Greater Effect Size Research Articles

Responsivity to Problem-Solving Skills Training in Mothers of Children With Cancer.

Bright IDEAS (BI) is a problem-solving skills training (PSST) program that has been demonstrated in earlier randomized controlled trials (RCTs) to be an effective and specific intervention for improving problem-solving skills and reducing negative affect in caregivers of children with cancer. The objectives of this study were to (a) offer an approach to defining meaningful treatment response and to determine the rates of responsivity to PSST; and (b) identify characteristics of PSST responders and nonresponders. Data from 154 mothers receiving the BI intervention were analyzed. Drawing on the literature on minimal clinically important differences, two criteria for determining responsivity were calculated for the primary outcome of problem-solving skills: (a) The reliable change index (RCI) based on group data, and; (b) The effect size (ES) of each participant's pre/postintervention change score as a function of the group's baseline SD. Thirty-three percent of the sample met both responsivity criteria immediately posttreatment (39% at follow-up) and 38% (39% at follow-up) met neither. An additional 29% demonstrated a small or greater ES (≥ 0.2) but did not meet the RCI criteria, suggesting possible benefit. The single consistent predictor of responsivity was participants' pretreatment problem-solving skills, with lower skills at baseline predicting greater improvement (p < .001). These findings highlight the need to go beyond group data in interpreting RCTs and to incorporate measures of meaningful treatment response. Our ability to predict and screen for meaningful treatment response is critical to more precise targeting, enhanced outcomes, and better resource allocation.

The Developmental and Educational Impact of Hearing Impairment in Aboriginal Children Living in Remote Australia – A Data Linkage Study

IntroductionHigh prevalence of otitis media (OM) and hearing impairment (HI) in Aboriginal children in Australia’s Northern Territory (NT) is well documented. HI may be associated with poorer outcomes in early childhood development, school attendance and academic achievement. However, these associations have not been investigated in this population.&#x0D; Objectives and ApproachRetrospective cohort studies were conducted to investigate the association between HI and three education-related outcomes in Aboriginal children living in remote NT communities. The explanatory variable for all studies was audiometrically determined hearing levels. The outcome measures were Australian Early Development Census (AEDC) results, representing developmental outcomes at around age 5 years; Year 1 school attendance rates; and, National Assessment Program – Literacy and Numeracy (NAPLAN) results for Year 3 for academic achievement. Relevant confounding variables from available linked datasets were controlled for in the statistical analyses.&#x0D; ResultsCompared with normal hearing children, after adjustment for selected confounding factors, children with HI had higher risk for being developmentally vulnerable in two or more of the five AEDC domains (adjusted odds ratio 1.69); lower AEDC domain score sum (-1.60~-2.40); scoring lower in Numeracy (by 15.2 points), Writing (by 13.4-15.6 points) and Spelling (by 5.0 points) domains of NAPLAN; and having lower attendance rates (attending 4.0-5.6 fewer days in Year 1). Severer HI categories generally yielded greater effect sizes. Notably, across the studies, some confounding variables included in the analysis yielded substantially greater effect sizes.&#x0D; Conclusion / ImplicationsOM-related HI has a negative impact on early childhood development, Year 1 school attendance and academic achievement in Year 3 in Aboriginal children living in remote NT communities. To improve the developmental and educational outcomes it is important to detect HI at an early age and provide effective educational support, in addition to clinical and audiometric management.

DNA methylation analysis of candidate genes associated with dementia in peripheral blood.

Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjustedp < 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.

The health belief model and theory of planned behavior applied to mammography screening: A systematic review and meta‐analysis

The Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) are used to explain screening behavior. Although reviews of each model have been conducted independently, none have compared the application of both to mammography screening. A systematic review of literature published in five databases from 1974 to 2020 was performed. Meta-analysis of the explanatory value of the HBM and TPB and effect sizes of their cognitive variables was conducted. Altogether, 673 papers reporting HBM studies and 577 reporting TPB studies were recovered, of which 43 HBM studies and 15 TPB studies met the eligibility criteria. Twelve studies reported on the explanatory value of either model. The explained variance for HBM ranged from 25% to 89% (mean R2 =.55), while the explained variance for TPB ranged from 16% to 81% (mean R2 =.24 [screening behavior as outcome] and 0.46 [intention as outcome]). The component of "cue to action" had the greatest effect size (mean OR 1.80 [95% CI: 1.58-2.04]). While the HBM and TPB both demonstrated positive explanatory value, most studies examined the individual constructs of each model and failed to report consistently on the effectiveness of the models.

Age differences in the relationships between risk factors and loss of kidney function: a general population cohort study

BackgroundAnnual decline in kidney function is a widely applied surrogate outcome of renal failure. It is important to understand the relationships between known risk factors and the annual decline in estimated glomerular filtration rate (eGFR) according to baseline age; however, these remain unclear.MethodsA community-based retrospective cohort study of adults who underwent annual medical examinations between 1999 and 2013 was conducted. The participants were stratified into different age groups (40–49, 50–59, 60–69, 70–79, and ≥ 80 years) to assess the risk for loss of kidney function. A mixed-effects model was used to estimate the association between risk factors and annual changes in eGFR.ResultsIn total, 51,938 participants were included in the analysis. The age group of ≥80 years included 8127 individuals. The mean annual change in eGFR was − 0.39 (95% confidence interval: − 0.41 to − 0.37) mL/min/1.73 m2 per year. Older age was related to faster loss of kidney function. In the older age group, higher systolic blood pressure, proteinuria, and current smoking were related to faster loss of kidney function (p trend < 0.01, 0.03, and < 0.01, respectively). Conversely, each age group showed similar annual loss of kidney function related to lower hemoglobin levels and diabetes mellitus (p trend 0.47 and 0.17, respectively).ConclusionsHigher systolic blood pressure, proteinuria, and smoking were related to faster loss of kidney function, and a greater effect size was observed in the older participants. More risk assessments for older people are required for personalized care.

Frailty Is a Better Predictor than Age of Mortality and Perioperative Complications after Surgery for Degenerative Cervical Myelopathy: An Analysis of 41,369 Patients from the NSQIP Database 2010-2018.

Background: The ability of frailty compared to age alone to predict adverse events in the surgical management of Degenerative Cervical Myelopathy (DCM) has not been defined in the literature. Methods: 41,369 patients with a diagnosis of DCM undergoing surgery were collected from the National Surgical Quality Improvement Program (NSQIP) Database 2010–2018. Univariate analysis for each measure of frailty (modified frailty index 11- and 5-point; MFI-11, MFI-5), modified Charlson Co-morbidity index and ASA grade) were calculated for the following outcomes: mortality, major complication, unplanned reoperation, unplanned readmission, length of hospital stay, and discharge to a non-home destination. Multivariable modeling of age and frailty with a base model was performed to define the discriminative ability of each measure. Results: Age and frailty have a significant effect on all outcomes, but the MFI-5 has the largest effect size. Increasing frailty correlated significantly with the risk of perioperative adverse events, longer hospital stay, and risk of a non-home discharge destination. Multivariable modeling incorporating MFI-5 with age and the base model had a robust predictive value (0.85). MFI-5 had a high categorical assessment correlation with a MFI-11 of 0.988 (p < 0.001). Conclusions and Relevance: Measures of frailty have a greater effect size and a higher discriminative value to predict adverse events than age alone. MFI-5 categorical assessment is essentially equivalent to the MFI-11 score for DCM patients. A multivariable model using MFI-5 provides an accurate predictive tool that has important clinical applications.

