Differential Treatment Research Articles

Inclusion of phase III clinical trial costs in health economic evaluations

IntroductionProtocol-driven trial activities contribute to the utility gain demonstrated in the phase III clinical trial of a new drug. If this utility gain cannot be distinguished from the effects of the new drug itself, protocol-driven trial costs cannot be easily dismissed for consistency reasons. This study aims to estimate the impact of including per-patient costs of phase III clinical trials on the incremental cost-effectiveness ratio (ICER).MethodsThe analysis utilized a modeling approach with secondary data from an ad-hoc literature review, considering both societal and payer perspectives. While the costs of phase III clinical trials may cancel out during the period of “normal” life-years due to the incremental cost calculation, they do not cancel out when differential early treatment termination occurs (e.g., due to differential mortality). Assuming the presence of differential mortality, per-patient phase III trial costs were calculated for the period of added life-years. These costs were then included in the ICER of a new drug, under the assumption that direct patient-related costs constitute 30–70% of the total trial costs. Capital costs were also incorporated from a societal perspective.ResultsBased on assumptions of $40,000 out-of-pocket expenses per patient enrolled in a phase III trial and a life expectancy gain of three months, incremental costs increased by $27,000 from a societal perspective. From a payer perspective, the estimate was $12,000.ConclusionsThe costs of phase III trials are a relevant component of the ICER, and excluding it is generally not appropriate for consistency reasons. Properly considering these trial costs is essential for a comprehensive evaluation of a new drug’s cost-effectiveness.

Exploring the impact of biological sex on intrinsic connectivity networks in PTSD: A data-driven approach

IntroductionSex as a biological variable (SABV) may help to account for the differential development and expression of post-traumatic stress disorder (PTSD) symptoms among trauma-exposed males and females. Here, we investigate the impact of SABV on PTSD-related neural alterations in resting-state functional connectivity (rsFC) within three core intrinsic connectivity networks (ICNs): the salience network (SN), central executive network (CEN), and default mode network (DMN). MethodsUsing an independent component analysis (ICA), we compared rsFC of the SN, CEN, and DMN between males and females, with and without PTSD (n = 47 females with PTSD, n = 34 males with PTSD, n = 36 healthy control females, n = 20 healthy control males) via full factorial ANCOVAs. Additionally, linear regression analyses were conducted with clinical variables (i.e., PTSD and depression symptoms, childhood trauma scores) in order to determine intrinsic network connectivity characteristics specific to SABV. Furthermore, we utilized machine learning classification models to predict the biological sex and PTSD diagnosis of individual participants based on intrinsic network activity patterns. ResultsOur findings revealed differential network connectivity patterns based on SABV and PTSD diagnosis. Males with PTSD exhibited increased intra-SN (i.e., SN-anterior insula) rsFC and increased DMN-right superior parietal lobule/precuneus/superior occipital gyrus rsFC as compared to females with PTSD. There were also differential network connectivity patterns for comparisons between the PTSD and healthy control groups for males and females, separately. We did not observe significant correlations between clinical measures of interest and brain region clusters which displayed significant between group differences as a function of biological sex, thus further reinforcing that SABV analyses are likely not confounded by these variables. Furthermore, machine learning classification models accurately predicted biological sex and PTSD diagnosis among novel/unseen participants based on ICN activation patterns. ConclusionThis study reveals groundbreaking insights surrounding the impact of SABV on PTSD-related ICN alterations using data-driven methods. Our discoveries contribute to further defining neurobiological markers of PTSD among females and males and may offer guidance for differential sex-related treatment needs.

Comparison of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma patients: a SEER population-based propensity score matching study.

