Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism.

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates.

We propose TetraHer, a method for estimating the liability heritability of binary phenotypes. TetraHer has five key features. First, it can be applied to data from complex pedigrees that contain multiple types of relationships. Second, it can correct for ascertainment of cases or controls. Third, it can accommodate covariates. Fourth, it can model the contribution of common environment. Fifth, it produces a likelihood that can be used for significance testing. We first demonstrate the validity of TetraHer on simulated data. We then use TetraHer to estimate liability heritability for 229 codes from the tenth International Classification of Diseases (ICD-10). We identify 107 codes with significant heritability (p < 0.05/229), which can be used in future analyses for investigating the genetic architecture of human diseases.

Avoiding Liability and Other Legal Land Mines in the Evolving Genomics Landscape.

This article reviews evolving legal implications for clinicians and researchers as genomics is used more widely in both the clinic and in translational research, reflecting rapid changes in scientific knowledge as well as the surrounding cultural and political environment. Professionals will face new and changing duties to make or act upon a genetic diagnosis, address direct-to-consumer genetic testing in patient care, consider the health implications of results for patients' family members, and recontact patients when test results change over time. Professional duties in reproductive genetic testing will need to be recalibrated in response to disruptive changes to reproductive rights in the United States. We also review the debate over who controls the flow of genetic information and who is responsible for its protection, considering the globally influential European Union General Data Protection Regulation and the rapidly evolving data privacy law landscape of the United States.

Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants.

We examined more than 97,000 families from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents contributing to neurodevelopmental disease risk in children. We identified within- and cross-disorder correlations between six phenotypes in parents and children, such as obsessive-compulsive disorder (R = 0.32-0.38, p < 10-126). We also found that measures of sub-clinical autism features in parents are associated with several autism severity measures in children, including biparental mean Social Responsiveness Scale scores and proband Repetitive Behaviors Scale scores (regression coefficient = 0.14, p = 3.38 × 10-4). We further describe patterns of phenotypic similarity between spouses, where spouses show correlations for six neurological and psychiatric phenotypes, including a within-disorder correlation for depression (R = 0.24-0.68, p < 0.001) and a cross-disorder correlation between anxiety and bipolar disorder (R = 0.09-0.22, p < 10-92). Using a simulated population, we also found that assortative mating can lead to increases in disease liability over generations and the appearance of "genetic anticipation" in families carrying rare variants. We identified several families in a neurodevelopmental disease cohort where the proband inherited multiple rare variants in disease-associated genes from each of their affected parents. We further identified parental relatedness as a risk factor for neurodevelopmental disorders through its inverse relationship with variant pathogenicity and propose that parental relatedness modulates disease risk by increasing genome-wide homozygosity in children (R = 0.05-0.26, p < 0.05). Our results highlight the utility of assessing parent phenotypes and genotypes toward predicting features in children who carry rare variably expressive variants and implicate assortative mating as a risk factor for increased disease severity in these families.

Liability-scale heritability estimation for biobank studies of low-prevalence disease.

Theory for liability-scale models of the underlying genetic basis of complex disease provides an important way to interpret, compare, and understand results generated from biological studies. In particular, through estimation of the liability-scale heritability (LSH), liability models facilitate an understanding and comparison of the relative importance of genetic and environmental risk factors that shape different clinically important disease outcomes. Increasingly, large-scale biobank studies that link genetic information to electronic health records, containing hundreds of disease diagnosis indicators that mostly occur infrequently within the sample, are becoming available. Here, we propose an extension of the existing liability-scale model theory suitable for estimating LSH in biobank studies of low-prevalence disease. In a simulation study, we find that our derived expression yields lower mean square error (MSE) and is less sensitive to prevalence misspecification as compared to previous transformations for diseases with ≤2% population prevalence and LSH of ≤0.45, especially if the biobank sample prevalence is less than that of the wider population. Applying our expression to 13 diagnostic outcomes of ≤3% prevalence in the UK Biobank study revealed important differences in LSH obtained from the different theoretical expressions that impact the conclusions made when comparing LSH across disease outcomes. This demonstrates the importance of careful consideration for estimation and prediction of low-prevalence disease outcomes and facilitates improved inference of the underlying genetic basis of ≤2% population prevalence diseases, especially where biobank sample ascertainment results in a healthier sample population.

Accounting for age of onset and family history improves power in genome-wide association studies.

