ObjectiveTo provide an overview of non-pharmacological interventions for behavioural and psychological symptoms in dementia (BPSD).DesignSystematic overview of reviews.Data sourcesPubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL and PsycINFO (2009–March 2015).Eligibility criteriaSystematic reviews (SRs) that included at least one comparative study evaluating any non-pharmacological intervention, to treat BPSD.Data extractionEligible studies were selected and data extracted independently by 2 reviewers.The AMSTAR checklist was used to assess the quality of the SRs.Data analysisExtracted data were synthesised using a narrative approach.Results38 SRs and 142 primary studies were identified, comprising the following categories of non-pharmacological interventions: (1) sensory stimulation interventions (12 SRs, 27 primary studies) that encompassed: acupressure, aromatherapy, massage/touch therapy, light therapy and sensory garden; (2) cognitive/emotion-oriented interventions (33 SRs; 70 primary studies) that included cognitive stimulation, music/dance therapy, dance therapy, snoezelen, transcutaneous electrical nerve stimulation, reminiscence therapy, validation therapy, simulated presence therapy; (3) behaviour management techniques (6 SRs; 32 primary studies) and (4) other therapies (5 SRs, 12 primary studies) comprising exercise therapy, animal-assisted therapy, special care unit and dining room environment-based interventions. Music therapy was effective in reducing agitation (SMD, −0.49; 95% CI −0.82 to −0.17; p=0.003), and anxiety (SMD, −0.64; 95% CI −1.05 to −0.24; p=0.002). Home-based behavioural management techniques, caregiver-based interventions or staff training in communication skills, person-centred care or dementia care mapping with supervision during implementation were found to be effective for symptomatic and severe agitation.ConclusionsA large number of non-pharmacological interventions for BPSD were identified. The majority of the studies had great variation in how the same type of intervention was defined and applied, the follow-up duration, the type of outcome measured, usually with modest sample size. Overall, music therapy and behavioural management techniques were effective for reducing BPSD.

BackgroundNon-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.Methods and FindingsWe performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I2=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I2=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.ConclusionsIn older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.

Objective To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Design Meta-epidemiological study. Data sources Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. Eligibility criteria for selecting studies From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories) . Results 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ 2 =0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ 2 =0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ 2 =0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ 2 =0.57). Conclusions Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations.

Novel mRNA isoforms for two members of the group III metabotropic glutamate receptors (mGluRs), called mGluR7b and mGluR8b, were identified from rat brain cerebral cortex and hippocampus. In both cases, the alternative splicing is generated by a similar out-of-frame insertion in the carboxyl-terminus that results in the replacement of the last 16 amino acids of mGluR7 and mGluR8 by 23 and 16 different amino acids, respectively. Distribution analysis for mGluR7 and mGluR8 isoforms revealed that the two splice variants are generally coexpressed in the same brain areas. The few exceptions were the olfactory bulb, in which only the mGluR7a form could be detected by reverse transcription-polymerase chain reaction, and the lateral reticular and ambiguous nuclei, which showed only mGluR8a labelling. Despite expression in the same regions, different mRNA abundance for the two variants of each receptor were observed. When transiently coexpressed in HEK 293 cells with the phospholipase C-activating chimeric G alpha qi9-G-protein, the a and b forms for both receptor subtypes showed a similar pharmacological profile. The rank order of potencies for both was: DL-amino-4-phosphonobutyrate > L-serine-O-phosphate > glutamate. However, the agonist potencies were significantly higher for mGluR8a, b compared with mGluR7a,b. In Xenopus oocytes, glutamate evoked currents only with mGluR8 when coexpressed with Kir 3.1 and 3.4. Glutamate-induced currents were antagonized by the group II/III antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine. In conclusion, the two isoforms of each receptor have identical pharmacological profiles when expressed in heterologous systems, despite structural differences in the carboxyl-terminal domains.

No abstract

Overall, the panel developed 12 recommendations for the delivery of non-pharmacological interventions to older patients at risk of developing or, with delirium.

BackgroundFalls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making.ObjectivesTo systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals.MethodsWe searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions.ResultsFifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis.ConclusionsThe aim of this overview of reviews of non-pharmacological interventions to prevent falls in older people in different settings, is to support clinicians and other healthcare workers with clinical decision-making by providing a comprehensive perspective of findings.

BackgroundThe epidemic of Alzheimer's disease (AD) represents a significant challenge for the health care and social service systems of many developed countries. AD affects both patients and family caregivers, on whom the main burden of care falls, putting them at higher risk of stress, anxiety, mortality and lower quality of life. Evidence remains controversial concerning the effectiveness of providing support to caregivers of AD patients, through case management, counseling, training, technological devices and the integration of existing care services. The main objectives of the UP-TECH project are: 1) to reduce the care burden of family caregivers of AD patients; and 2) to maintain AD patients at home.Methods/designA total of 450 dyads comprising AD patients and their caregivers in five health districts of the Marche region, Italy, will be randomized into three study arms. Participants in the first study arm will receive comprehensive care and support from a case manager (an ad hoc trained social worker) (UP group). Subjects in the second study arm will be similarly supported by a case manager, but in addition will receive a technological toolkit (UP-TECH group). Participants in the control arm will only receive brochures regarding available services. All subjects will be visited at home by a trained nurse who will assess them using a standardized questionnaire at enrollment (M0), 6 months (M6) and 12 months (M12). Follow-up telephone interviews are scheduled at 24 months (M24). The primary outcomes are: 1) caregiver burden, measured using the Caregiver Burden Inventory (CBI); and 2) the actual number of days spent at home during the study period, defined as the number of days free from institutionalizations, hospitalizations and stays in an observation unit of an emergency room.DiscussionThe UP-TECH project protocol integrates previous evidence on the effectiveness of strategies in dementia care, that is, the use of case management, new technologies, nurse home visits and efforts toward the integration of existing services in an ambitious holistic design. The analysis of different interventions is expected to provide sound evidence of the effectiveness and cost of programs supporting AD patients in the community.Trial registrationClinicalTrials.gov: http://NCT01700556