Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.

BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.

Low-fat cheese ameliorates glucose intolerance and normalizes insulin secretion in a rat model of type 2 diabetes by promoting ß-cell recovery.

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10 min (p < 0.05) but the iAUC was highly variable in all groups and statistical differences were not detected (p > 0.05). ß-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF (p < 0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced ß-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks.

Dairy product consumption and risk of non-alcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: It is unclear whether regular consumption of dairy products is associated with the risk of developing non-alcoholic fatty liver disease (NAFLD). Thus, we conducted a systematic review followed by a meta-analysis of studies reporting on the association of dairy consumption with NAFLD risk. METHODS AND RESULTS: We comprehensively searched PubMed, Web of Science, and Scopus for observational studies that evaluated the association between dairy intake and NAFLD likelihood that were published before September 1, 2022. The reported odds ratios (ORs) of fully adjusted models and their 95% confidence intervals (CIs) were pooled using a random-effects model for the meta-analysis. Out of 1206 articles retrieved, 11 observational studies, including 43,649 participants and 11,020 cases, were included. Pooled OR indicated a significant association between dairy intake and NAFLD (OR = 0.90; 95% CI: 0.83, 0.98; I2 = 67.8%, n = 11). Pooled ORs revealed that milk (OR: 0.86; 95% CI: 0.78, 0.95; I2 = 65.7%, n = 6), yogurt (OR: 0.88; 95% CI: 0.82; I2 = 0.0%, n = 4), and high-fat dairy (OR: 0.38; 95% CI: 0.19, 0.75; I2 = 0.0%, n = 5) consumption was inversely associated with NAFLD while cheese was not linked to NAFLD risk. CONCLUSION: We observed that consumption of dairy products is linked to a reduced risk of developing NAFLD. Overall, the data in the source articles is of low to moderate quality; therefore, further observational studies are required to support the current findings (PROSPERO Reg. number: CRD42022319028).

Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.

Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.

Association of dairy consumption patterns with the incidence of type 2 diabetes: Findings from Alberta's Tomorrow Project.

BACKGROUND AND AIMS: We aimed to extract dairy consumption patterns of men and women from a population-based cohort and then assess the association of each consumption pattern with incident T2D risk. METHODS AND RESULTS: This prospective study was conducted within the framework of Alberta's Tomorrow Project (ATP), in which 8615 men and 15,016 women provided information on dietary intake by completing a food-frequency questionnaire at baseline, and then were followed up over time to determine the incidence of T2D via questionnaires. Principal Component Analysis (PCA) was used to extract dairy consumption patterns (DCPs). The association between each extracted pattern and T2D incidence was estimated using multivariable logistic regression models.The incidence of T2D among men and women was 3.8 and 3.2%, respectively, and the mean duration of follow-up was 5.2 years. Three major DCPs were identified. After controlling for potential confounders, the OR for risk of T2D in men in the highest compared with those in the lowest quartile of the DCP3 (whole milk, regular cheese, and non-fat milk as a beverage and in cereal) was 0.64 (95%CI: 0.47 to 0.88, P-trend=0.001), whereas it was not significant for women. DCP1 and DCP2 were not associated with incident T2D in men or women. CONCLUSION: Adherence to a DCP characterized by higher consumption of whole milk, regular cheese, and non-fat milk was associated with decreased risk of incident T2D only in men. Our results support current evidence that a combination of different dairy products, regardless of their fat content, might be favorable for health maintenance, at least in men.

Evaluating clinician experience in value-based health care: the development and validation of the Clinician Experience Measure (CEM).

BACKGROUND: Clinicians' experiences of providing care constitute an important outcome for evaluating care from a value-based healthcare perspective. Yet no currently available instruments have been designed and validated for assessing clinicians' experiences. This research sought to address this important gap by developing and validating a novel instrument in a public health system in Australia. METHODS: A multi-method project was conducted using co-design with 12 clinician leaders from a range of NSW Health Local Health Districts to develop the Clinician Experience Measure (CEM). Validity and reliability analyses were conducted in two stages, first assessing face and content validity with a pool of 25 clinicians and then using psychometric analysis with data from 433 clinicians, including nurses, doctors and allied health and representing all districts within one jurisdiction in Australia. RESULTS: Data gathered from 25 clinicians via the face and content validity process indicated that the initial 31-items were relevant to the range of staff employed in the NSW state health system, with minor edits made to the survey layout and wording within two items. Psychometric analysis led to a rationalised 18-item final instrument, comprising four domains: psychological safety (4-items); quality of care (5-items); clinician engagement (4-items) and interprofessional collaboration (5-items). The 18-item four-factor model produced a good fit to the data and high levels of reliability, with factor loadings ranging from .62 to .94, with Cronbach's alpha (range: .83 to .96) and composite reliability (range: .85 to .97). CONCLUSIONS: The CEM is an instrument to capture clinicians' experiences of providing care across a health system. The CEM provides a useful tool for healthcare leaders and policy makers to benchmark and assess the impact of value-based care initiatives and direct change efforts.

Elevated miR-143 and miR-34a gene expression in human visceral adipose tissue are associated with insulin resistance in non-diabetic adults: a cross-sectional study.

OBJECTIVE: We aimed to evaluate the association of miR-143 and miR-34a expression in human visceral (VAT) and subcutaneous (SAT) adipose tissues with insulin resistance (IR). METHODS: VAT and SAT were obtained from 176 participants without diabetes. miR-143 and miR-34a expressions in VAT and SAT were measured using qRT-PCR. Fasting serum insulin and glucose concentration, homeostatic model assessment of IR index (HOMA-IR) and ß-cell function (HOMA-B), and quantitative insulin-sensitivity check index (QUICKI) were calculated. RESULTS: After adjustment for age, sex and body mass index (BMI), VAT miR-143 expression was positively associated with fasting plasma glucose (FPG), insulin, and HOMA-IR, and negatively associated with HOMA-B and QUICKI. miR-34a expression in VAT was directly associated with FPG, insulin, and HOMA-IR and negatively associated with QUICKI. In SAT, miR-34a expression was positively associated with insulin and negatively associated with QUICKI. The interaction terms of HOMA-IR and BMI categories were significant for both miR gene expressions in VAT. After stratifying participants based on BMI, the association of miR-143 and miR-34a expressions in VAT with IR indices remained significant only in obese patients. CONCLUSION: miR-143 and miR-34a expressions in VAT were independent predictors of IR in people without diabetes, and that this association was conditional on the degree of obesity. LEVEL OF EVIDENCE: Level of evidence III, cross-sectional analytic study.

Transient antibiotic-induced changes in the neonatal swine intestinal microbiota impact islet expression profiles reducing subsequent function.

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin [30 mg/kg body wt/day; n = 7, antibiotic (ANTI)] or placebo [vehicle control; n = 7, control (CON)] from postnatal day (PND)0-13 were euthanized at PND7, 14, and 49. The metabolic phenotype along with functional, immunohistological, and transcriptional phenotypes of the pancreatic islets were studied. The gut microbiome was characterized by 16S rRNA gene sequencing, and microbial metabolites and microbiome-sensitive host molecules were measured. Compared with CON, ANTI PND7 piglets had elevated transcripts of genes involved in glucagon-like peptide 1 ((GLP-1) synthesis or signaling in islets (P < 0.05) coinciding with higher plasma GLP-1 (P = 0.11), along with increased tumor necrosis factor α (Tnf) (P < 0.05) and protegrin 1 (Npg1) (P < 0.05). Antibiotic-induced relative increases in Escherichia, Coprococcus, Ruminococcus, Dehalobacterium, and Oscillospira of the ileal microbiome at PND7 normalized after antibiotic withdrawal. In ANTI islets at PND14, the expression of key regulators pancreatic and duodenal homeobox 1 (Pdx1), insulin-like growth factor-2 (Igf2), and transcription factor 7-like 2 (Tcf7l2) was downregulated, preceding a 40% reduction of ß-cell area (P < 0.01) and islet insulin content at PND49 (P < 0.05). At PND49, a twofold elevated plasma insulin concentration (P = 0.07) was observed in ANTI compared with CON. We conclude that antibiotic treatment of neonatal piglets elicited gut microbial changes accompanied by phasic alterations in key regulatory genes in pancreatic islets at PND7 and 14. By PND49, reduced ß-cell area and islet insulin content were accompanied by elevated nonfasted insulin despite normoglycemia, indicative of islet stress.

The association of dietary and plasma fatty acid composition with FTO gene expression in human visceral and subcutaneous adipose tissues.