Results of a Randomized, Open Label, Multicenter Trial Assessing the Safety, Dose and Schedule of RRx-001 (R001) in Reducing Severe Oral Mucositis (SOM) in Patients Receiving Chemoradiation (CRT) for Oral Cavity/oropharynx Squamous Cell Carcinoma (OSCC)

Severe oral mucositis (SOM, assessed WHO grade 3 or 4) occurs in up to 70% of patients receiving CRT for OSCC, many of whom require enteral nutrition or experience treatment interruption. Pharmacological targeting of nuclear factor erythroid related factor (Nrf2) represents an opportunity to mitigate radiation-associated toxicities mediated by oxidative species (OS). Preclinical studies demonstrate R001 activates Nrf2, a key regulator of gene expression encoding antioxidant, phase II detoxifying enzymes, and downstream Antioxidant Response Element signaling pathways. Activation of Nrf2 increases the threshold and buffering capacity of OS generated by CRT, and its multi-target activity provides a counterbalance to oxidative stress resulting in focal and systemic radioprotection. This proof of concept Phase 2a randomized clinical trial examined the safety, efficacy and schedule-dependent effects of R001 in reducing the incidence, severity and duration of SOM. Patients with OSCC treated with definitive or postoperative CRT were randomized to one of 4 treatment arms: 2 doses/week for 2 weeks before (pre) CRT (Arm 1); pre-CRT plus 2 doses or pre-CRT plus 6 weekly doses during CRT (Arm 2, 3 respectively); or standard of care (SOC) (Arm 4). The primary endpoint was duration of SOM through resolution < grade 2. Secondary endpoints included safety, time to onset, incidence, and duration of SOM and grade 4 mucositis through 60 and 70 Gy. Between June 2018 and July 2019 across 11 institutions, 53 patients were randomized, with 45 evaluable. Short 15-minute infusions of R001 were well tolerated with no associated serious adverse events (SAE). Side effects were comparable to SOC. Trends in treatment benefits for all endpoints were consistent across the 3 treatment arms, with the greatest effect size in Arm 1. R001 delayed time to onset (38 vs. 26 days) and duration of SOM (22 vs. 40 days), with 83% having resolution vs 60% with SOC, respectively. No patients developed grade 4 mucositis vs 30% SOC arm. A 95% decrease in duration of SOM (1 vs 17 days) through 60 Gy was also observed. Gastrostomy requirement was reduced by 45% (33% vs 60%). In this small open-label trial, R001 demonstrated a favorable benefit-risk profile with a markedly decreased incidence and duration of SOM through 60 Gy, 70 Gy and follow-up post CRT. Treatment effect was greatest in Arm 1 suggesting short periods of Nrf2 activation prior to generation of OS by CRT may be sufficient to increase the threshold and buffering capacity of antioxidants. Larger, blinded trials, confirming the observed dose, schedule and treatment effect are planned.

Bovine Tuberculosis (Mycobacterium bovis) Outbreak Duration in Cattle Herds in Ireland: A Retrospective Observational Study.

Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012–2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g., herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 years) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, being designated a CBFU (“feedlot”) and having high annual inward cattle movements within the “tails” subpopulation. Breakdown length was negatively associated with the year of commencement of breakdown (i.e., a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.

Correlates of Transitions Into Housing Instability Among Veterans Accessing Veterans Health Administration Health Care.

Prior research has explored the patterns and dynamics of homelessness; such an understanding is necessary to improve policy and programmatic responses and prevent new episodes of housing instability. The objectives of this study are to identify correlates of veterans' transitions into housing instability and inform initiatives aimed to address their needs, with a focus on how to prevent new episodes of housing instability. The cohort for this study includes 4,633,069 veterans who responded to the Veterans Health Administration's universal screen for housing instability at least twice between October 1, 2012, and September 30, 2016; 1.2% reported recent housing instability and 98.8% reported ongoing housing stability. The χ or Fisher exact tests, as appropriate, compared veterans' characteristics by housing status. A multivariate logistic regression identified independent risk factors associated with recent housing instability, controlling for sociodemographic, military service, diagnostic, and health services use variables. Sociodemographic and health services use variables increased veterans' odds of transitioning into housing instability. The diagnoses with the greatest effect sizes were drug use disorder (adjusted odds ratio=1.50, 95% confidence interval: 1.45-1.55) and opioid use disorder, which was associated with a >2-fold increase in the odds of experiencing recent housing instability (adjusted odds ratio=2.22, 95% confidence interval: 2.04-2.41). The present study provides evidence to inform existing and future interventions to prevent new episodes of housing instability. Veterans with opioid use disorder were at greatest risk of becoming unstably housed; increasing access to medication-assisted treatment in homeless-focused services is needed.

Associations of DXA-measured abdominal adiposity with cardio-metabolic risk and related markers in early adolescence in Project Viva.

Increased visceral adipose tissue (VAT) precedes development of insulin resistance and dyslipidemia in adults. The associations of abdominal adiposity derived from dual-energy X-ray absorptiometry (DXA), including VAT, subcutaneous abdominal adipose tissue (SAAT) and total abdominal adipose tissue (TAAT) with cardio-metabolic risk in adolescents are understudied. We examined the cross-sectional associations of DXA-measured abdominal adiposity with cardio-metabolic risk and related markers in early adolescence (mean [SD] age 13.0 [0.7] years). We collected data from 740 adolescents (374 girls and 366 boys) in Project Viva, a U.S. pre-birth cohort. We used DXA estimates of VAT, SAAT and TAAT area. We conducted overall and sex-stratified linear regression models, adjusting for age, sex (in overall models), race/ethnicity, puberty score and body mass index (BMI) z-score. Mean BMI z-score was 0.59 (1.28). After adjustment, greater VAT (per 1 SD score) was associated with higher metabolic risk z-score (β 0.14 units; 95% CI 0.08, 0.20), higher log high-sensitivity C-reactive protein (β 0.51 mg/L; 0.36, 0.66) and log leptin (β 0.36 ng/mL; 0.27, 0.44), and lower log adiponectin (β -0.08 ug/mL; -0.13, -0.02). SAAT and TAAT showed similar associations as VAT with comparable or greater effect sizes. In early adolescence, DXA-measured VAT, SAAT and TAAT are associated with cardio-metabolic risk and related markers, independent of current BMI. Among two adolescents with the same BMI, there is an associated higher cardio-metabolic risk in the adolescent with greater DXA-measured abdominal adiposity.

Impaired Sensorimotor Gating Using the Acoustic Prepulse Inhibition Paradigm in Individuals at a Clinical High Risk for Psychosis.

Many robust studies have investigated prepulse inhibition (PPI) in patients with schizophrenia. Recent evidence indicates that PPI may help identify individuals who are at clinical high risk for psychosis (CHR). Selective attention to prepulse stimulus can specifically enhance PPI in healthy subjects; however, this enhancement effect is not observed in patients with schizophrenia. Modified PPI measurement with selective attentional modulation using perceived spatial separation (PSS) condition may be a more robust and sensitive index of PPI impairment in CHR individuals. The current study investigated an improved PSSPPI condition in CHR individuals compared with patients with first-episode schizophrenia (FES) and healthy controls (HC) and evaluated the accuracy of PPI in predicting CHR from HC. We included 53 FESs, 55 CHR individuals, and 53 HCs. CHRs were rated on the Structured Interview for Prodromal Syndromes. The measures of perceived spatial co-location PPI (PSCPPI) and PSSPPI conditions were applied using 60- and 120-ms lead intervals. Compared with HC, the CHR group had lower PSSPPI level (Inter-stimulus interval [ISI] = 60 ms, P < .001; ISI = 120 ms, P < .001). PSSPPI showed an effect size (ES) between CHR and HC (ISI = 60 ms, Cohen's d = 0.91; ISI = 120 ms, Cohen's d = 0.98); on PSSPPI using 60-ms lead interval, ES grade increased from CHR to FES. The area under the receiver operating characteristic curve for PSSPPI was greater than that for PSCPPI. CHR individuals showed a PSSPPI deficit similar to FES, with greater ES and sensitivity. PSSPPI appears a promising objective approach for preliminary identification of CHR individuals.

The relationships between the results of contemporary tests of anorectal structure and sensorimotor function and the severity of fecal incontinence.

