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BACKGROUND: The development of alcohol use disorder (AUD) is a major concern in public health, and cognitive impairments caused by alcohol are involved in this process. Emerging neurobiological evidence suggests that donepezil, an anticholinesterase agent, may improve AUD treatment outcomes by enhancing neurocognitive functioning. Previous research has also suggested that cognitive remediation therapy (CRT) could potentially improve cognitive function and AUD treatment outcomes. We present the rationale and design of a trial to evaluate the combination of donepezil and cognitive remediation therapy (donepezil + CRT) as an intervention for AUD. METHODS: We propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as an intervention for AUD. The main goal of the study is to evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking days and improving neurocognitive functioning. A total of 160 patients (4 groups, 40 per each group) with AUD between the ages of 18-80 years will be recruited at Yale University and the VA Connecticut Healthcare System. Primary outcome measures include 1) heavy drinking by Timeline Follow Back (TLFB) over 13 weeks and 2) global neurocognitive functioning by a global index of neurocognitive function score at 7 and 13 weeks. DISCUSSION: This protocol paper describes the rationale and proposed methods for the randomized controlled trial for improving AUD treatment outcomes. This project has significant clinical potential to help patients suffering from AUD by improving their cognition and reducing alcohol consumption. TRIAL REGISTRATION: NCT05042102.
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Autism spectrum disorder (ASD) and schizophrenia (SZ) share traits, especially in social skills and negative symptoms, and to a lesser degree positive symptoms. Differential diagnosis can be challenging and discerning expressive and experiential negative symptoms may provide knowledge with potential diagnostic and functional relevance that can guide treatment. Two exploratory factor analyses (EFA) were conducted to reveal the underlying dimensions of negative and positive symptoms using the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms & Negative Symptoms (SAPS/SANS) and the Autism Diagnostic Observation Schedule-Generic (ADOS-G). Three factors emerged from the negative symptom EFA (70.5 % variance): NF1) Expressive Negative; NF2) Experiential Negative; and NF3) Preoccupation, Absorption & Expressive Affective Flattening. Three positive factors emerged (68.6 % variance): PF1) Hallucinations-Delusions; PF2) Grandiosity; and PF3) Thought Disorder-ADOS positive Symptoms. SZ showed higher PF1 scores, and ASD had higher PF3 scores. No differences between groups were observed in the negative factors. Across groups, all negative factors were inversely associated with quality of life. Only NF1 and NF2 and PF1 were detrimentally related to social functioning. A discriminant function analysis using all factors classified correctly 84.4 % of participants, with PF1, NF1 followed by NF2 being the best predictors of diagnosis. Expressive negative followed by Experiential negative symptoms are of diagnostic value independent of and beyond SZ-related positive symptoms and are related with detrimental functioning. Findings confirm the need to distinctively target negative symptoms, and specific SZ-related and ASD-related positive symptoms, and especially the use of several assessment tools for diagnostic classification.
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Animals vary in the way in which they utilize energy due to diet, genetics, and management. Energy consumed by the animal supports milk production, but considerable variation among-animals in energy utilization is thought to exist. The study objective was to estimate the among-animal variance in energy utilization in data collected from Jersey cows using indirect calorimetry. Individual animal-period data from 15 studies (n = 560) were used. The data set included 115 animals from 44 to 410 DIM producing 11.5 to 39.1 kg/d of milk. On average, the 63 treatments in the data set ranged 14.8 to 19.5% CP, 21.4 to 43.0% NDF, 16.2 to 33.3% starch, and 2.21 to 6.44% crude fat. Data were analyzed with the Glimmix procedure of SAS (9.4) with random effects of cow, treatment nested within period, square, and experiment. The percentage of among-animal, dietary treatment, and experimental variance was calculated as the variance associated with each fraction divided by the sum of variance from animal, dietary treatment, experiment, and residual which was considered the total variance. The percentage of among-animal variance was characterized as high or low when the value was greater than or less than the mean value of 29.2%. Among-animal variance explained approximately 29.3 - 42.5% of the total variance in DM intake (DMI), gross energy (GE), digestible energy (DE), metabolizable energy (ME), and net energy of lactation (NEL) in Mcal/d. When energetic components of feces, urine, and heat in Mcal/d were expressed per unit of DMI the among-animal variance decreased by 20.4, 4.82, and 9.55% units, respectively. However, among-animal variance explained 4.80, 8.78, and 5.02% units more of the total variation for methane energy, lactation energy, and tissue energy in Mcal/d when expressed per unit of DMI. Variance in energetic efficiencies of DE/GE, ME/GE, and ME/DE were explained to a lesser extent by among-animal variance (averaging 17.8 ± 1.95%). The among-animal contribution to total variance in milk energy was 28.8%. Milk energy was a large proportion of the energy efficiency calculation which included milk energy plus corrected tissue energy over net energy intake which likely contributed to the 22.2% of total among-animal variance in energy efficiency. Results indicate that among-animal variance explains a large proportion of the total variation in DMI. This contributes to the variance observed for energy fractions as well as energy components when expressed in Mcal/d. Variation in energetic loss associated with methane was primarily explained by differences among-animals and was increased when expressed per unit of DMI highlighting the role of inherent animal differences in these losses.