Genome-wide association studies (GWASs) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age of onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here, we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), which jointly accounts for age of onset and sex as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields statistically significant power gains over LT-FH and large power gains over genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data and to mortality in the UK Biobank and found 20 genome-wide significant associations with LT-FH++, compared to ten for LT-FH and eight for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.

Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study.

BACKGROUND: Adverse pregnancy outcomes (APO) may unmask or exacerbate a woman's underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls). METHODS: We studied up to 83,969‬ women (and up to 55,568‬ male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967-2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10-8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis. RESULTS: One standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05-1.10), pre-eclampsia (OR 1.08, 95% CI 1.05-1.11), and small for gestational age (OR 1.04, 95% CI 1.01-1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96-1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98-1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners' GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99-1.05), but not with other APOs. CONCLUSIONS: Hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.

Heritability of cancers in Japanese population: Estimation from recent cohort data.

Cancers are genetically categorized into common diseases showing a so-called multifactorial inheritance except for rare familial cancers. And as a measure to estimate the strength of genetic factors in the multifactorial diseases, heritability (h2) is generally used. However, there have been few reports on the estimation of heritability for cancers. We calculated the heritability from the incidence in subject population and the familial recurrence rate in first-degree relatives of the affected for cancers quoting the data from a large-scale prospective cohort study by Hidaka et al. published in 2020. This is the first report for heritability of any cancers in Japanese population. The results showed that heritability of overall cancers in Japanese population is 0.064, which is much lower than Nordic population reported by Mucci et al. that was 0.33. For individual cancers, stomach cancer (h2 = 0.14), colorectum cancer (0.006), lung cancer (0.08) and uterine cancer (0.16) accounted for half of the total patients, and each heritability tends to be lower than previously reported for the European descent. The results of this study suggest that heritability of cancers varies greatly by ethnicity. And these results should be important in terms of cancer genetics and in the genetic counseling for cancers.

Genomic SEM applied to explore etiological divergences in bipolar subtypes.

BACKGROUND: Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed. METHODS: We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes. RESULTS: BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes. CONCLUSIONS: Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.

A Bivariate Twin Study of Lifetime cannabis Initiation and Lifetime Regular Tobacco Smoking Across Three Different Countries.

Regular cigarette smoking and cannabis consumption are strongly positively related to each other, yet few studies explore their underlying variation and covariation. We evaluated the genetic and environmental decomposition of variance and covariance of these two traits in twin data from three countries with different social norms and legislation. Data from the Netherlands Twin Register, FinnTwin12/16, and the Minnesota Center for Twin Family Research (total N = 21,617) were analyzed in bivariate threshold models of lifetime regular smoking initiation (RSI) and lifetime cannabis initiation (CI). We ran unstratified models and models stratified by sex and country. Prevalence of RSI was lowest in the Netherlands and prevalence of CI was highest in Minnesota. In the unstratified model, genetic (A) and common environmental factors (C) contributed substantially to the liabilities of RSI (A = 0.47, C = 0.34) and CI (A = 0.28, C = 0.51). The two liabilities were significantly phenotypically (rP = 0.56), genetically (rA = 0.74), and environmentally correlated in the unstratified model (rC = 0.47and rE = 0.48, representing correlations between common and unique environmental factors). The magnitude of phenotypic correlation between liabilities varied by country but not sex (Minnesota rP ~ 0.70, Netherlands rP ~ 0.59, Finland rP ~ 0.45). Comparisons of decomposed correlations could not be reliably tested in the stratified models. The prevalence and association of RSI and CI vary by sex and country. These two behaviors are correlated because there is genetic and environmental overlap between their underlying latent liabilities. There is heterogeneity in the genetic architecture of these traits across country.

Do traumatic events and substance use co-occur during adolescence? Testing three causal etiologic hypotheses.

BACKGROUND: Why do potentially traumatic events (PTEs) and substance use (SU) so commonly co-occur during adolescence? Causal hypotheses developed from the study of posttraumatic stress disorder (PTSD) and substance use disorder (SUD) among adults have not yet been subject to rigorous theoretical analysis or empirical tests among adolescents with the precursors to these disorders: PTEs and SU. Establishing causality demands accounting for various factors (e.g. genetics, parent education, race/ethnicity) that distinguish youth endorsing PTEs and SU from those who do not, a step often overlooked in previous research. METHODS: We leveraged nationwide data from a sociodemographically diverse sample of youth (N = 11,468) in the Adolescent Brain and Cognitive Development Study. PTEs and substance use prevalence were assessed annually. To account for the many pre-existing differences between youth with and without PTE/SU (i.e. confounding bias) and provide rigorous tests of causal hypotheses, we linked within-person changes in PTEs and SU (alcohol, cannabis, nicotine) across repeated measurements and adjusted for time-varying factors (e.g. age, internalizing symptoms, externalizing symptoms, and friends' use of substances). RESULTS: Before adjusting for confounding using within-person modeling, PTEs and SU exhibited significant concurrent associations (ßs = .46-1.26, ps < .05) and PTEs prospectively predicted greater SU (ßs = .55-1.43, ps < .05) but not vice versa. After adjustment for confounding, the PTEs exhibited significant concurrent associations for alcohol (ßs = .14-.23, ps < .05) and nicotine (ßs = .16, ps < .05) but not cannabis (ßs = -.01, ps > .05) and PTEs prospectively predicted greater SU (ßs = .28-.55, ps > .05) but not vice versa. CONCLUSIONS: When tested rigorously in a nationwide sample of adolescents, we find support for a model in which PTEs are followed by SU but not for a model in which SU is followed by PTEs. Explanations for why PTSD and SUD co-occur in adults may need further theoretical analysis and adaptation before extension to adolescents.

Time to first report of signs of nicotine dependence among youth who use e-cigarettes and cigarettes in the United States: A nationally representative cohort study, findings from the Population Assessment of Tobacco and Health, 2013-2019.

OBJECTIVE: To determine the time to first report of signs of nicotine dependence among youth exclusive e-cigarette users and compare this time to that for exclusive cigarette users. METHODS: Secondary analysis of data (Waves 1-5; 2013-2019) from the Population Assessment of Tobacco and Health was conducted. Youth never tobacco users in the United States who reported exclusive past-30-day (P30D) e-cigarette or cigarette use (n = 2940, N = 5,391,642) in at least one wave were included in the current analysis. Survival analysis was used to estimate the time to the first report of three nicotine dependence indicators (i.e., "use within 30 minutes of waking"; "cravings" and "really needing to use") following the first report of P30D use. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). RESULTS: There were no significant differences in the time to first report of "use within 30 minutes of waking" (aHR = 1.1, 95% CI = 0.87-1.40) and "cravings" (aHR = 1.09, 95% CI = 0.81-1.47) between exclusive P30D e-cigarette use and exclusive P30D cigarette use. However, compared to exclusive P30D e-cigarette use, the hazard of first reporting "really needing to use" tobacco was 39% (aHR 1.39; 95% CI: 1.05-1.84) times higher for those who reported exclusive P30D cigarette use after controlling for covariates. CONCLUSION: Compared to exclusive P30D cigarette use, no differences in the time to first report of signs of nicotine dependence ("use within 30 minutes" and "cravings") were observed among exclusive P30D e-cigarette users. Policymakers and regulatory agencies should consider this evidence when assessing the abuse liability of e-cigarette products.

Artificial intelligence in healthcare: why not apply the medico-legal method starting with the Collingridge dilemma?

Technology has greatly influenced and radically changed human life, from communication to creativity and from productivity to entertainment. The authors, starting from considerations concerning the implementation of new technologies with a strong impact on people's everyday lives, take up Collingridge's dilemma and relate it to the application of AI in healthcare. Collingridge's dilemma is an ethical and epistemological problem concerning the relationship between technology and society which involves two approaches. The proactive approach and socio-technological experimentation taken into account in the dilemma are discussed, the former taking health technology assessment (HTA) processes as a reference and the latter the AI studies conducted so far. As a possible prevention of the critical issues raised, the use of the medico-legal method is proposed, which classically lies between the prevention of possible adverse events and the reconstruction of how these occurred.The authors believe that this methodology, adopted as a European guideline in the medico-legal field for the assessment of medical liability, can be adapted to AI applied to the healthcare scenario and used for the assessment of liability issues. The topic deserves further investigation and will certainly be taken into consideration as a possible key to future scenarios.

Alcohol use disorder and risk of specific methods of suicide death in a national cohort.

INTRODUCTION: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. METHODS: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932-1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. RESULTS: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006-1.040 for females, 0.046-0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). CONCLUSIONS: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.

Examining the predictive utility of behavioral economic demand indices and subjective effects on the actualized reinforcing value of menthol cigarettes and potential alternatives.

INTRODUCTION: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs. METHODS: Eighty participants who typically smoked menthol cigarettes completed this clinical lab study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following one-week of substituting their preferred MCA for their UBMC, participants completed a 90-min concurrent-choice self-administration task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the lab with subsequent response effort for UBMCs on the concurrent-choice task. RESULTS: Three demand indices for UBMC were positively associated with UBMC response effort: Essential Value (EV; p=.02), Omax (p=.02), and breakpoint (p=.04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p=.03), Pmax (p=.04), Omax (p=.03), and breakpoint (p=.03). Subjective effects captured by the mCEQ were not associated with response effort. CONCLUSIONS: Demand indices reflecting Persistence (i.e., sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (i.e., addiction potential) of combustible tobacco products similar to the longer self-administration task. IMPLICATIONS: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of cigarette purchase task efficiently capture information on the relative reinforcing value of usual brand menthol cigarettes and plausible alternative tobacco products, similar to a 90-min in-laboratory self-administration task.

Towards health with justice: making the tobacco industry accountable through administrative liability.

For many decades, the transnational tobacco industry has evaded the consequences of harming people and the planet. Despite selling a deadly product, it has continued to remain one of the most profitable industries in the world, now venturing into 'wellness and pharmaceutical' businesses as part of its diversification strategy. Meanwhile, efforts to make the tobacco industry pay through court systems have not progressed due to the inherent challenges within the judicial systems in most countries. This paper explores mechanisms for ensuring accountability through administrative liability, including the use of compensation mechanisms and adjudicatory bodies. Such mechanisms operationalise vital principles and practices derived from international law, such as the imposition of effective, proportionate, and dissuasive non-criminal sanctions, victims' right to compensation, and 'polluter pays' principles. Measures such as taxation, surcharges, penalties, financial guarantees or insurance, along with the establishment of adjudicatory bodies and trust funds, are discussed. In order to hold the tobacco industry to account for the wide range of harms caused by its products and its misconduct; policies on 'liability' must clearly articulate how the industry will compensate for past and future harms in a manner that deters it from causing further damage.

Behind the mask: a critical perspective on the ethical, moral, and legal implications of AI in ophthalmology.

PURPOSE: This narrative review aims to provide an overview of the dangers, controversial aspects, and implications of artificial intelligence (AI) use in ophthalmology and other medical-related fields. METHODS: We conducted a decade-long comprehensive search (January 2013-May 2023) of both academic and grey literature, focusing on the application of AI in ophthalmology and healthcare. This search included key web-based academic databases, non-traditional sources, and targeted searches of specific organizations and institutions. We reviewed and selected documents for relevance to AI, healthcare, ethics, and guidelines, aiming for a critical analysis of ethical, moral, and legal implications of AI in healthcare. RESULTS: Six main issues were identified, analyzed, and discussed. These include bias and clinical safety, cybersecurity, health data and AI algorithm ownership, the "black-box" problem, medical liability, and the risk of widening inequality in healthcare. CONCLUSION: Solutions to address these issues include collecting high-quality data of the target population, incorporating stronger security measures, using explainable AI algorithms and ensemble methods, and making AI-based solutions accessible to everyone. With careful oversight and regulation, AI-based systems can be used to supplement physician decision-making and improve patient care and outcomes.

Analysis of the characteristics, efficiency, and influencing factors of third-party mediation mechanisms for resolving medical disputes in public hospitals in China.

