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We investigate whether the diseases for which there was more biomedical innovation had larger 1999–2019 reductions in premature mortality. Biomedical innovation related to a disease is measured by the change in the mean vintage of descriptors of PubMed articles about the disease. We analyze data on 286 million descriptors of 27 million articles about over 800 diseases. Premature mortality from a disease is significantly inversely related to the lagged vintage of descriptors of articles about the disease. In the absence of biomedical innovation, age-adjusted mortality rates would not have declined. Some factors other than biomedical innovation (e.g., a decline in smoking and an increase in educational attainment) contributed to the decline in mortality. But other factors (e.g., a rise in obesity and the prevalence of chronic conditions) contributed to an increase in mortality. Biomedical innovation reduced the mortality of white people sooner than it reduced the mortality of black people.
Triceps skinfold thickness (TSF) is a surrogate marker of subcutaneous fat. Evidence is limited about the association of sex-specific TSF with the risk of all-cause mortality among maintenance hemodialysis (MHD) patients. We aimed to investigate the longitudinal relationship of TSF with all-cause mortality among MHD patients. A multicenter prospective cohort study was performed in 1034 patients undergoing MHD. The primary outcome was all-cause mortality. Multivariable Cox proportional hazards models were used to evaluate the association of TSF with the risk of mortality. The mean (standard deviation) age of the study population was 54.1 (15.1) years. 599 (57.9%) of the participants were male. The median (interquartile range) of TSF was 9.7 (6.3–13.3 mm) in males and 12.7 (10.0–18.0 mm) in females. Over a median follow up of 4.4 years (interquartile range, 2.4-7.9 years), there were 548 (53.0%) deaths. When TSF was assessed as sex-specific quartiles, compared with those in quartile 1, the adjusted HRs (95%CIs) of all-cause mortality in quartile 2, quartile 3 and quartile 4 were 0.93 (0.73, 1.19), 0.75 (0.58, 0.97) and 0.69 (0.52, 0.92), respectively (P for trend =0.005). Moreover, when analyzed by sex, increased TSF (≥9.7 mm for males and ≥18mm for females) was significantly associated with a reduced risk of all-cause mortality (quartile 3-4 vs. quartile 1-2; HR, 0.70; 95%CI: 0.55, 0.90 in males; quartile 4 vs. Quartile 1-3; HR, 0.69; 95%CI: 0.48, 1.00 in females). In conclusion, high TSF was significantly associated with lower risk of all-cause mortality in MHD patients.
Infant mortality, a reflection of socioeconomic and health conditions of a population, is shaped by diverse factors. This study delves into a pre-industrial population, scrutinizing neonatal and post-neonatal deaths separately. Family factors such as mortality crises, religion, and legitimacy are also explored. Data of 9,086 people obtained through multigenerational information from ecclesiastic records from 1603 to 1908 were analysed by means of a joinpoint regression analysis. Death risk was assessed with univariate and multivariate Cox Proportional Hazard models. Early neonatal mortality was 5.6% of births and showed a gradual and steady increase from 1630 to 1908, with no substantial improvement over the three centuries analysed. Late neonatal (4.3% of births) and post-neonatal mortality (18.7% of births) shared a different pattern, showing a decline between the mid-18th and mid-19th centuries, and an increase by the 20th century that could be caused by socioeconomic factors and the impact of several epidemics. In the historical population of Hallstatt, infant survival was influenced by the sex of the newborn, the death of the mother and the precedent sibling, and by the birth interval. Environmental and cultural factors, such as mortality crises and religion, influenced late neonatal and post-neonatal mortality, but not early neonatal mortality. The results highlight the need to independently assess early neonatal mortality in studies of infant mortality in historical populations, and to use as complete time periods as possible to capture differences in mortality patterns.
To evaluate the outcomes of patients with single ventricle physiology supported with extracorporeal membrane oxygenation as a bridge to first-stage palliation.
Methods:
This was a retrospective registry-based study. Data from the Extracorporeal Life Support Organization registry were used to identify single ventricle physiology patients supported with extracorporeal membrane oxygenation prior to palliation from 2016 to 2021. Descriptive statistics and multivariate analyses for associations with mortality were conducted.
