Basic processes and clinical applications of mental imagery in worry: A systematic review.

BACKGROUND: In this systematic review, we aimed to synthesise existing research on the phenomenology of mental imagery among high worriers compared to healthy individuals, and to characterise the nature and effectiveness of existing imagery-related interventions in treatment of worry. METHODS: PsycInfo, CENTRAL, EMBASE, Medline, Medline Epub, and PubMed were searched for studies examining the relationship between worry/GAD and mental imagery, or interventions using imagery in treatment of worry/GAD. We assessed study quality and used qualitative narrative synthesis to comprehensively map study results. RESULTS: The search yielded 2589 abstracts that were assessed for eligibility independently by two authors. From this, 183 full texts were screened and 50 qualitatively synthesised. Twenty-seven reported an association between worry/GAD and an aspect of mental imagery. Here, overactive negative and worry imagery, and diminished positive future imagining, were associated with worry/GAD. Twenty-three studies reported an intervention. This literature suggested mixed findings regarding efficacy, including for imaginal exposure as an independent technique for GAD. CONCLUSIONS: Findings support dysfunctional negative imagining and diminished positive prospective imagery in GAD. General imagining abilities remain intact, which is promising for efforts to utilise imagery in treatment. Further research is warranted to develop innovative clinical applications of imagery in treatment of GAD.

The roles and impacts of worldviews in the context of meditation-related challenges.

Previous research has shown that worldviews can serve as a coping response to periods of difficulty or struggle, and worldviews can also change on account of difficulty. This paper investigates the impacts worldviews have on the nature and trajectory of meditation-related challenges, as well as how worldviews change or are impacted by such challenges. The context of meditation-related challenges provided by data from the Varieties of Contemplative Experience research project offers a unique insight into the dynamics between worldviews and meditation. Buddhist meditation practitioners and meditation experts interviewed for the study report how, for some, worldviews can serve as a risk factor impacting the onset and trajectory of meditation-related challenges, while, for others, worldviews (e.g., being given a worldview, applying a worldview, or changing a worldview) were reported as a remedy for mitigating challenging experiences and/or their associated distress. Buddhist meditation practitioners and teachers in the contemporary West are also situated in a cultural context in which religious and scientific worldviews and explanatory frameworks are dually available. Furthermore, the context of "Buddhist modernism" has also promoted a unique configuration in which the theory and practice of Buddhism is presented as being closely compatible with science. We identify and discuss the various impacts that religious and scientific worldviews have on meditation practitioners and meditation teachers who navigate periods of challenge associated with the practice.

Biodegradation potential of residue generated during the in-situ burning of oil in the marine environment.

The biodegradability of residues derived from in-situ burning, an oil spill response strategy which involves burning an oil slick on the sea surface, has not yet been fully studied. With a growing risk of oil spills, the fate of the persistent burn residue containing potentially toxic substances must be better understood. Microcosms were used to study the microbial community response and potential biodegradability of in-situ burn residues generated from Ultra Low Sulphur (ULS) marine diesel. Microcosm studies were conducted using residues originating from the burning of unweathered and weathered diesel, with the addition of a fertilizer and a dispersant. Burn residues were incubated for 6 weeks at 7 °C in natural seawater with continual agitation in the dark. Samples were subsequently sacrificed for chemistry as well as 16S rRNA gene amplicon and shotgun metagenomic sequencing. Chemistry analyses revealed a reduction in hydrocarbon concentrations. Medium chain-length n-alkanes (nC16-nC24) decreased by 8% in unweathered burn residue microcosms and up to 26% in weathered burn residue microcosms. A significant decrease in polycyclic aromatic hydrocarbon (PAH) concentrations was observed only for naphthalene, fluorene and their alkylated homologs, in the microcosms amended with residue produced from burning weathered diesel. Decreases of 2-24%, were identified depending on the compound. Microcosms amended with burn residues had distinct microbial communities marked by an increase in relative abundance of putative hydrocarbon degraders as well as an increase of known hydrocarbon-degradation genes. These novel results suggest that if in-situ burning is performed on ULS marine diesel, some of the indigenous bacteria would respond to the newly available carbon source and some of the residual compounds would be biodegraded. Future studies involving longer incubation periods could give a better understanding of the fate of burn residues by shedding light on the potential biodegradability of the more recalcitrant residual compounds.

Cardiac xenotransplantation: from concept to clinic.

For many patients with terminal/advanced cardiac failure, heart transplantation is the most effective, durable treatment option, and offers the best prospects for a high quality of life. The number of potentially life-saving donated human organs is far fewer than the population who could benefit from a new heart, resulting in increasing numbers of patients awaiting replacement of their failing heart, high waitlist mortality, and frequent reliance on interim mechanical support for many of those deemed among the best candidates but who are deteriorating as they wait. Currently, mechanical assist devices supporting left ventricular or biventricular heart function are the only alternative to heart transplant that is in clinical use. Unfortunately, the complication rate with mechanical assistance remains high despite advances in device design and patient selection and management, and the quality of life of the patients even with good outcomes is only moderately improved. Cardiac xenotransplantation from genetically multi-modified (GM) organ-source pigs is an emerging new option as demonstrated by the consistent long-term success of heterotopic (non-life-supporting) abdominal and life-supporting orthotopic porcine heart transplantation in baboons, and by a recent 'compassionate use' transplant of the heart from a GM pig with 10 modifications into a terminally ill patient who survived for 2 months. In this review, we discuss pig heart xenotransplantation as a concept, including pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental overgrowth of the heart, as well as GM strategies in pigs to prevent or minimize these problems. Additional topics discussed include relevant results of heterotopic and orthotopic heart transplantation experiments in the pig-to-baboon model, microbiological and virologic safety concepts, and efficacy requirements for initiating formal clinical trials. An adequate regulatory and ethical framework as well as stringent criteria for the selection of patients will be critical for the safe clinical development of cardiac xenotransplantation, which we expect will be clinically tested during the next few years.

Synthetic sling or artificial urinary sphincter for men with urodynamic stress incontinence after prostate surgery: the MASTER non-inferiority RCT.

BACKGROUND: Stress urinary incontinence is common in men after prostate surgery and can be difficult to improve. Implantation of an artificial urinary sphincter is the most common surgical procedure for persistent stress urinary incontinence, but it requires specialist surgical skills, and revisions may be necessary. In addition, the sphincter is relatively expensive and its operation requires adequate patient dexterity. New surgical approaches include the male synthetic sling, which is emerging as a possible alternative. However, robust comparable data, derived from randomised controlled trials, on the relative safety and efficacy of the male synthetic sling and the artificial urinary sphincter are lacking. OBJECTIVE: We aimed to compare the clinical effectiveness and cost-effectiveness of the male synthetic sling with those of the artificial urinary sphincter surgery in men with persistent stress urinary incontinence after prostate surgery. DESIGN: This was a multicentre, non-inferiority randomised controlled trial, with a parallel non-randomised cohort and embedded qualitative component. Randomised controlled trial allocation was carried out by remote web-based randomisation (1 : 1), minimised on previous prostate surgery (radical prostatectomy or transurethral resection of the prostate), radiotherapy (or not, in relation to prostate surgery) and centre. Surgeons and participants were not blind to the treatment received. Non-randomised cohort allocation was participant and/or surgeon preference. SETTING: The trial was set in 28 UK urological centres in the NHS. PARTICIPANTS: Participants were men with urodynamic stress incontinence after prostate surgery for whom surgery was deemed appropriate. Exclusion criteria included previous sling or artificial urinary sphincter surgery, unresolved bladder neck contracture or urethral stricture after prostate surgery, and an inability to give informed consent or complete trial documentation. INTERVENTIONS: We compared male synthetic sling with artificial urinary sphincter. MAIN OUTCOME MEASURES: The clinical primary outcome measure was men's reports of continence (assessed from questions 3 and 4 of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form) at 12 months post randomisation (with a non-inferiority margin of 15%). The primary economic outcome was cost-effectiveness (assessed as the incremental cost per quality-adjusted life-year at 24 months post randomisation). RESULTS: In total, 380 men were included in the randomised controlled trial (n = 190 in each group), and 99 out of 100 men were included in the non-randomised cohort. In terms of continence, the male sling was non-inferior to the artificial urinary sphincter (intention-to-treat estimated absolute risk difference -0.034, 95% confidence interval -0.117 to 0.048; non-inferiority p = 0.003), indicating a lower success rate in those randomised to receive a sling, but with a confidence interval excluding the non-inferiority margin of -15%. In both groups, treatment resulted in a reduction in incontinence symptoms (as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form). Between baseline and 12 months' follow-up, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score fell from 16.1 to 8.7 in the male sling group and from 16.4 to 7.5 in the artificial urinary sphincter group (mean difference for the time point at 12 months 1.30, 95% confidence interval 0.11 to 2.49; p = 0.032). The number of serious adverse events was small (male sling group, n = 8; artificial urinary sphincter group, n = 15; one man in the artificial urinary sphincter group experienced three serious adverse events). Quality-of-life scores improved and satisfaction was high in both groups. Secondary outcomes that showed statistically significant differences favoured the artificial urinary sphincter over the male sling. Outcomes of the non-randomised cohort were similar. The male sling cost less than the artificial sphincter but was associated with a smaller quality-adjusted life-year gain. The incremental cost-effectiveness ratio for male slings compared with an artificial urinary sphincter suggests that there is a cost saving of £425,870 for each quality-adjusted life-year lost. The probability that slings would be cost-effective at a £30,000 willingness-to-pay threshold for a quality-adjusted life-year was 99%. LIMITATIONS: Follow-up beyond 24 months is not available. More specific surgical/device-related pain outcomes were not included. CONCLUSIONS: Continence rates improved from baseline, with the male sling non-inferior to the artificial urinary sphincter. Symptoms and quality of life significantly improved in both groups. Men were generally satisfied with both procedures. Overall, secondary and post hoc analyses favoured the artificial urinary sphincter over the male sling. FUTURE WORK: Participant reports of any further surgery, satisfaction and quality of life at 5-year follow-up will inform longer-term outcomes. Administration of an additional pain questionnaire would provide further information on pain levels after both surgeries. TRIAL REGISTRATION: This trial is registered as ISRCTN49212975. 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. 26, No. 36. See the NIHR Journals Library website for further project information.

Leakage of urine associated with physical exertion (e.g. sporting activities, sneezing or coughing) is common in men who have undergone prostate surgery, but it is difficult to improve. Many men still leak urine 12 months after their prostate surgery and may continue to wear protective pads or sheaths. The most common operation to improve incontinence is implantation of an artificial urinary sphincter. An artificial urinary sphincter is an inflatable cuff that is placed around the urethra, the tube that drains urine from the bladder. The cuff is inflated and compresses the urethra to prevent leaking. When the man needs to pass urine, he must deflate the cuff by squeezing a pump placed in his scrotum, which releases the compression on the urethra and allows the bladder to empty. Recently, a new device, the male sling (made from non-absorbable plastic mesh), has been developed. The sling, which is surgically inserted under the urethra, supports the bladder, but, in contrast to the artificial sphincter, it does not need to be deactivated by a pump and, therefore, the patient does not need to do anything to operate it. A sling is also easier for the surgeon to insert than a sphincter. However, in some men, the sling does not provide enough improvement in incontinence symptoms and another operation, to place an artificial urinary sphincter, is needed. The aim of this study was to determine if the male sling was as effective as the artificial urinary sphincter in treating men with bothersome incontinence after prostate surgery. The study took the form of a randomised controlled trial (the gold standard and most reliable way to compare treatments) in which men were randomised (allocated at random to one of two groups using a computer) to either a male sling or an artificial urinary sphincter operation. We asked men how they got on in the first 2 years after their operation. Regardless of which operation they had, incontinence and quality of life significantly improved and complications were rare. A small number of men did require another operation to improve their incontinence, and it was more likely that an artificial urinary sphincter was needed, rather than another sling operation, if a male sling was not successful. Satisfaction was high in both groups, but it was significantly higher in the artificial urinary sphincter group than in the male sling group. Those who received a male sling were less likely than those who received an artificial urinary sphincter to say that they would recommend their surgery to a friend.

Comparison of venous, capillary and interstitial blood glucose data measured during hyperbaric oxygen treatment from patients with diabetes mellitus.

INTRODUCTION: Patients undergoing hyperbaric oxygen treatments (HBOT) have been shown to experience a reduction in blood glucose (BG) levels during a treatment. This necessitates frequent assessment of BG levels. Continuous glucose monitoring (CGM) may represent an alternative to the current finger prick monitoring method in-chamber, however, continuous sensor glucose (SG) data has not been validated in situ. The aim was to determine the validity of continuous SG and intermittent BG monitoring with serum BG levels in diabetic patients during HBOT. METHODS: Measurements were obtained (finger prick [capillary sample], CGM [interstitial fluid], and serum [venous sample]) at baseline, and at 30, 60, 90 and 120 minutes during the hyperbaric treatment. Data were analysed by calculating intraclass correlation coefficients (ICC) and using mixed effects linear regression. RESULTS: The ICC results (n = 10 patients) between the three methods indicated very high and statistically significant absolute agreement at baseline (pre-dive) (ICC = 0.90, 95% CI 0.74-0.97), at 30 minutes (ICC = 0.85, 95% CI 0.61-0.96), 60 minutes (ICC = 0.86, 95% CI 0.58-0.96), 90 minutes (ICC = 0.87, 96% CI 0.63-0.96) and 120 minutes (ICC = 0.90, 95% CI 0.70-0.97). Capillary glucose and CGM SG readings were each within 1 mmol·L-1 on average of the serum glucose reading, with multi-level linear regression finding the average difference between the CGM SG and capillary glucose methods of BG sampling was not statistically significant (P = 0.81). CONCLUSIONS: The CGM SG data were comparable with glucose readings from capillary monitoring. Both CGM and capillary data were consistent with serum values.

Defining and measuring meditation-related adverse effects in mindfulness-based programs.

BACKGROUND: Research on the adverse effects of mindfulness-based programs (MBPs) has been sparse and hindered by methodological imprecision. METHODS: The 44-item Meditation Experiences Interview (MedEx-I) was used by an independent assessor to measure meditation-related side effects (MRSE) following three variants of an 8-week program of mindfulness-based cognitive therapy (n = 96). Each item was queried for occurrence, causal link to mindfulness meditation practice, duration, valence, and impact on functioning. RESULTS: Eighty-three percent of the MBP sample reported at least one MRSE. Meditation-related adverse effects (MRAEs) with negative valences or negative impacts on functioning occurred in 58% and 37% of the sample, respectively. Lasting bad effects occurred in 6-14% of the sample and were associated with signs of dysregulated arousal (hyperarousal and dissociation). CONCLUSION: Meditation practice in MBPs is associated with transient distress and negative impacts at similar rates to other psychological treatments.

Progress or Pathology? Differential Diagnosis and Intervention Criteria for Meditation-Related Challenges: Perspectives From Buddhist Meditation Teachers and Practitioners.

Studies in the psychology and phenomenology of religious experience have long acknowledged similarities with various forms of psychopathology. Consequently, it has been important for religious practitioners and mental health professionals to establish criteria by which religious, spiritual, or mystical experiences can be differentiated from psychopathological experiences. Many previous attempts at differential diagnosis have been based on limited textual accounts of mystical experience or on outdated theoretical studies of mysticism. In contrast, this study presents qualitative data from contemporary Buddhist meditation practitioners and teachers to identify salient features that can be used to guide differential diagnosis. The use of certain existing criteria is complicated by Buddhist worldviews that some difficult or distressing experiences may be expected as a part of progress on the contemplative path. This paper argues that it is important to expand the framework for assessment in both scholarly and clinical contexts to include not only criteria for determining normative fit with religious experience or with psychopathology, but also for determining need for intervention, whether religious or clinical. Qualitative data from Buddhist communities shows that there is a wider range of experiences that are evaluated as potentially warranting intervention than has previously been discussed. Decision making around these experiences often takes into account contextual factors when determining appraisals or need for intervention. This is in line with person-centered approaches in mental health care that emphasize the importance of considering the interpersonal and cultural dynamics that inevitably constitute the context in which experiences are evaluated and rendered meaningful.

Correlations between patient-reported outcomes and self-reported characteristics in adults with hemophilia B and caregivers of children with hemophilia B: analysis of the B-HERO-S study.

