Dose optimization of pancreatic enzyme replacement therapy is essential to mitigate muscle loss in patients with advanced pancreatic cancer and exocrine pancreatic insufficiency.

BACKGROUND & AIMS: Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI. METHODS: All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm2) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm2). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression. RESULTS: Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen. CONCLUSION: In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.

Exploring relationships with food after dietary intervention in patients with colorectal cancer: a qualitative analysis from the Protein Recommendations to Increase Muscle (PRIMe) trial.

PURPOSE: Patients with cancer often experience nutritional challenges and are vulnerable to muscle mass loss. While substantial research is directed towards understanding how nutritional interventions affect clinical outcomes, insights into patients' personal experiences during these trials remain limited. This qualitative study aimed to gain a deeper understanding of how participation in the Protein Recommendations to Increase Muscle (PRIMe) trial affected patients' relationships with food. METHODS: A subset of patients who completed a minimum of one follow-up visit in the PRIMe trial participated in a semi-structured interview about their experience implementing dietary modifications to increase protein intake. Data from 26 patients with a recent diagnosis of stage II-IV colorectal cancer (non-cachectic) were included. Interviews were audio recorded, transcribed verbatim, and qualitative content analysis was applied. RESULTS: Most patients were male (65.4%) with stage II or III (69.2%) colorectal cancer and were a mean age of 57 ± 10 years. Five key themes emerged to provide a deeper understanding of patients' relationship with food after the PRIMe trial: (1) new positive perspectives on nutrition and coping with a cancer diagnosis; (2) embracing a comprehensive approach to food and nutrition; (3) facilitators promoting adherence to the intervention; (4) barriers challenging adherence to the intervention; and (5) shaping future dietary intake. CONCLUSION: This qualitative study explored the emotional and psychological effects of a clinical nutrition trial on patients, focusing on their relationship with food. It underscored the trial's comprehensive intervention and its enduring influence on patients, extending beyond the immediate intervention phase. The role of current perspectives, motivation, and knowledge acquisition on ability to adhere to dietary changes to increase protein intake were emphasized by patients and are key considerations for both clinicians and researchers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02788955; registration posted on 2016-06-02.

Advancing body composition assessment in patients with cancer: First comparisons of traditional versus multicompartment models.

BACKGROUND AND AIMS: Measurement of body composition using computed tomography (CT) scans may be a viable clinical tool for low muscle mass assessment in oncology. However, longitudinal assessments are often infeasible with CT. Clinically accessible body composition technologies can be used to track changes in fat-free mass (FFM) or muscle, though their accuracy may be impacted by cancer-related physiological changes. The purpose of this study was to examine the agreement among accessible body composition method with criterion methods for measures of whole-body FFM measurements and, when possible, muscle mass for the classification of low muscle in patients with cancer. METHODS: Patients with colorectal cancer were recruited to complete measures of whole-body DXA, air displacement plethysmography (ADP), and bioelectrical impedance analysis (BIA). These measures were used alone, or in combination to construct the criterion multicompartment (4C) mode for estimating FFM. Patients also underwent abdominal CT scans as part of routine clinical assessment. Agreement of each method with 4C model was analyzed using mean constant error (CE = criterion - alternative), linear regression including root mean square error (RMSE), Bland-Altman limits of agreement (LoA) and mean percentage difference (MPD). Additionally, appendicular lean soft tissue index (ALSTI) measured by DXA and predicted by CT were compared for the absolute agreement, while the ALSTI values and skeletal muscle index by CT were assessed for agreement on the classification of low muscle mass. RESULTS: Forty-five patients received all measures for the 4C model and 25 had measures within proximity of clinical CT measures. Compared to 4C, DXA outperformed ADP and BIA by showing the strongest overall agreement (CE = 1.96 kg, RMSE = 2.45 kg, MPD = 98.15 ± 2.38%), supporting its use for body composition assessment in patients with cancer. However, CT cutoffs for skeletal muscle index or CT-estimated ALSTI were lower than DXA ALSTI (average 1.0 ± 1.2 kg/m2) with 24.0% to 32.0% of patients having a different low muscle classification by CT when compared to DXA. CONCLUSIONS: Despite discrepancies between clinical body composition assessment and the criterion multicompartment model, DXA demonstrates the strongest agreement with 4C. Disagreement between DXA and CT for low muscle mass classification prompts further evaluation of the measures and cutoffs used with each technique. Multicompartment models may enhance our understanding of body composition variations at the individual patient level and improve the applicability of clinically accessible technologies for classification and monitoring change over time.

