Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the Global Burden of Disease Study 2021.

BACKGROUND: Sex and gender shape health. There is a growing body of evidence focused on comprehensively and systematically examining the magnitude, persistence, and nature of differences in health between females and males. Here, we aimed to quantify differences in the leading causes of disease burden between females and males across ages and geographies. METHODS: We used the Global Burden of Disease Study 2021 to compare disability-adjusted life-year (DALY) rates for females and males for the 20 leading causes of disease burden for individuals older than 10 years at the global level and across seven world regions, between 1990 and 2021. We present absolute and relative differences in the cause-specific DALY rates between females and males. FINDINGS: Globally, females had a higher burden of morbidity-driven conditions with the largest differences in DALYs for low back pain (with 478·5 [95% uncertainty interval 346·3-632·8] more DALYs per 100 000 individuals among females than males), depressive disorders (348·3 [241·3-471·0]), and headache disorders (332·9 [48·3-731·9]), whereas males had higher DALY rates for mortality-driven conditions with the largest differences in DALYs for COVID-19 (with 1767·8 [1581·1-1943·5] more DALYs per 100 000 among males than females), road injuries (1012·2 [934·1-1092·9]), and ischaemic heart disease (1611·8 [1405·0-1856·3]). The differences between sexes became larger over age and remained consistent over time for all conditions except HIV/AIDS. The largest difference in HIV/AIDS was observed among those aged 25-49 years in sub-Saharan Africa with 1724·8 (918·8-2613·7) more DALYs per 100 000 among females than males. INTERPRETATION: The notable health differences between females and males point to an urgent need for policies to be based on sex-specific and age-specific data. It is also important to continue promoting gender-sensitive research, and ultimately, implement interventions that not only reduce the burden of disease but also achieve greater health equity. FUNDING: Bill & Melinda Gates Foundation.

Causal diagramming for assessing human system risk in spaceflight.

For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining-based on evaluation of the available evidence-when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk "silos" to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB's pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches.

Levels of evidence for human system risk evaluation.

NASA uses a continuous risk management process to seek out new knowledge of spaceflight-induced risk to human health and performance. The evidence base that informs the risk assessments in this domain is constantly changing as more information is gleaned from a continuous human presence in space and from ongoing research. However, the limitations of this evidence are difficult to characterize because fewer than 700 humans have ever flown in space, and information comes from a variety of sources that span disciplines, including engineering, medicine, food and nutrition, and many other life sciences. The Human System Risk Board (HSRB) at NASA is responsible for assessing risk to astronauts and communicating this risk to agency decision-makers. A critical part of that communication is conveying the uncertainty regarding the understanding of the changes that spaceflight induces in human processes and the complex interactions between humans and the spacecraft. Although the strength of evidence grades is common in the academic literature, these scores are often not useful for the problems of human spaceflight. The HSRB continues to update the processes used to report the levels of evidence. This paper describes recent updates to the methods used to assign the level of evidence scores to the official risk postures and to the causal diagrams used by the HSRB.

Health effects associated with chewing tobacco: a Burden of Proof study.

Chewing tobacco use poses serious health risks; yet it has not received as much attention as other tobacco-related products. This study synthesizes existing evidence regarding the health impacts of chewing tobacco while accounting for various sources of uncertainty. We conducted a systematic review and meta-analysis of chewing tobacco and seven health outcomes, drawing on 103 studies published from 1970 to 2023. We use a Burden of Proof meta-analysis to generate conservative risk estimates and find weak-to-moderate evidence that tobacco chewers have an increased risk of stroke, lip and oral cavity cancer, esophageal cancer, nasopharynx cancer, other pharynx cancer, and laryngeal cancer. We additionally find insufficient evidence of an association between chewing tobacco and ischemic heart disease. Our findings highlight a need for policy makers, researchers, and communities at risk to devote greater attention to chewing tobacco by both advancing tobacco control efforts and investing in strengthening the existing evidence base.

Health effects associated with exposure to secondhand smoke: a Burden of Proof study.

Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure-response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.

Health effects associated with exposure to intimate partner violence against women and childhood sexual abuse: a burden of proof study.

