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Background: There is no therapeutic competence and adherence scale for grief-focused cognitive behavioural therapy (grief-focused CBT). However, given the growing body of evidence for the efficacy of grief-focused CBT, such a scale is needed both to ensure the internal validity of clinical trials and to facilitate psychotherapy process research. Objective: To develop and undertake a psychometric evaluation of a therapeutic adherence and competence scale for grief-focused CBT. Method: The scale was developed in two steps. (I) Five experts on the treatment of prolonged grief disorder provided feedback on the relevance and appropriateness of the items. The scale was revised to reflect their feedback. The final therapeutic adherence and competence scale for grief (TACs-G) consisted of 15 adherence and 16 competence items. (II) Psychometric evaluation of the TACs-G was based on the rating of 48 randomly selected PG-CBT sessions by two independent raters. The videos were recorded in the context of a randomized controlled trial (RCT; DRKS00012317.) ICC was used to calculate inter-rater reliability and TACs-G stability over time (re-evaluation of 10 sessions after 12 months). Results: The five experts confirmed the relevance and appropriateness of the items. Interrater reliability was found to be high for the total adherence and competence scores (ICC = 0.889 and 0.782, respectively) and moderate to excellent for individual items (ICC = 0.509–1.00). The TACs-G stability over time was found to be strong for both adherence (ICC = 0.970) and competence total scores (ICC = 0.965). Conclusions: The TACs-G for CBT is a reliable instrument that can be used not only to ensure internal validity but is also suited for psychotherapy process studies. Additionally, it provides a valuable database for targeted feedback in training settings. HIGHLIGHTS This is the first study to report on the development and psychometrical evaluation of a grief-focused adherence and competence scale. Although an increasing number of clinical trials do report the efficacy of grief-focused cognitive–behavioural therapy, none of these studies used a standardized adherence and competence scale to control internal validity. In the present study, we introduced a therapeutic adherence and competence scale for grief (TACs-G) that can be applied efficiently across different research settings (e.g. manipulation check, dissemination), and report results of good to excellent psychometric properties. The scale itself could prove useful beyond the research setting as it could possibly serve as a basis for feedback in training settings.

Most people adapt to bereavement over time. For a minority, the grief persists and may lead to a prolonged grief disorder (PGD). Identifying grievers at risk of PGD may enable specific prevention measures. The present study examined the extent to which the subjective unexpectedness of the death predicted grief outcomes above and beyond known sociodemographic and objective loss-related variables in a sample drawn from a population-representative investigation. In our sample (n = 2,531), 811 participants (Mage 55.1 ± 17.8 years, 59.2% women) had experienced the loss of a significant person six or more months ago. Participants provided demographic and loss-related information, perceptions of the unexpectedness of the death and completed the Prolonged Grief Disorder-13 + 9 (PG-13 + 9). The PG-13 + 9 was used to determine PGD caseness. A binary logistic regression investigated predictors of PGD caseness, and a linear regression predictors of grief severity. ANCOVAs compared PGD symptoms between the groups who had experienced an “expected” vs. “unexpected” loss, while controlling for the relationship to the deceased and time since loss. The loss of a child (OR = 23.66; 95%CI, 6.03–68.28), or a partner (OR = 5.32; 95%CI, 1.79–15.83), the time since loss (OR = 0.99; 95%CI, 0.99–1.00) and the unexpectedness of the death (OR = 3.58; 95%CI, 1.70–7.69) were significant predictors of PGD caseness (Nagelkerke’s R2 = 0.25) and grief severity. Participants who had experienced the loss as unexpected (vs. expected) reported higher scores on all PGD symptoms. Unexpectedness of the death emerged as significant risk factor for PGD, even after controlling for demographic and other loss-related variables. While our findings replicate previous research on the importance of the relationship to the deceased as a risk factor for PGD, they also highlight the importance of assessing the subjective unexpectedness of a death and may help to identify risk groups who can profit from preventive interventions.

