Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948).

INTRODUCTION: Circadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness. The combination of leucovorin, fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) is a standard treatment for pancreatic ductal adenocarcinoma (PDAC), that generates grades 3-4 adverse events in the majority of patients and an estimated 15%-30% emergency admission rate. The MultiDom study evaluates whether mFOLFIRINOX safety can be improved using a novel circadian-based telemonitoring-telecare platform in patients at home. The detection of early warning signals of clinical toxicities could guide their early management, possibly preventing emergency hospital admissions. METHODS AND ANALYSIS: This multicentre, interventional, prospective, longitudinal, single-arm study hypothesises that the mFOLFIRINOX-related emergency admission rate will be 5% (95% CI 1.7% to 13.7%), among 67 patients with advanced PDAC. Study participation is 7 weeks for each patient, including a reference week before chemotherapy onset and 6 weeks afterwards. Accelerometry and body temperature are measured q1-min using a continuously worn telecommunicating chest surface sensor, daily body weight is self-measured with a telecommunicating balance and 23 electronic patient-reported outcomes (e-PROs) are self-rated using a tablet. Hidden Markov model, spectral analyses and other algorithms automatically compute physical activity, sleep, temperature, body weight change, e-PRO severity and 12 circadian sleep/activity parameters, including the dichotomy index I

[Impact of an intervention on the practice of venous thromboprophylaxis recommendations in a geriatric setting.] / Intervention sur la pratique des recommandations de thromboprophylaxie veineuse.

The practice of prevention of venous thromboembolic disease in hospitalized elderly patients does not comply with published recommendations, in 30% of cases. The objective of this study was to evaluate the impact of recalling the recommendations on the venous thromboprophylaxis.

Intensive glycaemic control and cognitive decline in patients with type 2 diabetes: a meta-analysis.

The aim of this meta-analysis was to compare the effect of intensive vs standard glycaemic control on cognitive decline in type 2 diabetic patients. A systematic search of PubMed and ALOIS was conducted from inception up to October 30, 2014. Randomised controlled trials (RCTs) of type 2 diabetic patients comparing the rate of change in cognitive function among participants assigned to intensive vs standard glycaemic control were included. An inverse-variance-weighted random effects model was used to calculate standardised mean differences (SMDs) and 95% CIs. A total of 24 297 patients from five RCTs were included in the meta-analysis. Follow-up ranged from 3.3 to 6.2 years. The result from the pooled analysis showed that intensive glycaemic control was not associated with a slower rate of cognitive decline in patients with type 2 diabetes, compared with standard glycaemic control (SMD=0.02; 95% CI=-0.03 to 0.08) although there was some heterogeneity across individual studies (I(2)=68%, P for heterogeneity=0.01). There are few diabetes control trials including cognitive endpoints and a small number of trials comparing intensive and standard treatment strategies. Currently, intensive glycaemic control should not be recommended for prevention of cognitive decline in patients with type 2 diabetes because there is no evidence of its effectiveness. Moreover, the use of intensive diabetes treatment results in an increase of risk of hypoglycaemia, which is linked to a greater risk of poor cognition.

Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study.

BACKGROUND: Type 2 diabetes increases the risk for dementia, but whether it affects cognition before old age is unclear. We investigated whether duration of diabetes in late midlife and poor glycaemic control were associated with accelerated cognitive decline. METHODS: 5653 participants from the Whitehall II cohort study (median age 54.4 years [IQR 50.3-60.3] at first cognitive assessment), were classified into four groups: normoglycaemia, prediabetes, newly diagnosed diabetes, and known diabetes. Tests of memory, reasoning, phonemic and semantic fluency, and a global score that combined all cognitive tests, were assessed three times over 10 years (1997-99, 2002-04, and 2007-09). Mean HbA1c was used to assess glycaemic control during follow-up. Analyses were adjusted for sociodemographic characteristics, health-related behaviours, and chronic diseases. FINDINGS: Compared with normoglycaemic participants, those with known diabetes had a 45% faster decline in memory (10 year difference in decline -0.13 SD, 95% CI -0.26 to -0.00; p=0.046), a 29% faster decline in reasoning (-0.10 SD, -0.19 to -0.01; p=0.026), and a 24% faster decline in the global cognitive score (-0.11 SD, -0.21 to -0.02; p=0.014). Participants with prediabetes or newly diagnosed diabetes had similar rates of decline to those with normoglycaemia. Poorer glycaemic control in participants with known diabetes was associated with a significantly faster decline in memory (-0.12 [-0.22 to -0.01]; p=0.034) and a decline in reasoning that approached significance (-0.07 [-0.15 to 0.00]; p=0.052). INTERPRETATION: The risk of accelerated cognitive decline in middle-aged patients with type 2 diabetes is dependent on both disease duration and glycaemic control. FUNDING: US National Institutes of Health, UK Medical Research Council.