In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells.

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.

Addressing health inequalities in times of austerity: implementation of a place-based approach in multitiered local government.

AIMS: This article focuses on how local authorities in England are tackling wider determinants of health and inequalities in their population's outcomes while budgets for public services are diminishing. METHODS: It reports the experience from one case study engaged in rolling out a devolved, place- and asset-based strategy over multiple tiers of local government. Relating these findings to relevant social theory, we draw out aspects of context and mechanisms of change. We offer plausible hypotheses for the experiences observed, which supports transferability and implementation of place-based strategies in other local authority areas struggling with similar challenges. RESULTS: Findings highlight the importance of high-level and political buy-in, as well as the role of the COVID-19 pandemic as a potential catalyst to rollout. Creating the foundations for a new, place-based working was important for achieving coherence among partners around what local government was trying to achieve. These included investment in infrastructure, both relational and tangible inputs such as organisational and human resources, to establish the conditions for systemic change towards early intervention and prevention. CONCLUSION: This study identified clear foundations for place-based action, plus enablers and barriers to significant transformation of practice towards asset-based approaches between local authorities, partners and the public.

Chinese family care partners of older adults in Canada have grit: A qualitative study.

AIM: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? DESIGN: This qualitative study was informed by critical realism. METHODS: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. FINDINGS: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. CONCLUSION: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. IMPLICATIONS FOR THE PROFESSION: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. IMPACT: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. REPORTING METHOD: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC INVOLVEMENT AND ENGAGEMENT: No patient or public involvement.

Disease burden of bacteraemia with extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in Korea.

BACKGROUND: Despite the significant impact of multi-drug-resistant bacteraemia, especially extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), the burden of disease has not been investigated thoroughly. AIM: To evaluate the clinical outcomes and socio-economic burden of ESBL-E and CRE bacteraemia nationwide in the Republic of Korea. METHODS: A search was undertaken for all cases of ESBL-E and CRE bacteraemia and matched controls in 10 hospitals in the Republic of Korea over 6 months. Patients with ESBL-E or CRE bacteraemia were classified as the R group, and matched controls with antibiotic-susceptible bacteraemia and without infection were classified as the S and N groups, respectively. Patients' clinical data were collected, and the economic burden was estimated based on medical expenses, loss of productivity and total costs. FINDINGS: In total, 795 patients were identified, including 265 patients with ESBL-E or CRE bacteraemia and their matched controls. The mean total length of stay for patients with ESBL-E and CRE in the R group was 1.53 and 1.90 times that of patients in the S group, respectively. The 90-day mortality rates for ESBL-E in the R and S groups were 12.1% and 5.6%, respectively, and the corresponding figures for CRE were 28.6% and 12.0%. There were significant differences in the total costs between the R, S and N groups for both ESBL-E and CRE (ESBL-E: $11,151 vs $8712 vs $6063, P=0.004; CRE: $40,464 vs $8748 vs $7279, P=0.024). CONCLUSION: The clinical and economic burden imposed by ESBL-E or CRE bacteraemia was extremely high. These findings suggest that efforts to control resistant bacteraemia are necessary to reduce this burden.

Guidance for Pharmacy Curricula to Incorporate Health, Wellness, and Health Inequities Stemming From Climate Change: The Report of the 2022-2023 AACP Argus Commission.

The 2022-2023 American Association of College of Pharmacy Argus Commission was charged to provide guidance to schools, curriculum committees, and faculty on how to incorporate health, wellness, and health inequities stemming from climate change into pharmacy curricula. The Argus Commission does not advocate for major changes in the curriculum or standards but suggests a concerted effort across the Academy to enhance the awareness of graduating students of the potential impact of climate change on health both now and in the future. Various examples, along with recommendations and suggestions, are provided of how the impact of climate change on health is currently being integrated into curricula in member schools, as well as a list of resources faculty can use to enhance their awareness of issues related to climate change and health. The Commission was also charged to provide guidance to the American Association of College of Pharmacy regarding future fundraising and business development opportunities. Recommendations in that regard are also included in this report.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

OBJECTIVE: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. METHODS: Diet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. RESULTS: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. CONCLUSIONS: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Biofuel-driven trigeneration systems for non-residential building applications: A holistic assessment from the energy, environmental and economic perspectives.

In the metropolises, it is unlikely to use merely solar and wind energy to pursue zero carbon building design. However, it would become possible if biofuel-driven trigeneration systems (BDTS) are adopted. It is thus essential to assess the application opportunity of BDTS in a holistic way. In this study, BDTS offered definite primary energy saving of up to 15% and carbon emissions reduction of at least 86% in different types of non-residential buildings as compared to the conventional systems. With 24/7 operation for the hotel and hospital buildings, the corresponding BDTS could even achieve zero carbon emissions. All the BDTS primed with compression-ignition internal combustion engine were not economically viable even in running cost due to the high local biodiesel price level. The BDTS primed with spark-ignition engine and fueled by biogas, however, would have economic merit when carbon price was considered for the conventional systems that fully utilize fossil fuels. Adoption of carbon tax and social cost could have the payback ceilings of 8 years and 2 years respectively for most of building types. Consequently, the results could reflect the application potential of BDTS for non-residential buildings, leading the pathway to carbon neutrality for sustainable sub-tropical cities.

External Genital Revisions after Gender-Affirming Penile Inversion Vaginoplasty: Surgical Assessment, Techniques, and Outcomes.

BACKGROUND: Following gender-affirming penile inversion vaginoplasty or vulvoplasty, patients may seek vulvar revision procedures for a variety of common aesthetic and functional concerns. These indications for revision and accompanying techniques are not well-described in the literature. METHODS: Patients who underwent vulvar revision surgery at the authors' institution were identified, and patient demographics, surgical indications, operative details, and complications were described. Common complaints requiring external genital revision were sorted into four categories: clitoral, labial, introital, and urethral. RESULTS: Thirty-five patients with a history of vaginoplasty underwent vulvar revision between May of 2017 and December of 2019. The mean age at surgical correction was 38.9 years. Ten patients (28.6 percent) had undergone prior secondary procedures (range, 1 to 3). Mean follow-up after revision surgery was 10.7 ± 8.7 months (range, 0 to 30.6 months). The majority of patients underwent concurrent revisions in multiple "categories". Labial aesthetic concerns were most common (n = 27, 77.1 percent), followed by clitoral (n = 20, 57.1 percent), urologic (n = 17, 48.6 percent), and introital complaints (n = 12, 34.3 percent). Twelve patients (34.3 percent) had canal stenosis requiring concurrent robot-assisted canal revision with peritoneal flaps. Complications included labial abscess (n = 1) and deep vein thrombosis (n = 1). Three patients (8.6 percent) underwent subsequent external genital revisions. Management approaches and surgical techniques for each of these common revision categories are provided. CONCLUSION: As more individuals seek vaginoplasty and vulvoplasty, surgeons must be prepared to address a range of common aesthetic and functional complaints requiring vulvar revision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Multiscale Assessment of Agricultural Consumptive Water Use in California's Central Valley.

Spatial estimates of crop evapotranspiration with high accuracy from the field to watershed scale have become increasingly important for water management, particularly over irrigated agriculture in semiarid regions. Here, we provide a comprehensive assessment on patterns of annual agricultural water use over California's Central Valley, using 30-m daily evapotranspiration estimates based on Landsat satellite data. A semiempirical Priestley-Taylor approach was locally optimized and cross-validated with available field measurements for major crops including alfalfa, almond, citrus, corn, pasture, and rice. The evapotranspiration estimates explained >70% variance in daily measurements from independent sites with an RMSE of 0.88 mm day-1. When aggregated over the Valley, we estimated an average evapotranspiration of 820 ± 290 mm yr-1 in 2014. Agricultural water use varied significantly across and within crop types, with a coefficient of variation ranging from 8% for Rice (1,110 ± 85 mm yr-1) to 59% for Pistachio (592 ± 352 mm yr-1). Total water uses in 2016 increased by 9.6%, as compared to 2014, mostly because of land-use conversion from fallow/idle land to cropland. Analysis across 134 Groundwater Sustainability Agencies (GSAs) further showed a large variation of agricultural evapotranspiration among and within GSAs, especially for tree crops, e.g., almond evapotranspiration ranging from 339 ± 80 mm yr-1 in Tracy to 1,240 ± 136 mm yr-1 in Tri-County Water Authority. Continuous monitoring and assessment of the dynamics and spatial heterogeneity of agricultural evapotranspiration provide data-driven guidance for more effective land use and water planning across scales.

The high-value pharmacy enterprise framework: Advancing pharmacy practice in health systems through a consensus-based, strategic approach.

PURPOSE: The high-value pharmacy enterprise (HVPE) framework and constituent best practice consensus statements are presented, and the methods used to develop the framework's 8 domains are described. SUMMARY: A panel of pharmacy leaders used an evidence- and expert opinion-based approach to define core and aspirational elements of practice that should be established within contemporary health-system pharmacy enterprises by calendar year 2025. Eight domains of an HVPE were identified: Patient Care Services; Business Services; Ambulatory and Specialty Pharmacy Services; Inpatient Operations; Safety and Quality; Pharmacy Workforce; Information Technology, Data, and Information Management; and Leadership. Phase 1 of the project consisted of the development of draft practice statements, performance elements, and supporting evidence for each domain by panelists, followed by a phase 2 in-person meeting for review and development of consensus for statements and performance elements in each domain. During phase 3, the project cochairs and panelists finalized the domain drafts and incorporated them into a full technical report and this summary report. CONCLUSION: The HVPE framework is a strategic roadmap to advance pharmacy practice by ensuring safe, effective, and patient-centered medication management and business practices throughout the health-system pharmacy enterprise. Grounded in evidence and expert recommendations, the statements and associated performance elements can be used to identify strategic priorities to improve patient outcomes and add value within health systems.

Ultimate COVID-19 Detection Protocol Based on Saliva Sampling and qRT-PCR with Risk Probability Assessment.

In the era of COVID-19 outbreak, various efforts are undertaken to develop a quick, easy, inexpensive, and accurate way for diagnosis. Although many commercial diagnostic kits are available, detailed scientific evaluation is lacking, making the public vulnerable to fear of false-positive results. Moreover, current tissue sampling method from respiratory tract requires personal contact of medical staff with a potential asymptomatic SARSCOV-2 carrier and calls for safe and less invasive sampling method. Here, we have developed a convenient detection protocol for SARS-COV-2 based on a non-invasive saliva self-sampling method by extending our previous studies on development of a laboratory-safe and low-cost detection protocol based on qRT-PCR. We tested and compared various self-sampling methods of self-pharyngeal swab and self-saliva sampling from non-carrier volunteers. We found that the self-saliva sampling procedure gave expected negative results from all of the non-carrier volunteers within 2 hours, indicating cost-effectiveness, speed and reliability of the saliva-based method. For an automated assessment of the sampling quality and degree of positivity for COVID-19, we developed scalable formulae based on a logistic classification model using both cycle threshold and melting temperature from the qRT-PCR results. Our newly developed protocol will allow easy sampling and spatial-separation between patient and experimenter for guaranteed safety. Furthermore, our newly established risk assessment formula can be applied to a large-scale diagnosis in health institutions and agencies around the world.

Multi-species Aquatic Toxicity Assessment of 1-Methyl-3-Nitroguanidine (MeNQ).

The Army is replacing traditional munitions with insensitive munitions (IM) resistant to accidental detonation. The aquatic toxicity of 1-methyl-3-nitroguanidine (MeNQ), which is being assessed for potential use in IM formulations, remains largely untested. The present study fills a number of critical data gaps for MeNQ aquatic toxicity by evaluating effects across two vertebrate and five invertebrate species. Specifically, responses in larval Pimephales promelas, Rana pipiens tadpoles, Chironomus dilutus, Lumbriculus variegatus, Hydra littoralis, Hyalella azteca, and Daphnia pulex were assessed in MeNQ exposures across various acute, subchronic, and chronic bioassays. Overall, survival was unaffected in most of the MeNQ exposures where significant lethal effects were only observed in D. pulex, H. littoralis, and C. dilutus and only at concentrations ≥ 2186 mg/L. Significant sublethal effects on growth were observed for C. dilutus at 903 mg/L and H. azteca at 1098 mg/L in 10-d assays. Significantly decreased reproduction was observed at 2775 mg/L for H. azteca in a chronic 35-d assay and at 174 mg/L for D. pulex in the 11-d three-brood assay representing a sublethal effect one order of magnitude more sensitive than the effective lethal concentration for D. pulex (2987 mg/L). Degradation of MeNQ in ultraviolet light (UV) greatly increased toxicity to D. pulex. Specifically, exposure to a MeNQ solution that was completely UV-degraded prior to D. pulex exposures resulted in an 11-d LC50 of 6.1 mg/L and a 50% reduction in reproduction at 3.125 mg/L, based on the original MeNQ parent-compound concentrations.