The health impacts of intimate partner violence against women and childhood sexual abuse are not fully understood. Here we conducted a systematic review by comprehensively searching seven electronic databases for literature on intimate partner violence-associated and childhood sexual abuse-associated health effects. Following the burden of proof methodology, we evaluated the evidence strength linking intimate partner violence and/or childhood sexual abuse to health outcomes supported by at least three studies. Results indicated a moderate association of intimate partner violence with major depressive disorder and with maternal abortion and miscarriage (63% and 35% increased risk, respectively). HIV/AIDS, anxiety disorders and self-harm exhibited weak associations with intimate partner violence. Fifteen outcomes were evaluated for their relationship to childhood sexual abuse, which was shown to be moderately associated with alcohol use disorders and with self-harm (45% and 35% increased risk, respectively). Associations between childhood sexual abuse and 11 additional health outcomes, such as asthma and type 2 diabetes mellitus, were found to be weak. Although our understanding remains limited by data scarcity, these health impacts are larger in magnitude and more extensive than previously reported. Renewed efforts on violence prevention and evidence-based approaches that promote healing and ensure access to care are necessary.

Updates to the NASA human system risk management process for space exploration.

This paper describes updates to NASA's approach for assessing and mitigating spaceflight-induced risks to human health and performance. This approach continues to evolve to meet dynamically changing risk environments: lunar missions are currently being designed and the ultimate destination will be Mars. Understanding the risks that astronauts will face during a Mars mission will depend on building an evidence base that informs not only how the humans respond to the challenges of the spaceflight environment, but also how systems and vehicles can be designed to support human capabilities and limitations. This publication documents updates to the risk management process used by the Human System Risk Board at NASA and includes changes to the likelihood and consequence matrix used by the board, the design reference mission categories and parameters, and the standardized evaluation of the levels of evidence that the board accepts when setting risk posture. Causal diagramming, using directed acyclic graphs, provides all stakeholders with the current understanding of how each risk proceeds from a spaceflight hazard to a mission-level outcome. This standardized approach enables improved communication among stakeholders and delineates how and where more knowledge can improve perspective of human system risks and which countermeasures can best mitigate these risks.

Serum insulin concentration in dogs with insulinoma as a clinical marker for presence of metastasis at the time of diagnosis.

BACKGROUND: Information regarding serum insulin concentration in dogs newly diagnosed with insulinoma and its association with clinical stage and survival time is lacking. OBJECTIVE: Examine association between serum insulin concentration and survival and clinical disease stage in dogs with insulinoma. ANIMALS: Fifty-nine client-owned dogs with a diagnosis of insulinoma from 2 referral hospitals. METHOD: Retrospective observational study. The χ2 test was used to compare the proportion of dogs with increased insulin concentration in groups with or without metastasis at the time of diagnosis. Linear mixed-effect models were built to compare differences in insulin concentration between dogs with and without evidence of metastasis at the time of original diagnosis. Cox's proportional hazards regression and Kaplan-Meier graphs were used to evaluate the association between insulin concentration and insulin groups and survival. RESULTS: Median serum insulin concentration was 33 mIU/L (range, 8-200 mIU/L) in dogs with World Health Organization (WHO) stage I disease and 45 mIU/L (range, 12-213 mIU/L) in dogs with WHO stage II and III disease. No difference was found in the proportion of dogs with increased insulin concentration with or without metastasis (P = .09). No association was identified between insulin concentration and survival (P = .63), and between dogs grouped by insulin concentration and survival (P = .51). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum insulin concentrations were not different between dogs with or without metastasis at diagnosis. The degree of insulinemia does not provide further information regarding the stage of the disease and is not associated with survival time in dogs with insulinoma.

Health effects associated with smoking: a Burden of Proof study.

