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Although many clinicians feel they already use shared decision making, research shows a perception-reality gap. A M Stiggelbout and colleagues discuss why it is important and highlight some best practices

IntroductionThe Problem Areas of Diabetes (PAID) questionnaire is a frequently used measure to assess diabetes-distress. The aim of this study was to identify clinically meaningful levels of diabetes-distress, using latent class analyses (LCA), and to determine which groups were at increased risk of elevated diabetes-distress in terms of sex, age, type of diabetes and glycaemic control.MethodsData were derived from four studies (total N=2966, 49% female, age range 18–95 years, 43% type 1 diabetes, diabetes duration range 0–79 years). LCAs were performed to examine possible latent groups in the distribution of answers on the individual PAID items. Demographic and diabetes-related characteristics were added to the model to estimate their effects on latent class membership and receiver operating curves curves to determine cut-offs.ResultsThree levels of diabetes distress were distinguished with defined cut-off scores and labelled as: low, moderate and high diabetes distress. Levels of distress did not associate with distinct clusters of items. Older people were more likely to be part of the low distress class; women and people with high HbA1c were more likely to be part of the high distress class. Sensitivity and specificity of the commonly used cut-off of 40 for high distress are 0.95 and 0.97, respectively. To distinguish the moderate distress group, cut-off scores of 17 and 39 are optimal with a sensitivity of 0.93 and a specificity of 0.94.ConclusionThree levels of diabetes-distress can be distinguished: low, moderate and high diabetes distress. Younger people, women and people with poor glycaemic control are at an increased risk for high levels of distress. A cut-off of 40 is satisfactory to detect people with high levels of diabetes-distress; a score of 0–16 indicates low diabetes distress and a score of 17–39 moderate diabetes distress.

Effectiveness of psychological treatment is often assessed using patient-reported health evaluations. However, comparison of such scores over time can be hampered due to a change in the meaning of self-evaluations, called 'response shift'. Insight into the occurrence of response shift seems especially relevant in the context of psychological interventions, as they often purposefully intend to change patients' frames of reference. The overall aim is to gain insight into the general relevance of response shift for psychological health intervention research. Specifically, the aim is to re-analyse data of published randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions targeting different health aspects, to assess (1) the occurrence of response shift, (2) the impact of response shift on interpretation of treatment effectiveness, and (3) the predictive role of clinical and background variables for detected response shift. We re-analysed data from RCTs on guided internet delivered cognitive behavioural treatment (CBT) for insomnia in the general population with and without elevated depressive symptoms, an RCT on meaning-centred group psychotherapy targeting personal meaning for cancer survivors, and an RCT on internet-based CBT treatment for persons with diabetes with elevated depressive symptoms. Structural equation modelling was used to test the three objectives. We found indications of response shift in the intervention groups of all analysed datasets. However, results were mixed, as response shift was also indicated in some of the control groups, albeit to a lesser extent or in opposite direction. Overall, the detected response shifts only marginally impacted trial results. Relations with selected clinical and background variables helped the interpretation of detected effects and their possible mechanisms. This study showed that response shift effects can occur as a result of psychological health interventions. Response shift did not influence the overall interpretation of trial results, but provide insight into differential treatment effectiveness for specific symptoms and/or domains that can be clinically meaningful.

Purpose This randomized controlled trial tested the effects of a specially designed strength and endurance training on the independence and quality of life in lung cancer patients in stages IIIA/IIIB/IV during palliative chemotherapy. Methods Between August 2010 and December 2011, 46 patients were randomized into two groups receiving either conventional physiotherapy or special physiotherapeutic training. The Barthel Index served as primary endpoint. The secondary endpoints were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C-30/LC-13) questionnaire, the 6-Minute Walk Test (6MWT), stair walking, the Modified Borg Scale, and muscle strength. Nonparametrical data were analyzed with the Wilcoxon and Mann–Whitney U test. For parametric, data student t tests were used. A p value of ≤.05 was accepted. Results Twenty-nine patients completed the trial (Intervention group (IG), n  = 18; control group (CG), n  = 11). Significant differences were detectable in the Barthel Index (IGmean = 92.08; CGmean = 81.67; p  = .041), in single scores of the EORTC QLQ C-30/LC-13 questionnaire (physical functioning, p  = .025; hemoptysis, p  = .019; pain in arms or shoulder, p  = .048; peripheral neuropathy, p  = .050; cognitive functioning, p  = .050), in the 6MWT, stair walking, strength capacity, and in the patient’s dyspnoea perception during submaximal walking activities (IG > CG). Conclusion According to these findings, lung cancer patients should receive enhanced physical activity intervention during palliative chemotherapy.