Results:
Primary outcome was death before hospital discharge. Patient characteristics including demographics and associated complications were evaluated as secondary outcomes. Sixty-five patients met inclusion criteria. Survival to discharge was 42%. Twenty-four (37%) patients died while on extracorporeal membrane oxygenation. There was no significant difference in demographics between survivors and non-survivors. Non-survivors had a significantly longer median duration on extracorporeal membrane oxygenation compared to survivors, 99-hrs [IQR (Interquartile Range), 160, 300] vs. 59-hrs [43, 124] (p<0.001). Multivariate analysis demonstrated extracorporeal membrane oxygenation duration (adjusted-OR [Odds Ratio] 1.01, 95% CI [Confidence Interval] 0.98, 0.99; p = 0.03) and requiring renal replacement therapy (42% vs. 19%; p = 0.04) were associated with mortality prior to discharge.
Conclusions:
Clinicians managing decompensated patients with single ventricle physiology may consider extracorporeal membrane oxygenation as a bridge to palliation. Survival to discharge was 42%. Evidence of renal injury and longer extracorporeal membrane oxygenation durations were associated with mortality. These data may be used to guide providers and to counsel families. However, more data are needed to refine indications and assess associations related to outcomes and decision-making.
To examine the potential indirect effect of meal frequency on mortality via obesity indices.
Design:
Prospective cohort study
Setting:
Korean Genome and Epidemiology Study.
Participants:
This cohort study involved 148 438 South Korean adults aged 40 years and older.
Results:
Meal frequency at the baseline survey was assessed using a validated FFQ. Outcomes included all-cause mortality, cancer mortality and CVD mortality. Cox proportional hazards regression models were employed to examine the relationship between meal frequency and the risk of mortality. Mediation analyses were performed with changes in obesity indices (BMI and weight circumference (WC)) as mediators. In comparison to the three-time group, the once-per-day and four-times-per-day groups had a higher risk for all-cause mortality. The irregular frequency group had a higher risk for CVD mortality. Both once-per-day and four-times-per-day groups exhibited higher risks for cancer mortality. The effect of meal frequency on all-cause mortality was partially mediated by WC. For specific-cause mortality, similar mediation effects were found.
Conclusions:
The data suggests that three meals per day have a lower mortality and longer life expectancy compared with other meal frequencies. Increased waist circumference partially mediates this effect. These findings support the implementation of a strategy that addresses meal frequency and weight reduction together.
This study examines mortality of the Amur tiger Panthera tigris altaica caused by traffic collision incidents in the Russian Far East from 1980 to 2023. Forty-six per cent of mortality incidents occurred within the last 4 years of this period (2020–2023) following an outbreak of African swine fever, which led to a reduction of prey available for tigers. Using multiple regression analysis, we identify significant predictors of tiger mortality, including road type, biotope, and distances to settlements and federally protected areas. We identified five locations with concentrations of tiger mortality, with four of these near protected areas comprising 54% of all incidents. Asphalt roads have an elevated risk of tiger deaths during the winter, whereas unpaved roads have elevated risk during warmer months. Wildlife-friendly road planning, including crossings and enhanced night-time controls, is crucial for reducing mortality and ensuring the survival of this species amidst increasing development of human infrastructure. This study highlights the urgent need for targeted conservation efforts to reduce traffic-related risks to the Amur tiger.
Due to the high postoperative mortality, tools for an adaequate risk stratification are important to identify high-risk patients undergoing the Norwood procedure. As a marker of ventricular wall stress, NT-proBNP might be of particular interest in these children.
Objectives:
This study evaluated whether NT-proBNP’s age-adjusted z-score (“zlog-NT-proBNP”) predicts outcomes after stage I Norwood procedure.
Methods:
Patients who underwent the Norwood procedure between 1 January 2011 and 31 December 2022, with perioperative NT-proBNP measurements available were enrolled. Since reference intervals of NT-proBNP are highly age-dependent, age-adjusted zlog-NT-proBNP was used. Serial zlog-NT-proBNP values were analysed to predict the occurrence of major adverse cardiovascular events after the Norwood procedure. Major adverse cardiovascular events was defined as death, resuscitation, or mechanical circulatory support. Secondary endpoints were re-operation and re-intervention for shunt.