Hong Kong Society of Clinical Blood Management recommendations for implementation of patient blood management.

Patient blood management (PBM) is a patient-centred, multidisciplinary approach to optimise red cell mass, minimise blood loss, and manage tolerance to anaemia in an effort to improve patient outcomes. Well-implemented PBM improves patient outcomes and reduces demand for blood products. The multidisciplinary approach of PBM can often allow patients to avoid blood transfusions, which are associated with less favourable clinical outcomes. In Hong Kong, there has been increasing demand for blood in the ageing population, and there are simultaneous blood safety and donor issues that are adversely affecting the blood supply. To address these challenges, the Hong Kong Society of Clinical Blood Management recommends implementation of a PBM programme in Hong Kong, including strategies such as optimising red blood cell mass, improving anaemia management, minimising blood loss, and rationalising the use of blood and blood products.

National trends in prescription drug expenditures and projections for 2020.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2020 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2020 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for specialty drugs, biosimilars, and diabetes medications. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2020 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2019, overall US pharmaceutical expenditures grew 5.4% compared to 2018, for a total of $507.9 billion. This increase was driven to similar degrees by prices, utilization, and new drugs. Adalimumab was the top drug in US expenditures in 2019, followed by apixaban and insulin glargine. Drug expenditures were $36.9 billion (a 1.5% increase from 2018) and $90.3 billion (an 11.8% increase from 2018) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals growth was driven by new products and price increases. Several new drugs that will likely influence spending are expected to be approved in 2020. Specialty and cancer drugs will continue to drive expenditures. CONCLUSION: For 2020 we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 9.0% to 11.0% and 2.0% to 4.0%, respectively, compared to 2019. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019 (COVID-19).

The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person-to-person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizol-based RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.

The Test-Retest Reliability of Force Plate-Derived Parameters of the Countermovement Push-Up as a Power Assessment Tool.

CONTEXT: Muscular power output of the upper limb is a key aspect of athletic and sporting performance. Maximal power describes the ability to immediately produce power with maximal velocity at the point of release, impact, or takeoff, with research highlighting that the greater an athlete's ability to produce maximal power, the greater the improvement in athletic performance. Despite the importance of upper-limb power for athletic performance, there is presently no gold-standard test for upper-limb force development performance. OBJECTIVE: The aim of this study was to investigate the test-retest reliability of force plate-derived measures of the countermovement push-up in active males. DESIGN: Test-retest design. SETTING: Controlled laboratory. PARTICIPANTS: Physically active college athletes (age 24 [3] y, height 1.79 [0.08] m, body mass 81.7 [9.9] kg). INTERVENTION: Subjects performed 3 repetitions of maximal effort countermovement push-up trials on Kistler force plates on 2 separate test occasions 7 days apart. MAIN OUTCOME MEASURES: Peak force, mean force, flight time, rate of force development, and impulse were analyzed from the force-time curve. RESULTS: No significant differences between the 2 trial occasions were observed for any of the derived performance measures. Intraclass correlation coefficient and within-subject coefficient of variation calculations indicated performance measures to have moderate to very high reliability (intraclass correlation coefficient = .88-.98), coefficient of variation = 5.5%-14.1%). Smallest detectable difference for peak force (7.5%), mean force (8.6%), and rate of force development (11.2%) were small to moderate. CONCLUSION: Force platform-derived kinetic parameters of countermovement push-up are reliable measurements of power in college-level athletes.

Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries.

Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics - population testing number and testing coverage - to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = -0.79, P = 5.975 × 10-9vs. rs = -0.3, P = 0.05) and case fatality rate (rs = -0.67, P = 9.067 × 10-6vs. rs = -0.21, P = 0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.