Early adolescent psychological distress and cognition, correlates of resting-state EEG, interregional phase-amplitude coupling.

Delineating neurobiological markers of youth mental health is crucial for early identification and treatment. One promising marker is phase-amplitude coupling (PAC), cross-frequency coupling between the phase of slower oscillatory activity and the amplitude of faster oscillatory activity in the brain. Prior research has demonstrated that PAC is associated with both cognition and mental health and can be modulated using neurostimulation. However, to date research investigating PAC has focused primarily on adults, and only within-region theta-gamma coupling in the context of mental health. We investigated associations between interregional resting-state PAC (posterior-anterior cortex), and cognition and psychological distress in N = 77 (Mage = 12.58 years, SD = 0.31; 51 % female) 12-year-olds. Firstly, while left theta-beta PAC showed a moderate positive correlation (r = 0.529, p < .01), right theta-gamma PAC showed a weak positive correlation, with psychological distress (r = 0.283, p < .05). In terms of cognition, moderate correlations were observed between: (i) increased left theta-beta PAC and increased psychomotor speed (r = -0.367, p < .05); (ii) increased left alpha-beta PAC and decreased attention (r = 0.355, p ≤0.01); and (iii) increased left alpha-beta PAC and decreased verbal learning and memory (r = -0.352, p < .01). Whereas weak associations were observed for: (i) increased left alpha-beta PAC and decreased executive functioning scores (r = 0.284, p < .05); and (ii) increased left alpha-gamma PAC and increased attention (r = -0.272, p < .05). The overall findings of this exploratory study are encouraging, although all the correlations were in the weak-to-moderate range and require replication. Further research may confirm interregional resting-state PAC as a biomarker that can help us better understand the link between mental health and cognition in adolescents and improve treatment of cognitive related deficits in mental illness.

An observational study of a cross platform risk assessment mobile application in a forensic inpatient setting.

Consumer-focused healthcare mobile applications have seen widespread adoption in recent years. Enterprise mobile applications in hospital settings have been slower to gain traction. In this study we examine the Dynamic Appraisal of Situational Aggression: Inpatient version (DASA), a short-term risk assessment tool which is well validated and widely used in the prediction of violent incidents, within an inpatient forensic setting. The application was piloted over a period of three months, collecting 847 total DASA scores on 21 different patients. Time stamping allowed for accurate correlation between risk assessment scoring and the violent risk incidents. The internal validity of the app was measured using Cronbach's alpha and was calculated at 0.798 indicating good internal validity. Using violent incidents as the dependent factor and the total DASA score as the independent factor, predictive validity of the app was calculated at 0.85, p = 0.007. The use of this application in a forensic setting was successful with good internal and predictive validity. A major benefit of this form of data collection was the electronic time stamping so that the correlation between risk estimation and events could be more closely correlated. Deployment of such an application in a general hospital setting would bring its own challenges but would be useful in other types of risk assessment and screening tools.

Diagnostic accuracy of SUVmax in predicting malignancy of supraclavicular lymph nodes from primary oesophageal cancer.

PURPOSE: To determine the diagnostic accuracy and optimum cut-off value of SUVmax on PET to predict malignancy of supraclavicular lymph nodes (SCLNs) in patients with oesophageal carcinoma. MATERIAL AND METHODS: All diagnosed cases of oesophageal cancer were retrospectively reviewed (2010-2016). Patients that had a confirmed diagnosis of oesophageal cancer with avid SCLNs on staging PET were included in the study. 33 SCLNs that subsequently underwent ultrasound guided biopsy for staging were analysed. The maximum uptake values (SUVmax) of the SCLNs and primary tumours were measured. A receiver operating characteristic (ROC) analysis was performed to determine the optimum cut off of SUVmax in predicting malignancy. RESULTS: 24/33 PET-detected SCLNs were malignant. ROC analysis identified the best nodal SUVmax cut-off to be 3.0. The diagnostic accuracy of PET was 76.0 % (sensitivity = 78.9 %, specificity = 66.6 %). For SCLNs with SUVmax > 3.0, PET showed a positive predictor value of 88.2 %; for SCLNs < 3.0, PET showed a negative predictor value of 50 %. The median SUVmax of pathologically negative and positive nodes were 2.8 (range 1.8-6.0) and 5.3 (range 1.9-13.4). The median primary tumour SUVmax was 13.8 (range 3.7-30.0). The SUVmax of metastatic lymph nodes were significant higher than those of benign lesions (p < 0.05). CONCLUSION: Our study revealed an accuracy rate of 76 % for PET detected SCLNs in patients with oesophageal carcinoma. For SCLNs with SUVmax > 3.0, PET had a high PPV (88 %), which can minimize the need for further diagnostic tests.

Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients.

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses on the anaesthetic management of patients undergoing surgery for hip fracture have focused on randomized trials. Furthermore, heterogeneity in outcome reporting across the studies has made it difficult to inform best practice guidelines for patient care. METHODS: This systematic review examined how perioperative outcomes were reported and defined in the context of comparing modes of anaesthesia for hip fracture surgery. Outcomes were included from randomised and non-randomised studies published between January 2000 and July 2017. Meta-analyses were performed for regional versus general anaesthesia, with sensitivity analyses performed for spinal versus general anaesthesia. RESULTS: By including data from 15 large observational studies in this meta-analysis, we have increased the number of patients for whom outcomes were assessed from approximately 3000 to 202 000. There was no significant difference in 30-day mortality (OR 1.02; 95% CI 0.96, 1.07, I2 31%; n=200 616), prevalence of pneumonia (OR 1.07; 95% CI 0.94, 1.23, I2 34%; n=65 011), acute myocardial infarction (OR 0.96; 95% CI 0.88, 1.04, I2 0%, n=64 904), delirium (OR 1.07; 95% CI 0.72, 1.58, I2 93%, n=19 923), or renal failure (OR 0.94; 95% CI 0.54, 1.64, I2 0%, n=27 873) for regional compared with general anaesthesia [corrected]. There was a small statistically significant difference for length of stay (standardized mean difference -0.03; 95% CI -0.05, -0.02; I2 0%; n=78 711) favouring regional anaesthesia, which is unlikely to be clinically significant. Sensitivity analyses for the same outcomes examining spinal only vs general anaesthesia showed minor statistical significance for length of stay favouring spinal. We also present data highlighting the scale of the inconsistencies in reported outcomes across 32 studies, making evaluation in a standardized manner very difficult. As an example, mortality was reported in nine different ways throughout the studies. CONCLUSIONS: We highlight the need for agreement on outcome definitions and for a minimum core outcome set to be measured and reported in hip fracture studies. This would strengthen the evidence-based approach to delivering optimal care.

The value of multimodality imaging in the investigation of a PSA recurrence after radical prostatectomy in the Irish hospital setting.

INTRODUCTION: The diagnostic evaluation of a PSA recurrence after RP in the Irish hospital setting involves multimodality imaging with MRI, CT, and bone scanning, despite the low diagnostic yield from imaging at low PSA levels. We aim to investigate the value of multimodality imaging in PC patients after RP with a PSA recurrence. METHODS: Forty-eight patients with a PSA recurrence after RP who underwent multimodality imaging were evaluated. Demographic data, postoperative PSA levels, and imaging studies performed at those levels were evaluated. RESULTS: Eight (21%) MRIs, 6 (33%) CTs, and 4 (9%) bone scans had PCa-specific findings. Three (12%) patients had a positive MRI with a PSA <1.0 ng/ml, while 5 (56%) were positive at PSA ≥1.1 ng/ml (p = 0.05). Zero patient had a positive CT TAP at a PSA level <1.0 ng/ml, while 5 (56%) were positive at levels ≥1.1 ng/ml (p = 0.03). Zero patient had a positive bone at PSA levels <1.0 ng/ml, while 4 (27%) were positive at levels ≥1.1 ng/ml (p = 0.01). CONCLUSION: The diagnostic yield from multimodality imaging, and isotope bone scanning in particular, in PSA levels <1.0 ng/ml, is low. There is a statistically significant increase in the frequency of positive findings on CT and bone scanning at PSA levels ≥1.1 ng/ml. MRI alone is of investigative value at PSA <1.0 ng/ml. The indication for CT, MRI, or isotope bone scanning should be carefully correlated with the clinical question and how it will affect further management.

The improved accuracy of planar bone scintigraphy by adding single photon emission computed tomography (SPECT-CT) to detect skeletal metastases from prostate cancer.

BACKGROUND: Planar bone scintigraphy (PBS) is a standard radiological technique to detect skeletal metastases from prostate cancer (PC), the addition of SPECT-CT to PBS improves its diagnostic accuracy. The aim of this study was to assess the additional value of targeted SPECT-CT with PBS in detecting skeletal metastasis form prostate cancer, considering resource implications in an Irish hospital setting. METHODS: 54 PC patients with increased radiotracer uptake on PBS were retrospectively recruited from 2012 to 2013. All underwent targeted evaluation with SPECT-CT. PBS and SPECT-CT images were reviewed by two nuclear medicine radiologists and reported independently. The final diagnosis was made based on the CT finding corresponding to the area of radiotracer uptake. RESULTS: The mean age was 70.9 years (48-88 years) and median PSA at presentation was 13.9 ng/ml (4.2-215 ng/ml). 68.5 % (n = 37) men received treatment for PC while 31.5 % (n = 17) patients had not received treatment prior to PBS. 164 areas of increased radiotracer uptake were identified on PBS; 13 areas were characterised as metastatic on SPECT-CT; iliac bone (n = 3), ribs (n = 1), skull (n = 2), sacrum (n = 1), ischium (n = 1), femur (n = 3), thoracic spine (n = 1) and cervical spine (n = 1). 151 areas were characterised as benign on SPECT-CT. One area of increased radiotracer uptake in the ribs was subsequently described as indeterminate after evaluation with SPECT-CT. CONCLUSION: SPECT-CT improves the diagnostic accuracy of PBS in detecting skeletal metastasis from PC and is superior to PBS alone in differentiating benign from malignant lesions. Notwithstanding resource implications of increased cost, specialist equipment and specialist manpower hours; we recommend the use of SPECT-CT in conjunction with PBS for targeted evaluation of suspicious bony lesions in this cohort of patients.

A comparative bibliometric analysis of the top 150 cited papers in hypospadiology (1945-2013).

INTRODUCTION: Hypospadias, the most common congenital malformation of the penis, is characterized by an abnormal ventral opening of the urethral meatus, abnormal ventral curvature of the penis, and an abnormal distribution of the foreskin around the glans, with a ventrally-deficient hooded foreskin, and has been described in modern peer-reviewed literature since Noble's description in 1853. A dramatic increase in the literature on hypospadiology has focused on two main topics: The aetiology of the condition including molecular mechanisms and environmental influences, as well as surgical techniques to repair the defect, however there have been a number of facets of research stemming from this poorly understood condition in a developing subspecialty (Figure). The majority of these publications focus on the evolution of surgical technique and management. Urethral reconstruction should offer the ability to stand to urinate and combine a satisfactory cosmetic result. The tubularized incised plate repair, popularized by Snodgrass et al., and the Mathieu repair, have been the mainstay for distal hypospadias, however, there have still been a large number of well-described techniques, with no consensus as to the ideal method of repair, some of which is attributed to non-uniform standards of reporting outcomes. There is also no standard objective means to qualitatively assess the importance of each of these contributions. OBJECTIVE: The objective of this study was to determine the top 150 peer-reviewed articles in the field of hypospadiology by way of citation analysis as a means to determine the importance/relevance of each contribution throughout 8 decades of research. STUDY DESIGN: A cited reference search was carried out for indexed citations within Web of Science™ Core Collection. The top 150 indexed cited articles containing the topic "hypospadias" in specific subject categories were compiled using a component of Science Citation Index command. References were then evaluated, and analysed across a number of indices, and over time. RESULTS: The mean number of citations was 76 for each article. The top 150 articles were published across 21 countries, with the majority originating from the USA. The lead research institution was the University of Texas (Southwestern) Medical Center. In total, the top 3 centers represented 33 publications within the top 150 citations. The most commonly utilized journal was the Journal of Urology. The most cited author was W.T. Snodgrass. 39% papers in the top 150 cited articles were published prior to 1990. Three out of the five papers cited in the 1940s dealt with operative technique to repair hypospadias. The period 2000-2010 in contrast, demonstrated a significant inverse correlation between molecular biology citations, and those for operative techniques, with the incidence of the latter dropping to 6% of all cited papers. DISCUSSION: This is the first study of its kind to analyse the most influential articles in hypospadiology, and their characteristics assessed for authorship, content and impact factor. Furthermore it allows data analysis by topic and between time points. This not only de-clutters the wealth of accumulated data on this subject, but also provides an important adjunct to education and training. As with this study, other citation analytical studies in urology found a significant preponderance in cited studies originating from the USA. The prevalence of the US in cited papers doesn't reflect any inherent bias, just a greater number of publications. CONCLUSION: Although there are inherent potential elements of bias in citation analysis, this study demonstrates that citation analysis in a complicated topic can provide a high-throughput, uncomplicated method of quickly deciphering important contributions of authors and institutions to the field of hypospadias research.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.

Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody.

