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Hearing aid (HA) use is known to improve health outcomes for people with hearing loss. Despite that, HA use is suboptimal, and communication issues and hearing-related activity limitations and participation restrictions often remain. Web-based self-management communication programs may support people with hearing loss to effectively self-manage the impact of hearing loss in their daily lives. The goal of the research is to examine the short- and long-term effects of a web-based self-management SUpport PRogram (SUPR) on communication strategy use (primary outcome) and a range of secondary outcomes for HA users aged 50 years and older. Clients of 36 HA dispensing practices were randomized to SUPR (SUPR recipients; n=180 HA users) and 34 to care as usual (controls; n=163 HA users). SUPR recipients received a practical support booklet and online materials delivered via email over the course of their 6-month HA rehabilitation trajectory. They were encouraged to appoint a communication partner and were offered optional email contact with the HA dispensing practice. The online materials included 3 instruction videos on HA handling, 5 videos on communication strategies, and 3 testimonial videos. Care as usual included a HA fitting rehabilitation trajectory only. Measurements were carried out at baseline, immediately postintervention, 6 months postintervention, and 12 months postintervention. The primary outcome measure was self-reported use of communication strategies (3 subscales of the Communication Profile for the Hearing Impaired [CPHI]). Secondary outcome measures included self-reported personal adjustment to hearing loss (CPHI); use, satisfaction and benefit of HAs and SUPR (use questionnaire; International Outcome Inventory for Hearing Aids [IOI-HA], Alternative Interventions [IOI-AI]); recommendation of HA dispensing services; self-efficacy for HA handling (Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids [MARS-HA]); readiness to act on hearing loss (University of Rhode Island Change Assessment adapted for hearing loss [URICA-HL]); and hearing disability (Amsterdam Inventory for Auditory Disability and Handicap [AIADH]). Linear mixed model analyses (intention to treat) showed no significant differences between the SUPR and control group in the course of communication strategy use (CPHI). Immediately postintervention, SUPR recipients showed significantly higher self-efficacy for advanced HA handling than the controls, which was sustained at 12 months (MARS-HA; mean difference immediately postintervention: 5.3, 95% CI 0.3 to 10.4; P=.04). Also, SUPR recipients showed significantly greater HA satisfaction than controls immediately postintervention (IOI-HA; 0.3, 95% CI 0.09 to 0.5; P=.006), which was sustained at 12 months, and significantly greater HA use than the controls immediately postintervention (IOI-HA; 0.3, 95% CI 0.02 to 0.5; P=.03), which was not sustained at 12 months. This study provides ground to recommend adding SUPR to standard HA dispensing care, as long-term, modest improvements in HA outcomes were observed. Further research is needed to evaluate what adjustments to SUPR are needed to establish long-term effectiveness on outcomes in the psychosocial domain. ISRCTN77340339; http://www.isrctn.com/ISRCTN77340339. RR2-10.1136/bmjopen-2016-015012.

Objectives: To evaluate the process of implementing a web-based support program (SUPR) for hearing aid users in the Dutch dispensing setting in order to allow interpretation of the randomized controlled trial's results (positive effects on hearing-aid related outcomes; no effects on psychosocial outcomes). Design: Measures: context of implementation, recruitment, SUPR's: reach, implementation fidelity, dose delivered, dose received, satisfaction, and benefit. Data collection: quantitative and qualitative. Study Sample: One hundred thirty-eight clients (mean age 68.1 years; 60% male) and 44 dispensers completed questionnaires. Five clients and 6 dispensers participated in interviews and focus groups. Results: Clients and dispensers were generally satisfied with SUPR's usefulness. SUPR-videos were watched by 7–37% of the clients. Around half of the dispensers encouraged clients to watch them or informed them about SUPR. Some clients found the SUPR-materials suboptimal, and changes in personnel and limited dispenser-training were barriers acting on a contextual level. Conclusions: This study identified several factors that contributed to the success of SUPR. Others factors, acting on various levels (e.g., intervention material, dispensers, and implementation context), were suboptimal and may explain the absent psychosocial effects. The identified factors are important to consider in further development of SUPR, and in other web-based support programs.

Background Symptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands. Methods All consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks. Results Twenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success. Conclusion The current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.

Purpose: The SUpport PRogram (SUPR) study was carried out in the context of a private academic partnership and is the first study to evaluate the long-term effects of a communication program (SUPR) for older hearing aid users and their communication partners on a large scale in a hearing aid dispensing setting. The purpose of this research note is to reflect on the lessons that we learned during the different development, implementation, and evaluation phases of the SUPR project. Procedure: This research note describes the procedures that were followed during the different phases of the SUPR project and provides a critical discussion to describe the strengths and weaknesses of the approach taken. Conclusion: This research note might provide researchers and intervention developers with useful insights as to how aural rehabilitation interventions, such as the SUPR, can be developed by incorporating the needs of the different stakeholders, evaluated by using a robust research design (including a large sample size and a longer term follow-up assessment), and implemented widely by collaborating with a private partner (hearing aid dispensing practice chain).

Purpose The current study aimed to identify factors that distinguish between older (50+ years) hearing aid (HA) candidates who do and do not purchase HAs after having gone through an HA evaluation period (HAEP). Method Secondary data analysis of the SUpport PRogram trial was performed ( = 267 older, 1st-time HA candidates). All SUpport PRogram participants started an HAEP shortly after study enrollment. Decision to purchase an HA by the end of the HAEP was the outcome of interest of the current study. Participants' baseline covariates (22 in total) were included as candidate predictors. Multivariable logistic regression modeling (backward selection and reclassification tables) was used. Results Of all candidate predictors, only pure-tone average (average of 1, 2, and 4 kHz) hearing loss emerged as a significant predictor (odds ratio = 1.03, 95% confidence interval [1.03, 1.17]). Model performance was weak (Nagelkerke = .04, area under the curve = 0.61). Conclusions These data suggest that, once HA candidates have decided to enter an HAEP, factors measured early in the help-seeking journey do not predict well who will and will not purchase an HA. Instead, factors that act during the HAEP may hold this predictive value. This should be examined.

BackgroundAn educational SUpport PRogramme called SUPR has been developed for hearing aid users (HAUs) and their communication partners (CPs) offering care beyond hearing aid fitting. SUPR teaches its users communication strategies, hearing aid handling skills and personal adjustment to hearing impairment.Methods/designUsing a cluster randomised controlled trial design, 70 Dutch hearing aid dispenser practices were randomised into hearing aid fitting (care as usual, 34 practices) and hearing aid fitting including SUPR (36 practices). The aim was to recruit a total of 569 older (aged 50+ years) first-time (n=258) and experienced (n=311) HAUs and their CPs. SUPR consists of a Practical Support Booklet and online material offered via email over a period of 6–7 months. The booklet provides practical information on hearing aids, advice on communication strategies and home exercises. The online material consists of educational videos on hearing aid functionality and usage, communication strategies and peer testimonials. Finally, noncommittal email contact with the dispenser is offered. Every HAU is asked to assign a CP who is advised to be involved intensively. Effect measurements for HAUs and their CPs will occur at baseline and at 6, 12 and 18 months follow-up via online questionnaires. The primary outcomes for HAUs will be the use of communication strategies as measured by the subscales of the Communication Profile for the Hearing Impaired. A process evaluation will be performed.Ethics and disseminationThe study was approved by the Dutch Institutional Review Board of the VU Medical University Center Amsterdam. This intervention could contribute to lowering the hearing impairment burden in our ageing society. The results will be disseminated through peer-reviewed publications and scientific conferences.Trial registration numberISRCTN77340339; Pre-results.

Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1-2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1-2 hours, this took 24 hours in blood vessels and 7 days in nerves.

Checkpoint kinase 1 (CHK1) is a key component of the ATR (ataxia telangiectasia-mutated and Rad3-related)-dependent DNA damage response pathway that protect cells from replication stress, a cell intrinsic phenomenon enhanced by oncogenic transformation. Here, we show that CHK1 is overexpressed and hyperactivated in T-cell acute lymphoblastic leukemia (T-ALL). CHEK1 mRNA is highly abundant in patients of the proliferative T-ALL subgroup and leukemia cells exhibit constitutively elevated levels of the replication stress marker phospho-RPA32 and the DNA damage marker γH2AX. Importantly, pharmacologic inhibition of CHK1 using PF-004777736 or CHK1 short hairpin RNA-mediated silencing impairs T-ALL cell proliferation and viability. CHK1 inactivation results in the accumulation of cells with incompletely replicated DNA, ensuing DNA damage, ATM/CHK2 activation and subsequent ATM- and caspase-3-dependent apoptosis. In contrast to normal thymocytes, primary T-ALL cells are sensitive to therapeutic doses of PF-004777736, even in the presence of stromal or interleukin-7 survival signals. Moreover, CHK1 inhibition significantly delays in vivo growth of xenotransplanted T-ALL tumors. We conclude that CHK1 is critical for T-ALL proliferation and viability by downmodulating replication stress and preventing ATM/caspase-3-dependent cell death. Pharmacologic inhibition of CHK1 may be a promising therapeutic alternative for T-ALL treatment.

Instructing and guiding patients after surgery is essential for successful recovery. However, the time that health-care professionals can spend with their patients postoperatively has been reduced because of efficiency-driven, shortened hospital stays. We evaluated the effect of a personalised e-health-care programme on return to normal activities after surgery. A multicentre, single-blind, randomised controlled trial was done at seven teaching hospitals in the Netherlands. Patients aged 18–75 years who were scheduled for laparoscopic cholecystectomy, inguinal hernia surgery, or laparoscopic adnexal surgery for a benign indication were recruited. An independent researcher randomly allocated participants to either the intervention or control group using computer-based randomisation lists, with stratification by sex, type of surgery, and hospital. Participants in the intervention group had access to a perioperative, personalised, e-health-care programme, which managed recovery expectations and provided postoperative guidance tailored to the patient. The control group received usual care and access to a placebo website containing standard general recovery advice. Participants were unaware of the study hypothesis and were asked to complete questionnaires at five timepoints during the 6-month period after surgery. The primary outcome was time between surgery and return to normal activities, measured using personalised patient-reported outcome measures. Intention-to-treat and per-protocol analyses were done. This trial is registered in the Netherlands National Trial Register, number NTR4699. Between Aug 24, 2015, and Aug 12, 2016, 344 participants were enrolled and randomly allocated to either the intervention (n=173) or control (n=171) group. 14 participants (4%) were lost to follow-up, with 330 participants included in the primary outcome analysis. Median time until return to normal activities was 21 days (95% CI 17–25) in the intervention group and 26 days (20–32) in the control group (hazard ratio 1·38, 95% CI 1·09–1·73; p=0·007). Complications did not differ between groups. A personalised e-health intervention after abdominal surgery speeds up the return to normal activities compared with usual care. Implementation of this e-health programme is recommended in patients undergoing intermediate-grade abdominal, gynaecological, or general surgical procedures. ZonMw.