Results:
A total of 139 patients underwent the Norwood procedure and had at least one NT-proBNP measurement available. Preoperative zlog-NT-proBNP measurements (median 3.7, interquartile range 3.1–4.19) showed no association with the occurrence of major adverse cardiovascular events or mortality. Zlog-NT-proBNP early after ICU admission (3.2, interquartile range 2.4–3.8) was predictive of mortality but showed no association with the occurrence of major adverse cardiovascular events. Zlog-NT-proBNP before ICU discharge (3.2, interquartile range 2.8–3.8) was significantly associated with the occurrence of both major adverse cardiovascular events (hazard ratio 1.83, 95% confidence interval 1.25–2.67, P = 0.002) and death (hazard ratio 2.1, 95% CI 1.4–3.2, P < 0.001).
Conclusions:
High zlog-NT-proBNP levels after the Norwood surgery were strongly associated with the occurrence of major adverse cardiovascular events and death. Therefore, zlog-NT-proBNP has the potential to identify high-risk patients before life-threatening complications occur.
Edited by
James Ip, Great Ormond Street Hospital for Children, London,Grant Stuart, Great Ormond Street Hospital for Children, London,Isabeau Walker, Great Ormond Street Hospital for Children, London,Ian James, Great Ormond Street Hospital for Children, London
Congenital heart disease (CHD) is the commonest birth defect, and children may present at all ages with variably corrected lesions for both elective and emergency surgery. No single anaesthetic approach can be recommended in this heterogeneous group of children, so a general strategy is presented based on applied physiology and the available evidence. Pathophysiological patterns are presented along with the common physiological consequences of cardiac disease in children: cardiac failure, cyanosis, pulmonary hypertension and arrhythmias. Children with congenital heart disease presenting for non-cardiac surgery are at increased perioperative risk compared to their unaffected peers. Risk factors are identified, and a scoring system to predict in-hospital mortality is presented. Preoperative assessment encompasses consideration of the optimal location for surgery as well as specific considerations, including echocardiography, infectious endocarditis prophylaxis and pacemaker/ defibrillators. In general, a balanced anaesthetic technique including controlled ventilation and opioids to reduce volatile exposure is preferred. However, with appropriate understanding of the underlying physiology, most anaesthetic techniques can be used safely and successfully in children with CHD.
The sutureless repair technique has been favoured due to its purported reduction in post-operative pulmonary venous obstruction rates. This study aims to compare the outcomes of conventional versus sutureless repair techniques in Total Anomalous Pulmonary Venous Drainage.
Methods:
In this retrospective single-centre analysis (2012–2022), we evaluated children who underwent conventional or sutureless repair for isolated total anomalous pulmonary venous drainage, excluding complex cardiac anomalies and incomplete data. Patients were categorised into conventional (Group C, n = 58) and sutureless (Group S, n = 41) groups. Primary outcomes included mortality, morbidity, and post-operative complications. Statistical analysis included Mann–Whitney U, chi-square, and Fisher’s exact tests where appropriate.
Results:
Supracardiac type predominated in both groups (53.4% in Group C and 70.7% in Group S), with higher cardiac type frequency in Group C (24.1% versus 2.4%, p = 0.016). Early complications occurred in 58.5% versus 53.4% of cases in Groups S and C, respectively (p = 0.767). The mortality rate (17.2% versus 14.6%, p = 0.944) and post-operative pulmonary venous obstruction (21.2% versus 19.0%, p = 0.809) were higher in Group C, though not significantly. Mean cardiopulmonary bypass times were comparable between groups (105 versus 89 minutes, p = 0.424).
Conclusions:
In this comprehensive analysis of paediatric Total Anomalous Pulmonary Venous Drainage repair, both conventional and sutureless techniques demonstrated comparable safety profiles and clinical outcomes. These findings suggest that surgical approach selection should be individualised based on patient characteristics and surgeon expertise. Further prospective studies with larger cohorts are needed to validate these observations.
The initial and updated Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STAT and STAT 2020) and Risk Adjusted Classification for Congenital Heart Surgery-1 and Risk Adjusted Classification for Congenital Heart Surgery-2 scoring systems are validated to predict early postoperative mortality following congenital heart surgery in children; however, their ability to predict long-term mortality has not been examined. We performed a retrospective cohort study using data from the Pediatric Cardiac Care Consortium, a US-based registry of cardiac interventions in 47 participating centres between 1982 and 2011. Patients included in this cohort analysis had select congenital heart surgery representing the spectrum of severity as determined by STAT and Risk Adjusted Classification for Congenital Heart Surgery-1 and were less than 21 years of age. We applied STAT, STAT 2020, Risk Adjusted Classification for Congenital Heart Surgery-1, and Risk Adjusted Classification for Congenital Heart Surgery-2 for prediction of early mortality and long-term postoperative survival probability by surgical risk category. Long-term outcomes were obtained by matching Pediatric Cardiac Care Consortium patients with deaths reported in the National Death Index through 2021. Of 20,753 eligible patients, 18,755 survived the postoperative period and 2,058 deaths occurred over a median follow up of 24.4 years (Interquartile Range: 21–28.4). Each scoring system performed well for predicting early postoperative mortality with the following c-statistics: STAT: 0.7872, Risk Adjusted Classification for Congenital Heart Surgery-1: 0.7872, STAT 2020: 0.7724 and Risk Adjusted Classification for Congenital Heart Surgery-2: 0.7668. The predictive ability for long-term risk of death was as follows: STAT: 0.6995, Risk Adjusted Classification for Congenital Heart Surgery-1 c = 0.6741, Risk Adjusted Classification for Congenital Heart Surgery-2: 0.7156 and STAT 2020: c = 0.7156. Risk-adjusted score systems for congenital heart surgery maintain adequate but diminishing discriminative power to predict long-term mortality. Future efforts are warranted to develop a tool with improved long-term survival prediction.
To investigate the relationship between maternal age and nutritional status, and test associations between maternal nutritional status and child mortality with a focus on maternal obesity.
Design:
Secondary analysis of data from nationally representative cross-sectional sample of women of reproductive ages (15–49 years) and their children under 5 years. The outcome variable for maternal nutritional status was BMI, classified into underweight (BMI < 18·50 kg/m2), normal weight (18·50–24·99 kg/m2), overweight (25·0–29·9 kg/m2) and obesity (>=30·0 kg/m2). Child mortality was captured with five binary variables measuring the risk of dying in specific age intervals (neonatal, post-neonatal, infant, childhood and under-five mortality).
Setting:
The most recent Demographic and Health Surveys from Democratic Republic of Congo (DRC).
Participants:
The final samples consisted of 7892 women of reproductive ages (15–49 years) and 19 003 children aged 0–59 months.
Results:
The prevalence of obesity was estimated at 3·4 %; it increased with maternal age. Furthermore, obesity unevenly affected provinces in the Democratic Republic of the Congo: Kinshasa, South Kivu, North Kivu and Maniema were most affected. Finally, maternal obesity showed mixed effects on child mortality.
Conclusion:
The prevalence of obesity is still low; however, provinces are unevenly affected. Therefore, interventions and programmes to improve nutrition should incorporate geographical disparities to tackle adverse child outcomes associated with maternal obesity, to limit negative consequences of maternal obesity, including non-communicable diseases which might be a strong impediment to reach Sustainable Development Goals (SDG) 2 and 3.
The normative principle that every individual is equally entitled to continued life is a subject of debate in ethics, health economics and policy. We reconsider this principle in the context of setting priorities for healthcare interventions. When applied without restriction, the principle overlooks quality of life concerns entirely. However, we contend that it remains ethically relevant in certain situations, particularly when patients suffer from conditions unrelated to the therapeutic areas and treatments under consideration. Thus, we defend the principle while also emphasizing the need for its application within tight limits.
Studies show that people with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC). These studies mostly predate the introduction of national bowel cancer screening programmes (NBCSPs) and it is unknown if these have reduced disparity in CRC-related mortality for people with SMI.
