Quality of life in people with epilepsy: The associations of anti-seizure medications and biopsychosocial variables.

People with epilepsy, on average, experience lower quality of life (QOL) than healthy controls. This study examined the associations between specific anti-seizure medications, biopsychosocial factors, and QOL in people with epilepsy. Analysis of covariance revealed that individuals taking three or more anti-seizure medications had significantly lower QOL than those taking levetiracetam. Findings also demonstrated that when examining biopsychosocial factors as predictors of QOL in hierarchical regression, anxiety, depression, and daytime sleepiness were significant predictors of QOL. Once these factors were entered into the model, number of medications was no longer significant. The final model predicted 59.6% of the variance in QOL. In clinical settings, providers should take a patient-centered approach that includes regular assessment of QOL and an emphasis on good psychological care for those coping with anxiety, depression, and sleep difficulty. These findings underscore the importance of addressing psychological health and sleep factors within the epilepsy population.

The medial entorhinal cortex is necessary for the stimulus control over hippocampal place fields by distal, but not proximal, landmarks.

A fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham-lesioned mice (n = 6) following 90° rotations of either distal landmarks or proximal cues in a cue- controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham-lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway.

Undocumented immigration and terrorism: Is there a connection?

Unauthorized immigration, already a divisive and controversial subject in American society, was reframed as a grave national security threat after the terrorist attacks on Sept. 11, 2001. Yet, despite substantial public, political and policy attention to the issue of undocumented immigration and terrorism, there has been relatively little empirical assessment of the relationship between unauthorized immigration flows and terrorist activity. We attempt to fill this gap by combining newly developed estimates of the unauthorized population, a novel use of sentencing and prosecutorial data to measure terrorism-related activity, and multiple data sources on the criminological, socioeconomic, and demographic context from all 50 states from 1990 to 2014. We then leverage this unique dataset to examine the longitudinal, macro-level relationship between undocumented immigration and various measures of terrorism. Results from fixed effects negative binomial models suggest that increased undocumented immigration over this period is not associated with terrorist attacks, radicalization, or terrorism prosecutions.

Evaluation of the Pain Impact Index for Community-Dwelling Older Adults Through the Application of Rasch Modelling.

OBJECTIVE: Evaluate the Pain Impact Index, a simple, brief, easy-to-use, and novel tool to assess the impact of chronic pain in community-dwelling older adults. METHODS: A Rasch modelling analysis was undertaken in Stata using a partial credit model suited to the Likert-type items that comprised the Index. The Index was evaluated for ordering of category thresholds, unidimensionality, overall fit to the Rasch model, measurement bias (Differential Item Functioning, DIF), targeting, and construct validity. RESULTS: The four-item Pain Impact Index was self-completed by 6454 community-dwelling Australians who were aged at least 70 years and experienced pain on most days. Two items showed evidence of threshold disordering, and this was resolved by collapsing response categories (from 5 to 3) for all items. The rescored Index conformed to the unidimensionality assumption and had satisfactory fit with the Rasch model (analyses conducted on a reduced sample size to mitigate the potential for overpowering: n = 377, P > 0.0125, power > 77%). When considering uniform DIF, the most frequent sources of measurement bias were age, knee pain, and upper back pain. When considering nonuniform DIF, the most frequent source of measurement bias was knee pain. The Index had good ability to differentiate between respondents with different levels of pain impact and had highest measurement precision for respondents located around the average level of pain impact in the study sample. Both convergent and discriminant validity of the Index were supported. CONCLUSION: The Pain Impact Index showed evidence of unidimensionality, was able to successfully differentiate between levels of pain impact, and had good evidence of construct validity.

Bystander CPR training: is non-classroom based CPR training as effective as a classroom based approach? A systematic review of randomised controlled trials.

INTRODUCTION: In Scotland, approximately 5% of out-of-hospital cardiac arrest patients survive to hospital discharge. Improving bystander cardiopulmonary resuscitation (CPR), especially in rural areas, could have a significant effect on the numbers of lives saved. The objective of this study was to systematically review whether non-classroom-based bystander CPR training is as effective as classroom-based training.. METHODS: A database search for randomised controlled trials that compared classroom-based to non-classroom-based training in bystanders (non-medical professionals) was performed in Medline and Embase with no date restrictions. Relevant studies were critically appraised. Differences in the efficacy of CPR training between the two study arms of non-classroom and classroom-based training were measured by outcomes of compression depth, compression rate and correct hand positioning. RESULTS: Eight studies in total met the inclusion criteria. Thirteen out of a total of 15 outcomes showed non-classroom-based CPR training to be as effective as or more effective than classroom-based training. A high risk of bias was identified in every study. CONCLUSION: From the available evidence, non-classroom-based training appears at least as effective as classroom-based training for CPR. This could have significant implications for delivery of CPR training nationally, especially in remote and rural areas. However, due to the variation in how outcomes were measured, and the high risk of the presence of bias in each of the studies, further research into CPR training strategies is strongly recommended.

