Characterization of Commercially Available Human Primary Alveolar Epithelial Cells.

In vitro lung research requires appropriate cell culture models that adequately mimic in vivo structure and function. Previously, researchers extensively used commercially available and easily expandable A549 and NCI-H441 cells, which replicate some but not all features of alveolar epithelial cells. Specifically, these cells are often restricted by terminally altered expression while lacking important alveolar epithelial characteristics. Of late, human primary alveolar epithelial cells (hPAEpCs) have become commercially available but are so far poorly specified. Here, we applied a comprehensive set of technologies to characterize their morphology, surface marker expression, transcriptomic profile, and functional properties. At optimized seeding numbers of 7,500 cells per square centimeter and growth at a gas-liquid interface, hPAEpCs formed regular monolayers with tight junctions and amiloride-sensitive transepithelial ion transport. Electron microscopy revealed lamellar body and microvilli formation characteristic for alveolar type II cells. Protein and single-cell transcriptomic analyses revealed expression of alveolar type I and type II cell markers; yet, transcriptomic data failed to detect NKX2-1, an important transcriptional regulator of alveolar cell differentiation. With increasing passage number, hPAEpCs transdifferentiated toward alveolar-basal intermediates characterized as SFTPC-, KRT8high, and KRT5- cells. In spite of marked changes in the transcriptome as a function of passaging, Uniform Manifold Approximation and Projection plots did not reveal major shifts in cell clusters, and epithelial permeability was unaffected. The present work delineates optimized culture conditions, cellular characteristics, and functional properties of commercially available hPAEpCs. hPAEpCs may provide a useful model system for studies on drug delivery, barrier function, and transepithelial ion transport in vitro.

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion.

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform's true impact on human health.

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses.

Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs' ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.

The cost-effectiveness of school-based interventions for chronic diseases: a systematic review.

BACKGROUND: Chronic diseases, or non-communicable diseases (NCD), are conditions of long duration and often influenced and contributed by complex interactions of several variables, including genetic, physiological, environmental, and behavioral factors. These conditions contribute to death, disability, and subsequent health care costs. Primary and secondary school settings provide an opportunity to deliver relatively low cost and effective interventions to improve public health outcomes. However, there lacks systematic evidence on the cost-effectiveness of these interventions. METHODS: We systematically searched four databases (PubMed/Medline, Cochrane, Embase, and Web of Science) for published studies on the cost-effectiveness of chronic-disease interventions in school settings. Studies were eligible for inclusion if they assessed interventions of any chronic or non-communicable disease, were conducted in a school setting, undertook a full cost-effectiveness analysis and were available in English, Spanish, or French. RESULTS: Our review identified 1029 articles during our initial search of the databases, and after screening, 33 studies were included in our final analysis. The most used effectiveness outcome measures were summary effectiveness units such as quality-adjusted life years (QALYs) (22 articles; 67%) or disability-adjusted life years (DALYs) (4 articles; 12%). The most common health condition for which an intervention targets is overweight and obesity. Almost all school-based interventions were found to be cost-effective (30 articles; 81%). CONCLUSION: Our review found evidence to support a number of cost-effective school-based interventions targeting NCDs focused on vaccination, routine physical activity, and supplement delivery interventions. Conversely, many classroom-based cognitive behavioral therapy for mental health and certain multi-component interventions for obesity were not found to be cost-effective.

Workforce estimate to treat mental disorders in the Kingdom of Saudi Arabia.

BACKGROUND: Mental, neurological, and substance abuse (MNS) disorders describe a range of conditions that affect the brain and cause distress or functional impairment. In the Middle East and North Africa (MENA), MNS disorders make up 10.88 percent of the burden of disease as measured in disability-adjusted life years. The Kingdom of Saudi Arabia (KSA) is one of the main providers of mental health services and one of the largest contributors to mental health research in the region. Within the past decade, mental health resources and services has increased. METHODS: We employ a needs-based workforce estimate as a planning exercise to arrive at the total number of psychiatrists, nurses, and psychosocial care providers needed to meet the epidemiological need of mental health conditions of the population of KSA. Estimates for a potential mental health workforce gap were calculated using five steps: Step 1-Quantify target population for priority mental health conditions. Step 2-Identify number of expected cases per year. Step 3-Set target service coverage for each condition. Step 4-Estimate cost-effective health care service resource utilization for each condition. Step 5-Estimate service resources needed for each condition. RESULTS: The planning exercise indicates an epidemiologic need for a total of 17,100 full-time-equivalent (FTE) health care providers to treat priority MNS disorders. KSA appears to have a need-based shortage of 10,400 health workers to treat mental disorders. A total of 100 psychiatrists, 5700 nurses, and 4500 psychosocial care providers would be additionally needed (that is, above and beyond current levels) to address the priority mental health conditions. The shortfall is particularly severe for nurses and psychosocial workers who make up 98.9 percent of the shortfall. This shortage is substantial when compared to other high-income countries. Overall, the workforce needed to treat MNS conditions translates to 49.2 health workers per 100,000 population. CONCLUSION: Challenges to addressing the shortfall are Saudi specific which includes awareness of cultural customs and norms in the medical setting. These challenges are compounded by the lack of Saudi nationals in the mental health workforce. Saudi nationals make up 29.5 percent of the physician workforce and 38.8 percent of the nursing workforce. Policymakers and planners supplement this shortfall with non-Saudi providers, who must be mindful of Saudi-specific cultural considerations. Potential solutions to reducing the shortfall of mental health care workers includes nurse task shifting and training of general practitioners to screen for, and treat, a subset of MNS disorders.

A rapid mixed-methods assessment of Libya's primary care system.

BACKGROUND: Libya has experienced decades of violent conflict that have severely disrupted health service delivery. The Government of National Unity is committed to rebuilding a resilient health system built on a platform of strong primary care. AIM: Commissioned by the government, we set out to perform a rapid assessment of the system as it stands and identify areas for improvement. DESIGN AND SETTING: We used a rapid applied policy explanatory-sequential mixed-methods design, working with Libyan data and Libyan policymakers, with supporting interview data from other primary care policymakers working across the Middle East and North Africa region. METHOD: We used the Primary Health Care Performance Initiative framework to structure our assessment. Review of policy documents and secondary analysis of WHO and World Bank survey data informed a series of targeted policymaker interviews. We used deductive framework analysis to synthesise our findings. RESULTS: We identified 11 key documents and six key policymakers to interview. Libya has strong policy commitments to providing good quality primary care, and a high number of health staff and facilities. Access to services and trust in providers is high. However, a third of facilities are non-operational; there is a marked skew towards axillary and administrative staff; and structural challenges with financing, logistics, and standards has led to highly variable provision of care. CONCLUSION: In reforming the primary care system, the government should consolidate leadership, clarify governance structures and systems, and focus on setting national standards for human resources for health, facilities, stocks, and clinical care.

A scoping review on the impact of the COVID-19 pandemic on physical activity and sedentary behavior in Saudi Arabia.

BACKGROUND: In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. METHODS: We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. RESULTS: Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2-18 years), and 16 studies included adults (age: 15-99 years). Data collection periods were < = 5 months, with 17 studies collecting data in 2020 only, one study in 2020-2021, and one study in 2021. The median analytic sample size was 363 (interquartile range 262-640). Three studies of children/adolescents collected behaviors online at one time using parental reporting, with one also allowing self-reporting. All three studies found that physical activity was lower during and/or following the lockdown than before the lockdown. Two studies found screen time, television watching, and playing video games were higher during or following the lockdown than before the lockdown. Sixteen adult studies assessed physical activity, with 15 utilizing self-reporting and one using accelerometry. Physical activity, exercise, walking, and park visits were all lower during or following the lockdown than before the lockdown. Six adult studies assessed sedentary behavior using self-report. Sitting time (4 studies) and screen time (2 studies) were higher during or following the lockdown than before the lockdown. CONCLUSIONS: Among children, adolescents, and adults, studies consistently indicated that in the short-term, physical activity decreased and sedentary behavior increased in conjunction with the movement restrictions. Given the widespread impact of the pandemic on other health behaviors, it would be important to continue tracking behaviors post-lockdown and identify subpopulations that may not have returned to their physical activity and sedentary behavior to pre-pandemic levels to focus on intervention efforts.