Methods
We compared mortality rates following CRC diagnosis at colonoscopy between a nationally representative sample of people with and without SMI who participated in Australia’s NBCSP. Participation was defined as the return of a valid immunochemical faecal occult blood test (iFOBT). We also compared mortality rates between people with SMI who did and did not participate in the NBCSP. SMI was defined as receiving two or more Pharmaceutical Benefits Scheme prescriptions for second-generation antipsychotics or lithium.
Results
Amongst NBCSP participants, the incidence of CRC in the SMI cohort was lower than in the controls (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.61–0.98). In spite of this, their all-cause mortality rate was 1.84 times higher (95% CI 1.12–3.03), although there was only weak evidence of a difference in CRC-specific mortality (HR 1.82; 95% CI 0.93–3.57). People with SMI who participated in the NBCSP had better all-cause survival than those who were invited to participate but did not return a valid iFOBT (HR 0.67, 95% CI 0.50–0.88). The benefit of participation was strongest for males with SMI and included improved all-cause and CRC-specific survival.
Conclusions
Participation in the NBCSP may be associated with improved survival following a CRC diagnosis for people with SMI, especially males, although they still experienced greater mortality than the general population. Approaches to improving CRC outcomes in people with SMI should include targeted screening, and increased awareness about the benefits or participation.
Trial registration
Australian and New Zealand Clinical Trials Registry (Trial ID: ACTRN12620000781943).
In this penultimate chapter, we take up the philosophical question of whether immortality is truly desirable, seeking to establish an important difference between existing for a finite and for an infinite stretch of time by introducing the following important consideration. If it remains possible for an event to occur, then even an extremely unlikely event is certain to occur, given infinite time. I shall suggest that this consideration leads to insuperable problems with the most popular scenarios currently being envisioned for achieving immortality by techno-scientific means. These problems, moreover, motivate us to think more deeply about death and thereby rethink the requirements of a genuinely meaningful human life. Drawing on Kierkegaard, Heidegger, and other existential thinkers, I suggest that human beings’ most abiding sources of meaningfulness come not from endlessly repeating certain profound experiences (which sometimes does wear out their appeal) but, instead, from our struggle to stay true to and so continue to creatively and responsibly disclose what such momentous events, often rare and singular, only partly reveal to us in the first place, as we often come to realize only in retrospect – much as Heidegger came only retrospectively to recognize and then spend his life creatively disclosing the seemingly inexhaustible ontological riches of that ambiguous “nothing” Being and Time first glimpsed in the momentous experience of existential death, but in a way that Heidegger only partly understood at that time.
Proposition 67 of Spinoza’s hyper-rationalistic Ethics proudly proclaims that: “A free man thinks of nothing less than of death.” Well, in this book I have thought a great deal about existential death, and a good bit about the “noth-ing of the nothing” that such death discloses. Still, I have probably thought of noth-ing less than of death, so Spinoza might have to count me “free” on a technicality. There are, at any rate, worse things than being freed on a technicality. One can be convicted on a technicality, for example, or even convicted by technicality. Indeed, the later Heidegger suggests that we have all been convicted by technicality, technicity, or technologicity, that is, by “the essence of technology.” According to his view of our late modern age of technological enframing, we have all been thrown by Western history into the prison city-state (or polis) of nihilistic technologicity.
Evidence is largely limited regarding the extent to which abnormal behavioural profiles, including physical inactivity, sedentary behaviour and inadequate sleep duration, impact long-term health conditions in individuals with pre-existing depression.
Aims
To investigate the associations between accelerometer-derived daily movement behaviours and mortality in individuals with pre-existing depression.
Method
Between 2013 and 2015, a total of 10 914 individuals with pre-existing depression were identified from the UK Biobank through multiple sources including self-reported symptoms, records of antidepressant usage and diagnostic recording based on the 10th Revision of the International Classification of Diseases (ICD-10) codes F32–F33. These participants were subsequently followed up until 2021. Wrist-worn accelerometers were used for objective measurement of sleep duration, sedentary behaviour, moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA) over a span of seven consecutive days.
