The Effectiveness of Assistive Technologies for Older Adults and the Influence of Frailty: Systematic Literature Review of Randomized Controlled Trials.

BACKGROUND: The use of assistive technologies (ATs) to support older people has been fueled by the demographic change and technological progress in many countries. These devices are designed to assist seniors, enable independent living at home or in residential facilities, and improve quality of life by addressing age-related difficulties. OBJECTIVE: We aimed to evaluate the effectiveness of ATs on relevant outcomes with a focus on frail older adults. METHODS: A systematic literature review of randomized controlled trials evaluating ATs was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Ovid Medline, PsycINFO, SocIndex, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CENTRAL (Cochrane Central Register of Controlled Trials), and IEEEXplore databases were searched from January 1, 2009, to March 15, 2019. ATs were included when aiming to support the domains autonomy, communication, or safety of older people with a mean age ≥65 years. Trials performed within a laboratory setting were excluded. Studies were retrospectively categorized according to the physical frailty status of participants. RESULTS: A total of 19 trials with a high level of heterogeneity were included in the analysis. Six device categories were identified: mobility, personal disease management, medication, mental support, hearing, and vision. Eight trials showed significant effectiveness in all or some of the primary outcome measures. Personal disease management devices seem to be the most effective, with four out of five studies showing significant improvement of disease-related outcomes. Frailty could only be assessed for seven trials. Studies including participants with significant or severe impairment showed no effectiveness. CONCLUSIONS: Different ATs show some promising results in well-functioning but not in frail older adults, suggesting that the evaluated ATs might not (yet) be suitable for this subgroup. The uncertainty of the effectiveness of ATs and the lack of high-quality research for many promising supportive devices were confirmed in this systematic review. Large studies, also including frail older adults, and clear standards are needed in the future to guide professionals, older users, and their relatives. TRIAL REGISTRATION: PROSPERO CRD42019130249; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130249.

Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.

