Clinician Perspectives of Gene Therapy as a Treatment Option for Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies. Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied. Methods: We conducted interviews with specialist clinicians treating patients with DMD in the United States (n = 8) and United Kingdom (n = 8). Interviews were completed in 2022, before any approved gene therapies, to gain insight into barriers and facilitators to implementing gene therapy and educational needs of clinicians. Results: Most respondents expressed cautious optimism about gene therapy. Responses varied regarding potential benefits with most expecting delayed progression and duration of benefit (1 year to lifelong). Concern about anticipated risks also varied; types of anticipated risks included immunological reactions, liver toxicity, and cardiac or renal dysfunction. Clinicians generally, but not uniformly, understood that gene therapy for DMD would not be curative. Most reported needing demonstrable clinical benefit to justify treatment-related risks. Conclusions: Our data demonstrate variability in knowledge and attitudes about gene therapy among clinicians who follow patients with DMD. As our knowledge base about DMD gene therapy grows, clinician education is vital to ensuring that accurate information is communicated to patients and families.

Functional Transitions among Older Adults in Rural China: Examining the Differential Roles of Care from Daughters' and Sons' Families.

OBJECTIVES: Informal care provided by adult children is of great importance for older adults' well-being in China. This paper investigates and compares the functional transitions among older adults living in rural areas who receive care from daughters' and from sons' families. METHOD: This study utilizes the 'Well-being of Elderly Survey in Anhui Province' (WESAP), from 2001 to 2021. Our sample included 2,797 individuals aged 60 years or over. Functional status was based on the activities of daily living (ADLs) and the instrumental activities of daily living (IADLs). We employed a random-effects ordered logit model to examine the functional transitions among the older adults. RESULTS: Receiving care from daughters' families is significantly associated with a lower likelihood of functional decline compared to receiving care from sons' families in rural China. The advantage associated with daughter care becomes more pronounced among older individuals with a severe functional difficulty compared to those with a mild or moderate functional difficulty. The difference is prevalent among older adults aged 75 and above, with less wealth or multiple chronic diseases, or who live alone. Furthermore, among those with severe functional difficulties, the daughter advantage is more significant for fathers as compared to mothers. DISCUSSION: Nowadays, daughters' families can provide high-quality informal care, often surpassing that offered by sons' families. This daughter advantage becomes even more significant among older adults who have a higher need for family care, such as those with severe disabilities and limited financial resources.

What Determines the Adoption of Conservation Agriculture? Evidence from Quebec.

Conservation agriculture (CA) is promoted by various organisations and scholars as alternative to conventional agriculture to meet growing food demand with minimal damage on environment; but its factors of adoption have not been well identified. The study uses the recent composite index of adoption of CA developed by Takam Fongang et al. (2023) to analyse the factors of adoption of conservation agriculture among maize and soybean farmers in Quebec. Using data from 93 maize and soybean producers and a Fractional logit model, the study shows that adoption of CA increases with farmer's favourable perceptions of yield and easiness of implementing CA, off-farm employment and higher education. The study therefore indicates that higher education, technical assistance and popularisation of performance of CA can play a significant role in boosting adoption of CA in Quebec.

Factors Associated with Patient-Caregiver Concordance about Life-Sustaining Treatment Preferences among Advanced Cancer Patients: A Cross-Sectional Study.