Abstract Background Research on effective recruitment and retention strategies for adolescents and young adults suffering from posttraumatic stress disorder is scarce. The aim of the current study was to provide data on recruitment sources, barriers, and facilitators for participation in a randomized controlled trial for young individuals with histories of sexual and/or physical abuse. Methods Study participants aged 14 to 21 were asked to complete a checklist on individual sources of recruitment, barriers, and facilitators for participation in the trial. Fifty-three out of the 80 study participants who were contacted completed the checklist (66.3%). Results Most respondents reported multiple recruitment sources, with online and media advertising search strategies indicated most frequently (45.4% of all mentions), followed by practitioner-referred sources (38.7%). Respondents’ reported barriers included additional demands of the trial (60.3%), followed by distress caused by having to talk about painful topics (15.5%). The most frequently indicated facilitators were the organizational setting (55.1%) and monetary incentives (22.2%), followed by social support (12.0%) and non-monetary incentives (10.2%). No significant differences were observed between adolescent and young adult respondents with the exception that adolescents reported significantly more frequently that they had learned about the trial from their caregiver. Conclusions Our findings permit the formulation of recommendations for planning and conducting trials with this clientele. Future research is needed on how specific barriers can be effectively overcome.

Anne in Swedish. How the Spirit of the Age and Production Terms Influence the Protagonist’s Character Traits in Swedish Translations and Adaptations of Anne of Green Gables L.M. Montgomery’s Anne of Green Gables (1908) has received much academic interest. Drawing on related research on the novel and its Swedish editions, my article investigates how the variation in the Swedish versions influences the characterization of Anne 1909–2018. My study acknowledges the feminist view within translation studies as expressed by Sherry Simon, and uses Norman Fairclough’s linguistic model for contextualization. The primary material consists of Montgomery’s original text, the translations and adaptations by Karin Jensen, Aslög Davidson, Margareta Sjögren-Olsson, and Christina Westman as well as correspondence between the publishing houses and translators. Further, I have interviewed Westman and corresponded with her publisher. The texts are analysed regarding omissions and additions. On a micro-level, all active verbs where Anne is the grammatical subject are analysed. My results show that all editions give prominence to Anne’s academic ambition. A major finding is that the 1941 and 1962 versions increase Anne’s ambition by using more active verbs and stronger expressions. Westman’s 2018 edition, however, is a subtle revision of the first Swedish translation, with the result that Anne’s ambition is diminished again. Despite girls and women having gained more freedom over the last 100 years, the latest edition thereby interrupts the tendency to stress Anne’s ambition. This is understood as a result of clashing discursive and social norms. On the other hand, the emphasis on Anne’s ambition in the 1941 and 1962 editions comes with a cost of religious, moral, intellectual, and emotional aspects, creating a one-dimensional Anne.

Present-centered therapy (PCT) was originally developed as a strong comparator for the non-specific effects of psychotherapy in the treatment of posttraumatic stress disorder. PCT qualifies as a not strictly supportive treatment as it is structured and homework is assigned between sessions. It does not focus on cognitive restructuring or exposure. A growing body of literature supports its beneficial effects. For example, it demonstrated only slightly inferior effect sizes and lower dropout rates compared to that of trauma-focused cognitive behavioral therapy in several trials with patients suffering from posttraumatic stress disorder. The current study is the first to evaluate the feasibility and the treatment effects of PCT in adults with prolonged grief disorder (PGD). Meta-analyses on psychotherapy for PGD have yielded moderate effect sizes. N = 20 individuals suffering from PGD were treated with PCT by novice therapists as part of a preparation phase for an upcoming RCT in an outpatient setting. Treatment consisted of 20–24 sessions á 50 min. All outcomes were assessed before treatment, at post-treatment, and at the 3-month follow-up. The primary outcome, PGD symptom severity, was assessed using the Interview for Prolonged Grief-13. Secondary outcomes were self-reported PGD severity, depression, general psychological distress, and somatic symptom severity. Furthermore, therapists evaluated their experiences with their first PCT patient and the treatment manual. In intent-to-treat analyses of all patients we found a significant decrease in interview-based PGD symptom severity at post-treatment (d = 1.26). Decreases were maintained up to the 3-month follow-up assessment (d = 1.25). There were also significant decreases in self-reported PGD symptoms, depression, and general psychological distress. No changes were observed for somatic symptoms. The completion rate was 85%. Therapists deemed PCT to be a learnable treatment program that can be adapted to the patient's individual needs. The preliminary results of PCT as a treatment for PGD demonstrate large effects and indicate good feasibility in outpatient settings. The treatment effects were larger than those reported in meta-analyses. Thus, PCT is a promising treatment for PGD. Possible future research directions are discussed.

