True Outcome Research Articles

Adaptive Clinical Trial Designs with Surrogates: When Should We Bother?

The success of a new drug is assessed within a clinical trial using a primary endpoint, which is typically the true outcome of interest—for example, overall survival. However, regulators sometimes approve drugs using a surrogate outcome—an intermediate indicator that is faster or easier to measure than the true outcome of interest—for example, progression-free survival—as the primary endpoint when there is demonstrable medical need. Although using a surrogate outcome (instead of the true outcome) as the primary endpoint can substantially speed up clinical trials and lower costs, it can also result in poor drug-approval decisions because the surrogate is not a perfect predictor of the true outcome. In this paper, we propose combining data from both surrogate and true outcomes to improve decision making within a late-phase clinical trial. In contrast to broadly used clinical trial designs that rely on a single primary endpoint, we propose a Bayesian adaptive clinical trial design that simultaneously leverages both observed outcomes to inform trial decisions. We perform comparative statics on the relative benefit of our approach, illustrating the types of diseases and surrogates for which our proposed design is particularly advantageous. Finally, we illustrate our proposed design on metastatic breast cancer. We use a large-scale clinical trial database to construct a Bayesian prior and simulate our design on a subset of clinical trials. We estimate that our design would yield a 16% decrease in trial costs relative to existing clinical trial designs, while maintaining the same Type I/II error rates. This paper was accepted by J. George Shanthikumar, Management Science Special Section on Data-Driven Prescriptive Analytics.

ДВИЖЕНИЕ «ПРАВО И РАЗВИТИЕ» (LAW AND DEVELOPMENT) В СВЕТЕ ПРОТИВОРЕЧИЙ ПРАВОВОЙ РЕЦЕПЦИИ

The western Law and Development movement engaged in legal assistance to the socioeconomic development of the third world states as well as the postsocialist countries by the Western patterns includes two different stages, the first one continues about a decade and a half from the beginning of the 1960s, the second lasts approximately twenty years starting the beginning of the 1990s. The article provides a detailed consideration of the history and the achieved results, the content of the activities as well as the theoretical sources of the movement in the jurisprudence, the sociology and the economics. The Law and Development movement encourages and assists in the legal reception from the Western legal orders. Taking into account the distinction between the political and the doctrinal legal reception, the movement acts within framework of the former because it uses the legal regulations as an instrument for achievement of extra-legal purposes. Informed by this approach, the legislation serves the present-day policy whereas the law, which is a special social regulator establishing freedom in a social life, does not find a proper expression in the legislation, a statute compliant with the law is not the legislator’s reference point. Hence the political legal reception does not contribute to a successful legal development, establishment of legal values and the rule of law. This predetermines a failure of the Law and Development movement as a whole. The true outcome of the movement is an impulse of some kind to the further independent legal development in the interested recipient countries.

Abstract 10397: Prevalence and Outcomes of Primary Cardiomyopathy in Marfan Syndrome

Introduction: Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients developing a secondary, dilated cardiomyopathy from chronic valvular regurgitation. Apart from significant valvular disease, patients with MFS have evidence of systolic dysfunction, suggestive of a primary cardiomyopathy. However, prior cross-sectional studies have been limited by small sample sizes and short durations of follow-up. Our aim was therefore to determine the true prevalence and long-term outcomes of a primary cardiomyopathy in MFS. Methods: We performed a retrospective chart review of all adult patients with a confirmed diagnosis of MFS followed at Stanford Health Care. Those with significant valvular dysfunction (≥moderate aortic or mitral regurgitation), coronary artery disease, or prior cardiac surgery were excluded. Myocardial dysfunction (MD) was defined as a left ventricular ejection fraction (EF) <55%, as assessed by echocardiography or on cardiac MRI. Genetic, sociodemographic, and potential cardiac risk modifiers were also recorded. Results: A total of 753 patients with confirmed MFS were identified and followed over a median of 8 years (IQR 4, 13). Of the initial cohort, 241 patients (47% male, 71% Caucasian) met inclusion criteria and defined the at-risk population. MD was present in 30 patients (12.4%), with a median age of onset at 32 years (IQR 24.5, 44.8), median EF of 50.9% (IQR 48.0, 53.8), and evidence of clinical heart failure (NYHA Class ≥2) in 10% of patients. There was no significant association with the majority of queried sociodemographic and traditional cardiovascular risk variables. MD was more commonly observed in patients with larger aortic root diameters (aortic root ≥ 4.0 cm: AOR=4.2, 95% CI=1.2-15.0, p=0.03); however, corresponding use of goal-directed medical heart failure therapies did not appear to be protective against the development of MD (p=0.5). Conclusions: Even in the absence of significant valvular pathology, MD is prevalent in MFS from a young age, indicative of a primary cardiomyopathy. While dysfunction is often subclinical and mild in nature, it can progress across the lifespan and appears to be refractory to standard medical heart failure therapies.

Disparities between perceived and true outcomes of infants born at 23-25 weeks' gestation.

Decision-making for infants born at 23-25weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25weeks' gestation, and if accuracy had changed over a decade. A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P<0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P<0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25weeks' gestation, which may translate into overly pessimistic counselling of parents.

Implant brand portfolios, the potential for camouflage of data, and the role of the Orthopaedic Data Evaluation Panel in total knee arthroplasty.

Knee arthroplasty surgery is a highly effective treatment for arthritis and disorders of the knee. There are a wide variety of implant brands and types of knee arthroplasty available to surgeons. As a result of a number of highly publicized failures, arthroplasty surgery is highly regulated in the UK and many other countries through national registries, introduced to monitor implant performance, surgeons, and hospitals. With time, the options available within many brand portfolios have grown, with alternative tibial or femoral components, tibial insert materials, or shapes and patella resurfacings. In this study we have investigated the effect of the expansion of implant brand portfolios and where there may be a lack of transparency around a brand name. We also aimed to establish the potential numbers of compatible implant construct combinations. Hypothetical implant brand portfolios were proposed, and the number of compatible implant construct combinations was calculated. A simple knee portfolio with cemented cruciate-retaining (CR) and posterior-stabilized (PS) components, with and without a patella, has four combinations. If there are two options available for each component, the numbers double for each option, resulting in 32 combinations. The effect of adding a third option multiplies the number by 1.3. Introducing compatible uncemented options, with the effect of hybrids, multiplies the number by 4. An implant portfolio with two femoral components (both in CR and PS), with two insert options and a patella, all in cemented and uncemented versions leads to 192 possible compatible implant construct combinations. There are implant brands available to surgeons with many more than two options. This study demonstrates that the addition of multiple variants within a knee brand portfolio leads to a large number (many hundreds) of compatible implant construct combinations. Revision rates of implant combinations are not currently reviewed at this level of granularity, leading to the risk of camouflage of true outcomes. Cite this article: Bone Joint J2021;103-B(10):1555-1560.

Incorporating baseline covariates to validate surrogate endpoints with a constant biomarker under control arm.

A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential outcomes. The causal association paradigm assesses the relationship of the treatment effect on the surrogate with the treatment effect on the true endpoint. Using the principal surrogacy criteria, we utilize the joint conditional distribution of the potential outcomes T, given the potential outcomes S. In particular, our setting of interest allows us to assume the surrogate under the placebo, , is zero-valued, and we incorporate baseline covariates in the setting of normally distributed endpoints. We develop Bayesian methods to incorporate conditional independence and other modeling assumptions and explore their impact on the assessment of surrogacy. We demonstrate our approach via simulation and data that mimics an ongoing study of a muscular dystrophy gene therapy.

Exploring the Relationship between Saber Pro Test Outcomes and Student Teacher Characteristics in Colombia: Recommendations for Improving Bachelor’s Degree Education

This explanatory sequential mixed methods study explores the perceptions of academic and administrative managers responsible for teacher training at a public university in Colombia, as well as their views on improving such training after learning about the performance of teachers student teachers in the 2019 Saber Pro test, the differences in their test scores, and the relationships and statistical correlations between these outcomes and the students’ personal, family, socioeconomic and academic characteristics. Our findings show significant differences in the student teachers’ mean scores and performance when data are grouped according to personal, socioeconomic and academic conditions; a significant relationship between performance and student teacher characteristics; and correlations between critical reading scores and the other competencies assessed. Our data also highlight the lack of knowledge among academic and administrative managers about students’ life circumstances and the diversity of factors that may impact their performance; the importance of correlational data; the difference between expected and true outcomes; the inequity under which students seem to pursue their education; the limitations in access to resources; the training required for teachers to be able to analyze quantitative data and use specific software; the impact of teachers’ critical reading skills on student outcomes; the importance of data-driven decision-making; and the need for teachers to engage in quantitative research practices.

List-Decodable Coded Computing: Breaking the Adversarial Toleration Barrier

We consider the problem of coded computing, where a computational task is performed in a distributed fashion in the presence of adversarial workers. We propose techniques to break the adversarial toleration threshold barrier previously known in coded computing. More specifically, we leverage list-decoding techniques for folded Reed-Solomon codes and propose novel algorithms to recover the correct codeword using side information. In the coded computing setting, we show how the master node can perform certain carefully designed extra computations to obtain the side information. The workload of computing this side information is negligible compared to the computations done by each worker. This side information is then utilized to prune the output of the list decoder and uniquely recover the true outcome. We further propose folded Lagrange coded computing (FLCC) to incorporate the developed techniques into a specific coded computing setting. Our results show that FLCC outperforms LCC by breaking the barrier on the number of adversaries that can be tolerated. In particular, the corresponding threshold in FLCC is improved by a factor of two asymptotically compared to that of LCC.

How Different Motivations for Making Informal Out-Of-Pocket Payments Vary in Their Influence on Users' Satisfaction with Healthcare, Local and National Government, and Satisfaction with Life?

Background The dominant view in the literature is that informal payments in healthcare universally are a negative phenomenon. By contrast, we theorize that the motivation healthcare users for making informal payments (IP) can be classified into three categories: (1) a cultural norm, (2) “grease the wheels” payments if users offered to pay to get better services, and (3) “sand the wheels” payments if users were asked to pay by healthcare personnel or felt that payments were expected. We further hypothesize that these three categories of payments are differently associated with a user's outcomes, namely, satisfaction with healthcare, local and national government, satisfaction with life, and satisfaction with life of children in the future. Methods We used microdata from the 2016 Life-in-Transition survey. Multivariate regression analysis is used to quantify relationships between these categories of payments and users' outcomes. Results Payments that are the result of cultural norms are associated with better outcomes. On the contrary, “sand the wheel” payments are associated with worse outcomes. We find no association between making “grease the wheels” payments and outcomes. Conclusions This is the first paper which evaluates association between three different categories of informal payments with a wide range of users' outcomes on a diverse sample of countries. Focusing on informal payments in general, rather than explicitly examining specific motivations, obscures the true outcomes of making IP. It is important to distinguish between three different motivations for informal payment, namely, cultural norms, “grease the wheels,” and “sand the wheels” since they have varying associations with user outcomes. From a policy making standpoint, variation in the links between different motivations for making IP and measures of satisfaction suggest that decision-makers should put their primary focus on situations where IP are explicitly asked for or are implied by the situation and that they should differentiate this from cases of gratitude payments. If such measures are not implemented, then policy makers may unintentionally ban the behaviour that is linked with increased satisfaction with healthcare, government, and life (i.e., paying gratitude).

Open Surgical and Endovascular Management of Hepatic Artery Aneurysms: A First Case Series Evaluation Following Updated Societal Guidelines

We reviewed true hepatic artery aneurysm (HAA) management and outcomes from a single academic center over a 20-year period. This is the first case series following the recent release of guidelines from the Society for Vascular Surgery (SVS).

Innovating in Circles

Innovations do not emerge in isolation but are at least to some extent recombinations of previously existing building blocks. In this paper, we will build on the recombination processes feature set broadening and deepening to show how individuals innovate with IT. In our understanding, the out-comes of innovative use can be performative (improving existing task performance) or creative (leading to new deliverables). We build on a longitudinal case of stresstracking initially designed to improve meditation, but ultimately increasing work productivity by using the meditation tool in an innovative way. Using a theoretically grounded analysis framework, we were able to derive eight propositions on the attainment of performative and creative outcome of innovative IT use. We postulate that innovation only occurs through repeating cycles of recombination processes. Particularly, we propose that it is instrumental to run through a phase that does not benefit any task-related outcomes to trigger true creative outcomes.

310 Outcomes of a Sleep and Stress-Focused Employee Wellness Program

Abstract Introduction The Sleep More, Stress Less Program (SMSL) is a University of Alabama (UA) employee wellness program designed to help participants implement health behavior changes to improve sleep quality and stress management. Workplace wellness programs offer a win-win for the employee and employer through improved health and reduced absenteeism. However, many programs fail to show effectiveness on health and workplace metrics, even with an increase in targeted health behaviors. This may be due—at least in part—to employee self-selection and data collection limitations. The SMSL program addresses these challenges by recruiting employees experiencing sleep and stress issues and using a rigorous assessment approach that records data on behavior changes, process goals, intermediate mechanisms, and health outcomes. We present findings from the SMSL program evaluation conducted Fall 2020. Methods The SMSL program is delivered online with both synchronous and asynchronous content (videos and exercises). The content combines evidence-based interventions for sleep and stress with the science of behavioral motivation. All adult (19–99 years) UA employees were eligible and recruitment occurred through the WellBama website and employee emails. Employees are encouraged to select programs that match their health issues. Participants complete an online pre-program assessment and track their sleep and stress for one week. Next, participants complete the SMSL educational program over the next three weeks. In the fifth week, participants track their sleep and stress and complete the online post-program assessment. Results 60 of the initial 85 participants completed all assessments (70.5%). Participants were primarily Female (79%) and Caucasian (77%) or Black (15%), and aged 24–68 (m=44) years. Moderate improvements were reported in total sleep time, sleep maintenance, and time to return to sleep after awakening. Similar improvements were observed in stress scores. Qualitative evaluation of participant behavior goals revealed a focus on sleep scheduling, stimulus reduction, and relaxation. Conclusion Employee wellness program evaluation is often affected by selection and measurement bias. The SMSL program targeted individuals experiencing stress and/or sleep problems and measured multiple outcomes to identify benefits over the 5-week program. Other wellness programs would benefit from this approach in order to capture true program outcomes. Support (if any) N/A

In Vitro Splicing Assay Proves the Pathogenicity of Intronic Variants in MRAP

Introduction: Familial glucocorticoid deficiency (FGD) is characterised by isolated glucocorticoid deficiency in a patient who retains normal mineralocorticoid production. FGD causing mutations in the MC2R accessory protein, MRAP, are often splice-site or nonsense mutations resulting in a truncated protein. Many of these mutations occur at the canonical donor splice-site of intron 3, where it has been shown previously that c.106 + 2_3dupTA, for example, results in skipping of the first coding exon with unknown consequences at the protein level. Patients and methods: DNA was isolated from three consanguineous individuals diagnosed with early onset FGD (0 - 13 months) with high ACTH and/or low cortisol levels and underwent whole exome sequencing. The proband in family 1 (P1) presented at 13 months and had a hyperpigmented sibling who died in neonatal period due to adrenal failure. Patient 2 (P2), who also had a family history of adrenal insufficiency, was noted to be hyperpigmented at birth with markedly raised ACTH, patient 3 (P3) was noted to have diffuse hyperpigmentation in the early neonatal period and on formal testing at 16m was found to have low serum cortisol. Variants were confirmed using Sanger sequencing and predicted splice-site mutations were investigated using an in vitro splicing assay. Results: Homozygous mutations in MRAP were identified in all three cases which were heterozygous in their parents. Previously described mutations, c.106 + 1delG (chr21:33671388delG; rs1476574441; CD050155) in P1 and c.106 + 2dupT (Chr21: 33671390_91insT; rs761576317; CI118288) in P2 at the canonical donor splice-site of intron 3, were identified, with the former predicted to destroy the splice site and the latter to weaken it. These mutations in vitro resulted in the complete skipping of exon 3, which contains the translational start site, and presumably result in no protein product. A novel homozygous mutation in intron 4, c.206 + 5G>T; (chr21:33679055G>T rs1064796398) was identified in P3, but was not predicted to alter splicing. In vitro, this mutation negates the canonical donor splice site and creates two different alternative sites, both resulting in frameshifts and predicted early termination of the protein (p.Val44fs*50, p.Pro72fs*90). Conclusion: All mutations reported here are predicted to produce no protein, either because the start site is excluded (for c.106 + 1delG and c.106 + 2dupT) or because the transcripts are likely to undergo nonsense mediated decay (for c.206 + 5G>T), resulting in the early onset FGD seen in the patients. Splice prediction protocols, although effective for variants within 2bp of exon/intron boundaries may not predict the true outcome of a base change whereas the splice assay conclusively revealed the effect of all three variants allowing us to assign pathogenicity to them.

A Bayesian dose-finding design for outcomes evaluated with uncertainty.

In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity. We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity. We assume that for some patients, instead of the usual binary dose-limiting toxicity outcome, we observe a physician-assessed probability of dose-limiting toxicity specific to a given patient. Data augmentation is used to estimate the posterior probabilities of dose-limiting toxicity at each dose level based on both the fully observed and partially observed patient outcomes. A simulation study is used to assess the performance of the design relative to using the continual reassessment method on the true dose-limiting toxicity outcomes (available in simulation setting only) and relative to simple thresholding approaches. Among the designs utilizing the partially observed outcomes, our proposed design has the best overall performance in terms of probability of selecting correct maximum tolerated dose and number of patients treated at the maximum tolerated dose. Incorporating uncertainty in dose-limiting toxicity assessment can improve the performance of the continual reassessment method design.

Course trajectories of anxiety disorders: Results from a 6-year follow-up in a general population study.

Objective:Little is known about the course of anxiety disorders in the general population. This study provides insights into the course of anxiety disorders in the general population taking into account transition to residual symptoms and to other diagnostic categories.Methods:Using data from three waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2; n = 6646), subjects with anxiety disorders (T0; n = 243) were divided into three mutually exclusive course trajectories according to their diagnostic status at 3-year (T1) and 6-year (T2) follow-up: remission group (no disorder at T2), intermittent course group (no disorder at T1 and disorder at T2) and chronic course group (disorder at all measurements). Transition to residual symptoms or other psychopathology were studied. In addition, predictors of course trajectories were assessed.Results:During 6-year follow-up, 77.8% of subjects achieved remission, 14.0% followed an intermittent course and 8.2% a chronic course. Of those in remission, residual anxiety symptoms remained in 46.6%, while 7.9% developed another disorder between T0 and T2. Compared with the remitting group, a chronic course was predicted by not living with a partner, multiple negative life events, neuroticism, lower mental functioning, severity of anxiety symptoms, use of mental health care and medication use.Limitations:The intermittent and chronic course groups were small, limiting statistical power. As a result, certain predictors may not have reached significance.Conclusions:In the general population at 6-year follow-up, 77.8% of subjects with anxiety disorders achieved remission. Because of transition to residual symptoms or another diagnostic category, only 52.4% of those subjects had a true favourable outcome.

Estimation of required sample size for external validation of risk models for binary outcomes.

Risk-prediction models for health outcomes are used in practice as part of clinical decision-making, and it is essential that their performance be externally validated. An important aspect in the design of a validation study is choosing an adequate sample size. In this paper, we investigate the sample size requirements for validation studies with binary outcomes to estimate measures of predictive performance (C-statistic for discrimination and calibration slope and calibration in the large). We aim for sufficient precision in the estimated measures. In addition, we investigate the sample size to achieve sufficient power to detect a difference from a target value. Under normality assumptions on the distribution of the linear predictor, we obtain simple estimators for sample size calculations based on the measures above. Simulation studies show that the estimators perform well for common values of the C-statistic and outcome prevalence when the linear predictor is marginally Normal. Their performance deteriorates only slightly when the normality assumptions are violated. We also propose estimators which do not require normality assumptions but require specification of the marginal distribution of the linear predictor and require the use of numerical integration. These estimators were also seen to perform very well under marginal normality. Our sample size equations require a specified standard error (SE) and the anticipated C-statistic and outcome prevalence. The sample size requirement varies according to the prognostic strength of the model, outcome prevalence, choice of the performance measure and study objective. For example, to achieve an SE < 0.025 for the C-statistic, 60–170 events are required if the true C-statistic and outcome prevalence are between 0.64–0.85 and 0.05–0.3, respectively. For the calibration slope and calibration in the large, achieving SE < 0.15would require 40–280 and 50–100 events, respectively. Our estimators may also be used for survival outcomes when the proportion of censored observations is high.

Rapid and accurate nucleobase detection using FnCas9 and its application in COVID-19 diagnosis

Rapid detection of DNA/RNA pathogenic sequences or variants through point-of-care diagnostics is valuable for accelerated clinical prognosis, as witnessed during the recent COVID-19 outbreak. Traditional methods relying on qPCR or sequencing are tough to implement with limited resources, necessitating the development of accurate and robust alternative strategies. Here, we report FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that utilizes a direct Cas9 based enzymatic readout for detecting nucleobase and nucleotide sequences without trans-cleavage of reporter molecules. We also demonstrate that FELUDA is 100% accurate in detecting single nucleotide variants (SNVs), including heterozygous carriers, and present a simple web-tool JATAYU to aid end-users. FELUDA is semi-quantitative, can adapt to multiple signal detection platforms, and deploy for versatile applications such as molecular diagnosis during infectious disease outbreaks like COVID-19. Employing a lateral flow readout, FELUDA shows 100% sensitivity and 97% specificity across all ranges of viral loads in clinical samples within 1hr. In combination with RT-RPA and a smartphone application True Outcome Predicted via Strip Evaluation (TOPSE), we present a prototype for FELUDA for CoV-2 detection closer to home.

Fragmentation of care in the blunt abdominal trauma patient: Capturing our true outcomes and impact on care.

Trauma care is associated with unplanned readmissions, which may occur at facilities other than the index treatment facility. This "fragmentation of care" may be associated with adverse outcomes. We evaluated a statewide database that includes readmissions to analyze the incidence and impact of FC. The California Office of Statewide Health Planning and Development patient discharge data set was evaluated for calendar years 2016 to 2018. Patients 15 years or older diagnosed with blunt abdominal solid organ injury during the index admission were identified. Readmissions were evaluated postdischarge at 1, 3, and 6 months. Patients readmitted within 6 months to a facility other than the index admission facility (fragmented care [FC]) were compared with those readmitted to their index admission facility (non-FC). Logistic regression modeling was used to evaluate risk of FC. Of the total 1,580 patients, there were 752 FC (47.6%) and 828 (52.4%) non-FC. Readmissions representing FC at months 1, 3, and 6 were 40.3%, 49.3%, and 53.4%, respectively. At index admission, the groups were demographically and clinically similar, with similar rates of abdominal operations and complications. Non-FC patients had a higher rate of abdominal reoperation at readmission (5.8% non-FC vs. 2.9% FC, p = 0.006). In an adjusted model, multiple readmissions (odds ratio [OR] 1.11, p = 0.014), readmission >30 days after index facility discharge (OR, 1.98; p < 0.001), and discharge to a nonmedical facility (OR, 2.46; p < 0.0001) were associated with increased odds of FC. Operative intervention at index admission was associated with lower odds of FC (OR, 0.77; p = 0.039). However, FC was not independently associated with demographic or insurance characteristics. The rate of FC among patients with blunt abdominal injury is high. The risk of FC is mitigated when patients are managed operatively during the index admission. Trauma systems should implement measures to ensure that these patients are followed postdischarge. Prognostic and epidemiological, level III; Care management, level IV.

Putting the family back into work and family research

Celebrating Journal of Vocational Behavior 50th Anniversary Special Issue, we acknowledge in this essay the strides made by work-family researchers in the last 50 years and propose new directions that would stimulate research on the interface of work and family from a vocational and organizational perspectives. The invited paper by Kossek, Perrigino and Gounden Rock (2021) reviews the different paths taken by the work-family and career literatures and suggests concrete ways in which future researchers can integrate work-family and careers perspective theoretically and empirically. In this contribution to Journal of Vocational Behavior 50th Anniversary, we add to Kossek and colleagues call by suggesting research on the interface of work and family should expand its scope by focusing on (a) true family outcomes – those that families, not employers, consider important; (b) family-level outcomes – outcomes that are observed when two or more people interact within the family unit, not just individual outcomes; and (c) the joint effect of work and social policies on work-related family decisions and outcomes – taking into account that families use all available resources available to them, not just those provided by their employer.

Intensive neurorehabilitation for patients with prolonged disorders of consciousness: protocol of a mixed-methods study focusing on outcomes, ethics and impact

BackgroundProlonged disorders of consciousness (PDOC) are amongst the severest sequelae of acquired brain injury. Evidence regarding epidemiology and rehabilitation outcomes is scarce. These knowledge gaps and psychological distress in families of PDOC patients may complicate clinical decision-making. The complex PDOC care and associated moral dilemmas result in high workload in healthcare professionals.Since 2019, all PDOC patients in the Netherlands have access to intensive neurorehabilitation up to 2 years post-injury provided by one rehabilitation center and four specialized nursing homes. Systematic monitoring of quantitative rehabilitation data within this novel chain of care is done in a study called DOCTOR. The optimization of tailored PDOC care, however, demands a better understanding of the impact of PDOC on patients, their families and healthcare professionals and their views on rehabilitation outcomes, end-of-life decisions and quality of dying. The True Outcomes of PDOC (TOPDOC) study aims to gain insight in the qualitative outcomes of PDOC rehabilitation and impact of PDOC on patients, their families and healthcare professionals.MethodsNationwide multicenter prospective cohort study in the settings of early and prolonged intensive neurorehabilitation with a two-year follow-up period, involving three study populations: PDOC patients > 16 years, patients’ family members and healthcare professionals involved in PDOC care. Families’ and healthcare professionals’ views on quality of rehabilitation outcomes, end-of-life decisions and dying will be qualitatively assessed using comprehensive questionnaires and in-depth interviews. Ethical dilemmas will be explored by studying moral deliberations. The impact of providing care to PDOC patients on healthcare professionals will be studied in focus groups.DiscussionTo our knowledge, this is the first nationwide study exploring quality of outcomes, end-of-life decisions and dying in PDOC patients and the impact of PDOC in a novel chain of care spanning the first 24 months post-injury in specialized rehabilitation and nursing home settings.Newly acquired knowledge in TOPDOC concerning quality of outcomes in PDOC rehabilitation, ethical aspects and the impact of PDOC will enrich quantitative epidemiological knowledge and outcomes arising from DOCTOR. Together, these projects will contribute to the optimization of centralized PDOC care providing support to PDOC patients, families and healthcare professionals.