This study was designed to compare the efficacy of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in terms of their therapeutic effect on small hepatocellular carcinoma (SHCC). The SEER database was employed to integrate SHCC patients who had received treatment with either LH (n = 1132) or RFA (n = 797). The LH group (n = 623) and the RFA group (n = 623) were matched with 1:1 propensity score matching (PSM) in order to reduce the possibility of selection bias. The Kaplan-Meier method and Cox proportional hazards regression method were employed to ascertain the prognostic factors associated with overall survival (OS) and disease-specific survival (DSS). Both before and after PSM, the 1, 3 and 5-years OS and DSS were significantly higher in the LH groups compared to the RFA group. Besides, for SHCC with tumor size ≤ 2cm (n = 418), even P values not reaching statistical significance, the survival curves were compatible with a superiority of LH over RFA for OS and DSS in overall (P = 0.054 and P = 0.077), primary SHCC (P = 0.110 and P = 0.058) and recurrent SHCC (P = 0.068 and P = 1.000) cohorts. In contrast, for SHCC with tumor size between 2 and 3 cm (n = 828), LH group always had a better OS and DSS in the all cohorts (all P < 0.05). In addition, higher AFP level, poor differentiation grade, recurrent tumor and treatment type were independent prognostic factors for OS, while poor differentiation grade, larger tumor size and treatment type were the independent prognostic factors for DSS (all P < 0.05). LH was associated with better OS and DSS than RFA in SHCC patients. Even in tumor size ≤ 2cm, LH still should be the first choice as its long-term survival benefits.

Exploratory Post Hoc Analysis of the CONVINCE Randomized Controlled Trial: Differential Treatment Effects of Hemodiafiltration (HDF) and Hemodialysis (HD) on Quality of Life

Exploratory Post Hoc Analysis of the CONVINCE Randomized Controlled Trial: Differential Treatment Effects of Hemodiafiltration (HDF) and Hemodialysis (HD) on Quality of Life

Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.

Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. UK secondary care dermatology outpatient clinics. Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Participants randomised 1:1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinded primary end-point assessor. Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10-70%) of that at baseline for alitretinoin compared with 50% (20-100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. This trial is registered as ISRCTN80206075. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Preclinical studies suggest that exposure to prostate-directed local therapy (LT) may influence the efficacy of subsequent systemic therapy including androgen receptor pathway inhibitors. However, there is insufficient clinical evidence to support this premise in patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC). To determine whether exposure to prior prostate-directed LT (radical prostatectomy [RP], radiation therapy [RT], or both) played any effect-modifying role in the treatment effect of apalutamide on metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC. This post hoc secondary analysis used individual patient data from SPARTAN (Study of Apalutamide [ARN-509] in Men With Non-Metastatic Castration-Resistant Prostate Cancer), a phase 3, double-blinded, placebo-controlled randomized clinical trial conducted at 332 sites in 26 countries. Between October 14, 2013, and December 15, 2016, patients with nmCRPC and a prostate-specific antigen doubling time of 10 months or less were randomly assigned to apalutamide vs placebo; all patients received androgen deprivation therapy. The final data analysis was performed on December 31, 2023. Prior prostate-directed LT. Separate Cox proportional hazards regression models were constructed for OS and MFS, which included prior LT, treatment group, and an interaction term, in addition to a minimally sufficient set of confounders. Adjusted hazard ratios (HRs) with 95% CIs for MFS and OS were determined for the apalutamide groups with or without prior LT. Among the 1179 evaluable patients included in this analysis, 795 received prior LT and 384 did not. The median age of patients with and without prior LT was 70 (IQR, 45-90) years and 75 (IQR, 50-95) years, respectively. The median follow-up was 52.0 (IQR, 51.5-52.8) months. A differential treatment effect of apalutamide on MFS was observed between patients with and without prior LT (P for interaction = .009), with greater benefits for those with prior LT (adjusted HR, 0.22 [95% CI, 0.17-0.27]) compared with those without prior LT (adjusted HR, 0.35 [95% CI, 0.25-0.51]). However, there was insufficient evidence of a differential treatment effect on OS among subgroups stratified by exposure to prior LT (P for interaction = .23), with improved OS in the subgroup with prior LT (adjusted HR, 0.72 [95% CI, 0.57-0.92]) but no significant difference in OS in the subgroup without prior LT (adjusted HR, 0.92 [95% CI, 0.64-1.31]). This post hoc analysis of the SPARTAN trial provides evidence of an interaction between prior LT and apalutamide in patients with nmCRPC, with a clinically significant and more favorable treatment effect from apalutamide on MFS among patients with prior LT. Further studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT01946204.

Healthcare utilization disparities among children with high-risk neuroblastoma treated on Children's Oncology Group clinical trials.

Disparities in relapse and survival from high-risk neuroblastoma (HRNBL) persist among children from historically marginalized groups even in highly standardized clinical trial settings. Research in other cancers has identified differential treatment toxicity as one potential underlying mechanism. Whether racial and ethnic disparities in treatment-associated toxicity exist in HRNBL is poorly understood. This is a retrospective study utilizing a previously assembled merged cohort of children with HRNBL on Children's Oncology Group (COG) post-consolidation immunotherapy trials ANBL0032 and ANBL0931 at Pediatric Health Information System (PHIS) centers from 2005 to 2014. Race and ethnicity were categorized to reflect historically marginalized populations as Hispanic, non-Hispanic Black (NHB), non-Hispanic other (NHO), and non-Hispanic White (NHW). Associations between race-ethnicity and intensive care unit (ICU)-level care utilization as a proxy for treatment-associated toxicity were examined with log binomial regression and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI). The analytic cohort included 370 children. Overall, 88 (23.8%) patients required ICU-level care for a median of 3.0days (interquartile range [IQR]: 1.0-6.5days). Hispanic children had nearly three times the risk of ICU-level care (RR 3.1, 95% CI: 2.1-4.5; fully adjusted RR [aRR] 2.5, 95% CI: 1.6-3.7) compared to NHW children and the highest percentage of children requiring cardiovascular-driven ICU-level care. Children of Hispanic ethnicity with HRNBL receiving clinical trial-delivered therapy were more likely to experience ICU-level care compared to NHW children. These data suggest that further investigation of treatment-related toxicity as a modifiable mechanism underlying outcome disparities is warranted.

Biased Social Media Debates About Terrorism? A Content Analysis of Journalistic Coverage of and Audience Reactions to Terrorist Attacks on YouTube

Social media are an important source of news during crises such as terrorist attacks. However, how news media and their audiences make sense of terrorism on social media is subject to bias, for example, given their differential treatment of terrorism by right-wing versus Islamist extremist perpetrators. In this study, we analyze how incident- and perpetrator-related characteristics of terrorist attacks are associated with bias in public debates about terrorism on YouTube. We focus on selectiveness in which attacks are covered (gatekeeping bias), how attacks are covered (presentation bias), and how audiences react to coverage (audience bias). Methodologically, we employ a manual and an automated content analysis of terrorism coverage by five international broadcasters on YouTube ( N = 643, 2018–2020) and related user comments ( N = 193,721). Our findings illustrate how sociocultural contexts shape news bias in terrorism coverage, both in the form of gatekeeping bias and presentation bias—but we conclude with less evidence for audience bias in public reactions to terrorism, at least on social media. Consequently, journalists should critically question working routines in covering crises to avoid reinforcing power imbalances, especially those from Western contexts.

Facial basis of stereotypes: Judgements of warmth and competence based on cross-group typicality/distinctiveness of faces.

Human migration is an increasingly common phenomenon and migrants are at risk of disadvantageous treatment. We reasoned that migrants may receive differential treatment by locals based on the closeness of their facial features to the host average. Residents of Türkiye, the country with the largest number of refugees currently, served as participants. Because many of these refugees are of Arabic origin, we created target facial stimuli varying along the axis connecting Turkish and Arabic morphological prototypes (excluding skin colour) computed using geometric morphometrics and available databases. Participants made judgements of two universal dimensions of social perception-warmth and competence-on these faces. We predicted that participants judging faces manipulated towards the Turkish average would provide higher warmth and competence ratings compared to judging the same faces manipulated towards the Arabic average. Bayesian statistical tools were employed to estimate parameter values in multilevel models with intercorrelated varying effects. The findings did not support the prediction and revealed raters (as well as target faces) to be an important source of variation in social judgements. In the absence of simple cues (e.g. skin colour, group labels), the effect of facial morphology on social judgements may be much more complex than previously assumed.

A side effect that should be considered in patients using metformin: lactic acidosis

The most serious and life-threatening side effect seen in patients using metformin is metabolic acidosis. If there is a history of diabetes in patients with high anion gap metabolic acidosis who present to the emergency department, metformin use should be questioned. In our case, metformin-related lactic acidosis was detected in a 67-year-old female patient who applied to the emergency department with a complaint of palpitations. The patient's kidney function tests were within normal range and he did not describe excessive drug intake. Despite the treatments administered in the emergency room, the patient's blood gas lactate level continued to increase and his acidosis deepened. After other causes of lactic acidosis were excluded, the patient was consulted with internal medicine and transferred to the intensive care unit. With this case report, we tried to draw attention to the fact that the patient group for which metformin will be used in the treatment should be carefully selected and that lactic acidosis, which is a fatal side effect, should be considered in the differential diagnosis and treatment should be started in those using this drug.

Research Progress on the Syndrome Differentiation and Treatment of Phlegm-Damp Type Polycystic Ovary Syndrome in Traditional Chinese and Western Medicine

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of childbearing age, with complex etiology and classification of traditional Chinese medicine syndromes, among which the phlegm-damp syndrome is the most prevalent. This article provides an overview of the common types and symptomatic characteristics of kidney deficiency type PCOS, the correlation with physicochemical indicators such as glucose and lipid metabolism levels, sex hormone indicators, inflammatory factor levels, as well as syndrome differentiation treatment and integrated traditional and Western medicine approaches, providing a certain scientific basis for clinical diagnosis and treatment.

Heterogeneous Treatment Effects in the Incredible Years Teacher Classroom Management Programme - A Latent Profile Approach.

Heterogeneous effects from interventions often remain hidden in between-group analyses, risking overgeneralized conclusions of treatment effects. In this exploratory study, we performed latent profile analysis to unveil differential treatment effects among children in The Incredible Years Teacher Classroom Management Programme (IY TCMP). This program has previously been shown to reduce behavioral problems in preschools and schools in total samples and subgroups. A total of 726 children (48.7% girls; Mage = 4.21 years; SDage = 0.86) from 92 childcare centers in Norway participated in either the intervention (n = 338) or the matched control condition (n = 388). First, by conducting latent profile analysis on baseline levels of child-teacher relationship (closeness, conflict), behavioral problems, and social competence, three distinct profiles were identified: High Risk (26.4%), Moderate Risk (42.8%), and Low Risk (30.7%) - each profile with unique characteristics. Second, we tested for within-profile, condition-by-time interactions following the intervention, showing distinct treatment responses for each profile. High-risk profiles profited most from the IY TCMP, with a substantial decrease in externalizing problems, more teacher closeness, and less teacher conflict. Moderate-risk profiles also gained better teacher-child relationships and improved social competence. The Low-Risk profiles showed no effects from the intervention. It is argued that latent profile analysis presents a feasible approach for examining within-sample heterogeneity in intervention research. It also reveals crucial information on treatment variability, as demonstrated in the Incredible Years Programme.

Impact of genomic background and developmental state on signaling pathways and response to therapy in glioblastoma patient-derived cells.

Glioblastoma (GBM) tumors represents diverse genomic epigenomic, and transcriptional landscapes, with significant intratumoral heterogeneity that challenges standard of care treatments involving radiation (RT) and the DNA-alkylating agent temozolomide (TMZ). In this study, we employed targeted proteomics to assess the response of a genomically-diverse panel of GBM patient-derived cancer stem cells (CSCs) to astrocytic differentiation, growth factor withdrawal and traditional high fetal bovine serum culture. Our findings revealed a complex crosstalk and co-activation of key oncogenic signaling in CSCs and diverse patterns of response to these external stimuli. Using RNA sequencing and DNA methylation, we observed common adaptations in response to astrocytic differentiation of CSCs across genomically distinct models, including BMP-Smad pathway activation, reduced cholesterol biosynthesis, and upregulation of extracellular matrix components. Notably, we observed that these differentiated CSC progenies retained a subset of stemness genes and the activation of cell survival pathways. We also examined the impact of differentiation state and genomic background on GBM cell sensitivity and transcriptional response to TMZ and RT. Differentiation of CSCs increased resistance to TMZ but not to RT. While transcriptional responses to these treatments were predominantly regulated by p53 in wild-type p53 GBM cells, its transcriptional activity was modulated by the differentiation status and treatment modality. Both mutant and wild-type p53 models exhibited significant activation of a DNA-damage associated interferon response in CSCs and differentiated cells, suggesting this pathway may play a wider role in GBM response to TMZ and RT. Our integrative analysis of the impact of GBM cell developmental states, in the context of genomic and molecular diversity of patient-derived models, provides valuable insights for pre-clinical studies aimed at optimizing treatment strategies.