OBJECTIVES: Concordance of preferences for end-of-life care regarding patients between patients with advanced cancer and family caregivers can improve the likelihood of honoring dying patients' wishes. However, there is a dearth of knowledge in mainland China. The purpose of this study was to examine patient-family caregiver concordance about patients' life-sustaining treatment preferences and associated factors among patients with advanced cancer in China. METHODS: From September 2019 to December 2021, a convenience sample of 406 dyads of advanced cancer patient-family caregiver were recruited from 2 tertiary hospitals in Wuhan, China. Participants completed a questionnaire about patient's preferences for life-sustaining treatment, respectively. The concordance was assessed by percent agreement and kappa coefficients. Associated factors were identified by univariate analysis and binary logistic regression. RESULTS: The average concordance rate on the preferences for life-sustaining treatment was 56.1%, ranging from 52.9% to 59.3%. Factors associated with a higher level of patient-family caregiver concordance were following: patients who were married, whose educational levels were at college or above, who had not been informed of diagnosis by a physician, who had been informed of the effects and side effects of related drugs by a physician, and who cared for a seriously ill family member or friend and caregivers whose educational level were primary or below. CONCLUSIONS: The patient-family caregiver concordance about patients' life-sustaining treatment preferences among patients with advanced cancer was poor. Patients' and caregivers' understanding of life-sustaining treatment and its efficacy in end-of-life should be facilitated. Relevant conversation should be encouraged between patients and caregivers, thus providing value-concordant end-of-life care for patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Health professionals need to carry out advanced care planning in oncology departments on mainland China to encourage patients and caregivers to discuss patients' end-of-life care preferences. Facilitating patients' and caregivers' understanding of life-sustaining treatment preferences may help improve the patient-caregiver concordance on life-sustaining treatment preferences among patients with advanced cancer.

Gender and circadian preferences influence emotions and motivation in secondary mathematics classrooms.

Many studies have reported poor school achievement in evening persons and general circadian fluctuations in cognition. The aim of this study was to analyze circadian fluctuations in a cross-sectional design and examine the effects of chronotype on situational emotions and intrinsic motivation. A cross-sectional survey study was conducted in three Turkish secondary schools with a total sample of 599 students (283 females and 316 males). Data were collected at the end of specific math lessons of the same grade level and content, using a form combining three scales. We found no gender-related differences in intrinsic motivation, while there were some differences in situational motivation. In math classes, female students exhibited higher level of interest, while boys scored higher on boredom. In addition, students who scored high on morning affect reported higher levels of interest, well-being, and less boredom. Students with higher stability (and lower fluctuations in mood and cognition during the day) reported a higher degree of enjoyment, perceived competence, perceived choice, and less pressure/tension in their math lessons. A positive association was observed between distinctness, interest, and well-being, while negative correlations existed between distinctness and boredom. This suggests that students with higher diurnal stability reported a higher level of interest, well-being, and a lower level of boredom. Additionally, the results of the analyses showed that morningness, distinctness, and eveningness were significant predictors of intrinsic motivation. Conversely, gender, time of application, morningness, and distinctness emerged as predictors for situational emotions in mathematics classes.

Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.

RATIONALE: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored. OBJECTIVES: This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse. METHODS: In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl. RESULTS: The estimated median lethal dose (LD50) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED50) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005-0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005-0.02 mg/kg), carfentanyl (0.0005-0.002 mg/kg), and isobutyryl-carfentanyl (0.001-0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl. CONCLUSIONS: In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency.

Chinese consumers' valuation for prepared plant-based meat products: Does environmental information matter?

Despite the growing interest in innovative nonanimal protein-prepared foods, knowledge about consumer demand for these newly prepared foods and their potential scope in the market could be improved. This study reports the results of a discrete choice experiment on consumers' (n = 1245) willingness to pay (WTP) for prepared plant-based meat (PPBM) in the context of Chinese food culture. Consumers were randomly assigned to a treated group with additional environmental information about PPBM. The estimation results of the random parameter logit model showed that when environmental information was provided, consumer preferences and WTP for frozen meatballs with mixed meat (beef-based and soy protein-based meat) and PBM (pure soy protein-based meat) significantly increased. However, their preference and WTP for food quality and safety attributes of meatballs decreased. Simultaneously, the availability of information reveals the heterogeneity of preferences. This study found that positive WTP for PPBM was limited to consumers with a low degree of food technology neophobia (FTN) and that consumers with a high degree of FTN may avoid purchasing meatballs made from PBM. In contrast, consumers with a higher time preference (i.e., impatient consumers) were likelier to pay for PPBM meatballs. PRACTICAL APPLICATION: PPBM is especially valuable in developing innovative nonanimal protein-prepared foods, and China has the potential to become the largest PPBM food market. Understanding consumers' preference for PPBM products and the impact of information provision on their WTP will assist food companies in devising suitable strategies for the development of new PPBM products. The findings of this study provide targeted market insights for the food industry to help guide the development of plant-based meat products more effectively.