A pilot randomized controlled trial of medication adherence therapy: Psychosocial leverage using a significant other (MAT-PLUS) for individuals on extended-release naltrexone.

BACKGROUND: Extended-release naltrexone (XR-NTX) is an important treatment option for individuals with opioid use disorder (OUD) and/or alcohol use disorder (AUD). However, problems with retention are a major barrier to its overall effectiveness, and interventions to improve adherence are underdeveloped. The purpose of this study was to pilot test the MAT-PLUS intervention, which combines assertive outreach and involvement of a treatment significant other (TSO) to improve adherence to XR-NTX. METHODS: Adults (N = 41) seeking treatment for OUD and/or AUD with XR-NTX were recruited from an inpatient addiction treatment center and randomized to the MAT-PLUS intervention or treatment as usual (TAU) for 16-weeks. TSOs (N = 19) of individuals in the MAT-PLUS condition were also enrolled. The primary outcome was the number of XR-NTX doses received and relapse to regular heavy use (opioid or alcohol) was a secondary outcome. RESULTS: Participants in the MAT-PLUS group received 3.4 doses compared to 2.5 in TAU, which was significant after controlling for SUD diagnosis (p < 0.05). Rates of receipts of all prescribed doses were 61.1 % in MAT-PLUS compared to 30.4 % in TAU, giving an NNT of 3.3. Relapse rates and days of heavy use did not vary by treatment group. CONCLUSIONS: This study demonstrates preliminary efficacy of the MAT-PLUS intervention for XR-NTX adherence. This study was limited by its small sample size and future research should broaden the intervention to apply across medications for SUD in larger samples. Family support with an emphasis on medication adherence has strong potential for improving addiction treatment outcomes.

Linguistic Variables and Gender Differences Within a Messenger-Based Psychosocial Chat Counseling Service for Children and Adolescents: Cross-Sectional Study.

BACKGROUND: Text messaging is widely used by young people for communicating and seeking mental health support through chat-based helplines. However, written communication lacks nonverbal cues, and language usage is an important source of information about a person's mental health state and is known to be a marker for psychopathology. OBJECTIVE: The aim of the study was to investigate language usage, and its gender differences and associations with the presence of psychiatric symptoms within a chat counseling service for adolescents and young adults. METHODS: For this study, the anonymized chat content of a German messenger-based psychosocial chat counseling service for children and adolescents ("krisenchat") between May 2020 and July 2021 was analyzed. In total, 661,131 messages from 6962 users were evaluated using Linguistic Inquiry and Word Count, considering the following linguistic variables: first-person singular and plural pronouns, negations, positive and negative emotion words, insight words, and causation words. Descriptive analyses were performed, and gender differences of those variables were evaluated. Finally, a binary logistic regression analysis examined the predictive value of linguistic variables on the presence of psychiatric symptoms. RESULTS: Across all analyzed chats, first-person singular pronouns were used most frequently (965,542/8,328,309, 11.6%), followed by positive emotion words (408,087/8,328,309, 4.9%), insight words (341,460/8,328,309, 4.1%), negations (316,475/8,328,309, 3.8%), negative emotion words (266,505/8,328,309, 3.2%), causation words (241,520/8,328,309, 2.9%), and first-person plural pronouns (499,698/8,328,309, 0.6%). Female users and users identifying as diverse used significantly more first-person singular pronouns and insight words than male users (both P<.001). Negations were significantly more used by female users than male users or users identifying as diverse (P=.007). Similar findings were noted for negative emotion words (P=.01). The regression model of predicting psychiatric symptoms by linguistic variables was significant and indicated that increased use of first-person singular pronouns (odds ratio [OR] 1.05), negations (OR 1.11), and negative emotion words (OR 1.15) was positively associated with the presence of psychiatric symptoms, whereas increased use of first-person plural pronouns (OR 0.39) and causation words (OR 0.90) was negatively associated with the presence of psychiatric symptoms. Suicidality, self-harm, and depression showed the most significant correlations with linguistic variables. CONCLUSIONS: This study highlights the importance of examining linguistic features in chat counseling contexts. By integrating psycholinguistic findings into counseling practice, counselors may better understand users' psychological processes and provide more targeted support. For instance, certain linguistic features, such as high use of first-person singular pronouns, negations, or negative emotion words, may indicate the presence of psychiatric symptoms, particularly among female users and users identifying as diverse. Further research is needed to provide an in-depth look into language processes within chat counseling services.

Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis.

Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth advantage was abolished in the gut of germ-free mice and restored in gnotobiotic mice colonized with members of the classes Bacteroidia and Clostridia. Reactive oxygen species (ROS) produced during the host response caused lysis of commensal microbes, resulting in the release of microbiota-derived aspartate that was used by S. Tm, in concert with nitrate-dependent anaerobic respiration, to outcompete commensal Enterobacteriaceae. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent S. Tm expansion during colitis.

The Boston Rehabilitative Impairment Study of the Elderly: a description of methods.

OBJECTIVES: To describe the methods of a longitudinal cohort study among older adults with preclinical disability. The study aims to address the lack of evidence guiding mobility rehabilitation for older adults by identifying those impairments and impairment combinations that are most responsible for mobility decline and disability progression over 2 years of follow-up. DESIGN: Longitudinal cohort study. SETTING: Metropolitan-based health care system. PARTICIPANTS: Community-dwelling primary care patients aged ≥65 years (N=430), with self-reported modification of mobility tasks because of underlying health conditions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Late Life Function and Disability Instrument (LLFDI) (primary outcome); Short Physical Performance Battery and 400-m walk test (secondary outcomes). RESULTS: Among 7403 primary care patients identified as being potentially eligible for participation, 430 were enrolled. Participants have a mean age of 76.5 years, are 68% women, and have on average 4.2 chronic conditions. Mean LLFDI scores are 55.5 for Function and 68.9 and 52.3 for the Disability Limitation and Frequency domains, respectively. CONCLUSIONS: Completion of our study aims will inform development of primary care-based rehabilitative strategies to prevent disability. Additionally, data generated in this investigation can also serve as a vital resource for ancillary studies addressing important questions in rehabilitative science relevant to geriatric care.

Who are frequent chatters? Characterization of frequent users in a 24/7 messenger-based psychological chat counseling service for children and adolescents.

Background: Online helplines have shown a high acceptance, feasibility, and usability, especially with young people. Helplines usually aim to provide one-time crisis intervention; however, there are users who frequently use such services, tying a disproportionately large proportion of service capacities. To date, there is no research on the characterization of frequent users of online helplines. Therefore, the aim of the present study is to characterize frequent chatters in a chat-based counseling context. Methods: This cross-sectional study retrospectively analyzed anonymous data of users who approached the German messenger-based psychological chat counseling service krisenchat between May 2020 and July 2021 (N = 6657), with a focus on frequent users - the "frequent chatters". Frequent chatters were defined as those who received an above average (M + 2 ∗ SD) amount of messages from counselors over a period of one week and had at least 7 days of contact with the service over the entire data collection period. Chi-square-tests and Mann-Whitney-U tests were conducted to identify differences between frequent users and the population of all users. Results: In total, n = 99 (1.5 %) users met the definition for frequent chatters and accounted for roughly a tenth (9.85 %) of all chats of the service. The mean frequent chatter was 17 years old (M = 17.29, SD = 3.56), female (n = 78, 82.1 %), and approached the service in the late afternoon (M = 5:00 pm, SD = 5:25 h). Compared to the general user population, frequent chatters reported significantly more severe concerns to counselors, of which 81.8 % included psychiatric symptoms, such as suicidality (43.4 %) and non-suicidal self-injury (41.4 %). In addition, frequent chatters were significantly more likely to contact krisenchat alongside the use of other professional help services. Further, frequent chatters wrote significantly longer and more messages during the counseling process and within a session than the general user population of krisenchat. Compared to the general user population, frequent chatters did not differ in their satisfaction with the service. Conclusion: Frequent users are known from telephone helplines and are also represented in a chat-based context. Compared to the general user population, they are more likely to report serious mental health conditions and half of them currently receive professional help, suggesting a high need for social support. In light of the increasing development of chat-based helplines, there is a need for further research on frequent chatters to develop tailored counseling strategies for their needs and to analyze options for an optimized service provision. Study registration: DRKS00026671.

The Impact of a Messenger-Based Psychosocial Chat Counseling Service on Further Help-Seeking Among Children and Young Adults: Longitudinal Study.

