Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges

Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) and refractory hypertension (RfH). Recent findings suggest that the former may be due to an alteration in the renin–angiotensin–aldosterone axis, while the latter seems to be more closely related to sympathetic hyper-activation. Both these pathophysiological mechanisms are also activated in patients with obstructive sleep apnoea (OSA). It is not surprising, therefore, that the prevalence of OSA in RH and RfH patients is very high (as reflected in several studies) and that treatment with continuous positive airway pressure (CPAP) manages to reduce blood pressure levels in a clinically significant way in both these groups of hypertensive patients. It is therefore necessary to incorporate into the multidimensional treatment of patients with RH and RfH (changes in lifestyle, control of obesity and drug treatment) a study of the possible existence of OSA, as this is a potentially treatable disease. There are many questions that remain to be answered, especially regarding the ideal combination of treatment in patients with RH/RfH and OSA (drugs, renal denervation, CPAP treatment) and patients’ varying response to CPAP treatment

2000 Wild Blueberry Project Reports

The 2000 edition of the Wild Blueberry Project Reports was prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Determination of Pesticide Residue Levels in Fresh and Processed Wild Blueberries 2. Factors Affecting the Microbiological Quality of IQF Blueberries 3. Effect of Processed Blueberry Products on Oxidation in Meat Based Food Systems 4. Separation of Maggot Infested Wild Blueberries in the IQF Processing Line 5. Water Use of Wild Blueberries 6. Control Tactics for Blueberry Pest Insects, 2000 7. IPM Strategies 8. Biology and Ecology of Blueberry Pest Insects 9. Survey of Stem Blight and Leaf Spot Diseases in Lowbush Blueberry Fields 10. Phosphorus/Nitrogen Fertilizer Ratio 11. Effect of Boron Application Methods on Boron Uptake in Lowbush Blueberries 12. Effect of Foliar Iron and Copper Application on Growth and Yield of Lowbush Blueberries 13. Effect of Soil pH on Nutrient Uptake 14. Effect of Nutri-Phite (tm) P+K on Growth and Yield of Lowbush Blueberry 15. Effect of Fertilizer Timing on Lowbush Blueberry Growth and Productivity 16. Assessment of Azafenidin for Weed Control in Wild Blueberries 17. Assessment of Rimsulfuron for Weed Control in Wild Blueberries 18. Assessment of Pendimethalin for Weed Control in Wild Blueberries 19. Assessment of VC1447 for Weed Control in Wild Blueberries 20. Cultural Management Using pH for Weed Control in Wild Blueberries 21. Evaluation of Sprout-Less Weeder® for Weed Control in Wild Blueberries 22. Evaluation of RoundUp Ultra® and Touchdown 5® for Weed Control in Wild Blueberries 23. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 24. Evaluation of Fungicides Efficacy in Wild Blueberry Fields 25. Velpar® and Sinbar/Karmex® Demonstration Plot Comparison Trial 26. Blueberry Extension Education Program in 2000 27. 2000 Hexazinone Groundwater Surve

Metabolically Healthy Obesity and High Carotid Intima-Media Thickness in Children and Adolescents: International Childhood Vascular Structure Evaluation Consortium

OBJECTIVE It has been argued that metabolically healthy obesity (MHO) does not increase cardiovascular disease (CVD) risk. This study examines the association of MHO with carotid intima-media thickness (cIMT), a proxy of CVD risk, in children and adolescents. RESEARCH DESIGN AND METHODS Data were available for 3,497 children and adolescents aged 6–17 years from five population-based cross-sectional studies in Brazil, China, Greece, Italy, and Spain. Weight status categories (normal, overweight, and obese) were defined using BMI cutoffs from the International Obesity Task Force. Metabolic status (defined as "healthy" [no risk factors] or "unhealthy" [one or more risk factors]) was based on four CVD risk factors: elevated blood pressure, elevated triglyceride levels, reduced HDL cholesterol, and elevated fasting glucose. High cIMT was defined as cIMT ≥90th percentile for sex, age, and study population. Logistic regression model was used to examine the association of weight and metabolic status with high cIMT, with adjustment for sex, age, race/ethnicity, and study center. RESULTS In comparison with metabolically healthy normal weight, odds ratios (ORs) for high cIMT were 2.29 (95% CI 1.58–3.32) for metabolically healthy overweight and 3.91 (2.46–6.21) for MHO. ORs for high cIMT were 1.44 (1.03–2.02) for unhealthy normal weight, 3.49 (2.51–4.85) for unhealthy overweight, and 6.96 (5.05–9.61) for unhealthy obesity. CONCLUSIONS Among children and adolescents, cIMT was higher for both MHO and metabolically healthy overweight compared with metabolically healthy normal weight. Our findings reinforce the need for weight control in children and adolescents irrespective of their metabolic status

Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study

Acknowledgements Cohort-specific acknowledgements are presented in the supplementary material. We also acknowledge collaboration with the EXPANSE consortium (funded by the EU H2020 programme, grant number 874627). We thank Elise Heuvelin, European Respiratory Society, Lausanne, Switzerland, for her assistance on the current project.Peer reviewedPublisher PD

Future and potential spending on health 2015-40 : development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential.Peer reviewe

Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US$10 trillion (95$20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only $40 (24–65) to$413 (263–668) in 2040 in low-income countries, and from $140 (90–200) to$1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC. Funding: The Bill & Melinda Gates Foundation

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens