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Psychotropic drugs are frequently and sometimes inappropriately used for the treatment of neuropsychiatric symptoms of people with dementia, despite their limited efficacy and side effects. Interventions to address neuropsychiatric symptoms and psychotropic drug use are multifactorial and often multidisciplinary. Suboptimal implementation of these complex interventions often limits their effectiveness. This systematic review provides an overview of barriers and facilitators influencing the implementation of complex interventions targeting neuropsychiatric symptoms and psychotropic drug use in long-term care.
To identify relevant studies, the following electronic databases were searched between 28 May and 4 June: PubMed, Web of Science, PsycINFO, Cochrane, and CINAHL. Two reviewers systematically reviewed the literature, and the quality of the included studies was assessed using the Critical Appraisal Skills Programme qualitative checklist. The frequency of barriers and facilitators was addressed, followed by deductive thematic analysis describing their positive of negative influence. The Consolidated Framework for Implementation Research guided data synthesis.
Fifteen studies were included, using mostly a combination of intervention types and care programs, as well as different implementation strategies. Key factors to successful implementation included strong leadership and support of champions. Also, communication and coordination between disciplines, management support, sufficient resources, and culture (e.g. openness to change) influenced implementation positively. Barriers related mostly to unstable organizations, such as renovations to facility, changes toward self-directed teams, high staff turnover, and perceived work and time pressures.
Implementation is complex and needs to be tailored to the specific needs and characteristics of the organization in question. Champions should be carefully chosen, and the application of learned actions and knowledge into practice is expected to further improve implementation.
The molybdenum disulfide (MoS2) and indium tin oxide (ITO) interface were studied by atom probe tomography (APT). Raman spectroscopy, scanning electron microscopy, and grazing-incidence x-ray diffraction measurements were performed as complementary characterization. Results confirm that nanowires plated shape with the 〈110〉-orientation are aligned perpendicular to the ITO film with principal reflections at (002), (100), (101), (201), and Raman spectroscopy vibrational modes at E12g at 378 cm−1 and A1g at 407 cm−1 correspond to 2H-MoS2. APT reveals MoS+2, MoS+3 as predominant evaporated molecular ions on the sample, indicating no significant diffusion/segregation of Mo or S species within the ITO layer.
Before drawing conclusions on the contribution of an effective intervention to daily practice and initiating dissemination, its quality and implementation in daily practice should be optimal. The aim of this process evaluation was to study these aspects alongside a randomized controlled trial investigating the effects of a multidisciplinary biannual medication review in long-term care organizations (NTR3569).
Process evaluation with multiple measurements.
Thirteen units for people with dementia in six long-term care organizations in the Netherlands.
Physicians, pharmacists, and nursing staff of participating units.
The PROPER intervention is a structured and biannually repeated multidisciplinary medication review supported by organizational preparation and education, evaluation, and guidance.
Web-based questionnaires, interviews, attendance lists of education sessions, medication reviews and evaluation meetings, minutes, evaluation, and registration forms.
Participation rates in education sessions (95%), medication reviews (95%), and evaluation meetings (82%) were high. The intervention’s relevance and feasibility and applied implementation strategies were highly rated. However, the education sessions and conversations during medication reviews were too pharmacologically oriented for several nursing staff members. Identified barriers to implementation were required time, investment, planning issues, and high staff turnover; facilitators were the positive attitude of professionals toward the intervention, the support of higher management, and the appointment of a local implementation coordinator.
Implementation was successful. The commitment of both higher management and professionals was an important factor. This may partly have been due to the subject being topical; Dutch long-term-care organizations are pressed to lower inappropriate psychotropic drug use.
The START (STrAtegies for RelaTives) intervention reduced depressive and anxiety symptoms of family carers of relatives with dementia at home over 2 years and was cost-effective.
To assess the clinical effectiveness over 6 years and the impact on costs and care home admission.
We conducted a randomised, parallel group, superiority trial recruiting from 4 November 2009 to 8 June 2011 with 6-year follow-up (trial registration: ISCTRN 70017938). A total of 260 self-identified family carers of people with dementia were randomised 2:1 to START, an eight-session manual-based coping intervention delivered by supervised psychology graduates, or to treatment as usual (TAU). The primary outcome was affective symptoms (Hospital Anxiety and Depression Scale, total score (HADS-T)). Secondary outcomes included patient and carer service costs and care home admission.
In total, 222 (85.4%) of 173 carers randomised to START and 87 to TAU were included in the 6-year clinical efficacy analysis. Over 72 months, compared with TAU, the intervention group had improved scores on HADS-T (adjusted mean difference −2.00 points, 95% CI −3.38 to −0.63). Patient-related costs (START versus TAU, respectively: median £5759 v. £16 964 in the final year; P = 0.07) and carer-related costs (median £377 v. £274 in the final year) were not significantly different between groups nor were group differences in time until care home (intensity ratio START:TAU was 0.88, 95% CI 0.58–1.35).
START is clinically effective and this effect lasts for 6 years without increasing costs. This is the first intervention with such a long-term clinical and possible economic benefit and has potential to make a difference to individual carers.
Declarations of interest
G.L., Z.W. and C.C. are supported by the UCLH National Institute for Health Research (NIHR) Biomedical Research Centre. G.L. and P.R. were in part supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart's Health NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Z.W. reports during the conduct of the study; personal fees from GE Healthcare, grants from GE Healthcare, grants from Lundbeck, other from GE Healthcare, outside the submitted work.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.
The introduction of fast-track licensing strategies increases the approval of anti-cancer drugs with ambiguous benefit-risk profiles. Thus, in many instances there is lacking evidence about overall survival (OS) at the time of marketing authorisation. Our objective was to monitor and characterise therapies with ambiguous benefit-risk profiles and identify any post-approval updates on median OS after at least three years of approval by the European Medicines Agency (EMA).
We included all originator anti-cancer drugs with initially ambiguous benefit-risk profiles that received marketing authorization from the EMA between 1 Jan 2009 and 31 May 2015. Our monitoring timeframe was at least three years after EMA-approval. To identify study updates, the following three sources were included: clinicaltrials.gov, European Public Assessment Reports (EPARs), and PubMed.
In total, we identified 102 eligible approval studies. Out of these, a negative difference in median OS or no information was available in forty-three (42.2%) instances. During monitoring, eleven updates with accessible information on median OS could be identified. Including monitoring results, there are still thirty-two remaining therapies (31.4%) where no or negative information (n = 27 [26.5%] and n = 5 [4.9%], respectively) regarding median OS was present at least three years after EMA approval.
One-third of oncology drugs with ambiguous benefit-risk profiles failed to demonstrate a survival benefit even several years following marketing authorization. Systematic and transparent post-approval monitoring mechanisms will be of high relevance to assure a clinically relevant patient benefit, since the trend towards faster access to medicines with uncertain benefit is increasing rather than declining.
The aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.
To explore the association between anxiety and future dementia.
Medline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.
Anxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).
Anxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.
We present very detailed images of the photosphere of an AGB star obtained with the PIONIER instrument, installed at the Very Large Telescope Interferometer (VLTI). The images show a well defined stellar disc populated by a few convective patterns. Thanks to the high precision of the observations we are able to derive the contrast and granulation horizontal scale of the convective pattern for the first time in a direct way. Such quantities are then compared with scaling relations between granule size, effective temperature, and surface gravity that are predicted by simulations of stellar surface convection.
Contrary to public perception, child sex offending (CSO) and paedophilia are not the same. Only half of all cases of CSO are motivated by paedophilic preference, and a paedophilic preference does not necessarily lead to CSO. However, studies that investigated clinical factors accompanying and contributing to paedophilia so far mainly relied on paedophiles with a history of CSO. The aim of this study was to distinguish between factors associated with sexual preference (paedophile versus non-paedophile) and offender status (with versus without CSO). Accordingly, a 2 (sexual preference) × 2 (offender status) factorial design was used for a comprehensive clinical assessment of paedophiles with and without a history of CSO (n = 83, n = 79 respectively), child sex offenders without paedophilia (n = 32) and healthy controls (n = 148). Results indicated that psychiatric comorbidities, sexual dysfunctions and adverse childhood experiences were more common among paedophiles and child sex offenders than controls. Offenders and non-offenders differed in age, intelligence, educational level and experience of childhood sexual abuse, whereas paedophiles and non-paedophiles mainly differed in sexual characteristics (e.g., additional paraphilias, onset and current level of sexual activity). Regression analyses were more powerful in segregating offender status than sexual preference (mean classification accuracy: 76% versus 68%). In differentiating between offence- and preference-related factors this study improves clinical understanding of both phenomena and may be used to develop scientifically grounded CSO prevention and treatment programmes. It also highlights that some deviations are not traceable to just one of these two factors, thus raising the issue of the mechanism underlying both phenomena.