PURPOSE: The human obesity susceptibility gene, FTO, associates with body mass and obesity in humans through regulation of energy expenditure and intake. We aimed to determine how fatty acids in plasma and in diet associate with FTO gene expression in subcutaneous and visceral adipose tissues. METHODS: In this study, 97 participants aged ≥ 18 years were selected from patients admitted to the hospital for abdominal surgeries. Habitual dietary intake of participants was collected using a valid and reliable food frequency questionnaire (FFQ), from which the intake of fatty acids was quantified. Plasma fatty acids were assessed by gas-liquid chromatography. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues obtained by biopsy was measured by Real-Time Quantitative Reverse Transcription PCR. Standardized ß-coefficients were calculated by multivariable linear regression. RESULTS: After adjusting for age, homeostasis model insulin resistance index (HOMA-IR), and body mass index, total fatty acid intake was significantly associated with FTO gene expression in visceral (STZß = 0.208, P = 0.037) and subcutaneous (STZß = 0.236, P = 0.020) adipose tissues. Dietary intake of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) had positive significant associations with the expression of FTO in visceral (STZß = 0.227, P = 0.023; STZß = 0.346, P < 0.001, respectively) and subcutaneous (STZß = 0.227, P = 0.026; STZß = 0.274, P = 0.006, respectively) adipose tissues. There were no associations between plasma fatty acids and FTO mRNA expression in either subcutaneous or visceral adipose tissues. CONCLUSION: The weak association of dietary total fatty acids, MUFA, and PUFA with FTO gene expression in both adipose tissues may highlight the importance of dietary fatty acids composition along with total fat intake in relation to FTO gene expression.

Changes in dairy product consumption and subsequent type 2 diabetes among individuals with prediabetes: Tehran Lipid and Glucose Study.

BACKGROUND: People with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes. METHOD: This cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years. RESULTS: After almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively. CONCLUSION: In individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients.

Metformin Preserves ß-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats.

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic ß-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and ß-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on ß-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human ß-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on ß-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited ß-cell glucose-stimulated insulin secretion in vitro, stimulation of ß-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, ß-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress ß-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on ß-cell function or cell mass and, instead, early metformin treatment may help protect ß-cells from exhaustion and decompensation.

Cost-effectiveness analysis of ceritinib vs. crizotinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong.

INTRODUCTION: Lower-dose ceritinib (450 mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK +) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK + NSCLC from a HK healthcare service provider's or government's perspective. METHODS: Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from a phase 3 trial comparing ceritinib with chemotherapy for advanced non-small cell lung cancer (ASCEND-4) and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib. RESULTS: The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios. CONCLUSION: Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK + advanced NCSLC in HK.

Clinical Controversies in Cervical Cancer Screening.

Through the implementation of systematic cervical cancer screening in the mid-20th century, the United States and other developed countries have seen death rates from cervical cancer decreased by ≥70%.The purpose of this article is to address several of the most controversial issues associated with cervical cancer screening recommendations in light of historical and evolving data. In this article, we will explore the controversies around the age at which to initiate and exit screening, human papilloma virus testing alone as a primary screening approach, and the impact of human papilloma virus vaccination on cervical cancer rates.

A systematic review of health status, health seeking behaviour and healthcare utilisation of low socioeconomic status populations in urban Singapore.

INTRODUCTION: It is well-established that low socioeconomic status (SES) influences one's health status, morbidity and mortality. Housing type has been used as an indicator of SES and social determinant of health in some studies. In Singapore, home ownership is among the highest in the world. Citizens who have no other housing options are offered heavily subsidised rental housings. Residents staying in such rental housings are characterised by low socioeconomic status. Our aim is to review studies on the association between staying in public rental housing in Singapore and health status. METHODS: A PubMed and Scopus search was conducted in January 2017 to identify suitable articles published from 1 January 2000 to 31 January 2017. Only studies that were done on Singapore public rental housing communities were included for review. A total of 14 articles including 4 prospective studies, 8 cross-sectional studies and 2 retrospective cohort studies were obtained for the review. Topics addressed by these studies included: (1) Health status; (2) Health seeking behaviour; (3) Healthcare utilisation. RESULTS: Staying in public rental housing was found to be associated with poorer health status and outcomes. They had lower participation in health screening, preferred alternative medicine practitioners to western-trained doctors for primary care, and had increased hospital utilisation. Several studies performed qualitative interviews to explore the causes of disparity and concern about cost was one of the common cited reason. CONCLUSION: Staying in public rental housing appears to be a risk marker of poorer health and this may have important public health implications. Understanding the causes of disparity will require more qualitative studies which in turn will guide interventions and the evaluation of their effectiveness in improving health outcome of this sub-population of patients.

Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity.

Epicatechin (EC) is a monomeric flavan-3-ol. We have previously demonstrated that glucose-intolerant rats fed flavan-3-ols exhibit improved pancreatic islet function corresponding with an increase in circulating EC-derived metabolites. Thus, we speculate that EC may act as a cellular signaling molecule in vivo to modulate insulin secretion. In this study we further examined the effects of different concentrations of EC on H2O2 or hyperglycemia-induced ROS production, as well as on saturated fatty acid (SFA)-impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cell line in vitro. We showed that EC at a high concentration (30 µmol/L), but not a low concentration (0.3 µmol/L), significantly decreased H2O2 or hyperglycemia-induced ROS production in INS-1 cells. However, EC (0.3 µmol/L) significantly enhanced SFA-impaired GSIS in INS-1 cells. Addition of KN-93, a CaMKII inhibitor, blocked the effect of EC on insulin secretion and decreased CaMKII phosphorylation. Addition of GW1100, a GPR40 antagonist, significantly attenuated EC-enhanced GSIS, but only marginally affected CaMKII phosphorylation. These results demonstrate that EC at a physiological concentration promotes GSIS in SFA-impaired ß-cells via activation of the CaMKII pathway and is consistent with its function as a GPR40 ligand. The findings support a role for EC as a cellular signaling molecule in vivo and further delineate the signaling pathways of EC in ß-cells.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

Safety of Active Rehabilitation for Persistent Symptoms After Pediatric Sport-Related Concussion: A Randomized Controlled Trial.

OBJECTIVES: To examine the safety and tolerability of an active rehabilitation program for adolescents who are slow to recover from a sport-related concussion, and secondarily to estimate the treatment effect for this intervention. DESIGN: Single-site, parallel, open-label, randomized controlled trial comparing treatment as usual (TAU) to TAU plus active rehabilitation. SETTING: Outpatient concussion clinic. PARTICIPANTS: Adolescents (N=19) aged 12 to 18 years with postconcussion symptoms lasting ≥1 month after a sports-related concussion. INTERVENTIONS: TAU consisted of symptom management and return-to-play advice, return-to-school facilitation, and physiatry consultation. The active rehabilitation program involved in-clinic subsymptom threshold aerobic training, coordination exercises, and visualization and imagery techniques with a physiotherapist (mean, 3.4 sessions) as well as a home exercise program, over 6 weeks. MAIN OUTCOME MEASURES: A blinded assessor systematically monitored for predetermined adverse events in weekly telephone calls over the 6-week intervention period. The treating physiotherapist also recorded in-clinic symptom exacerbations during aerobic training. The Post-Concussion Symptom Scale was the primary efficacy outcome. RESULTS: Nineteen participants were randomized, and none dropped out of the study. Of the 12 adverse events detected (6 in each group), 10 were symptom exacerbations from 1 weekly telephone assessment to the next, and 2 were emergency department visits. Four adverse events were referred to an external safety committee and deemed unrelated to the study procedures. In-clinic symptom exacerbations occurred in 30% (9/30) of aerobic training sessions, but resolved within 24 hours in all instances. In linear mixed modeling, active rehabilitation was associated with a greater reduction on the Post-Concussion Symptom Scale than TAU only. CONCLUSIONS: The results support the safety, tolerability, and potential efficacy of active rehabilitation for adolescents with persistent postconcussion symptoms.

Age, gender, and current living status were associated with perceived access to treatment among Canadians using a cross sectional survey.

BACKGROUND: Access, particularly timely access, to care is the Canadian public's most important healthcare concern. The drivers of perceived appropriateness of access to care among patients with at least one chronic health condition (CHC) are not, however, well defined. This study evaluated whether personal characteristics, self-reported health status and care received were associated with patients' perception of effective access in managing a chronic illness. METHODS: The study population (n = 619) was drawn from a representative sample of the adult Canadian population who reported having ≥1 CHC in the 2013-2014 Health Care in Canada survey. Ordinal regression, with the continuation ratio model, was used to evaluate association of perceived level of access to treatment with socio-demographic factors, perceived health status and care utilization experience. RESULTS: Factors most closely associated with patients' satisfaction with care access were: age, sex, current cohabitation, care affordability, and availability of support and information to help manage their CHCs. Individuals, particularly females, < 35 years, currently living alone, with poor access to professional support or information and who feel affordability of care has worsened over the past five years were more likely to report a poorer level of treatment access. CONCLUSIONS: Individuals living alone, who are younger, and women may be especially susceptible to lower perceived access to care of CHCs and a sense of pessimism about things not getting better. Further evaluation of the reasons behind these findings may help develop effective strategies to assist these populations to access the care they need.

Clinical outcome and prognosis of dogs with histopathological features consistent with epitheliotropic lymphoma: a retrospective study of 148 cases (2003-2015).

BACKGROUND: Limited information is available regarding the treatment and outcome of dogs with epitheliotropic lymphoma. The disease typically has a poor prognosis. OBJECTIVES: To characterize the clinical signs, identify prognostic factors and evaluate the treatment outcome of dogs with epitheliotropic lymphoma. METHODS: A retrospective review of medical records from 2003 to 2015. Treatment details, tumour response and survival time were recorded for 148 dogs. Potential prognostic factors were evaluated for their statistical effect on median survival time. RESULTS: The overall median survival time for dogs was 264 days (cutaneous: 130 days; mucocutaneous/mucosal: 491 days). On multivariate analysis, a shorter median survival time was associated with the cutaneous form (P < 0.001) and the presence of multiple lesions (P < 0.001). Among 80 dogs with cutaneous lesions, chemotherapy treatment (P < 0.001) and having a solitary lesion (P < 0.001) were associated with longer median survival. In 72 dogs with multiple cutaneous lesions, chemotherapy intervention (P < 0.001), retinoid treatment (P = 0.001) and complete remission (P = 0.001) were associated with longer median survival. In 68 dogs with mucocutaneous/mucosal lesions, decreasing age (P = 0.020) and a solitary lesion (P = 0.015) were associated with longer median survival. CONCLUSION: Canine epitheliotropic lymphoma may be divided into cutaneous and mucocutaneous/mucosal forms. Solitary lesions have a better prognosis. Dogs with multiple lesions appear to benefit from chemotherapy and retinoid treatment, with those attaining complete remission having longer survival times. Multi-agent chemotherapy could be considered in dogs with cutaneous lesions that fail to respond to single-agent chemotherapy.

IKKß inhibition prevents fat-induced beta cell dysfunction in vitro and in vivo in rodents.

AIMS/HYPOTHESIS: We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase ß (IKKß), which is activated by oxidative stress, is also implicated. METHODS: Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKß inhibitor salicylate. Thereafter, beta cell function was evaluated in vivo using hyperglycaemic clamps or ex vivo in islets isolated from fat-treated rats. We also exposed rat islets to oleate in culture, with or without salicylate and 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; BMS-345541 (BMS, another inhibitor of IKKß) and evaluated beta cell function in vitro. Furthermore, oleate was infused in mice treated with BMS and in beta cell-specific Ikkb-null mice. RESULTS: 48 h infusion of fat impaired beta-cell function in vivo, assessed using the disposition index (DI), in rats (saline: 1.41 ± 0.13; oleate: 0.95 ± 0.11; olive oil [OLO]: 0.87 ± 0.15; p < 0.01 for both fats vs saline) and in mice (saline: 2.51 ± 0.39; oleate: 1.20 ± 0.19; p < 0.01 vs saline) and ex vivo (i.e., insulin secretion, units are pmol insulin islet-1 h-1) in rat islets (saline: 1.51 ± 0.13; oleate: 1.03 ± 0.10; OLO: 0.91 ± 0.13; p < 0.001 for both fats vs saline) and the dysfunction was prevented by co-infusion of salicylate in rats (oleate + salicylate: 1.30 ± 0.09; OLO + salicylate: 1.33 ± 0.23) or BMS in mice (oleate + BMS: 2.25 ± 0.42) in vivo and by salicylate in rat islets ex vivo (oleate + salicylate: 1.74 ± 0.31; OLO + salicylate: 1.54 ± 0.29). In cultured islets, 48 h exposure to oleate impaired beta-cell function ([in pmol insulin islet-1 h-1] control: 0.66 ± 0.12; oleate: 0.23 ± 0.03; p < 0.01 vs saline), an effect prevented by both inhibitors (oleate + salicylate: 0.98 ± 0.08; oleate + BMS: 0.50 ± 0.02). Genetic inhibition of IKKß also prevented fat-induced beta-cell dysfunction ex vivo ([in pmol insulin islet-1 h-1] control saline: 0.16 ± 0.02; control oleate: 0.10 ± 0.02; knockout oleate: 0.17 ± 0.04; p < 0.05 control saline vs. control oleate) and in vivo (DI: control saline: 3.86 ± 0.40; control oleate: 1.95 ± 0.29; knockout oleate: 2.96 ± 0.24; p < 0.01 control saline vs control oleate). CONCLUSIONS/INTERPRETATION: Our results demonstrate a causal role for IKKß in fat-induced beta cell dysfunction in vitro, ex vivo and in vivo.