Sexual health variation among gang-involved youth in Washington state: Social ecological implications for research and practice.

INTRODUCTION: Gang-involved youth experience greater disparities in sexual health compared to non-gang-involved youth. Yet, little is known about how and why sexual behaviors vary within the youth gang population. Developing relevant and effective service approaches requires an understanding of this variation and the environmental factors that influence patterns of sexual health risk. METHODOLOGY AND RESULTS: Using latent class analysis, we identified four sexual behavior classes within a school-based sample of gang-involved youth in Washington State (N = 2060): Non-Sexually Active (54%), Limited Partners with Condom Use (14%), Multiple Partner with Sexting (19%), and High Sexual Vulnerability (13%). These classes were distinguished by age at sexual debut, number of sexual partners, condom use, and sexting. Interpersonal and macrosocial factors differentiated the classes, including multiform violence exposures, limited social support, and socioeconomic instability. We also found differences according to sexual identity and substance use. DISCUSSION: Findings highlight the need for service approaches that are responsive to both the individual needs of gang-involved youth and the factors that shape their living environments. We discuss the implications for research and practice, including the potential utility of a harm reduction framework to promote sexual health and reduce disparities in the youth gang population.

Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.

We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.

Nous comparons l'hématocrite, l'hémoglobine, le besoin de transfusion, la photothérapie récurrente, le taux de bilirubine sérique et la ferritine sérique à différentes périodes pour la traite du cordon ombilical (UCM) et le clampage retardé du cordon (DCC) chez les nourrissons nés à terme et prématurés. Une recherche complète dans diverses bases de données visait à comparer les études UCM et DCC jusqu'au 2 mai 2023. Les outils Cochrane et NIH ont évalué les ECR et les cohortes, respectivement. La méta-analyse a utilisé le logiciel Review Manager 5.4, calculant le MD et le RR avec des IC à 95 % pour les données continues et dichotomiques. Nous avons inclus 20 études portant sur un total de 5 189 nourrissons. Concernant les nourrissons prématurés, le niveau d'hématocrite n'a montré aucune différence significative entre la traite du cordon ombilical intact (iUCM) et la DCC (DM = -0,24, IC à 95 % [-1,11, 0,64]). De plus, l'incidence des décès néonatals était significativement plus élevée avec la technique UCM qu'avec la technique DCC (RR = 1,28, IC à 95 % [1,01 à 1,62]). Concernant les nourrissons à terme et peu prématurés, le niveau = 0,21, IC à 95 % [-1,28 à 1,69]), (DM = 0,96, IC à 95 % [-1,02 à 2,95]), respectivement. L'UCM a entraîné un risque plus élevé de décès néonatal chez les nourrissons prématurés par rapport au DCC. Cependant, l'incidence de la polyglobulie était plus faible dans le groupe UCM. De plus, l'UCM était associée à des taux plus élevés d'événements IVH graves. Sur la base de ces résultats, le DCC peut être préféré en raison de sa plus faible incidence d'IVH grave et de décès néonatals. d'hématocrite n'a montré aucune différence significative entre les techniques iUCM ou cUCM par rapport à la technique DCC (DM.

The effects of Yakson touch and gentle human touch on preterm infants: A systematic review and meta-analysis.

We aim to collect the evidence of efficacy of Gentle Guman Touch (GHT) and Yakson Touch in preterm neonates as pain relief, heart rate, oxygen saturation, and urine cortisol level. We made our search through PubMed, Web of Science, Scopus, and Cochrane by the mid of March 2023. Randomized control trials (RCTs) were included, and the Cochrane risk of bias tool was utilized to assess their quality. Using Review Manager software, a meta-analysis was conducted. We computed the mean difference (MD) with a 95% confidence interval (CI) for the continuous data. During the examination, the Neonatal Infant Pain Scale (NIPS) was significantly reduced in the touch group compared to the control group (MD = -3.40, 95% CI [-4.15 to -2.64], P-value= 0.00001). After the examination, the NIPS score was also reduced by both Yakson touch and GHT compared to the control (MD = -2.14, 95% CI [-3.42 to -0.85], P-value <0.00001). Yakson touch and GHT are non-pharmacological, easy, and safe methods that can be used for painful interventions to reduce the pain experience of preterm infants from variable interventions. Both methods improved infant sleep and behavior. Preterm infants' heart rates and oxygen saturation were unaffected by Yakson touch or GHT.