As a leading behavioral risk factor for numerous health outcomes, smoking is a major ongoing public health challenge. Although evidence on the health effects of smoking has been widely reported, few attempts have evaluated the dose-response relationship between smoking and a diverse range of health outcomes systematically and comprehensively. In the present study, we re-estimated the dose-response relationships between current smoking and 36 health outcomes by conducting systematic reviews up to 31 May 2022, employing a meta-analytic method that incorporates between-study heterogeneity into estimates of uncertainty. Among the 36 selected outcomes, 8 had strong-to-very-strong evidence of an association with smoking, 21 had weak-to-moderate evidence of association and 7 had no evidence of association. By overcoming many of the limitations of traditional meta-analyses, our approach provides comprehensive, up-to-date and easy-to-use estimates of the evidence on the health effects of smoking. These estimates provide important information for tobacco control advocates, policy makers, researchers, physicians, smokers and the public.

Acute kidney injury manifesting as renal tubular acidosis with proximal and distal renal tubular dysfunction in a dog with acute pancreatitis.

OBJECTIVE: To describe the clinical presentation and management of a critically ill dog with profound renal tubular acidosis (RTA) with proximal and distal renal tubular dysfunction. CASE SUMMARY: A 3-year-old neutered female Border Terrier was presented with frequent regurgitation resulting from acute pancreatitis with severe ileus. Venous acid-base analysis and complete urinalysis confirmed the presence of normal anion gap metabolic acidosis with inappropriately alkaline urine (pH 8), consistent with distal RTA. Urinalysis, urine amino acids, and urinary fractional excretion of electrolytes revealed glycosuria (with normoglycemia), aminoaciduria, and increased fractional excretion of sodium, calcium, and phosphate consistent with generalized proximal renal tubulopathy or Fanconi syndrome. The dog responded well to supportive care and alkaline therapy and made a complete recovery. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first description of RTA with proximal and distal renal tubular dysfunction in the veterinary literature. Furthermore, the authors hypothesize that the transient RTA was a manifestation of acute kidney injury secondary to acute pancreatitis, the first report of this in the literature.

Toxicity of zoledronic acid after intravenous administration: A retrospective study of 95 dogs.

BACKGROUND: There is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia. HYPOTHESIS/OBJECTIVES: The primary aim was to report the adverse events in dogs receiving intravenous administration of ZA. ANIMALS: Ninety-five dogs with ZA use. METHODS: A retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded. RESULTS: Ninety-five dogs met the inclusion criteria. Thirty-one (33%) received multiple intravenous infusions of ZA (range, 2-7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG-CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26-0.66) was not significantly different to the group which did not change VCOG-CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2-1.50; P = .93). CONCLUSIONS AND CLINICAL IMPORTANCE: Multiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

Clinical, computed tomographic and histopathological findings in two cats with pulmonary fibrosis of unknown aetiology.

CASE SERIES SUMMARY: Two cats were presented for further investigation of respiratory signs. One cat had a history of a cough and the other, tachypnoea. In each case, thoracic CT was performed, which revealed a generalised marked reticular pattern in the first cat and focal consolidation of the right caudal lung lobe in the second cat. The first cat was euthanased following completion of the imaging study and a post-mortem examination was performed. The second cat underwent surgical excision of the abnormal lung lobe and survived for 4 years after diagnosis. Histopathology performed on lung tissue removed from each cat was consistent with pulmonary fibrosis. RELEVANCE AND NOVEL INFORMATION: This small case series adds to the existing literature and highlights the heterogeneous clinical course and variable appearance of pulmonary fibrosis on CT of affected cats. These cases provide evidence that pulmonary fibrosis in cats incorporates a wide spectrum of fibrotic lung disease and demonstrates the possibility for prolonged survival following diagnosis where disease is localised and amenable to surgical resection.

The WHO Global Benchmarking Tool: a game changer for strengthening national regulatory capacity.

Many low-income and middle-income countries lack the capacity to effectively and efficiently regulate medical products in their countries. To support countries in strengthening their capacity, WHO has developed the Global Benchmarking Tool (GBT) as the global standard for objectively assessing regulatory capacity for medicines and vaccines. The GBT is a game changer because it is the first globally accepted tool for assessing and strengthening national regulatory authorities. The inclusion of an institutional development plan in the GBT methodology provides context-specific actionable steps countries can take to advance their system's functionality and maturity. The GBT facilitates coordination and improves the effectiveness of regulatory strengthening efforts. The tool also facilitates regulatory reliance and harmonisation, which helps to improve timely access to quality-assured medicines, and creates incentives for trade, particularly in countries and regions with a strong pharmaceutical manufacturing base. The GBT is a necessary tool for creating strong and effective regulatory systems, which are critical for ensuring the efficacy, safety and quality assurance of medicines and populations' timely access to these medicines. In outlining the benefits of the GBT, this paper also offers some specific ideas for strengthening the GBT framework and process.

