A comparison of intermediate and long-acting insulins in people with type 2 diabetes starting insulin: an observational database study

AimsInsulin is normally added to oral glucose-lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal. We evaluated outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins.MethodsInsulin-naïve people with type 2 diabetes (n = 8009), ≥ 35 years old, HbA(1c) ≥ 6.5% and begun on NPH (n = 1463), detemir (n = 357), glargine (n = 2197) or premix (n = 3992), were identified from a UK database of primary care records (The Health Improvement Network). Unadjusted and multivariate-adjusted analyses were conducted, with persistence of insulin therapy assessed by survival analysis.ResultsIn the study population (n = 4337), baseline HbA(1c) was 9.5 ± 1.6%, falling to 8.4 ± 1.5% over 12 months (change -1.1 ± 1.8%, p Discussion and conclusionIn routine clinical practice, people with type 2 diabetes commenced on NPH experienced a modest disadvantage in glycaemic control after 12 months compared with other insulins. When comparing the insulins, glargine achieved best HbA(1c) reduction, while premix showed greatest weight gain and the highest dose requirement, but had the best persistence of therapy.J. Gordon, R. D. Pockett, A. P. Tetlow, P. McEwan, P. D. Hom

Right ventricular dysfunction in children supported with pulsatile ventricular assist devices

ObjectivesTo describe the incidence and severity of right ventricular dysfunction (RVD) in pediatric ventricular assist device (VAD) recipients and to identify the preoperative characteristics associated with RVD and their effect on outcomes.MethodsChildren bridged to transplantation from 2004 to 2011 were included. RVD was defined as the use of a left VAD (LVAD) with an elevated central venous pressure of >16 mm Hg with inotropic therapy and/or inhaled nitric oxide for >96 hours or biventricular assist (BiVAD).ResultsA total of 57 children (median age, 2.97 years; range 35 days to 15.8 years) were supported. Of the 57, 43 (75%) had an LVAD, and of those, 10 developed RVD. The remaining 14 (25%) required BiVAD. Thus, RVD occurred in 24 of 57 patients (42%). Preoperative variables such as younger age (P = .01), use of extracorporeal mechanical support (P = .006), and elevated urea (P = .03), creatinine (P = .02), and bilirubin (P = .001) were associated with RVD. Multiple logistic regression analysis indicated that elevated urea and extracorporeal mechanical support (odds ratio, 26.4; 95% confidence interval, 2.3-307.3; and odds ratio, 27.8; 95% confidence interval, 2.5-312.3, respectively) were risk factors for BiVAD. The patients who developed RVD on LVAD had a complicated postoperative course but excellent survival (100%), comparable to those with preserved right ventricular function (91%). The survival for those requiring BiVAD was reduced (71%).ConclusionsRVD occurred in approximately 40% of pediatric VAD recipients and affects their peri-implantation morbidity and bridging outcomes. Preoperative extracorporeal membrane oxygenation and elevated urea were risk factors for BiVAD. Additional studies of the management of RVD in children after VAD implantation are warranted

Changes in Bone Turnover Marker Levels and Clinical Outcomes in Patients With Advanced Cancer and Bone Metastases Treated With Bone Antiresorptive Agents

Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTMs) in patients with advanced cancer. We evaluated association of changes in BTMs with overall survival (OS), disease progression (DP), and disease progression in bone (DPB) in patients with advanced cancer and bone metastases following denosumab or zoledronic acid treatment. Experimental Design: This is an integrated analysis of patient-level data from three identically designed, blinded, phase III trials with patients randomized to subcutaneous denosumab or intravenous zoledronic acid. Levels of the BTMs urinary N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBSAP) measured at study entry and month 3 were analyzed. OS, DP, and DPB were compared in patients with BTMs {greater than or equal to} median vs < median based on month 3 assessments. Results: uNTx levels {greater than or equal to} the median of 10.0 nmol/mmol at month 3 were associated with significantly reduced OS compared with levels < median (HR for death 1.85, P<0.0001). sBSAP levels {greater than or equal to} median of 12.6 ng/mL were associated with significantly reduced OS compared with levels < median (HR 2.44, P<0.0001). uNTx and sBSAP levels {greater than or equal to} median at month 3 were associated with significantly greater risk of DP (HR 1.31, P<0.0001 and HR 1.71, P<0.0001, respectively) and DPB (HR 1.11, P=0.0407 and HR 1.27, P<0.0001, respectively). Conclusions: BTM levels {greater than or equal to} median after 3 months of bone antiresorptive treatment were associated with reduced OS and increased risk of DP and DPB. Assessment of uNTx and sBSAP levels after bone antiresorptive therapy may add to identification of patients at risk for worse clinical outcomes

Resource use and direct medical costs of acute respiratory illness in the UK based on linked primary and secondary care records from 2001 to 2009