α-tomatineis an antifungal glycoalkaloid that provides basal defense to tomato (Solanum lycopersicum). However, tomato pathogens overcome this basal defense barrier by the secretion of tomatinases that degrade α-tomatineinto the less fungitoxic compounds β-tomatine and tomatidine. Although pathogenic on tomato, it has been reported that the biotrophic fungus Cladosporium fulvum is unable to detoxify α-tomatine. Here, we present a functional analysis of the glycosyl hydrolase (GH10), CfTom1, which is orthologous to fungal tomatinases. We show that C. fulvum hydrolyzes α-tomatineinto tomatidine in vitro and during the infection of tomato, which is fully attributed to the activity of CfTom1, as shown by the heterologous expression of this enzyme in tomato. Accordingly, Δcftom1 mutants of C. fulvum are more sensitive to α-tomatineand are less virulent than the wild-type fungus on tomato. Although α-tomatineis thought to be localized in the vacuole, we show that it is also present in the apoplast, where it is hydrolyzed by CfTom1 on infection. The accumulation of tomatidine during infection appears to be toxic to tomato cells and does not suppress defense responses, as suggested previously. Altogether, our results show that CfTom1 is responsible for the detoxification of α-tomatine by C. fulvum, and is required for full virulence of this fungus on tomato.

Background Results of studies concerning the association between obesity and depression are conflicting. Some find a positive association, some a negative association and some find no association at all. Most studies, however, examine a linear association between Body Mass Index (BMI) and depression. The present study investigates if a nonlinear (U-shaped) trend is preferable over a linear trend to describe the relationship between BMI and depression, which means that both underweight and obesity are associated with depression. Methods We investigated the existence of such a U-curve in a sample of 43,534 individuals, aged between 18–90 years, who participated in a cross-sectional study (Continuous Survey of Living Conditions) of physical and mental health in the general population of the Netherlands. We calculated linear and nonlinear (quadratic) ANOVA with polynomial contrast and curve fit regression statistics to investigate whether there was a U-shaped trend in the association between BMI and depression. Results We find a very significant U-shaped association between BMI categories (underweight, normal, overweight and obesity) and depression ( p ≤ 0.001). There is a trend indicating a significant difference in the association between males and females ( p = 0.05). We find a very significant U-shaped (quadratic) association between BMI (BMI 2 ) and depression ( p ≤ 0.001), continuous BMI is not linearly associated with depression ( p = 0.514). Conclusion The results of this study give evidence for a significant U-shaped trend in the association between BMI and depression.

Quantifying the variation of pathogens’ life history traits in multiple host systems is crucial to understand their transmission dynamics. It is particularly important for arthropod-borne viruses (arboviruses), which are prone to infecting several species of vertebrate hosts. Here, we focus on how host-pathogen interactions determine the ability of host species to transmit a virus to susceptible vectors upon a potentially infectious contact. Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease, chosen as a case study. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. Given available data on RVFV competent vectors, we found that, for similar infectious titers, infection rates in the Aedes genus were on average higher than in the Culex genus. Consequently, for Aedes -mediated infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. In lambs, we estimated the overall infectiousness to be 1.93 times higher in individuals which eventually died from the infection than in those recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.

Aims/hypothesis We wanted to identify a five-item short form of the Problem Areas in Diabetes Scale and a single-item measure for rapid screening of diabetes-related emotional distress. Methods Using an existing database of 1,153 patients with diabetes, we conducted a principal-components analysis to identify a set of five items and then conducted a reliability analysis and validity checks. From those five items, we identified the item with the strongest psychometric properties as a one-item screening tool. Results We identified a reliable and valid short version of the Problem Areas in Diabetes Scale (PAID) comprising five of the emotional-distress questions of the full PAID items (PAID-5, with items 3, 6, 12, 16, 19). The PAID-5 has satisfactory sensitivity (94%) and specificity (89%) for recognition of diabetes-related emotional distress. We also identified a one-item screening tool, the PAID-1 (Question 12: Worrying about the future and the possibility of serious complications), which has concurrent sensitivity and specificity of about 80% for the recognition of diabetes-related emotional distress. Conclusions/interpretation The PAID-5 and PAID-1 appear to be psychometrically robust short-form measures of diabetes-related emotional distress.

Nearly 100 years ago, Otto Warburg investigated the metabolism of growing tissues and discovered that tumors reprogram their metabolism. It is poorly understood whether and how hypertrophying muscle, another growing tissue, reprograms its metabolism too. Here, we studied pyruvate kinase muscle (PKM), which can be spliced into two isoforms (PKM1, PKM2). This is of interest, because PKM2 redirects glycolytic flux towards biosynthetic pathways, which might contribute to muscle hypertrophy too. We first investigated whether resistance exercise changes PKM isoform expression in growing human skeletal muscle and found that PKM2 abundance increases after six weeks of resistance training, whereas PKM1 decreases. Second, we determined that Pkm2 expression is higher in fast compared to slow fiber types in rat skeletal muscle. Third, by inducing hypertrophy in differentiated C2C12 cells and by selectively silencing Pkm1 and/or Pkm2 with siRNA, we found that PKM2 limits myotube growth. We conclude that PKM2 contributes to hypertrophy in C2C12 myotubes and indicates a changed metabolic environment within hypertrophying human skeletal muscle fibers. PKM2 is preferentially expressed in fast muscle fibers and may partly contribute to the increased potential for hypertrophy in fast fibers.

Background Many screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series ( n  = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p  = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p  = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program. Method The mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants. Discussion The outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening. Trial registration Clinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.