Improving quality of life in the elderly: hearing loss treatment with cochlear implants.

BACKGROUND: Hearing loss impacts health-related quality of life and general well-being and was identified in a Lancet report as one of the largest potentially modifiable factors for the prevention of age-related dementia. There is a lack of robust data on how cochlear implant treatment in the elderly impacts quality of life. The primary objective was to measure the change in health utility following cochlear implantation in individuals aged ≥ 60 years. METHODS: This study uniquely prospectively recruited a large multinational sample of 100 older adults (mean age 71.7 (SD7.6) range 60-91 years) with severe to profound hearing loss. In a repeated-measures design, pre and post implant outcome measures were analysed using mixed-effect models. Health utility was assessed with the Health Utilities Index Mark III (HUI3). Subjects were divided into groups of 60-64, 65-74 and 75 + years. RESULTS: At 18 months post implant, the mean HUI3 score improved by 0.13 (95%CI: 0.07-0.18 p < 0.001). There was no statistically significant difference in the HUI3 between age groups (F[2,9228] = 0.53, p = 0.59). The De Jong Loneliness scale reduced by an average of 0.61 (95%CI: 0.25-0.97 p < 0.014) and the Lawton Instrumental Activities of Daily Living Scale improved on average (1.25, 95%CI: 0.85-1.65 p < 0.001). Hearing Handicap Inventory for the Elderly Screening reduced by an average of 8.7 (95%CI: 6.7-10.8, p < 0.001) from a significant to mild-moderate hearing handicap. Age was not a statistically significant factor for any of the other measures (p > 0.20). At baseline 90% of participants had no or mild depression and there was no change in mean depression scores after implant. Categories of Auditory perception scale showed that all subjects achieved a level of speech sound discrimination without lip reading post implantation (level 4) and at least 50% could use the telephone with a known speaker. CONCLUSIONS: Better hearing improved individuals' quality of life, ability to communicate verbally and their ability to function independently. They felt less lonely and less handicapped by their hearing loss. Benefits were independent of age group. Cochlear implants should be considered as a routine treatment option for those over 60 years with bilateral severe to profound hearing loss. TRIAL REGISTRATION: ClinicalTrials.gov ( http://www. CLINICALTRIALS: gov/ ), 7 March 2017, NCT03072862.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis.

OBJECTIVE: Exercise training has been shown to have beneficial effects on liver function in adults overweight or with fatty liver disease. To establish which exercise programme characteristics were likely to elicit optimal improvements. DESIGN: Systematic review and meta-analysis of randomised, controlled trials. DATA SOURCES: PubMed, CINAHL and Cochrane controlled trials registry searched (1966 to 2 October 2015). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Exercise intervention, with or without dietary intervention, versus usual care in adults undertaking, exercise training, who were overweight, obese or exhibited fatty liver disease (non-alcoholic fatty liver disease or non-alcoholic steatohepatitis). RESULTS: We included 21 randomised controlled trials, totalling 1530 participants. Exercise intervention studies with total exercise programme workload >10 000 kcal produced significant improvements in intrahepatic fat, -3.46% (95% CI -5.20% to -1.73%), p<0.0001, I2=73%; effect size (standardised mean difference, SMD) -1.77 (-3.11 to -0.42), p=0.01, I2=77%. When data from only exercise studies were pooled, there was a reduction in fasting free fatty acids (FFAs) -74.15 µmol/L (95% CI -118.47 to -29.84), p=0.001, I2=67% with a large effect size (SMD) -0.94 (-1.36 to -0.52), p<0.0001, I2=0%. When data from only exercise studies were pooled, there was a significant reduction in insulin MD -1.88 UL (95% CI -3.43 to -0.34), p=0.02, I2=31%. The liver enzymes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase, were not significantly altered with exercise. CONCLUSIONS: Exercise training reduces intrahepatic fat and FFAs while increasing cardiorespiratory fitness. An aggregate exercise programme energy expenditure (>10 000 kcal) may be required to promote reductions in intrahepatic fat.

Longitudinal recovery following distal radial fractures managed with volar plate fixation.