BackgroundPrevious studies have shown that influenza is associated with a substantial healthcare burden in the United Kingdom (UK), but more studies are needed to evaluate the resource use and direct medical costs of influenza in primary care and secondary care.MethodsA retrospective observational database study in the UK to describe the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI), according to age, and risk status (NCT Number: 01521416). Patients with influenza, ARI or influenza-related respiratory infections during 9 consecutive pre-pandemic influenza peak seasons were identified by READ codes in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset. The study period was from 21st January 2001 to 31st March 2009.ResultsA total of 156,193 patients had ≥1 general practitioner (GP) episode of ARI, and a total of 82,204 patients received ≥1 GP prescription, at a mean of 2.5 (standard deviation [SD]: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions equated to £462,827 per year per 100,000 patients. The yearly cost of prescribed medication for ARI was £319,732, at an estimated cost of £11,596,350 per year extrapolated to the UK, with 40% attributable to antibiotics. The mean cost of hospital admissions equated to a yearly cost of £981,808 per 100,000 patients. The total mean direct medical cost of ARI over 9 influenza seasons was £21,343,445 (SD: £10,441,364), at £136.65 (SD: £66.85) per case.ConclusionsExtrapolating to the UK population, for pre-pandemic influenza seasons from 2001 to 2009, the direct medical cost of ARI equated to £86 million each year. More studies are needed to assess the costs of influenza disease to help guide public health decision-making for seasonal influenza in the UK

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Examining the effect of Libet clock stimulus parameters on temporal binding

Temporal binding refers to the subjective temporal compression between actions and their outcomes. It is widely used as an implicit measure of sense of agency, that is, the experience of controlling our actions and their consequences. One of the most common measures of temporal binding is the paradigm developed by Haggard, Clark and Kalogeras (2002) based on the Libet clock stimulus. Although widely used, it is not clear how sensitive the temporal binding effect is to the parameters of the clock stimulus. Here, we present five experiments examining the effects of clock speed, number of clock markings and length of the clock hand on binding. Our results show that the magnitude of temporal binding increases with faster clock speeds, whereas clock markings and clock hand length do not significantly influence temporal binding. We discuss the implications of these results

Algunes reflexions entorn de la conceptualització de la infància i adolescència en risc social a l'Estat espanyol

L'article realitza una aproximació a les interpretacions del concepte de risc social de la infancia per part de diversos autors d'àmbit estatal, tenint també en compte els marcs legals català i espanyol. Pretén aclarir quins són els criteris valoratius emprats, tant des de l'àmbit acadèmic com del professional, per interpretar les categoritzacions de la infància i l'adolescència en processos de dificultat i precarietat social. Des d'aquesta perspectiva, s'hi analitza l'estreta relació entre factors de risc, desemparament i marginació. S'hi rebutgen les interpretacions que responsabilitzen el propi menor de la desadaptació, i s'hi defensa la hipótesi de la necessitat d'una intervenció socioeducativa que treballi per una disminució dels factors de risc en el propi medi, mantenint el seu protagonisme en aquest procés.This article is an approach to the different acceptances of the concept social risk as well as the terms neglect and maladjustment, based on the reflections made by different authors and both statal and autonomous legal framework. It intends to clarify which are the criteria of values used in academic and professional ambits in order to understand the categoriesfound in the fields of childhood and adolescence in difficult and precarious conditions. The strong relation between risk factors, neglect and margination has been analysed from this point of view. In the same way the interpretations that hold the minor himself responsible for his maladjustment are rejected and the author defends the necessity of a socio-educational intervention, which reduces the risk factors in the child's environment, and the need of paying close attention to the child's main role in this process.El artículo realiza una aproximación a las interpretaciones del concepto de riesgo social de la infancia por parte de diversos autores de ámbito estatal, teniendo también en cuenta los marcos legales catalán y español. Pretende aclarar cuáles son los criterios valorativos utilizados, tanto desde el ámbito academico como profesional, para interpretar las categorizaciones de la infancia en procesos de dificultad y precariedad. Desde esta perspectiva, se analiza la estrecha relación entre factores de riesgo, desamparamiento y marginación. Se rechazan las interpretaciones que responsabilizan al propio menor de la desadaptación y se defiende la hipótesis de la necesidad de una intervención socioeducativa que trabaje para una disminución de los factores de riesgo en el propio medio, manteniendo su protagonismo en este proceso

Ionic-to-electronic current amplification in hybrid perovskite solar cells: ionically gated transistor-interface circuit model explains hysteresis and impedance of mixed conducting devices

Mobile ions in hybrid perovskite semiconductors introduce a new degree of freedom to electronic devices suggesting applications beyond photovoltaics. An intuitive device model describing the interplay between ionic and electronic charge transfer is needed to unlock the full potential of the technology. We describe the perovskite-contact interfaces as transistors which couple ionic charge redistribution to energetic barriers controlling electronic injection and recombination. This reveals an amplification factor between the out of phase electronic current and the ionic current. Our findings suggest a strategy to design thin film electronic components with large, tuneable, capacitor-like and inductor-like characteristics. The resulting simple equivalent circuit model, which we verified with time-dependent drift-diffusion simulations of measured impedance spectra, allows a general description and interpretation of perovskite solar cell behaviour

Behavioral states may be associated with distinct spatial patterns in electrocorticogram

To determine if behavioral states are associated with unique spatial electrocorticographic (ECoG) patterns, we obtained recordings with a microgrid electrode array applied to the cortical surface of a human subject. The array was constructed with the intent of extracting maximal spatial information by optimizing interelectrode distances. A 34-year-old patient with intractable epilepsy underwent intracranial ECoG monitoring after standard methods failed to reveal localization of seizures. During the 8-day period of invasive recording, in addition to standard clinical electrodes a square 1 × 1 cm microgrid array with 64 electrodes (1.25 mm separation) was placed on the right inferior temporal gyrus. Careful review of video recordings identified four extended naturalistic behaviors: reading, conversing on the telephone, looking at photographs, and face-to-face interactions. ECoG activity recorded with the microgrid that corresponded to these behaviors was collected and ECoG spatial patterns were analyzed. During periods of ECoG selected for analysis, no electrographic seizures or epileptiform patterns were present. Moments of maximal spatial variance are shown to cluster by behavior. Comparisons between conditions using a permutation test reveal significantly different spatial patterns for each behavior. We conclude that ECoG recordings obtained on the cortical surface with optimal high spatial frequency resolution reveal distinct local spatial patterns that reflect different behavioral states, and we predict that similar patterns will be found in many if not most cortical areas on which a microgrid is placed

The Good Behaviour Game intervention to improve behavioural and other outcomes for children aged 7-8 years: A cluster RCT

Background. Universal, school-based behaviour management interventions can produce meaningful improvements in children’s behaviour and other outcomes. However, the UK evidence base for these remains limited. Objective. The objective of this trial was to investigate the impact, value for money and longer-term outcomes of the Good Behaviour Game. Study hypotheses centred on immediate impact (hypothesis 1); subgroup effects (at-risk boys, hypothesis 2); implementation effects (dosage, hypothesis 3); maintenance/sleeper effects (12- and 24-month post-intervention follow-ups, hypothesis 4); the temporal association between mental health and academic attainment (hypothesis 5); and the health economic impact of the Good Behaviour Game (hypothesis 6). Design. This was a two-group, parallel, cluster-randomised controlled trial. Primary schools (n = 77) were randomly assigned to implement the Good Behaviour Game for 2 years or continue their usual practice, after which there was a 2-year follow-up period. Setting. The trial was set in primary schools across 23 local authorities in England. Participants. Participants were children (n = 3084) aged 7–8 years attending participating schools. Intervention. The Good Behaviour Game is a universal behaviour management intervention. Its core components are classroom rules, team membership, monitoring behaviour and positive reinforcement. It is played alongside a normal classroom activity for a set time, during which children work in teams to win the game to access the agreed rewards. The Good Behaviour Game is a manualised intervention delivered by teachers who receive initial training and ongoing coaching. Main outcome measures. The measures were conduct problems (primary outcome; teacher-rated Strengths and Difficulties Questionnaire scores); emotional symptoms (teacher-rated Strengths and Difficulties Questionnaire scores); psychological well-being, peer and social support, bullying (i.e. social acceptance) and school environment (self-report Kidscreen survey results); and school absence and exclusion from school (measured using National Pupil Database records). Measures of academic attainment (reading, standardised tests), disruptive behaviour, concentration problems and prosocial behaviour (Teacher Observation of Child Adaptation Checklist scores) were also collected during the 2-year follow-up period. Results. There was no evidence that the Good Behaviour Game improved any outcomes (hypothesis 1). The only significant subgroup moderator effect identified was contrary to expectations: at-risk boys in Good Behaviour Game schools reported higher rates of bullying (hypothesis 2). The moderating effect of the amount of time spent playing the Good Behaviour Game was unclear; in the context of both moderate (≥ 1030 minutes over 2 years) and high (≥ 1348 minutes over 2 years) intervention compliance, there were significant reductions in children’s psychological well-being, but also significant reductions in their school absence (hypothesis 3). The only medium-term intervention effect was for peer and social support at 24 months, but this was in a negative direction (hypothesis 4). After disaggregating within- and between-individual effects, we found no temporal within-individual associations between children’s mental health and their academic attainment (hypothesis 5). Last, our cost–consequences analysis indicated that the Good Behaviour Game does not provide value for money (hypothesis 6). Limitations. Limitations included the post-test-only design for several secondary outcomes; suboptimal implementation dosage (mitigated by complier-average causal effect estimation); and moderate child-level attrition (18.5% for the primary outcome analysis), particularly in the post-trial follow-up period (mitigated by the use of full information maximum likelihood procedures). Future work. Questions remain regarding programme differentiation (e.g. how distinct is the Good Behaviour Game from existing behaviour management practices, and does this makes a difference in terms of its impact?) and if the Good Behaviour Game is impactful when combined with a complementary preventative intervention (as has been the case in several earlier trials). Conclusion. The Good Behaviour Game cannot be recommended based on the findings reported here