Deprescribing:Moving beyond barriers and facilitators

Unnecessary polypharmacy continues to be a problem among older adults. The field of deprescribing (planned, supervised process of medication discontinuation) aims to address this problem. Deprescribing is a relatively new field despite having grown substantially in recent years. Much of the early research in this area focused on identifying barriers to and facilitators of deprescribing in clinical practice, which contributed to a large body of work on this topic. However, with continuing research around barriers and facilitators, we need to be mindful to undertake research that builds on existing knowledge, addresses known gaps, and advances the field. Additionally, there is a need in deprescribing research to shift focus to developing ways to address known barriers and harness knowledge of facilitators. That is, translating existing knowledge into strategies and tools that can impact clinical practice and lead to practical and sustained deprescribing efforts.</p

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Extending self-determination theory’s dual-process model to a new tripartite model to explain diminished functioning

In a three-study investigation, we pursued three purposes: (1) extend self-determination theory’s dual-process model to a new tripartite model—to recognize that environmental conditions sometimes render a psychological need dormant; (2) better explain adolescents’ diminished functioning; and (3) develop the Three States Questionnaire (TSQ). In Study 1, 402 high schoolers reported the satisfied, frustrated, and dormant state of their psychological needs (autonomy, competence, and relatedness) during classroom instruction to develop the TSQ. In Study 2, 320 high schoolers reported their satisfied, frustrated, and dormant states as well as 17 indicators of their effective, defiant, and diminished classroom functioning. The TSQ showed excellent psychometric properties, and the predictive power of the tripartite model was superior to that of the dual-process model in the prediction of all five indicators of diminished functioning (e.g., disengagement). In Study 3, 457 high schoolers’ perceived teachers’ motivating styles (supporting, controlling, and neglecting) predicted their three need states (satisfied, frustrated, and dormant), which predicted the quality of their classroom functioning (effective, defiant, and diminished). Overall, the dormant state was distinct from the other two states, it uniquely explained diminished functioning, and the tripartite model out-predicted the dual-process model

Human-animal relationships and interactions during the Covid-19 lockdown phase in the UK: Investigating links with mental health and loneliness

BACKGROUND The Covid-19 pandemic raises questions about the role that relationships and interactions between humans and animals play in the context of widespread social distancing and isolation measures. We aimed to investigate links between mental health and loneliness, companion animal ownership, the human-animal bond, and human-animal interactions; and to explore animal owners’ perceptions related to the role of their animals during lockdown. METHODS A cross-sectional online survey of UK residents over 18 years of age was conducted between April and June 2020. The questionnaire included validated and bespoke items measuring demographics; exposures and outcomes related to mental health, wellbeing and loneliness; the human-animal bond and human-animal interactions. RESULTS Of 5,926 participants, 5,323 (89.8%) had at least one companion animal. Most perceived their animals to be a source of considerable support, but concerns were reported related to various practical aspects of providing care during lockdown. Strength of the human-animal bond did not differ significantly between species. Poorer mental health pre-lockdown was associated with a stronger reported human-animal bond (b = -.014, 95% CI [-.023 - -.005], p = .002). Animal ownership compared with non-ownership was associated with smaller decreases in mental health (b = .267, 95% CI [.079 - .455], p = .005) and smaller increases in loneliness (b = -.302, 95% CI [-.461 - -.144], p = .001) since lockdown. CONCLUSION The human-animal bond is a construct that may be linked to mental health vulnerability in animal owners. Strength of the human-animal bond in terms of emotional closeness or intimacy dimensions appears to be independent of animal species. Animal ownership seemed to mitigate some of the detrimental psychological effects of Covid-19 lockdown. Further targeted investigation of the role of human-animal relationships and interactions for human health, including testing of the social buffering hypothesis and the development of instruments suited for use across animal species, is required