Upregulation of Toll-like receptor 2 (TLR2) plays a critical role in inflammation associated with ischemia/reperfusion-induced tissue damage. OPN-305 is the first humanized IgG4 monoclonal antibody against TLR2 in development and is intended for the prevention of reperfusion injury following renal transplantation and other indications. A phase I, single-center, prospective randomized, double-blind, placebo-controlled study was performed to evaluate single ascending doses of OPN-305 in 41 healthy male subjects (age range: 19-58 years) randomized to OPN-305 or placebo across six cohorts. OPN-305 was well tolerated across all doses, with no elevations in endogenous cytokines. A dose-proportional increase in maximum serum concentration (Cmax) was observed, with area under the curve increasing in a greater-than-dose-proportional manner with increasing elimination half-life. OPN-305 produced full TLR2 receptor blockade on CD14(+)CD45(+) cells (monocytes), from 14 (0.5 mg/kg) to >90 (10 mg/kg) days, with a linear effect on the duration of inhibition of interleukin-6 release after TLR2 stimulation.

Effect of Maitland mobilization and exercises for the treatment of shoulder adhesive capsulitis: a single-case design.

The purpose of this single-case design (ABCBC) was to investigate the response of shoulder motions, pain, and function to two commonly used physiotherapy management approaches. An individual with stage three shoulder adhesive capsulitis was treated with exercise (phase B) and exercise plus mobilization (phase C). Initially, a "baseline" phase (phase A) when treatment had not started was established for comparison. Two types of Maitland "accessory" glenohumeral mobilization techniques, anteroposterior mobilization in shoulder flexion and longitudinal caudad in shoulder abduction, were evaluated during phase C. The Shoulder Pain and Disability Index (SPADI) was used to monitor pain and functional disability, and four shoulder movements (flexion, abduction, internal, and external rotations) were measured. The results were evaluated by using single-case design analysis method of Split Middle Technique and visual observation. The SPADI scores deteriorated in phase A but improved in phase B1, C1, and B2. All four shoulder movements improved under both management approaches, although more gain in motion was observed when mobilizations were added to an exercise program. The exercise plus mobilization intervention shows promise as a cost-effective management. The deterioration in shoulder motion, pain, and function observed in phase A may suggest benefit of an earlier physiotherapy intervention.

Intracranial arachnoid cyst: anaesthetic management in pregnancy.

Arachnoid cysts may be intracranial or extracranial in the neuraxis and may present with headache and neurological signs or acutely with rupture and its complications. We report a case of spinal anaesthesia for elective caesarean section in a woman with an intracranial arachnoid cyst of the posterior fossa. We are unaware of any other such case reports published in the English language.

Anaesthesia for caesarean section in spinal muscular atrophy type III.

We describe the conduct of general anaesthesia for a patient with spinal muscular atrophy Type III (Kugelberg-Welander disease) undergoing elective caesarean section. Apart from a delayed return of skeletal muscle power following non-depolarising neuromuscular blockade the procedure was uneventful. We found no previously published reports of general anaesthesia for caesarean section in this condition in the English language literature. We review the available literature and discuss the potential anaesthetic problems in the management of obstetric patients with this degenerative neuromuscular disorder.

Pregnancy and lymphangioleiomyomatosis: anaesthetic management.

Lymphangioleiomyomatosis is a rare, progressive cystic pulmonary disease related to tuberous sclerosis complex, affecting almost exclusively females of childbearing age. Progression of the disease is variable but may lead to terminal respiratory failure. As the disease may be oestrogen-dependent, it can arise de novo in pregnancy or established disease may undergo exacerbation. We report on the successful labour and delivery of such a patient and present the results of an internet survey of 30 pregnancies in 15 patients worldwide with lymphangioleiomyomatosis conducted by our patient before delivery.

Lack of toxicity and persistence in the mouse associated with administration of candidate DNA- and modified vaccinia virus Ankara (MVA)-based HIV vaccines for Kenya.

Toxicity, biodistribution and persistence of candidate HIV vaccines pTHr.HIVA, a recombinant DNA, and MVA.HIVA, a recombinant modified vaccinia virus Ankara, were determined in the Balb/c mouse. The mice were injected with either two doses of intramuscular pTHr.HIVA DNA (50 microg each, separated by an interval of 14 days), two doses of intradermal MVA.HIVA (10(6) plaque-forming units each, separated by an interval of 14 days), or a combination of the two vaccines, each given in two doses, in a prime-boost regimen. The study showed no significant toxic effects, either local or systemic, under any of these employed dosing regimens. With the exception of the sites of delivery, the vaccine-derived HIVA DNA sequences were undetectable 5 weeks after the last dosing. Thus, both the vaccines alone and in a combination were considered safe and suitable for the use in phase I trials in humans.