Projected impact of population aging on non-communicable disease burden and costs in the Kingdom of Saudi Arabia, 2020-2030.

BACKGROUND: The number of people aged greater than 65 years per 100 people aged 20-64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. METHODS: Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. RESULTS: The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. CONCLUSIONS: Managing the growing NCD burden in KSA's aging population will require substantial healthcare spending increases over the coming years.

Behavioural economic interventions to reduce health care appointment non-attendance: a systematic review and meta-analysis.

BACKGROUND: Appointment non-attendance - often referred to as "missed appointments", "patient no-show", or "did not attend (DNA)" - causes volatility in health systems around the world. Of the different approaches that can be adopted to reduce patient non-attendance, behavioural economics-oriented mechanisms (i.e., psychological, cognitive, emotional, and social factors that may impact individual decisions) are reasoned to be better suited in such contexts - where the need is to persuade, nudge, and/ or incentivize patients to honour their scheduled appointment. The aim of this systematic literature review is to identify and summarize the published evidence on the use and effectiveness of behavioural economic interventions to reduce no-shows for health care appointments. METHODS: We systematically searched four databases (PubMed/Medline, Embase, Scopus, and Web of Science) for published and grey literature on behavioural economic strategies to reduce no-shows for health care appointments. Eligible studies met four criteria for inclusion; they were (1) available in English, Spanish, or French, (2) assessed behavioural economics interventions, (3) objectively measured a behavioural outcome (as opposed to attitudes or preferences), and (4) used a randomized and controlled or quasi-experimental study design. RESULTS: Our initial search of the five databases identified 1,225 articles. After screening studies for inclusion criteria and assessing risk of bias, 61 studies were included in our final analysis. Data was extracted using a predefined 19-item extraction matrix. All studies assessed ambulatory or outpatient care services, although a variety of hospital departments or appointment types. The most common behaviour change intervention assessed was the use of reminders (n = 56). Results were mixed regarding the most effective methods of delivering reminders. There is significant evidence supporting the effectiveness of reminders (either by SMS, telephone, or mail) across various settings. However, there is a lack of evidence regarding alternative interventions and efforts to address other heuristics, leaving a majority of behavioural economic approaches unused and unassessed. CONCLUSION: The studies in our review reflect a lack of diversity in intervention approaches but point to the effectiveness of reminder systems in reducing no-show rates across a variety of medical departments. We recommend future studies to test alternative behavioural economic interventions that have not been used, tested, and/or published before.

Emergency care in post-conflict settings: a systematic literature review.

BACKGROUND: Emergency care systems (ECS) organize and provide access to life-saving care both during transport and at health facilities. Not enough is known about ECS in uncertain contexts such as post-conflict settings. This review aims to systematically identify and summarize the published evidence on the delivery of emergency care in post-conflict settings and to guide health sector planning. METHODS: We searched five databases (PubMed MEDLINE, Web of Science, Embase, Scopus, and Cochrane) in September 2021 to identify relevant articles on ECS in post-conflict settings. Included studies (1) described a context that is post-conflict, conflict-affected, or was impacted by war or crisis; (2) examined the delivery of an emergency care system function; (3) were available in English, Spanish, or French; and (4) were published between 1 and 2000 and 9 September 2021. Data were extracted and mapped using the essential system functions identified in the World Health Organization (WHO) ECS Framework to capture findings on essential emergency care functions at the scene of injury or illness, during transport, and through to the emergency unit and early inpatient care. RESULTS: We identified studies that describe the unique burden of disease and challenges in delivering to the populations in these states, pointing to particular gaps in prehospital care delivery (both during scene response and during transport). Common barriers include poor infrastructure, lingering social distrust, scarce formal emergency care training, and lack of resources and supplies. CONCLUSION: To our knowledge, this is the first study to systematically identify the evidence on ECS in fragile and conflict-affected settings. Aligning ECS with existing global health priorities would ensure access to these critical life-saving interventions, yet there is concern over the lack of investments in frontline emergency care. An understanding of the state of ECS in post-conflict settings is emerging, although current evidence related to best practices and interventions is extremely limited. Careful attention should be paid to addressing the common barriers and context-relevant priorities in ECS, such as strengthening prehospital care delivery, triage, and referral systems and training the health workforce in emergency care principles.

