Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Summary Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO’s Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries’ health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO’s GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite noncommunicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world’s evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UH

Nonstimulated early visual areas carry information about surrounding context

Even within the early sensory areas, the majority of the input to any given cortical neuron comes from other cortical neurons. To extend our knowledge of the contextual information that is transmitted by such lateral and feedback connections, we investigated how visually nonstimulated regions in primary visual cortex (V1) and visual area V2 are influenced by the surrounding context. We used functional magnetic resonance imaging (fMRI) and pattern-classification methods to show that the cortical representation of a nonstimulated quarter-field carries information that can discriminate the surrounding visual context. We show further that the activity patterns in these regions are significantly related to those observed with feed-forward stimulation and that these effects are driven primarily by V1. These results thus demonstrate that visual context strongly influences early visual areas even in the absence of differential feed-forward thalamic stimulation

Curvature-Induced Defect Unbinding in Toroidal Geometries

Toroidal templates such as vesicles with hexatic bond orientational order are discussed. The total energy including disclination charges is explicitly computed for hexatic order embedded in a toroidal geometry. Related results apply for tilt or nematic order on the torus in the one Frank constant approximation. Although there is no topological necessity for defects in the ground state, we find that excess disclination defects are nevertheless energetically favored for fat torii or moderate vesicle sizes. Some experimental consequences are discussed.Comment: 12 pages, 15 eps figure

Prognostic Value of Bronchiolitis Obliterans Syndrome Stage 0-p in Single-Lung Transplant Recipients

Rationale: Early diagnosis of bronchiolitis obliterans syndrome (BOS) is critical in understanding pathogenesis and devising therapeutic trials. Although potential-BOS stage (BOS 0-p), encompassing early changes in FEV1 and forced expiratory flow, midexpiratory phase (FEF25–75%), has been proposed, there is a paucity of data validating its utility in single-lung transplantation. Objective: The aim of this study was to define the predictive ability of BOS 0-p in single-lung transplantation. Methods: We retrospectively analyzed spirometric data for 197 single-lung recipients. Sensitivity, specificity, and positive predictive value of BOS 0-p were examined over time using Kaplan-Meier methodology. Results: BOS 0-p FEV1 was associated with higher sensitivity, specificity, and positive predictive value than the FEF25–75% criterion over different time periods investigated. The probability of testing positive for BOS 0-p FEV1 in patients with BOS (sensitivity) was 71% at 2 years before the onset of BOS. The probability of being free from development of BOS 0-p FEV1 in patients free of BOS at follow-up (specificity) was 93% within the last year. Of patients who met the BOS 0-p FEV1 criterion, 81% developed BOS or died within 3 years. The specificity and positive predictive value curves for the BOS 0-p FEV1 were significantly different between patients with underlying restrictive versus obstructive physiology (p = 0.05 and 0.01, respectively). Conclusion: The FEV1 criterion for BOS 0-p provides useful predictive information regarding the risk of development of BOS or death in single-lung recipients. The predictive value of this criterion is higher in patients with underlying restriction and is superior to the FEF25–75% criterion.Supported in part by National Institutes of Health grants K23 HL077719 and K24HL04212 and American Lung Association RG-1059-N.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91970/1/2005 AJRCCM - Prognostic Value of Bronchiolitis Obliterans Syndrome Stage 0-p in Single-Lung Transplant Recipients.pd

Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia

Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (p <= 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease > 10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.Supported by National Institutes of Health NHLBI grants P50HL46487, NIH/NCRR 3 MO1 RR00042-33S3, NIH/NIA P60 AG08808-06, NHLBI, 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91973/1/2003 AJRCCM - Prognostic Implications of Physiologic and Radiographic Changes in Idiopathic Interstitial Pneumonia.pd

Fibroblastic Foci in Usual Interstitial Pneumonia: Idiopathic versus Collagen Vascular Disease

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease–associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease–associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease–associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.Supported in part by National Institutes of Health National Heart, Lung, and Blood Institute grant #P50HL46487, NIH/NCRR 3 MO1 RR00042–33S3, NIH/NIA P60 AG08808–06, NHLBI 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91974/1/2003 AJRCCM - Fibroblastic Foci in Usual Interstitial Pneumonia -Idiopathic versus Collagen Vascular Disease.pd

Prognostic Value of Bronchiolitis Obliterans Syndrome Stage 0-p in Single-Lung Transplant Recipients

Rationale: Early diagnosis of bronchiolitis obliterans syndrome (BOS) is critical in understanding pathogenesis and devising therapeutic trials. Although potential-BOS stage (BOS 0-p), encompassing early changes in FEV 1 and forced expiratory flow, midexpiratory phase (FEF 25-75% ), has been proposed, there is a paucity of data validating its utility in single-lung transplantation. Objective: The aim of this study was to define the predictive ability of BOS 0-p in single-lung transplantation. Methods: We retrospectively analyzed spirometric data for 197 single-lung recipients. Sensitivity, specificity, and positive predictive value of BOS 0-p were examined over time using Kaplan-Meier methodology. Results: BOS 0-p FEV 1 was associated with higher sensitivity, specificity, and positive predictive value than the FEF 25-75% criterion over different time periods investigated. The probability of testing positive for BOS 0-p FEV 1 in patients with BOS (sensitivity) was 71% at 2 years before the onset of BOS. The probability of being free from development of BOS 0-p FEV 1 in patients free of BOS at follow-up (specificity) was 93% within the last year. Of patients who met the BOS 0-p FEV 1 criterion, 81% developed BOS or died within 3 years. The specificity and positive predictive value curves for the BOS 0-p FEV 1 were significantly different between patients with underlying restrictive versus obstructive physiology (p ϭ 0.05 and 0.01, respectively). Conclusion: The FEV 1 criterion for BOS 0-p provides useful predictive information regarding the risk of development of BOS or death in single-lung recipients. The predictive value of this criterion is higher in patients with underlying restriction and is superior to the FEF 25-75% criterion. Keywords: bronchiolitis obliterans syndrome; diagnosis; lung transplantation; staging Bronchiolitis obliterans is the major complication limiting outcomes in lung transplantation (1-3). Its clinical correlate, bronchiolitis obliterans syndrome (BOS), is defined as a fall in FEV 1 of greater than 20% from baseline determined by the average of two measurements made at least 3 weeks apart (4). Development of BOS is associated with progressive irreversible decline in lung function with a poor response to therapeutic interventions (1, 2). This feature, and the knowledge that pathogenesis of BO involves progressive fibroproliferation (2, 5), underscores the need for early intervention and the need to develop predictors of this disease. Implementation of increasingly sensitive criteria for identifying early decline in pulmonary function may allow the prediction of BOS. As such, a potential-BOS stage (BOS 0-p), defined by a 10 to 19% decrease in FEV 1 and/or by a 25% or greater decrease in forced expiratory flow, midexpiratory phase (FEF 25-75% ), from baseline was added to the original staging system in 2001 (4). In bilateral lung transplant recipients, the FEV 1 but not the FEF 25-75% criterion for BOS 0-p was shown to be a reasonable predictor of BOS (6). However, the role of various criteria of BOS 0-p in predicting recipients with BOS remains to be established in single-lung transplant (SLT) recipients. This population is of particular interest because spirometric criteria, such as FEV 1 and FEF 25-75% , are influenced by degree and nature of native lung pathology This study provides novel data defining the ability of both FEV 1 and FEF 25-75% criteria for BOS 0-p to predict development of BOS in a large cohort of SLT recipients. Some of these results have been previously reported in the form of an abstract (8). METHODS Patients The study group comprised 197 consecutive SLT recipients who were alive 3 months post-transplantation and had post-transplant pulmonary functions available. The study was approved by the University of Michigan Institutional Review Board. All patients were followed by a standardized protocol as previously described (9). Pulmonary function testing was performed following standards established by the American Thoracic Society at each clinic visit (10). Definition of BOS Baseline FEV 1 and FEF 25-75% were determined according to the published guidelines (4). The criterion for BOS was met when two consecutive FEV 1 values at least 3 weeks apart fell below 80% of baseline FEV 1 . Therefore, BOS diagnosis included stages 1, 2, and 3. Medical records of the patients during this time period were reviewed to exclude confounding variables, including infection, acute rejection, bronchial stenosis, and recurrence of primary disease or any other factors that might explain this decline in lung function. The date of onset of BOS was defined as the date of the first of the two FEV 1 measurements used to establish the diagnosis. Definition of BOS 0-p BOS 0-p was determined by the FEV 1 and the FEF 25-75% criteria, as defined by the new guidelines (4), using a similar method as described above. A modified FEF 25-75% criterion for stage 0-p as defined by Hachem and others (6) in the bilateral lung transplant population was also analyzed. This modified FEF 25-75% redefines the baseline FEF 25-75% as the average of the two FEF 25-75% measurements obtained with the two highest FEV 1 measurements (6). Data Analysis Correlated times to event were analyzed using years-of-life-saved statistics (11). Kaplan-Meier methodology was used to estimate sensitivity, specificity, and positive predictive value (PPV) curves for relating the diagnosis of BOS 0-p by various criteria to development of BOS. These diagnostic curves are functions of the time between meeting, or not meeting, the BOS 0-p and BOS criteria as well as the available follow-up window. The appropriate patient population, event time scale, and follow-up time scale used to construct sensitivity, specificity, and PP

Sex Differences in Severe Pulmonary Emphysema

Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower bodymass index (BMI), shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of packyears, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.The National Emphysema Treatment Trial (NETT) was supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119); the Centers for Medicare and Medicaid Services (CMS; formerly the Health Care Financing Administration); and the Agency for Healthcare Research and Quality (AHRQ). J.L.C. is supported by funding from a Research Enhancement Award Program (REAP) from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91968/1/2007 Martinez AJRCCM Sex Differences in Empy.pd

Predictive processing increases intelligibility of acoustically distorted speech : Behavioral and neural correlates

Introduction: We examined which brain areas are involved in the comprehension of acoustically distorted speech using an experimental paradigm where the same distorted sentence can be perceived at different levels of intelligibility. This change in intelligibility occurs via a single intervening presentation of the intact version of the sentence, and the effect lasts at least on the order of minutes. Since the acoustic structure of the distorted stimulus is kept fixed and only intelligibility is varied, this allows one to study brain activity related to speech comprehension specifically. Methods: In a functional magnetic resonance imaging (fMRI) experiment, a stimulus set contained a block of six distorted sentences. This was followed by the intact counterparts of the sentences, after which the sentences were presented in distorted form again. A total of 18 such sets were presented to 20 human subjects. Results: The blood oxygenation level dependent (BOLD)-responses elicited by the distorted sentences which came after the disambiguating, intact sentences were contrasted with the responses to the sentences presented before disambiguation. This revealed increased activity in the bilateral frontal pole, the dorsal anterior cingulate/paracingulate cortex, and the right frontal operculum. Decreased BOLD responses were observed in the posterior insula, Heschl's gyrus, and the posterior superior temporal sulcus. Conclusions: The brain areas that showed BOLD-enhancement for increased sentence comprehension have been associated with executive functions and with the mapping of incoming sensory information to representations stored in episodic memory. Thus, the comprehension of acoustically distorted speech may be associated with the engagement of memory-related subsystems. Further, activity in the primary auditory cortex was modulated by prior experience, possibly in a predictive coding framework. Our results suggest that memory biases the perception of ambiguous sensory information toward interpretations that have the highest probability to be correct based on previous experience.Peer reviewe