Cost analysis and cost-effectiveness of open versus laparoscopic versus robot-assisted versus transanal total mesorectal excision in patients with rectal cancer:a protocol for a systematic review

INTRODUCTION: Nowadays, most rectal tumours are treated open or minimally invasive, using laparoscopic, robot-assisted or transanal total mesorectal excision. However, insight into the total costs of these techniques is limited. Since all three techniques are currently being performed, including cost considerations in the choice of treatment technique may significantly impact future healthcare costs. Therefore, this systematic review aims to provide an overview of evidence regarding costs in patients with rectal cancer following open, laparoscopic, robot-assisted and transanal total mesorectal excision. METHODS AND ANALYSIS: A systematic search will be conducted for papers between January 2000 and March 2022. Databases PubMed/MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library databases will be searched. Study selection, data extraction and quality assessment will be performed independently by four reviewers and discrepancies will be resolved through discussion. The Consensus Health Economic Criteria list will be used for assessing risk of bias. Total costs of the different techniques, consisting of but not limited to, theatre, in-hospital and postoperative costs, will be the primary outcome. ETHICS AND DISSEMINATION: No ethical approval is required, as there is no collection of patient data at an individual level. Findings will be disseminated widely, through peer-reviewed publication and presentation at relevant national and international conferences. TRIAL REGISTRATION NUMBER: CRD42021261125

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

Objectives: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. Methods: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. Results: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). Conclusions: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. S

Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

BACKGROUND AND AIMS: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients. METHODS: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDL(DGUC2)), by sequential salt density flotation (HDL(SEQ)) or by PEG precipitation (HDL(PEG)). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC). RESULTS: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 μM, HDL(DGUC2) and HDL(SEQ) were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDL(PEG) (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDL(DGUC2) for further experiments. With apoA-I at 3.2 μM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively (p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC. CONCLUSIONS: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Bright light therapy in pregnant women with major depressive disorder: Study protocol for a randomized, double-blind, controlled clinical trial

Background: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. Methods: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. Discussion: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Trial registration: Netherlands Trial Register NTR5476. Registered 5 November 2015

Prior consumption of a fat meal in healthy adults modulates the brain’s response to fat

Background: Consumption of fat is regulated by reward and homeostatic pathways, but no studies have examined the role of the intake of a high fat meal (HFM) on subsequent brain activation to oral stimuli. Objective: We evaluated how prior consumption of a HFM or water load (WL) modulates reward, homeostatic and taste brain responses to subsequent delivery of oral fat. Methods: A randomized 2-way crossover design (1-week apart) was used to compare prior consumption of a 250mL HFM (520kcal) (rapeseed oil (440kcal), emulsifier, sucrose, flavor cocktail) or non-caloric WL on brain activation to the delivery of repeated trials of an oral flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 male, age=25±2 years, BMI=22.4±0.8kg/m2). Analyses tested differences in brain activation to the CS and FS, and baseline cerebral blood flow (CBF), following the HFM and WL. Individual’s plasma cholecystokinin (CCK) concentration following the HFM was correlated with their BOLD activation. Results: Prior consumption of the HFM compared to the WL led to decreased anterior insula taste activation in response to both the CS (36.3%,P<0.05) and FS (26.5%,P<0.05). The HFM caused reduced amygdala activation (25.1%,P<0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula (5.7%,P<0.01)), homeostatic (hypothalamus (9.2%,P<0.01), thalamus (5.1%,P<0.05))), and reward areas (striatum (9.2%,P<0.01)) following the HFM. Individual’s plasma CCK concentration negatively correlated with brain activation in taste, oral somatosensory and reward areas. Conclusions: To reduce obesity, policy in industry is to lower the fat content of foods. Our results in healthy adults show that a HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain’s response to high fat counterparts, and guide future interventions to reduce obesity

Dental calculus and isotopes provide direct evidence of fish and plant consumption in Mesolithic Mediterranean

In this contribution we dismantle the perceived role of marine resources and plant foods in the subsistence economy of Holocene foragers of the Central Mediterranean using a combination of dental calculus and stable isotope analyses. The discovery of fish scales and flesh fragments, starch granules and other plant and animal micro-debris in the dental calculus of a Mesolithic forager dated to the end of the 8th millenium BC and buried in the Vlakno Cave on Dugi Otok Island in the Croatian Archipelago demonstrates that marine resources were regularly consumed by the individual together with a variety of plant foods. Since previous stable isotope data in the Eastern Adriatic and the Mediterranean region emphasises that terrestrial-based resources contributed mainly to Mesolithic diets in the Mediterranean Basin, our results provide an alternative view of the dietary habits of Mesolithic foragers in the Mediterranean region based on a combination of novel methodologies and data

The Impact of Insulin Pump Therapy on Glycemic Profiles in Patients with Type 2 Diabetes: Data from the OpT2mise Study

Background: The OpT2mise randomized trial was designed to compare the effects of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) on glucose profiles in patients with type 2 diabetes. Research Design and Methods: Patients with glycated hemoglobin (HbA1c) levels of ≥8% (64 mmol/mol) and ≤12% (108 mmol/mol) despite insulin doses of 0.7-1.8 U/kg/day via MDI were randomized to CSII (n=168) or continued MDI (n=163). Changes in glucose profiles were evaluated using continuous glucose monitoring data collected over 6-day periods before and 6 months after randomization. Results: After 6 months, reductions in HbA1c levels were significantly greater with CSII (-1.1±1.2% [-12.0±13.1 mmol/mol]) than with MDI (-0.4±1.1% [-4.4±12.0 mmol/mol]) (P&lt;0.001). Similarly, compared with patients receiving MDI, those receiving CSII showed significantly greater reductions in 24-h mean sensor glucose (SG) (treatment difference, -17.1 mg/dL; P=0.0023), less exposure to SG &gt;180 mg/dL (-12.4%; P=0.0004) and SG &gt;250 mg/dL (-5.5%; P=0.0153), and more time in the SG range of 70-180 mg/dL (12.3%; P=0.0002), with no differences in exposure to SG&lt;70 mg/dL or in glucose variability. Changes in postprandial (4-h) glucose area under the curve &gt;180 mg/dL were significantly greater with CSII than with MDI after breakfast (-775.9±1,441.2 mg/dL/min vs. -160.7±1,074.1 mg/dL/min; P=0.0015) and after dinner (-731.4±1,580.7 mg/dL/min vs. -71.1±1,083.5 mg/dL/min; P=0.0014). Conclusions: In patients with suboptimally controlled type 2 diabetes, CSII significantly improves selected glucometrics, compared with MDI, without increasing the risk of hypoglycemia