P-Factor(s) for Youth Psychopathology Across Informants and Models in 24 Societies.

OBJECTIVE: Although the significance of the general factor of psychopathology (p) is being increasingly recognized, it remains unclear how to best operationalize and measure p. To test variations in the operationalizations of p and make practical recommendations for its assessment, we compared p-factor scores derived from four models. METHODS: We compared p scores derived from principal axis (Model 1), hierarchical factor (Model 2), and bifactor (Model 3) analyses, plus a Total Problem score (sum of unit-weighted ratings of all problem items; Model 4) for parent- and self-rated youth psychopathology from 24 societies. Separately for each sample, we fitted the models to parent-ratings on the Child Behavior Checklist for Ages 6-18 (CBCL/6-18) and self-ratings on the Youth Self-Report (YSR) for 25,643 11-18-year-olds. Separately for each sample, we computed correlations between p-scores obtained for each pair of models, cross-informant correlations between p-scores for each model, and Q-correlations between mean item x p-score correlations for each pair of models. RESULTS: Results were similar for all models, as indicated by correlations of .973-.994 between p-scores for Models 1-4, plus similar cross-informant correlations between CBCL/6-18 and YSR Model 1-4 p-scores. Item x p correlations had similar rank orders between Models 1-4, as indicated by Q correlations of .957-.993. CONCLUSIONS: The similar results obtained for Models 1-4 argue for using the simplest model - the unit-weighted Total Problem score - to measure p for clinical and research assessment of youth psychopathology. Practical methods for measuring p may advance the field toward transdiagnostic patterns of problems.

Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E.

BACKGROUND: Cohorts A, C, and E of the phase Ib KEYNOTE-651 study evaluated pembrolizumab + binimetinib ± chemotherapy in microsatellite stable/mismatch repair-proficient metastatic colorectal cancer. PATIENTS AND METHODS: Patients received pembrolizumab 200 mg every 3 weeks plus binimetinib 30 mg twice daily alone (cohort A; previously treated with any chemotherapy) or with 5-fluorouracil, leucovorin, oxaliplatin (cohort C; previously untreated) or 5-fluorouracil, leucovorin, irinotecan (cohort E; previously treated with 1 line of therapy including fluoropyrimidine + oxaliplatin-based regimen) every 2 weeks. Binimetinib dose-escalation to 45 mg twice daily was planned in all cohorts using a modified toxicity probability interval design (target dose-limiting toxicity [DLT], 30%). The primary endpoint was safety; investigator-assessed objective response rate was secondary. RESULTS: In cohort A, 1/6 patients (17%) had DLTs with binimetinib 30 mg; none occurred in 14 patients with 45 mg. In cohort C, 3/9 patients (33%) had DLTs with binimetinib 30 mg; dose was not escalated to 45 mg. In cohort E, 1/5 patients (20%) had DLTs with binimetinib 30 mg; 5/10 patients (50%) had DLTs with 45 mg. Enrollment was stopped in cohort E binimetinib 45 mg and deescalated to 30 mg; 2/4 additional patients (50%) had DLTs with binimetinib 30 mg (total 3/9 [33%] had DLTs with binimetinib 30 mg). Objective response rate was 0% in cohort A, 9% in cohort C, and 15% in cohort E. CONCLUSION: Per DLT criteria, binimetinib + pembrolizumab (cohort A) was tolerable, binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, oxaliplatin (cohort C) did not qualify for binimetinib dose escalation to 45 mg, and binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, irinotecan (cohort E) required binimetinib dose reduction from 45 to 30 mg. No new safety findings were observed across cohorts. There was no apparent additive efficacy when binimetinib + pembrolizumab was added to chemotherapy. Data did not support continued enrollment in cohorts C and E.

