Explainable artificial intelligence (XAI): closing the gap between image analysis and navigation in complex invasive diagnostic procedures.

LITERATURE REVIEW: Cystoscopy is the gold standard for initial macroscopic assessments of the human urinary bladder to rule out (or diagnose) bladder cancer (BCa). Despite having guidelines, cystoscopic findings are diverse and often challenging to classify. The extent of the false negatives and false positives in cystoscopic diagnosis is currently unknown. We suspect that there is a certain degree of under-diagnosis (like the failure to detect malignant tumours) and over-diagnosis (e.g. sending the patient for unnecessary transurethral resection of bladder tumors with anesthesia) that put the patient at risk. CONCLUSIONS: XAI robot-assisted cystoscopes would help to overcome the risks/flaws of conventional cystoscopy. Cystoscopy is considered a less life-threatening starting point for automation than open surgical procedures. Semi-autonomous cystoscopy requires standards and cystoscopy is a good procedure to establish a model that can then be exported/copied to other procedures of endoscopy and surgery. Standards also define the automation levels-an issue for medical product law. These cystoscopy skills do not give full autonomy to the machine, and represent a surgical parallel to 'Autonomous Driving' (where a standard requires a human supervisor to remain in the 'vehicle'). Here in robotic cystoscopy, a human supervisor remains bedside in the 'operating room' as a 'human-in-the-loop' in order to safeguard patients. The urologists will be able to delegate personal- and time-consuming cystoscopy to a specialised nurse. The result of automated diagnostic cystoscopy is a short video (with pre-processed photos from the video), which are then reviewed by the urologists at a more convenient time.

Skin Cancer Excision Is More Efficient and Cost Effectivein a Specialist Secondary Care Service.

Aim To compare the relative efficiencies of skin excisions in primary and secondary care. Methods We compared the benign: malignant ratio for specimens referred by General Practice, General Surgery and the Skin Cancer Service to the regional pathology laboratory over one month. We used cost minimization analysis to compare the relative efficiencies of the services. Results 620 excisions were received: 139 from General Practice, 118 from General Surgery and 363 from the Skin Cancer Service. The number (%) of malignant lesions was 13 (9.4%) from General Practice, 18 (15.2%) from General Surgery and 137 (37.7%) from the Skin Cancer Service. Excision was cheaper in General Practice at €84.58 as compared to €97.49 in the hospital day surgical unit. However, the cost per malignant lesion excised was €1779.80 in general practice versus €381.78 in the Skin Cancer Service. Conclusion Our results indicate that moving skin cancer treatment to General Practice may result in an excess of benign excisions and therefore be both less efficient and less cost effective.

A systematic review of cannabidiol dosing in clinical populations.

AIMS: Cannabidiol (CBD) is a cannabis-derived medicinal product with potential application in a wide-variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts. METHODS: Publications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov. RESULTS: A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty-three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6-62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies. CONCLUSION: This review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.

A Dedicated Perineal Clinic ­ An Audit in Support

Aims To assess the quality of care in both the initial management of obstetric anal sphincter injury (OASI) and subsequent follow up postnatally in a tertiary maternity hospital without direct access to a perineal clinic. Methods Medical records were reviewed over a one-year period in University Maternity Hospital Limerick (UMHL) to determine the characteristics of patients sustaining OASI, how and where the repair was undertaken, the complications recorded and their follow up in the postpartum period. This pathway of care was compared with care currently available in three dedicated perineal clinics nationally. Results There were 44 patients with OASI recorded over a one-year period in UMHL. The majority were diagnosed in primiparous women having an operative vaginal delivery (OVD). Only 23 of 44 women had a documented review postnatally. Conclusion Audit of OASI is paramount to providing the best standard of care for affected women. It also aids clinician training and will be important in the establishment of a dedicated perineal clinic in UMHL.