Diagnostic investigations for fecal incontinence (FI) assess the structure and sensorimotor function of the anorectum. Investigations include anorectal manometry, anorectal sensory testing, pudendal nerve terminal motor latencies (PNTML), and endoanal sonography. The severity of FI and results of investigations are often discordant andtherate of symptom resolution following treatment remains <40%. High-resolution anorectal manometry (HRAM) and three-dimensional endoanal ultrasound (3D-US) have been introduced during the last decade.This study aims to assess the strength of relationships between contemporary investigation results and FI severity. Adults presenting for investigation of FI were assessed using the St Mark's FI severity score (SMIS),HRAM, anorectal sensory testing, PNTML, and 3D-US. 246 patients were included.There were significant relationships between the SMIS andHRAM (resting pressure rs = -0.23, 95% CI = (-0.34, -0.11), P<.001; squeeze pressure (rs = -0.26, 95% CI = (-0.37, -0.14), P< .001) and 3D-US (anterior EAS length rs = -0.22, 95% CI = (-0.34, -0.09), P= .001). The relationships between SMIS and HRAM had a greater effect size in those with urge-predominant symptoms (resting pressure: rs = -0.40, 95% CI = (-0.57, -0.20), P< .001, squeeze pressure: rs = -0.34, 95% CI = (-0.52, -0.12), P= .003).Overall, the variance in SMIS accounted for by anorectal investigations was 8.6% (R2 = 0.098, adjusted R2 = 0.086, P < .001). Anorectal investigations are not strong predictors of FI severity. These findings may reflect the multifactorial, heterogeneous pathophysiology of FI, the limitations of the SMIS and anorectal investigations, and contributing factors extrinsic to the anorectum.

Elements of eating pattern and intensity of dysmenorrhea – a cross-sectional study in sample of Polish women

Background: The importance of dietary pattern for pain relief in women with dysmenorrhea is increasingly discussed in the literature. It is believed that a proper eating pattern may have pain-relieving properties. Therefore, a development of a perfect composition of diet for patients with dysmenorrhea constitutes a major challenge. Aim of the study: The present study aimed to characterise the eating pattern of women with severe and moderate menstrual pain among Polish women with dysmenorrhea. Material and methods: The observational cohort study was conducted among 718 women, divided into two subgroups: Group 1 (G1) comprised women suffering from severe pain (N = 355), while Group 2 (G2) involved women with moderate pain (N = 363). Two measurement tools were used in the study: The Visual Analogue Scale (VAS) and an original questionnaire for assessing the frequency of consumption of selected groups of food products. Results: Average consumption of vegetables, fruits, dairy products and coffee was significantly lower in G1 than in G2. On the other hand, average consumption of meat, fish and fast food products was significantly higher in G1 than G2. The greatest effect size was observed for the consumption of coffee as well as fruits and vegetables. Women from G2 had a diet similar to the lacto-ovo-vegetarian diet, whereas those from G1 followed a Western model diet that contains fast food products as well as food rich in sugar, salt and saturated fatty acids. Conclusions: The proper diet should be promoted among women suffering from dysmenorrhea and the use of nutrition supported by a proper diet should be particularly important in the treatment offered to this group of patients.

Low Spatial Frequency Sensitivity and Emotional Face Processing in Adolescents: An Event-related Potential Study

ABSTRACT Slow maturation of visual pathways transmitting low spatial frequency (LSF) information may contribute to inaccurate facial emotion recognition in adolescence. We recorded ERPs from adolescents and adults to upright and inverted happy faces, fearful faces, and chairs, which were unfiltered, contained only LSFs, or only high spatial frequencies. P100s and N170s were larger for adolescents than adults, with the greatest effect size for LSF stimuli. For LSFs only, adolescents showed a larger N170 inversion effect for happy than for fearful faces, but adults showed the opposite response. Thus, immaturities in LSF pathways appear to impact facial expression processing in adolescents.

Understanding the cumulative risk of maternal prenatal biopsychosocial factors on birth weight: a DynaHEALTH study on two birth cohorts

BackgroundThere are various maternal prenatal biopsychosocial (BPS) predictors of birth weight, making it difficult to quantify their cumulative relationship.MethodsWe studied two birth cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) born...

The Design and Impact of an Interprofessional Education Event Among Pharmacy and Nursing Students in Palliative Care-RnRx.