BACKGROUND: Mental crises have high prevalences in adolescence. Early interventions appear to be highly important to diminish the risk of the deterioration, recurrence, or chronification of symptoms. In recent years, various providers have started offering live chat support in psychological crises. The messenger-based psychological counseling service krisenchat aims to support young people in crises and, if necessary, provide a recommendation for a referral to the health care system or to seek further help from a trusted adult person. OBJECTIVE: This study aimed to investigate the impact of using the counseling service of krisenchat on the further help-seeking behavior of young people, and to identify associated factors of further help-seeking. METHODS: This longitudinal study analyzed anonymous data from 247 individuals who used krisenchat between October 2021 and March 2022, and received a recommendation for further help-seeking. An online survey directly after the chat assessed the perceived helpfulness of the chat and well-being after the chat. After 4 weeks, further help-seeking, facilitators and barriers to help-seeking, and self-efficacy were assessed in an online follow-up survey. RESULTS: The most frequently recommended services or persons to seek further help from included a psychotherapist or social psychiatric service (75/225, 33.3%), a school psychologist or school social worker (52/225, 23.1%), and the user's parents (45/225, 20.0%). Of the 247 users, 120 (48.6%) indicated that they contacted the recommended service or person, and of these, 87 (72.5%) stated that they already had an appointment (or talk) with the respective service or person or that an appointment (or talk) was scheduled. The most frequently reported facilitators for further help-seeking were mental health literacy (54/120, 45.0%), improvement of self-efficacy (55/120, 45.8%), and symptom recognition (40/120, 33.3%). In users not displaying further help-seeking behavior, the most frequent barriers included stigmatization (60/127, 47.2%), lack of mental health literacy (59/127, 46.5%), need for self-reliance and autonomy (53/127, 41.7%), and negative family beliefs regarding help services (53/127, 41.7%). Subgroup comparisons indicated significantly higher levels of self-efficacy in users displaying further help-seeking behavior than in those not displaying further help-seeking behavior. Both subgroups did not differ in gender, age, recommended service or person, chat topics, perceived helpfulness, and well-being. CONCLUSIONS: The findings of this study indicate that children and young adults receiving counseling on krisenchat benefit in terms of seeking further help. Further help-seeking seems to be associated with higher levels of self-efficacy. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00026671; https://tinyurl.com/4fm5xe68.

Recurrent ventral curvature after corporoplasty with tunica vaginalis flap.

INTRODUCTION AND OBJECTIVE: Optimal means to correct ventral curvature (VC) is debated. Our preferred technique for curvature greater than 45° is corporoplasty using tunica vaginalis flap (TVF). We describe our complications with TVF for ventral lengthening. METHODS: Forty-four boys who underwent ventral lengthening with a corporoplasty with TVF were identified in a prospective database for proximal hypospadias repair by a single surgeon from 2008 to 2021. Corporotomy was performed by incising the tunica albuginea of the corpora cavernosa transversely at the point of maximum curvature. Harvested TVF was tailored to the size of the corporotomy and anastomosed to the edges of the tunica albuginea and on laid to the corporal defect with the mesothelial side of the TVF abutting the erectile tissue. RESULTS: Median age at surgery was 1.0 years (IQR 0.72-1.82). Median follow-up time was 4.9 years (IQR 2.6-8.0). Thirteen patients (27%) were older than 10 years of age at last follow up (median 13.3, range 10-20). Twenty-two boys (50%) received preoperative testosterone. The most common location of the meatus after degloving was penoscrotal (41%). Median VC after degloving was 90° (IQR 80-100). The urethral plate was transected in 43/44 (98%) of boys, improving median VC to 60° (IQR 40-60). After corporotomy, the median longitudinal distracted distance was 15 mm (IQR 12-17). Urethral reconstruction was most commonly achieved with the transverse island preputial flap technique or its modifications (39/44; 89%). Erections were reported in 42 boys (95%). None developed corporal diverticula, and two patients (4.5%) had ascended testis associated with TVF harvest. Seven percent of boys had recurrent ventral curvature (RVC; 3/44). Median RVC was 30° (IQR 30-45). One patient had RVC at the penoscrotal junction (not at site of prior corporoplasty) identified 11 years post operatively at age 15, and underwent dorsal plication. The other 2 patients were diagnosed less than 1 year post operatively. Both patients received testosterone due to small glans size, had double-face tubularized transverse island preputial flap as urethral and ventral skin coverage, and had endocrine and genetic consultation. Both had scarring of the preputial flap and of the corporoplasty. Scar excision and superficial transverse incisions on the tunica albuginea corrected RVC. CONCLUSIONS: The five-year outcome of ventral penile lengthening using TVF for corporoplasty is favorable with 7% of boys with RVC, and 4.5% with ascended testes associated with TVF harvest. None developed corporal diverticula.

