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Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Bill & Melinda Gates Foundation.

Introduction We report on the experience and coping mechanism of the fathers post adverse birth outcome from a population-based representative sample in the Indian state of Bihar. Methods A state-representative sample of fathers of stillborn babies and babies who died within neonatal period (newborn deaths) born between July 2020 and June 2021 were interviewed. They reported on socio-demography, supportive experience and coping mechanism post birth/death of their baby, and their opinion on if their baby could have been saved. The prevalence of supportive experience, and type and prevalence of coping mechanisms by select socio-demographic characteristics is reported for them, and the prevalence of seeing, holding, and naming of the baby for the fathers of stillborn. Results A total of 241 (71.5% participation) and 347 (71.2% participation) fathers of stillborn and of newborn deaths participated, respectively. Being able to talk to someone about their baby was reported by 174 (72.5%; 95% CI: 66.5–77.8) and 264 (77.0%; 95% CI: 72.2–81.1); and having received support to cope with loss by 194 (80.8%; 95% CI: 75.3–85.3) and 264 (77.0%; 95% CI: 72.2–81.1) fathers with stillborn and newborn death, respectively. Majority reported crying as a coping mechanism (70.8%; 95% CI: 64.7–76.3 for stillborn and 75.5%; 95% CI: 70.6–79.8 for newborn deaths), and aggression was the most common negative coping mechanism (29.6%; 95% CI: 24.1–35.7 for stillborn and 28.3%; 95% CI: 23.7–33.3 for newborn death). Majority were of the opinion their baby could have been saved had they gone to a higher-level health facility for delivery or medical attention (63.0% for stillborn and 67.7% for newborn death). Naming, seeing and holding of the stillborn was reported by 5.8%, 83.4% and 55% fathers who were present at the time of delivery, respectively. Conclusion This study highlights the need for perinatal bereavement strategies to be inclusive of the fathers along with the mothers and offer insights on formulation of those strategic programs. Trial registration Not applicable.

Background The standard face-to-face training for the integrated management of childhood illness (IMCI) continues to be plagued by concerns of low coverage of trainees, the prolonged absence of trainees from the health facility to attend training and the high cost of training. Consequently, the distance learning IMCI training model is increasingly being promoted to address some of these challenges in resource-limited settings. This paper examines participants’ accounts of the paper-based IMCI distance learning training programme in three district councils in Mbeya region, Tanzania. Methods A cross-sectional qualitative descriptive design was employed as part of an endline evaluation study of the management of possible serious bacterial infection in Busokelo, Kyela and Mbarali district councils of Mbeya Region in Tanzania. Key informant interviews were conducted with purposefully selected policymakers, partners, programme managers and healthcare workers, including beneficiaries and training facilitators. Results About 60 key informant interviews were conducted, of which 53% of participants were healthcare workers, including nurses, clinicians and pharmacists, and 22% were healthcare administrators, including district medical officers, reproductive and child health coordinators and programme officers. The findings indicate that the distance learning IMCI training model (DIMCI) was designed to address concerns about the standard IMCI model by enhancing efficiency, increasing outputs and reducing training costs. DIMCI included a mix of brief face-to-face orientation sessions, several weeks of self-directed learning, group discussions and brief face-to-face review sessions with facilitators. The DIMCI course covered topics related to management of sick newborns, referral decisions and reporting with nurses and clinicians as the main beneficiaries of the training. The problems with DIMCI included technological challenges related to limited access to proper learning technology (e.g., computers) and unfriendly learning materials. Personal challenges included work-study-family demands, and design and coordination challenges, including low financial incentives, which contributed to participants defaulting, and limited mentorship and follow-up due to limited funding and transport. Conclusion DIMCI was implemented successfully in rural Tanzania. It facilitated the training of many healthcare workers at low cost and resulted in improved knowledge, competence and confidence among healthcare workers in managing sick newborns. However, technological, personal, and design and coordination challenges continue to face learners in rural areas; these will need to be addressed to maximize the success of DIMCI.

OBJECTIVES: The Polish criteria for “intrauterine death” include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015–2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

This volume is a single up-to-date source on the entire global epidemiology of diseases, injuries and risk factors with a comprehensive statement of methods and a complete presentation of results. It includes refined methods to assess data, ensure epidemiological consistency, and summarize the disease burden. Global Burden of Disease and Risk Factors examines the comparative importance of diseases, injuries, and risk factors; it incorporates a range of new data sources to develop consistent estimates of incidence, prevalence, severity and duration, and mortality for 136 major diseases and injuries. Drawing from more than 8,500 data sources that include epidemiological studies, disease registers, and notifications systems, Global Burden of Disease and Risk Factors incorporates information from more than 10,000 datasets relating to population health and mortality, representing one of the largest syntheses of global information on population health to date.