A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease.

The inflammatory bowel diseases (IBD) known as Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.

Wastewater and warming effects on aquatic invertebrates: Experimental insights into multi-level biodiversity consequences

Wastewater effluents and global warming affect freshwater ecosystems and impact their crucial biodiversity. Our study aimed at characterizing individual and combined impacts of wastewater effluent and increased water temperature (as one aspect of climate change) on model freshwater communities. We tested the effect of experimental treatments on genetic diversity, survival, body weight, total lipid content, lipidome and metabolome of individual species as well as community composition and phylogenetic diversity. In a 21-day mesocosm experiment we assessed the responses of a simplified freshwater food web comprising of moss and seven species of benthic macroinvertebrate shredders and grazers (mayflies, stoneflies, caddisflies and amphipods) to four treatments in a full factorial design: control, increased water temperature, wastewater and a multiple stressor treatment combining increased temperature and wastewater. Physiological responses varied among taxa, with species-specific sensitivities observed in survival and lipid content. The lowest total lipid content was observed in caddisflies and a mayfly subjected to multiple stressor treatment. The effects of stressors were reflected in the altered metabolic pathways and lipid metabolism of the individual taxa, with differential treatment effects also observed between taxa. A notable decrease in phylogenetic diversity was observed across all experimental communities. Gammarus fossarum demonstrated a high susceptibility to environmental stressors at the genetic level. Hence, while commonly used indicators of ecosystem health (e.g. community composition) remained stable, molecular indicators (e.g. phylogenetic diversity, metabolome and lipidome) responded readily to experimental treatments. These findings underscore the vulnerability of macroinvertebrates to environmental stressors, even over relatively short exposure periods. They highlight the importance of molecular indicators in detecting immediate ecological impacts, offering valuable information for conservation strategies and understanding the ecological consequences in freshwater ecosystems.

Creating ‘safe’ spaces through exclusionary boundaries: Examining employers’ treatment of domestic workers during the COVID-19 pandemic in India

Our study illustrates how boundary mechanisms exacerbated the marginalization of paid domestic workers in India, after they resumed their employment at the end of the lockdown during the COVID-19 pandemic. We draw upon in-depth interviews with the middle-class employers of these workers to show how the employers renegotiated boundary rules and created bubbles of safe interaction for themselves. We contribute to boundary theory by explaining how pre-existing symbolic boundaries intensify and materialize into social boundaries. Social boundaries often result in unequal access to resources, further increasing disparities. But how do these boundaries get invoked? What forms do they take? So far, we do not have enough empirical research examining the creation and maintenance of social boundaries. This study shows how social boundaries get created and stabilized within gated communities through deployment of material resources, regulations and routinization of boundary tactics. These exclusionary social boundaries are further strengthened by the presence of an external agency, emerging as a new and significant actor in the hitherto private employer–worker relationship. Finally, we note that these boundaries result in normalized differential treatment of domestic workers, thus accentuating the class divide.

Initial evaluation of a personalized advantage index to determine which individuals may benefit from mindfulness-based cognitive therapy for suicide prevention

ObjectiveDevelop and evaluate a treatment matching algorithm to predict differential treatment response to Mindfulness-Based Cognitive Therapy for suicide prevention (MBCT-S) versus enhanced treatment-as-usual (eTAU). MethodsAnalyses used data from Veterans at high-risk for suicide assigned to either MBCT-S (n = 71) or eTAU (n = 69) in a randomized clinical trial. Potential predictors (n = 55) included available demographic, clinical, and neurocognitive variables. Random forest models were used to predict risk of suicidal event (suicidal behaviors, or ideation resulting in hospitalization or emergency department visit) within 12 months following randomization, characterize the prediction, and develop a Personalized Advantage Index (PAI). ResultsA slightly better prediction model emerged for MBCT-S (AUC = 0.70) than eTAU (AUC = 0.63). Important outcome predictors for participants in the MBCT-S arm included PTSD diagnosis, decisional efficiency on a neurocognitive task (Go/No-Go), prior-year mental health residential treatment, and non-suicidal self-injury. Significant predictors for participants in the eTAU arm included past-year acute psychiatric hospitalizations, past-year outpatient psychotherapy visits, past-year suicidal ideation severity, and attentional control (indexed by Stroop task). A moderation analysis showed that fewer suicidal events occurred among those randomized to their PAI-indicated optimal treatment. ConclusionsPAI-guided treatment assignment may enhance suicide prevention outcomes. However, prior to real-world application, additional research is required to improve model accuracy and evaluate model generalization.

The effects of takeover laws on corporate financing policies: global evidence

Using a cutting-edge estimation method to address heterogenous treatment effects arising from differential treatment timing, we examine the effect of international takeover laws on corporate financing. We find that firms reduce their equity financing in response to takeover laws. Further analyses indicate that takeover laws’ negative effect on equity financing is more pronounced for firms with higher financial constraints and for firms in countries with strong investor protections.

Selecting only the best and brightest? An assessment of migration policy selectivity and its effectiveness

Abstract This paper introduces a new set of comprehensive and cross-country-comparable indexes of migration policy selectivity. Crucially, these reflect the multidimensional nature of the differential treatment of migrants. We use these indexes to study the evolution of migration policy selectivity and estimate how they affect migration flows. Combining all publicly available and relevant data since WWII, we build three composite indexes that identify selectivity in terms of skills, economic resources and nationality. First, we use these to characterize migration policies in 42 countries between 1990 and 2014. Second, we examine the relationship between the selectivity of migration policy and migration flows. Each of the three dimensions of migration policy is found to correlate strongly and significantly with both the size and structure of migration flows.

Strategies for Differential Diagnosis and Management of Ichthyosis in Newborns

Congenital ichthyosis represents agroup of heterogeneous inherited skin diseases characterized by generalized keratinization disorder in the form of hyperkeratosis, caused by abnormalities in epidermal differentiation. The neonatal period is crucial for patients with ichthyosis due to the risk of developing complications, comorbidities, and fatal outcomes. Most complications arise from impaired skin barrier function. This article discusses the manifestations of ichthyosis in newborns, describes risks and complications, and suggests strategies for monitoring and treating patients. Purpose of the study: to present contemporary data on differential diagnosis and treatment strategies for newborn patients with congenital ichthyosis. Materials and Methods: review of Russian and international sources dedicated to the etiology, diagnosis, and treatment of ichthyosis was conducted. Results: Differential diagnosis of ichthyosis in the neonatal period is acrucial task, hence the most life-threatening subtypes are considered. The most severe progression with ahigh risk of fatal outcomes is characteristic of Harlequin ichthyosis. Collodion baby presents with less pronounced symptoms, is not afinal diagnosis, and may later develop clinical manifestations typical of ichthyosiform erythroderma, lamellar ichthyosis, or self-resolving congenital ichthyosis. Netherton syndrome is characterized by acombination of congenital ichthyosis with structural abnormalities of the hair shaft and apropensity for atopy. Epidermolytic ichthyosis, accompanied by the formation of blisters and erosions on the skin, requires differential diagnosis not only with other forms of ichthyosis but also with bullous epidermolysis, staphylococcal scalded skin syndrome, and toxic epidermal necrolysis. Every newborn with described manifestations requires support from amultidisciplinary team of specialists and timely therapeutic and diagnostic measures aimed at preventing the development of complications and deterioration of the patient’s condition. Conclusion: An analysis of global literature data and the practical experience of the authors indicate the complexities of differential diagnosis of ichthyosis forms in the neonatal period. To improve skin condition, prevent infectious complications, and correct electrolyte and respiratory disturbances, symptomatic treatment should begin before adefinitive diagnosis is established.