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OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.
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Servicios Comunitarios de Farmacia , Consenso , Técnica Delphi , Hepatitis C , Humanos , Hepatitis C/diagnóstico , Servicios Comunitarios de Farmacia/organización & administración , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Farmacias/organización & administraciónRESUMEN
Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.
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OBJECTIVE: Occupational function assessment is essential for rehabilitation of severe mental illness but lacks comprehensive tools. METHOD: This study examines the psychometric properties of the Chinese versions of the Vocational Cognitive Rating Scale (VCRS) and the Work Behavior Inventory (WBI) in 60 chronic patients from a psychiatric daycare center and identifies clinical correlates of occupational function measured on the Positive and Negative Syndrome Scale (PANSS). RESULTS: The Chinese VCRS and WBI showed adequate internal consistency, interrater and test-retest reliability, and good convergent validity with the Comprehensive Occupational Therapy Evaluation Scale. Factor analysis favored a one-factor solution of the VCRS; and a four-factor structure in the WBI including Efficiency, Social Interaction, Appropriateness, and Regularity. The VCRS and Efficiency were predicted by fewer disorganization but greater affective symptoms. Social Interaction was negatively predicted by resistance symptoms. Appropriateness was associated with all but negative symptoms. Regularity was predicted by fewer negative symptoms. Considering work behavior altogether, WBI total scores were predicted by fewer negative, fewer disorganization, and greater affective symptoms. CONCLUSIONS AND IMPLICATION FOR PRACTICE: Findings suggest that the Chinese VCRS and WBI have sound psychometric properties and are suitable for both clinical trials and for planning personalized rehabilitation programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Trastornos Mentales , Rendimiento Laboral , Humanos , Reproducibilidad de los Resultados , Trastornos Mentales/rehabilitación , Cognición , PsicometríaRESUMEN
OBJECTIVE: Employment rates among individuals with serious mental illness may be improved by engagement in the individual placement and support (IPS) model of supported employment. Results from a recent randomized controlled trial (RCT) indicate that virtual reality job interview training (VR-JIT) improves employment rates among individuals with serious mental illness who have been actively engaged in IPS for at least 90 days. This study reports on an initial implementation evaluation of VR-JIT during the RCT in a community mental health agency. METHODS: A sequential, complementary mixed-methods design included use of qualitative data to improve understanding of quantitative findings. Thirteen IPS staff trained to lead VR-JIT implementation completed VR-JIT acceptability, appropriateness, and feasibility surveys. Participants randomly assigned to IPS with VR-JIT completed acceptability (N=42) and usability (N=28) surveys after implementation. The authors also conducted five focus groups with IPS staff (N=11) and VR-JIT recipients (N=13) and semistructured interviews with IPS staff (N=9) and VR-JIT recipients (N=4), followed by an integrated analysis process. RESULTS: Quantitative results suggest that IPS staff found VR-JIT to be highly acceptable, appropriate for integration with IPS, and feasible for delivery. VR-JIT was highly acceptable to recipients. Qualitative results add important context to the quantitative findings, including benefits of VR-JIT for IPS staff as well as adaptations for delivering technology-based interventions to individuals with serious mental illness. CONCLUSIONS: These qualitative and quantitative findings are consistent with each other and were influenced by VR-JIT's adaptability and perceived benefits. Tailoring VR-JIT instruction and delivery to individuals with serious mental illness may help optimize VR-JIT implementation within IPS.
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Empleos Subvencionados , Realidad Virtual , Humanos , Grupos Focales , Capacitación en Servicio , Ensayos Clínicos Controlados Aleatorios como Asunto , Tecnología , Investigación CualitativaRESUMEN
Advancing technologies of the corn dry-milling ethanol production process includes the mechanical separation of fiber-containing particles from a portion of plant- and yeast-based nitrogenous particles. The resulting high-protein processed corn coproduct (HPCoP) contains approximately 52% crude protein (CP), 36% neutral detergent fiber (NDF), 6.4% total fatty acids (TFA). The objective of this experiment was to examine the effects of replacing nonenzymatically browned soybean meal with the HPCoP on dry matter intake (DMI), energy and N utilization, and milk production of lactating Jersey cows. Twelve multiparous Jersey cows were used in a triplicated 4 × 4 Latin square design consisting of four 28-d periods. Cows were blocked by milk yield and assigned randomly to 1 of 4 treatment diets that contained HPCoP (dry matter [DM] basis) at (1) 0%; (2) 2.6%; (3) 5.4%; and (4) 8.0%. Diets were formulated to be isonitrogenous and thus replace nonenzymatically browned soybean meal with HPCoP in the concentrate mix, while forage inclusion remained the same across diets. Increasing the concentration of HPCoP had no effect on DMI (mean ± SE; 19.9 ± 0.62 kg/d), but tended to linearly increase milk yield (27.8, 28.5, 29.8, and 29.0 ± 1.00 kg/d). Although no difference was observed in the concentration of milk protein with increasing inclusion of HPCoP (3.40% ± 0.057%), the concentration of fat linearly increased with the inclusion of HPCoP (5.05%, 5.19%, 5.15%, 5.47% ± 0.18%). No differences were observed in the digestibility of DM, NDF, CP, TFA, and gross energy averaging 66.6% ± 0.68%, 49.0% ± 1.03%, 66.1% ± 0.82%, 73.6% ± 1.73%, 66.3% ± 0.72%, respectively, with increasing HPCoP inclusion. The concentration of dietary gross energy linearly increased with increasing concentrations of HPCoP (4.25, 4.26, 4.28, and 4.31 ± 0.01 Mcal/kg), but no difference was observed in digestible energy and metabolizable energy (ME) across treatments averaging 2.83 ± 0.033 and 2.53 ± 0.043 Mcal/kg, respectively. Concentration of dietary net energy for lactation (NEL) tended to increase with increasing HPCoP (1.61, 1.72, 1.74, 1.72 ± 0.054 Mcal/kg) with the ratio of NEL:ME increasing linearly with increasing HPCoP inclusion (0.648, 0.676, 0.687, 0.677 ± 0.0124). Results of this study suggest that inclusion of the HPCoP can replace nonenzymatically browned soybean meal and support normal milk production.
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Lactancia , Zea mays , Femenino , Bovinos , Animales , Zea mays/metabolismo , Alimentación Animal/análisis , Leche/metabolismo , Dieta/veterinaria , Ácidos Grasos/metabolismo , Fibras de la Dieta/metabolismo , Glycine max , Saccharomyces cerevisiae/metabolismo , Nitrógeno/metabolismo , Rumen/metabolismo , Ensilaje/análisis , DigestiónRESUMEN
Surface silanols (Si-OH) play a vital role on fused silica surfaces in chromatography. Here, we used an atmospheric-pressure, gas-phase reactor to modify the inner surface of a gas chromatography, fused silica capillary column (0.53 mm ID) with a small, reactive silane (tris(dimethylamino)methylsilane, TDMAMS). The deposition of TDMAMS on planar witness samples around the capillary was confirmed with X-ray photoelectron spectroscopy (XPS), ex situ spectroscopic ellipsometry (SE), and wetting. The number of surface silanols on unmodified and TDMAMS-modified native oxide-terminated silicon were quantified by tagging with dimethylzinc (DMZ) via atomic layer deposition (ALD) and counting the resulting zinc atoms with high sensitivity-low energy ion scattering (HS-LEIS). A bare, clean native oxide - terminated silicon wafer has 3.66 OH/nm2, which agrees with density functional theory (DFT) calculations from the literature. After TDMAMS modification of native oxide-terminated silicon, the number of surface silanols decreases by a factor of ca. 10 (to 0.31 OH/nm2). Intermediate surface testing (IST) was used to characterize the surface activities of functionalized capillaries. It suggested a significant deactivation/passivation of the capillary with some surface silanols remaining; the modified capillary shows significant deactivation compared to the native/unmodified fused silica tubing. We believe that this methodology for determining the number of residual silanols on silanized fused silica will be enabling for chromatography.