Estimating the effect of non-pharmaceutical interventions to mitigate COVID-19 spread in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) quickly controlled the spread of SARS-CoV-2 by implementing several non-pharmaceutical interventions (NPIs), including suspension of international and national travel, local curfews, closing public spaces (i.e., schools and universities, malls and shops), and limiting religious gatherings. The KSA also mandated all citizens to respect physical distancing and to wear face masks. However, after relaxing some restrictions during June 2020, the KSA is now planning a strategy that could allow resuming in-person education and international travel. The aim of our study was to evaluate the effect of NPIs on the spread of the COVID-19 and test strategies to open schools and resume international travel. METHODS: We built a spatial-explicit individual-based model to represent the whole KSA population (IBM-KSA). The IBM-KSA was parameterized using country demographic, remote sensing, and epidemiological data. A social network was created to represent contact heterogeneity and interaction among age groups of the population. The IBM-KSA also simulated the movement of people across the country based on a gravity model. We used the IBM-KSA to evaluate the effect of different NPIs adopted by the KSA (physical distancing, mask-wearing, and contact tracing) and to forecast the impact of strategies to open schools and resume international travels. RESULTS: The IBM-KSA results scenarios showed the high effectiveness of mask-wearing, physical distancing, and contact tracing in controlling the spread of the disease. Without NPIs, the KSA could have reported 4,824,065 (95% CI: 3,673,775-6,335,423) cases by June 2021. The IBM-KSA showed that mandatory mask-wearing and physical distancing saved 39,452 lives (95% CI: 26,641-44,494). In-person education without personal protection during teaching would have resulted in a high surge of COVID-19 cases. Compared to scenarios with no personal protection, enforcing mask-wearing and physical distancing in schools reduced cases, hospitalizations, and deaths by 25% and 50%, when adherence to these NPIs was set to 50% and 70%, respectively. The IBM-KSA also showed that a quarantine imposed on international travelers reduced the probability of outbreaks in the country. CONCLUSIONS: This study showed that the interventions adopted by the KSA were able to control the spread of SARS-CoV-2 in the absence of a vaccine. In-person education should be resumed only if NPIs could be applied in schools and universities. International travel can be resumed but with strict quarantine rules. The KSA needs to keep strict NPIs in place until a high fraction of the population is vaccinated in order to reduce hospitalizations and deaths.

National medicines policy development, Saudi Arabia.

Medicines are at the core of every health system. The World Health Organization recommends countries develop national medicines policies that guide production, procurement, prescription and provision of medicines so that people can access the medicines they need at prices they can afford, while avoiding irrational use. However, the development of such policies is rarely straightforward. We describe important components of the national medicines policy in Saudi Arabia, which was developed within a broader transformation of the health system and the economy. The new policy formalizes existing best practices, shapes emerging policies and sets a direction for future development in four main areas. First, the policy seeks to consolidate institutional roles to provide greater cohesion; second it aims to reshape procurement and prescribing habits, with a greater focus on cost containment; third, it lays out policies which focus on assuring a secure supply of good-quality medicines, including essential medicines with limited profit potential and new products. Finally, the policy supports the growth of the domestic pharmaceutical industry, including the development of human resources. Many sectors and institutions joined in the development of the medicines policy, which was underpinned by a review of the past and current pharmaceutical context in Saudi Arabia, and good practices globally. The resulting policy was built on evidence and endeavours to give clear direction to the pharmaceutical industry and implementing agencies on rules and requirements, professional norms and institutional roles. At the same time, it maintains flexibility to allow for adaptation in a rapidly evolving institutional landscape.

