Decision Support Tool Identifies Ulcerative Colitis Patients Most Likely to Achieve Remission With Vedolizumab vs Adalimumab

Background & Aims We have previously validated a clinical decision support tool (CDST) (vedolizumab CDST [VDZ-CDST]) for clinical and endoscopic remission with VDZ in ulcerative colitis (UC). We aim to expand the validation for predicting histoendoscopic mucosal improvement (HEMI) with VDZ vs adalimumab (ADA). Methods In a post hoc analysis of a clinical trial for VDZ vs ADA in moderate to severe UC (VARSITY trial; NCT02497469), comparative accuracy was evaluated for the VDZ-CDST among an external validation cohort of VDZ- and ADA-treated patients for week 52 HEMI (Mayo endoscopic subscore 0-1 and Geboes score <3.2). Comparative effectiveness of VDZ and ADA was assessed after stratifying the cohort by baseline probability of response to VDZ using the VDZ-CDST. Results A total of 419 patients were included. The majority of patients enrolled in the VARSITY trial had a high (61%) or intermediate (29%) baseline predicted probability of response to VDZ. The baseline VDZ-CDST score was significantly more likely to predict week 52 HEMI for VDZ (area under the curve , 0.712; 95% confidence interval, 0.636-0.787) relative to ADA-treated patients (area under the curve, 0.538; 95% confidence interval, 0.377-0.700; P < .001 for AUC comparison). A significant (P < .001) association was observed between the VDZ-CDST and measured VDZ drug exposure over 52 weeks. Superiority of VDZ to ADA was only observed in patients with a high baseline predicted probability of response to VDZ. Conclusions Superiority of VDZ to ADA is dependent on baseline probability of response, and a VDZ-CDST is capable of identifying UC patients most appropriate for VDZ vs ADA.

Adaptive Block Testing

This article introduces Adaptive Block Testing (ABT), a method to test N units for a binary variable with known baseline probability pi for each unit, assuming that a test is available which may take arbitrary number of units and tests negative if all units are negative, and positive otherwise. A proof is given that the current method is optimal up to rounding. ABT is applicable to screen a large population of patients for the presence of the RNA of a virus, as for example the SARS-CoV-2, using block testing by polymerase chain reactions. ABT uses the block tests and adaptively chooses from the pool participants such that the entropy gain in each test is maximized. For a baseline probability of 1% of the tested patients to be sick, the method needs 2.4 times less tests than a block testing method with a block size of 10, the optimal block size for a standard block test at a baseline probability of 1%.

On the sheep-goat effect as the manifestation of phase-dependent mind-matter modulation: A hypothesis

The sheep-goat effect cannot be explained without considering mind of specific states. This work speculates mind-matter interaction, as was inferred by many including Erwin Schrödinger, for entertaining analytically-flavored “phenomenological” interpretation of the sheep-goat effect. A fundamental construct of this theory is the operation of mind-matter events in a spatial-temporal-attentional domain, which reduces to the spatial-temporal domain wherein purely objective events are registered, at the vanishing of the effect of attention. Time-dependent Schrodinger’s equation is then treated as a lower-dimensional case of a higher-dimensional mind-matter-event equation elaborated in the spatial-temporal-attentional complex. The domain-coupling when modulated by the phase difference between the temporal and attentional dimensions, can enhance or inhibit the deviation of the event registration in the spatial-temporal domain from its baseline probability. The outcome is akin the sheep-goat effect.

All the Single Ladies: Job Promotions and the Durability of Marriage

We study how promotions to top jobs affect the probability of divorce. We compare the relationship trajectories of winning and losing candidates for mayor and parliamentarian and find that a promotion to one of these jobs doubles the baseline probability of divorce for women, but not for men. We also find a widening gender gap in divorce rates for men and women after being promoted to CEO. An analysis of possible mechanisms shows that divorces are concentrated in more gender-traditional couples, while women in more gender-equal couples are unaffected. (JEL J12, J16, M12, M51)

HETEROGENEITY IN PROGRESSION OF COGNITIVE IMPAIRMENT AND VARIATIONS IN HEALTH EXPENDITURES AND HEALTH SERVICES USE

Cognitive aging and disease (e.g. dementia) are leading public health issues as longevity increases and the US population ages. We fit generalized linear models using data from the longitudinal Health and Retirement Study (2008-2014) on (Unweighted N=1,884) participants 70-years and older who met criteria for cognitive impairment not dementia (CIND), based on Aging, Demographics, and Memory Study specification, at baseline (2008) to test how impairment reversion, stability, and transition to dementia over 8-years affect change in biennial hospitalizations, nursing-home use, and out-of-pocket expenditures (OOP). Over 8-years, 13% reverted to normal cognition, 20% remained as CIND, 21% transitioned to dementia, and 46% died. In these groups, average OOP spending at baseline was $2311 (SE=$225), $2722 (SE=$278), $2180 (SE=$228), and $3653 (SE=$322), respectively. Average OOP spending increased to $3,095, $4,720, and $11,548 by the 8th year for those that reverted, stayed stable, and transitioned, respectively. Average OOP spending at the wave preceding death was $11,600. We observed substantial increases in nursing home use that were particularly pronounced among those that transitioned to dementia (Baseline Probability=0.04 increasing to 0.37 over 8-years) or died (0.09 increasing to 0.35 over 6-years), and similar but less pronounced differences in patterns of inpatient hospitalizations. Estimates were only slightly modified through adjustments to sociodemographic characteristics and comorbid conditions. We discuss how healthcare policy and clinical interventions focusing on early identification of impairment can potentially lead to improved and more efficient healthcare if better understanding of heterogeneities in impairment and cognitive disease progression is achieved.

Clostridium difficile infection increases acute and chronic morbidity and mortality

ObjectiveIn this study, we aimed to quantify short- and long-term outcomes of Clostridium difficile infection (CDI) in the elderly, including all-cause mortality, transfer to a facility, and hospitalizations.DesignRetrospective study using 2011 Medicare claims data, including all elderly persons coded for CDI and a sample of uninfected persons. Analysis of propensity score-matched pairs and the entire population stratified by the propensity score was used to determine the risk of all-cause mortality, new transfer to a long-term care facility (LTCF), and short-term skilled nursing facility (SNF), and subsequent hospitalizations within 30, 90, and 365 days.ResultsThe claims records of 174,903 patients coded for CDI were compared with those of 1,318,538 control patients. CDI was associated with increased risk of death (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.74–1.81; attributable mortality, 10.9%), new LTCF transfer (OR, 1.74; 95% CI, 1.67–1.82), and new SNF transfer (OR, 2.52; 95% CI, 2.46–2.58) within 30 days in matched-pairs analyses. In a stratified analysis, CDI was associated with greatest risk of 30-day all-cause mortality in persons with lowest baseline probability of CDI (hazard ratio [HR], 3.04; 95% CI, 2.83–3.26); the risk progressively decreased as the baseline probability of CDI increased. CDI was also associated with increased risk of subsequent 30-day, 90-day, and 1-year hospitalization.ConclusionsCDI was associated with increased risk of short- and long-term adverse outcomes, including transfer to short- and long-term care facilities, hospitalization, and all-cause mortality. The magnitude of mortality risk varied depending on baseline probability of CDI, suggesting that even lower-risk patients may benefit from interventions to prevent CDI.

Low foreign language proficiency reduces optimism about the personal future

Optimistic estimates about the personal future constitute one of the best-described and most-debated decision biases related to emotion. Nevertheless, it has been difficult to isolate manipulations that reduce optimistic estimates. Eliciting estimates in a foreign language is a promising candidate manipulation because foreign language use alters decision biases in scenarios with emotional components. Consequently, we tested whether foreign language use reduces optimistic estimates. In a laboratory experiment, participants ( n = 45) estimated their probability of experiencing life events either in their native language or a foreign language, in which they were highly proficient. We found no differences in these estimates or in the updating of these estimates after receiving feedback about the population baseline probability. Importantly, three online experiments with large sample sizes ( ns = 706, 530, and 473) showed that using a foreign language with low proficiency reduced comparative optimism. Participants in the online experiments had diverse proficiency levels and were matched on a variety of control metrics. Fine-grained analyses indicated that low proficiency weakens the coupling between probability estimates and rated arousal. Overall, our findings suggest that an important decision bias can be reduced when using a foreign language with low proficiency.

A random walk description of individual animal movement accounting for periods of rest

Animals do not move all the time but alternate the period of actual movement (foraging) with periods of rest (e.g. eating or sleeping). Although the existence of rest times is widely acknowledged in the literature and has even become a focus of increased attention recently, the theoretical approaches to describe animal movement by calculating the dispersal kernel and/or the mean squared displacement (MSD) rarely take rests into account. In this study, we aim to bridge this gap. We consider a composite stochastic process where the periods of active dispersal or ‘bouts’ (described by a certain baseline probability density function (pdf) of animal dispersal) alternate with periods of immobility. For this process, we derive a general equation that determines the pdf of this composite movement. The equation is analysed in detail in two special but important cases such as the standard Brownian motion described by a Gaussian kernel and the Levy flight described by a Cauchy distribution. For the Brownian motion, we show that in the large-time asymptotics the effect of rests results in a rescaling of the diffusion coefficient. The movement occurs as a subdiffusive transition between the two diffusive asymptotics. Interestingly, the Levy flight case shows similar properties, which indicates a certain universality of our findings.

Understanding Lapita as History

Although often seen as a singular historical phenomenon, it is likely that the prehistory witnessed archaeologically by Lapita pottery and other associated artifacts differed significantly in Near Oceania from the tale told about this pottery in Remote Oceania. There is a high baseline probability that Lapita evolved in the Bismarck Archipelago as part of an ancient, broadly distributed community of practice among diverse local residential communities. In contrast, around 3,000 years ago and after a number of generations in Near Oceania, some of the bearers of Lapita pottery sailed away to colonize what had hitherto been the uninhabited islands to the south and east. Thereafter, due perhaps to the greater distances among the major Remote Oceanic archipelagoes, Lapita as an archaeological complex bears witness mostly to the shared ancestry of these pioneers rather than to their continuing mutual engagement in a newly founded, more expansive regional community of practice.