Gaussian Copula Regression in the Presence of Thresholds

Park and Gupta’s (2012) introduction of the Gaussian Copula (GC) approach to deal with endogeneity has made a significant impact on empirical marketing research with many papers using this approach. Recent studies have however started to explore and examine the approach and its underlying assumptions more closely, resulting in a more critical picture of it. A particular challenge is the non-testable assumption that the dependency structure between the endogenous regressor and the error term should be described by a Gaussian copula. In general, there exists a limited understanding of what this assumption implies, what causes its violation, and potential remedies. Our study addresses this explicitly. We provide a detailed discussion of the dependency structure assumption and how thresholds in the data can lead to its violation and biased results. We use real and simulated data to show how threshold detection before applying the GC approach can overcome this problem and thereby provide researchers with a useful tool to increase the likelihood of the GC approach’s assumptions being met

A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice

Optimal vaccines are needed for sustained suppression of SARS-CoV-2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS-CoV-2 S1 subunit antigen (Ad5.SARS-CoV-2-S1) for COVID-19 immunization and evaluated its immunogenicity in mice. A single immunization with Ad5.SARS-CoV-2-S1 via S.C. injection or I.N delivery induced robust antibody and cellular immune responses. Vaccination elicited significant S1-specific IgG, IgG1, and IgG2a endpoint titers as early as 2 weeks, and the induced antibodies were long lasting. I.N. and S.C. administration of Ad5.SARS-CoV-2-S1 produced S1-specific GC B cells in cervical and axillary LNs, respectively. Moreover, I.N. and S.C. immunization evoked significantly greater antigen-specific T-cell responses compared to unimmunized control groups with indications that S.C. injection was more effective than I.N. delivery in eliciting cellular immune responses. Mice vaccinated by either route demonstrated significantly increased virus-specific neutralization antibodies on weeks 8 and 12 compared to control groups, as well as BM antibody forming cells (AFC), indicative of long-term immunity. Thus, this Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity following delivery to mice by S.C. and I.N. routes of administration, supporting the further development of Ad-based vaccines against COVID-19 and other infectious diseases for sustainable global immunization programs.</p

Both muscle quantity and quality are predictors of waiting list mortality in patients with end-stage liver disease

Background and aims: Malnutrition is highly prevalent in patients with end-stage liver disease (ESLD) and associated with impaired clinical outcome. Previous studies focused on one component of body composition and not in combination with nutritional intake, while both are components of the nutritional status. We aimed to evaluate the most important risk factors regarding body composition (muscle mass, muscle quality and fat mass) and nutritional intake (energy and protein intake) for waiting list mortality in patients with ESLD awaiting liver transplantation (LTx). Methods: Consecutive patients with ESLD listed for LTx between 2007 and 2014 were investigated. Muscle mass quantity (Skeletal Muscle Mass Index, SMI), and muscle quality (Muscle Attenuation, MA), and various body fat compartments were measured on computed tomography using SliceOmatic. Nutritional intake (e.g. energy and protein intake) was assessed. Multivariable stepwise forward Cox regression analysis was used for statistical analysis. Results: 261 Patients (mean age 54 years, 74.7% male) were included. Low SMI and MA were found to be statistically significant predictors of an increased risk for waiting list mortality in patients with ESLD, with a HR of 2.580 (95%CI 1.055–6.308) and HR of 9.124 (95%CI 2.871–28.970), respectively. No association between percentage adipose tissue, and protein and energy intake with waiting list mortality was found in this study. Conclusion: Both low muscle quantity and quality, and not nutritional intake, were independent risk factors for mortality in patients with ESLD

Current perspectives on video and audio recording inside the surgical operating room

The availability of intraoperative multimedia recording is increasing. Considering the growing call for physicians’ accountability, it is inevitable that multimedia will play an important role in aiding quality control by improving the adequacy of operative reporting. However, the perspectives of medical professionals on this matter are poorly known. In this cross-disciplinary survey, we aimed to investigate the current viewpoints concerning the use of multimedia recording in the operating room. We conducted an electronic survey among all affiliated members of the Association of Surgeons of the Netherlands, the Dutch Urological Association and the Dutch Society of Obstetrics and Gynecology containing questions regarding current use of intraoperative recording and the level of likelihood or objection for certain scenarios. The response rate was 27.8%. The survey encompasses 370 (54.5%) surgeons, 71 (10.5%) urologists, 80 (11.8%) gynecologists, and 158 (23.3%) residents in training. 52.4% of respondents feel that the currently used operative report is insufficient for future quality requirements. 58.5% think it is unlikely they would behave differently during surgery when intra-operative video recording is applied. 82.8% think it is unlikely that their surgical methods would be altered. 63.8% of respondents preferred only video registration when intraoperative recording is implemented. The majority of respondents agree that the current method of operative reporting is insufficient for future quality requirements. There is support for intraoperative video recording, however, legal transparency is needed before either intraoperative video or audio recording could be implemented to protect not only the patients, but also the healthcare providers.</p

Long-term medical and productivity costs of severe trauma

Background Through improvements in trauma care there has been a decline in injury mortality, as more people survive severe trauma. Patients who survive severe trauma are at risk of long-term disabilities which may place a high economic burden on society. The purpose of this study was to estimate the health care and productivity costs of severe trauma patients up to 24 months after sustaining the injury. Furthermore, we investigated the impact of injury severity level on health care utilization and costs and determined predictors for health care and productivity costs. Methods This prospective cohort study included adult trauma patients with severe injury (ISS≥16). Data on in-hospital health care use, 24-month post-hospital health care use and productivity loss were obtained from hospital registry data and collected with the iMTA Medical Consumption and Productivity Cost Questionnaire. The questionnaires were completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to investigate the drivers of health care and productivity costs. Results In total, 174 severe injury patients were included in this study. The median age of participants was 55 years and the majority were male (66.1%). The mean hospital stay was 14.2 (SD = 13.5) days. Patients with paid employment returned to work 21 weeks after injury. In total, the mean costs per patient were €24, 760 with in-hospital costs of €11, 930, post-hospital costs of €7, 770 and productivity costs of €8, 800. Having an ISS ≥25 and lower health status were predictors of high health care costs and male sex was associated with higher productivity costs. Conclusions Both health care and productivity costs increased with injury severity, although large differences were observed between patients. It is important for decision-makers to consider not only in-hospital health care utilization but also the long-term consequences and associated costs related to rehabilitation and productivity loss.</p

Music to prevent deliriUm during neuroSurgerY (MUSYC) Clinical trial

Introduction Delirium is a neurocognitive disorder characterised by an acute and temporary decline of mental status affecting attention, awareness, cognition, language and visuospatial ability. The underlying pathophysiology is driven by neuroinflammation and cellular oxidative stress. Delirium is a serious complication following neurosurgical procedures with a reported incidence varying between 4% and 44% and has been associated with increased length of hospital stay, increased amount of reoperations, increased costs and mortality. Perioperative music has been reported to reduce preoperative anxiety, postoperative pain and opioid usage, and attenuates stress response caused by surgery. We hypothesize that this beneficial effect of music on a combination of delirium eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. Methods This protocol concerns a single-centred prospective randomised controlled trial with 6 months follow-up. All adult patients undergoing a craniotomy at the Erasmus Medical Center in Rotterdam are eligible. The music group will receive recorded music through an overear headphone before, during and after surgery until postoperative day 3. Patients can choose from music playlists, offered based on music importance questionnaires administered at baseline. The control group will receive standard of clinical care Delirium is assessed by the Delirium Observation Scale and confirmed by a delirium-expert psychiatrist according to the DSM-5 criteria. Risk factors correlated with the onset of delirium, such as cognitive function at baseline, preoperative anxiety, perioperative medication use, depth of anaesthesia and postoperative pain, and delirium-related health outcomes such as length of stay, daily function, quality of life (ie, EQ-5D, EORTC questionnaires), costs and cost-effectiveness are collected. Ethics and dissemination This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Center Rotterdam, The Netherlands, approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Trial registration numbers NL8503 and NCT04649450. </p

T cell composition and polygenic multiple sclerosis risk

Background and purpose: Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population. Methods: We included genotyped participants from the population-based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS-PRSs on total T cell numbers (n = 1261), CD4+ and CD8+ lineages, and subsets therein (n= 675). In addition, T-cell-specific PRSs were constructed based on functional pathway data. Results: The MS-PRS negatively correlated with CD8+ T cell frequencies (p = 2.92 × 10−3), which resulted in a positive association with CD4+/CD8+ T cell ratios (p = 8.27 × 10−9). These associations were mainly driven by two of 195 genome-wide significant MS risk variants: the main genetic risk variant for MS, HLA-DRB1*15:01 and an HLA-B risk variant. We observed no significant associations for the T-cell-specific PRSs. Conclusions: Our results suggest that MS-associated genetic variants affect T cell composition during childhood in the general population.</p

Adherence to dietary guidelines and cognitive decline from middle age

BACKGROUND: Diet, in particular the Mediterranean diet, has been associated with better cognitive function and less cognitive decline in older populations. OBJECTIVES: To quantify associations of a healthy diet, defined by adherence to either the Mediterranean diet, the WHO guidelines, or Dutch Health Council dietary guidelines, with cognitive function and cognitive decline from middle age into old age. METHODS: From the Doetinchem Cohort Study, a large population-based longitudinal study, 3644 participants (51% females) aged 45-75 y at baseline, were included. Global cognitive function, memory, processing speed, and cognitive flexibility were assessed at 5-y time intervals up to 20-y follow-up. Adherence to the Mediterranean diet was measured with the modified Mediterranean Diet Score (mMDS), adherence to the WHO dietary guidelines with the Healthy Diet Indicator (HDI), and adherence to the Dutch Health Council dietary guidelines 2015 with the modified Dutch Healthy Diet 2015 index (mDHD15-index). The scores on the dietary indices were classified in tertiles (low, medium, high adherence). Linear mixed models were used to model level and change in cognitive function by adherence to healthy diets. RESULTS: The highest tertiles of the mMDS, HDI, and mDHD15-index were associated with better cognitive function compared with the lowest tertiles (P values &lt;0.01), for instance at age 65 y equal to being 2 y cognitively younger in global cognition. In addition, compared with the lowest tertiles, the highest tertiles of the mMDS, HDI, and mDHD15-index were statistically significantly associated with 6-7% slower global cognitive decline from age 55 to 75 y, but also slower decline in processing speed (for mMDS: 10%; 95% CI: 2, 18%; for mDHD15: 12%; 95% CI: 6, 21%) and cognitive flexibility (for mDHD15: 10%; 95% CI: 4, 18%). CONCLUSIONS: Healthier dietary habits, determined by higher adherence to dietary guidelines, are associated with better cognitive function and slower cognitive decline with aging from middle age onwards.</p

Factors associated with poor outcome in fetuses prenatally diagnosed with sacrococcygeal teratoma

Aim of the study: Outcome of fetuses, prenatally diagnosed with sacrococcygeal teratoma (SCT), is still poorly documented. This study assesses the incidence and prenatal predictors of outcome in all fetuses prenatally diagnosed with SCT. Methods: This is a retrospective study on all fetuses prenatally diagnosed with SCT from 1998 to 2018 in the Netherlands. Poor outcome was defined as terminations of pregnancy (TOP) because of expected unfavorable outcome, intrauterine fetal death, or early neonatal death. Potential risk factors for poor outcome were analyzed. Main results: Eighty-four fetuses were included. Sixteen (19.0%) TOPs were excluded from statistical analysis. Eleven of the remaining 68 fetuses had poor outcome. Overall mortality was 32.1%, with a mortality excluding TOPs of 13.1%. Thirteen fetal interventions were performed in 11 (13.1%) fetuses. Potential risk factors for poor outcome were the presence of fetal hydrops (OR: 21.0, CI: 2.6–275.1, p = 0.012) and cardiomegaly (OR: 10.3, CI: 1.9–55.8, p = 0.011). Conclusions: The overall mortality of fetuses prenatally diagnosed with SCTs including tTOP was 32.1%. This high mortality rate was mainly due to termination of pregnancy. Mortality excluding TOP was 13.1%. Potential risk factors for poor outcome were fetal hydrops and cardiomegaly.</p

Non-invasive prenatal test uptake in socioeconomically disadvantaged neighborhoods

Objective: Non-Invasive Prenatal Testing (NIPT) is increasingly being implemented worldwide. In public health programs, equitable access to healthcare is a fundamental principle which also applies to fetal aneuploidy screening. However, the out-of-pocket costs of NIPT may lead to sociodemographic disparities in uptake of screening. This study assessed whether there is a difference in the uptake of NIPT in socioeconomically disadvantaged neighborhoods compared to all other neighborhoods in the Netherlands, where NIPT is implemented in a national screening program (TRIDENT-2 study). Method: NIPT uptake, postal code and age of 156,562 pregnant women who received pre-test counselling for prenatal screening in 2018 were retrieved from the national prenatal screening database. Postal codes were used as a proxy to categorize neighborhoods as being either socioeconomically disadvantaged or other. The out-of-pocket costs for NIPT were €175. Results: NIPT uptake in socioeconomically disadvantaged neighborhoods was 20.3% whereas uptake in all other neighborhoods was 47.6% (p &lt; 0.001). The difference in NIPT uptake between socioeconomic disadvantaged neighborhoods and other areas was smaller for the youngest maternal age-group (≤25 years) compared to other age-groups. Conclusion: The variation in uptake suggest underlying disparities in NIPT uptake, which undermines the goals of a national fetal aneuploidy screening program of providing reproductive autonomy and equitable access. This has ethical and policy implications for ensuring fair and responsible implementation of fetal aneuploidy screening.</p