Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis.

Background: Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy. Objectives: We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC. Design: Monocentric, prospective study. Methods: We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy. Results: Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated. Conclusion: Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies. Trial registration: Not applicable.

Effects of cyclosporin and ustekinumab combination therapy in acute severe ulcerative colitis In this study, we looked at how to treat patients with a severe form of ulcerative colitis, a type of inflammatory bowel disease, when the usual treatments don't work. We tested a combination of two drugs, cyclosporine and ustekinumab, to see if it could help these patients in the long term. We included eleven patients who had already tried many other treatments and didn't get better. Most of them had also tried a drug called infliximab and had failed at least three other biological therapies. At the start, these patients were very sick, with high scores on disease activity measures. We gave them ustekinumab in addtion after a therapy with cyclosporin had been started before. The combination therapy continued for an average of almost 12 weeks. After 16 weeks, six patients showed improvement in their symptoms, and five were able to stop taking steroids. Five patients also had their colon lining looking healthy again when we looked inside with a scope after 16 weeks. And after 52 weeks, five patients had normal colon lining and healthy tissue under the microscope. Ultrasound showed that the thickness of their colon wall had decreased. Unfortunately, two patients had to have surgery to remove their colon, and three had to stop taking ustekinumab because it didn't help them. Overall, the combination therapy was safe and well-tolerated. In conclusion, combining cyclosporin and ustekinumab helped about half of the patients with severe ulcerative colitis get better and have healthy colon lining after 52 weeks. This suggests that more research is needed to understand the benefits of this treatment in these patients.

Personal Protective Equipment Protocols Lead to a Delayed Initiation of Patient Assessment in Mountain Rescue Operations.

van Veelen, Michiel J., Giulia Roveri, Ivo B. Regli, Tomas Dal Cappello, Anna Vögele, Michela Masè, Marika Falla, and Giacomo Strapazzon. Personal protective equipment protocols lead to a delayed initiation of patient assessment in mountain rescue operations. High Alt Med Biol. 24:127-131, 2023. Introduction: Mountain rescue operations can be challenging in austere environmental conditions and remote settings. Airborne infection prevention measures include donning of personal protective equipment (PPE), potentially delaying the approach to a patient. We aimed to investigate the time delay caused by these prevention measures. Methods: This randomized crossover trial consisted of 24 rescue simulation trials intended to be as realistic as possible, performed by mountain rescue teams in difficult terrain. We analyzed the time needed to perform an airborne infection prevention protocol during the approach to a patient. Time delays in scenarios involving patients already wearing versus not wearing face masks and gloves were compared using a linear mixed model Results: The airborne infection prevention measures (i.e., screening questionnaire, hand antisepsis, and donning of PPE) resulted in a time delay of 98 ± 48 (26-214) seconds on initiation of patient assessment. There was a trend to a shorter time to perform infection prevention measures if the simulated patient was already wearing PPE consisting of face mask and gloves (p = 0.052). Conclusion: Airborne infection prevention measures may delay initiation of patient assessment in mountain rescue operations and could impair clinical outcomes in time-sensitive conditions. Trial registration number 0105095-BZ Ethics Committee review board of Bolzano.

Awareness and use of home remedies in Italy's alps: a population-based cross-sectional telephone survey.

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.

Simulated Acute Hypobaric Hypoxia Effects on Cognition in Helicopter Emergency Medical Service Personnel - A Randomized, Controlled, Single-Blind, Crossover Trial.

OBJECTIVE: To evaluate, under replicable, blinded and standardised conditions, the effect of acute exposure to hypobaric hypoxia (HH) (equivalent to 200 or 3000 or 5000 m above sea level (asl)) on selected cognitive domains and physiological parameters in personnel of helicopter emergency medical service (HEMS). METHODS: We conducted a randomized clinical trial using a single-blind crossover design in an environmental chamber (terraXcube) to induce HH in 48 HEMS personnel. Participants performed cognitive tests (CT) before the ascent, after 5 min at altitude, and after simulated cardiopulmonary resuscitation (SCR). CT evaluated: sustained attention using the psychomotor vigilance test (PVT) that included measurement of reaction time (RT); risky decision making using the balloon analogue risk task (BART), and attention and speed of processing using the digit symbol substitution test (DSST). CT performance was subjectively rated with a visual analogue scale (VAS). Physiological data were recorded with a physiological monitoring system. Data were analysed using a linear mixed model and correlation analysis. RESULTS: Mean reaction time was significantly slower (p = 0.002) at HH (5000 m asl), but there were no independent effects of HH on the other parameters of the PVT, BART or DSST. Participants did not detect subjectively the slower RT at altitude since VAS performance results showed a positive correlation with mean RT (p = 0.009). DSST results significantly improved (p = 0.001) after SCR. CONCLUSION: Acute exposure of HEMS personnel to HH induced a slower RT but no changes in any other investigated measures of cognition. The reduced RT was not detected subjectively by the participants. Trial number 3489044136, ClinicalTrials.gov trial registration.

Health information-seeking behavior associated with linguistic group membership: latent class analysis of a population-based cross-sectional survey in Italy, August to September 2014.

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.

Effect of Acute Exposure to Altitude on the Quality of Chest Compression-Only Cardiopulmonary Resuscitation in Helicopter Emergency Medical Services Personnel: A Randomized, Controlled, Single-Blind Crossover Trial.

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.

Expert-based medication reviews to reduce polypharmacy in older patients in primary care: a northern-Italian cluster-randomised controlled trial.

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.

A Prospective Evaluation of the Acute Effects of High Altitude on Cognitive and Physiological Functions in Lowlanders.

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.

Epidemiology and associated factors of polypharmacy in older patients in primary care: a northern Italian cross-sectional study.

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 < 0.001) and chronic conditions (Spearman's rho 0.20, p < 0.001), higher 5-GDS scores (thus, lower affective status) (Spearman's rho 0.12, p = 0.003) and lower EQ-5D-5L scores (thus, lower quality of life) (Spearman's rho - 0.14, p = 0.001). Patients' age/sex, 6-CIT scores (cognitive status), BMI or PIM use were not correlated with the number of drugs. CONCLUSIONS: The prevalence of polypharmacy, PIMs and major DDIs was considerable. Results indicate that physicians should particularly observe their patients with multiple conditions, reduced health and affective status, independently from other patients' characteristics. Careful attention about indication, benefit and potential risk should be paid especially to patients on therapy with specific drug classes identified as potentially inappropriate or prone to major DDIs in older persons (e.g., benzodiazepines, NSAIDs, protonic pump inhibitors, antithrombotics/anticoagulants, antidepressants/antipsychotics). TRIAL REGISTRATION: The cluster-RCT on which this cross-sectional analysis is based was registered with Current Controlled Trials Ltd. (ID ISRCTN: 38449870 ) on 2013-09-11.

Quality improvement in chronic care by self-audit, benchmarking and networking in general practices in South Tyrol, Italy: results from an interventional study.

BACKGROUND: Systematic strategies promoting quality of care in general practice are yet under-represented in several European countries. OBJECTIVE: This interventional study assessed whether a combined intervention (self-audit, benchmarking, quality circles) improved quality of care in Salzburg, Austria and South Tyrol, Italy. The present publication reports the Italian results. METHODS: We developed quality indicators for general practice in a consensus process based on pre-existing quality programmes. The indicators addressed diagnosis and treatment regarding eight common chronic conditions. A quality score comprising 91 indicators was calculated (0-5 points per indicator depending on fulfilment, maximum 455 points). We collected anonymous data from the electronic health records of the participating physicians in 2012, 2013 and 2014. Wilcoxon signed-rank tests were used for pre-post analysis. RESULTS: Thirty-six GPs participated in the study. The median quality score increased significantly from 177.0 points at baseline to 272.0 points at the second follow-up (P = 0.000). Improvements concerned process and intermediate outcome indicators particularly between baseline and the first follow-up. CONCLUSION: Performance was relatively low at baseline and improved considerably, mainly in the first study period. The intervention investigated in this study can serve as a model for future quality programmes. A customized electronic health record for the implementation of this intervention as well as standardized and consistent documentation by GPs is a prerequisite. Use of a limited set of quality indicators (QIs) and regular QI modification is probably advisable to increase the benefits. Long-term prospective studies should investigate the impact of QI-based interventions on end-result outcomes.

