Ureterolithiasis after Cohen re-implantation – case report

BACKGROUND: In the past decades, the widespread use of cross-trigonal ureteral reimplants for the treatment of children with vesicoureteral reflux has resulted in a large population of patients with transversely lying ureters. As this population gets older they will consequently be entering an age group at higher risk for stone and urothelial cancer formation. If ureteroscopy becomes necessary, the transverse position of the ureter makes ureteric access often impossible. CASE PRESENTATION: We present the case of a young man who not only suffered from urolithiasis due to hyperparathyroidism, but also further jeopardized his treatment by omitting the fact that as a child he underwent Cohen reimplantation of the right ureter. CONCLUSIONS: This case illustrates the particular difficulties the endoscopist may face in this group of patients. Patients with difficult ureteric access, abnormal anatomy, or those with known cross-trigonal ureteric reimplantations should be managed in a specialised endourology unit

Predicting resistance as indicator for need to switch from first-line antiretroviral therapy among patients with elevated viral loads: Development of a risk score algorithm

Background: In resource-limited settings, where resistance testing is unavailable, confirmatory testing for patients with high viral loads (VL) delays antiretroviral therapy (ART) switches for persons with resistance. We developed a risk score algorithm to predict need for ART change by identifying resistance among persons with persistently elevated VL. Methods: We analyzed data from a Phase IV open-label trial. Using logistic regression, we identified demographic and clinical characteristics predictive of need for ART change among participants with VLs ≥1000 copies/ml, and assigned model-derived scores to predictors. We designed three models, including only variables accessible in resource-limited settings. Results: Among 290 participants with at least one VL ≥1000 copies/ml, 51 % (148/290) resuppressed and did not have resistance testing; among those who did not resuppress and had resistance testing, 47 % (67/142) did not have resistance and 53 % (75/142) had resistance (ART change needed for 25.9 % (75/290)). Need for ART change was directly associated with higher baseline VL and higher VL at time of elevated measure, and inversely associated with treatment duration. Other predictors included body mass index and adherence. Area under receiver operating characteristic curves ranged from 0.794 to 0.817. At a risk score ≥9, sensitivity was 14.7-28.0 % and specificity was 96.7-98.6 %. Conclusions: Our model performed reasonably well and may be a tool to quickly transition persons in need of ART change to more effective regimens when resistance testing is unavailable. Use of this algorithm may result in public health benefits and health system savings through reduced transmissions of resistant virus and costs on laboratory investigations

What Research Is Needed to Stop TB? Introducing the TB Research Movement

Christian Lienhardt and colleagues describe the development of the TB Research Movement, which aims to create a framework for concrete actions to harmonize and synergize TB research efforts globally

Barriers-enablers-ownership approach: A mixed methods analysis of a social intervention to improve surgical antibiotic prescribing in hospitals

Objectives To assess an intervention for surgical antibiotic prophylaxis (SAP) improvement within surgical teams focused on addressing barriers and fostering enablers and ownership of guideline compliance. Design The Queensland Surgical Antibiotic Prophylaxis (QSAP) study was a multicentre, mixed methods study designed to address barriers and enablers to SAP compliance and facilitate engagement in self-directed audit/feedback and assess the efficacy of the intervention in improving compliance with SAP guidelines. The implementation was assessed using a 24-month interrupted time series design coupled with a qualitative evaluation. Setting The study was undertaken at three hospitals (one regional, two metropolitan) in Australia. Participants SAP-prescribing decisions for 1757 patients undergoing general surgical procedures from three health services were included. Six bimonthly time points, pre-implementation and post implementation of the intervention, were measured. Qualitative interviews were performed with 29 clinical team members. SAP improvements varied across site and time periods. Intervention QSAP embedded ownership of quality improvement in SAP within surgical teams and used known social influences to address barriers to and enablers of optimal SAP prescribing. Results The site that reported senior surgeon engagement showed steady and consistent improvement in prescribing over 24 months (prestudy and poststudy). Multiple factors, including resource issues, influenced engagement and sites/time points where these were present had no improvement in guideline compliance. Conclusions The barriers-enablers-ownership model shows promise in its ability to facilitate prescribing improvements and could be expanded into other areas of antimicrobial stewardship. Senior ownership was a predictor of success (or failure) of the intervention across sites and time periods. The key role of senior leaders in change leadership indicates the critical need to engage other specialties in the stewardship agenda. The influence of contextual factors in limiting engagement clearly identifies issues of resource distributions/inequalities within health systems as limiting antimicrobial optimisation potential

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Virologic Failure of Protease Inhibitor-Based Second-Line Antiretroviral Therapy without Resistance in a Large HIV Treatment Program in South Africa

Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings HIV-infected patients $\geq$15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

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

Effect of medication review and cognitive behaviour treatment by community pharmacists of patients discharged from the hospital on drug related problems and compliance: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Drug related problems (DRPs) are common among elderly patients who are discharged from the hospital and are using several drugs for their chronic diseases. Examples of drug related problems are contra-indications, interactions, adverse drug reactions and inefficacy of treatment. Causes of these problems include prescription errors and non-compliance with treatment. The aim of this study is to examine the effect of <it>medication review </it>and <it>cognitive behaviour therapy </it>of discharged patients by community pharmacists to minimize the occurrence of drug related problems.</p> <p>Methods/Design</p> <p>A randomized controlled trial will be performed. Community pharmacists will be randomized into a control group and an intervention group. 342 Patients, aged over 60 years, discharged from general and academic hospitals, using five or more prescription drugs for their chronic disease will be asked by their pharmacy to participate in the study.</p> <p>Patients randomized to the control group will receive usual care according to the Dutch Pharmacy Standard. The medication of patients randomised to the intervention group will be reviewed by the community pharmacist with use of the national guidelines for the treatment of diseases, when patients are discharged from the hospital. The Pharmaceutical Care network Europe Registration form will be used to record drug related problems. Trained pharmacy technicians will counsel patients at home at baseline and at 1,3,6,9 and 12 months, using Cognitive Behaviour Treatment according to the Theory of Planned Behaviour. The patient's attitude towards medication and patient's adherence will be subject of the cognitive behaviour treatment. The counselling methods that will be used are <it>motivational interviewing </it>and <it>problem solving treatment</it>. Patients adherence towards drug use will be determined with use of the Medication Adherence Report Scale Questionnaire. There will be a follow-up of 12 months.</p> <p>The two primary outcome measures are the difference in occurrence of DRPs between intervention and control group and adherence with drug use. Secondary endpoints are attitude towards drug use, incidence of Re-hospitalisations related to medicines, functional status of the patient, quality of life and the cost-effectiveness of this intervention.</p> <p>Discussion</p> <p>Combining both medication review and Cognitive Behaviour Treatment may decrease DRPs and may result in more compliance with drug use among patients discharged from the hospital and using 5 or more chronic drugs.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR1194</p