=10) and the usual care arm (n=10). At baseline and 12 months follow-up, a standardised data collection form will be piloted to extract data directly from patient paper records in order to estimate the change in clinical practice. Semi-structured interviews and interclinic peer workshops will be conducted at 12 months follow-up, and qualitative data collected from these formats will be analysed thematically for explanatory themes that relate to the quantitative findings. ETHICS AND DISSEMINATION: Ethical review and approval has been obtained. Findings of the evaluation will be shared in a project report to key stakeholders, presented back to participants and written into a manuscript for an open access peer-reviewed scientific journal.

Single-nucleotide polymorphisms at five loci are associated with C-reactive protein levels in a cohort of Filipino young adults.

C-reactive protein (CRP) is a component of nonspecific immune defense and is a reliable marker of low-grade inflammation involved in obesity, type 2 diabetes and cardiovascular disease. Genome-wide association studies in middle-aged and elderly populations, predominantly of European descent, demonstrated associations of CRP levels with single-nucleotide polymorphisms (SNPs) at several loci. To examine whether the variants identified are replicated in Filipino young adults, we applied Tobit regression models to study the association of plasma CRP with 12 SNPs at seven loci in a cohort of 1691 Filipino young adults (aged 21.5±0.3 years) from the Cebu Longitudinal Health and Nutrition Survey. SNPs in or near CRP (P=3.2 × 10(-11)), HNF1A, IL6R, APOE-APOC1 and LEPR showed significant associations (P<0.05) and together explained 4.8% of the total variation in CRP. Modest interactions were observed between LEPR-rs1892534 and waist circumference (uncorrected P(interaction)=0.020) and between APOE-rs769449 and pathogen exposure (uncorrected P(interaction)=0.0073) in models predicting CRP. Our results demonstrated that variants in several loci are significantly associated with plasma CRP in Filipino young adults, suggesting shared genetic influences on circulating CRP across populations and age groups.

Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ.

Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ≤ 7.2 × 10(-16)), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10(-9)) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10(-7)). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ≤ 1.6 × 10(-9)). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C-G haplotype in both CLHNS mothers (P = 1.8 × 10(-25)) and offspring (P = 8.7 × 10(-32)). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1-ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos.

Development of family medicine education in Moldova with Carelift International.

BACKGROUND: As in other former Soviet republics, Moldova's health system has been dependent upon multispecialty and hospital care. The government has undertaken a planning process to develop a primary care-based system utilizing family physicians. Carelift International and Moldova State Medical and Pharmaceutical University joined together to design an educational program to help create a family medicine specialty in the country. METHODS: Introductory concepts were incorporated into a workshop co-sponsored by the World Health Organization, Carelift International, UNICEF and Moldova Ministry of Health. Faculty teams participated in Carelift's 8-week US program, comprising a range of topics in family medicine: educational development at all levels, public health applications, health care organization, insurance, financing, and technology. Training also included 1 week in Finland, a fellowship in Lithuania, an in-country workshop on rural health, and a supplemental 5-week US immersion program. OUTCOMES: A Department of Family Medicine was established, and a residency program instituted. It has already been strengthened with a 2-week introduction to the specialty, and rotations in family practice centers. Continued improvements and updates are planned. Urban and rural model family practice centers serve concurrent purposes of teaching, demonstrating and health care. Carelift shipped equipment for the principal center and a department library, and is equipping a teaching family practice center near the university. The Society of Family Physicians of Moldova was founded. The introduction of family medicine as a discipline into the health system of Moldova could be a valuable model for other former Soviet republics.