Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes.

The 6%-9% risk of an untoward outcome previously established by Warburton for prenatally detected de novo balanced chromosomal rearrangements (BCRs) does not account for long-term morbidity. We performed long-term follow-up (mean 17 years) of a registry-based nationwide cohort of 41 individuals carrying a prenatally detected de novo BCR with normal first trimester screening/ultrasound scan. We observed a significantly higher frequency of neurodevelopmental and/or neuropsychiatric disorders than in a matched control group (19.5% versus 8.3%, p = 0.04), which was increased to 26.8% upon clinical follow-up. Chromosomal microarray of 32 carriers revealed no pathogenic imbalances, illustrating a low prognostic value when fetal ultrasound scan is normal. In contrast, mate-pair sequencing revealed disrupted genes (ARID1B, NPAS3, CELF4), regulatory domains of known developmental genes (ZEB2, HOXC), and complex BCRs associated with adverse outcomes. Seven unmappable autosomal-autosomal BCRs with breakpoints involving pericentromeric/heterochromatic regions may represent a low-risk group. We performed independent phenotype-aware and blinded interpretation, which accurately predicted benign outcomes (specificity = 100%) but demonstrated relatively low sensitivity for prediction of the clinical outcome in affected carriers (sensitivity = 45%-55%). This sensitivity emphasizes the challenges associated with prenatal risk prediction for long-term morbidity in the absence of phenotypic data given the still immature annotation of the morbidity genome and poorly understood long-range regulatory mechanisms. In conclusion, we upwardly revise the previous estimates of Warburton to a morbidity risk of 27% and recommend sequencing of the chromosomal breakpoints as the first-tier diagnostic test in pregnancies with a de novo BCR.

Using World Health Organisation near miss approach to assess preventable maternal morbidity and mortality at a tertiary care hospital.

OBJECTIVE: To determine frequency of severe maternal complications, maternal near-miss cases and maternal deaths in obstetric patients in a tertiary care setting. METHODS: The prospective cross-sectional analytical study was conducted at the Obstetrics Unit of Combined Military Hospital, Kharian, Pakistan, from January to June 2019, and comprised cases of severe maternal complications, critical interventions and life-threatening situations. A conditions as defined by the World Health Organisation guidelines. Severe maternal outcome ratio, maternal near-miss, maternal mortality ratio, near-miss-to-mortality ratio and the mortality index were calculated. Data was analysed using SPSS 20. RESULTS: Of the 1054 live births during the study period, there were 42(3.9%) near-miss cases and 4(0.3%) maternal deaths. Management-based criteria identified 34(80%) cases, followed by clinical 14(33%) and laboratory criteria 2(4.7%). Maternal mortality ratio was 379/100,000 and near-miss-to-mortality ratio was 39/1000 live births. Severe maternal outcome ratio was 4.36 (42+4/1054). For near-miss cases, the mortality index was 8.6, and the maternal near-miss-to-maternal death ratio was 10.5:1. CONCLUSION: The use of a standardised near-miss criterion makes audit and comparison of results between hospitals and even countries having the same resources possible and reproducible.

Predicting overall and major postoperative morbidity in gastric cancer patients.

BACKGROUND: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks. METHODS: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed. RESULTS: The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk. CONCLUSIONS: The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients.

Risk of Death and Major Injury from Natural Winter Hazards in Helicopter and Snowcat Skiing in Canada.

