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

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

Reducing inappropriate polypharmacy: the process of deprescribing

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application

Action 3:30R: Process evaluation of a cluster randomised feasibility study of a revised teaching assistant-led extracurricular physical activity intervention for 8 to 10 year olds

Background: Numerous interventions to increase children's physical activity levels are published, yet, few studies report indicators of external validity. Process evaluations are critical for assessing intervention implementation, sustainability and effectiveness. A mixed-methods process evaluation, using the RE-AIM framework, was conducted to evaluate the internal and external validity of Action 3:30R, a revised teaching assistant-led after-school intervention which aimed to increase physical activity in children aged 8-10 years and was underpinned by Self-determination Theory (SDT). Methods: Data were collected and reported in line with the five components of RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance). Quantitative measures included logbooks, registers and self-reported teaching-efficacy, autonomy support, child enjoyment and perceived exertion questionnaires. Questionnaire data were collected at three points throughout the 15-week intervention. Observations by trained researchers were also conducted to assess fidelity to the intervention manual and its underpinning theory. Post-intervention focus groups with pupils and interviews with teaching assistants (TAs), school staff and external stakeholders explored the implementation and potential sustainability of Action 3:30R from stakeholders' perspectives. Results: Action 3:30R appealed to a broad range of pupils, including girls and less-active pupils. The Action 3:30R TA training was implemented as intended and was perceived as valuable professional development. Releasing staff for training was a barrier in two of the six intervention schools, which were unable to deliver the intervention as a result. Pupils enjoyed the intervention, and the Action 3:30R core principles underpinned by SDT were implemented with high fidelity, as was the intervention itself. Scheduling conflicts with other clubs and lack of parental support were perceived as the main barriers to recruitment and attendance. Lack of space and season were cited as the main barriers affecting the quality of delivery. The study shows evidence of maintenance, as one intervention school decided to continue Action 3:30R beyond the study. Funding and continued TA training were suggested as factors which may affect the maintenance of Action 3:30R. Conclusions: Action 3:30R is an enjoyable, autonomy-supportive after-school programme, which engages a range of pupils and offers TAs valuable training. RE-AIM provided helpful structure and is recommended for intervention evaluations. Trial registration: ISRCTN34001941. Prospectively registered 01/12/2016

General practitioners' deprescribing decisions in older adults with polypharmacy: a case vignette study in 31 countries.

BACKGROUND General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. METHODS In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. RESULTS Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). INTERPRETATION The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

How general practitioners would deprescribe in frail oldest-old with polypharmacy — the LESS study

Abstract Background Many oldest-old (> 80-years) with multimorbidity and polypharmacy are at high risk of inappropriate use of medication, but we know little about whether and how GPs would deprescribe, especially in the frail oldest-old. We aimed to determine whether, how, and why Swiss GPs deprescribe for this population. Methods GPs took an online survey that presented case-vignettes of a frail oldest-old patient with and without history of cardiovascular disease (CVD) and asked if they would deprescribe any of seven medications. We calculated percentages of GPs willing to deprescribe at least one medication in the case with CVD and compared these with the case without CVD using paired t-tests. We also included open-ended questions to capture reasons for deprescribing and asked which factors could influence their decision to deprescribe by asking for their agreement on a 5-point-Likert-scale. Results Of the 282 GPs we invited, 157 (56%) responded: 73% were men; mean age was 56. In the case-vignette without CVD, 98% of GPs deprescribed at least one medication (usually cardiovascular preventive medications) stating it had no indication nor benefit. They would lower the dose or prescribe pain medication as needed to reduce side effects. Their response was much the same when the patient had a history of CVD. GPs reported they were influenced by ‘risk’ and ‘benefit’ of medications, ‘quality of life’, and ‘life expectancy’, and prioritized the patient’s wishes and priorities when deprescribing. Conclusion Swiss GPs were willing to deprescribe cardiovascular preventive medication when it lacked indication but tended to retain pain medication. Developing tools for GPs to assist them in balancing the risks and benefits of medication in the context of patient values may improve deprescribing activities in practice