Systematic review on urinary continence rates after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: The objective was to investigate the current evidence and discern urinary continence rates post robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: A systematic review of the literature was carried out, searching the Embase, Scopus and PubMed databases between 1 January 2000 and 1 May 2020. The search terms "Robotic prostatectomy AND continence" were employed. Articles were selected in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Statistical analysis was performed using the programme R; cumulative analysis of percentage of men continent was calculated. RESULTS: A total of 3101 abstracts and 50 full text articles were assessed, with 22 publications included (n = 2813 patients). There were 21 randomised controlled trials and one partly randomised controlled trial with four publications comparing RALP to other prostate cancer treatments. Thirteen studies explored different RALP techniques, and five studies examined vesicourethral anastomosis (VUA). There were statistically significant improvements in early urinary continence rates in three studies analysing reconstructive techniques (83% vs 60%, p = 0.04; 26.5% vs 15.4%, p = 0.016; 77% vs 44.1%, p ≤ 0.001). Long-term continence rates were not significantly improved across all studies assessing reconstruction. One study comparing RALP vs laparoscopic radical prostatectomy (LRP) demonstrated a statistically significant improvement in continence at 3 months (80% vs 73.3%, p < 0.001); 6 months (83.3% vs 81.4%, p < 0.001); 12 months (95% vs 83.3%, p < 0.001) and 24 months (96.7% vs 85%, p < 0.001). Early continence was less favourable for RALP when compared to brachytherapy (BT) patients at 3 months (86% vs 98.7%, p < 0.05) and 6 months (90.5% vs 98.7%, p < 0.05). CONCLUSION: Early continence rates were improved across numerous techniques in RALP. These results were not translated into significantly improved long-term outcomes. Continence rates following RALP were favourable compared to LRP, similar to ORP and less favourable compared to BT. Our findings suggest that post-RALP continence can be further improved with alterations in robotic technique.

Persistence of inadequate consent training for interns.

BACKGROUND: Informed consent is a continuous process of communication with the patient and not merely the signing of a form. The Irish Medical Council's Guide to Good Practice and Ethics state that no part of the consent process should be delegated to an intern unless the procedure is a minor with which the intern is very familiar and all relevant information has first been explained to the intern. AIMS: We aimed to evaluate whether practices regarding interns and consent had changed in the past five years. METHODS: An anonymous Google Forms survey was distributed to interns from all intern networks between 24-August and 26-November 2021. RESULTS: Of 854 interns, there were 147(17.2%) survey responses. 129(87.8%) participants had consented for a procedure. 111(86%) responded that they had consented for procedures that they had not witnessed before. 92(71.3%) reported that their medical supervisor did not explain procedures to them prior to obtaining consent. 128(99.2%) of interns were not usually observed by a more senior doctor when obtaining consent. 116(89.9%) were expected to obtain consent from patients on a regular basis, with 78(60.5%) feeling pressured into doing so on at least one occasion. Results were largely unchanged compared to when the same survey was circulated in 2016. CONCLUSIONS: Interns remain routinely involved in the consent process without adequate training or supervision. This is unfair on our most junior doctors and on patients. Steps must be taken to ensure the IMC guidance is adhered to and this deficiency must be highlighted to Senior Clinicians.

Improving Anxiety and Depression in Pregnant Mothers Participating in Nurse Home Visitation.

The perinatal period is a time of significant adjustment for mothers, which may lead to alterations in mood that affect maternal mental health, which may also impact child development. The current article details the effectiveness of the addition of a psychiatric-mental health nurse practitioner (PMHNP) and mental health training for nurses on the anxiety and depression screening scores of mothers enrolled in a home visitation program. For clients with elevated anxiety and depression scores, the percentages of those who were referred to and received mental health services increased after the program's addition of the PMHNP and mental health training. Implications for future research and practice include continued focus on maternal mental health with improved access to assessment and treatment for all clients within home visitation. [Journal of Psychosocial Nursing and Mental Health Services, 62(4), 49-55.].

The ARTS (Avoiding Risks of Thrombosis and Bleeding in Surgery) Trial: Lessons Learnt in Setting Up an International Multicentre Clinical Trial of an Investigational Medicinal Product in the UK.

We describe our experience in setting up the UK arm of the ARTS trial and highlight regulatory and funding challenges in relation to an international multicentre setting for an investigational medicinal product.

Scientific and Regulatory Policy Committee Best Practices: Recommended ("Best") Practices for Informed (Non-blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies.

This article describes the Society of Toxicologic Pathology's (STP) five recommended ("best") practices for appropriate use of informed (non-blinded) versus masked (blinded) microscopic evaluation in animal toxicity studies intended for regulatory review. (1) Informed microscopic evaluation is the default approach for animal toxicity studies. (2) Masked microscopic evaluation has merit for confirming preliminary diagnoses for target organs and/or defining thresholds ("no observed adverse effect level" and similar values) identified during an initial informed evaluation, addressing focused hypotheses, or satisfying guidance or requests from regulatory agencies. (3) If used as the approach for an animal toxicity study to investigate a specific research question, masking of the initial microscopic evaluation should be limited to withholding only information about the group (control or test article-treated) and dose equivalents. (4) The decision regarding whether or not to perform a masked microscopic evaluation is best made by a toxicologic pathologist with relevant experience. (5) Pathology peer review, performed to verify the microscopic diagnoses and interpretations by the study pathologist, should use an informed evaluation approach. The STP maintains that implementing these five best practices has and will continue to consistently deliver robust microscopic data with high sensitivity for animal toxicity studies intended for regulatory review. Consequently, when conducting animal toxicity studies, the advantages of informed microscopic evaluation for maximizing sensitivity outweigh the perceived advantages of minimizing bias through masked microscopic examination.

Exploring the Relationship Between Modifiable Protective Factors and Mental Health Issues Among Children Experiencing Adverse Childhood Experiences Using a Resilience Framework.

The purpose of this study was to examine whether the National Scientific Council on the Developing Child (NSCDC) resilience framework statistically predicted whether a child with 4 or more adverse childhood experiences (ACEs) ever had a mental health issue. The study also explored which NSCDC modifiable resilience factors had the strongest relationship with mental health issues among children with 4 or more ACEs. Utilizing the 2019 National Survey of Children's Health, secondary data analysis was conducted using a sample of 1,225 children between 6 and 17 years old that had experienced 4 or more ACEs. Logistic regression examined whether the NSCDC framework was associated with a lower likelihood of mental health issues in school-aged children. Analysis found that the NSCDC framework predicted whether children with 4 or more ACEs ever had a mental health issue. Self-regulation had the strongest relationship with whether a child with 4 or more ACEs ever had a mental health issue. A supportive parent/caregiver relationship was also associated with a lower likelihood of ever having a mental health issue. The results demonstrate the promise of the NSCDC framework and modifiable protective factors to mitigate the impact of ACEs on mental health outcomes. Interventions that teach children skill-based self-regulation and parent/caregiver co-regulation while providing safe and supportive environments can build self-regulation to overcome ACEs. Promoting resilience-building parent-child relationships also have the potential to build resilience to mitigate ACEs.

Scientific and Regulatory Policy Committee Points to Consider for Medical Device Implant Site Evaluation in Nonclinical Studies.

Nonclinical implantation studies are a common and often critical step for medical device safety assessment in the bench-to-market pathway. Nonclinical implanted medical devices or drug-device combination products require complex macroscopic and microscopic pathology evaluations due to the physical presence of the device itself and unique tissue responses to device materials. The Medical Device Implant Site Evaluation working group of the Society of Toxicologic Pathology's (STP) Scientific and Regulatory Policy Committee (SRPC) was tasked with reviewing scientific, technical, and regulatory considerations for these studies. Implant site evaluations require highly specialized methods and analytical schemes that should be designed on a case-by-case basis to address specific study objectives. Existing STP best practice recommendations can serve as a framework when performing nonclinical studies under Good Laboratory Practices and help mitigate limitations in standards and guidances for implant evaluations (e.g., those from the International Organization for Standardization [ISO], ASTM International). This article integrates standards referenced by sponsors and regulatory bodies with practical pathology evaluation methods for implantable medical devices and combination products. The goal is to ensure the maximum accuracy and scientific relevance of pathology data acquired during a medical device or combination drug-device implantation study.

The Potential for Teacher-Student Relationships and the Whole School, Whole Community, Whole Child Model to Mitigate Adverse Childhood Experiences.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with poorer health and educational outcomes. With over 20% of children experiencing multiple ACEs, interventions must target protective factors to improve outcomes among these students. Teacher-student relationships (TSRs) integrated with the Whole School, Whole Community, Whole Child (WSCC) are one promising approach to building resilience to overcome ACEs. METHODS: A narrative literature review was conducted on ACEs, resilience, TSRs, and the WSCC model to explore the evidence and potential of TSR interventions integrated within the WSCC model to build resilience in students experiencing ACEs. RESULTS: Supportive adult relationships are one of the strongest protective factors against ACEs. TSR interventions have improved student and relationship outcomes. Few studies have explored the relationship between TSRs and ACEs or TSR ACEs interventions. The WSCC model provides opportunities to integrate TSRs and other protective factors into a schoolwide health model to build resilience. CONCLUSIONS: TSRs and the WSCC model are promising approaches to target protective factors to mitigate ACEs. Research is needed to further establish TSRs as a protective factor, explore TSR ACEs interventions, and determine best practices for integrating TSRs and resilience in the WSCC model.

A novel next-generation FVIIIa mimetic, Mim8, has a favorable safety profile and displays potent pharmacodynamic effects: Results from safety studies in cynomolgus monkeys.

BACKGROUND: Mim8 is a novel, next-generation factor VIIIa mimetic in development for subcutaneous prophylactic treatment of patients with hemophilia A with and without inhibitors. In vitro and in vivo models indicate that Mim8 has a distinct hemostatic potential. OBJECTIVES: To test the nonclinical safety and pharmacodynamics of Mim8. METHODS: The Mim8 nonclinical safety program in cynomolgus monkeys consisted of three studies of 4-26 weeks in duration with Mim8 doses ranging from 0.3-60 mg/kg/week intravenously or subcutaneously. After sacrifice, macroscopic and microscopic pathological examinations were performed. RESULTS: Mim8 was well tolerated with no noteworthy clinical observations. No signs of excessive coagulation or pathological macroscopic or microscopic findings were observed at doses 0.3-3 mg/kg/week subcutaneous. Thrombosis-related findings were detected during histopathological examination in a small proportion of animals (16%) receiving doses ranging 6-20 mg/kg/week. Dose-dependent increases in factor X (FX) and factor IX (FIX) concentrations were observed. Shortening of activated partial thromboplastin time (APTT) and increased thrombin generation under ex vivo hemophilia A-like conditions were observed at all Mim8 dose levels. CONCLUSIONS: Thrombosis-related findings observed at doses above 6 mg/kg/week Mim8 may have been exaggerated pharmacological reactions to a procoagulant compound in normocoagulant animals. Increases in FX and FIX concentrations could be because of a half-life prolongation due to binding to Mim8, but were limited at clinically relevant exposure levels. Subcutaneous administration of up to 3 mg/kg/week (several fold greater than expected clinical exposure) for 26 weeks resulted in relevant pharmacodynamic effects, observed in thrombin generation and APTT, with no signs of thrombi or excessive coagulation activation.

A Shifting Trend Towards Endovascular Intervention in the Treatment of Acute Mesenteric Ischemia.

Background Acute mesenteric ischemia (AMI) is a vascular emergency with a quite low incidence, but it is associated with disproportionately more severe morbidity and mortality. The aim of this study was to assess the current trend in the treatment of AMI and to see if endovascular intervention is an effective treatment modality in the selected group of patients. Methods A retrospective review of patients admitted with AMI between 2007 and 2018 was performed. Outcome measures were length of stay (LOS) at hospital and intensive care unit (ICU), and post-treatment mortality. Results A total of 98 patients with AMI were admitted during the study period. Patients undergoing endovascular treatment compared with surgery were younger (62.9 ± 13.7 years vs. 69.5 ± 12.8 years; p = 0.01). Shorter LOS in hospital and ICU was observed for those treated with endovascular approach (6.8 ± 3.4 and 3.25 ± 0.5 days) compared to the surgical group (25 ± 8.6 and 12.8 ± 26.8 days; p < 0.001). Out of 39 patients requiring ICU admission, 48.7% were surgically treated and 10.2% underwent endovascular intervention (p < 0.001). Mortality associated with surgery was 30.6% compared to only 6.6% with endovascular intervention (p < 0.001). Between 2007 and 2012, only one patient underwent endovascular intervention and 20 underwent surgery compared to 14 patients treated with endovascular approach and 16 with surgery between 2013 and 2018. Conclusion In this non-randomized, retrospective case series, patients with endovascular treatment fared clinically better and the intervention was found to be safe and feasible in the selected group of patients. We suggest a preference for this modality where possible. At our hospital, a trend favoring this approach is apparent during the last six years.

Characterization of the Nonendocrine Cell Populations in Human Embryonic Stem Cell-Derived (hESC) Islet-Like Clusters Posttransplantation.