Muscle and Adipose Wasting despite Disease Control: Unaddressed Side Effects of Palliative Chemotherapy for Pancreatic Cancer.

Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013-2019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm2/m2) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox's proportional hazards models. Tissue changes varied widely (∆SMI: -17.8 to +7.3 cm2/m2, ∆ATI: -106.1 to +37.7 cm2/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (-3.2 cm2/m2, p < 0.001; -12.4 cm2/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (-1.6 cm2/m2, p = 0.013) and GEM/NAB with greater adipose loss (-11.2 cm2/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.

Total energy expenditure assessed by 24-h whole-room indirect calorimeter in patients with colorectal cancer: baseline findings from the PRIMe study.

BACKGROUND: Total energy expenditure (TEE) determines energy requirements, but objective data in patients with cancer are limited. OBJECTIVES: We aimed to characterize TEE, investigate its predictors, and compare TEE with cancer-specific predicted energy requirements. METHODS: This cross-sectional analysis included patients with stages II-IV colorectal cancer from the Protein Recommendation to Increase Muscle (PRIMe) trial. TEE was assessed by 24-h stay in a whole-room indirect calorimeter before dietary intervention and compared with cancer-specific predicted energy requirements (25-30 kcal/kg). Generalized linear models, paired-samples t tests, and Pearson correlation were applied. RESULTS: Thirty-one patients (56 ± 10 y; body mass index [BMI]: 27.9 ± 5.5 kg/m2; 68% male) were included. Absolute TEE was higher in males (mean difference: 391 kcal/d; 95% CI: 167, 616 kcal/d; P < 0.001), patients with colon cancer (mean difference: 279 kcal/d; 95% CI: 73, 485 kcal/d; P = 0.010), and patients with obesity (mean difference: 393 kcal/d; 95% CI: 182, 604 kcal/d; P < 0.001). Appendicular lean soft tissue (ß: 46.72; 95% CI: 34.27, 59.17; P < 0.001) and tumor location (colon-ß: 139.69; 95% CI: 19.44, 259.95; P = 0.023) independently predicted TEE when adjusted for sex. Error between measured TEE and energy requirements predicted by 25 kcal/kg (mean difference: 241 kcal/d; 95% CI: 76, 405 kcal/d; P = 0.010) or 30 kcal/kg (mean difference: 367 kcal/d; 95% CI: 163, 571 kcal/d; P < 0.001) was higher for patients with obesity, and proportional error was observed (25 kcal/kg: r = -0.587; P < 0.001; and 30 kcal/kg: r = -0.751; P < 0.001). TEE (mean difference: 25 kcal/kg; 95% CI: 24, 27 kcal/kg) was below predicted requirements using 30 kcal/kg (-430 ± 322 kcal/d; P < 0.001). CONCLUSIONS: This is the largest study to assess TEE of patients with cancer using whole-room indirect calorimeter and highlights the need for improved assessment of energy requirements in this population. Energy requirements predicted using 30 kcal/kg overestimated TEE by 1.44 times in a controlled sedentary environment and TEE was outside of the predicted requirement range for most. Special considerations are warranted when determining TEE of patients with colorectal cancer, such as BMI, body composition, and tumor location. This is a baseline cross-sectional analysis from a clinical trial registered at clinicaltrials.gov as NCT02788955 (https://clinicaltrials.gov/ct2/show/NCT02788955).