Results
During a median follow-up of 6.9 years, 434 deaths occurred among individuals with pre-existing depression. We observed a U-shaped association between sleep duration and mortality in individuals with pre-existing depression, with the lowest risk occurring at approximately 9 h/day. Both MVPA and LPA exhibited an L-shaped pattern in relation to mortality, indicating that engaging in higher levels of physical activity was associated with lower risk of mortality in individuals with pre-existing depression, but the beneficial effect reached a plateau after 50 min/day for MVPA and 350 min/day for LPA. We found a positive association between sedentary time and mortality, and the risk apparently increased above 8 h/day. Moreover, substituting 1 hour/day of sedentary time with LPA or MVPA was significantly associated with a 12% (hazard ratio: 0.88, 95% CI: 0.83–0.94) and 24% (hazard ratio: 0.76, 95% CI: 0.61–0.94) lower risk of mortality, respectively.
Conclusions
Our study found the beneficial effect of adequate sleep duration, high levels of physical activity and short sedentary time on risk of mortality among individuals with pre-existing depression.
Nozick’s ‘utility monster’ is often regarded as impossible, because one life cannot be better than a large number of other lives. Against that view, I propose a purely marginalist account of utility monster defining the monster by a higher sensitivity of well-being to resources (instead of a larger total well-being), and I introduce the concept of collective utility monster to account for resource predation by a group. Since longevity strengthens the sensitivity of well-being to resources, large groups of long-lived persons may, if their longevity advantage is sufficiently strong, fall under the concept of collective utility monster, against moral intuition.
Humans age. Domestic animals age. But is that true for all species? Is ageing a necessary consequence of evolution? Yes - for a long time, this was the undisputed answer of classic evolutionary theories of ageing. This chapter tells the story about how this paradigm of inevitable ageing has been challenged and refuted. Thanks to decades of monitoring individual survival and death across species in captivity and in the wild, researchers have been able to study patterns of the ageing process’s ultimate consequence - age trajectories of mortality. Though ageing is a complex, multiscale process, increasing mortality with age is, overall, indicative of a loss of functioning with age - senescence. Constant or declining mortality with adult age is indicative of maintained or improved functioning - negligible or negative senescence. Evidence supports that ageing patterns across the tree of life are diverse. Whether current evidence for negligible or negative senescence truly reflects an absence of senescence or just an absence of evidence is an open challenge. Similarly, why certain types of species show certain types of senescence patterns is an open research question. Future evolutionary theories of ageing will have to include trade-offs justified by structural arguments - genetic structure, physiological structure, social structure, ecological structure - to explain types of ageing patterns across types of species.
Nosemosis, caused by microsporidian parasites of the genus Nosema, is considered a significant health concern for insect pollinators, including the economically important honeybee (Apis mellifera). Despite its acknowledged importance, the impact of this disease on honeybee survivorship remains unclear. Here, a standard laboratory cage trial was used to compare mortality rates between healthy and Nosema-infected honeybees. Additionally, a systematic review and meta-analysis of existing literature were conducted to explore how nosemosis contributes to increased mortality in honeybees tested under standard conditions. The review and meta-analysis included 50 studies that reported relevant experiments involving healthy and Nosema-infected individuals. Studies lacking survivorship curves or information on potential moderators, such as spore inoculation dose, age of inoculated bees, or factors that may impact energy expenditure, were excluded. Both the experimental results and meta-analysis revealed a consistent, robust effect of infection, indicating a threefold increase in mortality among the infected group of honeybee workers (hazard ratio for infected individuals = 3.16 [1.97–5.07] and 2.99 [2.36–3.79] in the experiment and meta-analysis, respectively). However, the meta-analysis also indicated high heterogeneity in the effect magnitude, which was not explained by our moderators. Furthermore, there was a serious risk of bias within studies and potential publication bias across studies. The findings underscore knowledge gaps in the literature. It is stressed that laboratory cage trials should be viewed as an initial step in evaluating the impact of Nosema on mortality and that complementary field and apiary studies are essential for identifying effective treatments to preserve honeybee populations.