Islet-like clusters derived from human embryonic stem cells (hESC) hold the potential to cure type 1 diabetes mellitus. Differentiation protocols of islet-like clusters lead to the generation of minor fractions of nonendocrine cells, which are mainly from endodermal and mesodermal lineages, and the risk of implanting these is unclear. In the present study, the histogenesis and the tumorigenicity of nonendocrine cells were investigated in vivo. Immunodeficient mice were implanted under the kidney capsule with islet-like clusters which were derived from differentiation of cells batches with either an intermediate or poor cell purity and followed for 8 or 26 weeks. Using immunohistochemistry and other techniques, it was found that the intermediate differentiated cell implants had limited numbers of small duct-like cysts and nonpancreatic tissue resembling gastrointestinal and retinal pigmented epithelium. In contrast, highly proliferative cystic teratomas were found at a high incidence at the implant site after 8 weeks, only in the animals implanted with the poorly differentiated cells. These findings indicate that the risk for teratoma formation and the amount of nonpancreatic tissue can be minimized by careful in-process characterization of the cells and thus highlights the importance of high purity at transplantation and a thorough ex-vivo characterization during cell product development.

Urology at your fingertips: the development of a urology m-learning app for medical students.

BACKGROUND: Surgical education has embraced advancing technology with an emphasis on e-learning in recent years. Smartphones are a useful tool for medical teaching and learning with increasing use by medical students to access e-books, medical calculators, podcasts, and medical applications (apps). Our aim was to develop a dedicated urology app for medical students as an adjunct to traditional teaching. METHODS: We published an e-book: Urology Handbook for Medical Students in 2017 based on the core urology curriculum for medical students. Subsequently, we developed a concise, simple and user-friendly smartphone app for medical students called "Urology Med", available for download on App Store and Google Play. RESULTS: This app is an introduction to urology for medical students but may also be useful for interns and surgical trainees. The app encompasses core urology topics subdivided into common urological presentations, urological examination, urological diseases, and urological devices. To make the app interactive, it includes 5 clinical cases that complement the reading material and six quizzes for self-assessment. A comprehensive checklist of 31 "must see" and "good to see" urology experiences is included. Within one month of launch, the app was downloaded 435 times in five countries across three continents. It has a 5-star rating on the Apple store. CONCLUSIONS: High educational standards with relevant content make e-learning a valuable learning tool for surgical education. The Urology Med app facilitates easy access to urology and is ideal for quick reading while working or revising.

Implementation of a nurse-led lower urinary tract symptoms (LUTS) clinic reduces general urology clinic workload in a Model 4 Hospital: a pilot study in Tallaght University Hospital.

BACKGROUND: With among the lowest urologist per population ratios in Europe, the demand for urology specialist review in Ireland far exceeds supply. Lower urinary tract symptoms (LUTS) account for a significant number of referrals. The traditional paradigm of every patient being reviewed in a consultant-led clinic is unsustainable. New models of care with nurse-led clinics represent an opportunity to optimise limited resources. METHODS: Existing long-waiting male LUTS referrals were triaged to a specialist nurse-led LUTS clinic. After urology CNS assessment, charts were reviewed by a consultant urologist and a plan formulated. Relevant data were prospectively collected and analysed. RESULTS: Fifty-eight new male patients with LUTS were seen over a 6-month period with an average waiting time of 15.8 months. Patients were assessed with uroflowmetry, IPSS and DRE. Mean age was 64, IPSS 14.5, Qmax 18.3 ml/s and PVR 89 ml. Thirty patients (52%) were discharged directly with lifestyle modification and medical therapy. Twenty-eight patients (48%) required one or more further investigations and subsequent review; 11 had flexible cystoscopy, 4 had urodynamics, 5 had prostate MRI, and 2 patients were listed for surgery (TURP and circumcision). The remaining 10 patients were for review post trial of lifestyle modifications and/or medical treatment. After review/investigations, 4 more patients were discharged. A total of 32 patients (55%) were discharged or listed for surgery after initial assessment. This total increased to 62% after a second review/investigations. CONCLUSION: Introduction of a CNS-led LUTS clinic has significantly reduced the number of patients requiring follow-up in general urology clinics, representing a quality improvement in service provision.

Adversity Considerations for Thyroid Follicular Cell Hypertrophy and Hyperplasia in Nonclinical Toxicity Studies: Results From the 6th ESTP International Expert Workshop.

The European Society of Toxicologic Pathology organized an expert workshop in May 2018 to address adversity considerations related to thyroid follicular cell hypertrophy and/or hyperplasia (FCHH), which is a common finding in nonclinical toxicity studies that can have important implications for risk assessment of pharmaceuticals, food additives, and environmental chemicals. The broad goal of the workshop was to facilitate better alignment in toxicologic pathology and regulatory sciences on how to determine adversity of FCHH. Key objectives were to describe common mechanisms leading to thyroid FCHH and potential functional consequences; provide working criteria to assess adversity of FCHH in context of associated findings; and describe additional methods and experimental data that may influence adversity determinations. The workshop panel was comprised of representatives from the European Union, Japan, and the United States. Participants shared case examples illustrating issues related to adversity assessments of thyroid changes. Provided here are summary discussions, key case presentations, and panel recommendations. This information should increase consistency in the interpretation of adverse changes in the thyroid based on pathology findings in nonclinical toxicity studies, help integrate new types of biomarker data into the review process, and facilitate a more systematic approach to communicating adversity determinations in toxicology reports.

Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (ß-Amyloid; Aß). Both IAPP and Aß can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD.

Serum Vitamin D status is associated with increased blastocyst development rate in women undergoing IVF.

RESEARCH QUESTION: To determine the relationship between vitamin D (VitD) status and embryological, clinical pregnancy and live birth outcomes in women undergoing IVF. DESIGN: Cross-sectional, observational study conducted at a university-affiliated private IVF clinic. A total of 287 women underwent 287 IVF cycles and received a fresh embryo transfer. Patients had their serum 25-hydroxyvitamin D2/D3 (VitD) determined on the day of oocyte retrieval, which was analysed in relation to blastocyst development rate, clinical pregnancy and live birth outcomes. RESULTS: In stepwise, multivariable logistic regression models, increases in blastocyst development rate, number and quality, along with embryo cryopreservation and utilization rates were associated with women with a sufficient VitD status (≥20 ng/ml). For a single increase in the number of blastocysts generated per cycle or embryos cryopreserved per cycle, the likelihood for the patient to be VitD sufficient was increased by 32% (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.10-1.58, P = 0.002 and OR 1.33, 95% CI 1.10-1.60, P = 0.004, respectively). Clinical pregnancy (40.7% versus 30.8%, P = 0.086) and live birth rates (32.9% versus 25.8%, P = 0.195) in the sufficient VitD group versus the insufficient group were not significantly different and VitD sufficiency was not significantly associated with these outcomes. CONCLUSION: A strong relationship was observed between blastocyst development and VitD sufficiency. However, there was no association between VitD and clinical pregnancy or live birth outcomes. Further larger studies are needed to investigate whether the observed effect on blastocyst development may have downstream implications on subsequent clinical pregnancy or live birth rates, and on a potential mechanism where sufficient VitD concentrations are linked to improved IVF outcomes.

MPA given orally during the first trimester for threatened miscarriage carries no specific risk for foetal abnormalities albeit the rate is higher than non-threatened pregnancies.

This observational study examines the outcomes of pregnancies arising in women referred for infertility, where those who experienced threatened miscarriage were treated with medroxyprogesterone acetate (MPA) tablets. The 14-year study period covers comprehensive real-time data entries into the validated electronic database including details of the infertility management, pregnancy outcomes and any foetal anomalies among the infants, each being tracked and recorded. Of 4057 clinical pregnancies, 1343 received MPA for threatened miscarriage; 934 (69.6 %) of which continued to livebirths. These were compared with the remaining 2714 clinical pregnancies without threatened miscarriage or MPA and which resulted in 2075 (76.5 %) livebirths. There were 134 developmental abnormalities recorded among the 3009 livebirths of which 78 (2.6 %) were categorised appropriate for the Western Australian Developmental Abnormalities Register; WARDA. These comprised 55 in the MPA group, 36 of which were categorised as serious (being 2.7 % of clinical pregnancies and 3.9 % of births). In the group without MPA, there were 79 abnormalities, of which 42 were categorised as serious (being 1.7 % of clinical pregnancies and 2.2 % of births). Specifically, there were no cases of androgenisation noted among the female infants. The abnormality rates were low overall and well within the annual WARDA ranges. We cautiously suggest that oral MPA can be considered for studies throughout pregnancy including the early first trimester to assess a potential role in reducing miscarriage, as well as advanced pregnancies to evaluate a potential role in reducing stillbirths and preterm delivery.