Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives.

CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs). e-CHACRs can be inserted at various genomic locations and carry two or more gRNAs, the first copying the e-CHACR and the second mutating and inactivating the cas9 transgene. Alternatively, ERACRs are inserted at the same genomic location as a gene drive, carrying two gRNAs that cut on either side of the gene drive to excise it. e-CHACRs efficiently inactivate Cas9 and can drive to completion in cage experiments. Similarly, ERACRs, particularly those carrying a recoded cDNA-restoring endogenous gene activity, can drive reliably to fully replace a gene drive. We compare the strengths of these two systems.

Risk-management decision-making data from a community-based sample of racially diverse women at high risk of breast cancer: rationale, methods, and sample characteristics of the Daughter Sister Mother Project survey.

BACKGROUND: To understand the dynamics that limit use of risk-management options by women at high risk of breast cancer, there is a critical need for research that focuses on patient perspectives. Prior research has left important gaps: exclusion of high-risk women not in risk-related clinical care, exclusion of non-white populations, and lack of attention to the decision-making processes that underlie risk-management choices. Our objective was to create a more inclusive dataset to facilitate research to address disparities related to decision making for breast cancer risk management. METHODS: The Daughter Sister Mother Project survey collects comprehensive information about the experiences of women at high risk of breast cancer. We collected novel measures of feelings about and reactions to cancer screenings; knowledge, barriers, and facilitators of risk-management options; beliefs related to cancer risk and risk management; and involvement with loved ones who had cancer. Eligible individuals were non-Hispanic white and non-Hispanic Black adult women who self-identified as having high risk of breast cancer and had no personal history of cancer. Between October 2018 and August 2019, 1053 respondents completed the online survey. Of these, 717 were confirmed through risk prediction modeling to have a lifetime breast cancer risk of ≥ 20%. Sociodemographic characteristics of this sample were compared to those of nationally representative samples of the US population: the 2019 Health Information National Trends Survey and the Pew Research Center report: Jewish Americans in 2020. RESULTS: The sample of 717 women at objectively high risk of breast cancer was largely (95%) recruited from non-clinical sources. Of these respondents, only 31% had seen a genetic counselor, 34% had had genetic testing specific to breast cancer risk, and 35% had seen at least one breast or cancer care specialist. The sample includes 35% Black respondents and 8% with Ashkenazi Jewish ancestry. Although encompassing a substantial range of ages, incomes, and education levels, respondents are overall somewhat younger, higher-income, and more educated than the US population as a whole. CONCLUSIONS: The DSM dataset offers comprehensive data from a community-based, diverse sample of women at high risk of breast cancer. The dataset includes substantial proportions of Black and Ashkenazi Jewish women and women who are not already in clinical care related to their breast cancer risk. This sample will facilitate future studies of risk-management behaviors among women who are and are not receiving high-risk care, and of variations in risk-management experiences across race and ethnicity.

Performance evaluation of predictive models for detecting MMR gene mutations associated with Lynch syndrome in cancer patients in a Chinese cohort in Taiwan.

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan. All patients underwent germline genetic testing and 36 (6.0%) carried a mutation in the MMR genes (MLH1, MSH2, MSH6, and PMS2). All models demonstrated good performance, with area under the receiver operating characteristic curves comparable to Western cohorts: PREMM5 0.80 (95% confidence interval [CI], 0.73-0.88), MMRPro 0.88 (95% CI, 0.82-0.94), MMRPredict 0.82 (95% CI, 0.74-0.90), and Myriad 0.76 (95% CI, 0.67-0.84). Notably, MMRPro exhibited exceptional performance across all subgroups regardless of family history (FH+ 0.88, FH- 0.83), cancer type (CRC 0.84, EC 0.85, OC 1.00), or sex (male 0.83, female 0.90). PREMM5 and MMRPredict had good accuracy in the FH+ subgroup (0.85 and 0.82, respectively) and in CRC patients (0.76 and 0.82, respectively). Using the ratio of observed and predicted mutation rates, MMRPro and PREMM5 had good overall fit, while MMRPredict and Myriad overestimated mutation rates. Risk threshold settings in different models led to different positive predictive values. We suggest a lower threshold (5%) for recommending genetic testing when using MMRPro, and a higher threshold (20%) when using PREMM5 and MMRPredict. Our findings have important implications for personalized mutation risk assessment and counseling on genetic testing.