Use of Medicare Benefit Scheme mental health services in young people who experienced self-harm and/or suicidal behaviours: Data from the Young Minds Matter survey.

OBJECTIVES: To examine healthcare utilisation patterns in a sample of young people with self-reported experiences of self-harm and/or suicidal behaviours. METHODS: A national survey examining mental health in a nationally representative sample of young Australians aged 12-17 years, linked to routinely collected healthcare and dispensing data. For respondents that self-reported experience of self-harm, suicidal ideation, suicidal plan and/or suicide attempt, we assessed attendance at a Medicare Benefits Scheme (MBS) subsidised MH service or non-MH general practitioner (GP) attendance at three time periods: 1) ever, 2) in the 12 months prior to completing the survey and 3) after completing the survey until 31 Dec 2015. We also assessed correlates associated with attendance and non-attendance at a MH service. RESULTS: The study included 311 young people. MH services were attended in the 12 months before the survey by 38.3% with attempted suicide, 28.7% with a suicidal plan, 28.9% with suicidal ideation and 29.4% with self-harm. MH treatment administered by a GP was the most common MH service (25%); followed treatment by psychologist (15%) and psychiatrist (5%). Attendance at a MH service was observed highest alongside more severe self-reported depression. CONCLUSIONS: Potential underutilisation of MBS MH services by young people with self-harm and/or suicidal behaviours.

Molecular and structural characterization of a novel high-prevalence antigen of the Augustine blood group system.

BACKGROUND: An antibody directed against a high-prevalence red blood cell (RBC) antigen was detected in a 67-year-old female patient of North African ancestry with a history of a single pregnancy and blood transfusion. So far, the specificity of the proband's alloantibody remained unknown in our immunohematology reference laboratory. STUDY DESIGN AND METHODS: Whole-exome sequencing (WES) was performed on the proband's DNA. The reactivity to the SLC29A1-encoded ENT1 adenosine transporter was investigated by flow cytometry analyses of ENT1-expressing HEK293 cells, and RBCs from Augustine-typed individuals. Erythrocyte protein expression level, nucleoside-binding capacity, and molecular structure of the proband's ENT1 variant were further explored by western blot, flow cytometry, and molecular dynamics calculations, respectively. RESULTS: A missense variant was identified in the SLC29A1 gene, which encodes the Augustine blood group system. It arises from homozygosity for a rare c.242A > G missense mutation that results in a nonsynonymous p.Asn81Ser substitution within the large extracellular loop of ENT1. Flow cytometry analyses demonstrated that the proband's antibody was reactive against HEK-293 cells transfected with control but not proband's SLC29A1 cDNA. Consistent with this finding, proband's antibody was found to be reactive with At(a-) (AUG:-2), but not AUG:-1 (null phenotype) RBCs. Data from structural analysis further supported that the proband's p.Asn81Ser variation does not alter ENT1 binding of its specific inhibitor NBMPR. CONCLUSION: Our study provides evidence for a novel high-prevalence antigen, AUG4 (also called ATAM after the proband's name) in the Augustine blood group system, encoded by the rare SLC29A1 variant allele AUG*04 (c.242A > G, p.Asn81Ser).

Prediction of whole body composition utilizing cross-sectional abdominal imaging in pediatrics.