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Silanos , Silicio , Capilares , Dióxido de Silicio , ÓxidosRESUMEN
Given the relationship between social cognition and functional outcome in schizophrenia, a number of social cognitive interventions have been developed, including Social Cognition Interaction Training (SCIT), a group-based, comprehensive, manualized intervention. In the current trial, we examined SCIT efficacy as well as potential moderators of treatment effects. Fifty-one outpatients were randomized to SCIT or a wait-list-control (WLC), with assessments of social cognition, neurocognition, self-report, symptoms, and functioning conducted at baseline and end of the active phase. Relative to WLC, we did not find significant improvements for SCIT on neurocognition, social cognition, self-report, or symptoms, though there was a trend-level, medium effect favoring the SCIT condition on interpersonal and instrumental role function. Post-hoc analyses indicated that baseline neurocognition did not impact degree of social cognitive or functional change. Shorter duration of illness was significantly associated with better post-training neurocognition and self-esteem and, at trend-level with better symptoms and social functioning. We discuss the importance of outcome measure selection and the need for continued evaluation of potential treatment moderators in order to better match people to existing treatments. Clinical trial registration: Clinicaltrials.gov, Identifier NCT00587561.
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BACKGROUND: There are limited data regarding optimal antiplatelet/antithrombotic therapy following transcatheter aortic valve replacement (TAVR). METHODS: In this single-centre retrospective study including TAVR patients from 2012 to 2020, ischemic and bleeding outcomes were compared between antiplatelet (dual antiplatelet [DAPT] vs. single antiplatelet [SAPT]) and oral anticoagulation (OAC) groups using incidence rate, Kaplan-Meier and Cox proportional hazards analysis. RESULTS: Total 492 patients (mean age 79.7 ± 7.7 years, 53.7% males, 83.5% Caucasian) were included. There was higher incidence of 1-year death or ischemia with DAPT vs. SAPT (23.6 vs. 14.8 per 100 patient-years [PY], incidence rate ratio [IRR] 1.60, 95% confidence interval [CI] 0.97-2.68, p = .05), especially in those without coronary artery disease (23.9 vs. 10.7 per 100 PY, IRR 2.24, 95% CI 1.10-4.47, p = .017). There was significantly higher major bleeding in those on OAC vs. no OAC (15 vs. 8 per 100 PY, IRR 1.87, 95% CI 1.10-3.11, p = .016), especially late (>1-year) bleeding (10.2 vs. 3.6 per 100 PY, IRR 2.81, 95% CI 1.33-5.92, p = .004). In multivariate analysis, DAPT was an independent predictor of death or ischemia (adjusted hazard ratio [aHR] 1.41, 95% CI 1.01-1.96, p = .041). OAC was an independent predictor of major bleeding (aHR 2.32, 95% CI 1.31-4.13, p = .004). CONCLUSIONS: There is signal to harm with routine use of DAPT post-TAVR. There is higher incidence of late bleeding post-TAVR with OAC, suggesting potential role for alternate antithrombotic strategies.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Femenino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrinolíticos/uso terapéutico , Válvula Aórtica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia/inducido químicamente , Isquemia/etiología , Estenosis de la Válvula Aórtica/cirugía , Factores de RiesgoRESUMEN
Background: Over the past 10 years, job interview training has emerged as an area of study among adults with schizophrenia and other serious mental illnesses who face significant challenges when navigating job interviews. The field of mental health services research has limited access to assessments of job interview skills with rigorously evaluated psychometric properties. Objective: We sought to evaluate the initial psychometric properties of a measure assessing job interview skills via role-play performance. Methods: As part of a randomized controlled trial, 90 adults with schizophrenia or other serious mental illnesses completed a job interview role-play assessment with eight items (and scored using anchors) called the mock interview rating scale (MIRS). A classical test theory analysis was conducted including confirmatory factor analyses, Rasch model analysis and calibration, and differential item functioning; along with inter-rater, internal consistency, and test-retest reliabilities. Pearson correlations were used to evaluate construct, convergent, divergent, criterion, and predictive validity by correlating the MIRS with demographic, clinical, cognitive, work history measures, and employment outcomes. Results: Our analyses resulted in the removal of a single item (sounding honest) and yielded a unidimensional total score measurement with support for its inter-rater reliability, internal consistency, and test-retest reliability. There was initial support for the construct, convergent, criterion, and predictive validities of the MIRS, as it correlated with measures of social competence, neurocognition, valuing job interview training, and employment outcomes. Meanwhile, the lack of correlations with race, physical health, and substance abuse lent support for divergent validity. Conclusion: This study presents initial evidence that the seven-item version of the MIRS has acceptable psychometric properties supporting its use to assess job interview skills reliably and validly among adults with schizophrenia and other serious mental illnesses. Clinical Trial Registration: NCT03049813.
