Compassion Meditation for Distressed Older Veterans: A Feasibility Study.

OBJECTIVES: Older Veterans are at elevated risk for psychological distress and may encounter barriers to accessing mental health services. Compassion Meditation (CM) promotes positive emotions and outcomes among distressed individuals; thus, we conducted a preliminary feasibility study of CM among distressed older Veterans. METHODS: Participants included 25 Veterans aged 55+ (M = 69.0, SD = 10.6) with anxiety and/or depressive symptoms, recruited from primary care, mostly male (76.0%), and White (60.0%). CM consisted of 10 groups, which were transitioned from in-person to telehealth due to COVID-19. Feasibility indices included rates of intervention initiation and completion, and attendance. Participants completed measures of symptom severity and well-being pre- and post-intervention. RESULTS: Of 25 enrolled participants, 88.0% (n = 22) attended at least one session, and 52% (n = 13) completed the intervention (attended six or more sessions). Among intervention completers, the average number of sessions attended was 9.46. Seven Veterans withdrew from intervention due to difficulties engaging via telehealth. CONCLUSIONS: These findings support the feasibility of CM training in older Veterans with psychological distress, though dropouts highlighted potential need for additional strategies to facilitate telehealth participation. CLINICAL IMPLICATIONS: Older Veterans appear amenable to meditation-based practices, provided they are easy to access.

Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess.

A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620-$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296-$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs.Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).

Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia.

OBJECTIVE: Homework is a key theoretical component of cognitive-behavioral therapies, however, the effects of homework on clinical outcomes have largely been evaluated between-persons rather than within-persons. METHODS: The effects of homework completion on treatment response were examined in a randomized trial comparing Behavioral Activation Treatment for Anhedonia (BATA, n = 38), a novel psychotherapy, to Mindfulness-Based Cognitive Therapy (MBCT, n=35). The primary endpoint was consummatory reward sensitivity, measured weekly by the Snaith Hamilton Pleasure Scale (SHAPS), up to 15 weeks. Multilevel models evaluated change in SHAPS scores over time and the effects of clinician-reported and participant-reported homework. RESULTS: BATA and MBCT resulted in significant, equivalent reductions in SHAPS scores. Unexpectedly, participants who completed greater mean total amounts of homework did not improve at a faster rate (i.e., no between-person effect). However, sessions with greater than average participant-reported homework completion were associated with greater than average reductions in SHAPS scores (i.e., a within-person effect). For clinician-reported homework, this effect was only evident within the BATA condition. CONCLUSION: This study shows psychotherapy homework completion relates to symptomatic improvement in cognitive-behavioral treatments for anhedonia when session-to-session changes are examined within-person. On the contrary, we found no evidence that total homework completion predicted greater improvements between-person. When possible, psychotherapy researchers should evaluate their constructs of interest across multiple sessions (not just pre/post) to allow more direct tests of hypotheses predicted by theoretical models of individual change processes.

Longitudinal associations between perceived stress and anhedonia during psychotherapy.

BACKGROUND: Chronic stress alters reward sensitivity and contributes to the emergence of anhedonia. In clinical samples, the perception of stress is a strong predictor of anhedonia. While there is substantial evidence demonstrating psychotherapy reduces perceived stress, little is known regarding the effects of treatment-related decreases in perceived stress on anhedonia. METHODS: The current study investigated reciprocal relations between perceived stress and anhedonia using a cross-lagged panel model approach in a 15-week clinical trial examining the effects of Behavioral Activation Treatment for Anhedonia (BATA), a novel psychotherapy to treat anhedonia, compared to a Mindfulness-Based Cognitive Therapy (MBCT) comparison intervention (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). RESULTS: Treatment completers (n = 72) experienced significant reductions in anhedonia (M = -8.94, SD = 5.66) on the Snaith-Hamilton Pleasure Scale (t(71) = 13.39, p < .0001), and significant reductions in perceived stress (M = -3.71, SD = 3.88) on the Perceived Stress Scale (t(71) = 8.11, p < .0001) following treatment. Across all treatment-seeking participants (n = 87), a longitudinal autoregressive cross-lagged model revealed significant paths showing that higher levels of perceived stress at treatment Week 1 predicted reductions in anhedonia at treatment Week 4; lower levels of perceived stress at Week 8 predicted reductions in anhedonia at Week 12. Anhedonia did not significantly predict perceived stress at any stage of treatment. CONCLUSIONS: This study showed specific timing and directional effects of perceived stress on anhedonia during psychotherapy treatment. Individuals with relatively high perceived stress at the start of treatment were more likely to report relatively lower anhedonia a few weeks into treatment. At mid-treatment, individuals with low perceived stress were more likely to report lower anhedonia towards the end of treatment. These results demonstrate that early treatment components reduce perceived stress, thus allowing for downstream changes in hedonic functioning during mid-late treatment. The findings presented here suggest it will be critically important for future clinical trials evaluating novel interventions for anhedonia to measure stress levels repeatedly, as an important mechanism of change. TRIAL NAME: Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase. TRIAL URL: https://clinicaltrials.gov/ct2/show/NCT02874534. TRIAL REGISTRATION NUMBER: NCT02874534.

Multilevel growth curve analyses of behavioral activation for anhedonia (BATA) and mindfulness-based cognitive therapy effects on anhedonia and resting-state functional connectivity: Interim results of a randomized trial✰.

BACKGROUND: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. METHODS: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. RESULTS: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. CONCLUSIONS: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study.

BACKGROUND: Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations. METHODS: Patients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60. RESULTS: A total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3-5 days in the vancomycin arm and 3-7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection. CONCLUSION: Based on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01975662 . Registered on 5 November 2013.

Complicating the dominant morality discourse: mothers and fathers' constructions of substance use during pregnancy and early parenthood.

INTRODUCTION: Consumption of substances is a highly controversial behaviour, with those who do so commonly viewed as deviants, even criminals, or else as out of control addicts. In other work we showed that the use of substances by women who are pregnant or have recently become parents was mainly viewed by health and social care providers as morally wrong. Problematic substance use was framed through the narrow lens of gendered responsibilisation, resulting in women being seen primarily as foetal incubators and primary caregivers of infants. METHODS: In this follow-up paper we examine descriptive and qualitative data from a convenience sample of biological mothers and fathers (N = 34) recruited as part of a larger mixed methods study of the development and early implementation of an integrated primary maternity care program. We present a description of the participants' backgrounds, family circumstances, health status, and perception of drug-related stigma. This is succeeded by a thematic analysis of their personal views on substance use during both pregnancy and the transition to parenthood. RESULTS: Our results show that while many mothers and fathers hold abstinence as the ideal during pregnancy and early parenting, they simultaneously recognize the autonomy of women to judge substance use risk for themselves. Participants also call attention to social structural factors that increase/decrease harms associated with such substance use, and present an embodied knowledge of substance use based on their tacit knowledge of wellness and what causes harm. CONCLUSIONS: While these two main discourses brought forward by parents concerning the ideal of abstinence and the autonomy of women are not always reconcilable and are partially a reflection of the dissonance between dominant moral codes regarding motherhood and the lived experiences of people who use substances, service providers who are attuned to these competing discourses are likely to be more effective in their delivery of health and social services for vulnerable families. More holistic and nuanced perspectives of health, substance use, and parenting may generate ethical decision-making practice frameworks that guide providers in meeting and supporting the efforts of mothers and fathers to achieve well-being within their own definitions of problematic substance use.

Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial.

BACKGROUND: Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. METHODS/DESIGN: The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment.The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. DISCUSSION: If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. TRIAL REGISTRATION: The trial is listed on clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013).

Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up.

OBJECTIVE: To determine whether primary extracorporeal high-intensity focused ultrasound (HIFU) is safe, feasible and effective for managing small renal tumours. PATIENTS AND METHODS: Although surgery currently remains the standard treatment for localized renal cell carcinoma (RCC), the increasing incidence of small renal cancers has led to a shift towards nephron-sparing surgery, with associated morbidity in 20-25% of cases, and minimally invasive ablative therapies present an alternative management. HIFU results in 'trackless' homogenous tissue ablation and when administered via an extracorporeal device, is entirely noninvasive. The study comprised 17 patients (mean tumour size 2.5 cm) with radiologically suspicious renal tumours who underwent extracorporeal HIFU using the Model-JC System (Chongqing HAIFU™, China), under general anaesthesia with one overnight hospital stay. Real-time diagnostic ultrasonography was used for targeting and monitoring. Patients were followed with a clinical review and gadolinium-enhanced magnetic resonance imaging at 12 days and every 6 months for a mean of 36 months. The outcomes measures were patient morbidity and oncological efficacy of HIFU treatment. RESULTS: Of the 17 patients, 15 were treated according to protocol; two procedures were abandoned due to intervening bowel. There were no major complications related to HIFU. Radiological evidence of ablation was apparent at 12 days in seven of the 15 patients. Before the 6-month follow-up one patient had surgery due to persisting central enhancement. Fourteen patients were evaluated at the 6-month follow-up; eight tumours had involuted (mean 12% decrease in tumour area). Four patients had irregular enhancement on imaging and had alternative therapies. Ten patients remain on follow-up at a mean (range) of 36 (14-55) months after HIFU (mean 30% decrease in tumour area). There was central loss of enhancement in all. CONCLUSIONS: Renal HIFU achieves stable lesions in two-thirds of patients, with minimal morbidity, and might be appropriate in selected cases. Further trials with accurate histological follow-up are essential to fully evaluate this novel technique.