AIMS: To synthesise the literature and perform a meta-analysis detailing the longitudinal recovery in the first two years following a distal radius fracture (DRF) managed with volar plate fixation. MATERIALS AND METHODS: Three databases were searched to identify relevant articles. Following eligibility screening and quality assessment, data were extracted and outcomes were assimilated at the post-operative time points of interest. A state-of-the-art longitudinal mixed-effects meta-analysis model was employed to analyse the data. RESULTS: The search identified 5698 articles, of which 46 study reports met the selection criteria. High levels of disability and impairment were reported in the immediate post-operative period with subsequently a rapid initial improvement followed by more gradual improvement for up to one year. The results highlight that the period associated with the greatest physical recovery is in the first three months and suggest that the endpoint of treatment outcomes is best measured at one year post-surgery. CONCLUSION: Clinically meaningful improvements in outcomes can be expected for 12 months, after which progress plateaus and reaches normal values. This paper adopted a novel approach to meta-analyses in that the research question was of a longitudinal nature, which required a unique method of statistical analysis. Cite this article: Bone Joint J 2017;99-B:1665-76.

Reliability of the direct observation of procedural skills assessment tool for ultrasound-guided regional anaesthesia.

The Direct Observation of Procedural Skills (DOPS) form is used as a workplace-based assessment tool in the current Australian and New Zealand College of Anaesthetists curriculum. The objective of this study was to evaluate the reliability of DOPS when used to score trainees performing ultrasound-guided regional anaesthesia. Reliability of an assessment tool is defined as the reproducibility of scores given by different assessors viewing the same trainee. Forty-nine anaesthetists were recruited to score two scripted videos of trainees performing a popliteal sciatic nerve block and an axillary brachial plexus block. Reliability, as measured by intraclass correlation coefficients, was -0.01 to 0.43 for the individual items in DOPS, and 0.15 for the 'Overall Performance for this Procedure' item. Assessors demonstrated consistency of scoring within DOPS, with significant correlation of sum of individual item scores with the 'Overall Performance for this Procedure' item (r=0.78 to 0.80, P<0.001), and with yes versus no responses to the 'Was the procedure completed satisfactorily?' item (W=24, P=0.0004, Video 1, and W=65, P=0.003, Video 2). While DOPS demonstrated a good degree of internal consistency in this setting, inter-rater reliability did not reach levels generally recommended for formative assessment tools. Feasibility of the form could be improved by removing the 'Was the procedure completed satisfactorily?' item without loss of information.

Influence of Field Position on Rugby League Players Requiring Shoulder Reconstruction.

A consecutive series of patients sustaining their index anterior instability while playing Rugby League and requiring shoulder reconstruction was retrospectively reviewed and evaluated. The details of their on-field position and hand dominance at time of injury, the side of injury, and mechanism of injury were collated and statistically analyzed. A total of 173 Bankart repairs were performed on 132 patients, and 102 players had one injury while 30 had 2 or more injuries. Players are more likely to injure their non-dominant side (P=0.009) in the first-time injury. Whereas second and subsequent injuries were not associated with a particular side (P=0.81). Applying a Bonferroni correction to the chi-squared goodness-of-fit test of position at time of injury revealed players on the wing had a significantly lower frequency of injury (P<0.001), whereas the full back had a significantly higher frequency of injury (P<0.001). 30 players sustained 69 re-dislocations with the lock and fullback positions incurring significantly more re-injuries and the wing position fewer re-injuries than expected (P<0.006). Understanding which player positions on the rugby league field are more likely to sustain an anterior instability will assist medical and support staff to optimize the pre-season conditioning and post surgical rehabilitation of players.

Design and validation of the Regional Anaesthesia Procedural Skills Assessment Tool.

The aim of this study was to create and evaluate the validity, reliability and feasibility of the Regional Anaesthesia Procedural Skills tool, designed for the assessment of all peripheral and neuraxial blocks using all nerve localisation techniques. The first phase was construction of a 25-item checklist by five regional anaesthesia experts using a Delphi process. This checklist was combined with a global rating scale to create the tool. In the second phase, initial validation by 10 independent anaesthetists using a test-retest methodology was successful (Cohen kappa ≥ 0.70 for inter-rater agreement, scores between test to retest, paired t-test, p > 0.12). In the third phase, 70 clinical videos of trainees were scored by three blinded international assessors. The RAPS tool exhibited face validity (p < 0.026), construct validity (p < 0.001), feasibility (mean time to score < 3.9 min), and overall reliability (intraclass correlation coefficient 0.80 (95% CI 0.67-0.88)). The Regional Anaesthesia Procedural Skills tool used in this study is a valid and reliable assessment tool to score the performance of trainees for regional anaesthesia.

Epidemiology of training injuries in amateur taekwondo athletes: a retrospective cohort study.

The objectives of this study were to estimate the incidence and describe the pattern and severity of training injuries in taekwondo, and to compare pattern and severity of training injuries with competition injuries. One hundred and fifty-two active Australian amateur taekwondo athletes, aged 12 years or over, completed an online survey comprising questions on training exposure and injury history over the preceding 12 months. The main outcome measures were: overall injury incidence rate per athlete-year; training injury incidence rate per athlete-year, per 1000 athlete-training-sessions, and per 1000 athlete-hours of training; injury severity; and injury proportions by anatomical region and by type of injury. Injury incidence rates were calculated with 95% confidence intervals using standard methods, while injury proportions were compared using Fisher's exact test. The vast majority (81.5%) of taekwondo injuries in an average athlete-year occurred during training. The training injury incidence rate was estimated to be 1.6 (95% CI: 1.4, 1.9) per athlete-year, 11.8 (95% CI: 10.4, 13.4) per 1000 athlete-training-sessions, and 7.0 (95% CI: 6.1, 7.9) per 1000 athlete-hours of training. Among athletes with five or fewer injuries, the severity and injury pattern of training injuries were, by and large, the same as for competition injuries. Approximately sixty percent (60.3%) of training injuries required treatment by a health professional. Considering the burden of training injuries exceeds that of competition injuries, taekwondo governing bodies and stakeholders are encouraged to devote more efforts towards the identification of risk factors for, and prevention of, training injuries in the sport of taekwondo.

Risk factors for injury in Olympic-style competition taekwondo: a systematic review.

AIM: The aim of this review was to systematically collate and qualitatively evaluate the epidemiologic data on risk factors related to injuries in taekwondo athletes. METHODS: Electronic searches of relevant literature were carried out in the AusportMed, CINAHL, PubMed, Scopus, and SPORTDiscus databases. A study was included if: 1) it was a prospective experimental or observational investigation; 2) it contained data on Olympic-style taekwondo athletes; and 3) it contained data on risk factors for injuries. All eligible studies were assessed by two independent reviewers. RESULTS: Sixteen studies were deemed eligible for inclusion, of which a total of nine unique data sets were identified. Six potential risk factors were found to have been prospectively investigated to date, of which only three were shown to be associated with the occurrence of injury. The available data indicated that competing in heavier weight divisions was associated with increased overall injury incidence rates. In addition, adolescent athletes and athletes lacking blocking skills were both found to be associated with increased occurrence of concussion injuries. CONCLUSION: There is a paucity of identified risk factors for injury in taekwondo. Future epidemiologic research should consider a wider range of potential risk factors, in particular modifiable risk factors, and translate ascertained factors into practical preventive efforts.

Performance of clinical scoring systems in acute organophosphate poisoning.

INTRODUCTION: Clinical scoring systems are used to predict mortality rate in hospitalized patients. Their utility in organophosphate (OP) poisoning has not been well studied. METHODS: In this retrospective study of 396 patients, we evaluated the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Simplified Acute Physiology Score (SAPS) II, Mortality Prediction Model (MPM) II, and the Poisoning Severity Score (PSS). Demographic, laboratory, and survival data were recorded. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated to study the relationship between individual scores and mortality rate. RESULTS: The mean (standard deviation) age of the patients was 31.4 (12.7) years, and at admission, their pseudocholinesterase (median, interquartile) level was 317 (222-635) U/L. Mechanical ventilation was required in 65.7% of the patients and the overall mortality rate was 13.1%. The mean (95% confidence interval) scores were as follows: APACHE-II score, 16.4 (15.5-17.3); SAPS-II, 34.4 (32.5-36.2); MPM-II score, 28.6 (25.7-31.5); and PSS, 2.4 (2.3-2.5). Overall, the AUC for mortality was significantly higher for APACHE-II (0.77) and SAPS-II (0.77) than the PSS (0.67). When patients were categorized, the AUCs were better for WHO Class II (0.71-0.82) than that for Class I compounds (0.60-0.66). For individual compounds, the AUC for APACHE-II was highest in quinalphos (0.93, n = 46) and chlorpyrifos (0.86, n = 38) and lowest in monocrotophos (0.60, n = 63). AUCs for SAPS-II and MPM-II were marginally but not significantly lower than those for APACHE-II. The PSS was generally a poorer discriminator compared to the other scoring systems across all categories. CONCLUSIONS: In acute OP poisoning, the generic scoring systems APACHE-II and SAPS-II outperform the PSS. These tools may be used to predict the mortality rate in OP poisoning.

The role of extracorporeal membrane oxygenation for treatment of the adult respiratory distress syndrome: review and quantitative analysis.

The role of extracorporeal membrane oxygenation (ECMO) has not been formally validated for patients with adult respiratory distress syndrome. In anticipation of publication of the conventional ventilation versus ECMO in severe adult respiratory failure (CESAR) trial, the role of ECMO in this setting was reviewed. An electronic search for studies reporting the use of ECMO for the treatment of adult respiratory distress syndrome revealed two randomised controlled trials and three non-controlled trials. Bayesian analysis on the two randomised controlled trials produced an odds ratio mortality of 1.28 (credible interval 0.24 to 6.55) demonstrating no significant harm or benefit. Pooling was not possible for the non-controlled studies because of differing admission status and ECMO selection criteria and an inability to control for these differences in the absence of individual patient data. A large number (n =35) of case series have been published with generally more positive results. We also present a comprehensive narrative commentary on the history, current practice and future for ECMO. ECMO, as rescue therapy for adult respiratory distress syndrome, appears to be an unvalidated rescue treatment option. Analysis and review of trial data does not support its application; however the body of reported cases suggests otherwise. Until the CESAR trial provides an authoritative answer ECMO will continue to be offered on a case by case basis.

Improving the quality of patient care using reliability measures: a classification tree approach.

This paper considers the application and interpretation of new reliability measures for a classification tree-based medical risk assessment tool. Following the construction of a classification tree reliability measures may then be used to provide an estimate of the precision of the classification and the probability in each terminal node of the classification tree. Identification of unreliable nodes (those that have low precision) in this application may indicate patient groups requiring closer monitoring or scenarios in which further information about the patient is required, thereby providing medical practitioners with an avenue for more informed decision making.

Nosocomial transmission of Mycobacterium tuberculosis in a children's hospital.

An infant was admitted for evaluation of respiratory distress and tracheomalacia. After several weeks of hospitalization, both the infant and her mother were diagnosed with culture-positive pulmonary tuberculosis (TB). Sixteen pediatric patients and 293 health care workers were evaluated for exposure to Mycobacterium tuberculosis. Tuberculin skin test conversions occurred in 6.7% of patients and 1.9% of pediatric health care workers. While nosocomial transmission of TB is relatively rare in children's hospitals, this report highlights the differences between TB control efforts in pediatric vs. adult facilities, including the importance of screening the adult visitors of children admitted with suspected TB.

Confidence limits for the ratio of two rates based on likelihood scores: non-iterative method.

This paper describes a method for creating a confidence interval for the ratio of rates using the score statistic. This non-iterative and easy to apply procedure produces confidence intervals that are suitable for use with Poisson data and simulation results indicate that it is close to the nominal level for a wide range of scenarios.

Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of 2-methoxystypandrone and its analogues.

2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC(50) value of 4.6 microM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels-Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure-activity relationships of these compounds have been described.

Type IV collagen is detectable in most, but not all, basement membranes of Caenorhabditis elegans and assembles on tissues that do not express it.

Type IV collagen in Caenorhabditis elegans is produced by two essential genes, emb-9 and let-2, which encode alpha1- and alpha2-like chains, respectively. The distribution of EMB-9 and LET-2 chains has been characterized using chain-specific antisera. The chains colocalize, suggesting that they may function in a single heterotrimeric collagen molecule. Type IV collagen is detected in all basement membranes except those on the pseudocoelomic face of body wall muscle and on the regions of the hypodermis between body wall muscle quadrants, indicating that there are major structural differences between some basement membranes in C. elegans. Using lacZ/green fluorescent protein (GFP) reporter constructs, both type IV collagen genes were shown to be expressed in the same cells, primarily body wall muscles, and some somatic cells of the gonad. Although the pharynx and intestine are covered with basement membranes that contain type IV collagen, these tissues do not express either type IV collagen gene. Using an epitope-tagged emb-9 construct, we show that type IV collagen made in body wall muscle cells can assemble into the pharyngeal, intestinal, and gonadal basement membranes. Additionally, we show that expression of functional type IV collagen only in body wall muscle cells is sufficient for C. elegans to complete development and be partially fertile. Since type IV collagen secreted from muscle cells only assembles into some of the basement membranes that it has access to, there must be a mechanism regulating its assembly. We propose that interaction with a cell surface-associated molecule(s) is required to facilitate type IV collagen assembly.

Characterization of alpha1(IV) collagen mutations in Caenorhabditis elegans and the effects of alpha1 and alpha2(IV) mutations on type IV collagen distribution.

Type IV collagen is a major component of basement membranes. We have characterized 11 mutations in emb-9, the alpha1(IV) collagen gene of Caenorhabditis elegans, that result in a spectrum of phenotypes. Five are substitutions of glycines in the Gly-X-Y domain and cause semidominant, temperature-sensitive lethality at the twofold stage of embryogenesis. One is a glycine substitution that causes recessive, non-temperature-sensitive larval lethality. Three putative null alleles, two nonsense mutations and a deletion, all cause recessive, non-temperature-sensitive lethality at the threefold stage of embryogenesis. The less severe null phenotype indicates that glycine substitution containing mutant chains dominantly interfere with the function of other molecules. The emb-9 null mutants do not stain with anti-EMB-9 antisera and show intracellular accumulation of the alpha2(IV) chain, LET-2, indicating that LET-2 assembly and/or secretion requires EMB-9. Glycine substitutions in either EMB-9 or LET-2 cause intracellular accumulation of both chains. The degree of intracellular accumulation differs depending on the allele and temperature and correlates with the severity of the phenotype. Temperature sensitivity appears to result from reduced assembly/secretion of type IV collagen, not defective function in the basement membrane. Because the dominant interference of glycine substitution mutations is maximal when type IV collagen secretion is totally blocked, this interference appears to occur intracellularly, rather than in the basement membrane. We suggest that the nature of dominant interference caused by mutations in type IV collagen is different than that caused by mutations in fibrillar collagens.

Inhibition of human immunodeficiency virus integrase by bis-catechols.

The human immunodeficiency virus type 1 (HIV-1) integrase protein is required for the productive infection of T-lymphoid cells in culture (R. L. LaFemina, C. L. Schneider, H. L. Robbins, P. L. Callahan, K. LeGrow, E. Roth, W. A. Schleif, and E. A. Emini, J. Virol. 66:7414-7419, 1992). This observation suggests that chemical inhibitors of integrase may prevent the spread of HIV in infected individuals. In our search for such potential chemotherapeutic agents, we observed that beta-conidendrol inhibits both the sequence-dependent and sequence-independent endonucleolytic activities of integrase with comparable potencies in vitro (50% inhibitory concentration, 500 nM). Structurally related compounds tested for their abilities to inhibit integrase generated a limited structure-activity analysis which demonstrated that potency is associated with the bis-catechol structure: two pairs of adjacent hydroxyls on separate benzene rings. beta-Conidendrol did not inhibit several other endonucleases and/or phosphoryltransferases. Although beta-conidendrol was not effective in preventing HIV-1 infection in cell culture, the in vitro data demonstrate that it is possible to identify selective agents targeted against this essential HIV-1 function.