Efficacy of Massage on Pain Intensity in Post-Cesarean Women: a Systematic Review and Meta-Analysis.

Background: Cesarean section is a common surgical procedure that may be considered a safe alternative to natural birth and helps to resolve numerous obstetric conditions. Still, the Cesarean section is painful; relieving pain after a Cesarean section is crucial, therefore analgesia is necessary for the postoperative period. However, analgesia is not free of complications and contraindications, so massage may be a cost-effective method for decreasing pain post-Cesarean. Our study aims to determine the massage role in pain intensity after Cesarean sections. Methods: We searched five electronic databases for relevant studies. Data were extracted from the included studies after screening procedures. We calculated the pooled mean difference (MD) and standardized mean difference (SMD) for our continuous outcomes, using random or fixed-effect meta-analysis according to heterogenicity status. Interventional studies were assessed for methodological quality using the Cochrane risk-of-bias assessment tool, while observational studies were assessed using the National Institutes of Health's tools. Results: Our study included 10 RCTs and five observational studies conducted with over 1,595 post-Cesarean women. The pooled MDs for pain intensity considering baseline values either immediately or post 60-90 minutes were favoring the massagegroup over the control group as follows:(stand. MD = -2.64, 95% CI [-3.80, -1.48], p >.00001; MD = -2.64, 95% CI [-3.80, -1.48], p >.00001, respectively). While pooled MDsregarding post-intervention only eitherimmediately or post 60-90 minutes were:(stand. MD = -2.04, 95% CI [-3.26, -0.82], p =.001; stand. MD = -2.62, 95% CI [-3.52, -1.72],p > .00001, respectively). Conclusion: Our study found that using massage was superior to the control groups in decreasing pain intensity either when the pain was assessed immediately after or 60-90 minutes post-massage application.

The role of manganese in morphogenesis and pathogenesis of the opportunistic fungal pathogen Candida albicans.

Metals such as Fe, Cu, Zn, and Mn are essential trace nutrients for all kingdoms of life, including microbial pathogens and their hosts. During infection, the mammalian host attempts to starve invading microbes of these micronutrients through responses collectively known as nutritional immunity. Nutritional immunity for Zn, Fe and Cu has been well documented for fungal infections; however Mn handling at the host-fungal pathogen interface remains largely unexplored. This work establishes the foundation of fungal resistance against Mn associated nutritional immunity through the characterization of NRAMP divalent metal transporters in the opportunistic fungal pathogen, Candida albicans. Here, we identify C. albicans Smf12 and Smf13 as two NRAMP transporters required for cellular Mn accumulation. Single or combined smf12Δ/Δ and smf13Δ/Δ mutations result in a 10-80 fold reduction in cellular Mn with an additive effect of double mutations and no losses in cellular Cu, Fe or Zn. As a result of low cellular Mn, the mutants exhibit impaired activity of mitochondrial Mn-superoxide dismutase 2 (Sod2) and cytosolic Mn-Sod3 but no defects in cytosolic Cu/Zn-Sod1 activity. Mn is also required for activity of Golgi mannosyltransferases, and smf12Δ/Δ and smf13Δ/Δ mutants show a dramatic loss in cell surface phosphomannan and in glycosylation of proteins, including an intracellular acid phosphatase and a cell wall Cu-only Sod5 that is key for oxidative stress resistance. Importantly, smf12Δ/Δ and smf13Δ/Δ mutants are defective in formation of hyphal filaments, a deficiency rescuable by supplemental Mn. In a disseminated mouse model for candidiasis where kidney is the primary target tissue, we find a marked loss in total kidney Mn during fungal invasion, implying host restriction of Mn. In this model, smf12Δ/Δ and smf13Δ/Δ C. albicans mutants displayed a significant loss in virulence. These studies establish a role for Mn in Candida pathogenesis.

Protective Factors Against Aggression and Antisocial Attitudes Among Probation Youth with Childhood Adversity Histories.