Background: ICD-11 features Complex Posttraumatic Stress Disorder (CPTSD) as a new diagnosis. To date, very few studies have investigated CPTSD in young patients, and there is a need for evidence on effective treatment. Objective: The present study evaluates the applicability of developmentally adapted cognitive processing therapy (D-CPT) for CPTSD in young patients in a secondary analysis of the treatment condition of a randomized controlled trial (RCT) investigating the efficacy of D-CPT. Methods: The D-CPT treatment group in the original study included 44 patients (14–21 years) with DSM-IV PTSD after childhood abuse. We used the ICD-11 algorithm to divide the sample into a probable CPTSD and a non-CPTSD group. We performed multilevel models for interviewer-rated and self-rated PTSD symptoms with fixed effects of group (CPTSD, non-CPTSD) and time (up to 12 months follow-up) and their interaction. Treatment response rates for both groups were calculated. Results: Nineteen (43.2%) patients fulfilled criteria for probable ICD-11 CPTSD while 25 (56.8%) did not. Both CPTSD and non-CPTSD groups showed symptom reduction over time. The CPTSD group reported higher symptom severity before and after treatment. Linear improvement and treatment response rates were similar for both groups. D-CPT reduced symptoms of disturbances in self-regulation in both groups. Discussion: Both, patients with and without probable ICD-11 CPTSD seemed to benefit from D-CPT and the treatment also reduced disturbances in self-regulation. Conclusion: This study presents initial evidence of the applicability of D-CPT in clinical practice for young patients with CPTSD. It remains debatable whether CPTSD implies different treatment needs as opposed to PTSD.

Background: Prolonged grief disorder (PGD) will be newly included in the ICD-11, while a clinically similar diagnosis, persistent complex bereavement disorder (PCBD), has already been added to the DSM-5. Only few studies have evaluated these criteria-sets for prolonged grief. Objective: The aim of this study was to evaluate the ICD-11 accessory symptom threshold and compare the diagnostic performance of the two criteria-sets in treatment-seeking bereaved persons. Method: 113 grief treatment-seeking bereaved persons completed the Interview for Prolonged Grief-13. We used receiver operator characteristic analysis to determine an optimum ICD-11 accessory symptom threshold. We calculated diagnostic rates for PGD and PCBD and examined associations of PGD and PCBD caseness with concurrently assessed psychopathology and prolonged grief symptoms assessed one month later. Results: An ICD-11 threshold of six accessory symptoms distinguished optimally between interview-diagnosed participants with and without prolonged grief. The prevalence of PGD (69%) was significantly higher than that of PCBD (48%) and of PGD with a 6-symptom threshold (47%). PGD caseness was associated with the relation to the deceased, 6-symptom threshold PGD and PCBD caseness with the time since loss. All criteria-sets were linked to concurrent prolonged grief, depression, and general mental distress. PCBD and 6-symptom threshold PGD but not PGD were associated with prolonged grief severity one month later. Conclusions: The results support the validity of PGD and PCBD but, at the same time, they provide further support for differing prevalence rates. Using an empirically determined ICD-11 accessory symptom threshold could prevent the pathologisation of grief reactions.

Abstract Background Prolonged grief disorder (PGD) has emerged as a well-defined and relatively common mental disorder that will be included in the upcoming revision of the International Classification of Diseases. Recent trials with grief-specific, mostly cognitive behavioral interventions for patients with a clinically relevant diagnosis of PGD showed large effect sizes. However, a small trial suggested that non-specific behavioral activation might suffice to improve PGD. So, more evidence for the relative efficacy of grief-specific treatments is needed, as is more research on the predictors of treatment success. The purpose of the proposed trial is to evaluate a newly developed and successfully pilot-tested, prolonged grief-specific, integrative cognitive behavioral therapy (PG-CBT) compared to an active yet unspecific treatment, present-centered therapy (PCT). Methods In a multicenter, randomized controlled trial with 204 adults with a primary diagnosis of PGD, PG-CBT is compared to PCT, assuming the superiority of PG-CBT. Both treatments consist of 20 to 24 individual sessions, with an overall treatment length of about 6 months. The primary outcome, grief symptom severity, is assessed by blinded interviewers 12 months after randomization. Secondary outcomes are grief symptom severity at post treatment, in addition to self-reported overall mental health symptoms, depressive and somatoform symptoms at post treatment and 12 months post randomization. Possible moderators and mediators of treatment success are also explored. Discussion The trial is designed to avoid bias as much as possible (stratified randomization performed independently, blinded outcome assessment, intention-to-treat-analysis, balanced treatment dose, continuous supervision, control for allegiance effects) thereby enhancing internal validity. At the same time, some aspects of the trial will ensure clinical relevance (recruiting at outpatient clinics that are part of routine health care and keeping exclusion criteria to a minimum). Since the trial is powered adequately for the primary outcome, all secondary analyses including moderator analyses are exploratory by nature. The results will extend the knowledge on efficacious treatment of PGD and its predictors. Trial registration German Clinical Trials Register, ID: DRKS00012317. Registered on 6 September 2017.

Phonological representation for adult speakers is generally assumed to include sub-lexical information at the level of the phoneme. Some have suggested, however, that young children operate with more holistic lexical representations. If young children use whole-word representation and adults employ phonemic representation, then a component of phonological development includes a transition from holistic to segmental storage of phonological information. The present study addresses the nature of this transition by investigating the prevalence and patterns of intra-word production variability during the first year of lexical acquisition (1;0-2;0). Longitudinal data from four typically developing children were analysed to determine variability at each age. Patterns of variability are discussed in relation to chronological age and productive vocabulary size. Results show high overall rates of variability, as well as a peak in variability corresponding to the onset of combinatorial speech, suggesting that phonological reorganization may commence somewhat later than previously thought. (Contains 1 footnote.)

Abstract Background Belief in complementary and alternative medicine practices is related to reduced preparedness for vaccination. This study aimed to assess home remedy awareness and use in South Tyrol, where vaccination rates in the coronavirus pandemic were lowest in Italy and differed between German- and Italian-speaking inhabitants. Methods A population-based survey was conducted in 2014 and analyzed using descriptive statistics, multiple logistic regression, and latent class analysis. Results Of the representative sample of 504 survey respondents, 357 (70.8%) participants (43.0% male; primary language German, 76.5%) reported to use home remedies. Most commonly reported home remedies were teas (48.2%), plants (21.0%), and compresses (19.5%). Participants from rural regions were less likely (odds ratio 0.35, 95% confidence interval 0.19–0.67), while female (2.62, 1.69–4.10) and German-speaking participants (5.52, 2.91–9.88) were more likely to use home remedies. Latent classes of home remedies were “alcoholic home remedies” (21.4%) and “non-alcohol-containing home remedies” (78.6%). Compared to the “non-alcohol-containing home remedies” class, members of the “alcoholic home remedies” class were more likely to live in an urban region, to be male and German speakers. Conclusion In addition to residence and sex, language group membership associates with awareness and use of home remedies. Home remedies likely contribute to socio-cultural differences between the language groups in the Italian Alps. If the observed associations explain the lower vaccination rates in South Tyrol among German speakers requires further study.

Abstract Background The adoption of a healthy lifestyle plays a crucial role for the health and well-being of health care professionals. Previous e- and mHealth interventions relied on deliberative psychological processes (e.g., intention, planning) to target lifestyle changes, while revealing mixed efficacy. The additional potential of non-deliberative, automatic processes (i.e., habits) for behavior change has been understudied in interventions so far. The Habit Coach mHealth intervention combines deliberative and non-deliberative processes to support health care professionals in forming healthy physical activity, nutrition and mindfulness habits in daily life. The aim of this paper is to outline the study protocol including a detailed description of the mHealth intervention, evaluation plan, and study design. The purpose of this trial is to understand healthy habit formation in health care professionals over time. Methods A one-arm, multicenter mHealth intervention study will be conducted. Behavioral and psychosocial predictors will be collected via within-app questionnaires across a 100-day period at baseline, post, as well as at weekly assessments. To understand habit formation across time, linear mixed models will be used. Discussion This trial aims to unravel the role of motivational and volitional determinants for healthy habit formation across multiple health behaviors in health care professionals embedded in a mHealth intervention. Trial registration This trial is registered in the German Clinical Trials Register, DRKS-ID DRKS00027156. Date of registration 17 November 2021.