The utility of dopamine transporter scans for diagnosing Parkinsonian disorders

Introduction Dopamine transporter scans are increasingly being used in the diagnosis of clinically undefined Parkinsonism. Aims To assess the indications for imaging usage and its impact on future clinical management. Methods Retrospective review of scans ordered and their corresponding results over a five-year period. A chart review was carried out on a cohort of scans to assess changes in clinical management. Results One hundred and eighty scans (69% of total) were reported as showing evidence of dopaminergic deficit. A chart review in 81 patients showed a change in clinical management in 53 patients (65%). Scans were ordered inappropriately in 34 patients (13%). Discussion 123I-FP-CIT SPECT scans are being more frequently ordered and if used correctly can alter clinical management. Increased education on indications for use is required to reduce waste of resources and risk to patients.

Piscirickettsia salmonis infection in cultured lumpfish (Cyclopterus lumpus L.).

A Piscirickettsia salmonis infection was diagnosed in lumpfish (Cyclopterus lumpus L.) juveniles held in a marine research facility on the west coast of Ireland. The main clinical signs and pathology included marked ascites, severe multifocal liver necrosis and severe diffuse inflammation and necrosis of the exocrine pancreas and peri-pancreatic adipose tissue. Numerous Piscirickettsia-like organisms were observed by histopathology in the affected organs, and the bacterial species was characterized by molecular analysis. Sequencing of the partial 16S rDNA gene and internal transcribed spacer region showed the lumpfish sequences to be closely related to previously identified Atlantic salmon (Salmo salar L.) sequences from Ireland. To the authors' knowledge, this is the first detection of P. salmonis in lumpfish worldwide. The infection is considered potentially significant in terms of lumpfish health and biosecurity.

First record of Tetramicra brevifilum in lumpfish (Cyclopterus lumpus, L.).

A microsporidian species with 98.3-98.4% nucleotide identity to Tetramicra brevifilum (Journal of Fish Diseases, 3, 1980, 495) was diagnosed in lumpfish (Cyclopterus lumpus, L.) broodstock held at a breeding and rearing facility in western Ireland. The fish were wild-caught from the west coast of Ireland, and the first case was diagnosed one year after capture. Clinical signs included severe bloating, lethargy, exophthalmos, anorexia, white patches on the cornea and externally visible parasitic cysts on skin and fins. Necropsy revealed severe ascites, white nodules and vacuoles in all the internal organs and partial liquefaction of the skeletal muscle. On histological examination, microsporidian xenomas were observed in all internal organs, the skin, skeletal muscle, gills and the eyes. The microsporidian species was identified by molecular analysis and transmission electron microscopy. This is the first record of T. brevifilum infecting lumpfish, and the disease is considered to be of potential significance to the rising aquaculture industry of this species.

Does Demand for Breast Augmentation Reflect National Financial Trends?

Aesthetic plastic surgery is a consumer-driven industry, subject to influence by financial forces. A changing economic environment may thus impact on the demand for surgery. The aim of this study was to explore trends in demand for bilateral breast augmentation (BBA) in consecutively presenting patients over an 11-year period and to examine if a correlation exists between these trends and changes in Gross Domestic Product (GDP), a key economic indicator. This study revealed a correlation between annual number of breast augmentation procedures performed and GDP values (r 2 = 0.34, p value = 0.059). Additionally, predicted number of BBA procedures, based on predicted GDP growth in Ireland, strongly correlated with actual number of BBA performed (r 2 = 0.93, p value = 0.000001). Predicted GDP growth can potentially forecast future demand for BBA in our cohort allowing plastic surgeons to modify their practice accordingly. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite.

Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the loss of barrier function and an elevated sensitivity to environmental insults. An increased release of the endogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients has been reported. The aim of this study was, therefore, to determine the effects of endocannabinoids on bronchial epithelial cell permeability and to investigate the mechanisms involved. Calu-3 human bronchial epithelial cells were cultured at air-liquid interface to allow development of tight junctions. Changes in Transepithelial Electrical Resistance (TEER), a reflection of epithelial permeability, were measured at various time points post-treatment, and expression of the tight junction proteins, occludin and ZO-1, were determined using Western immunoblotting. Anandamide produced a significant reduction in TEER, which was unaffected by cannabinoid receptor antagonists, but attenuated by URB597, an inhibitor of fatty acid amide hydrolase, and by a combination of cyclooxygenase (COX) and lipoxygenase (LOX) blockade. The anandamide metabolite, arachidonic acid, showed similar TEER decrease that was also prevented in the presence of COX and LOX inhibitor. Expression of occludin and ZO-1 were also reduced by anandamide. These findings indicate a pro-inflammatory-like effect of anandamide on bronchial epithelial permeability, mediated by cyclooxygenase and lipoxygenase metabolites, and suggest that inhibition of anandamide degradation might provide a novel approach to treat airway inflammation.

The Clinical Utility of a Low Serum Ceruloplasmin Measurement in the Diagnosis of Wilson Disease.

The first step in screening for potential Wilson disease is serum ceruloplasmin testing, whereby a level of less than 0.2g/L is suggestive of the disease. We aimed to determine what proportion of an Irish population had a low ceruloplasmin level, whether low measurements were appropriately followed-up and what were the clinical outcomes. We conducted a retrospective review of all serum ceruloplasmin measurements between August 2003 and October 2009 in a large tertiary referral centre in Southern Ireland. Clinical data, serum ceruloplasmin, liver function tests, urinary copper and liver biopsy reports were all recorded where available. 1573 patients had a serum ceruloplasmin measurement during the 7-year study period. 96 patients (6.1%) had a ceruloplasmin level < 0.2g/L and of these only 3 patients had Wilson disease. There was only 1 new diagnosis. Only 27 patients (28.1%) had some form of confirmatory testing performed. In our centre's experience, the positive predictive value of a significantly low ceruloplasmin level is 11.1% (95% CI 2.91-30.3%). In practice a low serum ceruloplasmin measurement is often not followed by appropriate confirmatory testing. Measuring serum ceruloplasmin as a singular diagnostic test for Wilson disease or as part of the battery of unselected liver screening tests is inappropriate and low-yield.

Cosmetic surgical practice: are we complying with professional standards?

UNLABELLED: Aesthetic surgery is a rapidly expanding industry and patient safety is a fundamental issue. The need for regulation has been outlined by the Professional Standards for Cosmetic Practice Report, published by the Royal College of Surgeons in January 2013 which highlighted standards of patient care. The aim of this study was to review institutional compliance with these standards. A retrospective chart review of 40 consecutive patients who underwent either bilateral breast augmentation or bilateral breast reduction between November 2012 and November 2013 within our unit was performed. Compliance with standards relating to practice management, patient consultation, patient communication and record-keeping was examined. While details of past medical history were recorded in most cases, few consultations referred to psychiatric history and cosmetic surgical history specifically. Perioperative documentation and compliance with surgical safety processes were excellent. As a self-regulating profession, it is important that plastic surgeons take the lead in auditing their practice against such published standards. We urge all professionals who carry out cosmetic procedures to regularly review their practice, thereby promoting accountability and maintaining the trust of the general public in the aesthetic surgery industry. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impulsive and compulsive behaviors in Parkinson's disease.

Impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence, and risk factors of patients with PD. Results of behavioral studies assessing the neuropsychological profile of patients with PD emphasize that the ICBs, which are behavioral addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis, are discussed, and therapeutic guidelines for the management of ICBs in PD are given.

Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma.