BACKGROUND: Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials have yielded negative results and effectiveness may be outweighed by harms. OBJECTIVES: To assess the efficacy and safety of antipsychotics for the treatment of agitation and psychosis in people with Alzheimer's disease and vascular dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid Sp), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register, and the International Clinical Trials Registry Portal on 7 January 2021. Two review authors independently screened the title and abstract of the hits, and two review authors assessed the full text of studies that got through this screening. SELECTION CRITERIA: We included randomised, placebo-controlled, parallel-arm trials comparing the effects of antipsychotics and placebo for the treatment of agitation or psychosis in people with dementia due to Alzheimer's disease or vascular dementia, or both, irrespective of age, severity of cognitive impairment, and setting. (The majority of) participants had to have clinically significant agitation (including aggression) or psychosis or both at baseline. We excluded studies about antipsychotics that are no longer available in the USA or EU, or that are used for emergency short-term sedation. We also excluded head-to-head trials and antipsychotic withdrawal trials. DATA COLLECTION AND ANALYSIS: The primary outcomes were (1) reduction in agitation or psychosis in participants with agitation or psychosis, respectively at baseline, and (2) the number of participants with adverse events: somnolence, extrapyramidal symptoms, any adverse event, any serious adverse event (SAE), and death. Two review authors independently extracted the necessary data and assessed risk of bias with the Cochrane risk of bias tool. We calculated the pooled effect on agitation and psychosis for typical and atypical antipsychotics separately, and the pooled risk of adverse effects independent of the target symptom (agitation or psychosis). We used RevMan Web for the analyses. MAIN RESULTS: The search yielded 8233 separate hits. After assessing the full-text of 35 studies, we included 24 trials that met the eligibility criteria. Six trials tested a typical antipsychotic, four for agitation and two for psychosis. Twenty trials tested an atypical antipsychotic, eight for agitation and 12 for psychosis. Two trials tested both drug types. Seventeen of 26 comparisons were performed in patients with Alzheimer's disease specifically. The other nine comparisons also included patients with vascular dementia or mixed dementia. Together, the studies included 6090 participants (12 to 652 per study). The trials were performed in institutionalised, hospitalised and community-dwelling patients, or a combination of those. For typical antipsychotics (e.g. haloperidol, thiothixene), we are uncertain whether these drugs improve agitation compared with placebo (standardised mean difference (SMD) -0.36, 95% confidence interval (CI) -0.57 to -0.15, 4 studies, n = 361); very low-certainty evidence, but typical antipsychotics may improve psychosis slightly (SMD -0.29, 95% CI -0.55 to -0.03, 2studies, n= 240; low-certainty evidence) compared with placebo. These drugs probably increase the risk of somnolence (risk ratio (RR) 2.62, 95% CI 1.51 to 4.56, 3 studies, n = 466; moderate-certainty evidence) and increase extrapyramidal symptoms (RR 2.26, 95% CI 1.58 to 3.23, 3 studies, n = 467; high-certainty) evidence. There was no evidence regarding the risk of any adverse event. The risks of SAEs (RR 1.32, 95% CI 0.65 to 2.66, 1 study, n = 193) and death (RR 1.46, 95% CI 0.54 to 4.00, 6 studies, n = 578) may be increased slightly, but these estimates were very imprecise, and the certainty was low. The effect estimates for haloperidol from five trials were in line with those of the drug class. Atypical antipsychotics (e.g. risperidone, olanzapine, aripiprazole, quetiapine) probably reduce agitation slightly (SMD -0.21, 95% CI -0.30 to -0.12, 7 studies, n = 1971; moderate-certainty evidence), but probably have a negligible effect on psychosis (SMD -0.11, 95% CI -0.18 to -0.03, 12 studies, n = 3364; moderate-certainty evidence). These drugs increase the risk of somnolence (RR 1.93, 95% CI 1.57 to 2.39, 13 studies, n - 3878; high-certainty evidence) and are probably also associated with slightly increased risk of extrapyramidal symptoms (RR 1.39, 95% CI 1.14 to 1.68, 15 studies, n = 4180; moderate-certainty evidence), serious adverse events (RR 1.32, 95% CI 1.09 to 1.61, 15 studies, n= 4316; moderate-certainty evidence) and death (RR 1.36, 95% CI 0.90 to 2.05, 17 studies, n= 5032; moderate-certainty evidence), although the latter estimate was imprecise. The drugs probably have a negligible effect on the risk of any adverse event (RR 1.05, 95% CI 1.02 to 1.09, 11 studies, n = 2785; moderate-certainty evidence). The findings from seven trials for risperidone were in line with those for the drug class. AUTHORS' CONCLUSIONS: There is some evidence that typical antipsychotics might decrease agitation and psychosis slightly in patients with dementia. Atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible. The apparent effectiveness of the drugs seen in daily practice may be explained by a favourable natural course of the symptoms, as observed in the placebo groups. Both drug classes increase the risk of somnolence and other adverse events. If antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative.

Comparison of International Therapy Guidelines with Regard to the Treatment of Malignant Catatonia.

OBJECTIVE: Malignant catatonia (MC) is an extremely rare, life-threatening disorder. It is characterized by catatonic symptoms accompanied by autonomic instability, hyperthermia, and changes in laboratory values. In many cases, MC is not recognized as such. Evidence-based guidelines are essential to ensure quality of treatment, but what do current national and international guidelines recommend? METHOD: Online search for international guidelines from English-, French-, Italian-, and German-speaking countries whose medical care meets high standards addressing the treatment of MC. These were analyzed and compared regarding statements on MC, recommendations, and strength of scientific evidence. RESULTS: Fifteen of the identified guidelines were included. Only 5 of 15 comment on the treatment of MC. As for other rare diseases, no detailed recommendations are available. Suggested therapies are limited to benzodiazepines and electroconvulsive therapy. Levels of evidence and grades of recommendation are predominantly low. CONCLUSION: Many international guidelines do not mention MC. It is not possible to derive a clear algorithm for the treatment of MC from most current guidelines. A thorough update of most guidelines appears to be necessary. Lack of awareness and knowledge of MC among physicians and medical professionals might lead to inadequate or delayed care, worsened outcome, or death.

Treatment of the Neuroleptic Malignant Syndrome in International Therapy Guidelines: A Comparative Analysis.

INTRODUCTION: The neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated to the use of antipsychotics. Since it requires rapid and efficient medical care, high-quality treatment guidelines should be available. In this article, we analyzed and compared different international therapy guidelines for the treatment of schizophrenia, in which NMS treatment recommendations might be contained. METHODS: We performed an Internet-based search for schizophrenia guidelines via the website of the respective medical society. Guidelines in English, French, Italian, and German from countries whose medical care meets high standards were selected for further analysis and comparison of the NMS treatment recommendations (if present), and their underlying evidence. RESULTS: The NMS is mentioned in 12 of 14 guidelines. Only 9 report concrete therapy recommendations (benzodiazepines/dantrolene/bromocriptine/amantadine/intensive care and/or electroconvulsive therapy (ECT)), however, with high heterogeneity. Only 5 guidelines included all possible drug therapy options and ECT, but with differing combination strategies, dosages, application forms, and combinability of options. The level of evidence of the different recommendations was estimated as low. DISCUSSION: One-third of the selected guidelines do not report any NMS therapy recommendations. Most guidelines mentioning the NMS do not provide therapy recommendations that include all relevant treatment options. The results show a very high heterogeneity, and the recommendations and statements are of low-evidence levels. The lack of knowledge about the NMS and its treatment may delay the onset of therapy, impair the quality of treatment, and lead to a worse outcome or death.

The Pharmacological Treatment of Arterial Hypertension in Frail, Older Patients­a Systematic Review

BACKGROUND: It is debated whether the treatment goals and decision-making algorithms for elderly patients with hypertension should be the same as those for younger patients. The American and European guidelines leave decisions about antihypertensive treatment in frail, institutionalized patients up to the treating physician. We therefore systematically searched the literature for publications on the phamacotherapy of arterial hypertension in frail patients. METHODS: The MEDLINE, Embase, and Central databases were systematically searched for randomized, controlled trials (RCTs) and non-randomized studies, including observational studies, on the pharmacotherapy of arterial hypertension in elderly patients since the introduction of the concept of frailty, published over the period 1992-2017. RESULTS: Out of 19 282 citations for randomized, controlled trials and 5659 for non-randomized trials and observational studies, four RCTs and three observational studies were included in the further analysis. The included RCTs showed a trend to- wards a benefit from pharmacotherapy of hypertension in frail patients with respect to mortality, cardiovascular disease, functional status, and quality of life. On the other hand, some of the observational studies indicated a lower rate of falls and lower mortality among patients who received no antihypertensive treatment. CONCLUSION: In view of the conflicting findings of RCTs and non-randomized studies, the lower representation of frail subjects in RCTs, and the high risk of bias in non- randomized studies, the findings of the studies included in this review do not enable the formulation of any strictly evidence-based treatment recommendations. As a rule of thumb, the authors propose that a target systolic blood pressure of <150 mmHg should be aimed at in patients whose gait speed is less than 0.8 m/s, while a target range of 130-139 mmHg can be set for patients over age 80 who are no more than mildly frail.

Communicating prognosis to women with early breast cancer - overview of prediction tools and the development and pilot testing of a decision aid.

BACKGROUND: Shared decision-making in oncology requires information on individual prognosis. This comprises cancer prognosis as well as competing risks of dying due to age and comorbidities. Decision aids usually do not provide such information on competing risks. We conducted an overview on clinical prediction tools for early breast cancer and developed and pilot-tested a decision aid (DA) addressing individual prognosis using additional chemotherapy in early, hormone receptor-positive breast cancer as an example. METHODS: Systematic literature search on clinical prediction tools for the effects of drug treatment on survival of breast cancer. The DA was developed following criteria for evidence-based patient information and International Patient Decision Aids Standards. We included data on the influence of age and comorbidities on overall prognosis. The DA was pilot-tested in focus groups. Comprehension was additionally evaluated through an online survey with women in breast cancer self-help groups. RESULTS: We identified three prediction tools: Adjuvant!Online, PREDICT and CancerMath. All tools consider age and tumor characteristics. Adjuvant!Online considers comorbidities, CancerMath displays age-dependent non-cancer mortality. Harm due to therapy is not reported. Twenty women participated in focus groups piloting the DA until data saturation was achieved. A total of 102 women consented to participate in the online survey, of which 86 completed the survey. The rate of correct responses was 90.5% and ranged between 84 and 95% for individual questions. CONCLUSIONS: None of the clinical prediction tools fulfilled the requirements to provide women with all the necessary information for informed decision-making. Information on individual prognosis was well understood and can be included in patient decision aids.

A Proposal for the Retrospective Identification and Categorization of Older People With Functional Impairments in Scientific Studies-Recommendations of the Medication and Quality of Life in Frail Older Persons (MedQoL) Research Group.