INTRODUCTION: Guests and guides partaking in helicopter and snowcat skiing (collectively known as mechanized skiing) are exposed to numerous natural winter hazards that can result in injury or death, but detailed quantitative risk estimates are currently lacking. This lack represents a considerable barrier for evaluating existing risk management practices and implementing evidence-based improvements. METHODS: We collected historical incident and exposure information from mechanized skiing operations in Canada to perform a retrospective risk analysis. Our analysis dataset includes 713 incidents that resulted in injuries or fatalities among guests or guides during a total of 3,258,000 skier days from the 1970 to 2016 winter season. RESULTS: Overall risk of death from natural winter hazards in mechanized skiing was 18.6 fatalities per million skier days (1997-2016). Although the risk of death from avalanches decreased substantially over the entire study period, avalanches remain the largest contributor to the overall risk of death (77%), followed by tree wells and other non-avalanche-related snow immersions. The risk of death from avalanches in snowcat skiing is about half of that in helicopter skiing, but other snow immersion fatalities are more common. The risk of major injury to guests is primarily associated with other falls and collisions. The risk of major injury for guides is higher in snowcat skiing than in helicopter skiing. CONCLUSION: We recommend the design of an industry-wide incident and near-miss reporting system to support evidence-based improvements of safety practices.

A wide landscape of morbidity and mortality risk associated with marital status in 0.5 million Chinese men and women: a prospective cohort study.

Background: A comprehensive depiction of long-term health impacts of marital status is lacking. Methods: Sex-stratified phenome-wide association analyses (PheWAS) of marital status (living with vs. without a spouse) were performed using baseline (2004-2008) and follow-up information (ICD10-coded events till Dec 31, 2017) from the China Kadoorie Biobank (CKB). We estimated adjusted hazard ratios (aHRs) to evaluate the associations of marital status with morbidity risks of phenome-wide significant diseases or sex-specific top-10 death causes in China documented in 2017. Additionally, the association between marital status and mortality risks among participants with major chronic diseases at baseline was assessed. Findings: During up to 11.1 years of the median follow-up period, 1,946,380 incident health events were recorded among 210,202 men and 302,521 women aged 30-79. Marital status was found to have phenome-wide significant associations with thirteen diseases among men (p < 9.92 × 10-5) and nine diseases among women (p < 9.33 × 10-5), respectively. After adjusting for all disease-specific covariates in the final model, participants living without a spouse showed increased risks of schizophrenia, schizotypal and delusional disorders (aHR [95% CI]: 2.55, [1.83-3.56] for men; 1.49, [1.13-1.97] for women) compared with their counterparts. Additional higher risks in overall mental and behavioural disorder (1.31, 1.13-1.53), cardiovascular disease (1.07, 1.04-1.10) and cancer (1.06, 1.00-1.12) were only observed among men without a spouse, whereas women living without a spouse were at lower risks of developing genitourinary diseases (0.89, 0.85-0.93) and injury & poisoning (0.93, 0.88-0.97). Among 282,810 participants with major chronic diseases at baseline, 39,166 deaths were recorded. Increased mortality risks for those without a spouse were observed in 12 of 21 diseases among male patients and one of 23 among female patients. For patients with any self-reported disease at baseline, compared with those living with a spouse, the aHRs (95% CIs) of mortality risk were 1.29 (1.24-1.34) and 1.04 (1.00-1.07) among men and women without a spouse (pinteraction<0.0001), respectively. Interpretation: Long-term associations of marital status with morbidity and mortality risks are diverse among middle-aged Chinese adults, and the adverse impacts due to living without a spouse are more profound among men. Marital status may be an influential factor for health needs. Funding: The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, and the UK Wellcome Trust.

Risk of de novo esophageal cancer in liver transplant recipients: systematic review and meta-analysis.

Background: De novo malignancy is the leading cause of death in liver transplant recipients. Numerous studies consistently show a significantly increased risk of esophageal cancer after liver transplantation. Therefore, this study aims to investigate the incidence and risk factors associated with de novo esophageal cancer post-liver transplantation. Methods: PubMed, Embase, Medline and Cochrane Library were systematically searched. Screening, quality assessment, and data extraction were completed. The search was completed in November 2023. Standardized incidence rates (SIRs) were used to measure the risk of esophageal cancer among liver transplant recipients, along with corresponding 95% confidence intervals (CI). A random effects model was employed for comprehensive analysis, and results were presented using a forest plot. Sensitivity analysis was undertaken by systematically excluding individual studies one by one, while potential publication bias was assessed using funnel plots and Egger's test. Additionally, subgroup analyses were also performed to explore sources of heterogeneity. Results: Out of 1,037 articles collected, only twelve met the inclusion criteria after rigorous screening. Statistical analysis showed a significantly increased risk of esophageal cancer following liver transplantation compared to the general population (SIR =6.75, 95% CI: 4.35-10.46). Conclusions: The risk of esophageal cancer significantly increases after liver transplantation, so regular gastrointestinal endoscopy is necessary after the procedure.