BACKGROUND: Although body composition is an important determinant of pediatric health outcomes, we lack tools to routinely assess it in clinical practice. We define models to predict whole-body skeletal muscle and fat composition, as measured by dual X-ray absorptiometry (DXA) or whole-body magnetic resonance imaging (MRI), in pediatric oncology and healthy pediatric cohorts, respectively. METHODS: Pediatric oncology patients (≥5 to ≤18 years) undergoing an abdominal CT were prospectively recruited for a concurrent study DXA scan. Cross-sectional areas of skeletal muscle and total adipose tissue at each lumbar vertebral level (L1-L5) were quantified and optimal linear regression models were defined. Whole body and cross-sectional MRI data from a previously recruited cohort of healthy children (≥5 to ≤18 years) was analyzed separately. RESULTS: Eighty pediatric oncology patients (57% male; age range 5.1-18.4 y) were included. Cross-sectional areas of skeletal muscle and total adipose tissue at lumbar vertebral levels (L1-L5) were correlated with whole-body lean soft tissue mass (LSTM) (R2 = 0.896-0.940) and fat mass (FM) (R2 = 0.874-0.936) (p < 0.001). Linear regression models were improved by the addition of height for prediction of LSTM (adjusted R2 = 0.946-0.971; p < 0.001) and by the addition of height and sex (adjusted R2 = 0.930-0.953) (p < 0.001)) for prediction of whole body FM. High correlation between lumbar cross-sectional tissue areas and whole-body volumes of skeletal muscle and fat, as measured by whole-body MRI, was confirmed in an independent cohort of 73 healthy children. CONCLUSION: Regression models can predict whole-body skeletal muscle and fat in pediatric patients utilizing cross-sectional abdominal images.

Emulating a target trial of intensive nurse home visiting in the policy-relevant population using linked administrative data.

BACKGROUND: Populations willing to participate in randomized trials may not correspond well to policy-relevant target populations. Evidence of effectiveness that is complementary to randomized trials may be obtained by combining the 'target trial' causal inference framework with whole-of-population linked administrative data. METHODS: We demonstrate this approach in an evaluation of the South Australian Family Home Visiting Program, a nurse home visiting programme targeting socially disadvantaged families. Using de-identified data from 2004-10 in the ethics-approved Better Evidence Better Outcomes Linked Data (BEBOLD) platform, we characterized the policy-relevant population and emulated a trial evaluating effects on child developmental vulnerability at 5 years (n = 4160) and academic achievement at 9 years (n = 6370). Linkage to seven health, welfare and education data sources allowed adjustment for 29 confounders using Targeted Maximum Likelihood Estimation (TMLE) with SuperLearner. Sensitivity analyses assessed robustness to analytical choices. RESULTS: We demonstrated how the target trial framework may be used with linked administrative data to generate evidence for an intervention as it is delivered in practice in the community in the policy-relevant target population, and considering effects on outcomes years down the track. The target trial lens also aided in understanding and limiting the increased measurement, confounding and selection bias risks arising with such data. Substantively, we did not find robust evidence of a meaningful beneficial intervention effect. CONCLUSIONS: This approach could be a valuable avenue for generating high-quality, policy-relevant evidence that is complementary to trials, particularly when the target populations are multiply disadvantaged and less likely to participate in trials.

Erythrocyte type 1 equilibrative nucleoside transporter expression in sickle cell disease and sickle cell trait.

Hypoxia-mediated red blood cell (RBC) sickling is central to the pathophysiology of sickle cell disease (SCD). The signalling nucleoside adenosine is thought to play a significant role in this process. This study investigated expression of the erythrocyte type 1 equilibrative nucleoside transporter (ENT1), a key regulator of plasma adenosine, in adult patients with SCD and carriers of sickle cell trait (SCT). Relative quantitative expression analysis of erythrocyte ENT1 was carried out by Western blot and flow cytometry. Patients with SCD with steady state conditions, either with SS or SC genotype, untreated or under hydroxycarbamide (HC) treatment, exhibited a relatively high variability of erythrocyte ENT1, but with levels not significantly different from normal controls. Most strikingly, expression of erythrocyte ENT1 was found to be significantly decreased in patients with SCD undergoing painful vaso-occlusive episode and, unexpectedly, also in healthy SCT carriers. Promoting hypoxia-induced adenosine signalling, the reduced expression of erythrocyte ENT1 might contribute to the pathophysiology of SCD and to the susceptibility of SCT individuals to altitude hypoxia or exercise to exhaustion.

Drivers of Dietary Choice After a Diagnosis of Colorectal Cancer: A Qualitative Study.

BACKGROUND: Dietary changes often accompany management of a cancer diagnosis, but how and why patients with colorectal cancer (CRC) make dietary decisions requires further investigation. OBJECTIVE: To learn about patients' food-related beliefs and understand whether and why dietary changes were made by patients starting chemotherapy after a CRC diagnosis. DESIGN: A qualitative semi-structured interview study was conducted as a secondary analysis among a subset of patients with stages II-IV CRC enrolled at baseline in a randomized controlled trial. PARTICIPANTS/SETTING: Twenty-nine patients participated in the interview. Data were collected at the University of Alberta (Edmonton, Alberta, Canada) from 2016-2019 before any trial intervention. QUALITATIVE DATA ANALYSIS: Audio-recorded interviews were transcribed verbatim then coded inductively by two research team members. Qualitative content analysis was applied to capture emergent themes. RESULTS: Patients reported varied degrees of dietary change that stemmed from internal and external influences. Four main themes emerged to describe patients' dietary decisions after a CRC diagnosis: 1) Medical Influences: eating to live; 2) Health Beliefs: connecting lived experiences with new realities; 3) Static Diets: no changes postdiagnosis; and 4) Navigating External Influences: confluence of personal agency and social constraints. CONCLUSION: The extent to which patients altered their dietary choices depended on perspectives and beliefs. These included the degree to which dietary decisions provided some agency (ie, feeling of control) for dealing with physical ramifications of cancer treatment, individuals' personal understandings of healthy foods, and the role of diet in managing their new physical reality postdiagnosis. This information provides registered dietitian nutritionists and health care providers with insight into dietary intentions of select patients being treated for CRC. These findings can guide future research focused on effective strategies for streamlined nutritional support that aligns with patient needs.

24-Month results of the BRAVO study: A prospective, multi-center study evaluating the clinical outcomes of a ventral hernia cohort treated with OviTex® 1S permanent reinforced tissue matrix.

Background: This study evaluated the performance of OviTex® 1S (TELA Bio Inc., Malvern, PA, USA) over 24 months when used for ventral hernia repair. Methods: This was a prospective, single-arm, multi-center clinical trial (ClinicalTrials.gov/NCT03074474). A ninety-two patient cohort with ventral hernias were enrolled. The surgical approach (open, laparoscopic, or robotic) and plane of placement (retrorectus, intraperitoneal, or pre-peritoneal) were at the discretion of the surgeon. Patients were characterized as high risk for a surgical site occurrence (SSO) based on the following comorbidities: BMI between 30 and 40, active smoker, chronic obstructive pulmonary disease (COPD), diabetes mellitus, coronary artery disease, advanced age ( ≥ 75 years). Subjects underwent physical examinations to evaluate safety events and completed quality of life surveys at 1 months, 3 months, 12 months, and 24 months post-surgery. Results: Sixty-five of the 92 enrolled patients (70.7%) completed 24-month follow-up. The Kaplan Meier estimate for risk of recurrence at day 730 (24 months) was 2.6%; among subjects who completed their 24-month visit or had a previous recurrence, the unadjusted rate of recurrence was 4.5% (3/66). SSOs were observed in 38.0% of patients (35/92). The most prevalent SSO was surgical site infection occurring in 20.7% (19/92) of patients, followed by seroma formation, which occurred in 13.0% of patients; however, only 3.3% required intervention. HerQLes and EQ-5D assessments showed improvement from baseline as soon as 3 months post-surgery. Continued improvement was observed through 24 months. Conclusions: Overall the BRAVO study demonstrates that use of the ovine reinforced tissue matrix OviTex 1S is a viable option for use in ventral hernia repair. Additional studies with longer term follow-up data are needed to draw definitive conclusions on the use of OviTex 1S.

A novel non-invasive index of oxygenation and prediction of outcomes for patients on high-flow nasal cannula: a pilot study.

Predicting success of a therapy in acute respiratory failure is clinically important. The FOx index (high-flow rate × FiO2 )/SpO2 was retrospectively applied to 70 patients who required high-flow nasal prongs for hypoxaemic and hypercapnic respiratory failure. The FOx index could predict between success and failure of high-flow nasal prongs at 6 hours, using non-invasive markers. This adds to the clinician's toolbox in managing respiratory failure and represents important proof of concept for a prospective study.

Changes in Survival Outcomes of Patients With Neuroendocrine Neoplasms Over the Past 15 Years: A Real-World Study.

BACKGROUND: The past 2 decades have observed a number of advances in therapeutic approaches to patients with neuroendocrine neoplasms (NENs). This study aims to assess whether survival outcomes have changed among patients with NENs over the past 15 years, in a real-world, population-based study. MATERIALS AND METHODS: We accessed administrative databases within the province of Alberta, Canada, and we reviewed patients with invasive NENs diagnosed 2004 to 2019. Patients were classified according to the year of diagnosis into 3 groups: 2004 to 2008; 2009 to 2013; and 2014 to 2019. Kaplan-Meier survival estimates were used to compare overall survival (OS) according to different baseline characteristics (including the year of diagnosis). Multivariable Cox regression modeling was used to examine factors associated with the risk of death in this cohort. RESULTS: We included a total of 3431 patients in the study cohort. Using multivariable Cox regression analysis, the following factors were associated with worse survival: older age at diagnosis (hazard ratio [HR]: 3.45; 95% CI [confidence interval]: 2.74-4.35), male sex (HR: 1.38; 95% CI: 1.21-1.56), lung primary site (HR for lung vs. appendicular primary: 1.39; 95% CI: 1.01-1.92), Stage 4 disease (HR: 2.80; 95% CI: 2.38-3.30), South zone of the province (HR for South zone vs. Calgary zone: 1.85; 95% CI: 1.49-2.30), and higher comorbidity index (HR for ≥3 vs. 0: 2.66; 95% CI: 2.19-3.24). Although Kaplan-Meier method showed significant difference in OS according to diagnosis period, multivariable regression model showed that the period of diagnosis did not appear to impact OS (HR for diagnosis period 2004 to 2009 vs. 2014 to 2019: 1.04; 95% CI: 0.89-1.22). CONCLUSIONS: Over the study period (2004 to 2019), patients diagnosed during later periods did not appear to experience better OS compared with patients diagnosed at an earlier time.

Skeletal muscle is prognostic in resected stage III malignant melanoma.

BACKGROUND: Sarcopenia (low skeletal muscle index, SMI) and myosteatosis (low skeletal muscle radiodensity, SMD) have been associated with worse survival in cancer. This study evaluated associations of body composition with survival in patients with resected stage III melanoma. METHODS: A retrospective review was performed of resected stage III melanoma patients in Alberta, Canada from 2007 to 2017. Preoperative CT scans were analyzed to determine SMI and SMD. Cohort-specific SMI and SMD cut-offs that optimally predicted overall survival (OS) were identified through stratification, in addition to testing cut-offs previously established in the literature. Overall (OS), melanoma-specific (MSS), and recurrence-free survival (RFS) were determined from date of surgery and analysed using multivariable Cox regressions with age, sex, BMI, stage subgroup, ECOG PS, and tumor location as covariates. RESULTS: We included 330 patients in the final analysis. Mean age was 56 years and 62.4% of patients were male. At time of censoring 150 patients (45.6%) had died. Sarcopenia based on literature cut-offs was associated with decreased OS (HR 1.55, 95% CI 1.00-2.21, p = 0.016). Using cohort-specific cut-offs, sarcopenic patients also had significantly decreased OS (HR 1.87, 95% CI 1.27-2.76, p = 0.002). Myosteatosis defined using cohort-specific cut-offs predicted worse OS (HR 2.15, 95% CI 1.42-3.25, p < 0.001), MSS (HR 2.29, 95% CI 1.40-3.75, p = 0.001) and RFS (HR 1.52, 95% CI 1.02-2.27, p = 0.041). Increased BMI ( ≥ 25) and visceral fat index were not significantly associated with survival. CONCLUSIONS: Sarcopenia and myosteatosis, defined using two sets of cut-offs, are associated with decreased OS and MSS in resected stage III melanoma.