Les médicaments sont au cœur de tout système de santé. L'Organisation mondiale de la Santé recommande aux pays d'élaborer des politiques pharmaceutiques nationales qui déterminent la production, l'obtention, la prescription et la fourniture de médicaments, afin que la population puisse accéder aux traitements requis à un prix abordable sans toutefois tomber dans un usage irrationnel. Mais cette élaboration est rarement simple. Dans le présent document, nous abordons les principaux aspects de la politique pharmaceutique nationale en Arabie saoudite, développée dans le cadre d'une vaste transformation de l'économie et du système de santé. Cette nouvelle politique officialise les bonnes pratiques existantes, façonne les projets émergents et définit une orientation pour l'évolution future dans quatre domaines clés. Premièrement, elle cherche à renforcer le rôle des institutions pour améliorer la cohésion. Deuxièmement, elle vise à remanier les habitudes d'obtention et de prescription, en se focalisant sur la maîtrise des coûts. Troisièmement, elle établit des mesures destinées à assurer un approvisionnement sûr en médicaments de qualité, y compris en nouveaux produits et médicaments essentiels au potentiel de rentabilité limité. Et quatrièmement, elle soutient la croissance de l'industrie pharmaceutique dans le pays, notamment le développement des ressources humaines. De nombreux secteurs et institutions ont contribué à l'élaboration de cette politique, qui s'appuie sur une analyse du contexte pharmaceutique antérieur et actuel en Arabie saoudite ainsi que sur les bonnes pratiques mondiales. Le résultat repose sur des éléments et efforts tangibles. Il montre clairement à l'industrie pharmaceutique et aux organismes de mise en œuvre la marche à suivre en matière de règles et d'exigences, de normes professionnelles et de rôles institutionnels. Et dans le même temps, il prévoit suffisamment de flexibilité pour s'adapter à un paysage institutionnel en constante mutation.

Los medicamentos son el núcleo de todo el sistema sanitario. La Organización Mundial de la Salud recomienda a los países que desarrollen políticas nacionales de medicamentos que guíen la producción, la adquisición, la prescripción y el suministro de estos, de modo que las personas puedan acceder a los medicamentos que necesitan a precios que puedan pagar, evitando al mismo tiempo un uso irracional. Sin embargo, la elaboración de estas políticas no suele ser sencilla. En este documento se describen componentes importantes de la política nacional de medicamentos en Arabia Saudita, que se desarrolló en el marco de una transformación más amplia del sistema sanitario y la economía. La nueva política formaliza las mejores prácticas existentes, da forma a las políticas emergentes y establece una dirección para el desarrollo futuro en cuatro áreas principales. En primer lugar, la política busca consolidar las funciones institucionales para proporcionar una mayor cohesión; en segundo lugar, pretende remodelar los hábitos de adquisición y prescripción, centrándose más en la contención de los costes; en tercer lugar, establece políticas que se centran en asegurar el suministro de medicamentos de buena calidad, incluidos los productos nuevos y los medicamentos esenciales con un potencial de beneficio limitado. Por último, la política apoya el crecimiento de la industria farmacéutica nacional, incluido el desarrollo de los recursos humanos. Varios sectores e instituciones participaron en la elaboración de la política de medicamentos, que se sustentó en una revisión del contexto farmacéutico pasado y actual en Arabia Saudita, y de las buenas prácticas a nivel mundial. La política resultante se creó a partir de pruebas y se esfuerza por dar una orientación clara a la industria farmacéutica y a los organismos de ejecución sobre las reglas y requisitos, las normas profesionales y las funciones institucionales. Asimismo, mantiene la flexibilidad para permitir la adaptación en un panorama institucional que evoluciona muy rápido.

Responsiveness of the healthcare system in the Kingdom of Saudi Arabia: evidence from a nationally representative survey.