An intuitionistic fuzzy graph's variation coefficient measure with application to selecting a reliable alliance partner.

Group decision-making (GDM) is crucial in various components of graph theory, management science, and operations research. In particular, in an intuitionistic fuzzy group decision-making problem, the experts communicate their preferences using intuitionistic fuzzy preference relations (IFPRs). This approach is a way that decision-makers rank or select the most desirable alternatives by gathering criteria-based information to estimate the best alternatives using a wider range of knowledge and experience. This article proposes a new statistical measure in a fuzzy environment when the data is ambiguous or unreliable to solve a decision-making problem. This study uses the variation coefficient measure combined with intuitionistic fuzzy graphs (IFG) and Laplacian energy (LE) to solve a GDM problem that utilizes intuitionistic fuzzy preference relations (IFPRs) to select a reliable alliance partner. Initially, the Laplacian energy determines the weight of individual standards, and the obtained weight average further estimates the overall criterion weight vector. We establish the authority criteria weights using the variation coefficient measure and then ultimately rank the alternatives for each criterion using the same measure. We examine four distinct companies Alpha, Beta, Delta, and Zeta to conduct a realistic GDM to choose which alliance partner would be ideal. We successfully implemented the suggested technique, determining that Alpha satisfies company standards and is ranked first among other companies. Moreover, this technique is useful for all kinds of Intuitionistic fuzzy group decision-making problems to select optimal ones.

Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study.

Background: Patient-reported outcomes (PROs) reflect patient perceptions of disease and treatment and are important for evaluating new therapies. Objectives: Evaluate the effects of once-daily concizumab prophylaxis on health-related quality of life (HRQoL), treatment burden, and treatment preference in males aged ≥12 years with hemophilia A/B with inhibitors. Methods: Patients enrolled in the multicenter, open-label explorer7 phase 3 study (ClinicalTrials.gov identifier: NCT04083781) were randomized to receive no prophylaxis (arm 1) or concizumab prophylaxis (arm 2) or were nonrandomly allocated to concizumab prophylaxis (arms 3 and 4). The study included questionnaires to assess patients' perception of HRQoL (Haemophilia Quality of Life Questionnaire for Adults), treatment burden (Hemophilia Treatment Experience Measure), and treatment preference (Haemophilia Patient Preference Questionnaire). Results: The estimated treatment difference between patients receiving concizumab prophylaxis vs no prophylaxis at week 24 for Haemophilia Quality of Life Questionnaire for Adults "total score" was -22.6 points (95% CI, -42.5; -2.7), directionally favoring patients receiving concizumab prophylaxis. For Hemophilia Treatment Experience Measure "total score," the estimated treatment difference was -19.9 points (95% CI, -34.3, -5.6) in favor of concizumab vs no prophylaxis. The majority of patients receiving concizumab expressed a preference for concizumab over their previous treatment, the main reasons being "fewer bleeds," "require less time," and "less painful to inject." Across all PROs, there were less responses collected than anticipated, limiting interpretations. Conclusion: PROs collected during the explorer7 study showed improvements in some domains of HRQoL, treatment burden, and patient treatment preference in persons with hemophilia A or B with inhibitors receiving concizumab prophylaxis compared with no prophylaxis.

Physician and Patient Preferences for Treatment of Anemia Associated with Chronic Kidney Disease in Japan: A Survey Including Best-Worst Scaling.

Background: Several treatment options are available for anemia associated with chronic kidney disease (CKD); however, there remains a lack of awareness of physician and patient preferences regarding these treatments. We aimed to explore physicians' and patients' perceptions and preferences regarding the management of anemia of CKD in Japan. Methods: A web-based survey, including best-worst scaling (BWS), was conducted with physicians who had treated ≥1 patient with anemia of CKD in the preceding year, and with patients with CKD who self-reported a clinical diagnosis of anemia of CKD or low hemoglobin levels. A three-step approach was used comprising cognitive interviews, a pilot survey, and a main survey. The BWS survey results were analyzed using multinomial logit and hierarchical Bayesian models. Results: The survey was completed by 906 participants: 103 patients (average age 60.6 years; 77.7% male) and 803 physicians (166 nephrologists, 214 cardiologists, 137 diabetologists, and 286 general internists). Almost all (96.0%) physicians surveyed considered anemia of CKD to be an important condition to treat. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors had the highest treatment satisfaction among physicians, whereas patients had the highest satisfaction with both erythropoietin-stimulating agent therapy and HIF-PH inhibitors. Approximately one-third (35.9%) of patients surveyed indicated that they were receiving treatment. When comparing the relative importance of attributes and levels, physicians favored efficacy (particularly improvement in hemoglobin levels), whereas patients favored safety (particularly a lower rate of severe adverse events). Conclusion: Although a majority of physicians consider treatment of CKD-related anemia important, differences in the perceptions and usage of medications exist between medical specialties. Preferences for the management of anemia of CKD vary between physicians and patients; therefore, patient involvement in treatment decisions may help optimize outcomes.

Abundances of ectomycorrhizal exploration types show the type-dependent temporal dynamics over the seasons-a controlled growth container experiment.

Ectomycorrhizas are ubiquitous symbiotic associations between host trees and soil fungi. While the seasonal changes of the taxonomic community structure of ectomycorrhizal fungi have been studied extensively, the temporal dynamics of ectomycorrhizal exploration types which have been proposed for elucidating the functional roles of ectomycorrhizas have not been fully examined. The purpose of the study is to test the hypothesis of whether the abundance of the exploration types in the hosts with different phenology shows different temporal patterns over the seasons. Two host species, deciduous Quercus acutissima and evergreen Q. glauca, were planted in growth containers with natural forest soils and were grown in single or combined species treatment, under similar environmental conditions and in shared soil spore banks of the ectomycorrhizal fungi. The ectomycorrhizal exploration types that occurred on these two host species in two different treatments were observed for two growing seasons. The observed exploration types, namely contact, short-distance, and long-distance type as well as the overall abundance of the ectomycorrhizas showed distinct temporal patterns although no specific response to the host seasonal phenology was found. The abundances of the contact type showed no relation to the seasons whereas those of the short- and the long-distance type increased with time. The formation of the long-distance type was strongly influenced by the host species treatments while that of the other two types was not so. Therefore, the different exploration types demonstrate distinct temporal patterns depending on the types but no specific seasonal responses.

Weighing the Options: Which PrEP (Pre-exposure Prophylaxis) Modality Attributes Influence Choice for Young Gay and Bisexual Men in the United States?

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.

Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID.

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

Online medical consultation in China: Demand-side analysis of obese patients' preferences and willingness-to-pay for online obesity consultations.

Objective: With obesity a major health concern and call on healthcare resources in China, we explored the preferences and willingness to pay (WTP) for obesity OMC, including the influencing factors behind WTP and preferences. Method: We recruited 400 obese participants to undertake a discrete choice experiment (DCE) and the contingent value method (CVM) survey. We used CVM to measure obese participants' WTP for one-click services (OCS) and used DCE to estimate obesity participants' preferences and WTP for OMC with different attributes. Results: Obese participants were willing to pay more than RMB80 on average for OCS, and more than 50% of participants had a WTP over RMB50 and 5% had a WTP over RMB300, reflecting the strong willingness of Chinese obese patients to pay for OMC. Educational background, income, ethnicity, previous OMC experience and accessibility to offline hospitals with different levels impacted WTP. The relative importance score of attributes in descending order was cost, doctors' hospital level, doctors' level, online waiting time, consultation time and consultation form. Obese patients preferred lower cost, doctors from higher-level hospitals, doctors with higher expertise levels, shorter waiting time and consultation duration, and telephone consultation were preferred. 30-min waiting time, 15-min consultation duration and telephone consultation were the most economically efficient set we found. Conclusion: To maximize health resources, provincial tertiary and municipal hospitals face different paths to developing obesity OMC platforms. We encouraged young doctors to use OMC. OMC regulators should implement consumer protection policies to optimize OMC pricing and address potential 'unfair' pricing.

Patella is rarely resurfaced during primary total knee arthroplasty in clinical trials conducted in Greece: a systematic review.

