Evaluation of home-delivered live-voice auditory training for adult hearing aid users involving their communication partners: a randomised controlled trial.

OBJECTIVE: To examine the benefits of home-delivered auditory training for adult hearing aid users using live-voice conversations in the presence of a single-talker distractor (experimental group) or in quiet (active-control group). DESIGN: Randomised controlled trial. The experimental group held conversations with their nominated communication partner in the presence of a single-talker distractor set to a challenging level, 30 min/day, 5 days/week over 4 weeks. The active-control group held comparable conversations in quiet. Behavioural outcome measures of speech-in-noise perception, cognition and self-reported hearing difficulties were assessed pre- and post-training. Participant feedback was obtained. STUDY SAMPLE: Thirty-nine hearing aid users (32 males, 7 females, mean age = 73.02 years, SD = 4.71 years) and their communication partners. RESULTS: The experimental group significantly improved and outperformed the active-control group for words-in-noise perception. Both groups achieved improvements in self-reported hearing difficulty while only the experimental group improved on dual-task. Subjectively, both groups found live-voice conversations beneficial and reported increased concentration and listening skills. CONCLUSIONS: Home-delivered live-voice auditory training with communication partners shows potential to improve outcomes for adult hearing aid users, regardless of the presence or absence of a competing speech distractor. Further research is required to assess mechanisms of benefit and distractor effects within carefully controlled experiments.

Patient-reported outcome measurement in community-acquired pneumonia: feasibility of routine application in an elderly hospitalized population.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide, but few studies have evaluated the feasibility of routine patient-reported outcome measures (PROMs) in this illness. This study investigates the feasibility and limitations of three credible PROM instruments in a representative hospitalized cohort to identify potential barriers to routine application. METHODS: A sample of multimorbid hospitalized subjects meeting a standardized CAP definition was recruited. Demographic and clinical data of those able and unable to participate in PROM assessment were compared. The EQ-5D-5L, CAP-Sym 18 Questionnaire, and Late-Life Function and Disability Instrument (LLFDI) were administered (via face-to-face interview) at admission and discharge and (via phone interview or mail) at 30 and 90 days post-discharge. Feasibility measures included the proportion of individuals able to participate in assessment, attrition rates, data completeness, and instrument completion times. Scores at admission and 30 days post-discharge were examined for association with age. RESULTS: Of 82 subjects screened, 44 (54%) participated. Cognitive impairment (n = 12, 15%) commonly precluded participation. Seventeen (39%) participants were lost to follow-up by 90 days. Missing data at item level was negligible for all instruments, regardless of the mode of completion. Completion of the three instruments collectively in a face-to-face interview took a median of 17 min (IQ range 13-21) per participant. The burden of reported symptoms at admission was higher for younger participants aged 18-74 years (mean (standard deviation)) CAP-Sym 18 score at admission 34.2 (18.6) vs. 19.0 (11.3) for those aged ≥ 75 years. CONCLUSIONS: Routine application of PROMs can provide valuable information relating to multiple aspects of clinical recovery for individuals hospitalized with CAP. However, heterogeneous demographic characteristics and complex underlying health status introduce challenges to feasibility and interpretability of these instruments in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02835040.

Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: A Stepped-Wedge Randomized Clinical Trial.

IMPORTANCE: Community-acquired pneumonia remains a leading cause of hospitalization, mortality, and health care costs worldwide. Randomized clinical trials support the use of adjunctive corticosteroids, early progressive mobilization, antibiotic switching rules, and dietary interventions in improving outcomes. However, it is uncertain whether implementing these interventions will translate into effectiveness under routine health care conditions. OBJECTIVE: To evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, stepped-wedge, cluster-randomized clinical trial with 90-day follow-up was conducted between August 1, 2016, and October 29, 2017, in the general internal medicine service at 2 tertiary hospitals in Melbourne, Australia, among a consecutive sample of patients with community-acquired pneumonia. The primary analysis and preparation of results took place between May 14 and November 25, 2018. INTERVENTIONS: Treating clinical teams were advised to prescribe prednisolone acetate, 50 mg/d, for 7 days (in the absence of any contraindication) and de-escalate from parenteral to oral antibiotics according to standardized criteria. Algorithm-guided early mobilization and malnutrition screening and treatment were also implemented. MAIN OUTCOMES AND MEASURES: Hospital length of stay, mortality, readmission, and intervention-associated adverse events (eg, gastrointestinal bleeding and hyperglycemia). RESULTS: A total of 917 patients were screened, and 816 (351 women and 465 men; mean [SD] age, 76 [13] years) were included in the intention-to-treat analysis, with 401 patients receiving the intervention and 415 patients in the control group. An unadjusted geometric mean ratio of 0.95 (95% CI, 0.78-1.16) was observed for the difference in length of stay (days) between the intervention and control groups. Similarly, no significant differences were observed for the secondary outcomes of mortality and readmission, and the results remained unchanged after further adjustment for sex and age. The study reported higher proportions of gastrointestinal bleeding in the intervention group (9 [2.2%]) compared with the controls (3 [0.7%]), with an unadjusted estimated difference in mean proportions of 0.008 (95% CI, 0.005-0.010). CONCLUSIONS AND RELEVANCE: This bundled intervention including adjunctive corticosteroids demonstrated no evidence of effectiveness and resulted in a higher incidence of gastrointestinal bleeding. Efficacy of individual interventions demonstrated in clinical trials may not necessarily translate into effectiveness when implemented in combination and may even result in net harm. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02835040.

Multimorbidity rehabilitation versus disease-specific rehabilitation in people with chronic diseases: a pilot randomized controlled trial.

BACKGROUND: Multimorbidity (the co-existence of two or more chronic conditions in an individual) is a growing healthcare burden internationally; however, healthcare and disease management, including rehabilitation, is often delivered in single-disease siloes. The aims of this study were to (1) evaluate the safety and feasibility of multimorbidity rehabilitation compared to a disease-specific rehabilitation program in people with multimorbidity and (2) gather preliminary data regarding clinical outcomes and resource utilization to inform the design of future trials. METHODS: A pilot feasibility randomized controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Seventeen individuals with a chronic disease eligible for disease-specific rehabilitation (pulmonary, cardiac, heart failure rehabilitation) and at least one other chronic condition were recruited. The intervention group attended multimorbidity exercise rehabilitation and the control group attended disease-specific exercise rehabilitation. Participants attended twice-weekly exercise training and weekly education for 8 weeks. Feasibility measures included numbers screened, recruited, and completed. Other outcome measures were change in functional exercise capacity (6-minute walk test (6MWT)), health-related quality of life (HRQoL), activities of daily living (ADL), and resource utilization. RESULTS: Sixty-one people were screened to recruit seventeen participants (nine intervention, eight control); one withdrew prior to rehabilitation. Participants were mostly male (63%) with a mean (SD) age of 69 (9) years and body mass index of 29 (6). The intervention group attended a mean (SD) of 12 (6) sessions, and the control group attended 11 (4) sessions. One participant (6%) withdrew after commencing; two (12%) were lost to follow-up. The intervention group 6MWT distance increased by mean (SD) of 22 (45) meters (95% confidence interval - 16 to 60) compared to 22 (57) meters (95% confidence interval - 69 to 114) (control). CONCLUSIONS: It was feasible to recruit people with multimorbidity to a randomized controlled trial of rehabilitation. A large RCT with the power to make significant conclusions about the impact on the primary and secondary outcomes is now required. TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Registry available at http://www.anzctr.org.au ACTRN12614001186640. Registered 12/11/2014.

A rehabilitation programme for people with multimorbidity versus usual care: A pilot randomized controlled trial.

BACKGROUND: Multimorbidity, the coexistence of two or more chronic conditions, is common in clinical practice. Rehabilitation for people with multimorbidity may provide access to a rehabilitation programme that can address common symptoms and risk factors for multiple chronic diseases. OBJECTIVE: The aims of this study were to (1) evaluate the feasibility of a rehabilitation programme compared to usual medical care (UMC) in people with multimorbidity and (2) gather preliminary data regarding clinical effects and impact on functional exercise capacity, activities of daily living, health-related quality of life and resource utilization. DESIGN: A pilot feasibility parallel randomized controlled trial was undertaken. Adults with multimorbidity were randomized to the rehabilitation programme (intervention) or UMC (control). The duration of the rehabilitation programme was 8 weeks and comprised exercise (1 h, twice weekly) and education (1 h, once weekly). The UMC group did not participate in a structured exercise programme. RESULTS: One hundred people were screened to recruit 16 participants, with a 71% completion rate for the intervention group. The rehabilitation group achieved a mean (standard deviation) improvement in 6-minute walk distance of 44 (41) m and the UMC group of 23 (29) m. CONCLUSIONS: This study suggests that it would be feasible to conduct a larger randomized control trial investigating a rehabilitation programme for people with multimorbidity. Low uptake of the study suggests that refinement of the inclusion criteria, recruitment sources and programme model will be needed to achieve the number of participants required.

Inducible heat shock protein 70 enhances HPV31 viral genome replication and virion production during the differentiation-dependent life cycle in human keratinocytes.

Increasing data indicate heat shock proteins (HSPs) including inducible HSP70 (HSP70i) are involved in the replicative cycles of various viruses including adenoviruses (Ads), polyomaviruses (PyVs), and some RNA viruses. Cell-free system studies implicate HSP70i in human papillomavirus type 11 (HPV11) genome replication with E1 and E2 proteins, and there is evidence that HSP70 is involved in capsid assembly and disassembly for PyVs and HPVs. HSP70 expression is increased in HPV16 E6/E7 gene transduced human primary keratinocytes, and frequently detected in early stage uterine cervical cancer at levels in conjunction with lesion severity. In this study we carry out analyses in the natural host epithelial tissues to assess the role of inducible HSP70 (HSP70i) in the HPV infectious life cycle. For these studies we used the organotypic (raft) culture system to recapitulate the full viral life cycle of the high-risk HPV31. Upon heat shock of HPV31-infected organotypic tissues, we find high and sustained expression of HSP70i coincident with enhanced HPV genome replication and virion production. Whereas there is no clear effect on L1 expression levels, we find HSP70i and L1 interact and HSP70i colocalizes with and enhances the nuclear localization of L1 in differentiated cells. Ad-mediated gene transfer was used to study the effects of HSP70i in naturally HPV-infected differentiating tissues and showed results similar to those in heat shocked rafts. These results indicate that increased HSP70i augments late activities in the viral life cycle. We conclude that HSP70i contributes directly to HPV replicative viral activities and the production of infectious virions.

A recombinant adenovirus expressing wild-type Bax induces apoptosis in prostate cancer cells independently of their Bcl-2 status and androgen sensitivity.

Using a binary co-transfection strategy of Ad/GT Bax and Ad/PGK-GV16, we have succeeded in inducing overexpression of Bax protein in three prostate cell lines (androgen-insensitive DU145 and PC3, and androgen-sensitive LNCaP). The expression of Bax protein by this system was sufficient to induce all three prostate lines to undergo apoptosis. The fact that DU145 cells which have a p53 mutation and are deficient in Bax, responded to this treatment, suggests that this effect is independent of these pathways. Initiation of the cleavage of Caspase-3 (CPP32/Yama/apopain) and PARP (poly (ADP-ribose) polymerase) by the introduction of Bax were confirmed by western blot analysis. Bcl-2 expression is relevant in the progression of prostate cancer and contributes to an androgen, apoptotic-resistant phenotype in the advanced stages. We examined stable Bcl-2 overexpressing DU145, PC3 and LNCaP cell lines as models of advanced prostate cancer. The adenoviral co-transfection system induced Bax protein expression and apoptosis even in these Bcl-2 transfected cell lines. Taken together, our results suggest that this Bax expression system might represent a useful gene therapy strategy when applied to the treatment of prostate cancer and its efficacy would be independent of the Bcl-2 status and androgen sensitivity of these cancers.