Childhood adversity is linked to adolescent aggression and antisocial attitudes, which are common predictors of delinquency and violence. Early interruption of these negative trajectories is important for preventing serious criminality. Efforts to bolster protective factors such as social-emotional skills and positive relationships may attenuate this link, but research is needed to clarify salient factors for court-involved youth. Using risk assessment data for a diverse sample of youth on probation (N = 5378), this study investigated the role of adverse childhood experiences in increasing aggression and antisocial attitudes and the degree to which protective factors (self-regulation, future orientation, positive parenting, prosocial connections) mitigated those relationships. Multivariate models controlling for antisocial peers demonstrated that childhood maltreatment was the most salient form of adversity for increasing both aggression and antisocial attitudes. All protective factors were associated with reduced aggression and antisocial attitudes and, in moderation models, muted the impact of childhood adversity on both outcomes. These findings highlight the need for practice efforts geared toward bolstering protective factors for youth on probation, especially among those with child maltreatment histories.

Point prevalence of delirium among critically ill patients in Saudi Arabia: A multicenter observational study.

Background: Delirium in critically ill patients is independently associated with poor clinical outcomes. There is a scarcity of published data on the prevalence of delirium among critically ill patients in Saudi Arabia. Therefore, we sought to determine, in a multicenter fashion, the prevalence of delirium in critically ill patients in Saudi Arabia and explore associated risk factors. Methods: A cross-sectional point prevalence study was conducted on January 28, 2020, at 14 intensive care units (ICUs) across 3 universities and 11 other tertiary care hospitals in Saudi Arabia. Delirium was screened once using the Intensive Care Delirium Screening Checklist. We excluded patients who were unable to participate in a valid delirium assessment, patients admitted with traumatic brain injury, and patients with documented dementia in their medical charts. Results: Of the 407 screened ICU patients, 233 patients were enrolled and 45.9% were diagnosed with delirium. The prevalence was higher in mechanically ventilated patients compared to patients not mechanically ventilated (57.5% vs. 33.6%; P < 0.001). In a multivariate model, risk factors independently associated with delirium included age (adjusted odds ratio [AOR], 1.021; 95% confidence interval [CI], 1.01-1.04; P = 0.008), mechanical ventilation (AOR, 2.39; 95% CI, 1.34-4.28; P = 0.003), and higher severity of illness (AOR, 1.01; 95% CI, 1.001-1.021; P = 0.026). Conclusion: In our study, delirium remains a prevalent complication, with distinct risk factors. Further studies are necessary to investigate long-term outcomes of delirium in critically ill patients in Saudi Arabia.

Expert versus Youth Raters on Measuring Social and Therapeutic Climate in Secure Juvenile Placement.

Growing concern about the use of incarceration is driving significant reform in juvenile legal system decision-making and is likely to have a substantial impact on the role residential options play in the future continuum of care. It appears inevitable that surviving institutions or alternative residential models will be increasingly scrutinized for their impact on youth development. While rehabilitative models focused on youth development are a promising and growing part of residential institutions, few tools are available to measure quality. For institutions to sustain a focus on quality assessment, programs should use an organized and specified treatment model`` against which staff behavior can be assessed. This study examined the concurrent validity and item functioning of corresponding youth and expert ratings of social and therapeutic climate across multiple sites in a state-wide juvenile residential setting (n = 225 paired observations). Results suggest that the reliability of expert ratings of therapeutic climate exceeds the reliability of youth ratings, whereas reliability for other indicators of social climate are roughly equal between rater types. In addition, youth and expert ratings had weak concurrent validity. Implications for the use of youth versus expertly trained raters for measuring social and therapeutic environment are discussed.

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.

PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0. RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0). CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.

Cdc42 regulates reactive oxygen species production in the pathogenic yeast Candida albicans.

