With a little help from my friends: Developing an assisted automated peritoneal dialysis program in Western Australia

Background: Nurse-assisted automated peritoneal dialysis (AAPD) offers a model of care that has been successfully used in frail dialysis populations internationally. AAPD offers cost savings over hospitalisation on peritoneal dialysis (PD) or in-centre haemodialysis (HD). Method: A pilot AAPD model of care was developed in Western Australia (WA). Patient evaluation was measured utilising a perceptions of dialysis survey, clinical events, hospitalisation and peritonitis rates, Charlson Comorbidity Index (CCI), KDQoL-SF 36 and a survey. Staff opinions and perceived competency were measured by an online survey. Economic analysis was undertaken. Results: A successful collaborative model was developed. 40 staff were trained and competency significantly improved during program delivery (p < 0.0001). 15 patients with an average CCI score of 8.7 used the service for 18 periods of care over 18 months (mean 33 days SD 47). Two non-renal cause deaths and two episodes of peritonitis occurred. Patient opinions were extremely positive. Cost savings were estimated at $620,000. Conclusion: In WA, an AAPD pilot program has been successfully developed and delivered. A sustainable model has overcome initial hurdles. Staff have gained new skills and delivered effective care, demonstrated by high patient acceptance. The program was cost-effective compared to staying in hospital or transferring to HD

A kinetic and theoretical study of the borate catalysed reactions of hydrogen peroxide: the role of dioxaborirane as the catalytic intermediate for a wide range of substrates

Our recent work has provided new insights into the equilibria and species that exist in aqueous solution at different pHs for the boric acid – hydrogen peroxide system, and the role of these species in oxidation reactions. Most recently, (M. C. Durrant, D. M. Davies and M. E. Deary, Org. Biomol. Chem., 2011, 9,7249–7254), we have produced strong theoretical and experimental evidence for the existence of a previously unreported monocyclic three membered peroxide species, dioxaborirane, that is the likely catalytic species in borate mediated electrophilic reactions of hydrogen peroxide in alkaline solution. In the present paper, we extend our study of the borate–peroxide system to look at a wide range of substrates that include substituted dimethyl anilines, methyl-p-tolyl sulfoxide, halides, hydrogen sulfide anion, thiosulfate ,thiocyanate, and hydrazine. The unusual selectivity–reactivity pattern of borate catalysed reactions compared with hydrogen peroxide and inorganic or organic peracids previously observed for theorganic sulfides (D. M. Davies, M. E. Deary, K. Quill and R. A. Smith, Chem.–Eur. J., 2005, 11, 3552–3558) is also seen with substituted dimethyl aniline nucleophiles. This provides evidence that the pattern is not due to any latent electrophilic tendency of the organic sulfides and further supports dioxaborirane being the likely reactive intermediate, thus broadening the applicability of this catalytic system. Moreover, density functional theory calculations on our proposed mechanism involving dioxaborirane are consistent with the experimental results for these substrates. Results obtained at high concentrations of both borate and hydrogen peroxide require the inclusion the diperoxodiborate dianion in the kinetic analysis .A scheme detailing our current understanding of the borate–peroxide system is presented

Comparing the clinical effectiveness of different new-born hearing screening strategies. A decision analysis

BACKGROUND: Children with congenital hearing impairment benefit from early detection and treatment. At present, no model exists which explicitly quantifies the effectiveness of universal newborn hearing screening (UNHS) versus other programme alternatives in terms of early diagnosis. It has yet to be considered whether early diagnosis (within the first few months) of hearing impairment is of importance with regard to the further development of the child compared with effects resulting from a later diagnosis. The objective was to systematically compare two screening strategies for the early detection of new-born hearing disorders, UNHS and risk factor screening, with no systematic screening regarding their influence on early diagnosis. METHODS: Design: Clinical effectiveness analysis using a Markov Model. Data Sources: Systematic literature review, empirical data survey, and expert opinion. Target Population: All newborn babies. Time scale: 6, 12 and 120 months. Perspective: Health care system. Compared Strategies: UNHS, Risk factor screening (RS), no systematic screening (NS). Outcome Measures: Quality weighted detected child months (QCM). RESULTS: UNHS detected 644 QCM up until the age of 6 months (72,2%). RS detected 393 child months (44,1%) and no systematic screening 152 child months (17,0%). UNHS detected 74,3% and 86,7% weighted child months at 12 and 120 months, RS 48,4% and 73,3%, NS 23,7% and 60,6%. At the age of 6 months UNHS identified approximately 75% of all children born with hearing impairment, RS 50% and NS 25%. At the time of screening UNHS marked 10% of screened healthy children for further testing (false positives), RS 2%. UNHS demonstrated higher effectiveness even under a wide range of relevant parameters. The model was insensitive to test parameters within the assumed range but results varied along the prevalence of hearing impairment. CONCLUSION: We have shown that UNHS is able to detect hearing impairment at an earlier age and more accurately than selective RS. Further research should be carried out to establish the effects of hearing loss on the quality of life of an individual, its influence on school performance and career achievement and the differences made by early fitting of a hearing aid on these factors

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.

Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new N-ethyl-N-nitrosurea (ENU)-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, whereas homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, Ocm, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric P-value analysis showed that hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally

Independent Validation of an Existing Model Enables Prediction of Hearing Loss after Childhood Bacterial Meningitis

Objective: This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice. Study design: 116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values. Results: Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort. Conclusions: Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing

The p.V37I Exclusive Genotype Of GJB2: A Genetic Risk-Indicator of Postnatal Permanent Childhood Hearing Impairment

Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%–0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10−10; OR 62.92, 95% CI 21.27–186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI

Opening Address of the Antiquarian Section at the Cambridge Meeting

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