A randomised controlled trial of a code-word enuresis alarm

Objective: To compare a novel code-word alarm with a commercially available wireless alarm for treating enuresis Design: Randomised controlled trial with blinding of study personnel and outcome assessors Setting: A tertiary paediatric centre Patients: Children aged six to eighteen with at least three wet nights per week in the previous 6 months referred by doctors Outcomes: Primary outcome: the proportion who achieved a full response (14 consecutive dry nights) by 16 weeks. Secondary outcomes: change in frequency of wetting, duration of alarm training, percentage of wet nights that the child woke to the alarm, adherence to treatment, adverse events and satisfaction with treatment. Results: Of the 353 participants, 176 were assigned to the code-word alarm and 177 to control. At 16 weeks, 54% (95% CI, 47% to 61%) in the experimental group and 47% (95% CI, 40% to 55%) in the control group had achieved a full response (p=0.22), with 74% and 66% respectively attaining a 50% or more reduction in wetting frequency (p=0.14). The experimental group woke more often than the control group (median percentage of waking 88% versus 77%, p=0.003) and had greater reduction in wet nights (median reduction 10 versus 9 nights per fortnight). Fewer in the experimental group discontinued therapy before achieving a full response (27% versus 37% discontinued, p=0.04). There were no significant differences in relapse rates at 6 months, adverse events or satisfaction between the two alarms. In a post hoc subgroup analysis of children with monosymptomatic enuresis, more in the experimental group achieved a full response (66% versus 52%, p=0.047), with higher median percentage of waking (89% versus 79%, p=0.006) and greater reduction in wet nights (median reduction 12 versus 9 nights per fortnight). Conclusions: Although the code-word alarm increased waking, no difference in full response rates was demonstrated between the two alarms.The study was funded by an NHMRC Project Grant (570761). AT was supported by an NHMRC Program Grant (633003) to the Screening & Test Evaluation Program

Effects of trace levels of nitrous oxide on psychomotor performance.

Twenty-four male student volunteers were exposed to 50 ppm of nitrous oxide or air in an exposure chamber for 4 h in two experimental sessions. The subjects completed a battery of psychomotor tests during the final 40 min of the exposure sessions. Nitrous oxide, at this low concentration, did not produce any statistically significant changes in performance

Fracturing ranked surfaces

Discretized landscapes can be mapped onto ranked surfaces, where every element (site or bond) has a unique rank associated with its corresponding relative height. By sequentially allocating these elements according to their ranks and systematically preventing the occupation of bridges, namely elements that, if occupied, would provide global connectivity, we disclose that bridges hide a new tricritical point at an occupation fraction $p=p_{c}$, where $p_{c}$ is the percolation threshold of random percolation. For any value of $p$ in the interval $p_{c}< p \leq 1$, our results show that the set of bridges has a fractal dimension $d_{BB} \approx 1.22$ in two dimensions. In the limit $p \rightarrow 1$, a self-similar fracture is revealed as a singly connected line that divides the system in two domains. We then unveil how several seemingly unrelated physical models tumble into the same universality class and also present results for higher dimensions

A Randomised Controlled Trial of Two Infusion Rates to Decrease Reactions to Antivenom

Background: Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions. Methods and findings: This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell’s viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20–25 min) versus 120 min (IQR:75–120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:−10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94). Conclusions: A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background&lt;p&gt;&lt;/p&gt; Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.&lt;p&gt;&lt;/p&gt; Results&lt;p&gt;&lt;/p&gt; Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Mechanisms of micro-terror? Early career CMS academics’ experiences of ‘targets and terror’ in contemporary business schools

In this article, we apply the concept of ‘targets and terror’, previously used in the healthcare sector, to the audit culture within business schools. We explore to what extent terror, or the inculcation of fear through processes of domination, is identifiable in the micro-level experiences of early career academics. Drawing on an international study of 38 Critical Management Studies early career academics from 15 countries, we develop a theoretical framework combining Bourdieu’s modes of domination and Meyerson and Scully’s Tempered Radicalism, which helps us identify top-down and horizontal processes of micro-terror and bottom-up processes of micro-terrorism, specifically self-terrorisation and counter-terrorisation. In extending the study of ‘targets and terror’ cultures to contemporary business schools, we develop a clearer understanding of how domination plays out in the everyday processes of management and self-management. From Bourdieu’s modes of domination, we discern a dark picture of institutional and interpersonal overt and symbolic violence in the name of target achievement. The Tempered Radicalism lens helps us to understand early career academic challenges that can lead to self-terrorisation but also brings possible ways forward, showing early career academics how to resist mechanisms of micro-terror through their own small acts of counter-terrorisation, providing some hope specifically as the basis for collective resistance

Difficulty Accessing Syringes Mediates the Relationship Between Methamphetamine Use and Syringe Sharing Among Young Injection Drug Users

Injection drug users (IDU) who use methamphetamine (MA) are at an increased risk of HIV infection due to engagement in injection-related risk behavior including syringe sharing. In this cohort study of young IDU aged 18-30, we investigated the relationship between injection MA use and syringe sharing, and whether difficulty accessing sterile syringes mediated this association. Behavioral questionnaires were completed by 384 IDU in Vancouver, Canada between October 2005 and May 2008. Generalized estimating equations were used to estimate direct and indirect effects. The median age of participants was 24 (IQR: 22–27) and 214 (55.7%) were male. Injecting MA was independently associated with syringe sharing. Mediation analyses revealed that difficulty accessing sterile syringes partially mediated the association between injecting MA and syringe sharing. Interventions to reduce syringe sharing among young methamphetamine injectors must address social and structural barriers to accessing HIV prevention programs

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use