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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Outcome of traumatic extradural haematoma in Hong Kong

Aim. Traumatic extradural haematoma (EDH) is a neurosurgical emergency and timely surgical intervention for significant EDH is the gold standard. This study aims to determine the incidence and mortality of consecutive patients with traumatic EDH admitted to the Emergency Department (ED) of Prince of Wales Hospital (PWH), a University Hospital Trauma Centre in Hong Kong. Patients and methods. Retrospective analysis of prospectively collected data for all consecutive trauma cases admitted through the ED during 2001–2004. EDH was diagnosed by CT in all cases. Both primary and delayed onset EDH were included, as were patients with combined EDH and other intracranial lesions (e.g. subdural haematoma). Age, sex, cause of injury, associated intracranial lesions, skull fracture, Glasgow Coma Scale, pupil reactivity, treatment, length of stay and clinical outcome were determined. Results. Two thousand and two hundred and eight patients were in the trauma registry for 2001–2004. Total 1080 head injured patients; 89 patients had traumatic EDH, mean of 1.9 patients per month. Seventy (79%) patients were male, with a mean age of 37.7 years. Fifty (56%) patients were from road traffic crashes, 27 (30%) sustained falls, 10 (11%) had direct head trauma. On admission, 62 (70%) patients were GCS 13–15, 9 (10%) GCS 9–12 and 18 (20%) GCS 3–8. Sixty-six (74%) patients had a skull fracture. Thirty (34%) patients underwent neurosurgical operation. Overall, nine patients (10%) died; eight patients were GCS < 8; five had bilateral fixed and dilated pupils; one had a single fixed and dilated pupil. Four patients died after neurosurgical operation, three of whom had fixed dilated pupils and were GCS 3 prior to surgery. Median length of hospital stay for survivors was 10.4 days. Conclusion. Survival from traumatic EDH was 90% (80/89) and 91% (73/80) of survivors had a Glasgow Outcome Score of 4 or 5 (good or moderate). The combination of bilateral fixed dilated pupils and GCS 3 suggests severe primary brain injury. Emergency evacuation of intracranial haematomas is unlikely to improve the outcome for these patients. Even in an urban environment with short prehospital times and rapid access to neurosurgery, outcome in patients who are GCS 3 following EDH is likely to be poor

Association between Ambient Temperatures and Mental Disorder Hospitalizations in a Subtropical City: A Time-Series Study of Hong Kong Special Administrative Region

Background: Mental disorders have been found to be positively associated with temperature in cool to cold climatic regions but the association in warmer regions is unclear. This study presented the short-term association between temperatures and mental disorder hospitalizations in a subtropical city with a mean annual temperature over 21 °C. Methods: Using Poisson-generalized additive models and distributed-lagged nonlinear models, daily mental disorder hospitalizations between 2002 and 2011 in Hong Kong were regressed on daily mean temperature, relative humidity, and air pollutants, adjusted for seasonal trend, long-term trend, day-of-week, and holiday. Analyses were stratified by disease class, gender and age-group. Results: 44,600 admissions were included in the analysis. Temperature was positively associated with overall mental-disorder hospitalizations (cumulative relative risk at 28 °C vs. 19.4 °C (interquartile range, lag 0–2 days) = 1.09 (95% confidence interval 1.03, 1.15)), with the strongest effect among the elderly (≥75 years old). Transient mental disorders due to conditions classified elsewhere and episodic mood disorders also showed strong positive associations with temperature. Conclusion: This study found a positive temperature–mental-disorder admissions association in a warm subtropical region and the association was most prominent among older people. With the dual effect of global warming and an aging population, targeted strategies should be designed to lower the disease burden

Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative

The folate receptor (FR) is highly expressed on most epithelial cancer cells, while normal cells show only restricted expression of FR. As a result, the FR is an ideal target for receptor-based molecular imaging and therapy of cancer and has become a promising target in oncology. To date, several folate-based chemotherapeutics and imaging probes such as radiopharmaceuticals for single photon emission computed tomography (SPECT) have been developed. However, an (18)F-labeled folic acid derivative suitable for positron emission tomography (PET) imaging that can be routinely applied is still lacking. In this study, a new fluorinated and radiofluorinated folic acid derivative, (18/19)F-click folate, was synthesized using click chemistry. In a convenient and very efficient two-step radiosynthesis, the isolated (18)F-click folate was obtained in good radiochemical yields of 25-35% with a specific activity of 160+/-70 GBq/micromol after >or=90 min synthesis time. The new compound was pharmacologically evaluated in vitro and in vivo. The affinity of the non-radioactive (19)F-click folate to the FR was determined in displacement studies with FR expressing KB tumor cells using (3)H-folic acid. In these in vitro binding studies, a nanomolar affinity with a K(i) of 9.76+/-3.13 nM was found for (19)F-click folate. The (18)F-labeled click folate derivative was then applied for in vivo PET studies and ex vivo biodistribution experiments using nude mice bearing KB tumor xenografts. The post mortem dissection experiments showed a high specific uptake of (18)F-click folate derivative in FR-expressing tissues. Uptake in KB tumor xenografts and kidneys (FR-positive tissue) amounted to 3.13%ID/g (94% specific blockade) and 16.53%ID/g (75% specific blockade), respectively. PET imaging using (18)F-click folate permitted a visualization of KB tumors, and blockade studies confirmed the specific accumulation of the radiotracer in vivo. However, strong hepatobiliary excretion of the new tracer led to elevated accumulation of radioactivity in the abdominal region. In conclusion, the click chemistry approach is convenient to accomplish and provided high radiochemical yields of (18)F-click folate. The new tracer showed good in vitro but limited in vivo properties. Ultimately, the (18)F-click folate emphasizes the potential of (18)F-labeled folates for receptor-based tumor PET imaging