Across eukaryotes, Rho GTPases such as Rac and Cdc42 play important roles in establishing cell polarity, which is a key feature of cell growth. In mammals and filamentous fungi, Rac targets large protein complexes containing NADPH oxidases (NOX) that produce reactive oxygen species (ROS). In comparison, Rho GTPases of unicellular eukaryotes were believed to signal cell polarity without ROS, and it was unclear whether Rho GTPases were required for ROS production in these organisms. We document here the first example of Rho GTPase-mediated post-transcriptional control of ROS in a unicellular microbe. Specifically, Cdc42 is required for ROS production by the NOX Fre8 of the opportunistic fungal pathogen Candida albicans. During morphogenesis to a hyphal form, a filamentous growth state, C. albicans FRE8 mRNA is induced, which leads to a burst in ROS. Fre8-ROS is also induced during morphogenesis when FRE8 is driven by an ectopic promoter; hence, Fre8 ROS production is in addition controlled at the post-transcriptional level. Using fluorescently tagged Fre8, we observe that the majority of the protein is associated with the vacuolar system. Interestingly, much of Fre8 in the vacuolar system appears inactive, and Fre8-induced ROS is only produced at sites near the hyphal tip, where Cdc42 is also localized during morphogenesis. We observe that Cdc42 is necessary to activate Fre8-mediated ROS production during morphogenesis. Cdc42 regulation of Fre8 occurs without the large NOX protein complexes typical of higher eukaryotes and therefore represents a novel form of ROS control by Rho GTPases.

A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract.

BACKGROUND: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited. METHODS: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0-1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing. RESULTS: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median follow-up of 7.38 months (range, 5.23-21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3-4 treatment-related adverse events occurred in 38.4% of patients. CONCLUSIONS: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.

Substance Use Profiles Among Gang-Involved Youth: Social Ecology Implications for Service Approaches.

Substance use is a frequently cited health risk behavior in the youth gang literature, yet little is known about how substance use patterns vary among gang-involved youth or the social ecological factors that contribute to potential variation. Developing relevant and effective service approaches will require an understanding of this variation and the malleable factors that are likely to promote or inhibit particular patterns of use. Using latent class analysis, we identified four substance use classes within a school-based sample of gang-involved youth (n = 2,770): Non-Users (38%), Past Users (15%), Casual Users (27%), and Frequent Multi-Users (21%). These classes were distinguished by substance type, frequency of use, and source of access. Demographic and substance use-specific ecological factors across the family, peer, school, and neighborhood contexts were found to significantly differentiate these classes. Specifically, acceptance of use by parents, friends, and neighbors, along with a lack of family rules and high accessibility in the neighborhood, significantly differentiated use patterns. Findings highlight the need for service approaches that are responsive to the unique needs of individuals and their environments. Implications for practice are discussed, including the potential utility of applying a harm reduction service framework to address youth gang substance use.

A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma.

BACKGROUND: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway frequently is activated in patients with urothelial carcinoma (UC). In the current study, the authors performed a phase 2 study evaluating the efficacy of the pan-isoform class I PI3K inhibitor buparlisib in patients with platinum-refractory metastatic UC. METHODS: Two cohorts were recruited: an initial genetically unselected cohort and a subsequent expansion cohort of patients with PI3K/Akt/mTOR pathway-altered tumors. The primary endpoint was the 2-month progression-free survival rate. A rate of ≥80% was considered promising using a Simon 2-stage minimax design. Secondary endpoints included safety and correlation of markers of PI3K pathway activation with outcome. RESULTS: Six of 13 evaluable patients within the initial cohort demonstrated stable disease and 1 demonstrated a partial response, which was below the cutoff of 9 patients required to proceed to stage 2. Three of the patients with stable disease and the patient with a partial response harbored somatic TSC1 alterations. Four patients subsequently were recruited onto an expansion cohort: 3 patients with TSC1 alterations and 1 patient with a PIK3CA-activating mutation. No patient achieved disease control at 8 weeks and accrual was halted. Of the 19 patients evaluable for toxicity, 17 demonstrated treatment-related toxicities, 2 of whom had to discontinue therapy. CONCLUSIONS: Buparlisib was found to demonstrate modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations; however, this was not a robust predictor of response to buparlisib. The pattern of genetic coalterations likely influences drug sensitivity. Given the modest clinical activity and substantial toxicity of buparlisib, future trials of PI3K inhibitors in patients with UC should focus on isoform-selective PI3K inhibitors in genomically selected patients. LAY SUMMARY: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway frequently is upregulated in patients with metastatic urothelial carcinoma (UC). This trial explored buparlisib, an inhibitor of the pathway, in patients with heavily pretreated metastatic UC. Although the drug was found to have modest efficacy, with 6 patients experiencing stable disease and 1 patient achieving a partial response at 8 weeks on therapy, significant side effects also were observed. Patients with specific genetic alterations responded to treatment. Further studies of PI3K pathway inhibition are warranted using newer agents that have superior toxicity profiles and are more selective inhibitors of the pathway.

Building the Transdisciplinary Resistance Collective for Research and Policy: Implications for Dismantling Structural Racism as a Determinant of Health Inequity.

Structural racism is a multilevel system of ideologies, institutions, and processes that have created and reified racial/ethnic inequities. As a system, it works in concert across institutions to propagate racial injustice. Thus, efforts to address structural racism and its implications for health inequity require transdisciplinary collaboration. In this article, we begin by describing the process through which we have leveraged our discipline-specific training -- spanning education, epidemiology, social work, sociology, and urban planning -- to co-construct a transdisciplinary analysis of the determinants of racial health inequity. Specifically, we introduce the underlying theories that guide our framework development and demonstrate the application of our integrated framework through a case example. We conclude with potential research and policy implications.

Neighborhoods and health during the transition to adulthood: A scoping review.

Research suggests that neighborhoods play an important role in shaping health outcomes across the life course, but the neighborhood-health link during the transition to adulthood period (18-29 years) is not well studied. A scoping review of 24 studies used thematic analysis to examine the theoretical and methodological approaches of the neighborhood-health literature during this period. Themes illustrate the varied approaches used in this research, including diversity in how neighborhood is defined, theoretical variation regarding the importance of the transition period and the neighborhood-health link, and the importance of gender and race/ethnicity to this area of study. While the literature on this topic is fragmented, with varied definitions and minimal theoretical coherence, all studies found some degree of support for the relationship between neighborhoods and health during the transition to adulthood. Our analysis suggests that future research should focus on developing a theoretical foundation for these relationships in order to clarify key concepts and advance a science to better understand how and why neighborhoods affect health during this period.

A tailored cognitive behavioral program for juvenile justice-referred females at risk of substance use and delinquency: A pilot quasi-experimental trial.

This pilot quasi-experimental trial tested a gender-responsive cognitive behavioral group intervention with 87 court-involved female adolescents (5 juvenile courts) who were at indicated risk for substance use disorder. Participants in the intervention (n = 57) received twice weekly group sessions for 10 weeks (20 sessions) focused on building emotional, thought and behavior regulation skills and generalizing these skills to relationally-based scenarios (GOAL: Girls Only Active Learning). Youth in the control condition (n = 30) received services as usual, which included non-gender-specific aggression management training, individual counseling and no services. The GOAL program was found to be acceptable to youth and parents and feasible to implement within a juvenile court setting using skilled facilitators. Compared to services as usual, the program significantly and meaningfully reduced self-reported delinquent behavior (ß = 0.84, p < 0.05) over 6 months, and exhibited trend level effects for reduced substance use (ß = 0.40, p = 0.07). The program had mixed or no effects on family conflict and emotion regulation skills. These findings are discussed in light of treatment mechanisms and gender-responsive services.

Arabic intensive care delirium screening checklist's validity and reliability: A multicenter study.

PURPOSE: To develop an Arabic version of Intensive Care Delirium Screening Checklist (ICDSC) and assess its validity and reliability among critically ill patients. MATERIALS AND METHODS: Multicentered study of convenience sample of adult ICU patients. Arabic translation was performed with rigorous back-to-back translation methods. Concurrent validity was established by calculating the sensitivity and specificity of two examiner assessments compared to a psychiatric evaluation. Kappa coefficients describe interrater reliability, whereas Cronbach α and composite reliability depict internal consistency. RESULTS: Three hundred critically ill patients were enrolled. Of these, validity testing was assessed in 180 patients. ICDSC screening was positive for delirium in 11% of enrolled patients. The area under the receiver operator characteristic (ROC) curve is 0.9413, with predicted sensitivity 70% (95% confidence interval [CI]: 60-81%) and specificity 99% (95% CI: 98-100%). The Arabic ICDSC showed acceptable internal consistency (Cronbach α = 0.63 and composite reliability = 0.64). Interrater agreement was excellent (Kappa coefficient [Ò¡] = 0.85). CONCLUSIONS: Arabic ICDSC is a valid and reliable delirium-screening tool among Arabic-speaking ICU population. Future studies could address whether these findings are generalizable to a higher proportion of mechanically ventilated patients, and address acceptability and reliability in other Arabic language critical care settings.

Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer.

Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non-muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.