Evaluation of serum cortisol concentration as a prognostic indicator for nonsurvival to hospital discharge in critically ill dogs.

OBJECTIVE: To investigate whether serum cortisol (SC) concentration is a useful prognostic indicator for survival versus nonsurvival to hospital discharge in critically ill dogs. ANIMALS: 229 client-owned dogs. PROCEDURES: Medical records were retrospectively reviewed to identify critically ill dogs that were hospitalized between January 2010 and May 2018 and that had SC concentrations measured ≤ 3 days after admission. Results for SC concentrations were compared for dogs grouped by survival versus nonsurvival to hospital discharge, with versus without sepsis, and other variables of interest. The predictive value of SC concentration for nonsurvival to hospital discharge was assessed (OR, sensitivity, and specificity) for cutoffs determined from a ROC curve or reference limit. RESULTS: Median SC concentration was higher in dogs that did not survive to hospital discharge (8.5 µg/dL; interquartile [25th to 75th percentile] range, 4.8 to 11.8 µg/dL), compared with concentration in those that were discharged alive (4.5 µg/dL; interquartile range, 2.5 to 6.9 µg/dL). The area under the ROC curve was 0.72 (95% confidence interval [CI], 0.64 to 0.81) for SC concentration predicting nonsurvival. The calculated optimum cutoff of SC concentration was 7.6 µg/dL, at which the OR, sensitivity, and specificity for nonsurvival were 5.4 (95% CI, 2.7 to 10.9), 58%, and 80%, respectively. Alternatively, when the upper reference limit for SC concentration (5.8 µg/dL) was used as the cutoff, the OR, sensitivity, and specificity for nonsurvival were 3.6 (95% CI, 1.8 to 7.1), 67%, and 64%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that SC concentration could be used as part of an overall assessment of prognosis in critically ill dogs.

Incidence of postoperative complications and outcome of 48 dogs undergoing surgical management of insulinoma.

BACKGROUND: Information regarding outcome of dogs undergoing surgical management for insulinoma is based on studies of a small number of dogs. OBJECTIVES: To report the outcomes of dogs undergoing surgery as treatment for insulinoma, the prevalence of postoperative diabetes mellitus (DM) in this group and to determine if development of DM can be predicted. ANIMALS: Forty-eight client-owned dogs, with a histopathological diagnosis of insulinoma, from three European referral hospitals. METHODS: Retrospective observational study. Dogs were identified from a search of electronic hospital records. Cox's regression was used to determine factors associated with postoperative survival and relapse, and logistic regression was used to determine factors associated with the development of DM. RESULTS: Median survival time (MST) was 372 days (range 1-1680 days), with dogs with stage I disease having the longest survival time. Stage I dogs had MST of 652 days (range 2-1680 days), whereas dogs with either stage II or III disease had MST of 320 days (range 1-1260 days; P = 0.045). Postoperative hyperglycemia was identified in 33% (16/48) of the dogs, of which 9 (19% of the total population) developed persistent DM. No factors that could be used as predictors for development of DM were identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Stage of disease and postoperative hypoglycemia were associated with greater odds of relapse and decreased survival time; these could be used when discussing prognosis. In this study, postoperative DM developed more commonly than previously reported, but no factors were identified that might be useful predictors.

Factors associated with overweight cats successfully completing a diet-based weight loss programme: an observational study.