When treating older adults, a main factor to consider is physical frailty. Because specific assessments in clinical trials are frequently lacking, critical appraisal of treatment evidence with respect to functional status is challenging. Our aim was to identify and categorize assessments for functional status given in clinical trials in older adults to allow for a retrospective characterization and indirect comparison of treatment evidence from these cohorts. We conducted 4 separate systematic reviews of randomized and nonrandomized controlled clinical trials in older people with hypertension, diabetes, depression, and dementia. All assessments identified that reflected functional status were analyzed. Assessments were categorized across 4 different functional status levels. These levels span from functionally not impaired, slightly impaired, significantly impaired, to severely impaired/disabled. If available from the literature, cut-offs for these 4 functioning levels were extracted. If not, or if the existing cut-offs did not match the predefined functional levels, cut-off points were defined by an expert group composed of geriatricians, pharmacists, pharmacologists, neurologists, psychiatrists, and epidemiologists using a patient-centered approach. We identified 51 instruments that included measures of functional status. Although some of the assessments had clearly defined cut-offs across our predefined categories, many others did not. In most cases, no cut-offs existed for slightly impaired or severely impaired older adults. Missing cut-offs or values to adjust were determined by the expert group and are presented as described. The functional status assessments that were identified and operationalized across 4 functional levels could now be used for a retrospective characterization of functional status in randomized controlled trials and observational studies. Allocated categories only serve as approximations and should be validated head-to-head in future studies. Moreover, as general standard, upcoming studies involving older adults should include and explicitly report functional impairment as a baseline characteristic of all participants enrolled.

Alternative package leaflets improve people's understanding of drug side effects-A randomized controlled exploratory survey.

BACKGROUND: Current German and EU package leaflets (PLs) do not distinguish to what extent listed side effects are indeed side effects caused by drug intake or instead symptoms that occur regardless of drug use. We recently showed that most health professionals misinterpret the frequencies of listed side effects as solely caused by the drug. The present study investigated whether (1) these misinterpretations also prevail among laypeople and (2) alternative PLs reduce these misinterpretations. METHODS: In March 2017, 397 out of 400 laypeople approached completed an online survey. They were randomized to one of four PL formats: three alternative PLs (drug facts box with/without reading instruction, narrative format with numbers) and one standard PL. Each PL listed four side effects for a fictitious drug: two were presented as occurring more often, one as equally often, and one as less often with drug intake. The alternative formats (interventions) included information on frequencies with and without drug intake and included a statement on the causal relation. The standard PL (control) only included information on frequency ranges with drug intake. Questions were asked on general occurrence and causality of side effects. RESULTS: Participants randomized to the standard PL were unable to answer questions on causality. For side effects occurring more often (equally; less often) with drug intake, only 1.9% to 2.8% (equally: 1.9%; less often: 1.9%) provided correct responses about the causal nature of side effects, compared to 55.0% to 81.9% (equally: 23.8% to 70.5%; less often: 21.0% to 43.2%) of participants who received alternative PLs. It remains unclear whether one alternative format is superior to the others. CONCLUSION: In conclusion, information on the frequency of side effects in current package leaflets is misleading. Comparative presentation of frequencies for side effects with and without drug intake including statements on the causal relation significantly improves understanding.

Understanding adverse drug reactions in package leaflets - an exploratory survey among health care professionals.

BACKGROUND: Current German or UK package leaflets do not contain an explicit notice that the listing of side effects does not imply that they are caused by the drug. Causal interpretations by patients and lay people are frequently observed. The authors examined whether health professionals understand that there is not necessarily a causal relation between drug intake and the frequency of side effects and whether adding placebo comparison improves understanding. METHODS: Exploratory survey consisting of eight assessments, each containing 2-6 survey items, and focus groups with one survey sample using questionnaires on adverse reactions in standard package leaflets and modified package leaflets supplemented with placebo comparison. Participants were convenience samples of 379 health professionals including 153 physicians (80 gynaecologists, 124 diabetes experts - physicians, nurses, and others, 39 medical students in their last year at university, 49 first year health science and education students with completed vocational training and professional experience in various health care professions and 87 pharmacists/pharmacy students). They were asked to rate how often the different adverse reactions listed were caused by drug intake. All surveys were carried out within university seminars and postgraduate lectures from April 2014 to June 2015 in Germany. Response rate was 86 % or higher. RESULTS: Without placebo comparison, the majority of participants responded that the drug causes adverse reactions with the frequency given in the package leaflet or even more often (95 % of health science students, 100 % of medical students, 60 to 80 % of physicians and 66 % of pharmacists/pharmacy students). Simply adding placebo comparison in a table did not prevent misunderstanding. Analysis of focus groups with health science students supported the lack of understanding. CONCLUSIONS: In the present surveys, health professionals had major difficulties understanding frequency information on side effects in package leaflets. The great majority erroneously implied a causal relation between drug intake and the frequency of side effects, even though most side effects listed are symptoms commonly experienced in daily life.

Environmental risk assessment of antibiotics including synergistic and antagonistic combination effects.

The interaction-based hazard index (HIint) allows a prediction of mixture effects different from linear additivity by including information on binary mixtures between the chemicals. The aim of this study is to make a solid estimate on the possible synergistic potential of combined antibiotics and to quantify the subsequent effect for the case of the receiving river Elbe, Germany. Pieces of information on binary interactions between antibiotic groups were used from literature and from knowledge on human antibiotic combination therapy. Applying a moderate and a worst-case scenario, in terms of the interaction magnitude, resulted in 50 to 200% higher environmental risks, compared to the classical assessment approach applying simple concentration addition. A subsequent sensitivity analysis revealed that the data strength for some binary antibiotic combinations is too low to be considered for a solid estimate of synergistic effects. This led to the definition of certain preconditions in order to decide whether or not to include certain interaction information (e.g. the necessary number of interaction studies). The exclusion of information with low data strength resulted in an attenuated risk increase of 20 to 50%, based on the currently available scientific information on binary antibiotic mixtures. In order to include antibiotics with the highest share in the overall risk (macrolides, quinolones, and cephalosporins) as well as their corresponding metabolites, investigations should focus on binary interactions between them.

Representative input load of antibiotics to WWTPs: Predictive accuracy and determination of a required sampling quantity.

Predicting the input loads of antibiotics to wastewater treatment plants (WWTP) using certain input data (e.g. prescriptions) is a reasonable method if no analytical data is available. Besides the spatiotemporal uncertainties of the projection itself, only a few studies exist to confirm the suitability of required excretion data from literature. Prescription data with a comparatively high resolution and a sampling campaign covering 15 months were used to answer the question of applicability of the prediction approach. As a result, macrolides, sulfamethoxazole and trimethoprim were almost fully recovered close to 100% of the expected input loads. Nearly all substances of the beta-lactam family exhibit high elimination rates during the wastewater transport in the sewer system with a low recovery rate at the WWTP. The measured input loads of cefuroxime, ciprofloxacin and levofloxacin fluctuated greatly through the year which was not obvious from relatively constant prescribed amounts. The latter substances are an example that available data are not per se sufficient to monitor the actual release into the environment. Furthermore, the extensive data pool of this study was used to calculate the necessary number of samples to determine a representative annual mean load to the WWTP. For antibiotics with low seasonality and low input scattering a minimum of about 10 samples is required. In the case of antibiotics exhibiting fluctuating input loads 30 to 40 evenly distributed samples are necessary for a representative input determination. As a high level estimate, a minimum number of 20-40 samples per year is proposed to reasonably estimate a representative annual input load of antibiotics and other micropollutants.

Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse sewage samples.

In a research project on risk management of harmful substances in water cycles, clindamycin and 12 further antibiotics were determined in different sewage samples. In contrast to other antibiotics, an increase of the clindamycin concentration in the final effluent in comparison to the influent of the sewage treatment plant (STP) was observed. A back transformation from the main metabolite clindamycin sulfoxide to clindamycin during the denitrification process has been discussed. Therefore, the concentration of this metabolite was measured additionally. Clindamycin sulfoxide was stable in the STP and the assumption of back transformation of the metabolite to clindamycin was confuted. To explain the increasing clindamycin concentration in the STP, the ratio of clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry spells with concentrated samples and with long dwell time in the sewer system. A short hydraulic retention in waste water system and diluted samples in periods of extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin concentration. A plausible explanation of this behavior could be that clindamycin was adsorbed strongly to a component of the sewage during this long residence time and in the STP, clindamycin was released. In the common sample preparation in the lab, clindamycin was not released. Measurements of clindamycin and clindamycin sulfoxide in the influent and effluent of STP is advised for sewage monitoring.