We studied the patient and non-patients factors of inappropriate psychotropic drug (PD) prescription for neuropsychiatric symptoms (NPS) in nursing home patients with severe dementia.
In a cross-sectional study, the appropriateness of prescriptions was explored using the Appropriate Psychotropic drug use In Dementia (APID) index sum score. This index assesses information from medical records on indication, evaluation, dosage, drug–drug interactions, drug–disease interactions, duplications, and therapy duration. Various measurements were carried out to identify the possible patient and non-patient factors. Linear multilevel regression analysis was used to identify factors that are associated with APID index sum scores. Analyses were performed for groups of PDs separately, i.e. antipsychotics, antidepressants, anxiolytics, and hypnotics.
The sample consisted of 338 patients with a PD prescription that used 147 antipsychotics, 167 antidepressants, 85 anxiolytics, and 76 hypnotics. It was found that older patients and more severe aggression, agitation, apathy, and depression were associated with more appropriate prescriptions. Additionally, less appropriate prescriptions were found to be associated with more severe anxiety, dementia diagnoses other than Alzheimer dementia, more physician time available per patient, more patients per physician, more years of experience of the physician, and higher nurse's workload.
The association of more pronounced NPS with more appropriate PD prescriptions implies that physicians should pay more attention to the appropriateness of PD prescriptions when NPS are less manifest. Non-patient-related factors are also associated with the appropriateness of PD prescriptions. However, especially considering that some of these findings are counter-intuitive, more research on the topic is recommended.
Objectives: Pedophilia (P) is a psychiatric disease associated with sexual attraction toward children and often accompanied by child sexual offending (CSO). Consequently, it is important to address the understanding of executive dysfunctions that may increase the probability of CSO. Moreover, this research field has been lacking to disentangle executive deficits associated with pedophilia (as a deviant sexual preference) from those associated with CSO (as a deviant sexual behavior). Methods: The German multi-sided research network NeMUP offers the opportunity to overcome these limitations. By applying the Cambridge Automated Neuropsychological Test Battery in four carefully matched groups of men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual offending against children; (3) child molesters without pedophilia (N=19), and (4) non-offending controls (N=49), we were able to analyze executive functioning in pedophilia and CSO independently. Results: Both CSO groups as compared to both non-CSO groups exhibited worsened response inhibition ability. However, only non-pedophilic offenders showed additionally disabled strategy use ability. Regarding set-shifting abilities, the P+CSO group showed the best performance. We also found that performances were affected by age: only in pedophiles, response inhibition worsened with age, while age-related deficits in set-shifting abilities were restricted to non-pedophilic participants. The latter also differentiated between both sexual preference groups. Conclusions: Our results are the first to demonstrate that executive dysfunctions are related to offense status rather than pedophilic preference. Furthermore, there was evidence for differentiating age and performance correlations between pedophiles and non-pedophiles, which warrants further investigation. (JINS, 2017, 23, 460–470)
The Chocó-Tumbesian region of western Ecuador is one of the 25 global biodiversity hotspots harbouring high numbers of endemic species, which are heavily threatened by habitat loss and fragmentation. Moreover, ongoing climate change in the tropics drives species uphill as lower-lying areas are becoming constantly drier. Such upslope movement can pose major challenges for less mobile species, such as understorey birds which are confined to mature forests and unable to cross habitat gaps. Consequently, these species are threatened by a combination of upslope range shifts and forest fragmentation. In our study, we investigated population numbers and habitat requirements of the Ecuadorian Tapaculo Scytalopus robbinsi, which is endemic to the premontane cloud forests of south-western Ecuador. Comparing the microhabitat structure within territories with control sites revealed that Ecuadorian Tapaculos prefer old secondary forests. Moreover, connectivity between forest fragments was the strongest predictor of the presence of territories within them. We estimated the mean upslope shift of the distribution range as 100 m per decade and developed a model of habitat availability for the revised range. Extrapolating the number of territories from the study area to the distributional range of the Ecuadorian Tapaculo showed that the global population size is smaller than previously assumed. Our results suggest that the Ecuadorian Tapaculo is strongly affected by forest loss and degradation. Therefore, to prevent a continuing decline in population numbers or even extinction, conservation measures focusing on restoring connectivity between fragments and increasing habitat quality and quantity for the remaining populations need to be prioritised.
