Effects of ZNF804A on auditory P300 response in schizophrenia

The common variant rs1344706 within the zinc-finger protein gene ZNF804A has been strongly implicated in schizophrenia (SZ) susceptibility by a series of recent genetic association studies. Although associated with a pattern of altered neural connectivity, evidence that increased risk is mediated by an effect on cognitive deficits associated with the disorder has been equivocal. This study investigated whether the same ZNF804A risk allele was associated with variation in the P300 auditory-evoked response, a cognitively relevant putative endophenotype for SZ. We compared P300 responses in carriers and noncarriers of the ZNF804A risk allele genotype groups in Irish patients and controls (n=97). P300 response was observed to vary according to genotype in this sample, such that risk allele carriers showed relatively higher P300 response compared with noncarriers. This finding accords with behavioural data reported by our group and others. It is also consistent with the idea that ZNF804A may have an impact on cortical efficiency, reflected in the higher levels of activations required to achieve comparable behavioural accuracy on the task used.     

Cerebrovascular Accident Under Anesthesia During Dental Surgery

Stroke, or cerebrovascular accident (CVA), is a medical emergency that may lead to permanent neurological damage, complications, and death. The rapid loss of brain function due to disruption of the blood supply to the brain is caused by blockage (thrombosis, arterial embolism) or hemorrhage. The incidence of CVA during anesthesia for noncardiac nonvascular surgery is as high as 1% depending on risk factors. Comprehensive preoperative assessment and good perioperative management may prevent a CVA. However, should an ischemic event occur, appropriate and rapid management is necessary to minimize the deleterious effects caused to the patient. This case report describes a patient who had an ischemic CVA while under general anesthesia for dental alveolar surgery and discusses the anesthesia management.Key Words: General anesthesia, Cerebrovascular event, Complication, Dentistry.Central nervous system infarction occurs over a clinical spectrum.¹ A cerebrovascular accident (CVA), or stroke, is a sudden interruption in the blood supply to the brain, accompanied by overt signs.¹ Most strokes (85%) are caused by an abrupt occlusion of a cerebral artery leading to loss of adequate blood supply to a specific area of the brain (ischemic stroke).² Ischemic strokes are either thrombotic or embolic. A thrombotic stroke occurs when a blood clot (thrombus) forms in one of the arteries that supply blood to the brain.³ An embolic stroke occurs when a blood clot or other debris forms away from the brain and is carried through the bloodstream to lodge in narrower brain arteries. Another cause of stroke is when bleeding occurs into brain tissue from a ruptured blood vessel (hemorrhagic stroke).³Stroke is a leading cause of morbidity and mortality.⁴ Perioperative acute ischemic stroke is a recognized complication of noncardiac, nonvascular surgery.⁵ Among the general population, the rate of acute ischemic stroke in the perioperative period has been reported to be as high as 0.7%.⁵ The incidence increases to 1.0% as age increases above 65 years.⁵ Other major risk factors that predispose to acute ischemic stroke in the perioperative period include: renal disease, atrial fibrillation, previous history of stroke, valvular disease, congestive heart failure, male sex, diabetes mellitus, and race.^5–7Adequate preoperative assessment of risk is imperative.⁸ When possible, patients should receive optimum medical treatment in the interest of attenuating the impact of risk factors in the perioperative period.⁸ However, when strokes occur, rapid, immediate treatment is required to prevent permanent brain damage.⁹     

Novel PEGylated Basal Insulin LY2605541 Has a Preferential Hepatic Effect on Glucose Metabolism

The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic clamps with tracer and hepatic balance measurements. Clamp period infusions were peripheral venous regular insulin (0.1 nmol ⋅ kg⁻¹ ⋅ h⁻¹ [control], n = 6) or LY (bolus [nmol/kg], continuous [nmol ⋅ kg⁻¹ ⋅ h⁻¹]: 0.5, 0.5 [n = 6]; 0.375, 0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as intraportal glucagon (basal). During the clamp, the dogs switched from net hepatic glucose output to uptake (rates reached 2.1 ± 1.2, 0.9 ± 2.1, 8.6 ± 2.3, and 6.0 ± 1.1 µmol ⋅ kg⁻¹ ⋅ min⁻¹ within 5 h in control, LY_0.25, LY_0.375, and LY_0.5, respectively). Non-HGU in LY increased less than in control; the ratio of change from basal in non-HGU to change in net hepatic glucose balance, calculated when glucose infusion rates (GIRs) were ~20 µmol ⋅ kg^-1 ⋅ min⁻¹ in all groups, was higher in control (1.17 ± 0.38) versus LY_0.25 (0.39 ± 0.33), LY_0.375 (−0.01 ± 0.13), and LY_0.5 (−0.09 ± 0.07). Likewise, the change from baseline in glucose R_d-to-R_a ratio was greatest in control (1.4 ± 0.3 vs. 0.6 ± 0.4, 0.5 ± 0.2, and 0.6 ± 0.2 in LY_0.25, LY_0.375, and LY_0.5, respectively). In contrast to exogenously administered human insulin, LY demonstrated preferential hepatic effects, similar to endogenously secreted insulin. Therefore, the analog might reduce complications associated with current insulin therapy.     