Dietary supplement and complementary and alternative medicine use among older adults in Australia and the United States.

BACKGROUND: Dietary supplement and complementary and alternative medication (CAM) use can contribute to drug interactions, polypharmacy, nonadherence with prescription medications, and healthcare expenses, whereas evidence supporting benefits of using these products is sparse. There is a lack of current published literature describing the patterns or predictors of their use in community-dwelling older adults. MATERIALS AND METHODS: We performed a cross-sectional analysis of community-dwelling adults from Australia and the US, aged 70 years and older (65 years for US minorities), enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study. At study enrollment, eligible participants were required to be without concurrent 5-year life-limiting illness and free of documented evidence of cardiovascular disease, dementia, or significant physical disability. During the final study visit, a questionnaire was administered to collect information about supplement/CAM use. Data from 15,729 participants who completed this questionnaire between January 2017 and January 2018 were analyzed. Descriptive statistics were used to report the prevalence and types of products used. Factors associated with use were determined using multivariate regression. RESULTS: Mean age of respondents was 79.6 years; 56.4% were female, 88.8% were from Australia, 56.5% reported 12 years of education or less, and 98.7% were living at home. Two-thirds (66.2%) of participants reported use of one or more supplement/CAM in the previous month. Products most commonly used included vitamin D (33.8% of participants), fish oil (22.7%), calcium (20.6%), glucosamine (14.8%), and multivitamin (12.9%). Female sex, US residency, higher education, polypharmacy (prescription medications), and frailty (in women) were significantly associated with higher use of supplements/CAMs. CONCLUSIONS: Dietary supplement and CAM use is common among community-dwelling older adults in the United States and Australia. Given the high prevalence of use, collaboration between healthcare providers and older adult patients is important to insure safe and optimal use of these products.

An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism.

The mechanisms by which the early-life microbiota protects against environmental factors that promote childhood obesity remain largely unknown. Using a mouse model in which young mice are simultaneously exposed to antibiotics and a high-fat (HF) diet, we show that Lactobacillus species, predominant members of the small intestine (SI) microbiota, regulate intestinal epithelial cells (IECs) to limit diet-induced obesity during early life. A Lactobacillus-derived metabolite, phenyllactic acid (PLA), protects against metabolic dysfunction caused by early-life exposure to antibiotics and a HF diet by increasing the abundance of peroxisome proliferator-activated receptor γ (PPAR-γ) in SI IECs. Therefore, PLA is a microbiota-derived metabolite that activates protective pathways in the small intestinal epithelium to regulate intestinal lipid metabolism and prevent antibiotic-associated obesity during early life.

The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.

BACKGROUND: The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. METHODS: This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. RESULTS: This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). CONCLUSIONS: Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

Factors Impacting Retention of Aged Care Workers: A Systematic Review.

Retention of care support workers in residential aged care facilities and home-based, domiciliary aged care is a global challenge, with rapid turnover, low job satisfaction, and poorly defined career pathways. A mixed-methods systematic review of the workforce literature was conducted to understand the factors that attract and retain care staff across the aged care workforce. The search yielded 49 studies. Three studies tested education and training interventions with the aim of boosting workforce retention and the remaining 46 studies explored opinions and experiences of care workers in 20 quantitative, four mixed-methods and 22 qualitative studies. A range of factors impacted retention of aged care staff. Two broad themes emerged from the analysis: individual and organisational factors facilitating retention. Individual factors related to personal satisfaction with the role, positive relationships with other staff, families, and residents, and a cooperative workplace culture. Organisational factors included opportunities for on-the-job training and career development, appropriate wages, policies to prevent workplace injuries, and job stability. Understaffing was often cited as a factor associated with turnover, together with heavy workloads, stress, and low job satisfaction. With global concerns about the safety and quality of aged care services, this study presents the data associated with best practice for retaining aged care workers.

Consumer and Healthcare Professional Led Priority Setting for Quality Use of Medicines in People with Dementia: Gathering Unanswered Research Questions.

BACKGROUND: Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. OBJECTIVE: To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. METHODS: The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family, and friends) and healthcare professionals. Survey findings were supplemented with key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were 'unanswered'. RESULTS: A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. CONCLUSION: A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Modifications in basal and stress-induced hypothalamic AMP-activated protein kinase (AMPK) activity in rats chronically treated with an angiotensin II receptor blocker.

5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats.