Anti-Hypertensive Therapy and Risk Factors Associated with Hypotension during Colonoscopy under Conscious Sedation*

Abstract Background & Aims: Pre-operative use of select antihypertensive therapy has been associated with peri-operative hypotension in the surgical setting. Our aim was to determine the effect of anti-hypertensive medications on blood pressure (BP) and procedural outcomes in gastrointestinal endoscopy. methods: Our study was a prospective, crosssectional survey of outpatients undergoing colonoscopy with conscious sedation. We enrolled patients with hypertension that took anti-hypertensive medications within 24 hours of the procedure and patients without hypertension that were not on BP-lowering agents. We recorded mean BP prior to, during, and after the procedure. Results: 626 patients (338 males; mean age 56.0 ± 10.4 years) were enrolled, and 158 patients were on anti-hypertensive therapy. There were 57 patients who developed hypotension, defined as systolic BP <90 mmHg and/or diastolic BP <60 mmHg, during the colonoscopy. Taking a BP medication, regardless of class, was not associated with an increased risk of procedural hypotension (all p >0.05). Age, body mass index, gender, duration, fentanyl dose, midazolam dose, and co-morbidities (asthma, chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease) were also not associated (all p >0.05). Instead, a lower pre-procedure systolic BP (OR=0.97, 95% CI=0.95-0.99; p=0.004) and diastolic BP (OR=0.95, 95% CI=0.92-0.97; p<0.001) were identified as the only risk factors. Conclusion: Patients should continue their anti-hypertensive therapy leading u

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Acute Care for Elders (ACE) Team Model of Care: A Clinical Overview

The Institute of Medicine (IOM) Reports of To Err is Human and Crossing the Quality Chasm have called for more interprofessional and coordinated hospital care. For over 20 years, Acute Care for Elders (ACE) Units and models of care that disseminate ACE principles have demonstrated outcomes in-line with the IOM goals. The objective of this overview is to provide a concise summary of studies that describe outcomes of ACE models of care published in 1995 or later. Twenty-two studies met the inclusion. Of these, 19 studies were from ACE Units and three were evaluations of ACE Services, or teams that cared for patients on more than one hospital unit. Outcomes from these studies included increased adherence to evidence-based geriatric care processes, improved patient functional status at time of hospital discharge, and reductions in length of stay and costs in patients admitted to ACE models compared to usual care. These outcomes represent value-based care. As interprofessional team models are adopted, training in successful team functioning will also be needed

Testing the feasibility and dietary impact of a "produce prescription" program for adults with undermanaged type 2 diabetes and food insecurity in Australia

Background: There is growing interest in Food is Medicine programs that incorporate food-based interventions into health care for patients with diet-related conditions. Objectives: We aimed to test the feasibility of a “produce prescription” program and its impact on diet quality for people with type 2 diabetes (T2D) experiencing food insecurity in Australia. Methods: We conducted a pre–post intervention study in n = 50 adults experiencing food insecurity with T2D and glycated hemoglobin (HbA1c) ≥8%. Once enrolled, participants received healthy food boxes weekly free of charge, with the contents sufficient to create 2 meals/d, 5 d/wk for the entire household, over 12 wk. Participants were also provided with tailored recipes and behavioral change support. The primary outcome was change in diet quality assessed by 24-h diet recalls. Secondary outcomes included differences in cardiovascular disease risk factors; blood micronutrients; and feasibility indicators. Differences in the baseline and 12-wk mean primary and secondary outcomes were assessed by paired t tests. Results: Participants were older adults with mean ± SD age 63 ± 9 y (range: 40–87 y), HbA1c 9.8% ± 1.5%, and 46% were female. Overall, 92% completed the final study follow-up for the primary outcome. Compared with baseline, diet quality improved at week 12, with an increase in the mean overall diet quality (Alternate Healthy Eating Index score) of 12.9 (95% CI: 8.7, 17.1; P < 0.001), driven by significant improvements in vegetables, fruits, whole grains, red/processed meat, trans fat, sodium, and alcohol consumption. Blood lipids also improved (total:HDL cholesterol: −0.48; 95% CI: −0.72, −0.24; P < 0.001), and there was significant weight loss (−1.74 kg; 95% CI: −2.80, −0.68 kg, P = 0.002), but no changes in other clinical outcomes. Participants reported high levels of satisfaction with the program. Conclusions: These findings provide strong support for an adequately powered randomized trial to assess effects of produce prescription as an innovative approach to improve clinical management among individuals with T2D experiencing food insecurity. This trial was registered at https://anzctr.org.au/ as ACTRN12621000404820

Metformin in women with type 2 diabetes in pregnancy (MiTy) : a multicentre, international, randomised, placebo-controlled trial

Background Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. Methods In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m² or ≥30 kg/m²) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22weeks plus 6 days’ gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5.3 mmol/L [95 mg/dL], 2-h postprandial glucose <6.7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1–4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. Findings Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks’ gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [–10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] mmol/L vs 6·27 [0·90] mmol/L; difference –0·2 [–0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference –0·4 [95% CI –0·5 to –0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference –1·8 [–2·7 to –0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference –218 [–353 to –82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference –1·41 [–2·6 to –0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 [27%] events in the metformin group and 38 [22%] events in the placebo group). Interpretation We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain, insulin dosage, and rate of caesarean sections, and improved glyacaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy

Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations. Despite attempts to bridge the disparities gap, there remains an unmet need to expand minority engagement and participation in clinical trials to better define the impact of therapy on efficacy outcomes, quality of life, and role of biomarkers in diverse patient populations. The IRONMAN registry (ClinicalTrials.gov identifier: NCT03151629 ), a global, prospective, population-based study, was borne from this unmet medical need to address persistent gaps in our knowledge of advanced prostate cancer. Through integrated collection of clinical outcomes, patient-reported outcomes, epidemiologic data, and biospecimens, IRONMAN has the goal of expanding our understanding of how and why prostate cancer outcomes differ by race and ethnicity. To this end, the Diversity Working Group of the IRONMAN registry has developed informed strategies for site selection, recruitment, engagement and retention, and trial design and eligibility criteria to ensure broad inclusion and needs awareness of minority participants. In concert with systematic strategies to tackle the complex levels of disparate care, our ultimate goal is to expand minority engagement in clinical research and bridge the disparities gap in prostate cancer care