Haemosporidian parasites are widespread in avian species and modulate their ecology, behaviour, life-history and fitness. The prevalence of these vector-transmitted parasites varies with host intrinsic and extrinsic factors, such as host resistance and behaviour, and habitat-related characteristics. In this study, we evaluated the prevalence of avian haemosporidians in great tit Parus major populations inhabiting two areas with different degrees of exposure to aerial emissions from pulp mills, to assess if this type of pollution impacted parasite prevalence. We also compared the physiological condition of infected and uninfected individuals. Haemosporidian infection prevalence was high (58%), varied seasonally, but was not associated with air pollution exposure. Fledged birds presented higher infection rates than nestlings and infected fledged birds had higher levels of blood glutathione peroxidase activity. These results allow us to infer that infection by blood parasites may activate antioxidant defences, possibly to protect the organism from the negative oxidative stress side-effects of immune activation against parasites. Because oxidative stress is one of the mechanisms responsible for ageing and senescence and may affect fitness, the relationship between parasitism and oxidative stress markers should be further investigated through studies that include experimental manipulation of infection in model organisms.
If patients are treated according to their personal preferences, depression treatment success is higher. It is not known which treatment options for late-life depression are preferred by patients aged 75 years and over and whether there are determinants of these preferences.
The data were derived from the German “Late-life depression in primary care: needs, health care utilization, and costs (AgeMooDe)” study. Patients aged 75+ years (N = 1,230) were recruited from primary care practices. Depressive symptoms were determined using the Geriatric Depression Scale (GDS-15). Support for eight treatment options was determined.
Medication, psychotherapy, talking to friends and family, and exercise were the preferred treatment options. Having a GDS score ≥ 6 significantly lowered the endorsement of some treatment options. For each treatment option, the probability of choosing the indecisive category “I do not know” was significantly increased in participants with moderate depressive symptoms.
Depressive symptoms influence the preference for certain treatment options and also increase indecision in patients. The high preference for psychotherapy suggests a much higher demand for late-life psychotherapy in the future. Healthcare systems should begin to prepare to meet this anticipated need. Future studies should include previous experience with treatment methods as a confounding variable.
In biological monitoring, deploying an effective standardised quantitative sampling method, optimised by trap design and sampling effort, is an essential consideration. To exemplify this using dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae and Aphodiinae) communities, three pitfall trap designs (un-baited (TN), baited at ground level (flat trap, TF), and baited above the trap (hanging trap, TH)), employed with varying levels of sampling effort (number of traps=1, 2, 3 … 10; number of days=1, 2, 3), were evaluated for sampling completeness and efficiency in the Eastern Cape, South Africa. Modelling and resampling simulation approaches were used to suggest optimal sampling protocols across environmentally diverse sites. Overall, TF recovered the greatest abundance and species richness of dung beetles, but behavioural guilds showed conflicting trends: endocoprids preferred TH while paracoprids and telocoprids preferred TF. Resampling simulation of trap type and the two components of sampling effort suggested that six TF traps left for three days was most efficient in obtaining a representative sample and allowed differentiation between trap types, allowing the improved efficiency to be recognised. The effect of trap type on non-target specimens, particularly ants, was also investigated. TF and TH caught almost no by-catch, which is ethically desirable.
This study explores the appropriateness of psychotropic drug (PD) use for neuropsychiatric symptoms (NPS) in nursing home patients with dementia.
A cross-sectional study on 559 patients with dementia residing on dementia special care units in Dutch nursing homes was conducted. Appropriateness of PD use was assessed using the Appropriate Psychotropic drug use In Dementia (APID) index. The APID index score is calculated using information about individual PDs from patients’ medical records. The index encompasses seven (different) domains of appropriateness, i.e. indication, evaluation, dosage, drug-drug interactions, drug-disease interactions, duplications, and therapy duration.
A total of 578 PDs were used for NPS by 60% of the nursing home patients. Indication, evaluation, and therapy duration contributed the most to inappropriate use. Ten per cent of the PDs scored fully appropriate according to the APID index sum score, 36% scored fully appropriate for indication, 46% scored fully appropriate for evaluation, and 58% scored fully appropriate for therapy duration. Antidepressants were used the most appropriately, and antiepileptics the most inappropriately.
The minority of the PD use was fully appropriate. The results imply that PD use for NPS in dementia can be improved; the appropriateness should be optimized with a clinical focus on the appropriate indications, evaluations, and therapy duration.