Abstract Background Evidence suggests an increasing demand for culturally and linguistically responsive disease prevention programs and health interventions. It is important to understand how individuals seek health information to address the potential needs of the health care system. Methods Latent classes of health information-seeking behaviors in a linguistically mixed region of Italy were explored through a population-based telephone survey of ten health information sources. Data were collected in August and September 2014 from 504 adults in South Tyrol, Italy (primary language German, 68%; Italian, 28%), and analyzed using latent class analysis and latent class multinomial logistic regression models. Results Three classes of health information-seeking behaviors emerged: “multidimensional” (23.3%), “interpersonal” (38.6%) and “technical/online” (38.1%). Compared to the “technical/online” class, “interpersonal” class members were older, had lower education than high school, and were less likely to be of Italian ethnicity. “Multidimensional” class members were more likely to be female, older, and of German ethnicity than those in the “technical/online” class. Conclusions Linguistic ethnicity explains membership in classes on health information-seeking behavior. Policymakers and healthcare providers should consider the health information-seeking behaviors of population subgroups to promote health and medical care in linguistic minority groups.

Abstract Background Evidence regarding clinically relevant effects of interventions aiming at reducing polypharmacy is weak, especially for the primary care setting. This study was initiated with the objective to achieve clinical benefits for older patients (aged 75+) by means of evidence-based reduction of polypharmacy (defined as ≥8 prescribed drugs) and inappropriate prescribing in general practice. Methods The cluster-randomised controlled trial involved general practitioners and patients in a northern-Italian region. The intervention consisted of a review of patient’s medication regimens by three experts who gave specific recommendations for drug discontinuation. Main outcome measures were non-elective hospital admissions or death within 24 months (composite primary endpoint). Secondary outcomes were drug numbers, hospital admissions, mortality, falls, fractures, quality of life, affective status, cognitive function. Results Twenty-two GPs/307 patients participated in the intervention group, 21 GPs/272 patients in the control group. One hundred twenty-five patients (40.7%) experienced the primary outcome in the intervention group, 87 patients (32.0%) in the control group. The adjusted rates of occurrence of the primary outcome did not differ significantly between the study groups (intention-to-treat analysis: adjusted odds ratio 1.46, 95%CI 0.99–2.18, p = 0.06; per-protocol analysis: adjusted OR 1.33, 95%CI 0.87–2.04, p = 0.2). Hospitalisations as single endpoint occurred more frequently in the intervention group according to the unadjusted analysis (OR 1.61, 95%CI 1.03–2.51, p = 0.04) but not in the adjusted analysis (OR 1.39, 95%CI 0.95–2.03, p = 0.09). Falls occurred less frequently in the intervention group (adjusted OR 0.55, 95%CI 0.31–0.98; p = 0.04). No significant differences were found regarding the other outcomes. Definitive discontinuation was obtained for 67 (16.0%) of 419 drugs rated as inappropriate. About 6% of the prescribed drugs were PIMs. Conclusions No conclusive effects were found regarding mortality and non-elective hospitalisations as composite respectively single endpoints. Falls were significantly reduced in the intervention group, although definitive discontinuation was achieved for only one out of six inappropriate drugs. These results indicate that (1) even a modest reduction of inappropriate medications may entail positive clinical effects, and that (2) focusing on evidence-based new drug prescriptions and prevention of polypharmacy may be more effective than deprescribing. Trial registration Current Controlled Trials (ID ISRCTN: 38449870), date: 11/09/2013.

Abstract Background A precondition for developing strategies to reduce polypharmacy and its well-known harmful consequences is to study its epidemiology and associated factors. The objective of this study was to analyse the prevalence of polypharmacy (defined as ≥8 prescribed drugs), of potentially inappropriate medications (PIMs) and major drug-drug interactions (DDIs) among community-dwelling general practice patients aged ≥75 years and to identify characteristics being associated with polypharmacy. Methods This cross-sectional study is derived from baseline data (patients’ demographic/biometric characteristics, diagnoses, medication-related data, cognitive/affective status, quality of life) of a northern-Italian cluster-RCT. PIMs and DDIs were assessed using the 2012 Beers criteria and the Lexi-Interact® database. Data were analysed using descriptive methods, Wilcoxon rank-sum tests, Fisher’s exact tests and Spearman correlations. Results Of the eligible patients aged 75+, 13.4% were on therapy with ≥8 drugs. Forty-three general practitioners and 579 patients participated in the study. Forty five point nine percent of patients were treated with ≥1 Beers-listed drugs. The most frequent PIMs were benzodiazepines/hypnotics (19.7% of patients) and NSAIDs (6.6%). Sixty seven point five percent of patients were exposed to ≥1 major DDI, 35.2% to ≥2 major DDIs. Antithrombotic/anticoagulant medications (30.4%) and antidepressants/antipsychotics (23.1%) were the most frequently interacting drugs. Polypharmacy was significantly associated with a higher number of major DDIs (Spearman’s rho 0.33, p