PURPOSE: The aim of the present study was to report the approach of Greek surgeons regarding patellar management and provide the outcomes and the rate of the need for secondary patella resurfacing. METHODS: Following the PRISMA guidelines, PubMed, Scopus, and The Cochrane Central Register of Controlled Trials (CENTRAL) databases were accessed in January 2024. Clinical studies evaluating the outcomes of patients undergoing primary TKA were considered eligible for this systematic review if the following predefined criteria were fulfilled: (1) published in English, (2) were conducted in Greece, and had a minimum of 2-year follow-up. The methodological quality and publication bias were assessed using the Modified Coleman Methodology Score (mCMS) and ROBIS tool, respectively. Data was presented in tables using absolute values from individual studies. Pooled data were presented as means, ranges, and percentages. RESULTS: Six clinical studies with a total of 1084 TKAs were included. Four studies were retrospectives, and two studies were prospective. Patella was only resurfaced in 0.6% of total TKAs. TKA without patellar resurfaced, which resulted in an improvement in functional outcome. Among studies, the overall need for revision incidence was 7.6% (68 out of 892 TKAs). Additionally, Aseptic loosening (2.4%) was the most common reason for revision due to patellofemoral joint complications, followed by secondary patellar resurfacing (2.1%) and deep infection (1.3%). The mean mCMS demonstrated a fair methodological quality level, and the ROBIS toll a low risk of bias in all four domains. CONCLUSION: The available evidence supports that Greek surgeons mainly do not resurface the patella. However, patellar non-resurfacing yields good functional outcomes and presents relatively low revision rates for secondary patellar resurfacing. LEVEL OF EVIDENCE: IV.

Corticotropin-releasing factor and GABA in the ventral tegmental area modulate partner preference formation in male and female prairie voles (Microtus ochrogaster).

Introduction: The mesolimbic reward system is associated with the promotion and rewarding benefits of social relationships. In the socially monogamous prairie vole (Microtus ochrogaster), the establishment of a pair bond can be displayed by a robust preference for a breeding partner and aggressive rejection of unfamiliar conspecifics. Mesolimbic dopamine signaling influences bond-related behaviors within the vole through dopamine transmission and receptor activity in the nucleus accumbens. However, only one experiment has examined how the ventral tegmental area (VTA), a region that produces much of the fore- and mid-brain dopamine, regulates these social behaviors. Specifically, inhibition of either glutamate or GABA neurons in the VTA during a brief courtship promoted a partner preference formation in male prairie voles. The VTA is a heterogeneous structure that contains dopamine, GABA, and glutamate neurons as well as receives a variety of projections including corticotropin-releasing factor (CRF) suggested to modulate dopamine release. Methods: We used pharmacological manipulation to examine how GABA and CRF signaling in the VTA modulate partner preference formation in male and female prairie voles. Specifically, we used a 3 h partner preference test, a social choice test, to assess the formation of a partner preference following an infused bicuculline and CRF during a 1 h cohabitation and muscimol and CP154526, a CRFR1 antagonist, during a 24 h cohabitation with an opposite-sex conspecific. Results: Our study demonstrated that bicuculline, a GABA A receptor antagonist, and CRF in the VTA promoted a partner preference, whereas low-dose muscimol, a GABA A receptor agonist, and CP154526, a CRFR1 antagonist, inhibited a partner preference in both male and female prairie voles. Conclusion: This study demonstrated that GABA and CRF inputs into the VTA is necessary for the formation of a partner preference in male and female prairie voles.

Preference for solitude paradox: The psychological influence of social isolation despite preference.

BACKGROUND: Although a preference for solitude (PS) may mitigate the negative effects of social isolation (SI) owing to the enjoyment of time alone, its impact on mental health and its underlying factors remain unclear. METHODS: An Internet survey was conducted with 9000 individuals aged 20-79 years in September 2023 and the analyses were performed across three generations. SI was defined as contact with non-cohabitating family members or relatives and friends/neighbors less than once a week. The PS scale, which was used to assess whether a person preferred spending time alone, stratified respondents into three PS-level groups. Mental health status was evaluated using the K6 (distress symptoms), the WHO-5 (well-being), and the UCLA Loneliness Score (severity of loneliness) as the main outcomes. The mediation analyses assessed whether troublesomeness in socializing, a potential negative aspect of PS, could explain the association between PS and mental health status. RESULTS: A mixed-design two-way analysis of covariance showed that both SI and PS had significant main effects on all outcomes without interactions across generations, indicating that SI and higher PS were associated with poor mental health status. The association between higher PS and poor mental status was mediated by socializing troublesomeness across generations. LIMITATIONS: The cross-sectional design prevented making causal inferences from the results. Additionally, sampling bias from Internet surveys may limit the generalizability of the results. CONCLUSIONS: The results confirmed that there is no protective effect of PS on social isolation-related poor mental health. The hassle of socializing may partly explain why people with a higher PS experience poor mental status, including greater loneliness.