Daily variation in natural disaster casualties: information flows, safety, and opportunity costs in tornado versus hurricane strikes.

Casualties from natural disasters may depend on the day of the week they strike. With data from the Spatial Hazard Events and Losses Database for the United States (SHELDUS), daily variation in hurricane and tornado casualties from 5,043 tornado and 2,455 hurricane time/place events is analyzed. Hurricane forecasts provide at-risk populations with considerable lead time. Such lead time allows strategic behavior in choosing protective measures under hurricane threat; opportunity costs in terms of lost income are higher during weekdays than during weekends. On the other hand, the lead time provided by tornadoes is near zero; hence tornados generate no opportunity costs. Tornado casualties are related to risk information flows, which are higher during workdays than during leisure periods, and are related to sheltering-in-place opportunities, which are better in permanent buildings like businesses and schools. Consistent with theoretical expectations, random effects negative binomial regression results indicate that tornado events occurring on the workdays of Monday through Thursday are significantly less lethal than tornados that occur on weekends. In direct contrast, and also consistent with theory, the expected count of hurricane casualties increases significantly with weekday occurrences. The policy implications of observed daily variation in tornado and hurricane events are considered.

Valuing COVID-19 Morbidity Risk Reductions.

Many economic analyses, including those that address the COVID-19 pandemic, focus on the value of averting deaths and do not include the value of averting nonfatal illnesses. Yet incorporating the value of averting nonfatal cases may change conclusions about the desirability of the policy. While per case values may be small, the number of nonfatal cases is often large, far outstripping the number of fatal cases. The value of averting nonfatal cases is also increasingly important in evaluating COVID-19 policy options as vaccine- and infection-related immunity and treatments reduce the case-fatality rate. Unfortunately, little valuation research is available that explicitly addresses COVID-19 morbidity. We describe and implement an approach for approximating the value of averting nonfatal illnesses or injuries and apply it to COVID-19 in the United States. We estimate gains from averting COVID-19 morbidity of about 0.01 quality-adjusted life year (QALY) per mild case averted, 0.02 QALY per severe case, and 3.15 QALYs per critical case. These gains translate into monetary values of about $5,300 per mild case, $11,000 per severe case, and $1.8 million per critical case. While these estimates are imprecise, they suggest the magnitude of the effects.

Observations on the Occurrence, Transmission and Management of the COVID-19 Pandemic Derived from Physics.

Three important observations derived from the ongoing COVID-19 pandemic could result in the development of novel approaches to deal with it and avoid or at least minimize the occurrence and impact of future outbreaks. First, the dramatic increase in pandemics in the past decade alone suggests that the current relationship of humans with the environment is quickly becoming unstable, with potentially catastrophic consequences. In order to reduce the toll in life and property, we would need to shift our emphasis from control of nature to a symbiosis with nature. This, then, can become the new framework for dealing effectively with environmental issues such as climate change, whereby properly applied medical science would provide the necessary impetus for action. Second, the existence of superspreaders of infection among populations in this pandemic requires that we develop objective tests, most likely of a genetic nature, to identify them rather than apply indiscriminate and draconian controls across the board. Not identifying superspreaders in a timely fashion could allow this pandemic to turn into a black swan event, with a catastrophic impact on society. Third, we need to refocus our efforts in dealing with this pandemic from the virus itself to the human hosts. An objective morbidity risk index can be developed such that most of us can go about our daily business without the fear of becoming seriously ill, while measures can be implemented to protect those who are most vulnerable to this virus. These observations point clearly to a need for a paradigm shift.