Nearly all reports of interprofessional education (IPE) in palliative care have excluded pharmacy students. This article describes an IPE event between pharmacy and nursing students and assesses its impact on IPE competencies. Second-year nursing students and third-year pharmacy students participated in an evening-long event, focused on a married couple who each require palliative care-one for end-of-life planning and one for chronic disease progression. The impact of the event was assessed using the Interprofessional Collaborative Competency Attainment Scale (ICCAS) and qualitative feedback. Two hundred nine (96.7%) completed the ICCAS, and 16 of the 20 statements of the ICCAS showed large positive effect sizes (Cohen d ≥ 0.8), with the remaining 4 showing moderate positive effect sizes (Cohen d ≥ 0.5). The greatest effect sizes were related to improved awareness of complementary skillsets and knowledge between the professions. Addressing team conflict and including the patient/family in decision-making showed the least improvement. While ongoing interactions are ideal for the development of skills related to conflict and team development, this article demonstrates that even a 1-time activity can have an impact on students' interprofessional care competence.

Results of a randomized, open-label, multicenter trial to assess the safety, dose, and schedule ofRRx-001(001) in reducing incidence, severity and duration of severe oral mucositis (SOM) inpatients receiving concomitant chemoradiation (CRT) for advanced head and neck cancer (HNC).

12081 Background: SOM occurs in 70% of patients receiving CRT for HNC with consequent pain, treatment interruptions and increased costs of care. Supraphysiologic levels of oxidative stress are key SOM initiators. 001 activates nuclear factor erythroid related factor 2 (Nrf2) increasing expression of multiple antioxidant genes including superoxide dismutase glutathione peroxidase and glutathione S-transferase. This trial examined the effect of dose and schedule on safety and efficacy of 001. Primary efficacy endpoint was duration of SOM (WHO criteria assessed); secondary endpoints included time to onset, incidence grade 4 through 60Gy and 70Gy. Methods: Locally advanced HNC treated with definitive or postoperative CRT (cisplatin + RT) received one of 3 001 schedules: (ARM1) 2 doses/wk for 2 weeks (prior to) CRT. ARMS 2, 3: prior to + 2 doses or 6 doses with CRT respectively or standard of care (SOC). Results: 53 patients randomized, 45 evaluable. Benefit trends for endpoints were consistent across all 3 001 arms with greatest effect size in pre-treatment only, ARM1. Compared to SOC, 001 reduced duration of SOM by 45% (40 vs 22 days). Through 60Gy and 70Gy a reduction of 95% and 79% in duration SOM was also observed (17 vs 1 day, and 23 vs 5 days) respectively. No patients in ARM1 developed grade 4, (0% vs SOC 30%). Side effects were comparable to SOC. Conclusions: In this small, open label trial, 001 demonstrated a favorable risk-benefit profile supported by reductions in overall SOM duration including through 60Gy and 70Gy with no grade ARM1 was most effective suggesting short periods of Nrf2 activation before CRT oxidative stress generation may increase the threshold and buffering capacity of upregulated antioxidants. Larger, blinded trials, confirming the observed dose, schedule and treatment effects are warranted. Clinical trial information: NCT03515538 .

Efficacy of immune check point inhibitors (ICIs) in metastatic gastric or gastroesophageal junction (GEJ) cancer by patient subgroups: A systemic review and meta-analysis.