Background Bereaved parents experience higher rates of depressive and post-traumatic stress symptoms after the stillbirth of a baby than after live-birth. Yet, these effects remain underreported in the literature and, consequently, insufficiently addressed in health provider education and practice. We conducted a participatory based study to explore the experiences of grieving parents during their interaction with health care providers during and after the stillbirth of a baby. Methods This community-based participatory study utilized four focus groups comprised of twenty-seven bereaved parents (44% fathers). Bereaved parents conceptualized the study, participating at all stages of research, analyses, and drafting. Data were reduced into a main theme and subthemes, then broad-based member checked to ensure fidelity and nuances within themes. Results The major theme that emerged centered on provider acknowledgement of the baby as an irreplaceable individual. Subthemes reflected 1) acknowledgement of parenthood and grief, 2) recognition of the traumatic nature of stillbirth, and 3) acknowledgement of enduring grief coupled with access to support. It was important that providers realized how grief was experienced within health care and social support systems, concretized by their desire for long-term, specialized support. Conclusions Both mothers and fathers feel that acknowledgement of their baby as an individual, their parenthood, and their enduring traumatic grief by healthcare providers are key elements required in the process of initiating immediate and ongoing care after the stillbirth of a baby.

Background Three million babies are stillborn each year and 3.6 million die in the first month of life. In India, early neonatal deaths make up four-fifths of neonatal deaths and infant mortality three-quarters of under-five mortality. Information is scarce on cause-specific perinatal and neonatal mortality in urban settings in low-income countries. We conducted verbal autopsies for stillbirths and neonatal deaths in Mumbai slum settlements. Our objectives were to classify deaths according to international cause-specific criteria and to identify major causes of delay in seeking and receiving health care for maternal and newborn health problems. Methods Over two years, 2005–2007, births and newborn deaths in 48 slum areas were identified prospectively by local informants. Verbal autopsies were collected by trained field researchers, cause of death was classified by clinicians, and family narratives were analysed to investigate delays on the pathway to mortality. Results Of 105 stillbirths, 65 were fresh (62%) and obstetric complications dominated the cause classification. Of 116 neonatal deaths, 87 were early and the major causes were intrapartum-related (28%), prematurity (23%), and severe infection (22%). Bereavement was associated with socioeconomic quintile, previous stillbirth, and number of antenatal care visits. We identified 201 individual delays in 121/187 birth narratives (65%). Overall, delays in receiving care after arrival at a health facility dominated and were mostly the result of referral from one institution to another. Most delays in seeking care were attributed to a failure to recognise symptoms of complications or their severity. Conclusions In Mumbai’s slum settlements, early neonatal deaths made up 75% of neonatal deaths and intrapartum-related complications were the greatest cause of mortality. Delays were identified in two-thirds of narratives, were predominantly related to the provision of care, and were often attributable to referrals between health providers. There is a need for clear protocols for care and transfer at each level of the health system, and an emphasis on rapid identification of problems and communication between health facilities. Trial registration ISRCTN96256793

In multicellular organisms, the surface barrier is essential for maintaining the internal environment. In mammals, the barrier is the stratum corneum. Fatty acid transport protein 4 (FATP4) is a key factor involved in forming the stratum corneum barrier. Mice lacking Fatp4 display early neonatal lethality with features such as tight, thick, and shiny skin, and a defective skin barrier. These symptoms are strikingly similar to those of a human skin disease called restrictive dermopathy. FATP4 is a member of the FATP family that possesses acyl-CoA synthetase activity for very long chain fatty acids. How Fatp4 contributes to skin barrier function, however, remains to be elucidated. In the present study, we characterized two Caenorhabditis elegans genes, acs-20 and acs-22, that are homologous to mammalian FATPs. Animals with mutant acs-20 exhibited defects in the cuticle barrier, which normally prevents the penetration of small molecules. acs-20 mutant animals also exhibited abnormalities in the cuticle structure, but not in epidermal cell fate or cell integrity. The acs-22 mutants rarely showed a barrier defect, whereas acs-20;acs-22 double mutants had severely disrupted barrier function. Moreover, the barrier defects of acs-20 and acs-20;acs-22 mutants were rescued by acs-20, acs-22, or human Fatp4 transgenes. We further demonstrated that the incorporation of exogenous very long chain fatty acids into sphingomyelin was reduced in acs-20 and acs-22 mutants. These findings indicate that C. elegans Fatp4 homologue(s) have a crucial role in the surface barrier function and this model might be useful for studying the fundamental molecular mechanisms underlying human skin barrier and relevant diseases.

Background：Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit （NICU） of China.Methods：All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results：A total of 744 newborns died during the l-year survey,accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3% of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases （56.5%） occupied the largest proportion ofpreterm deaths while infection （27%） and neurologic diseases （22%） were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents＇ concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions：Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

When a newborn requires immediate hospitalization due to a potentially life-threatening situation, parents face a sudden and significant increase in stress. This situation and the potential loss of their child will bring great grief and loss to the parents, which may lead to conditions that foster dysfunctional family dynamics. This article describes the author's experience providing hospice care to a dying infant with a group B streptococcus infection in the neonatal intensive care unit. The author served as the primary care nurse from April 5th to July 6th, 2019. Data were collected during direct care provision, observations, and interactions with parents, while overall systemic assessments were used in analysis to establish that the health problems of the case were: (1) existing infection: related to group B streptococcus; (2) ineffective tissue perfusion: insufficient perfusion of multiple organs, including brain, heart, lung, and kidney, due to sepsis infection; and (3) caregiver grief: facing the death