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Background: The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.Objective: We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG).Design and Participants: Observational cohort study of 13,508 normoglycemic patients (n = 4460; 33% taking statins) and 4563 IFG patients (n = 1865; 41% taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999-2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan-Meier method.Main Measures: The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality.Key Results: After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95% CI, 1.05 to 1.35; p = 0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p = 0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95% CI, 0.66 to 0.80; p < 0.0001) and IFG patients (HR 0.77, 95% CI, 0.64 to 0.91; p = 0.0029) with statin use.Conclusion: In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19-24%) risk. [ABSTRACT FROM AUTHOR]

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

Rodenticides are a key component of rodent management strategies, but birds of prey are susceptible to non-target exposure. New rules on sale and use of rodenticide products were introduced across the UK in 2016 in an industry-led stewardship scheme, with the aim of reducing this risk. To determine if this intervention has achieved its aim, exposure to second generation anticoagulant rodenticides (SGARs) was measured in buzzards. Liver samples from 790 buzzards collected between 2005 and 2022 (excluding 2016 and 2017 samples) were analyzed and the percentage presence and concentrations of SGARs from pre-stewardship and post-stewardship samples were compared. There was no statistically significant decrease in the percentage of buzzards exposed to bromadiolone, difenacoum or combined SGAR residues after the introduction of stewardship. The percentage of buzzards exposed to brodifacoum increased significantly post-stewardship, from 8 % to 27 %. There were no significant decreases in the concentrations of individual SGARs post-stewardship but concentration of combined SGARs increased significantly post-stewardship. Individual buzzards were significantly more likely to be exposed to multiple SGARs post-stewardship. Rodenticide poisoning was recorded as the cause of death for 5 % of pre- and post-stewardship buzzards with detectable levels of SGARs, and 90 % of these had combined SGAR residues >0.1 mg/kg. These findings suggest that the industry-led stewardship scheme has not yet had the intended impact of reducing SGAR exposure in non-target wildlife. The study highlights a substantial increase in exposure of buzzards to brodifacoum and to multiple SGARs post-stewardship, indicating that further changes to the stewardship scheme may be necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care. However, there are no published standard global clinical care guidelines for patients with Sanfilippo syndrome. To address this, a literature review was conducted to evaluate the current evidence base and to identify evidence gaps. The findings were reviewed by an international steering committee composed of clinical experts with extensive experience in managing patients with Sanfilippo syndrome. The goal was to create a consensus set of basic clinical guidelines that will be accessible to and informed by clinicians globally, as well as providing a practical resource for families to share with their local care team who may not have experience with this rare disease. This review distills 178 guideline statements into an easily digestible document that provides evidence-based, expert-led recommendations for how to approach common management challenges and appropriate monitoring schedules in the care of patients with Sanfilippo syndrome., (© 2022. The Author(s).)

We studied if clinicians could gain sufficient working knowledge of a computer-assisted diagnostic decision support system (DDSS) (SimulConsult), to make differential diagnoses (DDx) of genetic disorders. We hypothesized that virtual training could be convenient, asynchronous, and effective in teaching clinicians how to use a DDSS. We determined the efficacy of virtual, asynchronous teaching for clinicians to gain working knowledge to make computer-assisted DDx. Our study consisted of three surveys (Baseline, Training, and After Use) and a series of case problems sent to clinicians at Vanderbilt University Medical Center. All participants were able to generate computer-assisted DDx that achieved passing scores of the case problems. Between 75% and 92% agreed/completely agreed the DDSS was useful to their work and for clinical decision support and was easy to use. Participants' use of the DDSS resulted in statistically significant time savings in key tasks and in total time spent on clinical tasks. Our results indicate that virtual, asynchronous teaching can be an effective format to gain a working knowledge of a DDSS, and its clinical use could result in significant time savings across multiple tasks as well as facilitate synergistic interaction between clinicians and lab specialists. This approach is especially pertinent and offers value amid the COVID-19 pandemic., (© 2021 Wiley Periodicals LLC.)

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Therapies for infiltrative inflammation in multiple sclerosis (MS) have advanced greatly, but neurodegeneration and compartmentalized inflammation remain virtually untargeted as in other diseases of the nervous system. Consequently, many therapies are available for the relapsing-remitting form of MS, but the progressive forms remain essentially untreated. The objective of the International Progressive MS Alliance is to expedite the development of effective therapies for progressive MS through new initiatives that foster innovative thinking and concrete advancements. Based on these principles, the Alliance is developing a new funding programme that will focus on experimental medicine trials. Here, we discuss the reasons behind the focus on experimental medicine trials, the strengths and weaknesses of these approaches and of the programme, and why we hope to advance therapies while improving the understanding of progression in MS. We are soliciting public and academic feedback, which will help shape the programme and future strategies of the Alliance.

Brain renin-angiotensin system (RAS) activation is thought to mediate deoxycorticosterone acetate (DOCA)-salt hypertension, an animal model for human primary hyperaldosteronism. Here, we determined whether brainstem angiotensin II is generated from locally synthesized angiotensinogen and mediates DOCA-salt hypertension. To this end, chronic DOCA-salt-hypertensive rats were treated with liver-directed siRNA targeted to angiotensinogen, the angiotensin II type 1 receptor antagonist valsartan, or the mineralocorticoid receptor antagonist spironolactone (n = 6-8/group). We quantified circulating angiotensinogen and renin by enzyme-kinetic assay, tissue angiotensinogen by Western blotting, and angiotensin metabolites by LC-MS/MS. In rats without DOCA-salt, circulating angiotensin II was detected in all rats, whereas brainstem angiotensin II was detected in 5 out of 7 rats. DOCA-salt increased mean arterial pressure by 19 ± 1 mmHg and suppressed circulating renin and angiotensin II by >90%, while brainstem angiotensin II became undetectable in 5 out of 7 rats (<6 fmol/g). Gene silencing of liver angiotensinogen using siRNA lowered circulating angiotensinogen by 97 ± 0.3%, and made brainstem angiotensin II undetectable in all rats (P<0.05 vs. non-DOCA-salt), although brainstem angiotensinogen remained intact. As expected for this model, neither siRNA nor valsartan attenuated the hypertensive response to DOCA-salt, whereas spironolactone normalized blood pressure and restored brain angiotensin II together with circulating renin and angiotensin II. In conclusion, despite local synthesis of angiotensinogen in the brain, brain angiotensin II depended on circulating angiotensinogen. That DOCA-salt suppressed circulating and brain angiotensin II in parallel, while spironolactone simultaneously increased brain angiotensin II and lowered blood pressure, indicates that DOCA-salt hypertension is not mediated by brain RAS activation., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Purpose: The field of psycho-oncology is relatively undeveloped, with little information existing regarding the use of psychologists at cancer centers. Comprising 30 leading cancer centers across the United States, the National Comprehensive Cancer Network (NCCN) set out to understand the trends in its Member Institutions., Methods: The NCCN Best Practices Committee surveyed NCCN Member Institutions regarding their use of psychologists. The survey was administered electronically in the spring/summer of 2017., Results: The survey was completed by 18 cancer centers. Across institutions, 94% have psychologists appointed to provide direct care to their cancer center patients. The number of licensed psychologist full-time equivalents (FTEs) on staff who provide direct patient care ranged from < 1.0 FTE (17%) to 17.0-17.9 FTEs (6%). Regarding psychologist appointments, 41% have both faculty and staff appointments, 41% have all faculty appointments, and 18% have all staff appointments. Forty-three percent of institutions indicated that some licensed psychologists at their centers (ranging from 1%-65%) do not provide any direct clinical care, and 57% indicated that all licensed psychologist on staff devote some amount of time to direct clinical care. The percent of clinical care time that is spent on direct clinical care ranged from 15%-90%., Conclusion: There is great variability in psychology staffing, academic appointments, and the amount of direct patient care provided by on-staff psychologists at cancer centers.

This article reviews cognitive behavioral therapy techniques for sleep in the cancer realm. There are unique factors associated with cancer that can exacerbate sleep issues. Stimulus control, sleep restriction, relaxation, paradoxical intention, and cognitive therapy are discussed as specific components of cognitive behavioral therapy for sleep, and practical techniques for implementation are provided. Individual considerations in implementing these techniques are also discussed, including factors such as age, ethnicity, gender, relationship status, educational level, work status, cancer history, pharmacologic treatments, and health beliefs.