Laparoscopic versus open peritoneal dialysis catheter insertion cost analysis

Background

Peritoneal dialysis (PD) is a cost-effective alternative to hemodialysis (HD). PD catheters have traditionally been inserted through a small open incision, but insertion using laparoscopic visualization has become increasingly popular and is associated with less catheter malfunction. The aim of this study was to compare costs of laparoscopic and open insertion strategies while taking into account postoperative complications and future salvage procedures.

Methods

A decision analysis model was constructed to simulate 1 y outcomes after PD catheter insertion by either the open or laparoscopic approach. Possible outcomes after PD catheter placement included functional catheter, infection, and catheter malfunction. Ultimately, patients continued with successful PD or switched to HD. Baseline probabilities, costs, and ranges were determined from a critical review of the literature. Sensitivity analyses were performed to determine the model strength over a range of clinically relevant probabilities.

Results

The total annual costs, including postoperative management and dialysis treatment, were $69,491 for laparoscopic insertion and $69,960 for open insertion. In case of a catheter malfunction, an initial attempt at salvage by fluoroscopy-guided wire manipulation cost less than a first attempt by laparoscopic repositioning.

Conclusions

When accounting for a year of postoperative management and treatment, laparoscopic insertion can be less costly than open insertion in the hands of an experienced surgeon. Despite higher initial costs, PD catheter insertion under laparoscopic visualization can have lower total costs due to fewer postoperative complications. With increasing emphasis on cost-effective care, laparoscopic insertion is a valuable tool for initiating PD.     

Trends in community violence in England and Wales 2005–2009

Purpose

Injury records from Emergency Departments (EDs) have been studied over the last decade as part of the work of the National Violence Surveillance Network (NVSN) and provide information about local, regional and national violence levels and trends in England and Wales. The purpose of the current study is to evaluate overall, gender, age-specific and regional trends in community violence in England and Wales from an ED perspective from January 2005 to December 2009.

Methods

Violence-related injury data were collected prospectively in a stratified sample of 77 EDs (Types 1, 3 and 4) in the nine Government Office Regions in England and in Wales. All 77 EDs were recruited on the basis that they had implemented and continued to comply with the provisions of the 1998 Data Protection Act and Caldicott guidance. Attendance date, age and gender of patients who reported injury in violence were identified using assault-related attendance codes, specified at the local level. Time series statistical methods were used to detect both regional and national trends.

Results

In total 221,673 (163,384 males: 74%) violence-related attendances were identified. Overall estimated annual injury rate was 6.5 per 1000 resident population (males 9.8 and females 3.4 per 1000). Violence affecting males and females decreased significantly in England and Wales over the 5-year period, with an overall estimated annual decrease of 3% (95% CI: 1.8–4.1%, p < 0.05). Attendances decreased significantly for both genders across four out of the five age groups studied. Attendances were found to be highest during the months of May and July and lowest in February. Substantial differences in violence-related ED attendances were identified at the regional level.

Conclusions

From this ED perspective overall violence in England and Wales decreased over the period 2005–2009 but increased in East Midlands, London and South West regions. Since 2006, overall trends according to Crime Survey for England and Wales (CSEW), police and ED measures were similar, though CSEW and ED measures reflect far greater numbers of violent incidents than police data. Causes of decreases in violence in regions need to be identified and shared with regions where violence increased.     

Comparing patient generated blood glucose diary records with meter memory in type 2 diabetes

Aim

To assess agreement between meter and diary self monitoring of blood glucose (SMBG) records, over a year, in a sample of patients with type 2 diabetes.

Methods

Meter and diary records were available, for 95 individuals, who took part in the Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes study.Pearson's correlation coefficient was used to explore the relationships between the types of error. Maximum likelihood estimation was used to explore changes over time through a structural equation modelling approach. Paired samples t-tests were used to determine if the presence of errors led to a significant difference between the mean diary and meter SMBG concentrations or coefficients of variation. Multiple regression was used to explore possible predictors of the error indices.

Results

Mean over-reporting, under-reporting, concordance and overall reliability were 8.4%, 10.0%, 83.5% and 71.3%, respectively. The first week of monitoring had significantly more under-reporting, over-reporting and less concordance and overall reliability than subsequent weeks. The majority of concordance errors were not clinically significant. Those that were, tended to occur during the first three months of monitoring. Participants’ at one trial site were significantly more likely to have recording errors than those at the largest site.

Conclusions

Error levels were similar to those described previously in type 1 diabetes and there was a suggestion of an initial learning curve for record keeping. For some individuals diary records would not be considered acceptable if held to the same standards as blood glucose meters.