Background Helicopter emergency medical services personnel operating in mountainous terrain are frequently exposed to rapid ascents and provide cardiopulmonary resuscitation (CPR) in the field. The aim of the present trial was to investigate the quality of chest compression only (CCO)‐CPR after acute exposure to altitude under repeatable and standardized conditions. Methods and Results Forty‐eight helicopter emergency medical services personnel were divided into 12 groups of 4 participants; each group was assigned to perform 5 minutes of CCO‐CPR on manikins at 2 of 3 altitudes in a randomized controlled single‐blind crossover design (200, 3000, and 5000 m) in a hypobaric chamber. Physiological parameters were continuously monitored; participants rated their performance and effort on visual analog scales. Generalized estimating equations were performed for variables of CPR quality (depth, rate, recoil, and effective chest compressions) and effects of time, altitude, carryover, altitude sequence, sex, qualification, weight, preacclimatization, and interactions were analyzed. Our trial showed a time‐dependent decrease in chest compression depth (P=0.036) after 20 minutes at altitude; chest compression depth was below the recommended minimum of 50 mm after 60 to 90 seconds (49 [95% CI, 46–52] mm) of CCO‐CPR. Conclusions This trial showed a time‐dependent decrease in CCO‐CPR quality provided by helicopter emergency medical services personnel during acute exposure to altitude, which was not perceived by the providers. Our findings suggest a reevaluation of the CPR guidelines for providers practicing at altitudes of 3000 m and higher. Mechanical CPR devices could be of help in overcoming CCO‐CPR quality decrease in helicopter emergency medical services missions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04138446.

Cognitive function impairment due to high altitude exposure has been reported with some contradictory results regarding the possible selective cognitive domain involvement. We prospectively evaluated in 36 lowlanders, exposed for 3 consecutive days to an altitude of 3,269 m, specific cognitive abilities (attention, processing speed, and decision-making) required to safely explore the mountains, as well as to work at altitude. We simultaneously monitored the physiological parameters. Our study provides evidence of a reduced processing speed in lowlanders when exposed to altitude in the first 24 h. There was a fairly quick recovery since this impairment was no more detectable after 36 h of exposure. There were no clinically relevant effects on decision-making, while psychomotor vigilance was unaffected at altitude except for individuals with poor sleep. Significant changes were seen in physiological parameters (increased heart rate and reduced peripheral oxygen saturation). Our results may have practical implications, suggesting that individuals should practice prudence with higher ascent when performing risky activities in the first 24–36 h, even at altitudes below 3,500 m, due to an impairment of the cognitive performance that could worsen and lead to accidents.

Abstract Background Polypharmacy is common in older people and associated with potential harms. The aim of this study was to analyse the characteristics of an older multimorbid population with polypharmacy and to identify factors contributing to excessive polypharmacy in these patients. Methods This cross-sectional analysis is based on the PRIMA-eDS trial, a large randomised controlled multicentre study of polypharmacy in primary care. Patients’ baseline data were used for analysis. A number of socioeconomic and medical data as well as SF-12-scores were entered into a generalized linear mixed model to identify variables associated with excessive polypharmacy (taking ≥10 substances daily). Results Three thousand nine hundred four participants were recruited. Risk factors significantly associated with excessive polypharmacy were frailty (OR 1.45; 95% CI 1.22–1.71), > 8 diagnoses (OR 2.64; 95% CI 2.24–3.11), BMI ≥30 (OR 1.18; 95% CI 1.02–1.38), a lower SF-12 physical health composite score (OR 1.47; 95% CI 1.26–1.72), and a lower SF-12 mental health composite score (OR 1.33; 95% CI 1.17–1.59) than the median of the study population (≤36.6 and ≤ 48.7, respectively). Age ≥ 85 years (OR 0.83; 95% CI 0.70–0.99) led to a significantly lower risk for excessive polypharmacy. No association with excessive polypharmacy could be found for female sex, low educational level, and smoking. Regarding the study centres, being recruited in the UK led to a significantly higher risk for excessive polypharmacy compared to being recruited in Germany 1/Rostock (OR 1.71; 95% CI 1.27–2.30). Being recruited in Germany 2/Witten led to a slightly significant lower risk for excessive polypharmacy compared to Germany 1/Rostock (OR 0.74; 95% CI 0.56–0.97). Conclusions Frailty, multimorbidity, obesity, and decreased physical as well as mental health status are risk factors for excessive polypharmacy. Sex, educational level, and smoking apparently do not seem to be related to excessive polypharmacy. Physicians should especially pay attention to their frail, obese patients who have multiple diagnoses and a decreased health-related quality of life, to check carefully whether all the drugs prescribed are evidence-based, safe, and do not interact in an unfavourable way. Trial registration This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

Abstract Background The benefit from a blood pressure lowering therapy with beta blockers may not outweigh its risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of beta blockers in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. Methods Systematic review of the literature using a stage approach with searches for systematic reviews and meta-analyses first, and individual studies only if the previous searches are inconclusive. The target population were older adults (≥65 years old) with hypertension. We included studies reporting on the effectiveness and/or safety of beta blockers on clinically relevant endpoints (e.g. mortality, cardiovascular events, and stroke) in the management of hypertension. The recommendations were developed according to the GRADE methodology. Results Fifteen studies were included, comprising one meta-analysis, four randomized controlled trials, six secondary analyses of randomized controlled trials and four observational studies. Seven studies involved only older adults and eight studies reported subgroup analyses by age. With regard to a composite endpoint (death, stroke or myocardial infarction) beta blockers were associated with a higher risk of events then were other antihypertensive agents. Further, beta blockers showed no benefit compared to other antihypertensive agents or placebo regarding mortality. They appear to be less effective than other antihypertensive agents in reducing cardiovascular events. Contradictory results were found regarding the effect of beta blockers on stroke. None of the studies explored the effect on quality of life, hospitalisation, functional impairment/status, safety endpoints or renal failure. Conclusion The quality of current evidence to interpret the benefits of beta blockers in hypertension is rather weak. It cannot be recommended to use beta blockers in older adults as first line agent for hypertension.

Abstract Background Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. Methods Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention. Results Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c

In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, the role of each central nervous system (CNS)-resident cell type during inflammation, neurodegeneration, and remission has been frequently addressed. Although protocols for the isolation of different individual CNS-resident cell types exist, none can harvest all of them within a single experiment. In addition, isolation of individual cells is more demanding in adult mice and even more so from the inflamed CNS. Here, we present a protocol for the simultaneous purification of viable single-cell suspensions of all principal CNS-resident cell types (microglia, oligodendrocytes, astrocytes, and neurons) from adult mice—applicable in healthy mice as well as in EAE. After dissociation of the brain and spinal cord from adult mice, microglia, oligodendrocytes, astrocytes and, neurons were isolated via magnetic-activated cell sorting (MACS). Validations comprised flow cytometry, immunocytochemistry, as well as functional analyses (immunoassay and Sholl analysis). The purity of each cell isolation averaged 90%. All cells displayed cell-type-specific morphologies and expressed specific surface markers. In conclusion, this new protocol for the simultaneous isolation of all major CNS-resident cell types from one CNS offers a sophisticated and comprehensive way to investigate complex cellular networks ex vivo and simultaneously reduce mice numbers to be sacrificed.

A number of previous works have shown that information about a subject is encoded in sparse kinematic information, such as the one revealed by so-called point light walkers. With the work at hand, we extend these results to classifications of soft biometrics from inertial sensor recordings at a single body location from a single step. We recorded accelerations and angular velocities of 26 subjects using integrated measurement units (IMUs) attached at four locations (chest, lower back, right wrist and left ankle) when performing standardized gait tasks. The collected data were segmented into individual walking steps. We trained random forest classifiers in order to estimate soft biometrics (gender, age and height). We applied two different validation methods to the process, 10-fold cross-validation and subject-wise cross-validation. For all three classification tasks, we achieve high accuracy values for all four sensor locations. From these results, we can conclude that the data of a single walking step (6D: accelerations and angular velocities) allow for a robust estimation of the gender, height and age of a person.