Social Capital and Formal Volunteering Among Family and Unpaid Caregivers of Older Adults.

Using data from 1745 caregivers in the National Study of Caregiving (2017), this study explores the connection between caregiving and formal volunteering by identifying the relationship between social capital and formal volunteering among family and other unpaid caregivers of older adults. In addition, this study examines the representative prevalence of formal volunteering in caregivers. We conducted logistic regression models along with established volunteerism correlates from the prior research literature. Approximately a quarter of caregivers participated in volunteering (25.4%). Being male, having higher educational attainment, being a spouse, living separately from the care recipient, caregiving for multiple care recipients, having a better quality of relationship with the care recipient, having better psychological well-being, receiving more social support, attending religious services, and participating in group activity were positively associated with formal volunteer participation. Findings underscore the role of both human and social capital, including the caregiving context, in formal volunteering among caregivers.

Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.

Background: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. Objectives: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. Design: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. Setting: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). Participants: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. Interventions: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. Main outcome measures: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. Results: Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported. Limitations: The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted. Conclusions: Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate. Future work: Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence. Trial registration: This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.

Many people who are trying to stop drinking alcohol can find it difficult to remain alcohol free. There is a medication called acamprosate (Campral) that can reduce cravings thereby increasing the likelihood of abstinence. However, some people have trouble taking the right amount of acamprosate tablets needed every day at the right time, preferably at mealtimes. This means the medication is not as effective. We have tested some new ways to help support people taking acamprosate. We tested three different strategies to find the best way to support people taking acamprosate. We recruited 739 people aged 18 and over who were receiving alcohol treatment to stop drinking and were taking acamprosate. We randomly allocated these people to three groups. The first was Standard Support, the usual support people receive when taking acamprosate. The second group received Standard Support plus Medication Management. This consisted of 12 telephone calls over 6 months with a trained pharmacist to discuss the importance of taking the right amount of the medication, how the medication works and strategies to help people take the medication correctly. The third group received Standard Support, Medication Management and Contingency Management. This involved giving people shopping vouchers for participating with Medication Management calls. The maximum value of vouchers per person was £120. People who were in the group receiving Medication Management and Contingency Management took a greater number of acamprosate tablets. We also found that Medication Management plus Contingency Management was more cost-effective; there were greater gains in health with a smaller cost per person compared to Standard Support alone. This shows that there is likely to be a benefit to patients of Medication Management plus Contingency Management for supporting people taking acamprosate.

Vigabatrin (Sabril) for the Treatment of Refractory Complex Focal Seizures in Adults: Pharmacologic and Clinical Considerations.

To review the pharmacokinetics, efficacy, and adverse effects of vigabatrin (Sabril) and its role in managing refractory focal unaware seizures in adults. In the present investigation, a search of English-language literature from 1999 through 2023 was conducted using vigabatrin and Sabril as search terms to identify relevant studies and review articles. A 2000 double-blind, placebo-controlled multicenter study found that out of 90 adult patients, 48% of those treated with vigabatrin achieved a 50% or greater reduction in the frequency of complex partial seizures, compared to 26% of placebo-treated patients. This study also observed that vigabatrin was well tolerated by 72.4% of patients, with the most common side effects being drowsiness, dizziness, headache, and fatigue. Further studies with a significant risk of vigabatrin-associated visual field loss necessitate vigabatrin only being an option for refractory cases. Additional studies suggest that despite the potential risk of vision loss and adverse effects, adult patients continue to use vigabatrin long-term. Sabril is an antiepileptic medication prescribed as an additional treatment for refractory complex partial seizures in patients at least ten years old who have not responded well to other alternative therapies. Multiple clinical trials indicate that Sabril sufficiently reduces the frequency of seizures when used as an adjunct treatment of refractory complex focal seizures. However, it is important to carefully monitor patients for any adverse effects, particularly long-term use, and to discontinue the drug if serious side effects occur.

Outcomes of Gender-Affirming Voice and Communication Modification Training for Non-binary Individuals: A Case Series.

OBJECTIVES: There is currently no research reporting solely on outcomes of voice and communication modification training (VCMT) in individuals who identify as non-binary and genderqueer (NBGQ) in the English literature. This study aimed to describe the objective and subjective impact of VCMT on the voice of NBGQ individuals undergoing a 12-week gender-affirming VCMT program. METHODS: A retrospective consecutive case series of NBGQ individuals enrolled in a VCMT program was performed. Demographics, Transgender Self-Evaluation Questionnaire (TSEQ), fundamental frequency (F0), and frequency range were collected before and after the program. RESULTS: Four NBGQ individuals enrolled between January 2019 and June 2021; the mean age was 27.0 years. While all four participants represented in this case series showed improvement in at least one of their initial goals, only one improved both their F0 and TSEQ scores; the other three participants had mixed results. CONCLUSION: NBGQ individuals experienced improvements in self-reported outcomes and changes in acoustic measures after completing VCMT in our case series. Individuals experienced significant improvement in subjective outcomes despite small changes in acoustic measures, and vice versa. More research is needed to better understand the voice and communication needs of NBGQ individuals, along with their outcomes with VCMT. LEVEL OF EVIDENCE: Level 4.

Factors associated with discharge against medical advice in alcohol withdrawal patients.

This study aimed to examine characteristics associated with discharge against medical advice from the hospital in alcohol withdrawal patients, supporting the work of hospital staff and Alcohol Care Teams and identifying characteristics that may help target patients most likely to discharge against medical advice. We used Hospital Episode Statistics Data to identify demographic and clinical variables and compare these in alcohol withdrawal patients who discharged against medical advice from hospital, compared with those who were discharged by the clinical team. Factors significantly associated with alcohol withdrawal patients discharging against medical advice from hospital were: being admitted as an emergency; discharged on a weekend; living with no fixed abode; being male; being younger and having a shorter length of stay. This study identifies characteristics that can be used to support acute hospitals and Alcohol Care Teams, particularly in the allocation of resources to reduce discharges against medical advice and subsequent readmissions to the hospital. Particular consideration should be given to clinical provision in hospitals in emergency departments and on weekends, and also those patients who are admitted and are of no fixed abode.

Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

AIMS: To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. METHODS: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. RESULTS: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. CONCLUSION: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way.

"It helps me find balance": older adult perspectives on the intersection of caregiving and volunteering.

Caregiving is an increasingly prevalent experience that can negatively impact health and well-being. Volunteerism, long associated with positive benefits for older adults, is one potential strategy that can be used to counteract caregiver stress. A national cohort of existing older adult volunteers was engaged to explore the intersection of volunteering and caregiving through qualitative analysis of respondent comments using the lens of role theory. Survey responses from 533 older volunteers were analyzed. Role conflict and role enhancement themes were examined, with time constraints and reduced energy emerging as the perceived causes of conflict between the caregiver and volunteer roles. Caregivers discussed benefits to their caregiving role, including respite, learning, access to information and resources relevant to caregiving, increased socialization and improved physical and cognitive health. Findings indicate that volunteering can be framed as a health and well-being intervention for caregivers.

Outcomes of Gender-Affirming Voice and Communication Modification for Transgender Individuals.

OBJECTIVES: Transgender individuals' voices are closely related to gender identity. A primary goal of gender-affirming voice modification is to help individuals alter their voices to improve gender congruence; however, there is a paucity of research to support this approach. This study aimed to evaluate the outcomes of a 12-week gender-affirming voice and communication modification program. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective consecutive case series of transgender women enrolled in a voice and communication modification program was performed. Demographics, Trans Woman Voice Questionnaire (TWVQ), fundamental frequency (F0 ), and frequency range were collected before and after the program. A Wilcoxon signed-rank test assessed changes in outcomes. Spearman's rank-order correlation coefficients quantified associations between self-reported outcomes and acoustic measures. RESULTS: A total of 16 trans women individuals were enrolled. The mean age was 31.5 years. After program completion, TWVQ improved 20.4 points, F0 increased 26.5 Hz (spontaneous speech) and 25.7 Hz (reading), and the range increased 24.7 Hz (spontaneous speech) and 0.1 Hz (reading). None of the changes in acoustic measures significantly correlated with improvement in TWVQ scores in the cohort. CONCLUSION: Trans women experience improvements in self-reported outcomes and changes in acoustic measures after completing a gender-affirming voice and communication modification program. Individuals may experience significant improvement in subjective outcomes despite small changes in acoustic measures and vice versa. LEVEL OF EVIDENCE: 4 (case series) Laryngoscope, 132:1615-1621, 2022.

Protein degradation profile reveals dynamic nature of 20S proteasome small molecule stimulation.

Small molecules have been discovered to stimulate the 20S core particle (CP) of the proteasome to degrade proteins. However, the impact a 20S CP stimulator can have on the regulation of protein levels has not been fully characterized. Previous studies have focused on using one kind of stimulator to enhance the degradation of specific 20S CP substrates. We present here a study that utilizes several 20S CP stimulators to determine how each can affect the degradation of proteins in a biochemical assay with purified proteins and of an overexpressed GFP-fusion protein in cells. We also evaluate the effects of two stimulators on the whole cellular proteome in HEK-293T cells using label-free quantitative proteomic analysis for a broader understanding on their impact. Our studies demonstrate that 20S CP stimulation is likely to promote the degradation of significantly disordered proteins; however, the specific effect on the regulation of protein levels appears to be dependent on the mechanism of action of each stimulator due to the dynamic nature of the 20S CP. Our results reveal the potential of tailoring small molecule stimulators to influence the degradation of certain protein types and 20S CP substrates.

20-year-old man • sudden-onset chest pain • worsening pain with cough and exertion • Dx?

► Sudden-onset chest pain ► Worsening pain with cough and exertion ► No improvement with naproxen.

Double-blind, placebo-controlled trial of mifepristone on cognition and depression in alcohol dependence.

BACKGROUND: Alcohol dependence is a significant issue contributing to disease burden. Changes in cortisol concentrations during alcohol withdrawal are associated with cognitive deficits and symptoms of depression. Current treatments are only successful for a small proportion of people and do not target cognitive deficits and symptoms of depression experienced by those who are alcohol dependent. The aim of this research is to determine the potential efficacy of mifepristone, a type II glucocorticoid receptor antagonist, to prevent symptoms of depression and cognitive deficits following alcohol detoxification. METHODS: This was a phase 2 therapeutic use trial. It was a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo treatment. The trial aimed to recruit 120 participants who met the inclusion criteria: (1) male, (2) aged 18-60 years inclusive, and (3) alcohol dependent for 5 or more years. Participants were randomised to 600 mg a day mifepristone (200 mg morning, afternoon, and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Primary outcome measures were cognitive function (measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB)) and symptoms of depression (measured using the Beck Depression Inventory (BDI)) at 4 weeks post-randomisation. RESULTS: Difficulties recruiting participants due to significant changes in the provision of inpatient care for alcohol dependence resulted in only 27 participants recruited to the trial, with data available for 21 participants. Fourteen participants were randomised to receive mifepristone and 13 to receive placebo. CONCLUSION: Larger trials would be needed to draw conclusions about the efficacy of mifepristone. TRIAL REGISTRATION: ISRCTN registry ISRCTN54001953 . Registered on 29 September 2011.

Fluorescent Probes with Unnatural Amino Acids to Monitor Proteasome Activity in Real-Time.

The proteasome is an essential protein complex that, when dysregulated, can result in various diseases in eukaryotic cells. As such, understanding the enzymatic activity of the proteasome and what can alter it is crucial to elucidating its roles in these diseases. This can be done effectively by using activity-based fluorescent substrate probes, of which there are many commercially available that target the individual protease-like subunits in the 20S CP of the proteasome. Unfortunately, these probes have not displayed appropriate characteristics for their use in live cell-based assays. In the work presented here, we have developed a set of probes which have shown improved fluorescence properties and selectivity toward the proteasome compared to other cellular proteases. By including unnatural amino acids, we have found probes which can be utilized in various applications, including monitoring the effects of small molecule stimulators of the proteasome in live cells and comparing the relative proteasome activity across different cancer cell types. In future studies, we expect the fluorescent probes presented here will serve as tools to support the discovery and characterization of small molecule modulators of proteasome activity.

Phonotraumatic Injury in Fitness Instructors: Risk Factors, Diagnoses, and Treatment Methods.

Fitness instructors are at risk for phonotraumatic injury caused by a combination of occupation-driven environmental and physiologic factors. OBJECTIVES: This study analyzes phonotraumatic injury in a cohort of fitness instructors to define the spectrum of disease, inform treatment, and make educational recommendations. STUDY DESIGN: Retrospective chart review. METHODS: Fitness instructors seen over a 2-year period comprised the study population. Stroboscopic findings, recommended treatment modalities, and treatment outcomes, including postoperative recurrence (when applicable) were analyzed. Demographic information (gender, age), past medical history, VHI-10 scores, and concurrent relevant vocal demands (performer vs. non-performer) were reviewed. Descriptive statistics and bivariate analyses with Fisher's exact test and Wilcoxon rank sum test were used to determine statistical significance of various factors in relation to phonotraumatic injury and response to treatment. Cochran-Armitage trend tests were performed to analyze trends in injuries across fitness types in relation to increased vocal demand. Occupational concerns reported by subjects were analyzed descriptively. RESULTS: The subject cohort consisted of 24 fitness instructors (20F; 4M) who taught a variety of fitness methods. Thirteen subjects (54.2%) were diagnosed with pseudocysts (five unilateral, eight bilateral), five (20.8%) with bilateral midfold masses, five (20.8%) with polyps (four unilateral, one bilateral), and one (4.2%) with cyst. Fourteen subjects (58.3%) were prescribed medication (oral steroids, reflux medication, and/or allergy medication). All were referred for behavioral management. Ten (41.7%) chose surgical intervention after failure to return to satisfactory function with behavioral management; Four (40%) experienced postoperative lesion recurrence. There were no statistically significant findings in relation to demographic information, past medical history, concurrent relevant vocal demands, or occupational vocal demands with choice for surgery. Trend test analysis found that lesions that are typically more likely to require surgical intervention (eg, polyps) tended to be found more frequently as vocal demand increased. The primary occupational concerns reported by subjects were related to amplification (lack of amplification, inadequate amplification/amplification problems) and scheduling (too many consecutive classes without adequate breaks). CONCLUSION: Fitness instructors are subject to a variety of phonotraumatic vocal fold injuries, nearly half which require surgical treatment. One in four recurs after such intervention. Instructors could benefit greatly from education on vocal health, strategies to improve and/or reduce voice use while in the fitness environment, and to help aid in recognizing early "red flags" for phonotraumatic injury. Occupational factors that place fitness instructors at risk for phonotraumatic injury (scheduling, environment, amplification) may be improved with education directed to studio owners and managers.

Enantiomeric 4'-Truncated 3-deaza-1',6'-isoneplanocins: Synthesis and antiviral properties including Ebola.

Enantiomeric 3-deaza-1',6'-isoneplanocins (C-3 unsubstituted 7a/7b and C-3 with a bromine 8a/8b) lacking the 4'-hydroxymethyl as mechanistically designed anti-viral targets have been prepared by utilizing the Ullmann reaction. Anti-Ebola properties were found for the D-like 7a and 8a and L-like 8b. All four products showed effects against human cytomegalovirus while D-like 7a/8a affected measles; 7a was effective versus norovirus and 8a inhibited Pichinde. Both 7a and 8a produced SAHase inhibitory effects. However, the anti-EBOV activity of 7a and 8a cannot be readily correlated with this observation due with their contrasting IC50 values (8a > 7a). It is to be noted that 7b showed no effects on this enzyme and 8b was minimally inhibitory. These results offer preliminary insight into the differing mechanisms of action of D- and L- like structures and enlighten structural features to guide additional antiviral agent pursuit in the isoneplanocin series.

Methods to Discover and Evaluate Proteasome Small Molecule Stimulators.

Protein accumulation has been identified as a characteristic of many degenerative conditions, such as neurodegenerative diseases and aging. In most cases, these conditions also present with diminished protein degradation. The ubiquitin-proteasome system (UPS) is responsible for the degradation of the majority of proteins in cells; however, the activity of the proteasome is reduced in these disease states, contributing to the accumulation of toxic protein. It has been hypothesized that proteasome activity, both ubiquitin-dependent and -independent, can be chemically stimulated to reduce the load of protein in diseased cells. Several methods exist to identify and characterize stimulators of proteasome activity. In this review, we detail the ways in which protease activity can be enhanced and analyze the biochemical and cellular methods of identifying stimulators of both the ubiquitin-dependent and -independent proteasome activities.

Public Health Surveillance Studies of Alcohol Industry Market and Political Strategies: A Systematic Review.

OBJECTIVE: This review examines public health surveillance (PHS) studies of alcohol industry actors that explore the implications of the integration of business and political strategies for public health. METHOD: Eligible for inclusion were studies published in English language peer-reviewed journals since 1980 that sought to investigate both alcohol industry business and political strategies and their implications for public health. Studies were also required to present economic, political, and health data together. Seven databases were searched until May 2018. RESULTS: Six studies were identified as eligible for inclusion in this review, undertaken in high-, middle-, and low-income countries and published between 2000 and 2015. Political strategies are driven largely by business interests, whether at the company, sectoral, or industry level, and corporate social responsibility activities may be integrated within overall strategies. There is a high degree of collaboration in political strategy development between companies, facilitated by growing concentration among global producers operating in increasingly oligopolistic markets. There are limited insights into the dynamics of market competition and limited methodological data available. CONCLUSIONS: PHS studies play a valuable role in identifying aspects of alcohol industry strategies that warrant more detailed and carefully designed research, as well as in elucidating global health implications. Further research in PHS and other kinds of studies will assist efforts to reduce the global burden of disease caused by alcohol.