PURPOSE: Pain, anxiety, depression, and other aspects of health-related quality of life (HRQoL) are important issues for people with hemophilia and caregivers of children with hemophilia. Patient-reported outcome (PRO) instruments may be used to assess aspects of HRQoL; however, the use of PROs in clinical management of patients with hemophilia is limited and inconsistent. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the impact of hemophilia B on HRQoL and other psychosocial aspects in affected adults and caregivers of children with hemophilia B. This post hoc analysis assessed correlations between PRO scores and psychosocial questions commonly asked in comprehensive care settings among B-HERO-S respondents. PATIENTS AND METHODS: B-HERO-S consisted of two online surveys, one administered to adults with hemophilia B (n=299) and one administered to caregivers of children with hemophilia B (n=150). The adult survey included EQ-5D-5L with visual analog scale, BPI, HAL, and PHQ-9. The caregiver survey included PHQ-9 and GAD-7. Questions related to demographics, hemophilia treatment, and psychosocial questions asked in comprehensive care visits were also included in the surveys. A post hoc analysis was performed to assess correlations between responses to selected psychosocial questions with PRO scores. RESULTS: For adults with hemophilia B, greater pain severity and pain interference scores were associated with work-related problems, functional limitations, and relationship, psychological, and treatment issues. Significant correlations were also noted between some of these psychosocial outcomes and depressive symptoms. For caregivers, greater depression and anxiety were associated with employment issues, their child's functional, relationship, and psychological issues, having had difficulty or concerns with treatment/factor availability or affordability, and having less frequent HTC visits. CONCLUSION: High correlations were observed between PRO scores measuring pain, depression, and anxiety and questions commonly used in the comprehensive care setting to assess the psychosocial impact of hemophilia.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.

BACKGROUND: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. OBJECTIVES: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). REVIEW METHODS: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. RESULTS: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. LIMITATIONS: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. CONCLUSIONS: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. FUTURE WORK: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016040190. FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

Mindfulness-based interventions and their effects on emotional clarity: A systematic review and meta-analysis.

BACKGROUND: An inability to identify or describe internal emotional experience has been linked to a range of affective disorders. Despite burgeoning research on mindfulness-based interventions and their possible effects on emotion regulation, the effects of such interventions on emotional clarity is unclear. This review examines the evidence for the effect of mindfulness-based interventions on self-reported emotional clarity. METHOD: Published studies indexed by PsycINFO, PubMed and Scopus, as available in April 2017, were systematically reviewed. Interventions that included mindfulness practice or philosophy, and reported a suitable measure of emotional clarity at pre- and post-intervention were selected. A random-effects meta-analysis was performed. Subgroup comparisons were also conducted to test for differences between clinical and non-clinical samples, between specific and approximate measures of emotional clarity, and between controlled and uncontrolled trials. RESULTS: Seventeen studies met the criteria for inclusion. The overall estimated effect size for pre- to post-intervention was small to moderate, Hedges' g = 0.42, 95% CI [0.25, 0.59] and for between groups results was small to large, Hedges' g = 0.52, 95% CI [0.15, 0.90]. LIMITATIONS: Studies varied substantially in design quality and study characteristics. Furthermore, while interventions in the reviewed studies all had mindfulness components, many had other components in addition to mindfulness. Consequently, this review is limited by the heterogeneity of studies and results should be interpreted with caution. CONCLUSIONS: There is preliminary evidence to suggest that mindfulness-based interventions may increase emotional clarity. However, more homogenous and targeted experiments are required to confirm these initial findings.

Male synthetic sling versus artificial urinary sphincter trial for men with urodynamic stress incontinence after prostate surgery (MASTER): study protocol for a randomised controlled trial.

BACKGROUND: Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. METHODS/DESIGN: Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. DISCUSSION: A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Registry: Number ISRCTN49212975 . Registered on 22 July 2013. First patient randomised on 29 January 2014.

The varieties of contemplative experience: A mixed-methods study of meditation-related challenges in Western Buddhists.

Buddhist-derived meditation practices are currently being employed as a popular form of health promotion. While meditation programs draw inspiration from Buddhist textual sources for the benefits of meditation, these sources also acknowledge a wide range of other effects beyond health-related outcomes. The Varieties of Contemplative Experience study investigates meditation-related experiences that are typically underreported, particularly experiences that are described as challenging, difficult, distressing, functionally impairing, and/or requiring additional support. A mixed-methods approach featured qualitative interviews with Western Buddhist meditation practitioners and experts in Theravada, Zen, and Tibetan traditions. Interview questions probed meditation experiences and influencing factors, including interpretations and management strategies. A follow-up survey provided quantitative assessments of causality, impairment and other demographic and practice-related variables. The content-driven thematic analysis of interviews yielded a taxonomy of 59 meditation-related experiences across 7 domains: cognitive, perceptual, affective, somatic, conative, sense of self, and social. Even in cases where the phenomenology was similar across participants, interpretations of and responses to the experiences differed considerably. The associated valence ranged from very positive to very negative, and the associated level of distress and functional impairment ranged from minimal and transient to severe and enduring. In order to determine what factors may influence the valence, impact, and response to any given experience, the study also identified 26 categories of influencing factors across 4 domains: practitioner-level factors, practice-level factors, relationships, and health behaviors. By identifying a broader range of experiences associated with meditation, along with the factors that contribute to the presence and management of experiences reported as challenging, difficult, distressing or functionally impairing, this study aims to increase our understanding of the effects of contemplative practices and to provide resources for mediators, clinicians, meditation researchers, and meditation teachers.

Safety, tolerability, and immunogenicity of a single dose 4-antigen or 3-antigen Staphylococcus aureus vaccine in healthy older adults: Results of a randomised trial.

BACKGROUND: The decline in immune function with age is a challenge to vaccine development. Following an initial study in adults aged 18-64years, this study evaluated the safety and immunogenicity of Staphylococcus aureus (S. aureus) 4-antigen (SA4Ag) and 3-antigen (SA3Ag) vaccine in older adults. SA3Ag included capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to the nontoxic mutant form of diphtheria toxin (CRM197) and a recombinant version of clumping factor A (ClfA). SA4Ag included these antigens, with the addition of a recombinant manganese transporter C (rP305A or MntC). Both vaccines were unadjuvanted. METHODS: In this double-blind, sponsor-unblinded, placebo-controlled, phase 1/2 study, 284 healthy adults (aged 65-85years) were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A, SA3Ag, or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; immunogenicity was also assessed using a competitive Luminex® immunoassay (cLIA). T-cell responses were measured in a small subgroup of subjects using intracellular cytokine staining (ICS) assays. RESULTS: The results demonstrated rapid and robust functional immune responses to all antigens in healthy older adults. A high proportion of active vaccine recipients met the pre-defined antibody thresholds for each antigen at Day 29. SA4Ag elicited a dose-level response to rP305A with up to a 13-fold rise in cLIA titres at Day 29. Opsonophagocytic activity (OPA) assays showed >50- and >20-fold rises in functional titres using S. aureus strains expressing CP5 and CP8, respectively, at Day 29. T-cell cytokine responses were not substantially above background levels. There were no safety concerns in this study population and no increases in adverse events with higher rP305A dose levels. CONCLUSIONS: Single-dose vaccination of SA4Ag and SA3Ag in healthy adults aged 65-85years safely induced rapid and robust functional immune responses, supporting further development of SA4Ag for the prevention of S. aureus disease in adults up to age 85years. TRIAL REGISTRATION NUMBER: NCT01643941.

Renal xenotransplantation: experimental progress and clinical prospects.

There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses. Between 1989 and 2015, pig kidney graft survival in nonhuman primates increased from 23 days to almost 10 months. There appear to be no clinically significant physiological incompatibilities in renal function between pigs and primates. The organ-source pigs will be housed in a biosecure environment, and thus the risk of transferring an exogenous potentially pathogenic microorganism will be less than that after allotransplantation. Although the risk associated with porcine endogenous retroviruses is considered small, techniques are now available whereby they could potentially be excluded from the pig. The US Food and Drug Administration suggests that xenotransplantation should be restricted to "patients with serious or life-threatening diseases for whom adequately safe and effective alternative therapies are not available." These might include those with (i) a high degree of allosensitization to human leukocyte antigens or (ii) rapid recurrence of primary disease in previous allografts. The potential psychosocial, regulatory, and legal aspects of clinical xenotransplantation are briefly discussed.

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.

BACKGROUND: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. METHODS: The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. RESULTS: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. CONCLUSIONS: One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Executive summary.

The International Xenotransplantation Association has updated its original "Consensus Statement on Conditions for Undertaking Clinical Trials of Porcine Islet Products in Type 1 Diabetes," which was published in Xenotransplantation in 2009. This update is timely and important in light of scientific progress and changes in the regulatory framework pertinent to islet xenotransplantation. Except for the chapter on "informed consent," which has remained relevant in its 2009 version, all other chapters included in the initial consensus statement have been revised for inclusion in this update. These chapters will not provide complete revisions of the original chapters; rather, they restate the key points made in 2009, emphasize new and under-appreciated topics not fully addressed in 2009, suggest relevant revisions, and communicate opinions that complement the consensus opinion. Chapter 1 provides an update on national regulatory frameworks addressing xenotransplantation. Chapter 2 a, previously Chapter 2, suggests several important revisions regarding the generation of suitable source pigs from the perspective of the prevention of xenozoonoses. The newly added Chapter 2b discusses conditions for the use of genetically modified source pigs in clinical islet xenotransplantation. Chapter 3 reviews porcine islet product manufacturing and release testing. Chapter 4 revisits the critically important topic of preclinical efficacy and safety data required to justify a clinical trial. The main achievements in the field of transmission of all porcine microorganisms, the rationale for more proportionate recipient monitoring, and response plans are reviewed in Chapter 5. Patient selection criteria and circumstances where trials of islet xenotransplantation would be both medically and ethically justified are examined in Chapter 6 in the context of recent advances in available and emerging alternative therapies for serious and potentially life-threatening complications of diabetes. It is hoped that this first update of the International Xenotransplantation Association porcine islet transplant consensus statement will assist the islet xenotransplant scientific community, sponsors, regulators, and other stakeholders actively involved in the clinical translation of islet xenotransplantation.

Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18-30 years) with hemophilia.

The Hemophilia Experiences, Results and Opportunities (HERO) initiative assessed psychosocial issues reported by people with moderate to severe hemophilia and was led by a multidisciplinary international advisory board. This analysis reports data from young adult respondents (aged 18-30 years), including both US and overall global (including US respondents) results, and investigates treatment outcomes, quality of life, and impacts of hemophilia on relationships. More young adults in HERO received prophylaxis than on-demand treatment, although a majority reported not using factor products exactly as prescribed, and 50% of global respondents and 26% of US respondents reported issues with access to factor replacement therapy in the previous 5 years. Many young adults with hemophilia reported comorbidities, including bone/skeletal arthritis, chronic pain, and viral infections, and nearly half of young adults reported anxiety/depression. Most reported pain interference with daily activities in the past 4 weeks, although a majority reported participating in lower-risk activities and approximately half in intermediate-risk activities. Most young adults were very or quite satisfied with the support of partners/spouses, family, and friends, although roughly one-third reported that hemophilia affected their ability to develop close relationships with a partner. A majority of young adults reported that hemophilia has had a negative impact on employment, and 62% of global respondents and 78% of US respondents were employed at least part-time. Together these data highlight the psychosocial issues experienced by young adults with hemophilia and suggest that increased focus on these issues may improve comprehensive care during the transition to adulthood.

Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection.

BACKGROUND: We explored the relationship between virological response in the first year of treatment and long-term outcomes in the BENCHMRK studies. METHODS: Patients failing antiretroviral treatment with 3-class resistant HIV-1 received double-blinded raltegravir (or placebo) with optimized background therapy (OBT) until week 156, followed by open-label raltegravir with OBT up to week 240. In this exploratory analysis of patients randomized to raltegravir, virological response over weeks 16-48 was categorized as continuous suppression (CS; viral RNA [vRNA] always <50 copies/ml), low-level viraemia (LLV; vRNA always <400 copies/ml, >50 copies/ml at least once), or not suppressed (NS; vRNA >400 copies/ml at least once). The association between these first-year vRNA response categories and baseline factors was analysed with univariate and multivariate models. Virological and immunological outcomes for years 2-5 were assessed by first-year vRNA response category (observed failure approach). RESULTS: Baseline vRNA, baseline CD4(+) T-cell count and rapid viral decay (vRNA <50 copies/ml between weeks 2-12) correlated with first-year vRNA response (P<0.001); only rapid viral decay remained significant by multiple regression. Virological response rates were similar in the LLV and CS groups and lowest in the NS group. CD4(+) T-cell count increased through week 240 in the CS and LLV groups. Time to loss of virological response (confirmed vRNA ≥400 copies/ml) through week 240 did not support as strong a difference between the LLV and CS groups (log-rank P=0.11) as previously reported through weeks 156 and 192 (P<0.05). CONCLUSIONS: Treatment-experienced patients on a raltegravir-based regimen with early LLV may have long-term virological and immunological benefit when their therapy is maintained.