Rational design of an essential diagnostics network to support Universal Health Coverage: a modeling analysis.

BACKGROUND: Diagnostic investigations, including pathology and laboratory medicine (PALM) and radiology, have been largely absent from international strategies such as the Sustainable Development Goals. Further, there is little international guidance on which health system tiers different diagnostics should be placed, a critical step in developing a country-level diagnostics network. We describe a modeling strategy to produce tier-specific diagnostic recommendations based on disease burden, current treatment pathways, and existing infrastructure in a country. METHODS: The relational model assumes that diagnostics should be available at the lowest tier where patients might receive medical management. Using Ghana as an exemplar, the 20 diseases forecasted by 2030 and 2040 to cause the greatest burden in low- and middle-income countries were mapped to three generalized tiers in the Ghanaian health system (Primary, Secondary, and Tertiary care) for three levels of each disease (triage, uncomplicated, and complicated). The lowest tier at which a diagnostic could potentially be placed was restricted by existing infrastructure, though placement still required there be a medical justification for the diagnostic at that tier. RESULTS: The model recommended 111 unique diagnostic investigations with 17 at Primary tier, an additional 45 at Secondary tier and a further 49 at Tertiary tier. Estimated capital costs were $8,330 at Primary tier and between $571,000 to $777,000 at Secondary tier. Twenty-eight different laboratory tests were recommended as send-outs from Primary to Secondary tier, and twelve as send-outs to Tertiary tier. CONCLUSIONS: This model provides a transparent framework within which countries can customize diagnostic planning to local disease priorities, health system patient treatment pathways, and infrastructural limitations to best support Universal Health Coverage.

Evaluating urban-rural access to pathology and laboratory medicine services in Tanzania.

Placement of pathology and laboratory medicine (PALM) services requires balancing efficiency (maximizing test volume) with equitable urban-rural access. We compared the association between population density (proxy for efficiency) and travel time to the closest facility (proxy for equitable access) across levels of Tanzania's public sector health system. We linked geospatial data for Tanzania from multiple sources. Data on facility locations and other geographic measures were collected from government and non-governmental databases. We classified facilities assuming increasing PALM availability by tier: (1) dispensaries, (2) health centres, (3) district hospitals and (4) regional/referral hospitals. We used the AccessMod 5 algorithm to estimate travel time to the closest facility for each tier across Tanzania with 500-m resolution. District-level average population density and travel time to the closest facility were calculated and presented using medians and interquartile ranges. Spatial correlations between these variables were estimated using the global Moran's I and bivariate Local Indicator of Spatial Autocorrelation, specifying a queen's neighbourhood matrix. Spatial analysis was restricted to 171 contiguous districts. The study included 5406 dispensaries, 675 health centres, 186 district hospitals and 37 regional/referral hospitals. District-level travel times were shortest for Tier 1 (median: [IQR]: 45.4 min [30.0-74.7]) and longest for Tier 4 facilities (160.2 min [107.3-260.0]). There was a weak spatial autocorrelation across tiers (Tier 1: -0.289, Tier 2: -0.292, Tier 3: -0.271 and Tier 4: -0.258) and few districts were classified as significant spatial outliers. Across tiers, geographic patterns of populated districts surrounded by neighbours with short travel time and sparsely populated districts surrounded by neighbours with long travel time were observed. Similar spatial correlation measures across health system levels suggest that Tanzania's health system reflects equitable urban-rural access to different PALM services. Longer travel times to hospital-based care could be ameliorated by shifting specialized diagnostics to more accessible lower tiers.

Geospatial evaluation of trade-offs between equity in physical access to healthcare and health systems efficiency.

INTRODUCTION: Decisions regarding the geographical placement of healthcare services require consideration of trade-offs between equity and efficiency, but few empirical assessments are available. We applied a novel geospatial framework to study these trade-offs in four African countries. METHODS: Geolocation data on population density (a surrogate for efficiency), health centres and cancer referral centres in Kenya, Malawi, Tanzania and Rwanda were obtained from online databases. Travel time to the closest facility (a surrogate for equity) was estimated with 1 km resolution using the Access Mod 5 least cost distance algorithm. We studied associations between district-level average population density and travel time to closest facility for each country using Pearson's correlation, and spatial autocorrelation using the Global Moran's I statistic. Geographical clusters of districts with inefficient resource allocation were identified using the bivariate local indicator of spatial autocorrelation. RESULTS: Population density was inversely associated with travel time for all countries and levels of the health system (Pearson's correlation range, health centres: -0.89 to -0.71; cancer referral centres: -0.92 to -0.43), favouring efficiency. For health centres, negative spatial autocorrelation (geographical clustering of dissimilar values of population density and travel time) was weaker in Rwanda (-0.310) and Tanzania (-0.292), countries with explicit policies supporting equitable access to rural healthcare, relative to Kenya (-0.579) and Malawi (-0.543). Stronger spatial autocorrelation was observed for cancer referral centres (Rwanda: -0.341; Tanzania: -0.259; Kenya: -0.595; Malawi: -0.666). Significant geographical clusters of sparsely populated districts with long travel times to care were identified across countries. CONCLUSION: Negative spatial correlations suggested that the geographical distribution of health services favoured efficiency over equity, but spatial autocorrelation measures revealed more equitable geographical distribution of facilities in certain countries. These findings suggest that even when prioritising efficiency, thoughtful decisions regarding geographical allocation could increase equitable physical access to services.

Empiric Therapeutic Anticoagulation and Mortality in Critically Ill Patients With Respiratory Failure From SARS-CoV-2: A Retrospective Cohort Study.

The pathophysiology of respiratory failure associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains under investigation. One hypothesis is that progressive endothelial damage from the virus leads to microvascular thrombosis. It is uncertain if empiric therapeutic anticoagulation provides benefit over standard deep vein thrombosis (DVT) prophylaxis in critically ill patients with SARS-CoV-2. A retrospective cohort study was performed to evaluate adult patients admitted to the intensive care unit at 3 hospitals with polymerase chain reaction-confirmed SARS-CoV-2-associated respiratory failure requiring invasive mechanical ventilation. A Kaplan-Meier survival analysis was used to compare patients who were initiated on therapeutic anticoagulation prior to the time of intubation and those receiving standard DVT prophylaxis doses. The primary outcome was the difference in the 28-day mortality of patients between the 2 groups. Twenty-eight-day mortality did not differ between groups, occurring in 26.1% of patients who received therapeutic anticoagulation and 29.5% of those who received a prophylactic dose only (hazard ratio, 0.52; P = .055). There was no difference in 28-day mortality between groups in patients who were admitted with a serum D-dimer ≥ 2 µg/mL (hazard ratio, 0.67; P = .41). Empiric therapeutic anticoagulation in patients who require invasive mechanical ventilation for confirmed SARS-CoV-2 infection does not improve 28-day mortality compared with standard DVT prophylaxis, even among those with elevated D-dimer levels.

From potential to practice: how accelerating access to HPV tests and screen and treat programmes can help eliminate cervical cancer.

Human papillomavirus (HPV) vaccination campaigns to prevent cervical cancer are being considered and implemented in countries around the world. While vaccination will protect future generations, it will not help the millions of women currently infected, leading to an estimated 311 000 deaths per year globally. This paper examines a selection of strategies that when applied to both existing and new technologies, could accelerate access to HPV testing. Authors from the US Agency for International Development, the National Institutes of Health, and the Bridge to Health Medical and Dental, a non-governmental organisation, joined forces to propose a scalable and country-directed solution for preventing cervical cancer using an end-to-end approach. Collectively, the authors offer seven evidence-based strategies, that when used alone or in combination have the ability to reduce HPV-caused cervical cancer deaths and disability. These strategies include (1) consistent HPV test intervals to decrease HPV DNA test costs; (2) exploring market shaping opportunities; (3) employing iterative user research methodologies like human-centred design; (4) target product profiles for new HPV tests; (5) encouraging innovation around cervical cancer screen and treat programmes; (6) developing national cancer control plans; and (7) integrating cervical cancer screen and treat services into existing infrastructure. By using the strategies outlined here, in combination with HPV vaccination campaigns, national governments will be able to scale and expand cervical cancer screening programmes and provide evidence-based treatment programmes for HPV-infected women.

Histology and Cytopathology Capacity in the Public Health Sector in Kenya.

PURPOSE: Histology and cytopathology services are necessary for cancer diagnosis and treatment. However, the current capacity of Kenya's pathology laboratories is unknown. A national survey was conducted among public sector pathology laboratories to assess their capacity to perform histology, fine-needle aspiration, and bone marrow aspiration. METHODS: Between April and June 2017, we identified all public hospitals that provide pathology services in Kenya. In total, two national and 13 county referral hospitals met the inclusion criteria and were sent a standardized, pretested, self-administered questionnaire. RESULTS: A total of 11 hospitals (73%) completed the survey. The reported total caseload of histology, fine-needle aspiration, and bone marrow aspiration for 2016 was 26,472. All of the facilities staffed a pathologist and were providing cancer-related diagnostic services. Nine (82%) of the hospitals maintain a register of diagnosed cancer cases, but only one (11%) of those uses an electronic system. Six (55%) of the surveyed hospitals were able to perform histology with a median turnaround time of 14 days. Six (55%) laboratories regularly referred some specimens elsewhere for interpretation, but three of these centers relied on patients for transportation of the specimen to the referral institution. No laboratories were accredited by an external organization; however, 10 (91%) of the laboratories were working toward achieving accreditation, but only for clinical pathology services. CONCLUSION: This study describes the current status of histology and cytopathology capacity in Kenya's public sector hospitals. It provides useful baseline information needed by the Ministry of Health to develop necessary capacity building and referral-strengthening interventions. A high proportion of hospitals are working to achieve accreditation points toward their commitment to providing quality services to the Kenyan public.

Age-Standardized Mortality Rates in the Caribbean: One Source, Three Different Interpretations.

Purpose A recent publication in Morbidity and Mortality Weekly Report ( MMWR) provided the opportunity to calculate differences in published cancer mortality estimates for Caribbean jurisdictions from three organizations: MMWR, the International Agency for Research on Cancer, and the Institute for Health Metrics and Evaluation. This comparison study serves to educate end users of these data. Methods We downloaded the publicly available cancer mortality estimates for 15 jurisdictions and the United States from the three organizations. We compared reported age-standardized mortality rates for each jurisdiction and calculated the range among estimates for each jurisdiction. We repeated this analysis after applying the same world population standard to all estimates. Results For males, the ranges of the Caribbean estimates were between 49% (Grenada and Trinidad) and 201% (US Virgin Islands) of the MMWR value, with an average of 88%. For females, the ranges were between 15% (Trinidad) and 171% (US Virgin Islands) of the MMWR value, with an average of 64%. After all estimates were compared using the same population standard, the ranges of the Caribbean estimates for males were between 6% (Grenada) and 111% (US Virgin Islands) of the MMWR value, with an average of 34%. For females, the ranges were between 7% (Grenada) and 97% (US Virgin Islands), with an average of 28%. Conclusion The use of different standard populations complicates comparisons across organizations. Data modeling does not completely compensate for quality of source data, as our analysis demonstrated by the differences in mortality rates despite the good quality of the vital registration in the Caribbean.

Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions.

Insufficient awareness of the centrality of pathology and laboratory medicine (PALM) to a functioning health-care system at policy and governmental level, with the resultant inadequate investment, has meant that efforts to enhance PALM in low-income and middle-income countries have been local, fragmented, and mostly unsustainable. Responding to the four major barriers in PALM service delivery that were identified in the first paper of this Series (workforce, infrastructure, education and training, and quality assurance), this second paper identifies potential solutions that can be applied in low-income and middle-income countries (LMICs). Increasing and retaining a quality PALM workforce requires access to mentorship and continuing professional development, task sharing, and the development of short-term visitor programmes. Opportunities to enhance the training of pathologists and allied PALM personnel by increasing and improving education provision must be explored and implemented. PALM infrastructure must be strengthened by addressing supply chain barriers, and ensuring laboratory information systems are in place. New technologies, including telepathology and point-of-care testing, can have a substantial role in PALM service delivery, if used appropriately. We emphasise the crucial importance of maintaining PALM quality and posit that all laboratories in LMICs should participate in quality assurance and accreditation programmes. A potential role for public-private partnerships in filling PALM services gaps should also be investigated. Finally, to deliver these solutions and ensure equitable access to essential services in LMICs, we propose a PALM package focused on these countries, integrated within a nationally tiered laboratory system, as part of an overarching national laboratory strategic plan.

Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action.

Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health. The national strategic laboratory plan should deliver a tiered, networked laboratory system as a central element. Appropriate financing should be provided, at a level of at least 4% of health expenditure. Financing of new technologies such as molecular diagnostics is challenging for LMICs, even though many of these tests are cost-effective. Point-of-care testing can substantially reduce test-reporting time, but this benefit must be balanced with higher costs. Our research analysis highlights a considerable deficiency in advocacy for PALM; pathologists have been invisible in national and international health discourse and leadership. Embedding PALM in LMICs can only be achieved if pathologists advocate for these services, and undertake leadership roles, both nationally and internationally. We articulate eight key recommendations to address the current barriers identified in this Series and issue a call to action for all stakeholders to come together in a global alliance to ensure the effective provision of PALM services in resource-limited settings.

Global Health Pathology Research: Purpose and Funding.

Like in all areas of science, it is important for funders and investigators of pathology to work together to develop a well-designed, well-executed clinical research agenda. In the first section of this article, the authors discuss how the National Institutes of Health (NIH) peer-review process applies to global health pathology research projects. Then, the authors present an illustrative sampling of NIH-funded projects with performance sites in low- and middle-income countries with 2 examples focused on cancer and anatomic pathology. Finally, the authors relate the research agenda to overarching strategic recommendations for enhancing global pathology.

An Essential Pathology Package for Low- and Middle-Income Countries.

Objectives: We review the current status of pathology services in low- and middle-income countries and propose an "essential pathology package" along with estimated costs. The purpose is to provide guidance to policy makers as countries move toward universal health care systems. Methods: Five key themes were reviewed using existing literature (role of leadership; education, training, and continuing professional development; technology; accreditation, management, and quality standards; and reimbursement systems). A tiered system is described, building on existing proposals. The economic analysis draws on the very limited published studies, combined with expert opinion. Results: Countries have underinvested in pathology services, with detrimental effects on health care. The equipment needs for a tier 1 laboratory in a primary health facility are modest ($2-$5,000), compared with $150,000 to $200,000 in a district hospital, and higher in a referral hospital (depending on tests undertaken). Access to a national (or regional) specialized laboratory undertaking disease surveillance and registry is important. Recurrent costs of appropriate laboratories in district and referral hospitals are around 6% of the hospital budget in midsized hospitals and likely decline in the largest hospitals. Primary health facilities rely largely on single-use tests. Conclusions: Pathology is an essential component of good universal health care.

Systems and capacity to address noncommunicable diseases in low- and middle-income countries.

Noncommunicable diseases (NCDs) are increasingly getting attention from different forums, including media outlets, health agencies, and the public and private sectors. Progress is being made in addressing NCDs, though more slowly in low- and middle-income countries (LMICs) as compared with high-income settings. Here, we offer an analysis of the challenges faced in LMICs. We discuss realistic strategies to understand and develop capacity needs (workforce, finances, and infrastructure) and systems (institutions and processes) to sustainably optimize NCD prevention and care in LMICs.

Hypertensive emergency and severe hypertension: what to treat, who to treat, and how to treat.

Remember to treat patients, not numbers. Use fast acting shortterm medicines only when convincing evidence of rapidly evolving end-organ damage is present. For all patients, emergent or asymptomatic, the treatment goal is long-term control of hypertension. Potent IV agents for the im-mediate control of elevated blood pressure need to be used cautiously,bearing in mind both the side effects and the hazards of overly rapid control of hypertension. Conventional oral medication regimens demonstrated to modify the risks of chronic hypertension should be used whenever possible and as early as is practical to promote gradual control of hypertension. Whenever a patient presents for the evaluation of severe hypertension in an emergent setting, take the opportunity to encourage appropriate ongoing follow-up; after all, hypertension is not a single episode, it is an ongoing threat to good health.

Flumazenil reversal of lorazepam-induced acute delirium.

We report the case of a 63-year-old man who presented to the Emergency Department (ED) with a 1-week history of sore throat, hoarseness and dysphagia. During his ED workup, the patient experienced an acute delirium 25 min after being given 2 mg of Lorazepam. The patient's mentation returned to normal within 1-2 min of being given 1 mg of Flumazenil. We discuss the various behavioral side effects of benzodiazepines and the indications for the use of Flumazenil.