Responding to Mass, Computer-Generated, and Malattributed Comments

A number of technological and political forces have transformed the once staid and insider dominated notice-and-comment process into a forum for large scale, sometimes messy, participation in regulatory decisionmaking. It is not unheard of for agencies to receive millions of comments on rulemakings; often these comments are received as part of organized mass comment campaigns. In some rulemakings, questions have been raised about whether public comments were submitted under false names, or were automatically generated by computer “bot” programs. In this Article, we examine whether and to what extent such submissions are problematic and make recommendations for how rulemaking agencies should respond as a matter of law, policy, and technology.Our overarching conclusion is that agencies should adopt both low- and high-tech measures to limit the negative impact of these sorts of comments. Mass, malattributed, and computer-generated comments, however, do not represent a crisis for the regulatory state at this time. They have not been found to violate federal law and do not generally undermine the integrity of notice-and-comment rulemaking, and we are not aware of evidence of widespread substantive harms in particular rulemaking efforts or to the rulemaking system overall. However, appropriate responses, especially those that take advantage of new technology, could reduce the cost and negative impacts of technology-enabled comments. Adopting such techniques could, for example, improve the opportunity for a diverse public to participate in the federal rulemaking process meaningfully and augment current practices with new forms of citizen engagement. Indeed, in addition to exploring how new technologies—the very same technologies that enable mass, malattributed, and computer-generated comments—can help with analyzing those comments, we also explore throughout how technology can help regulatory officials make sense of public input and draw greater insights from public comments of all kinds. Finally, other jurisdictions at the state and local level and internationally are turning to new technology to enable innovative forms of public participation, thus improving the quality of rule and policymaking. These activities illustrate hopeful opportunities for future experimentation.This Article, based on a report commissioned by the Administrative Conference of the United States, expresses the authors’ views only and does not necessarily reflect those of the Administrative Conference or the federal government

Blood Pressure Surge with Alarm Is Reduced after Exercise and Diet Intervention in Firefighters

BACKGROUND: Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response. PURPOSE: To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention. METHODS: SBP and DBP and BP surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings. RESULTS: Twenty five firefighters (43.4 ± 13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ± 12.9 to 10.5 ± 11.7 mmHg, P \u3c 0.05; DBP surge from 8.2 ± 10.8 to 4.9 ± 5.6 mmHg, P \u3e 0.05) after intervention. We confirm that clinical (127.6 ± 9.1 to 120 ± 8.2 mmHg) and central (122.7 ± 11.3 to 118.2 ± 10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ± 1.5 to 11.2 ± 2.2 U/ml) and nitric oxide (40.4 ± 7 to 48.9 ± 16.9 μmol/l) levels improve with an exercise and diet intervention. CONCLUSION: These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders

Baseline characteristics and comparability of older multimorbid patients with polypharmacy and general practitioners participating in a randomized controlled primary care trial.

OBJECTIVES Recruiting general practitioners (GPs) and their multimorbid older patients for trials is challenging for multiple reasons (e.g., high workload, limited mobility). The comparability of study participants is important for interpreting study findings. This manuscript describes the baseline characteristics of GPs and patients participating in the 'Optimizing PharmacoTherapy in older multimorbid adults In primary CAre' (OPTICA) trial, a study of optimization of pharmacotherapy for multimorbid older adults. The overall aim of this study was to determine if the GPs and patients participating in the OPTICA trial are comparable to the real-world population in Swiss primary care. DESIGN Analysis of baseline data from GPs and patients in the OPTICA trial and a reference cohort from the FIRE ('Family medicine ICPC Research using Electronic medical records') project. SETTING Primary care, Switzerland. PARTICIPANTS Three hundred twenty-three multimorbid (≥ 3 chronic conditions) patients with polypharmacy (≥ 5 regular medications) aged ≥ 65 years and 43 GPs recruited for the OPTICA trial were compared to 22,907 older multimorbid patients with polypharmacy and 227 GPs from the FIRE database. METHODS We compared the characteristics of GPs and patients participating in the OPTICA trial with other GPs and other older multimorbid adults with polypharmacy in the FIRE database. We described the baseline willingness to have medications deprescribed of the patients participating in the OPTICA trial using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. RESULTS The GPs in the FIRE project and OPTICA were similar in terms of sociodemographic characteristics and their work as a GP (e.g. aged in their fifties, ≥ 10 years of experience, ≥ 60% are self-employed, ≥ 80% work in a group practice). The median age of patients in the OPTICA trial was 77 years and 45% of trial participants were women. Patients participating in the OPTICA trial and patients in the FIRE database were comparable in terms of age, certain clinical characteristics (e.g. systolic blood pressure, body mass index) and health services use (e.g. selected lab and vital data measurements). More than 80% of older multimorbid patients reported to be willing to stop ≥ 1 of their medications if their doctor said that this would be possible. CONCLUSION The characteristics of patients and GPs recruited into the OPTICA trial are relatively comparable to characteristics of a real-world Swiss population, which indicates that recruiting a generalizable patient sample is possible in the primary care setting. Multimorbid patients in the OPTICA trial reported a high willingness to have medications deprescribed. TRIAL REGISTRATION Clinicaltrials.gov ( NCT03724539 ), KOFAM (Swiss national portal) ( SNCTP000003060 ), Universal Trial Number (U1111-1226-8013)

High Pulse Pressure Impairs Cerebral Artery Endothelial Function in Young, but Not Old, Mice

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent dilation was similar between the static and low pulse pressure conditions. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young mice, mediated by less nitric oxide bioavailability and greater oxidative stress. Cerebral arteries from old mice had impaired cerebral artery endothelium-dependent dilation at static pressure compared with young cerebral arteries. However, exposure to low or high pulse pressure did not cause any further impairments to endothelium-dependent dilation in old cerebral arteries compared with static pressure. The old cerebral arteries had less distension during exposure to high pulse pressure and greater stiffness compared with young cerebral arteries. These results indicate that acute exposure to high pulse pressure impairs endothelium-dependent dilation in young, but not old, cerebral arteries. The greater stiffness of cerebral arteries from old mice potentially protects against the negative consequences of high pulse pressure

Deprescribing guidelines:An international symposium on development, implementation, research and health professional education

Deprescribing is a clinically important and feasible innovation that ensures medication efficacy, reduces harms, and mitigates polypharmacy. It involves reducing doses or stopping medications that are not useful, no longer needed, or which may be causing harm. It may also involve changing to a safer agent or using non-pharmacological approaches for care instead. Clinical guidelines combined with behaviour changes (of health care providers (HCPs), the public, and health care decision-makers) are needed to integrate deprescribing into routine practice. Using rigorous international standards, the Bruyère Research Institute Deprescribing Guidelines research team validated a ground-breaking deprescribing guideline methodology and developed or co-developed 5 evidence-based deprescribing guidelines. In March 2018, the team hosted an international symposium convening HCPs, researchers, public agencies, policymakers, and patient advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate knowledge exchange amongst guideline developers, users, and the public; initiate partnerships and collaborations for new deprescribing guideline recommendations and effectiveness research; and to continue work on HCP deprescribing education activities. An interprofessional planning committee developed an overall agenda, and small groups worked on session objectives and formats for different components: methods for rigorous deprescribing guideline development, implementation experiences, research/evaluation experiences and educational needs. Through a series of keynote speakers, panel discussions, and small working groups, the symposium provided a forum for participants to meet one another, learn about their different experiences with deprescribing guidelines, and develop collaborations for future initiatives. One hundred thirty participants, from 10 countries and representing over 100 institutions and organizations took part. Symposium proceedings are presented in this issue of RSAP for sharing with the wider community engaged in the care of patients with problematic polypharmacy.</p

Effectiveness of automated appointment reminders in Psychosis Community Services:A randomised controlled trial

We report on the first open-label, parallel group randomised controlled trial of automated appointment reminders in a psychosis community service in the UK. Ninety-five patients were randomly allocated to receiving/not receiving automated messaging reminders 7 days and 1 day before appointments. All ‘Attended’ and ‘Missed’ appointment outcomes over 6 months were analysed using cluster regression analysis. Reminded appointments were significantly more frequently attended than non-reminded appointments (unadjusted odds ratio (OR) = 3.54, 95% CI 1.36–9.22, P = 0.01; adjusted OR = 2.95, 95% CI 1.05–8.85, P &lt; 0.05). Automated messaging reminders can provide a robust strategy for promoting engagement with psychosis services