Use of an electronic decision support tool to reduce polypharmacy in elderly people with chronic diseases: cluster randomised controlled trial.

OBJECTIVE: To evaluate the effects of a computerised decision support tool for comprehensive drug review in elderly people with polypharmacy. DESIGN: Pragmatic, multicentre, cluster randomised controlled trial. SETTING: 359 general practices in Austria, Germany, Italy, and the United Kingdom. PARTICIPANTS: 3904 adults aged 75 years and older using eight or more drugs on a regular basis, recruited by their general practitioner. INTERVENTION: A newly developed electronic decision support tool comprising a comprehensive drug review to support general practitioners in deprescribing potentially inappropriate and non-evidence based drugs. Doctors were randomly allocated to either the electronic decision support tool or to provide treatment as usual. MAIN OUTCOME MEASURES: The primary outcome was the composite of unplanned hospital admission or death by 24 months. The key secondary outcome was reduction in the number of drugs. RESULTS: 3904 adults were enrolled between January and October 2015. 181 practices and 1953 participants were assigned to electronic decision support (intervention group) and 178 practices and 1951 participants to treatment as usual (control group). The primary outcome (composite of unplanned hospital admission or death by 24 months) occurred in 871 (44.6%) participants in the intervention group and 944 (48.4%) in the control group. In an intention-to-treat analysis the odds ratio of the composite outcome was 0.88 (95% confidence interval 0.73 to 1.07; P=0.19, 997 of 1953 v 1055 of 1951). In an analysis restricted to participants attending practice according to protocol, a difference was found favouring the intervention (odds ratio 0.82, 95% confidence interval 0.68 to 0.98; 774 of 1682 v 873 of 1712, P=0.03). By 24 months the number of prescribed drugs had decreased in the intervention group compared with control group (uncontrolled mean change -0.42 v 0.06: adjusted mean difference -0.45, 95% confidence interval -0.63 to -0.26; P<0.001). CONCLUSIONS: In intention-to-treat analysis, a computerised decision support tool for comprehensive drug review of elderly people with polypharmacy showed no conclusive effects on the composite of unplanned hospital admission or death by 24 months. Nonetheless, a reduction in drugs was achieved without detriment to patient outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10137559.

Sudden Cardiac Arrest and Cardiopulmonary Resuscitation with Automated External Defibrillator in the Austrian Mountains: A Retrospective Study.

Background: Few data exist on the likelihood of surviving sudden cardiac arrest in the mountains. The aim of this study was to analyze the epidemiology and outcomes of patients suffering sudden cardiac arrest and undergoing cardiopulmonary resuscitation (CPR) with automated external defibrillator (AED) in the Austrian mountains. Materials and Methods: We analyzed all cardiac arrest cases in the Austrian mountains reported in the nationwide Austrian Alpine Police database from October 26, 2005, to December 31, 2015. To obtain information on outcomes, these patient data were manually merged with patient data from the main Austrian referral center for mountain emergencies, Innsbruck Medical University Hospital. Results: Overall, 781 cases of sudden cardiac arrest in the Austrian mountains were recorded. In 136 cases (17%), CPR with AED was attempted. The most frequent activities at the time of sudden cardiac arrest were hiking (n = 63, 46%) and skiing or snowboarding (n = 44, 32%). In the nationwide Austrian Alpine Police database, only 4 (3%) patients survived, whereas in the Innsbruck Medical University Hospital database, there were seven survivors who received CPR and AED. All survivors had received immediate CPR with an AED. Five patients had good neurological outcome (cerebral performance category 1-2). Conclusions: In the Austrian mountains, CPR was attempted in less than 20% of sudden cardiac arrest cases. The few that survived had received immediate CPR with an AED. To better understand the circumstances and outcome of sudden cardiac arrest in the mountains, out-of hospital and in-hospital data should be linked.

[Health Information Behavior of the South Tyrolean Population: An Epidemiological Cross-Sectional Study]. / Informationsverhalten der Südtiroler Bevölkerung zu Gesundheitsfragen ­ eine epidemiologische Querschnittsstudie.

OBJECTIVES: Investigation of the health information behavior, self-rated health, confidence in health issues and specific attitudes to health among the South Tyrolean population. METHODS: Our study is an epidemiological cross-sectional study; data were collected via telephone interviews, using a questionnaire developed for this purpose that covered various aspects of information and health-related behavior. For the elaboration of the typology of the most distinctive stereotypes in terms of health information and health-related behavior, a hierarchical cluster analysis was performed. RESULTS: We assessed 504 correct telephone interviews. The majority of the respondents considered themselves health-conscious and preferred heterogeneous information media. The most used information media for health issues were mass media, i. e. newspapers or magazines and television or radio. The internet was used less as a source of information. Younger individuals assessed themselves to be healthier than older people, and older women aged 65 years or more were the most health-impaired group. Respondents had greatest confidence in their general practitioner, their own feeling or experience. Thus, in terms of health information and health behavior, the following four classes of people could be distinguished, namely "internet information elite", "robust fatalists", "stricken" and "health-conscious mainstreamers". CONCLUSION: Our results show that the South Tyrolean population has a high level of health consciousness and gathers health information from various media. The characterization of different patient typologies of information processing in combination with health-related behavior indicates that information about health and illness should be appropriately addressed to the respective stereotype.

Polypharmacy in older patients with chronic diseases: a cross-sectional analysis of factors associated with excessive polypharmacy.

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).

Effectiveness and safety of beta blockers in the management of hypertension in older adults: a systematic review to help reduce inappropriate prescribing.

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.

Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing.

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 <8.5% because of scarce data on clinically relevant benefits of their use. Twenty-two of the included studies were funded by pharmaceutical companies and authored or co-authored by employees of the sponsor. CONCLUSIONS: Other than the surrogate endpoint of improved glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4 inhibitors might have a lower risk of hypoglycaemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed that evaluate the risks and benefits of DPP-4 inhibitors for the management of type 2 diabetes mellitus in older adults, using clinically relevant outcomes and including representative samples of older adults with information on their frailty status and comorbidities. Studies are also needed that are independent of pharmaceutical company involvement.

Novel Methods for Surface EMG Analysis and Exploration Based on Multi-Modal Gaussian Mixture Models.

This paper introduces a new method for data analysis of animal muscle activation during locomotion. It is based on fitting Gaussian mixture models (GMMs) to surface EMG data (sEMG). This approach enables researchers/users to isolate parts of the overall muscle activation within locomotion EMG data. Furthermore, it provides new opportunities for analysis and exploration of sEMG data by using the resulting Gaussian modes as atomic building blocks for a hierarchical clustering. In our experiments, composite peak models representing the general activation pattern per sensor location (one sensor on the long back muscle, three sensors on the gluteus muscle on each body side) were identified per individual for all 14 horses during walk and trot in the present study. Hereby we show the applicability of the method to identify composite peak models, which describe activation of different muscles throughout cycles of locomotion.

Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA-eDS): study protocol for a randomized controlled trial.

BACKGROUND: Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial. METHODS: The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO-database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA-eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death. DISCUSSION: The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

One Small Step for a Man: Estimation of Gender, Age and Height from Recordings of One Step by a Single Inertial Sensor.

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.