Cohort profile: King's Health Partners bladder cancer biobank.

BACKGROUND: Bladder cancer (BC) is the 9th most common cancer worldwide, but little progress has been made in improving patient outcomes over the last 25 years. The King's Health Partners (KHP) BC biobank was established to study unanswered, clinically relevant BC research questions. Donors are recruited from the Urology or Oncology departments of Guy's Hospital (UK) and can be approached for consent at any point during their treatment pathway. At present, patients with bladder cancer are approached to provide their consent to provide blood, urine and bladder tissue. They also give access to medical records and linkage of relevant clinical and pathological data across the course of their disease. Between June 2017 and June 2019, 531 out of 997 BC patients (53.3%) gave consent to donate samples and data to the Biobank. During this period, the Biobank collected fresh frozen tumour samples from 90/178 surgical procedures (of which 73 were biopsies) and had access to fixed, paraffin embedded samples from all patients who gave consent. Blood and urine samples have been collected from 38 patients, all of which were processed into component derivatives within 1 to 2 h of collection. This equates to 193 peripheral blood mononuclear cell vials; 238 plasma vials, 224 serum vials, 414 urine supernatant vials and 104 urine cell pellets. This biobank population is demographically and clinically representative of the KHP catchment area. CONCLUSION: The King's Health Partners BC Biobank has assembled a rich data and tissue repository which is clinically and demographically representative of the local South East London BC population, making it a valuable resource for future BC research.

Repurposing of drugs for COVID-19: a systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review was to evaluate the data currently available regarding the repurposing of different drugs for COVID-19 treatment. Participants with suspected or diagnosed COVID-19 were included in this study. The interventions that have been considered were repurposed drugs and comparators that included standard of care treatment or placebo. EVIDENCE ACQUISITION: We searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915). EVIDENCE SYNTHESIS: From 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (P=0.68). Adverse events with HCQ have a significant difference compared to the control group (P=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (P=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power. CONCLUSIONS: Due to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of COVID-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events.

Decisions around Deceased Organ Donation in Young South Asian Individuals in the United Kingdom.

There is a large disparity between the demand and availability of organs for transplantation from within the UK's ethnic minority groups. Our aims were to identify the perceptions, knowledge of and level of engagement with organ donation since the law changed in England in 2020. A questionnaire survey using Google Forms was designed based on prior literature and information on NHSBT website. It was distributed through media outlets and cultural/professional organizations. Status on Organ Donation Registry and Quiz scores were analyzed against multiple variables. Three hundred and sixty-five people between 18 and 24 years old completed the questionnaire. 72.3% were female, 57% were health-care students, 86.3% were of South Asian ethnicity, and 11% were immigrant respondents. Overall, 43.6% were registered to donate. South Asian groups, particularly those of Pakistani ethnicity and migrant students, were less likely to register to donate. Being more knowledgeable about the organ donation process, females, nonreligious groups, and health-care students are more likely to be registered to donate. This study identified barriers around deceased organ donation decisions and demonstrates the need for further targeted and continual education to the young South Asians individuals, to produce positive associations that will percolate to older and future generations.

Identifying Recurrence Risk Factors in CT-Confirmed Acute Appendicitis in Adults Managed Non-operatively During the COVID-19 Pandemic.

BACKGROUND/OBJECTIVE:  Acute appendicitis (AA) is predominantly managed with appendectomy, but can be treated non-operatively, leading to a high risk of recurrence. Non-operative management has been more common since the COVID-19 pandemic affected the feasibility of performing surgery. This case-control study analyzed non-operatively managed patients in order to identify clinical and radiological factors associated with recurrence risk.  Methods: Over 12 months, 48 adults with CT-proven AA managed non-operatively were identified, and followed up for at least six further months to assess them for recurrence (readmission to hospital more than 14 days after discharge and after symptom resolution, requiring treatment for appendicitis). Clinical and CT data were collected and a Cox regression survival analysis was performed to produce hazards ratios (HRs). RESULTS:  Of the 48 patients, 12 (25%) experienced a recurrence up until the end of the follow-up period, eight of whom were then treated operatively, and four treated non-operatively. On the univariate analysis, greater recurrence risk was observed in patients with diabetes mellitus, higher heart rate (on admission and maximum value during admission), lower white cell count and neutrophils and appendiceal wall thinning on CT. On the multivariate analysis, diabetes mellitus (HR=7.72, p=0.021) and higher heart rate (HR=1.08, p=0.018) were associated with statistically significant greater recurrence risk. CONCLUSIONS:  Diabetes mellitus and higher heart rate on admission are associated with greater recurrence risk of AA managed non-operatively. No CT findings were associated with statistically significant greater risk. Clinicians should, therefore, consider DM and heart rate when making decisions on appendicitis management, especially during the COVID-19 pandemic but also beyond it.

The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans.

INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-Coronavirus (SARS-CoV-2) in Wuhan, China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global Coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review was to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a-priori protocol registration with PROSPERO (181483), systematic research of the published literature was conducted on April 24, 2020, using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database to identify relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA Guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 preprint articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.

Scoping review: bladder cancer in Nigeria - what are the gaps in clinical care and research?

OBJECTIVES: There are currently no national guidelines regarding bladder cancer treatment and clinical care pathways in Nigeria. The aim of this scoping review was to identify any gaps in the knowledge of epidemiology, clinical care and translational research in order to aid the development of a defined clinical care pathway and guide future research. METHODS: A scoping review was conducted by searching Medline, Ovid Gateway, The Cochrane library and Open Grey literature using predefined search terms from date of inception to June 2020. Studies were included if they discussed the epidemiology or treatment pathway of bladder cancer. All data were charted and were analysed in a descriptive manner. A consultation phase was also conducted consisting of a multidisciplinary team of clinicians and bladder cancer survivors. RESULTS: A total of 19 studies were deemed suitable for inclusion. The themes included the epidemiology of bladder cancer (high prevalence of schistosomiasis), research surrounding the biology of the disease and translational research including potential biomarkers. The consultation phase highlighted some possible sociocultural and infrastructural issues relating to both the diagnosis and treatment of bladder cancer, with poor knowledge of bladder cancer and its symptoms within the general population identified as a key issue. CONCLUSION: Even though the factors surrounding the relationship between schistosomiasis and the histopathology of bladder cancer remain unclear, there is potential for screening for schistosomiasis in endemic regions of sub-Saharan Africa. Other key areas for future research include the dissemination of information to the general population surrounding bladder cancer and its symptoms to encourage prompt diagnosis.

Use of Duloxetine for Postprostatectomy Stress Urinary Incontinence: A Systematic Review.

CONTEXT: The recommended treatment of postprostatectomy stress urinary incontinence (PPSUI) after failure of pelvic floor muscle training is primarily surgical intervention with a male sling or artificial urinary sphincter. The use of pharmacological therapy in this setting is unlicensed and controversial. OBJECTIVE: To systematically review the available evidence regarding the efficacy and safety of duloxetine for the treatment of stress urinary incontinence following prostate surgery (radical or endoscopic). EVIDENCE ACQUISITION: The EMBASE, MEDLINE/PubMed, and Cochrane Central Register of Controlled Trials were searched from inception up until April 17, 2020. All studies evaluating the role of duloxetine in men with PPSUI were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed data extraction. The quality of evidence and risk of bias were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE); Cochrane; and Risk of Bias in Nonrandomised Studies of Interventions (ROBINS-I) tools. EVIDENCE SYNTHESIS: The search yielded 234 studies. After excluding duplicates, 140 titles and abstracts were screened, and eight reports (348 patients) were eligible for inclusion in the final review. Duloxetine was assessed in two scenarios: (1) early use to reduce the time to attain continence and (2) treatment of persistent PPSUI. Most men had mild-to-moderate incontinence at baseline. Overall, duloxetine resulted in a mean dry rate of 58% (25-89%), mean improvement in pad number of 61% (12-100%), and mean improvement in 1-h pad weight of 68% (53-90%) at short-term follow-up (mean 1-9 mo; low to moderate certainty of evidence). However, mean adverse event rates were relatively high, and treatment was discontinued in 38% (low certainty of evidence). CONCLUSIONS: Duloxetine has demonstrated good short-term cure and/or improvement in treating men with persistent PPSUI, as well as in reducing the time to attain continence. However, a proportion of men discontinue treatment due to adverse events. The overall certainty evidence is moderate to low, with heterogeneity between studies and methodological limitations. However, we have highlighted the need for further randomised trials with longer follow-up, utilising consistent outcome reporting measures. Despite these limitations, the findings from this review will aid patient counselling regarding this less invasive treatment option, thereby allowing personalisation of care centred around the values and preferences of individual patients. PATIENT SUMMARY: Duloxetine has good success rates in the short term, in terms of improving incontinence symptoms in men who have undergone prostate surgery. However, some men experience side effects bad enough to require cessation of treatment. Further studies are needed to determine whether duloxetine maintains its effectiveness in the long term.

Endoscopic surveillance for bladder cancer: a systematic review of contemporary worldwide practices.

BACKGROUND: The aim of this systematic review was to identify the current endoscopic surveillance strategies in use across the world and to determine whether these were sufficient or if any recommendations for changes in the guidelines could be made. This review focused on the cystoscopic follow-up of non-muscle invasive bladder cancer (NMIBC) patients and muscle invasive bladder cancer (MIBC) patients who had undergone bladder sparing treatments. METHODS: A literature search was carried out on Medline and Embase using OVID gateway according to a pre-defined protocol. Systematic screening of the identified studies was carried out by two authors. Quality assessment was performed using the Joanna Briggs critical appraisal tools. Data was extracted on various aspects including the follow-up regime utilised, patients included, outcomes investigated and a summary of the results. The studies were compared in a narrative nature. RESULTS: A total of 2,604 studies were identified from the search strategy, of which 14 were deemed suitable for inclusion following the screening process. The studies identified were from nine countries and were mainly observational or qualitative. There was a huge variation in the follow-up regimes utilised within the studies with no clear consensus as to which regime was the most suitable. However, all studies utilised an initial cystoscopy at three months post-TURBT. No studies were identified which investigated the endoscopic follow-up strategies for MIBC patients who opted for bladder conservation with chemoradiation. CONCLUSIONS: There is no universally accepted protocol for endoscopic follow-up of patients with NMIBC bladder cancer. Guidance on cystoscopic monitoring of bladder in patients who have undergone chemoradiation for MIBC is also lacking.

Scoping review protocol: bladder cancer in Nigeria: what are the gaps in clinical care and research?

INTRODUCTION: Bladder cancer (BC) is the 10th common cancer worldwide and ranks seventh in Nigeria. This scoping review aims to identify the gaps in clinical care and research of BC in Nigeria as part of the development of a larger national research programme aiming to improve outcomes and care of BC. METHODS AND ANALYSIS: This review will be conducted according to Arksey and O'Malley scoping review methodology framework. The following electronic databases will be searched: Medline (using the PubMed interface), Ovid Gateway (Embase and Ovid), Cochrane library and Open Grey literature. Two independent reviewers will screen titles and abstracts and subsequently screen full-text studies for inclusion, any lack of consensus will be discussed with a third reviewer. Any study providing insight into the epidemiology or treatment pathway of BC (RCTs, observations, case series, policy paper) will be included. A data chart will be used to extract relevant data from the included studies. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. A consultation process will be carried out with a multidisciplinary team of Nigerian healthcare professionals, patients and scientists. ETHICS AND DISSEMINATION: The results will be disseminated through peer-reviewed publications. By highlighting the key gaps in the literature, this review can provide direction for future research and clinical guidelines in Nigeria (and other low-income and middle-income countries), where BC is more prevalent due to local risk factors and healthcare settings.

Safety of "hot" and "cold" site admissions within a high-volume urology department in the United Kingdom at the peak of the COVID-19 pandemic.

OBJECTIVES: To determine the safety of urological admissions and procedures during the height of the COVID-19 pandemic using "hot" and "cold" sites. The secondary objective is to determine risk factors of contracting COVID-19 within our cohort. PATIENTS AND METHODS: A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high-volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a "cold" site requiring a negative COVID-19 swab 72-hours prior to admission and patients were required to self-isolate for 14-days preoperatively, while all acute admissions were admitted to the "hot" site.Complications related to COVID-19 were presented as percentages. Risk factors for developing COVID-19 infection were determined using multivariate logistic regression analysis. RESULTS: A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the urology team; 101 (16.5%) on the "cold" site and 510 (83.5%) on the "hot" site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID-19 postoperatively with one (0.2%) postoperative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). CONCLUSIONS: Continuation of urological procedures using "hot" and "cold" sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a postoperative mortality.