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Background Reliable statistics on the underlying cause of death are essential for monitoring the health in a population. When there is insufficient information to identify the true underlying cause of death, the death will be classified using less informative codes, garbage codes. If many deaths are assigned a garbage code, the information value of the cause-of-death statistics is reduced. The aim of this study was to analyse the use of garbage codes in the Norwegian Cause of Death Registry (NCoDR). Methods Data from NCoDR on all deaths among Norwegian residents in the years 1996–2019 were used to describe the occurrence of garbage codes. We used logistic regression analyses to identify determinants for the use of garbage codes. Possible explanatory factors were year of death, sex, age of death, place of death and whether an autopsy was performed. Results A total of 29.0% (290,469/1,000,128) of the deaths were coded with a garbage code; 14.1% (140,804/1,000,128) with a major and 15.0% (149,665/1,000,128) with a minor garbage code. The five most common major garbage codes overall were ICD-10 codes I50 (heart failure), R96 (sudden death), R54 (senility), X59 (exposure to unspecified factor), and A41 (other sepsis). The most prevalent minor garbage codes were I64 (unspecified stroke), J18 (unspecified pneumonia), C80 (malignant neoplasm with unknown primary site), E14 (unspecified diabetes mellitus), and I69 (sequelae of cerebrovascular disease). The most important determinants for the use of garbage codes were the age of the deceased (OR 17.4 for age ≥ 90 vs age < 1) and death outside hospital (OR 2.08 for unknown place of death vs hospital). Conclusion Over a 24-year period, garbage codes were used in 29.0% of all deaths. The most important determinants of a death to be assigned a garbage code were advanced age and place of death outside hospital. Knowledge of the national epidemiological situation, as well as the rules and guidelines for mortality coding, is essential for understanding the prevalence and distribution of garbage codes, in order to rely on vital statistics.

Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.

Background Information on cause of death may help appraise the degree to which the high excess mortality after hip fracture reflects pre-existing comorbidities or the injury itself. We aimed to describe causes of death and cause-specific excess mortality through the first year after hip fracture. Methods For studying the distribution of causes of death by time after hip fracture, we calculated age-adjusted cause-specific mortality at 1, 3, 6 and 12 months in patients hospitalized with hip fracture in Norway 1999–2016. Underlying causes of death were obtained from the Norwegian Cause of Death Registry and grouped by the European Shortlist for Causes of Death. For estimating excess mortality, we performed flexible parametric survival analyses comparing mortality hazard in patients with hip fracture (2002–2017) with that of age- and sex matched controls drawn from the Population and Housing Census 2001. Results Of 146,132 Norwegians with a first hip fracture, a total of 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (mainly the fall causing the fracture) were the underlying cause for 53.8% of deaths, followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioural disorders (2.0%) and diseases of the nervous system (1.3%). By one-year post-fracture, external causes and circulatory diseases together accounted for approximately half of deaths (26.1% and 27.0%, respectively). In the period 2002–2017, cause-specific one-year relative mortality hazard in hip fracture patients vs. population controls ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system in women, and correspondingly, from 2.4 to 5.3 in men. Conclusions Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the most frequently reported underlying cause of death among older patients who survive less than one year after their fracture.

Background For injury deaths, the underlying cause of death is defined as the circumstances leading to the injury. When this information is missing, the ICD-10 code X59 (Exposure to unspecified factor) is used. Lack of knowledge of factors causing injuries reduces the value of the cause of death statistics. The aim of this study was to identify predictors of X59-coded deaths in Norway, and to assess methods to identify the true underlying cause of injury deaths. Methods We used data from the Norwegian Cause of Death Registry from 2005 to 2014. We used logistic regression to identify determinants of X59-coded deaths. For redistribution of the X59 deaths, we used a multinomial logistic regression model based on the cases where injury circumstances were known. The data were divided into training and test sets. The model was developed on the training set and assessed on the test set before it was applied to the X59 deaths. The models used death certificate information on the nature of injury and demographic characteristics as predictor variables. Furthermore, we mailed a query to the certifying physicians of X59 deaths reported in the year 2015, where we asked for additional information on the circumstances leading to the fatal injury. Results There were 24,963 injury deaths reported to the Cause of Death Registry of Norway 2005–2014. Of these, 6440 (25.8%) lacked information on the circumstances leading to the death. The strongest predictor for a X59 death was the nature of injury (hip fracture), followed by lack of information on the scene of injury. Applying our redistribution algorithm, we estimated that 97% of the X59-coded deaths were accidental falls. The strongest covariate was the nature of injury, followed by place of death and age at death. In 2015, there were 591 X59-coded deaths. Queries were sent to the certifying doctors in 559 cases. Among the informative replies to the query, 88% of the deaths were reclassified to accidental falls. Conclusions A large proportion of injury deaths in Norway lack information on the circumstances leading to the fatal injury. Typically, these deaths represent accidental falls causing hip fracture in elderly individuals.

Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Bill & Melinda Gates Foundation.

IntroductionFalls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period.MethodsWe performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017.ResultsIn 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837–16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326–9032) in Greece to 19 796 per 100 000 (UI 15 536–24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990.ConclusionsFrom 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.

Background The epidemiology of trauma deaths in Europe is less than well investigated. Thus, our goal was to study the contemporary patterns of trauma deaths within a defined population with an exceptionally high trauma autopsy rate. Methods This was a retrospective evaluation of 260 consecutive trauma autopsies for which we collected demographic, pre‐hospital and in‐hospital data. Patients were analyzed for injury severity by standard scoring systems (Abbreviated Injury Scale [AIS], Revised Trauma Score [RTS], and Injury Severity Score [ISS]), and the Trauma and Injury Severity Scale [TRISS] methodology. Results The fatal trauma incidence was 10.0 per 100,000 inhabitants (17.4 per 100,000 age‐adjusted ≥ 55 years). Blunt mechanism (87%), male gender (75%), and pre‐hospital deaths (52%) predominated. Median ISS was 38 (range: 4–75). Younger patients (<55 years) who died in the hospital were more often hypotensive (SBP < 90 mmHg; p = 0.001), in respiratory distress (RR < 10/min, or > 29/min; p < 0.0001), and had deranged neurology on admission (Glasgow Coma Score [GCS] ≤ 8; p < 0.0001), compared to those ≥ 55 years. Causes of death were central nervous system (CNS) injuries (67%), exsanguination (25%), and multiorgan failure (8%). The temporal death distribution is model‐dependent and can be visualized in unimodal, bimodal, or trimodal patterns. Age increased (r = 0.43) and ISS decreased (r = –0.52) with longer time from injury to death (p < 0.001). Mean age of the trauma patients who died increased by almost a decade during the study period (from mean 41.7 ± 24.2 years to mean 50.5 ± 25.4 years; p = 0.04). The pre‐hospital:in‐hospital death ratio shifted from 1.5 to 0.75 (p < 0.007). Conclusions While pre‐hospital and early deaths still predominate, an increasing proportion succumb after arrival in hospital. Focus on injury prevention is imperative, particularly for brain injuries. Although hemorrhage and multiorgan failure deaths have decreased, they do still occur. Redirected attention and focus on the geriatric trauma population is mandated.

Background The increasing incidence of prosthesis revision surgery in the Western world has led to an increased focus on the capacity for stem removal. We previously reported on a femoral stem implanted in goats with an approximate 15% reduction in retention force by drilling longitudinally orientated grooves on the side of the stem. In this current study, we aimed to histologically evaluate the bony apposition towards this stem and correlate this apposition with the pullout force. Methods We analyzed the femora of 22 goats after stem removal. All stems remained in place for 6 months, and the goats were allowed regular loading of the hip during this time. For histological evaluation, all femora were immersed in EDTA and decalcified until sufficiently soft for standard technique preparation. We evaluated bone apposition, the presence of foreign particle debris and other factors. The apposition was evaluated with a scoring system based on semi-quantitative bone apposition in four quadrants. Kappa statistics were calculated for the score. We correlated the retention force with the amount of bone apposition. Results The stem drilling was the only significant factor influencing the retention force (p = 0.020). The bone apposition Kappa score comparing poor and good apposition scores was fair ( κ  = 0.4, 95% CI 0.00–0.88). Signs of foreign body reaction were noted in 5 of 22 goats. Conclusions Based on the current findings in an experimental goat model, it appears that the effect of drilling tissue/bone out of the longitudinal grooves has a more significant impact on the retention force required to remove the stem than the amount of bone apposition outside the stem grooves. This observation may be further explored in the research of stem designs that are potentially easier to remove.

Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain-7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.