Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Effect of Cage Change Frequency on Perinatal Mortality in C57BL/6J Mice.

Perinatal mortality is a common problem in mouse breeding colonies. Few studies have examined the influence of environmental changes on mouse pup survival. In this study, monogamous breeding cages of C57BL/6J mice were set up and randomized into 3 cage change groups: 1) cage change at 8 d after parturition, 2) cage change at 3 d after parturition, or 3) cage change at 3 d after parturition with the addition of a polycarbonate hut in the cage. Pairs were bred to produce a minimum of 4 litters. Pup survival to weaning relative to experimental cage change date, and survival rates after cage change were evaluated. The results revealed no significant differences between experimental groups. The majority of pup loss occurred within the first 24 h after birth for those pups that were alive at birth. Overall, the postpartum day of cage change did not affect the perinatal survival of mouse pups.

A closer look at weight loss interventions in primary care: a systematic review and meta-analysis.

Purpose: The major aims were to quantify patient weight loss using various approaches adminstered by a primary care provider for at least 6 months and to unveil relevant contextual factors that could improve patient weight loss on a long-term basis. Methods: A systematic review and meta-analysis was conducted using Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science from inception to December 5, 2022. COVIDENCE systematic review software was used to identify and abstract data, as well as assess data quality and risk of bias. Results: Seven studies included 2,187 people with obesity testing (1) anti-obesity medication (AOM), (2) AOM, intensive lifestyle counseling + meal replacements, and (3) physician training to better counsel patients on intensive lifestyle modification. Substantial heterogeneity in the outcomes was observed, as well as bias toward lack of published studies showing no effect. The random effect model estimated a treatment effect for the aggregate efficacy of primary care interventions -3.54 kg (95% CI: -5.61 kg to -1.47 kg). Interventions that included a medication component (alone or as part of a multipronged intervention) achieved a greater weight reduction by -2.94 kg (p < 0.0001). In all interventions, efficacy declined with time (reduction in weight loss by 0.53 kg per 6 months, 95% CI: 0.04-1.0 kg). Conclusion: Weight loss interventions administered by a primary care provider can lead to modest weight loss. Weight loss is approximately doubled if anti-obesity medication is part of the treatment. Nevertheless, attenuated weight loss over time underscores the need for long-term treatment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/ CRD4202121242344], identifier (CRD42021242344).

Building on value-based health care: Towards a health system perspective.

A variety of methodologies have been developed to help health systems increase the 'value' created from their available resources. The urgency of creating value is heightened by population ageing, growth in people with complex morbidities, technology advancements, and increased citizen expectations. This study develops a policy framework that seeks to reconcile the various approaches towards value-based policies in health systems. The distinctive contribution is that we focus on the value created by the health system as a whole, including health promotion, thus moving from value-based health care towards a value-based health system perspective. We define health system value to be the contribution of the health system to societal wellbeing. We adopt a framework of five dimensions of value, embracing health improvement, health care responsiveness, financial protection, efficiency and equity, which we map onto a society's aggregate wellbeing. Actors within the health system make different contributions to value, and we argue that their perspectives can be aligned with a unifying concept of health system value. We provide examples of policy levers and highlight key actors and how they can promote certain aspects of health system value. We discuss advantages of value-based approach based on the notion of wellbeing and some practical obstacles to its implementation.

Baseline Characteristics of PATHWEIGH: A Stepped-Wedge Cluster Randomized Study for Weight Management in Primary Care.