BACKGROUND: Medical disputes, which are prevalent in China, are a growing global public health problem. The Chinese government has proposed third-party mediation (TPM) to resolve this issue. However, the characteristics, efficiency, and influencing factors of TPM in resolving medical disputes in public hospitals in China have yet to be determined. METHODS: We conducted a systematic study using TPM records from medical disputes in Gansu Province in China from 2014 to 2019. A χ2 test was used to compare differences between groups, and binary logistic analysis was performed to determine the factors influencing the choice of TPM for resolving medical disputes. RESULTS: We analyzed 5,948 TPM records of medical disputes in Gansu Province in China. The number of medical disputes and the amount of compensation awarded in public hospitals in the Gansu Province increased annually from 2014 to 2019, with most of the disputes occurring in secondary and tertiary hospitals. Approximately 89.01% of the medical disputes were handled by TPM; the average compensation amount with TPM was Chinese Yuan (CNY) 48,688.73, significantly less than that awarded via court judgment and judicial mediation. TPM was more likely to succeed in settling medical disputes in the < CNY10,000 compensation group than in the no-compensation group (odds ratio [OR] = 3.14, 95% confidence interval [CI] 1.53-6.45). However, as the compensation amount increased, the likelihood of choosing TPM decreased significantly. Moreover, TPM was less likely to be chosen when medical disputes did not involve death (OR = 0.49, 95% CI 0.36-0.45) or when no-fault liability was determined (vs. medical accidents; OR = 0.37, 95% CI 0.20-0.67). CONCLUSION: Our findings demonstrate that TPM mechanisms play a positive role in efficiently reducing compensation amounts and increasing medical dispute resolution rates which was the main settlement method in resolving medical disputes in public hospitals of Gansu Province in China. TPM could help greatly reduce conflicts between doctors and patients, avoid litigation, and save time and costs for both parties. Moreover, compensation amounts, non-fatal outcomes, and no-fault liability determinations influence the choice of TPM for settling medical disputes.

Risk management and empirical study of the doctor-patient relationship: based on 1790 litigation cases of medical damage liability disputes in China.

BACKGROUND: Compensation for medical damage liability disputes (CMDLD) seriously hinders the healthy development of hospitals and undermines the harmony of the doctor-patient relationships (DPR). Risk management in the DPR has become an urgent issue of the day. The study aims to provide a comprehensive description of CMDLD in China and explore its influencing factors, and make corresponding recommendations for the management of risks in the DPR. METHODS: This study extracted data from the China Judgment Online - the official judicial search website with the most comprehensive coverage. Statistical analysis of 1,790 litigation cases of medical damage liability disputes (COMDLD) available from 2015 to 2021. RESULTS: COMDLD generally tended to increase with the year and was unevenly distributed by regions; the compensation rate was 52.46%, the median compensation was 134,900 yuan and the maximum was 2,234,666 yuan; the results of the single factor analysis showed that there were statistically significant differences between the compensation for different years, regions, treatment attributes, and trial procedures (P < 0.05); the correlation analysis showed that types of hospitals were significantly negatively associated with regions (R=-0.082, P < 0.05); trial procedures were significantly negatively correlated with years (R=-0.484, P < 0.001); compensat- ion was significantly positively correlated with years, regions, and treatment attributes (R = 0.098-0.294, P < 0.001) and negatively correlated with trial procedures (R=-0.090, P < 0.01); regression analysis showed that years, treatment attributes, and regions were the main factors affecting the CMDLD (P < 0.05). CONCLUSIONS: Years, regions, treatment attributes, and trial procedures affect the outcome of CMDLD. This paper further puts forward relevant suggestions and countermeasures for the governance of doctor-patient risks based on the empirical results. Including rational allocation of medical resources to narrow the differences between regions; promoting the expansion and sinking of high-quality resources to improve the level of medical services in hospitals at all levels; and developing a third-party negotiation mechanism for medical disputes to reduce the cost of medical litigation.

Treating the innocent victims of trolleys and war.

Both trolleys and war leave innocent victims to suffer death and injury. Trolley problems accounting for the injured, and not only the dead, tease out intuitions about liability that enhance our understanding of the obligation to provide compensation and medical care to civilian victims of war. Like many trolley victims, civilians in war may suffer justifiable, excusable, or negligent harms that demand compensation. Chief among these is collateral harm befalling civilians. Collateral harm is endemic to war and comprises permissible but unavoidable death or injury following necessary and proportionate military operations. Although state armies sometimes offer condolence payments for civilian death, injury, and property loss, they deny liability. Instead, they use compensation to enhance counterinsurgency efforts and assuage feelings of agent regret. As part of the medical rules of eligibility, Coalition forces in Iraq and Afghanistan also provided medical care to victims of collateral harm. However, they denied care to similarly sick or injured civilians. While compensation is often justified to cure the harm civilians suffer, the differential use of medical resources is not. Rather, medical care remains subject to the principle of beneficence and medical need. The duty to provide civilian healthcare in war, particularly in wars of humanitarian intervention, is far-reaching and imposes significant costs that military and medical ethics are yet to recognize.