Factors Influencing Adherence to the Risk Management Program for Women With a Genetic Predisposition to Breast Cancer: Real-World Data from a French Multicenter Program.

BACKGROUND: Risk management programs targeting women with genetic predispositions to breast cancer (BC), eg, BRCA1 and BRCA2, are effective assuming full adherence with the program protocol. However, high risk to BC in women and equal access to care may not result in high and uniform adherence with the program. OBJECTIVE: To elucidate factors influencing adherence with screening program in women with genetic predispositions to BC. MATERIAL AND METHODS: We retrieved data from a multicenter pathogenic-related BC surveillance program across 4 French regions. We used multilevel logistic modeling to analyze factors of adherence with the program, with "on-time" or postponed screening as the dependent variable. RESULTS: Seven hundred and seventy-eight participants were followed for a 4.7-year median. We observed 2796 annual screening rounds and 5.4% postponed rounds with a 6-month margin. Women with prevalent BC and carriers of BRCA1 and BRCA2 mutations did not have on-time annual screenings any more than women low cancer risk. Better adherence was observed with screenings after the 2nd round, with higher total number of rounds. Having one or more recalls was significantly associated with worse adherence. No contextual factors affected adherence. Furthermore, postponed rounds increased between 2018 and 2020 compared to 2015 and 2017. CONCLUSION: Having a higher BC risk status does not result in better adherence to the risk management program. However, factors directly related to screening rounds reduced postponements. Future research should address the benefits of screening-related organizational factors that contribute to adherence improvement.

Acceptability of data linkage to identify women at risk of postnatal complication for the development of digital risk prediction tools and interventions to better optimise postnatal care, a qualitative descriptive study design.

BACKGROUND: Pregnancy acts as a cardiovascular stress test. Although many complications resolve following birth, women with hypertensive disorder of pregnancy have an increased risk of developing cardiovascular disease (CVD) long-term. Monitoring postnatal health can reduce this risk but requires better methods to identity high-risk women for timely interventions. METHODS: Employing a qualitative descriptive study design, focus groups and/or interviews were conducted, separately engaging public contributors and clinical professionals. Diverse participants were recruited through social media convenience sampling. Semi-structured, facilitator-led discussions explored perspectives of current postnatal assessment and attitudes towards linking patient electronic healthcare data to develop digital tools for identifying postpartum women at risk of CVD. Participant perspectives were gathered using post-it notes or a facilitator scribe and analysed thematically. RESULTS: From 27 public and seven clinical contributors, five themes regarding postnatal check expectations versus reality were developed, including 'limited resources', 'low maternal health priority', 'lack of knowledge', 'ineffective systems' and 'new mum syndrome'. Despite some concerns, all supported data linkage to identify women postnatally, targeting intervention to those at greater risk of CVD. Participants outlined potential benefits of digitalisation and risk prediction, highlighting design and communication needs for diverse communities. CONCLUSIONS: Current health system constraints in England contribute to suboptimal postnatal care. Integrating data linkage and improving education on data and digital tools for maternal healthcare shows promise for enhanced monitoring and improved future health. Recognised for streamlining processes and risk prediction, digital tools may enable more person-centred care plans, addressing the gaps in current postnatal care practice.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

AIMS: To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM). METHODS: We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up. A minimum of two studies evaluating the same intervention-outcome combination were needed to conduct meta-analyses, otherwise studies were described narratively. Meta-regression was used to evaluate whether associations varied by additional variables. We assessed risk of bias using the Critical Appraisal Skills Programme checklist. PROSPERO record CRD42018102380. RESULTS: We included 31 studies in the review with a total sample size of 8624 participants, and 26 studies in meta-analyses. Two-thirds of studies followed up participants at 1 year or less. Pharmacological interventions were associated with reduced risk of T2DM (0.80 [95% CI 0.64-1.00], n = 6 studies), as were lifestyle interventions albeit with a smaller effect size (0.88 [95% CI 0.76-1.01], n = 12 studies). Dietary and physical activity interventions were associated with a small reduction in fasting plasma glucose, particularly in longer interventions, but inconsistent effects were seen for other continuous outcomes. CONCLUSIONS: Although possibly due to chance, interventions to reduce hyperglycaemia after GDM may be effective. Future research should improve understanding of how interventions affect glucose control and how to optimise interventions for this population.

Biomathematical modeling of fatigue due to sleep inertia.

Biomathematical models of fatigue capture the physiology of sleep/wake regulation and circadian rhythmicity to predict changes in neurobehavioral functioning over time. We used a biomathematical model of fatigue linked to the adenosinergic neuromodulator/receptor system in the brain as a framework to predict sleep inertia, that is, the transient neurobehavioral impairment experienced immediately after awakening. Based on evidence of an adenosinergic basis for sleep inertia, we expanded the biomathematical model with novel differential equations to predict the propensity for sleep inertia during sleep and its manifestation after awakening. Using datasets from large laboratory studies of sleep loss and circadian misalignment, we calibrated the model by fitting just two new parameters and then validated the model's predictions against independent data. The expanded model was found to predict the magnitude and time course of sleep inertia with generally high accuracy. Analysis of the model's dynamics revealed a bifurcation in the predicted manifestation of sleep inertia in sustained sleep restriction paradigms, which reflects the observed escalation of the magnitude of sleep inertia in scenarios with sleep restriction to less than âˆ¼ 4 h per day. Another emergent property of the model involves a rapid increase in the predicted propensity for sleep inertia in the early part of sleep followed by a gradual decline in the later part of the sleep period, which matches what would be expected based on the adenosinergic regulation of non-rapid eye movement (NREM) sleep and its known influence on sleep inertia. These dynamic behaviors provide confidence in the validity of our approach and underscore the predictive potential of the model. The expanded model provides a useful tool for predicting sleep inertia and managing impairment in 24/7 settings where people may need to perform critical tasks immediately after awakening, such as on-demand operations in safety and security, emergency response, and health care.

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Decision-making for bilateral risk-reducing mastectomy for an increased lifetime breast cancer risk: A qualitative metasynthesis.

OBJECTIVE: Previvor is a term applied to a person with an identified, elevated lifetime cancer risk but without an actual cancer diagnosis. Previvorship entails the selection of risk management strategies. For women with a genetic mutation that increases their predisposition for a breast cancer diagnosis, bilateral risk-reducing mastectomy (BRRM) is the most effective prevention strategy. However, BRRM can change a woman's breast appearance and function. The purpose of this qualitative metasynthesis (QMS) was to better understand the decision-making process for BRRM among previvors. METHODS: A theory-generating QMS approach was used to analyze and synthesize qualitative findings. Research reports were considered for inclusion if: (1) women over 18 years of age possessed a genetic mutation increasing lifetime breast cancer risk or a strong family history of breast cancer; (2) the sample was considering, or had completed, BRRM; (3) the results reported qualitative findings. Exclusion criteria were male gender, personal history of breast cancer, and research reports which did not separate findings based on cancer diagnosis and/or risk-reduction surgery. RESULTS: A theory and corresponding model emerged, comprised of seven themes addressing the decision-making process for or against BRRM. While some factors to decision-making were decisive for surgery, others were more indefinite and contributed to women changing, processing, or suspending their decision-making for a period of time. CONCLUSIONS: Regardless of the decision previvors make about BRRM, physical and psychosocial well-being should be considered and promoted through shared decision-making in the clinical setting.

Advanced prescription of injectable anticancer drugs: Safety assessment in a European Comprehensive Cancer Centre using the risk matrix approach.

AIMS: The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. METHODS: An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. RESULTS: During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. CONCLUSIONS: Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data.

A model for managing quality control for a network of clinical chemistry instruments measuring the same analyte.

OBJECTIVES: Monitoring quality control for a laboratory or network with multiple instruments measuring the same analyte is challenging. We present a retrospective assessment of a method to detect medically significant out-of-control error conditions across a group of instruments measuring the same analyte. The purpose of the model was to ensure that results from any of several instruments measuring the same analytes in a laboratory or a network of laboratories provide comparable results and reduce patient risk. Limited literature has described how to manage QC in these very common situations. METHODS: Single Levey-Jennings control charts were designed using peer group target mean and control limits for five common clinical chemistry analytes in a network of eight analyzers in two different geographical sites. The QC rules used were 13s/22s/R4s, with the mean being a peer group mean derived from a large population of the same instrument and the same QC batch mean and a group CV. The peer group data used to set the target means and limits were from a quality assurance program supplied by the instrument supplier. Both statistical and clinical assessments of significance were used to evaluate QC failure. Instrument bias was continually monitored. RESULTS: It was demonstrated that the biases of each instrument were not statistically or clinically different compared to the peer group's average over six months from February 2023 until July 2023. Over this period, the error rate determined by the QC model was consistent with statistical expectations for the 13s/22s/R4s rule. There were no external quality assurance failures, and no detected error exceeded the TEa (medical impact). Thus, the combined statistical/clinical assessment reduced unnecessary recalibrations and the need to amend results. CONCLUSIONS: This paper describes the successful implementation of a quality control model for monitoring a network of instruments, measuring the same analytes and using externally provided quality control targets. The model continually assesses individual instrument bias and imprecision while ensuring all instruments in the network meet clinical goals for quality. The focus of this approach is on detecting medically significant out-of-control error conditions.

QC Constellation: a cutting-edge solution for risk and patient-based quality control in clinical laboratories.

OBJECTIVES: Clinical laboratories face limitations in implementing advanced quality control (QC) methods with existing systems. This study aimed to develop a web-based application to addresses this gap, and improve QC practices. METHODS: QC Constellation, a web application built using Python 3.11, integrates various statistical QC modules. These include Levey-Jennings charts with Westgard rules, sigma-metric calculations, exponentially weighted moving average (EWMA) and cumulative sum (CUSUM) charts, and method decision charts. Additionally, it offers a risk-based QC section and a patient-based QC module aligning with modern QC practices. The codes and the web application links for QC Constellation were shared at https://github.com/hikmetc/QC_Constellation, and http://qcconstellation.com, respectively. RESULTS: Using synthetic data, QC Constellation demonstrated effective implementation of Levey-Jennings charts with user-friendly features like checkboxes for Westgard rules and customizable moving averages graphs. Sigma-metric calculations for hypothetical performance values of serum total cholesterol were successfully performed using allowable total error and maximum allowable measurement uncertainty goals, and displayed on method decision charts. The utility of the risk-based QC module was exemplified by assessing QC plans for serum total cholesterol, showcasing the application's capability in calculating risk-based QC parameters including maximum unreliable final patient results, risk management index, and maximum run size and offering risk-based QC recommendations. Similarly, the patient-based QC and optimization modules were demonstrated using simulated sodium results. CONCLUSIONS: In conclusion, QC Constellation emerges as a pivotal tool for laboratory professionals, streamlining the management of quality control and analytical performance monitoring, while enhancing patient safety through optimized QC processes.

The 2023 report of the MJA-Lancet Countdown on health and climate change: sustainability needed in Australia's health care sector.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020, 2021 and 2022. It examines five broad domains: health hazards, exposures and impacts; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the sixth report of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Our results highlight the health and economic costs of inaction on health and climate change. A series of major flood events across the four eastern states of Australia in 2022 was the main contributor to insured losses from climate-related catastrophes of $7.168 billion - the highest amount on record. The floods also directly caused 23 deaths and resulted in the displacement of tens of thousands of people. High red meat and processed meat consumption and insufficient consumption of fruit and vegetables accounted for about half of the 87 166 diet-related deaths in Australia in 2021. Correction of this imbalance would both save lives and reduce the heavy carbon footprint associated with meat production. We find signs of progress on health and climate change. Importantly, the Australian Government released Australia's first National Health and Climate Strategy, and the Government of Western Australia is preparing a Health Sector Adaptation Plan. We also find increasing action on, and engagement with, health and climate change at a community level, with the number of electric vehicle sales almost doubling in 2022 compared with 2021, and with a 65% increase in coverage of health and climate change in the media in 2022 compared with 2021. Overall, the urgency of substantial enhancements in Australia's mitigation and adaptation responses to the enormous health and climate change challenge cannot be overstated. Australia's energy system, and its health care sector, currently emit an unreasonable and unjust proportion of greenhouse gases into the atmosphere. As the Lancet Countdown enters its second and most critical phase in the leadup to 2030, the depth and breadth of our assessment of health and climate change will be augmented to increasingly examine Australia in its regional context, and to better measure and track key issues in Australia such as mental health and Aboriginal and Torres Strait Islander health and wellbeing.

Studying the Impact of European Union Regulatory Interventions for Minimising Risks From Medicines: Lessons Learnt and Recommendations.

PURPOSE: The European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) launched a strategy to examine the public health impact of major regulatory interventions aimed at minimising risks of medicinal products. We conducted a lessons learnt analysis of impact studies completed between 2015 and 2023. METHODS: We surveyed PRAC Sponsors and (Co-)Rapporteurs involved in the evaluation of 12 impact studies (10 commissioned by EMA and 2 conducted collaboratively by Member States) to explore how these support regulatory decision-making. Questions covered achievement of study objectives, risk minimisation effectiveness, added value for regulatory decision-making, and recommendations for future impact studies. Themes were generated using thematic content analysis. RESULTS: Survey responses from 15 PRAC Sponsors and (Co-)Rapporteurs from 10 European Union Member States were included in the analysis. Among four cross-sectional surveys and eight drug utilisation studies, 50% achieved all objectives, the other studies partially due to limitations. Two studies concluded that risk minimisation measures were overall effective, two were effective with variation across countries, two were partially effective and four studies showed limited effectiveness. Two studies were deemed inconclusive due to limitations. The reasons for the limited effectiveness of risk minimisation may be explored using mixed-method approaches. Assessment of study feasibility and a priori discussion of effectiveness measurements is important. CONCLUSION: Despite limitations, impact research adds value to regulatory decision-making by addressing knowledge gaps and providing additional information on unintended consequences of regulatory interventions. Our recommendations will help to improve planning, conducting and interpretating future impact studies.

Mapping study for health emergency and disaster risk management competencies and curricula: literature review and cross-sectional survey.

BACKGROUND: With the increasing threat of hazardous events at local, national, and global levels, an effective workforce for health emergency and disaster risk management (Health EDRM) in local, national, and international communities is urgently needed. However, there are no universally accepted competencies and curricula for Health EDRM. This study aimed to identify Health EDRM competencies and curricula worldwide using literature reviews and a cross-sectional survey. METHODS: Literature reviews in English and Japanese languages were performed. We searched MEDLINE, EMBASE, CINAHL (English), and the ICHUSHI (Japanese) databases for journal articles published between 1990 and 2020. Subsequently, a cross-sectional survey was sent to WHO Health EDRM Research Network members and other recommended experts in October 2021 to identify competency models and curricula not specified in the literature search. RESULTS: Nineteen studies from the searches were found to be relevant to Health EDRM competencies and curricula. Most of the competency models and curricula were from the US. The domains included knowledge and skills, emergency response systems (including incident management principles), communications, critical thinking, ethical and legal aspects, and managerial and leadership skills. The cross-sectional survey received 65 responses with an estimated response rate of 25%. Twenty-one competency models and 20 curricula for managers and frontline personnel were analyzed; managers' decision-making and leadership skills were considered essential. CONCLUSION: An increased focus on decision-making and leadership skills should be included in Health EDRM competencies and curricula to strengthen the health workforce.

The Total Worker Health® (TWH) approach: a systematic review of its application in different occupational settings.

BACKGROUND: The National Institute for Occupational Safety and Health (NIOSH), in 2011, developed the "Total Worker Health®" (TWH) as a holistic approach to protect and promote the workers' safety, health, and well-being. After over ten years from the TWH development, the aim of the present systematic review is to provide a comprehensive overview of the worldwide TWH initiatives. METHODS: PubMed, Scopus and ISI Web of Science were searched for TWH studies published up to the 31st of July 2023, and 43 investigations could be included. The review was registered on the International prospective register of systematic reviews PROSPERO with the reference number CRD42023416972. RESULTS: Issues that emerged as relevant for the TWH operationalization were the awareness about the TWH approach and fundamentals, the leadership commitment, and a participatory engagement of the workforce: these aspects all contributed to acceptable and effective setting oriented TWH plans, specifically tailored on the peculiarities of the workplace, including small enterprises and multiemployer worksites. Evaluation and continual improvement were reported as fundamental for the successful implementation of TWH initiatives. Limited resources for safety and health initiatives, in terms of time, people, and funds, together with difficulties in the identification of safety and health priorities and a poor participatory culture were recognized as obstacles to the TWH application. Training resulted the core component of the TWH leadership and workforce preparedness, with beneficial results in terms of safety culture and adoption of preventive measures. CONCLUSIONS: Although interesting aspects emerged from our review, future longitudinal investigations should confirm the effectiveness, easy integration, and long-term sustainability of TWH models in different workplaces, in order to effectively support safe and health-enhancing works able to improve innovation and productivity.

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.

Seeking systems-based facilitators of safety and healthcare resilience: a thematic review of incident reports.

Patient safety incident reports are a key source of safety intelligence. This study aimed to explore whether information contained in such reports can elicit facilitators of safety, including responding, anticipating, monitoring, learning, and other mechanisms by which safety is maintained. The review further explored whether, if found, this information could be used to inform safety interventions. Anonymized incident reports submitted between August and October 2020 were obtained from two large teaching hospitals. The Systems Engineering Initiative for Patient Safety (SEIPS) tool and the resilience potentials (responding, anticipating, monitoring, and learning) frameworks guided thematic analysis. SEIPS was used to explore the components of people, tools, tasks, and environments, as well as the interactions between them, which contribute to safety. The resilience potentials provided insight into healthcare resilience at individual, team, and organizational levels. Sixty incident reports were analysed. These included descriptions of all the SEIPS framework components. People used tools such as electronic prescribing systems to perform tasks within different healthcare environments that facilitated safety. All four resilient capacities were identified, with mostly individuals and teams responding to events; however, monitoring, anticipation, and learning were described for individuals, teams, and organizations. Incident reports contain information about safety practices, much of which is not identified by traditional approaches such as root cause analysis. This information can be used to enhance safety enablers and encourage greater proactive anticipation and system-level learning.

Experiences of hereditary cancer care among transgender and gender diverse people: "It's gender. It's cancer risk it's everything".

Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross-sectional qualitative study. Nineteen semi-structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender-affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk-reducing mastectomy and top surgery, exploring co-emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision-making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.

Analysis of adverse events related to extracorporeal membrane oxygenation from a nationwide database of patient-safety accidents in Japan.

Although adverse events related to extracorporeal membrane oxygenation have been reported, epidemiological data on life-threatening events are insufficient to study the causes of such adverse events. Data from the Japan Council for Quality Health Care database were retrospectively analyzed. The adverse events extracted from this national database included events associated with extracorporeal membrane oxygenation reported between January 2010 and December 2021. We identified 178 adverse events related to extracorporeal membrane oxygenation. At least 41 (23%) and 47 (26%) accidents resulted in death and residual disability, respectively. The most common adverse events were cannula malposition (28%), decannulation (19%), and bleeding (15%). Among patients with cannula malposition, 38% did not undergo fluoroscopy-guided or ultrasound-guided cannulation, 54% required surgical treatment, and 18% required trans-arterial embolization. In this epidemiological study in Japan, 23% of the adverse events related to extracorporeal membrane oxygenation had fatal outcomes. Our findings suggest that a training system for cannulation techniques may be needed, and hospitals offering extracorporeal membrane oxygenation should perform emergency surgeries.