Patient Preferences for Ulcerative Colitis Treatment in the Middle East Region: A Discrete-Choice Experiment.

Background and Aims: Treatments for ulcerative colitis (UC) differ in safety, efficacy, and route of administration; patient preferences for treatment attributes should be considered in treatment decisions. No study to date has explored patient preferences for moderate-to-severe UC treatment in Middle Eastern countries. Methods: A discrete-choice experiment aimed to quantify treatment preferences in patients with moderate-to-severe UC in 5 Middle Eastern countries (Saudi Arabia, Kuwait, Jordan, the United Arab Emirates, and Lebanon). Respondents chose between experimentally designed profiles for hypothetical UC treatments with varying efficacy (time until UC symptoms improve and chance of UC symptom control after 1 year), side effects (annual risk of serious infection, 5-year risk of malignancy), mode and frequency of administration, and need for occasional steroid use. A random-parameters logit model was used to estimate preference weights for these attributes, from which conditional relative importance estimates and maximum acceptable increases in risks of serious infection and malignancy were derived. Results: Among 365 adults with moderate-to-severe UC who completed the survey (mean age, 36 years; 50% female), 5-year risk of malignancy and symptom control after 1 year had the greatest conditional relative importance. Respondents were generally willing to accept statistically significant increases in annual risk of serious infection and 5-year risk of malignancy in exchange for better efficacy, changes in mode of administration and dosing schedule, and avoiding occasional steroid use. Conclusion: Of the attributes evaluated, individuals with UC in Middle Eastern countries most value avoiding 5-year risk of malignancy and a higher probability of symptom control, on average.

Treatment Preferences of Adult Patients with Attention-Deficit/Hyperactivity Disorder - A Discrete Choice Experiment.

Background: Understanding patient preferences for treatments may facilitate shared decision-making. This study assessed adult patient preferences for attention-deficit/hyperactivity disorder (ADHD) treatments in a sample of 600 patients in the United States (US). Methods: A web-based discrete choice experiment (DCE) survey was conducted among treated adults with ADHD. Participants were recruited from Dynata's US panel (06/22/2023-07/06/2023). Attributes and levels, identified based on clinical inputs and published data, included efficacy and safety. Participants' preferences were estimated using conditional logistic regression. Willingness to trade-off and attributes' relative importance were calculated. Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities. Results were stratified by current treatment status. Sensitivity analyses including participants who passed validity tests were conducted. Results: Among the 600 participants (mean age 37.9 years; 66.2% female; 50.8% treated), all attributes had a statistically significant impact on preferences for ADHD treatments (p < 0.001); the most important attribute was improvement in ADHD symptoms (36%), followed by risks of nausea (25%), insomnia (20%), anxiety (8%), dry mouth (6%), and feeling jittery (5%). Together, safety attributes accounted for >60% of relative importance in decision-making. Participants were willing to forgo 0.59, 0.57, 0.49, 0.32, and 0.17 percentage points of symptom improvement to achieve one-percentage-point reduced risk of insomnia, nausea, anxiety, feeling jittery, and dry mouth, respectively. Centanafadine profile had consistently higher adjusted total utilities than its comparators. Similar results were obtained in the subgroup and sensitivity analyses. Conclusion: Efficacy was the most important attribute for patients when making treatment decision, but taken together, AEs had greater relative importance than efficacy alone. Accordingly, a profile resembling that of centanafadine would be preferred by an average patient compared to key competitors due to its favorable safety profile. These findings may help improve treatment decision-making, enhance treatment satisfaction, and foster adherence.