CAG Repeat Length and Suicidality in Huntington\u27s disease

Abstract: The purpose of this study was to determine if a correlation exists between suicide and CAG repeat length in Huntington’s disease. Methodology: A case-control study using the COHORT Study de-identified database was conducted. Responses were collected from 163 participants. Depression, substance abuse history and use of benzodiazepines were covariates. Responses to the UHDRS behavioral section pertaining to the frequency and severity of suicidal ideation (“feels life is not worth living”, “has suicidal thoughts”) were analyzed. Results: Despite taking depression, benzodiazepine use, and history of substance abuse into account, there was a predictive relationship between CAG repeat length and frequency of suicidal ideation (p = .010). When the effect of depression was taken into account, there was no significant relationship between CAG repeat length and the severity of suicidal ideation. Recommendations: The findings from this quantitative analysis supported using CAG length in a clinician’s risk factor assessment to determine the frequency of suicidality

Ozanimod: A Practical Review for Nurses and Advanced Practice Providers

Ozanimod is the first sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). In clinical trials, participants with moderately to severely active UC who received once-daily oral ozanimod demonstrated significantly improved rates of clinical, endoscopic, and histologic outcomes than participants receiving placebo. Ozanimod is also approved for the treatment of relapsing forms of multiple sclerosis (MS). This review summarizes safety data from UC and MS clinical trials and discusses treatment considerations when using ozanimod in clinical practice. Ozanimod is an oral, small molecule agent with a novel mechaism of action that differentiates it from other UC therapies. Ozanimod was generally well tolerated in clinical trials, and the incidence of adverse events of special interest based on prior associations with S1P receptor modulation was low overall. Of note, the risk for clinically significant bradycardia upon treatment initiation was mitigated by gradual dose titration, few patients experienced lymphopenia or serious infections, macular edema and malignancy occurred infrequently, and most hepatic events were transient and did not require treatment discontinuation. Given the safety and efficacy profile of ozanimod, it may be an early treatment option in patients with moderate disease or in those hesitant to use biologics, and it could also be beneficial after other treatments have failed. Further investigation is needed to determine the positioning of ozanimod within the UC treatment armamentarium

Whose Preferences Matter? A Patient-Centered Approach for Eliciting Treatment Goals

BACKGROUND: Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients\u27 preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. OBJECTIVE: We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs). METHODS: We conducted five nominal group technique (NGT) meetings to elicit and prioritize treatment goals from patients and HCPs. Five to nine participants in each group responded silently to one question about their treatment goals. Responses were shared, consolidated, and ranked to develop a prioritized list for each group. The ranked lists were combined. Goals were rated and sorted into categories. Multidimensional scaling and hierarchical cluster analysis were used to derive a visual representation, or cognitive map, of the data and to identify conceptual clusters, reflecting how frequently items were sorted into the same category. RESULTS: Five NGT groups yielded 34 unique patient-generated treatment goals and 31 unique HCP-generated goals. There were differences between patients and HCPs in the goals generated and how they were clustered. Patients\u27 goals tended to focus on the impact of specific symptoms on their day-to-day lives, whereas providers\u27 goals focused on slowing down the course of disease progression. CONCLUSIONS: Differences between the treatment goals of patients and HCPs underscore the limitations of using HCP- or investigator-identified goals. This new adaptation of cognitive mapping is a patient-centered approach that can be used to generate and organize the outcomes and attributes for values clarification exercises while minimizing investigator bias and maximizing relevance to patients

A Novel Tool to Improve Shared Decision Making and Adherence in Multiple Sclerosis: Development and Preliminary Testing

Background. Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. Objectives. We sought to develop a shared decision-making (SDM) tool for MS DMTs, evaluate patient and provider responses to the tool, and address challenges encountered during development to guide a future trial. Methods. We created a patient-centered design process informed by image theory to develop the MS-SUPPORT SDM tool. Development included semistructured interviews and alpha and beta testing with MS patients and providers. Beta testing assessed dissemination and clinical integration strategies, decision-making processes, communication, and adherence. Patients evaluated the tool before and after a clinic visit. Results. MS-SUPPORT combines self-assessment with tailored feedback to help patients identify their treatment goals and preferences, correct misperceptions, frame decisions, and promote adherence. MS-SUPPORT generates a personal summary of their responses that patients can share with their provider to facilitate communication. Alpha testing (14 patients) identified areas needing improvement, resulting in reorganization and shortening of the tool. MS-SUPPORT was highly rated in beta testing (15 patients, 4 providers) on patient-provider communication, patient preparation, adherence, and other endpoints. Dissemination through both patient and provider networks appeared feasible. All patient testers wanted to share the summary report with their provider, but only 60% did. Limitations. Small sample size, no comparison group. Conclusions. The development process resulted in a patient-centered SDM tool for MS that may facilitate patient involvement in decision making, help providers understand their patients\u27 preferences, and improve adherence, though further testing is needed. Beta testing in real-world conditions was critical to prepare the tool for future testing and inform the design of future studies

Developmental nutrition modulates metabolic responses to projected climate change

The current policy has the world on track to experience around 3°C of warming by 2100. The responses of organisms to our warming world will be mediated by changes in physiological processes, including metabolic rate. Metabolic rate represents the energetic cost of living, and is fundamental to understanding the energy required to sustain populations. Current evidence indicates that animals have a limited capacity to adapt to warmer environments by reducing their metabolic rate. Consequently, animals may be more reliant on metabolic plasticity to ameliorate the thermodynamic effect of rising temperatures on physiological rates. However, metabolic plasticity is influenced by other environmental factors, including the nutritional quality of food. Elevated levels of atmospheric CO2 are expected to reduce the protein and increase the carbohydrate concentration in plants, but we do not know how this will affect the response of metabolic rate to climate warming. Here we test the interactive effects of developmental dietary protein and carbohydrate concentrations on the metabolic plasticity of adult Drosophila melanogaster in response to a 3°C increase in temperature while accounting for variation associated with body mass and activity (resting metabolic rate). We show that the thermal sensitivity of resting metabolic rate is modulated by developmental nutrition with animals reared on nutritionally poor, low-protein diets showing the greatest increase in resting metabolic rate in response to simulated climate warming. We also show that if the nutritional quality of resources is unaffected by climate change, then temperature-induced increases in resting metabolic rate will be offset by decreases in mass, but the absolute energy requirements of animals will be elevated relative to current conditions despite this. If, on the other hand, temperatures rise and resources become more calorie-dense and carbohydrate-rich, then the resting metabolic rate of animals will remain relatively unchanged, but decreases in mass and activity may drive down the absolute energy requirements of animals. In the absence of evolutionary adaptation, these findings suggest that the combined plastic response of physiological, morphological and behavioural traits to temperature and nutrition may be an important determinant of the ultimate outcome of climate change for populations

Evaluation of a Novel Preference Assessment Tool for Patients with Multiple Sclerosis

Background: We developed a preference assessment tool to help assess patient goals, values, and preferences for multiple sclerosis (MS) management. All preference items in the tool were generated by people with MS. The aim of this study was to evaluate this tool in a national sample of people with MS. Methods: English-speaking patients with MS aged 21 to 75 years with access to the internet were recruited. Participants completed the preference tool online, which included separate modules assessing three core preference areas: treatment goals, preferences for attributes of disease-modifying therapies, and factors influencing a change in treatment. The tool generated a summary of participants\u27 treatment goals and preferences. Immediately after viewing the summary, participants were asked to evaluate the tool. Rankings of preference domains were compared with rankings obtained in another study. Results: In 135 people with MS who completed the tool and evaluation, the highest ranked goal was brain health (memory, thinking, brain), followed by disability concerns (walking, strength, vision). Rankings were highly similar to those in the referent study. Nearly all participants reported that the tool helped them understand their goals and priorities regarding MS and that the summary appropriately reflected what is important to them. Most participants (87%) wanted to discuss their treatment goals and priorities with their clinician. Conclusions: This preference assessment tool successfully captured patients\u27 goals, values, and preferences for MS treatment and could potentially be used to help patients communicate their preferences to their clinician

Table S1 from Temperature and nutrition do not interact to shape the evolution of metabolic rate

Summary information of selective environments and parent group

Tables S2 and S3 from Temperature and nutrition do not interact to shape the evolution of metabolic rate

Statistical tables for females and male

R code from Temperature and nutrition do not interact to shape the evolution of metabolic rate

Text file containing the R script to run statistical analyse