e16587 Background: Patients with metastatic gastric or GEJ cancer have short duration of response to chemotherapy and poor outcome. Treatment with ICIs has been investigated for this population with inconsistent results. It is uncertain whether the effect of ICIs is comparable in different subgroups. Methods: Randomized controlled trials (RCTs) that compared standard treatment to treatment with ICIs, either as a monotherapy or in combination with chemotherapy, for metastatic gastric or GEJ cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) were extracted and pooled in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: patients’ age at time of randomization (age &lt; /≤ 65 years versus ≥/ &gt; 65 years), gender (female versus male), ethnicity (Asians versus the rest of the world), Eastern Cooperative Oncology Group performance status (0 versus 1), primary tumor location (gastric versus GEJ) and histological subtype (diffuse versus other subtypes). Data on progression free survival (PFS) and on OS in patients with programmed death ligand (PDL1) positive were also collected. Results: Four RCTs comprising 1,765 patients were analyzed. Treatment with ICIs compared to standard therapy did not significantly improve OS (HR = 0.84, 95% CI 0.66-1.07, p = 0.17), PFS (HR = 1.22, 95% CI 0.75-1.96, p = 0.52), or OS in patients with PDL1 positive disease (HR = 0.86, 95% CI 0.73-1.02, p = 0.08). The effect of ICIs on OS was similar in all subgroups. Non-significantly greater effect sizes were seen in younger patients (HR = 0.82 versus 0.86, p for subgroup difference 0.80), male (HR = 0.81 versus 0.97, p = 0.32), performance status 0 (HR = 0.84 versus 0.88, p = 0.81), GEJ tumors (HR = 0.76 versus 0.89, p = 0.44) and non-diffuse subtype (HR = 0.71 versus 0.79, p = 0.62). Conclusions: Compared to standard treatment, ICIs in metastatic gastric or GEJ cancer did not improve OS significantly. As none of the evaluated subgroups has shown increased magnitude of effect to ICIs, other biomarkers for ICIs response are desired in order to optimize the risk versus benefit balance of these patients.

Acute Psychological Effects of Resistance Exercise in Men With Symptoms of Muscle Dysmorphia: A Pilot Study.

SantaBarbara, NJ, Nosrat, S, Whitworth, JW, Ciccolo, JT. acute psychological effects of resistance exercise in men with symptoms of muscle dysmorphia: A pilot study. J Strength Cond Res 37(2): 277-283, 2023-This study tested the acute psychological effects of resistance exercise in men with symptoms of muscle dysmorphia. Twenty-one men completed 4 on-site sessions including a single session of moderate- (70% of 10 repetition maximum [RM]) and high- (100% of 10RM) intensity resistance exercise in a counter balanced order separated by at least 48 hours. State body image, perceived muscle size, exercise enjoyment, and ratings of perceived exertion (RPE) were assessed before, during, and after each session, and statistical significance was set a priori at p < 0.05. State body image significantly improve from pre to post during both sessions ( p < 0.01), with greater effect sizes seen for the high- ( d = 0.57) compared with the moderate- ( d = 0.39) intensity session. Perceived muscle size improved from pre to post during the high-intensity only ( p < 0.01, d = 0.66), and subjects enjoyed the high-intensity session significantly more than the moderate-intensity session ( p = 0.01), despite significantly higher RPE at each timepoint ( p < 0.01). Results contend with previous findings that show more positive psychological effects of moderate- compared with high-intensity resistance exercise. Education and client observation are essential to be aware of the potential for muscle dysmorphia. In instances where muscle dysmorphia is suspected, referral to qualified mental health professionals is recommended.

Cortical Thickness in Crouzon-Pfeiffer Syndrome: Findings in Relation to Primary Cranial Vault Expansion.

Background:Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon–Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern.Methods:Records from 34 Crouzon–Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern effect sizes on global/lobar CT were calculated as secondary outcomes.Results:Occipital expansion patients demonstrated 0.02 mm thicker cortex globally (P = 0.81) with regional findings, including: thicker cortex in frontal (0.02 mm, P = 0.77), parietal (0.06 mm, P = 0.44) and occipital (0.04 mm, P = 0.54) regions; and thinner cortex in temporal (−0.03 mm, P = 0.69), cingulate (−0.04 mm, P = 0.785), and, insula (−0.09 mm, P = 0.51) regions. Greatest effect sizes were observed between left lambdoid synostosis and the right cingulate (d = −1.00) and right lambdoid synostosis and the left cingulate (d = −1.23). Left and right coronal synostosis yielded effect sizes of d = −0.56 and d = −0.42 on respective frontal lobes.Conclusions:Both frontal and occipital primary cranial vault expansions correlate to similar regional CT in Crouzon–Pfeiffer patients. Lambdoid synostosis appears to be associated with cortical thinning, particularly in the cingulate gyri.