BACKGROUND: Responsiveness is one of the widely used metrics in assessing the performance of healthcare systems. An analysis of the determinants of health care demand and supply and how the Saudi health system responds to the needs of patients (inpatient and outpatient) is needed; hence the need for this study. METHODS: We analysed data from the Saudi Health Systems Responsiveness survey - a nationally representative survey of 10,000 households interviewed in 2017. Using this dataset, we descriptively analysed the level of responsiveness of inpatient and outpatient services (using the standard World Health Organization (WHO) responsiveness dimensions). Based on a logit modelling approach, the relationship between responsiveness and its key determinants was analysed in terms of healthcare demand and supply. RESULTS: Over four fifths of respondents are satisfied with the level of inpatient and outpatient responsiveness. Furthermore, we find that those in bad health tend to show lower levels of satisfaction with inpatient and outpatient care. We also find some evidence that age, gender, and to some extent nationality act as correlates of health system responsiveness. Specifically, we find evidence that Saudi nationals are less satisfied with health services compared to foreign nationals. CONCLUSION: Based on these findings improving the responsiveness of public healthcare facilities would need to be prioritized. Focusing on patients in worse health and lower socio-economic status should also be one of the main priorities.

A needs-based methodology to project physicians and nurses to 2030: the case of the Kingdom of Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA), as part of its 2030 National Transformation Program, set a goal of transforming the healthcare sector to increase access to, and improve the quality and efficiency of, health services. To assist with the workforce planning component, we projected the needed number of physicians and nurses into 2030. We developed a new needs-based methodology since previous global benchmarks of health worker concentration may not apply to the KSA. METHODS: We constructed an epidemiologic "needs-based" model that takes into account the health needs of the KSA population, cost-effective treatment service delivery models, and worker productivity. This model relied heavily on up-to-date epidemiologic and workforce surveys in the KSA. We used demographic population projections to estimate the number of nurses and physicians needed to provide this core set of services into 2030. We also assessed several alternative scenarios and policy decisions related to scaling, task-shifting, and enhanced public health campaigns. RESULTS: When projected to 2030, the baseline needs-based estimate is approximately 75,000 workers (5788 physicians and 69,399 nurses). This workforce equates to 2.05 physicians and nurses per 1000 population. Alternative models based on different scenarios and policy decisions indicate that the actual needs for physicians and nurses may range from 1.64 to 3.05 per 1000 population in 2030. CONCLUSIONS: Based on our projections, the KSA will not face a needs-based health worker shortage in 2030. However, alternative model projections raise important policy and planning issues regarding various strategies the KSA may pursue in improving quality and efficiency of the existing workforce. More broadly, where country-level data are available, our needs-based strategy can serve as a useful step-by-step workforce planning tool to complement more economic demand-based workforce projections.

Projecting health labor market dynamics for a health system in transition: planning for a resilient health workforce in Saudi Arabia.

BACKGROUND: Health workforce planning is critical for health systems to safeguard the ability to afford, train, recruit, and retain the appropriate number and mix of health workers. This balance is especially important when macroeconomic structures are also reforming. The Kingdom of Saudi Arabia is moving toward greater diversification, privatization, and resiliency; health sectorreform is a key pillar of this transition. METHODS: We used the Ministry of Health Yearbook data on the number of workers and health expenditures from 2007 to 2018 and projected health labor market supply and demand of workers through 2030, evaluated the potential shortages and surpluses, and simulated different policy scenarios to identify relevant interventions. We further focused on projections for health workers who are Saudi nationals and health worker demand within the public sector (versus the private sector) to inform national objectives of reducing dependency on foreign workers and better deploying public sector resources. RESULTS: We projected the overall health labor market to demand 9.07 physicians and nurses per 1,000 population (356,514) in 2030; the public sector will account for approximately 67% of this overall demand. Compared to a projected supply of 10.16 physicians and nurses per 1,000 population (399,354), we estimated an overall modest surplus of about 42,840 physicians and nurses in 2030. However, only about 17% of these workers are estimated to be Saudi nationals, for whom there will be a demand shortage of 287,895 workers. Among policy scenarios considered, increasing work hours had the largest effect on reducing shortages of Saudi workers, followed by bridge programs for training more nurses. Government resources can also be redirected to supporting more Saudi nurses while still ensuring adequate numbers of physicians to meet service delivery goals in 2030. CONCLUSION: Despite projected overall balance in the labor market for health workers in 2030, without policy interventions, severe gaps in the Saudi workforce will persist and limit progress toward health system resiliency in Saudi Arabia. Both supply- and demand-side policy interventions should be considered, prioritizing those that increase productivity among Saudi health workers, enhance training for nurses, and strategically redeploy financial resources toward employing these workers.