BACKGROUND: The most common approach for controlled weight loss in cats is dietary caloric restriction, using a purpose-formulated diet. Most previous studies have only assessed short-term outcomes, and no previous study has examined overall success (i.e. odds of reaching target weight). The aim of this study was to determine the factors associated with overweight cats successfully completing a diet-based weight loss programme to reach target weight. RESULTS: Sixty-two cats were included, and 28 (45%) completed their weight loss programme. The remaining 34 cats (55%) did not reach target weight, of which 2 (3%) were euthanised for unrelated reasons. Reasons for cats stopping the programme prematurely included inability to contact owner (n = 19), owner requested that the programme be completed prior to reaching target weight (n = 5), the cat developed another illness (n = 3), refusal to comply with requirements for weight management (n = 2), owner illness (n = 2), and personal issues of the owner (n = 1). Multiple logistic regression analysis revealed that rate of weight loss and weight loss required were positively (odds ratio [OR] 157.81, 95% confidence interval [CI] 10.00-2492.67) and negatively (OR 0.89, 95% CI 0.81-0.98) associated with the odds of completing the weight loss programme, respectively. CONCLUSIONS: Future studies should consider developing better methods of supporting the owners of the most obese cats during weight management, since these cats are least likely to complete reach target weight.

Emotions and beliefs after a disaster: a comparative analysis of Haiti and Indonesia.

A number of studies have examined emotional and belief responses following a disaster, yet there has been limited comparative analysis of responses to disasters in different places. This paper reviews the results of 366 questionnaires that evaluated key emotional and belief concepts in Haiti after the earthquake on 12 January 2010 (n=212) and in Indonesia after the earthquake in Yogyakarta on 27 May 2006 (n=154). The results indicate significant differences between the responses in the two settings, particularly in relation to feelings of impunity, self-blame for the disaster, regret about pre-earthquake behaviour, and a sense of justice in the world. Furthermore, the impacts of age, education, and gender on responses also were different in the two case study sites. Overall, the results suggest that understanding the cultural, religious, and social contexts of different disaster locales is important in comprehending the emotions and beliefs that manifest themselves in the wake of a major disaster.

Transforming women's oral-systemic health through discovery, development and delivery.

Due to the complexity of women's health issues that involve the interplay between oral and systemic health, a multidisciplinary approach to research and practice is critical to ensure health and quality of life among women across the lifespan. The 2nd Annual Conference entitled 'Transforming Women's Health: Discovery, Development and Delivery of the Oral-Systemic Connection', was held in Tampa (FL, USA) on 26-27 January 2013. The conference addressed complex oral-systemic women's health issues structured by three organizational pillars: discovery, development and delivery, with overarching topic areas of oral human papillomavirus infection, autoimmune conditions and the Affordable Care Act. This conference served as an effective method for bringing together multiple disciplines to discuss emerging women's health issues.

Correlates of 2009 H1N1 influenza vaccination among day care-aged children, Miami-Dade County.

BACKGROUND: The aim of this study was to assess factors influencing 2009 H1N1 influenza vaccination among a demographically diverse group of day care-aged children. Day care children were chosen because they were an initial target group for vaccination and are at higher risk of influenza infection than children cared for at home. METHODS: A cross-sectional study was conducted from March to May 2010 among parents of day care aged children in 13 day care facilities in Miami-Dade County. Data was collected by an anonymous self-administered two-page 20 question survey which consisted of demographic variables and information regarding 2009 H1N1 influenza vaccine knowledge, attitude and acceptance. Data was analyzed using SAS to conduct both bivariate and multivariate analyses. RESULTS: There were 773 participants in the study. The response rate ranged from 42% to 72.2% among day care centers. A total of 172 parents (22.3%) and 225 (29.1%) children had received the 2009 H1N1 influenza vaccine. Non-Hispanic White and Black parents were more likely to vaccinate their children than Hispanic and Haitian parents. Primary reasons for non-vaccination included vaccine safety (36.7%) and side effects (27.1%). Among parents who spoke with a health care professional, 274 (61.4%) stated the health care professional recommended the vaccine. CONCLUSION: Misperceptions about influenza vaccination among parents created a barrier to 2009 H1N1 influenza vaccination. Parents who got the vaccine, who believed the vaccine was safe and whose children had a chronic condition were more likely to immunize their children. Clear, reliable and consistent vaccine information to the public and health care providers and initiatives targeting minority groups may increase vaccination coverage among this population.