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Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).
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Glioblastoma , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Viroterapia Oncolítica/efectos adversos , Virus Oncolíticos/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: In time, we may be able to detect the early onset of symptoms of depression and even predict relapse using behavioural data gathered through mobile technologies. However, barriers to adoption exist and understanding the importance of these factors to users is vital to ensure maximum adoption. METHOD: In a discrete choice experiment, people with a history of depression (N = 171) were asked to select their preferred technology from a series of vignettes containing four characteristics: privacy, clinical support, established benefit and device accuracy (i.e., ability to detect symptoms), with different levels. Mixed logit models were used to establish what was most likely to affect adoption. Sub-group analyses explored effects of age, gender, education, technology acceptance and familiarity, and nationality. RESULTS: Higher level of privacy, greater clinical support, increased perceived benefit and better device accuracy were important. Accuracy was the most important, with only modest compromises willing to be made to increase other factors such as privacy. Established benefit was the least valued of the attributes with participants happy with technology that had possible but unknown benefits. Preferences were moderated by technology acceptance, age, nationality, and educational background. CONCLUSION: For people with a history of depression, adoption of technology may be driven by the desire for accurate detection of symptoms. However, people with lower technology acceptance and educational attainment, those who were younger, and specific nationalities may be willing to compromise on some accuracy for more privacy and clinical support. These preferences should help shape design of mHealth tools.
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Depresión , Telemedicina , Humanos , Depresión/diagnóstico , Depresión/terapia , Prioridad del Paciente , EscolaridadRESUMEN
Introduction: Communities of color have faced disproportionate morbidity and mortality from COVID-19, coupled with historical underrepresentation in US clinical trials, creating challenges for equitable participation in developing and testing a safe and effective COVID-19 vaccine. Methods: To increase diversity, including racial and ethnic representation, in local Los Angeles County NIH-sponsored Phase 3 SARS-CoV-2 vaccine clinical trials, we used deliberative community engagement approaches to form a Community Consultant Panel (CCP) that partnered with trial research teams. Thirteen members were recruited, including expertise from essential workers, community-based and faith-based organizations, or leaders from racial and ethnic minority communities. Results: Working closely with local investigators for the vaccine studies, the CCP provided critical insight on best practices for community trust building, clinical trial participation, and reliable information dissemination regarding COVID-19 vaccines. Modifying recruitment, outreach, and trial protocols led to majority-minority participants (55%-78%) in each of the three vaccine clinical trials. CCP's input led to cultural tailoring of recruitment materials, changes in recruitment messaging, and supportive services to improve trial accessibility and acceptability (transportation, protocols for cultural competency, and support linkages to care in case of an adverse event). Barriers to clinical trial participation unable to be resolved included childcare, requests for after-hours appointment availability, and mobile locations for trial visits. Conclusion: Using deliberative community engagement can provide critical and timely insight into the community-centered barriers to COVID-19 vaccine trial participation, including addressing social determinants of health, trust, clinical trial literacy, structural barriers, and identifying trusted messenger and reliable sources of information.