PURPOSE: To describe the characteristics of patients and practice of clinicians during standard-of-care for weight management in a large, multiclinic health system before the implementation of PATHWEIGH, a pragmatic weight management intervention. METHODS: We analyzed baseline characteristics of patients, clinicians, and clinics during standard-of-care for weight management before the implementation of PATHWEIGH, which will be evaluated for effectiveness and implementation in primary care using an effectiveness-implementation hybrid type-1 cluster randomized stepped-wedge clinical trial design. A total of 57 primary care clinics were enrolled and randomized to 3 sequences. Patients included in the analysis met the eligibility requirements of age ≥18 years and body mass index (BMI) ≥25 kg/m2 and had a weight-prioritized visit (defined a priori) during the period March 17, 2020 to March 16, 2021. RESULTS: A total of 12% of patients aged ≥18 years and with a BMI ≥25 kg/m2 seen in the 57 practices during the baseline period (n = 20,383) had a weight-prioritized visit. The 3 randomization sequences of 20, 18, and 19 sites were similar, with an overall mean patient age of 52 (SD 16) years, 58% women, 76% non-Hispanic White patients, 64% with commercial insurance, and with a mean BMI of 37 (SD 7) kg/m2. Documented referral for anything weight related was low (<6%), and 334 prescriptions of an antiobesity drug were noted. CONCLUSIONS: Of patients aged ≥18 years and with a BMI ≥25 kg/m2 in a large health system, 12% had a weight-prioritized visit during the baseline period. Despite most patients being commercially insured, referral to any weight-related service or prescription of antiobesity drug was uncommon. These results fortify the rationale for trying to improve weight management in primary care.

Effects of Housing Density on Reproductive Performance, Intracage Ammonia, and Welfare of Mice Continuously Housed as Breeders in Standard Mouse and Rat Caging.

Maintaining compliance with cage density recommendations in The Guide for the Care and Use of Laboratory Animals precludes continuous trio breeding in standard-sized mouse cages. This study evaluated and compared several parameters of reproductive performance, intracage ammonia concentration, and fecal corticosterone levels in 2 strains of mice, C57BL/6J (B6) and B6.129S(Cg)-Stat1tm1Dlv/J (STAT1-/-), housed as continuous breeding pairs or trios in standard-sized mouse cages, and continuous breeding trios in standard-sized rat cages. Reproductive performance data indicated that STAT1-/- trios raised in rat cages weaned significantly more pups per litter than did STAT1-/- trios raised in mouse cages, and B6 mice had higher pup survival rates at weaning than did STAT1-/- mice in mouse cages housing continuous breeding trios. In addition, the Production Index was significantly higher for B6 breeding trios in rat cages than for B6 trios in mouse cages. Intracage ammonia concentration increased with cage density, with significantly higher ammonia concentrations in mouse cages housing trios compared with rat cages housing trios. However, fecal corticosterone levels did not differ significantly regardless of genotype, breeding configuration, or cage size, and daily health checks revealed no clinical abnormalities under any of the conditions evaluated. These results suggest that, although continuous trio breeding in standard-sized mouse cages does not seem to compromise mouse welfare, it offers no advantage in reproductive performance compared with pair breeding, and in some cases, it might be disadvantageous in this regard. Further, high intracage ammonia in mouse cages containing breeding trios might necessitate more frequent cage changes.

The societal value of SARS-CoV-2 booster vaccination in Indonesia.

OBJECTIVES: To estimate the expected socio-economic value of booster vaccination in terms of averted deaths and averted closures of businesses and schools using simulation modelling. METHODS: The value of booster vaccination in Indonesia is estimated by comparing simulated societal costs under a twelve-month, 187-million-dose Moderna booster vaccination campaign to costs without boosters. The costs of an epidemic and its mitigation consist of lost lives, economic closures and lost education; cost-minimising non-pharmaceutical mitigation is chosen for each scenario. RESULTS: The cost-minimising non-pharmaceutical mitigation depends on the availability of vaccines: the differences between the two scenarios are 14 to 19 million years of in-person education and $153 to $204 billion in economic activity. The value of the booster campaign ranges from $2,500 ($1,400-$4,100) to $2,800 ($1,700-$4,600) per dose in the first year, depending on life-year valuations. CONCLUSIONS: The societal benefits of booster vaccination are substantial. Much of the value of vaccination resides in the reduced need for costly non-pharmaceutical mitigation. We propose cost minimisation as a tool for policy decision-making and valuation of vaccination, taking into account all socio-economic costs, and not averted deaths alone.

Data needs for integrated economic-epidemiological models of pandemic mitigation policies.

The COVID-19 pandemic and the mitigation policies implemented in response to it have resulted in economic losses worldwide. Attempts to understand the relationship between economics and epidemiology has led to a new generation of integrated mathematical models. The data needs for these models transcend those of the individual fields, especially where human interaction patterns are closely linked with economic activity. In this article, we reflect upon modelling efforts to date, discussing the data needs that they have identified, both for understanding the consequences of the pandemic and policy responses to it through analysis of historic data and for the further development of this new and exciting interdisciplinary field.

PATHWEIGH, pragmatic weight management in adult patients in primary care in Colorado, USA: study protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Despite the overwhelming prevalence and health implications of obesity, it is rarely adequately addressed in a health care setting. PATHWEIGH is a pragmatic approach to weight management that uses tools built into the electronic medical record to overcome barriers and guide care. Implementation strategies are employed to facilitate adoption and use of the PATHWEIGH tools and processes. The current study will compare the effectiveness of PATHWEIGH versus standard of care (SOC) on patient weight loss in primary care and explore factors for its successful implementation. METHODS: A stepped wedge cluster randomized trial design will be used within an effectiveness-implementation hybrid study. Adult patient weight loss and weight loss maintenance will be compared in PATHWEIGH versus SOC in 57 family and internal medicine clinics in a large health system in Colorado, USA. Effectiveness will be evaluated using generalized linear mixed models to determine statistical differences in weight loss and weight loss maintenance at 6, 12, and 18 months. Patient-, provider-, and clinic-level predictors will be identified using mediator and moderator analyses. Conceptually guided by the Practical, Robust, Implementation and Sustainability Model (PRISM), a mixed methods approach including quantitative (practice surveys, use tracking) and qualitative (interviews, observations) data collection will be used to determine factors impeding and facilitating adoption, implementation, and maintenance of PATHWEIGH and evaluate specified implementation strategies. A cost analysis of the practice and system costs and resources required by PATHWEIGH relative to the reimbursement collected will be performed. DISCUSSION: The effectiveness and implementation of PATHWEIGH, and their interrelatedness, for patient weight loss are collectively the focus of the current trial. Findings from this study are expected to serve as a blueprint for available and effective weight management in primary care medical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04678752 . Registered on December 21, 2020.

Implementation and Qualitative Evaluation of a Primary Care Redesign Model with Expanded Scope of Work for Medical Assistants.

BACKGROUND: Implementation of primary care models involving expanded scope of work and redesigned workflows for medical assistants (MAs) as primary care team members can be challenging. Implementation strategies and participatory evaluation informed by implementation science frameworks may inform organizational decisions about model scale-up and sustainment. OBJECTIVE: This paper reports implementation strategies and qualitative evaluation of a primary care redesign (PCR) model implementation that included an expanded scope of work for MAs. DESIGN: Qualitative evaluation of implementation strategies and clinician and staff experience with implementation of PCR using semi-structured key informant interviews. The evaluation was guided by the RE-AIM framework and the Consolidated Framework for Implementation Research. PARTICIPANTS: Sixty-nine clinicians, staff, practice leaders, and administrators from 7 primary care practices (4 general internal medicine, 3 family medicine) implementing PCR. INTERVENTIONS: The PCR model included enhanced rooming and documentation support. The health system used multiple strategies to implement PCR, including rapid improvement events, changing clinic space configurations, developing electronic health record templates and performance dashboards, and practice coaching. APPROACH: The Consolidated Framework for Implementation Research and the RE-AIM evaluation and planning framework guided development of semi-structured interview guides. A deductive, structural coding approach was used for analysis. KEY RESULTS: PCR implementation was facilitated by clear communication about the intervention source, mechanisms for feedback about model goals, and physical environments and electronic health record (EHR) systems that supported the added staff and modified clinic workflow. Clinicians and staff benefited from the ability to see the model in action prior to go-live and opportunities for consistent provider-MA pairings. CONCLUSIONS: The PCR model can support achieving the Quadruple Aim when fully implemented with paired MAs and clinicians who are well prepared to follow redesigned workflows and function as a team. Implementation can be effectively supported by a participatory evaluation guided by implementation science frameworks.

Optimizing social and economic activity while containing SARS-CoV-2 transmission using DAEDALUS.

To study the trade-off between economic, social and health outcomes in the management of a pandemic, DAEDALUS integrates a dynamic epidemiological model of SARS-CoV-2 transmission with a multi-sector economic model, reflecting sectoral heterogeneity in transmission and complex supply chains. The model identifies mitigation strategies that optimize economic production while constraining infections so that hospital capacity is not exceeded but allowing essential services, including much of the education sector, to remain active. The model differentiates closures by economic sector, keeping those sectors open that contribute little to transmission but much to economic output and those that produce essential services as intermediate or final consumption products. In an illustrative application to 63 sectors in the United Kingdom, the model achieves an economic gain of between £161 billion (24%) and £193 billion (29%) compared to a blanket lockdown of non-essential activities over six months. Although it has been designed for SARS-CoV-2, DAEDALUS is sufficiently flexible to be applicable to pandemics with different epidemiological characteristics.

The effect of distance on maternal institutional delivery choice: Evidence from Malawi.

In many low- and middle-income countries, geographical accessibility continues to be a barrier to health care utilization. In this paper, we aim to better understand the full relationship between distance to providers and utilization of maternal delivery services. We address three methodological challenges: non-linear effects between distance and utilization; unobserved heterogeneity through non-random distance "assignment"; and heterogeneous effects of distance. Linking Malawi Demographic Health Survey household data to Service Provision Assessment facility data, we consider distance as a continuous treatment variable, estimating a Dose-Response Function based on generalized propensity scores, allowing exploration of non-linearities in the effect of an increment in distance at different distance exposures. Using an instrumental variables approach, we examine the potential for unobserved differences between women residing at different distances to health facilities. Our results suggest distance significantly reduces the probability of having a facility delivery, with evidence of non-linearities in the effect. The negative relationship is shown to be particularly strong for women with poor health knowledge and lower socio-economic status, with important implications for equity. We also find evidence of potential unobserved confounding, suggesting that methods that ignore such confounding may underestimate the effect of distance on the utilization of health services.

Optimal national prioritization policies for hospital care during the SARS-CoV-2 pandemic.

In response to unprecedented surges in the demand for hospital care during the SARS-CoV-2 pandemic, health systems have prioritized patients with COVID-19 to life-saving hospital care to the detriment of other patients. In contrast to these ad hoc policies, we develop a linear programming framework to optimally schedule elective procedures and allocate hospital beds among all planned and emergency patients to minimize years of life lost. Leveraging a large dataset of administrative patient medical records, we apply our framework to the National Health Service in England and show that an extra 50,750-5,891,608 years of life can be gained compared with prioritization policies that reflect those implemented during the pandemic. Notable health gains are observed for neoplasms, diseases of the digestive system, and injuries and poisoning. Our open-source framework provides a computationally efficient approximation of a large-scale discrete optimization problem that can be applied globally to support national-level care prioritization policies.

Allocating resources to support universal health coverage: development of a geographical funding formula in Malawi.

BACKGROUND: Universal health coverage (UHC) requires that local health sector institutions-such as local authorities-are properly funded to fulfil their service delivery commitments. In this study, we examine how formula funding can align sub-national resource allocations with national priorities. This is illustrated by outlining alternative options for using mathematical formula to guide the allocation of national drug and service delivery budgets to district councils in Malawi in 2018/2019. METHODS: We use demographic, epidemiological and health sector budget data with information on implementation constraints to construct three variant allocation formulae. The first gives an equal per capita allocation to each district, and is included as a baseline to compare alternatives. The second allocates funds to districts using estimates of the resources required to provide Malawi's essential health package of priority cost-effective interventions to the full population in need of each intervention. The third adjusts these estimates to reflect a practicable level of attainable coverage for each intervention, based on the current configurations of health services and demand for interventions. FINDINGS: Compared with current district allocations, not underpinned by an explicit formula, the formulae presented in this study suggest sizeable shifts in the allocations received by many districts. In some cases, the magnitude of these shifts exceed 50% reductions or doubling of district budgets. The large shifts illustrate inequities in the current system of budget allocation and the potential improvements possible. CONCLUSION: The use of mathematical formulae can guide the efficient and equitable allocation of healthcare funds to local health authorities. The formulae developed were facilitated by the existence of an explicit package of priority interventions. The approach can be replicated in wide range of countries seeking to achieve UHC.

Cutaneous and Pulmonary Mucormycosis in Rag1- and Il2rg-deficient Rats.

Immunodeficient rats are valuable in transplantation studies, but are vulnerable to infection from opportunistic organisms such as fungi. Immunodeficient Rag1- and Il2rg-deficient (RRG) rats housed at our institution presented with dark, proliferative, keratinized dermal growths. Histologic and PCR results indicated that the predominant organism associated with these lesions was fungus from the family Mucoraceae, mostly of the genus Rhizopus. The Mucoraceae family of fungi are environmental saprophytes and are often found in rodent bedding. These fungi can cause invasive opportunistic infections in immunosuppressed humans and animals. We discuss husbandry practices for immunosuppressed rodents with a focus on controlling fungal contaminants.

Rural and urban differences in health system performance among older Chinese adults: cross-sectional analysis of a national sample.

BACKGROUND: Despite improvement in health outcomes over the past few decades, China still experiences striking rural-urban health inequalities. There is limited research on the rural-urban differences in health system performance in China. METHOD: We conducted a cross-sectional analysis to compare health system performance between rural and urban areas in five key domains of the health system: effectiveness, cost, access, patient-centredness and equity, using data from the WHO Study on Global AGEing and adult health (SAGE), China. Multiple logistic and linear regression models were used to assess the first four domains, adjusting for individual characteristics, and a relative index of inequality (RII) was used to measure the equity domain. FINDINGS: Compared to urban areas, rural areas had poorer performance in the management and control of hypertension and diabetes, with more than 50% lower odds of having breast (AOR = 0.44; 95% CI: 0.30, 0.64) and cervical cancer screening (AOR = 0.49; 95% CI: 0.29, 0.83). There was better performance in rural areas in the patient-centredness domain, with more than twice higher odds of getting prompt attention, respect, clarity of the communication with health provider and involvement in decision making of the treatment in inpatient care (AOR = 2.56, 2.15, 2.28, 2.28). Although rural residents incurred relatively less out-of-pocket expenditures (OOPE) for outpatient and inpatient services than urban residents, they were more likely to incur catastrophic expenditures on health (AOR = 1.30; 95% CI 1.16, 1.44). Wealth inequality was found in many indicators related to the effectiveness, costs and access domains in both rural and urban areas. Rural areas had greater inequalities in the management of hypertension and coverage of cervical cancer (RII = 7.45 vs 1.64). CONCLUSION: Our findings suggest that urban areas have achieved better prevention and management of non-communicable disease than rural areas, but access to healthcare was equivalent. A better understanding of the causes of the observed variations is needed to develop appropriate policy interventions which address these disparities.

Squaring the cube: Towards an operational model of optimal universal health coverage.

Universal Health Coverage (UHC) has become a key goal of health policy in many developing countries. However, implementing UHC poses tough policy choices about: what treatments to provide (the depth of coverage); to what proportion of the population (the breadth of coverage); at what price to patients (the height of coverage). This paper uses a theoretical mathematical programming model to derive analytically the optimal balance between the range of services provided and the proportion of the population covered under UHC, using the general principles of cost-effectiveness analysis. In contrast to most CEA, the model allows for variations in both the costs of provision and the social benefits of treatments, depending on the deprivation level of the population. We illustrate empirically the optimal trade-off between the size of the benefits package and the proportion of the population securing access to each treatment for a hypothetical East African country, based on WHO data on the costs and benefits of treatments at different coverage levels. We begin with a scenario allowing coverage levels to vary, then apply differential equity weights to the benefits of coverage, and finally illustrate a scenario where interventions are either provided at 95% coverage or not at all (as is usually done in health benefits package design) for comparison. The results present the optimal trade-off between the social benefits of pursuing full population coverage, at the expense of expanding the benefits package for 'easier to reach' populations.