BACKGROUND: Patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis with median survival reported as 9 months. The failure of systemic chemotherapy to improve prognosis may be due to inadequate penetration of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) has the potential to improve outcomes by facilitating bypass of the BBB. We describe the first use of carboplatin for the treatment of advanced DIPG using a robot-guided catheter implantation technique. METHODS: A 5-year-old boy presented with a pontine mass lesion. The tumor continued to progress despite radiotherapy. Using an in-house modification to neuroinspire stereotactic planning software (Renishaw Plc., Gloucestershire, UK), the tumor volume was calculated as 43.6 ml. A transfrontal trajectory for catheter implantation was planned facilitating the in-house manufacture of a recessed-step catheter. The catheter was implanted using a neuromate robot (Renishaw Plc., Gloucestershire, UK). The initial infusion of carboplatin (0.09 mg/ml) was commenced with real-time T2-weighted MRI, facilitating estimation of the volume of infusate distribution. Infusions were repeated on a total of 5 days. RESULTS: The catheter implantation and infusions were well tolerated. A total volume of 49.8 ml was delivered over 5 days. T2-weighted MRI on completion of the final infusion demonstrated signal change through a total volume of 35.1 ml, representing 95 % of the targeted tumor volume. Follow-up at 4 weeks revealed clinical signs of improvement and increased T2 signal change throughout the volume of distribution. However, there was tumor progression in the regions outside the volume of distribution. CONCLUSIONS: This case demonstrates the feasibility of accurately and safely delivering small-diameter catheters to the brainstem using a robot-guided implantation procedure, and real-time MRI tracking of infusate distribution.

Wellbeing and mental health outcomes amongst hospital healthcare workers during COVID-19.

BACKGROUND: Global healthcare systems have been particularly impacted by the COVID-19 pandemic. Healthcare workers (HCWs) are widely reported to have experienced increased levels of baseline psychological distress relative to the general population, and the COVID-19 pandemic may have had an additive effect. However, previous studies are typically restricted to physicians and nurses with limited data available on hospital HCWs. We aimed to conduct a cross-sectional, psychological evaluation of Irish HCWs during COVID-19. METHODS: HCWs across five adult acute level-4 Dublin-based hospitals completed an online survey of wellbeing and COVID-19 experience. RESULTS: There were 1898 HCWs who commenced the survey representing 10% of the total employee base. The sample comprised nurses (33%), doctors (21%), Health and Social Care Professionals (HSCPs) (24%) and 'Other' disciplines (22%), and 81% identified as female. Clinical levels of depression, anxiety and PTSD symptoms were endorsed by 31%, 34% and 28% of respondents, respectively. Professional grouping effects included: nurses reporting significantly greater levels of COVID-19 exposure, infection, COVID-fear, moral injury, and post-traumatic distress; HSCPs were significantly less likely to report mood dysfunction. In terms of gender, males were significantly less likely to report negative pandemic experiences, low resilience, and significantly more likely to endorse 'minimal' depression, anxiety, and traumatic distress. Logistic regression modelling revealed mental health outcomes (depression, anxiety and PTSD symptoms) were associated with increased frontline exposure, fewer career years' experience, elevated pre-pandemic stress, and female gender. DISCUSSION: To our knowledge, this is the largest evaluation of psychological wellbeing amongst HCWs in acute hospitals in the Dublin region. Our findings have implications for healthcare workforce wellbeing and future service delivery.

The effect of manually facilitated flexion of the thoracic spine on the interspinous space among horses with impinging dorsal spinous processes of the thoracic vertebrae.

Impinging dorsal spinous processes (IDSP) are typically diagnosed and graded using radiography, during which the effect of the horses' thoracolumbar posture on the interspinous spaces is not commonly considered. Posture can be altered from a spontaneous, relatively extended, or lordotic, position by manual facilitation of thoracic flexion ('thoracic lift'). This study aimed to ascertain if the thoracic vertebral interspinous space distances were increased by using facilitated thoracic flexion to alter the posture in horses diagnosed with IDSP. Seven horses of mixed breed and sex, median age 9.1 years (interquartile range, 7.2-12.4 years), with a diagnosis of thoracic IDSP with no history of spinal surgery, were included in the study. Two sets of radiographs were obtained. The initial set was taken in the horses' spontaneous posture and the second in the manually facilitated flexed posture. Each image was anonymised allowing blinded measurement of the interspinous spaces. Analysis was performed using Hodges-Lehmann median differences estimates. An increase in the median interspinous space distance was achieved after manual facilitation of thoracic flexion at every thoracic intervertebral space (5th-18th thoracic [T] vertebra). The greatest median increase was seen between T7-T8 and T12-T13 (3.1 mm and 3.0 mm, respectively) whereas the lowest median increase was seen between T17-T18 (0.7 mm). In this study, thoracic interspinous space distances could be increased by using manual facilitation to alter the thoracic posture in horses with IDSP, which could affect grading and decision making.

LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study.

AIMS: Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have been established as a common genetic cause of Parkinson's disease (PD). The distribution of LRRK2 mRNA and protein in the human brain has previously been described, although it has not been reported in PD cases with the common LRRK2 G2019S mutation. METHODS: To further elucidate the role of LRRK2 in PD, we determined the localization of LRRK2 mRNA and protein in post-mortem brain tissue from control, idiopathic PD (IPD) and G2019S positive PD cases. RESULTS: Widespread neuronal expression of LRRK2 mRNA and protein was recorded and no difference was observed in the morphological localization of LRRK2 mRNA or protein between control, IPD and G2019S positive PD cases. Using quantitative real-time polymerase chain reaction, we demonstrated that there is no regional variation in LRRK2 mRNA in normal human brain, but we have identified differential expression of LRRK2 mRNA with significant reductions recorded in limbic and neocortical regions of IPD cases compared with controls. Semi-quantitative analysis of LRRK2 immunohistochemical staining demonstrated regional variation in staining intensity, with weak LRRK2 immunoreactivity consistently recorded in the striatum and substantia nigra. No clear differences were identified in LRRK2 immunoreactivity between control, IPD and G2019S positive PD cases. LRRK2 protein was identified in a small proportion of Lewy bodies. CONCLUSIONS: Our data suggest that widespread dysregulation of LRRK2 mRNA expression may contribute to the pathogenesis of IPD.

Stereotactic Ablative Radiation Therapy for Large (≥5 cm) Non-small Cell Lung Carcinoma.

AIMS: Stereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting. MATERIALS AND METHODS: We evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan-Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables. RESULTS: In total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58-91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0-9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm3 (range 12.1-203.3 cm3). The median overall survival was 20.9 months (95% confidence interval 12.6-29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4-24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9-20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76-94%), 71% (95% confidence interval 58-84%) and 57% (95% confidence interval 40-74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) - alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities. CONCLUSION: SABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control.

Medicine, media and the law: The effect on training in obstetrics and gynaecology.

The inextricable link between medicine and the legal profession has flourished in the 21st century, with countless newspaper articles and social media content on medical cases visible at every juncture. This is particularly true in the speciality of obstetrics and gynaecology, with one of the highest rates of litigation of all medical specialities. We aimed to evaluate the influence of media and the legal environment on the career of trainees in obstetrics and gynaecology. Under the auspices of the Irish national training body, we distributed a 26-item questionnaire to doctors-in-training (DIT) working in obstetrics and gynaecology in the Republic of Ireland. Descriptive statistics and Chi-squared analyses were performed on the anonymised data. 151 DIT responded to the questionnaire, with a response rate of 86.2 % (sample size = 175). The majority were female (79.9 %, n = 121), Irish (85.5 %, n = 106) and had no children (67.0 %, n = 83). 86.7 % (n = 131) felt that the media did not have a positive impact on patients receiving care, and, further, unfairly represented the speciality (94.1 %; n = 142). Additionally, DIT felt that medico-legal issues had a negative impact on issues such as retention and recruitment. These two areas were implicated in over three quarters of DIT considering leaving the speciality. This study demonstrates that DIT perceive media scrutiny and litigation to have a negative effect on the speciality of obstetrics and gynaecology. Further support integrated into specialist training, is needed to ensure that trainees are adequately equipped to deal with both mainstream and social media as well as interactions they may have with the legal profession as they progress through their career.