Covid-19 and non-communicable diseases: evidence from a systematic literature review.

BACKGROUND: Since early 2020, the Covid-19 pandemic has engulfed the world. Amidst the growing number of infections and deaths, there has been an emphasis of patients with non-communicable diseases as they are particularly susceptible to the virus. The objective of this literature review is to systematize the available evidence on the link between non-communicable diseases and Covid-19. METHODS: We have conducted a systematic review of the literature on Covid-19 and non-communicable diseases from December, 2019 until 15th of November, 2020. The search was done in PubMed and in doing so we used a variety of searching terms in order to isolate the final set of papers. At the end of the selection process, 45 papers were selected for inclusion in the literature review. RESULTS: The results from the review indicate that patients with certain chronic illnesses such as diabetes, hypertension (and other cardiovascular diseases), chronic respiratory illnesses, chronic kidney and liver conditions are more likely to be affected by Covid-19. More importantly, once they do get infected by the virus, patients with chronic illnesses have a much higher likelihood of having worse clinical outcomes (developing a more severe form of the disease or dying) than an average patient. There are two hypothesized channels that explain this strong link between the chronic illnesses enumerated above and Covid 19: (i) increased ACE2 (angiotensin-converting enzyme 2) receptor expressions, which facilitates the entry of the virus into the host body; and (ii) hyperinflammatory response, referred to as "cytokine storm". Finally, the literature review does not find any evidence that diabetes or hypertension related medications exacerbate the overall Covid-19 condition in chronic illness patients. CONCLUSIONS: Thus, the evidence points out to 'business as usual' disease management model, although with greater supervision. However, given the ongoing Covid-19 vulnerabilities among people with NCDs, prioritizing them for the vaccination process should also figure high on the agenda on health authorities.

The capacity of primary health care facilities in Saudi Arabia: infrastructure, services, drug availability, and human resources.

BACKGROUND: Primary healthcare (PHC) is an essential component of an effective healthcare system. The Kingdom of Saudi Arabia's (KSA) health reforms prioritize tackling the increasing noncommunicable disease burden by prioritizing PHC, centering it as the core of the newly proposed Model of Care. To identify challenges and opportunities to scale up PHC capacity, understanding the current capacity of primary health care centers (PHCC) is critical. A limited number of publications review PHC capacity in KSA, focusing on specific regions/sectors; this paper is a first to examine PHC capacity on a national level. METHODS: The study uses a countrywide Facility Survey that collected data in 2018 from 2319 PHCCs, generating information on their characteristics, number of health workers, services provided, and capacity elements captured through the Service Availability and Drug Availability constructed indices. Descriptive analysis was performed by rural-urban classification. Ordinary Least Squares (OLS) regressions were used to understand correlates to health workers and equipment availability. Finally, a logistic regression was fitted for selected services. Regressions controlled for various measures to determine correlates with facilities' capacity. RESULTS: On a national level, there are 0.74 PHCCs per 10,000 population in KSA. There are variations in the distribution of PHCCs across regions and within regions across rural and urban areas. PHCCs in urban areas have more examination rooms but lower examination room densities. Offering 24 × 7 services in PHCCs is infrequent and dependency on paper-based medical recording remains common. More urban regions are more likely to offer general services but less likely to offer burn management and emergency services. PHCCs are mostly staffed with general medicine, family medicine, and obstetrics & gynecology physicians, whose numbers are more concentrated in urban areas; however, their densities are higher in rural areas. Finally, psychiatrists and nutritionists are rare to find in PHCCs. CONCLUSIONS: Decision-makers need to consider several factors when designing PHC policies. For instance, PHC accreditation needs to be prioritized given its positive correlation with service provision and health workers availability. PHC 24 × 7 operation also needs considerations in rural areas due to the high dependency on PHCCs. Finally, there is a substantial need for improvements in e-health.

Human resources for health interventions in high- and middle-income countries: findings of an evidence review.

Many high- and middle-income countries face challenges in developing and maintaining a health workforce which can address changing population health needs. They have experimented with interventions which overlap with but have differences to those documented in low- and middle-income countries, where many of the recent literature reviews were undertaken. The aim of this paper is to fill that gap. It examines published and grey evidence on interventions to train, recruit, retain, distribute, and manage an effective health workforce, focusing on physicians, nurses, and allied health professionals in high- and middle-income countries. A search of databases, websites, and relevant references was carried out in March 2019. One hundred thirty-one reports or papers were selected for extraction, using a template which followed a health labor market structure. Many studies were cross-cutting; however, the largest number of country studies was focused on Canada, Australia, and the United States of America. The studies were relatively balanced across occupational groups. The largest number focused on availability, followed by performance and then distribution. Study numbers peaked in 2013-2016. A range of study types was included, with a high number of descriptive studies. Some topics were more deeply documented than others-there is, for example, a large number of studies on human resources for health (HRH) planning, educational interventions, and policies to reduce in-migration, but much less on topics such as HRH financing and task shifting. It is also evident that some policy actions may address more than one area of challenge, but equally that some policy actions may have conflicting results for different challenges. Although some of the interventions have been more used and documented in relation to specific cadres, many of the lessons appear to apply across them, with tailoring required to reflect individuals' characteristics, such as age, location, and preferences. Useful lessons can be learned from these higher-income settings for low- and middle-income settings. Much of the literature is descriptive, rather than evaluative, reflecting the organic way in which many HRH reforms are introduced. A more rigorous approach to testing HRH interventions is recommended to improve the evidence in this area of health systems strengthening.

Challenges and policy opportunities in nursing in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia's (KSA) health sector is undergoing rapid reform in line with the National Transformation Program, as part of Saudi's vision for the future, Vision 2030. From a nursing human resources for health (HRH) perspective, there are challenges of low nursing school capacity, high employment of expatriates, labor market fragmentation, shortage of nurses in rural areas, uneven quality, and gender challenges. CASE PRESENTATION: This case study summarizes Saudi Ministry of Health (MOH) and Saudi Health Council's (SHCs) evaluation of the current challenges facing the nursing profession in the KSA. We propose policy interventions to support the transformation of nursing into a profession that contributes to efficient, high-quality healthcare for every Saudi citizen. Key to the success of modernizing the Saudi workforce will be an improved pipeline of nurses that leads from middle and high school to nursing school; followed by a diverse career path that includes postgraduate education. To retain nurses in the profession, there are opportunities to make nursing practice more attractive and family friendly. Interventions include reducing shift length, redesigning the nursing team to add more allied health workers, and introducing locum tenens staffing to balance work-load. There are opportunities to modernize existing nurse postgraduate education, open new postgraduate programs in nursing, and create new positions and career paths for nurses such as telenursing, informatics, and quality. Rural pipelines should be created, with incentives and increased compensation packages for underserved areas. CONCLUSIONS: Critical to these proposed reforms is the collaboration of the MOH with partners across the healthcare system, particularly the private sector. Human resources planning should be sector-wide and nursing leadership should be strengthened at all levels.

Principles for circadian orchestration of metabolic pathways.

Circadian rhythms govern multiple aspects of animal metabolism. Transcriptome-, proteome- and metabolome-wide measurements have revealed widespread circadian rhythms in metabolism governed by a cellular genetic oscillator, the circadian core clock. However, it remains unclear if and under which conditions transcriptional rhythms cause rhythms in particular metabolites and metabolic fluxes. Here, we analyzed the circadian orchestration of metabolic pathways by direct measurement of enzyme activities, analysis of transcriptome data, and developing a theoretical method called circadian response analysis. Contrary to a common assumption, we found that pronounced rhythms in metabolic pathways are often favored by separation rather than alignment in the times of peak activity of key enzymes. This property holds true for a set of metabolic pathway motifs (e.g., linear chains and branching points) and also under the conditions of fast kinetics typical for metabolic reactions. By circadian response analysis of pathway motifs, we determined exact timing separation constraints on rhythmic enzyme activities that allow for substantial rhythms in pathway flux and metabolite concentrations. Direct measurements of circadian enzyme activities in mouse skeletal muscle confirmed that such timing separation occurs in vivo.