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BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.
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Labio Leporino , Fisura del Paladar , Insuficiencia Velofaríngea , Niño , Femenino , Humanos , Preescolar , Fisura del Paladar/cirugía , Fisura del Paladar/complicaciones , Labio Leporino/cirugía , Labio Leporino/complicaciones , Habla , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Paladar Duro , Insuficiencia Velofaríngea/cirugía , Insuficiencia Velofaríngea/complicacionesRESUMEN
BACKGROUND: Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD). METHODS: This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer. RESULTS: Intrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2-19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2-20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. CONCLUSION: This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
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Neoplasias de la Mama , Carcinomatosis Meníngea , Humanos , Femenino , Trastuzumab/efectos adversos , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/patología , Carcinomatosis Meníngea/tratamiento farmacológico , Carcinomatosis Meníngea/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
AIMS: Development and rollout of vaccines offers the best opportunity for population protection against the SARS-CoV-2 (COVID-19) virus. However, hesitancy towards the vaccines might impede successful uptake in the United Kingdom, particularly in young adults who demonstrate the highest rates of hesitancy. This prospective study explored COVID-19 vaccine hesitancy in young adults and whether the reasons behind these attitudes changed during the initial stages of the United Kingdom's vaccine rollout. METHOD: Data on vaccination intention were collected from a British university student cohort at three time points: October 2020, February 2021, and March 2021. This online survey included items on intention to receive a vaccine and a free-text response for the reasons behind this intention. Cochran's Q tests examined changes in rates of hesitancy and acceptance over time and free-text responses were analysed thematically. RESULTS: At baseline, 893 students provided data, with 476 participants completing all three time points. Hesitancy declined over time, with 29.4% of participants expressing hesitancy at baseline, reducing to 9.1% at wave 2 and 5.9% at wave 3. The most commonly endorsed themes for those willing to accept a vaccine were self-protection against COVID-19 and pro-social reasons, including protecting the population or unspecific others, and ending the pandemic/returning to normal life. The most commonly endorsed hesitancy themes related to 'confidence' in the vaccines and potential personal risk, including insufficient testing/scientific evidence, concern about side effects, and long-term effects. These reasons remained the most commonly endorsed at both waves 2 and 3. CONCLUSIONS: While a decline in hesitancy was observed over time, the key reasons behind both vaccine acceptance and hesitancy remained consistent. Reasons behind hesitancy aligned with those of the general public, providing support for the use of generalist interventions. Pro-social reasons frequently underpinned vaccine acceptance, so cohort-specific interventions targeting those factors may be of benefit.
Asunto(s)
COVID-19 , Vacunas , Adulto Joven , Humanos , Vacunas contra la COVID-19 , Estudios Prospectivos , COVID-19/prevención & control , SARS-CoV-2RESUMEN
Returning citizens struggle to obtain employment after release from prison, and navigating job interviews is a critical barrier they encounter. Implementing evidence-based interview training is a major gap in prison-based vocational services. We conducted a randomized controlled trial (RCT) to evaluate the feasibility and initial effectiveness of Virtual Reality Job Interview Training within two prisons. Forty-four male returning citizens were randomized to receive service-as-usual (SAU) with VR-JIT (SAU+VR-JIT, n = 28) or SAU (n = 16). Participants reported VR-JIT was highly acceptable and usable. SAU+VR-JIT, as compared to SAU, had significant improvements (with large effect sizes) in interview skills, interview training motivation, and interview anxiety (all p < .05; ηp2 > .15), and greater employment by 6-month follow-up (OR = 7.4, p = .045). VR-JIT can potentially help fill a major gap in prison-based services. Future research is needed to validate VR-JIT effectiveness and evaluate VR-JIT implementation strategies within prisons.