Effects of individual differences, society, and culture on youth-rated problems and strengths in 38 societies.

BACKGROUND: Clinicians increasingly serve youths from societal/cultural backgrounds different from their own. This raises questions about how to interpret what such youths report. Rescorla et al. (2019, European Child & Adolescent Psychiatry, 28, 1107) found that much more variance in 72,493 parents' ratings of their offspring's mental health problems was accounted for by individual differences than by societal or cultural differences. Although parents' reports are essential for clinical assessment of their offspring, they reflect parents' perceptions of the offspring. Consequently, clinical assessment also requires self-reports from the offspring themselves. To test effects of individual differences, society, and culture on youths' self-ratings of their problems and strengths, we analyzed Youth Self-Report (YSR) scores for 39,849 11-17 year olds in 38 societies. METHODS: Indigenous researchers obtained YSR self-ratings from population samples of youths in 38 societies representing 10 culture cluster identified in the Global Leadership and Organizational Behavioral Effectiveness study. Hierarchical linear modeling of scores on 17 problem scales and one strengths scale estimated the percent of variance accounted for by individual differences (including measurement error), society, and culture cluster. ANOVAs tested age and gender effects. RESULTS: Averaged across the 17 problem scales, individual differences accounted for 92.5% of variance, societal differences 6.0%, and cultural differences 1.5%. For strengths, individual differences accounted for 83.4% of variance, societal differences 10.1%, and cultural differences 6.5%. Age and gender had very small effects. CONCLUSIONS: Like parents' ratings, youths' self-ratings of problems were affected much more by individual differences than societal/cultural differences. Most variance in self-rated strengths also reflected individual differences, but societal/cultural effects were larger than for problems, suggesting greater influence of social desirability. The clinical significance of individual differences in youths' self-reports should thus not be minimized by societal/cultural differences, which-while important-can be taken into account with appropriate norms, as can gender and age differences.

How can the education sector support children's mental health? Views of Australian healthcare clinicians.

OBJECTIVES: Policy makers in developed countries have long considered the education system an avenue for supporting mental health care for children. Whilst educators have identified many challenges to providing this support (e.g. non-core role, stigma, overcrowded curriculum), understanding clinicians' views on the role of educators and schools and how clinicians and schools could work together to achieve good mental health outcomes are important questions. However, clinician voices in how schools and health should work together for children's mental health care are frequently missing from the debate. We aimed to report clinicians' views about how the education system could support student's mental health and improve access to mental health care for children and adolescents. METHODS: 143 clinicians (approximately 35 each of child and adolescent psychiatrists, pediatricians, child psychologists and general practitioners (GPs)) from the states of Victoria and South Australia participated in semi-structured phone interviews between March 2018 and February 2019. Inductive content analysis was applied to address the broad study aims. FINDINGS: Key themes emerged: (1) The role of schools in supporting individual children; (2) School based programs to support children and families; and (3) Challenges of implementing these suggestions. Clinicians across all professional groups suggested the education system could play an important role in improving access to mental health services through harnessing existing staff or co-locating mental health clinicians. They also suggested schools could identify at risk children and implement coping and social skills programs. CONCLUSIONS: Schools and educators could play a key role in prevention and early intervention of children's mental health problems. However, before recommending exactly how to do this, key evidence gaps need to be addressed.