The role of concomitant alcohol and drug use in increased risk for burn mortality outcomes.

BACKGROUND: Burn injuries are a major cause of mortality and morbidity in low- and middle-income countries, with high rates in Sub-Saharan Africa. The risks may be heightened for persons who present with concomitant use of alcohol and illicit substances, which increase the risk for injury and severely compromise prognosis following injury. METHODS: This study utilised a national dataset on hospitalised burns in South Africa to explore the risk for mortality relative to morbidity. To assess the influence of alcohol and drugs in mortality outcomes, the analysis was restricted to adult cases, 18 years and older (N = 918). The primary statistical procedures used in the analysis were logistic regression models. FINDINGS: The results indicate that burn victims with full thickness and partial thickness burn degree and more than 30% TBSA had a significantly increased risk of mortality. In addition, the risk for mortality was increased ten times when concomitant alcohol and drugs were indicated compared to cases where these were absent. The length of stay in hospital diminished the risk for mortality by about 10%. INTERPRETATION: The findings may be explained by the role of skin as the main barrier against infections and the concurrent increase in risk of infection based on the degree and extent of any damage. The combined presence of both alcohol and drugs may predispose towards more severe burns and greatly compromise liver function with heightened risk for sepsis and death.

Charlson Comorbidity Index: ICD-9 Update and ICD-10 Translation.

BACKGROUND: The original Charlson Comorbidity Index (CCI) encompassed 19 categories of medical conditions that were identifiable in medical records. Subsequent publications provided scoring algorithms based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The recent adoption of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes in the United States created a need for a new scoring scheme. In addition, a review of existing claims-based scoring systems suggested 3 areas for improvement: the lack of explicit identification of secondary diabetes, the lack of differentiation between HIV infection and AIDS, and insufficient guidance on scoring hierarchy. In addition, addressing the third need raised the issue of disease severity in renal disease. OBJECTIVES: This initiative aimed to create an expanded and refined ICD-9 scoring system for CCI, addressing the classification of issues noted above, create a corresponding ICD-10 system, assess the comparability of ICD-9- and ICD-10-based scores, and validate the new scoring scheme. METHODS: We created ICD-9 and ICD-10 code tables for 19 CCI medical conditions. The new scoring scheme was labeled CDMF CCI and was tested using claims-based data for individuals aged ≥65 years who participated in a Humana Medicare Advantage plan during at least 1 of 3 consecutive 12-month periods. Two 12-month periods were during the ICD-9 era and the third 12-month period was during the ICD-10 era. Because many individuals were counted in more than one 12-month period, we described the study population as comprising 3 panels. We used regression models to analyze the association between the CCI score and same-year inpatient admissions and near-term (90-day) mortality. Additional testing was done by comparing the mean CCI score or disease prevalence in the 3 subpopulations of people with HIV/AIDS, renal disease, or diabetes. Finally, we calculated area under the receiver operating characteristics (AUC-ROC) curve values by applying the Deyo system and our ICD-9 and ICD-10 scoring systems. RESULTS: The CDMF ICD-9 and ICD-10 scoring scheme yielded comparable scores across the 3 panels, and inpatient admissions and mortality rates consistently increased in each panel as the CCI score increased. Comparisons of the performance of the Deyo system and our proposed CDMF ICD-9 system in the 3 key subpopulations showed that the CDMF ICD-9 system produced a lower CCI score in the presence of HIV infection without AIDS, achieved similar detection ability of diabetes, and allowed good differentiation between mild-to-moderate and severe renal disease. AUC-ROC values were similar between the CDMF ICD-9 coding system and the Deyo system. CONCLUSION: Our results support the implementation of the CDMF CCI scoring instrument to triage individual patients for disease- and care-management programs. In addition, the CDMF scheme allows for a more precise understanding of chronic disease at a population level, thus allowing health systems and plans to design services and benefits to meet multifactorial clinical needs. Preliminary validation sets the stage for further testing using long-term follow-up data and for the adaptation of this coding scheme to a chart review instrument.

Family Loading and Morbidity Risk of Attention-deficit Hyperactivity Disorder in Patients with Alcohol-dependence Syndrome.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and substance-use disorders often co-occur. AIM: Aim of this study was to look at the family loading of ADHD (in adults and children) in patients with alcohol-dependence syndrome (ADS) along with the estimation of morbidity risk (MR) for developing ADHD. METHODS: Thirty-five male patients with ADS along with their 369 first-degree relatives (FDRs) - both children and adults - were recruited. RESULTS: ADHD and residual ADD (ADDRT) were significantly more common in the early-onset (EO) ADS group and their FDR. In ADHD children, high MR (27.27%) for developing EO of ADS was noted. DISCUSSION: Findings from this study raise an avenue for research in the Indian population about the shared risk between ADS and ADHD.

Baseline risk and marginal willingness to pay for health risk reduction.

Empirical results presented in this paper suggest that parents' marginal willingness to pay (MWTP) for a reduction in morbidity risk from heart disease is inversely related to baseline risk (i.e., the amount of risk initially faced) both for themselves and for their children. For instance, a 40% reduction from the mean of baseline risk results in an increase in MWTP by 70% or more. Thus, estimates of monetary benefits of public programs to reduce heart disease risk would be understated if the standard practice is followed of evaluating MWTP at initial risk levels and then multiplying this value by the number of cases avoided. Estimates are supported by: (1) unique quantitative information on perceptions of the risk of getting heart disease that allow baseline risk to be defined at an individual level and (2) improved econometric procedures to control for well-known difficulties associated with stated preference data.

aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities: a simplified auditing tool for community-acquired gastrointestinal surgical emergencies.

BACKGROUND: In a previous study, we found that Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) overpredicts morbidity risk in emergency gastrointestinal surgery. Our aim was to find a POSSUM equation adjustment. METHODS: A prospective observational study was performed on 2,361 patients presenting with a community-acquired gastrointestinal surgical emergency. The first 1,000 surgeries constituted the development cohort, the second 1,000 events were the first validation intramural cohort, and the remaining 361 cases belonged to a second validation extramural cohort. RESULTS: (1) A modified POSSUM equation was obtained. (2) Logistic regression was used to yield a statistically significant equation that included age, hemoglobin, white cell count, sodium and operative severity. (3) A chi-square automatic interaction detector decision tree analysis yielded a statistically significant equation with 4 variables, namely cardiac failure, sodium, operative severity, and peritoneal soiling. CONCLUSIONS: A modified POSSUM equation and a simplified scoring system (aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities [LUCENTUM]) are described. Both tools significantly improve prediction of surgical morbidity in community-acquired gastrointestinal surgical emergencies.

Knowing your neighbourhood: local ecology and personal experience predict neighbourhood perceptions in Belfast, Northern Ireland.

Evolutionary theory predicts that humans should adjust their life-history strategies in response to local ecological threats and opportunities in order to maximize their reproductive success. Cues representing threats to individuals' lives and health in modern, Western societies may come in the form of local ages at death, morbidity rate and crime rate in their local area, whereas the adult sex ratio represents a measure of the competition for reproductive partners. These characteristics are believed to have a strong influence over a wide range of behaviours, but whether they are accurately perceived has not been robustly tested. Here, we investigate whether perceptions of four neighbourhood characteristics are accurate across eight neighbourhoods in Belfast, Northern Ireland. We find that median age at death and morbidity rates are accurately perceived, whereas adult sex ratios and crime rates are not. We suggest that both neighbourhood characteristics and personal experiences contribute to the formation of perceptions. This should be considered by researchers looking for associations between area-level factors.

Modelling of Radiological Health Risks from Gold Mine Tailings in Wonderfonteinspruit Catchment Area, South Africa.

Mining is one of the major causes of elevation of naturally-occurring radionuclide material (NORM) concentrations on the Earth's surface. The aim of this study was to evaluate the human risk associated with exposure to NORMs in soils from mine tailings around a gold mine. A broad-energy germanium detector was used to measure activity concentrations of these NORMs in 66 soil samples (56 from five mine tailings and 10 from the control area). The RESidual RADioactivity (RESRAD) OFFSITE modeling program (version 3.1) was then used to estimate the radiation doses and the cancer morbidity risk of uranium-238 ((238)U), thorium-232 ((232)Th), and potassium-40 ((40)K) for a hypothetical resident scenario. According to RESRAD prediction, the maximum total effective dose equivalent (TEDE) during 100 years was found to be 0.0315 mSv/year at year 30, while the maximum total excess cancer morbidity risk for all the pathways was 3.04 × 10(-5) at year 15. The US Environmental Protection Agency considers acceptable for regulatory purposes a cancer risk in the range of 10(-6) to 10(-4). Therefore, results obtained from RESRAD OFFSITE code has shown that the health risk from gold mine tailings is within acceptable levels according to international standards.

How "lucky" we are that the Fukushima disaster occurred in early spring: predictions on the contamination levels from various fission products released from the accident and updates on the risk assessment for solid and thyroid cancers.

The present paper studies how a random event (earthquake) and the subsequent disaster in Japan affect transport and deposition of fallout and the resulting health consequences. Therefore, except for the original accident in March 2011, three additional scenarios are assessed assuming that the same releases took place in winter 2010, summer 2011 and autumn 2011 in order to cover a full range of annual seasonality. This is also the first study where a large number of fission products released from the accident are used to assess health risks with the maximum possible efficiency. Xenon-133 and (137)Cs are directly estimated within the model, whereas 15 other radionuclides are calculated indirectly using reported isotopic ratios. As much as 85% of the released (137)Cs would be deposited in continental regions worldwide if the accident occurred in winter 2010, 22% in spring 2011 (when it actually happened), 55% in summer 2011 and 48% if it occurred during autumn 2011. Solid cancer incidents and mortalities from Fukushima are estimated to be between 160 and 880 and from 110 to 640 close to previous estimations. By adding thyroid cancers, the total number rises from 230 to 850 for incidents and from 120 to 650 for mortalities. Fatalities due to worker exposure and mandatory evacuation have been reported to be around 610 increasing total estimated mortalities to 730-1260. These estimates are 2.8 times higher than previously reported ones for radiocaesium and (131)I and 16% higher than those reported based on radiocaesium only. Total expected fatalities from Fukushima are 32% lower than in the winter scenario, 5% that in the summer scenario and 30% lower than in the autumn scenario. Nevertheless, cancer fatalities are expected to be less than 5% of those from the tsunami (~20,000).

Risk factors for headache in children.

BACKGROUND: 10% to 30% of all children worldwide suffer from headaches at least once a week, potentially constituting a serious health problem that may lead to impairment in multiple areas. Therefore, one aim of the epidemiological longitudinal study "Children, Adolescents, and Headache" (KiJuKo) is the study of potential risk factors for the development of recurrent headaches. METHODS: In the first survey (2003), questionnaires were sent to 8800 households with a child between 7 and 14 years of age. Three further surveys followed, one each year from 2004 to 2006. A number of predictors having to do with family characteristics and leisure activities were identified on the basis of the first survey and were then studied in the second survey (n = 2952) with respect to their influence on the new occurrence of headaches. RESULTS: The risk of developing recurrent headaches between the first and the second survey was elevated by a factor of approximately 1.8 for boys who experienced quarrels in the family more than once per week, and by a factor of 2.1 for boys who only "sometimes" had free time for themselves. The risk of developing recurrent headaches was 25% higher in girls whose parents' behavior towards the child positively or negatively reinforced the occurrence of headaches. CONCLUSIONS: These findings are in accordance with those of other studies showing that, for boys, the frequency of quarreling in the family and the extent of leisure time are major factors in the development of recurrent headaches. For girls, the manner in which the parents respond to the child's headache seems to be important.