Patient information leaflets for Transrectal Ultrasound guided prostate biopsy: Results of North Thames deanery survey

<p>Abstract</p> <p>Background</p> <p>We evaluated the quality of patient information leaflets for Trans-Rectal Ultrasound guided prostate biopsies (TRUS-Bx) in North Thames region. TRUS-Bx information leaflets were requested from 24 hospitals in the region. All hospitals were contacted by telephone, and non-responders were followed-up by postal survey. Leaflets received were evaluated for a clear description of the procedure, directions to TRUS-Bx location, a clear description of the procedure, contact for queries/concerns, information about preparation prior to procedure, information about regular medication, information on how to obtain results, instructions for follow-up arrangements, analgesia used and risk of morbidity/mortality. Additionally, the leaflets were evaluated for diagrams to clarify the procedure and the anatomy, and sources of additional information, such as reference to published articles or prostate cancer patient support groups/internet websites.</p> <p>Findings</p> <p>In summary, a total of 17 leaflets (77%) were received. Of these, the majority (94%) had a clear description of the procedure, contact for queries/concerns (82%), information about preparation prior to TRUS-Bx (71%). Directions to TRUS-Bx location (29%), and analgesia used (35%), was very poorly described, and information on obtaining results and follow-up arrangements were described in only 12 (71%) leaflets. Complications such as risks of infection, haematuria, haematospermia and rectal bleeding, were generally explained (71%-76% of leaflets), urinary retention was mentioned in only 5 (29%) leaflets and mortality in only 1 case. Descriptive diagrams of the procedure and prostate anatomy were very rarely used, and sources of additional information were limited to 1 published article and reference to 1 prostate cancer support group.</p> <p>Conclusions</p> <p>This study demonstrates that there is large variation in the information supplied in TRUS-Bx patient information leaflets in the North Thames region, with some leaflets lacking vital information. It is proposed that a standard patient information leaflet incorporating all the factors in the checklist should be designed, with the incorporation of a new BAUS procedure specific consent form for TRUS-Bx.</p

The impact of direct-acting antivirals on hepatitis C viraemia among people who inject drugs in England; real-world data 2011–2018

Direct‐acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled‐up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self‐reported treatment access. Bio‐behavioural data from an annual, national surveillance survey of PWID (2011–2018) estimated trends in viraemic prevalence among HCV antibody‐positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody‐positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65–0.94) and 2018 (aOR 0.79, 95% CI 0.66–0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53–1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13–1.41), imprisonment (aOR 1.14, 95% CI 1.04–1.31) and homelessness (aOR 1.17, 95% CI 1.04–1.31). Among non‐viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody‐positive PWID in England since 2016, alongside DAA scale‐up, and some indication that treatment access has improved in the same period. Population‐level monitoring and focus on harm reduction is critical for achieving and evaluating elimination

Wireless tissue palpation: Head characterization to improve tumor detection in soft tissue

For surgeons performing open procedures, the sense of touch is a valuable tool to directly access buried structures and organs, to identify their margins, detect tumors, and prevent undesired cuts. Minimally invasive surgical procedures provide great benefits for patients; however, they hinder the surgeon's ability to directly manipulate the tissue. In our previous work, we developed a Wireless Palpation Probe (WPP) to restore tissue palpation in Minimally Invasive Surgery (MIS) by creating a real-time stiffness distribution map of the target tissue. The WPP takes advantage of a field-based magnetic localization algorithm to measure its position, orientation, and tissue indentation depth, in addition to a barometric sensor measuring indentation tissue pressure. However, deformations of both the tissue and the silicone material used to cover the pressure sensors introduce detrimental nonlinearities in sensor measurements. In this work, we calibrated and characterized different diameter WPP heads with a new design allowing exchangeability and disposability of the probe head. Benchtop trials showed that this method can effectively reduce error in sensor pressure measurements up to 5% with respect to the reference sensor. Furthermore, we studied the effect of the head diameter on the device's spatial resolution in detecting tumor simulators embedded into silicone phantoms. Overall, the results showed a tumor detection rate over 90%, independent of the head diameter, when an indentation depth of 5 mm is applied on the tissue simulator

Understanding continent-wide variation in vulture ranging behavior to assess feasibility of Vulture Safe Zones in Africa: Challenges and possibilities

Protected areas are intended as tools in reducing threats to wildlife and preserving habitat for their long-term population persistence. Studies on ranging behavior provide insight into the utility of protected areas. Vultures are one of the fastest declining groups of birds globally and are popular subjects for telemetry studies, but continent-wide studies are lacking. To address how vultures use space and identify the areas and location of possible vulture safe zones, we assess home range size and their overlap with protected areas by species, age, breeding status, season, and region using a large continent-wide telemetry datasets that includes 163 individuals of three species of threatened Gyps vulture. Immature vultures of all three species had larger home ranges and used a greater area outside of protected areas than breeding and non-breeding adults. Cape vultures had the smallest home range sizes and the lowest level of overlap with protected areas. Rüppell\u27s vultures had larger home range sizes in the wet season, when poisoning may increase due to human-carnivore conflict. Overall, our study suggests challenges for the creation of Vulture Safe Zones to protect African vultures. At a minimum, areas of 24,000 km2 would be needed to protect the entire range of an adult African White-backed vulture and areas of more than 75,000 km2 for wider-ranging Rüppell\u27s vultures. Vulture Safe Zones in Africa would generally need to be larger than existing protected areas, which would require widespread conservation activities outside of protected areas to be successful

Endothelial Dysfunction and Specific Inflammation in Obesity Hypoventilation Syndrome

BACKGROUND: Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION: To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY: 14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS: OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS: Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00603096

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Enhanced West Nile virus surveillance in the North Kent marshes, UK

Background As part of efforts to more fully understand the potential risks posed by West Nile virus (WNV) and Usutu virus (USUV) in the UK, and following on from previous reports of a potential bridge vector Culex modestus for these viruses, at wetland sites in North Kent, mosquito surveillance was undertaken more widely across the Isle of Sheppey, the Hoo Peninsula and the Kent mainland. Methods Larval surveys were conducted and Mosquito Magnet® adult traps were used to collect adult mosquitoes. Pools of female mosquitoes were tested for the presence of WNV using real-time reverse transcriptase polymerase chain reaction. A subset of samples was tested for USUV. Results Culex modestus was found in both the pre-imaginal and imago stage at all five locations surveyed, accounting for 90% of adult mosquitoes collected. WNV or USUV were not detected in any sample. Conclusions Although no mosquitoes have been shown to be virus positive, the field survey data from this study demonstrated the dominance of an important bridge vector species for WNV in this region. Its wide geographical distribution highlights the need to update risk assessments on WNV introduction, and to maintain vigilance for WNV in the South East of England

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Ventricular Dysrhythmias Associated with Poisoning and Drug Overdose: A 10-Year Review of Statewide Poison Control Center Data from California

Background: Ventricular dysrhythmias are a serious consequence associated with drug overdose and chemical poisoning. The risk factors for the type of ventricular dysrhythmia and the outcomes by drug class are not well documented. Objective: The aim of this study was to determine the most common drugs and chemicals associated with ventricular dysrhythmias and their outcomes. Methods: We reviewed all human exposures reported to a statewide poison control system between 2002 and 2011 that had a documented ventricular dysrhythmia. Cases were differentiated into two groups by type of arrhythmia: (1) ventricular fibrillation and/or tachycardia (VT/VF); and (2) torsade de pointes (TdP). Results: Among the 300 potential cases identified, 148 cases met the inclusion criteria. Of these, 132 cases (89&nbsp;%) experienced an episode of VT or VF, while the remaining 16 cases (11&nbsp;%) had an episode of TdP. The most commonly involved therapeutic classes of drugs associated with VT/VF were antidepressants (33/132, 25&nbsp;%), stimulants (33/132, 25&nbsp;%), and diphenhydramine (16/132, 12.1&nbsp;%). Those associated with TdP were antidepressants (4/16, 25&nbsp;%), methadone (4/16, 25&nbsp;%), and antiarrhythmics (3/16, 18.75&nbsp;%). Drug exposures with the greatest risk of death in association with VT/VF were antidepressant exposure [odds ratio (OR) 1.71; 95&nbsp;% confidence interval (CI) 0.705–4.181] and antiarrhythmic exposure (OR 1.75; 95&nbsp;% CI 0.304–10.05), but neither association was statistically significant. Drug exposures with a statistically significant risk for TdP included methadone and antiarrhythmic drugs. Conclusions: Antidepressants and stimulants were the most common drugs associated with ventricular dysrhythmias. Patients with suspected poisonings by medications with a high risk of ventricular dysrhythmia warrant prompt ECG monitoring

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities