Patient-Level Explainable Machine Learning to Predict Major Adverse Cardiovascular Events from SPECT MPI and CCTA Imaging

Background: Machine learning (ML) has shown promise in improving the risk prediction in non-invasive cardiovascular imaging, including single-photon emission computed tomography (SPECT) and coronary computed tomography angiography (CCTA). However, most algorithms used remain black boxes to clinicians in how they compute their predictions. Furthermore, objective consideration of the multitude of available clinical data, along with the visual and quantitative assessments from CCTA and SPECT, are critical for optimal patient risk stratification. We aim to provide an explainable ML approach to predict major adverse cardiovascular events (MACE) using clinical, CCTA, and SPECT data. Methods: Consecutive patients who underwent clinically indicated CCTA and SPECT myocardial imaging for suspected coronary artery disease (CAD) were included and followed up for MACEs. We employed an Automated Machine Learning (AutoML) approach to predict MACE using clinical, CCTA, and SPECT data. Various mainstream models with different sets of hyperparameters have been explored, and critical predictors of risk are obtained using explainable techniques on the global and patient levels. Results: A total of 956 patients were included (mean age 61.1 ±14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive CAD on CTA and ischemia on SPECT were observed in 14% of patients. ML prediction’s sensitivity, specificity, and diagnostic accuracy in predicting a MACE were 69.61%, 99.77%, and 96.54%, respectively. The top 10 global predictive features included 8 CCTA attributes (segment involvement score, number of vessels with severe plaque ≥70, ≥50% stenosis in the left marginal coronary artery, calcified plaque, ≥50% stenosis in the left circumflex coronary artery, plaque type in the left marginal coronary artery, stenosis degree in the second obtuse marginal of the left circumflex artery, and stenosis category in the marginals of the left circumflex artery) and 2 clinical features (past medical history of MI or left bundle branch block, being an ever smoker). Conclusion: ML can accurately predict risk of developing adverse events (MACE) in patients suspected of ischemic heart disease (CAD) undergoing SPECT and CCTA. ML feature-ranking can also show, at a sample- as well as at a patient-level, which features are key in making such a prediction

Burden of Neurological Disorders Across the US From 1990-2017

IMPORTANCE Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US. OBJECTIVE To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017. DESIGN, SETTING, AND PARTICIPANTS This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus. EXPOSURES Any of the 14 listed neurological diseases. MAIN OUTCOME AND MEASURE Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated. RESULTS The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (−29.1% [95% UI, −32.4% to −25.8%]); spinal cord injury prevalence (−38.5% [95% UI, −43.1% to −34.0%]); meningitis prevalence (−44.8% [95% UI, −47.3% to −42.3%]), deaths (−64.4% [95% UI, −67.7% to −50.3%]), and DALYs (−66.9% [95% UI, −70.1% to −55.9%]); and encephalitis DALYs (−25.8% [95% UI, −30.7% to −5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus. CONCLUSIONS AND RELEVANCE There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders

The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis

ObjectiveTo perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy.MethodsMedline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate.ResultsWe included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6–11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5–3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively.ConclusionsEvidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.</jats:sec

Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

Background Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016. Methods We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate. Findings Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% [–1·5 to −1·2]) than mortality did (–4·5% [–5·0 to −4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality). Interpretation If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV

Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and Subclinical Cushing Syndrome:a systematic review and meta-analysis

Objective Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing’s syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. Methods MEDLINE In-Process &amp; Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. Results We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3–27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5–9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97–7.2) or obesity (RR 3.4, 95% CI: 0.95–12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. Conclusions Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management. </jats:sec

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Systematic review of electronic health records to manage chronic conditions among displaced populations.

OBJECTIVES: The objective of this study was to assess the impact of electronic health records (EHRs) on health outcomes and care of displaced people with chronic health conditions and determine barriers and facilitators to EHR implementation in displaced populations. DESIGN: A systematic review protocol was developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Systematic Reviews. DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, Health Technology Assessment, Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was searched from inception to 12 April 2021. ELIGIBILITY CRITERIA FOR SELECTED STUDIES: Inclusion criteria were original research articles, case reports and descriptions of EHR implementation in populations of displaced people, refugees or asylum seekers with related chronic diseases. Grey literature, reviews and research articles unrelated to chronic diseases or the care of refugees or asylum populations were excluded. Studies were assessed for risk of bias using a modified Cochrane, Newcastle-Ottawa and Joanna Briggs Institute tools. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data from each study using Covidence. Due to heterogeneity across study design and specific outcomes, a meta-analysis was not possible. An inductive thematic analysis was conducted using NVivo V.12 (QSR International, Melbourne, Australia). An inductive analysis was used in order to uncover patterns and themes in the experiences, general outcomes and perceptions of EHR implementation. RESULTS: A total of 32 studies across nine countries were included: 14 in refugee camps/settlements and 18 in asylum countries. Our analysis suggested that EHRs improve health outcomes for chronic diseases by increasing provider adherence to guidelines or treatment algorithms, monitoring of disease indicators, patient counselling and patient adherence. In asylum countries, EHRs resource allocation to direct clinical care and public health services, as well as screening efforts. EHR implementation was facilitated by their adaptability and ability to integrate into management systems. However, barriers to EHR development, deployment and data analysis were identified in refugee settings. CONCLUSION: Our results suggest that well-designed and integrated EHRs can be a powerful tool to improve healthcare systems and chronic disease outcomes in refugee settings. However, attention should be paid to the common barriers and facilitating actions that we have identified such as utilising a user-centred design. By implementing adaptable EHR solutions, health systems can be strengthened, providers better supported and the health of refugees improved

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning