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.

Urology Residency Training at the Time of COVID-19 in Italy: 1 Year After the Beginning.

The coronavirus disease 2019 (COVID-19) pandemic has led to significant changes in urology practice and residency programs. One year ago, the first nationwide survey on this topic showed a dramatic impact of the acute phase of the pandemic on residents' training activities. Aiming to assess for the first time how the COVID-19 scenario reshaped the pattern of urology training over a whole pandemic year, a cross-sectional, 38-item, web-based survey was developed. Residents scored the percentage decrease of their involvement in various clinical and surgical activities during the period of March 2020-March 2021 (as compared with the pre-COVID period). Overall, 312/585 (53.3%) residents from 27 schools of urology were included. The proportions of those experiencing a significant decrease of training exposure were 13.6%, 28.8%, 26.7%, 46.9%, 37.6%, and 33.3% (as compared with 40.2%, 85.8%. 82.3%, 69.7%, 59.7%, and 50.2% in the previous survey) for on-call activities, outpatient visits, diagnostic procedures, endoscopic surgery, open surgery, and minimally invasive surgery, respectively. The most impactful reductions in training activities were reached by final-year residents. Our findings highlight that, even if less burdensome than expected, urology residency training (especially in endoscopic surgery) was highly affected throughout the whole past year. This critical gap of skills may jeopardize residents' training even beyond the COVID-19 pandemic. PATIENT SUMMARY: In this study, we assessed whether the training activities of Italian urology residents were impacted negatively by a whole year of COVID-19 pandemic (March 2020-March 2021). We also compared our results with those reported in a previous survey evaluating how the coronavirus disease 2019 (COVID-19) pandemic changed the training pattern of urology residents during the peak of the outbreak in March 2020. We found a critical decrease in residents' activities (especially for those in their final years of residency and for surgical procedures) that, even if lower than expected, might negatively impact their education and training in the future.

Implementing telemedicine for the management of benign urologic conditions: a single centre experience in Italy.

PURPOSE: To assess the use of telemedicine with phone-call visits as a practical tool to follow-up with patients affected by urological benign diseases, whose clinic visits had been cancelled during the acute phase of the COVID-19 pandemic. METHODS: Patients were contacted via phone-call and a specific questionnaire was administered to evaluate the health status of these patients and to identify those who needed an "in-person" ambulatory visit due to the worsening of their condition. Secondarily, the patients' perception of a potential shift towards a "telemedicine" approach to the management of their condition and to indirectly evaluate their desire to return to "in-person" clinic visits. RESULTS: 607 were contacted by phone-call. 87.5% (531/607) of the cases showed stability of the symptoms so no clinic in-person or emergency visits were needed. 81.5% (495/607) of patients were more concerned about the risk of contagion than their urological condition. The median score for phone visit comprehensibility and ease of communication of exams was 5/5; whilst patients' perception of phone visits' usefulness was scored 4/5. 53% (322/607) of the interviewees didn't own the basic supports required to be able to perform a real telemedicine consult according to the required standards. CONCLUSION: Telemedicine approach limits the number of unnecessary accesses to medical facilities and represents an important tool for the limitation of the risk of transmission of infectious diseases, such as COVID-19. However, infrastructures, health workers and patients should reach out to a computerization process to allow a wider diffusion of more advanced forms of telemedicine, such as televisit.

Deferring Elective Urologic Surgery During the COVID-19 Pandemic: The Patients' Perspective.

OBJECTIVES: To explore the perspective of urological patients on the possibility to defer elective surgery due to the fear of contracting COVID-19. METHODS: All patients scheduled for elective urological procedures for malignant or benign diseases at 2 high-volume centers were administered a questionnaire, through structured telephone interviews, between April 24 and 27, 2020. The questionnaire included 3 questions: (1) In light of the COVID-19 pandemic, would you defer the planned surgical intervention? (2) If yes, when would you be willing to undergo surgery? (3) What do you consider potentially more harmful for your health: the risk of contracting COVID-19 during hospitalization or the potential consequences of delaying surgical treatment? RESULTS: Overall, 332 patients were included (51.5% and 48.5% in the oncology and benign groups, respectively). Of these, 47.9% patients would have deferred the planned intervention (33.3% vs 63.4%; P < .001), while the proportion of patients who would have preferred to delay surgery for more than 6 months was comparable between the groups (87% vs 80%). These answers were influenced by patient age and American Society of Anesthesiologists score (in the Oncology group) and by the underlying urological condition (in the benign group). Finally, 182 (54.8%) patients considered the risk of COVID-19 potentially more harmful than the risk of delaying surgery (37% vs 73%; P < .001). This answer was driven by patient age and the underlying disease in both groups. CONCLUSIONS: Our findings reinforce the importance of shared decision-making before urological surgery, leveraging patients' values and expectations to refine the paradigm of evidence-based medicine during the COVID-19 pandemic and beyond.

Traditional and Virtual Congress Meetings During the COVID-19 Pandemic and the Post-COVID-19 Era: Is it Time to Change the Paradigm?

The speed and reach of the COVID-19 pandemic have forced rapid changes in how we conduct medical practice and research. The rapid evolution in how scientific meetings are conducted may have long-term benefits. A new reality in which technology and sociality are merged may offer a more engaging and adaptable scientific congress experience with more flexible and dynamic use of content modulated to the needs of each attendee.

Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic?

CONTEXT: Coronavirus disease 2019 (COVID-19) pandemic has caused increased interest in the application of telehealth to provide care without exposing patients and physicians to the risk of contagion. The urological literature on the topic is sparse. OBJECTIVE: To perform a systematic review of the literature and evaluate all the available studies on urological applications of telehealth. EVIDENCE ACQUISITION: After registration on PROSPERO, we searched PubMed and Scopus databases to collect any kind of studies evaluating any telehealth interventions in any urological conditions. The National Toxicology Program/Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies was used to estimate the risk of bias. A narrative synthesis was performed. EVIDENCE SYNTHESIS: We identified 45 studies (11 concerning prostate cancer [PCa], three hematuria management, six urinary stones, 14 urinary incontinence [UI], five urinary tract infections [UTIs], and six other conditions), including 12 randomized controlled trials. The available literature indicates that telemedicine has been implemented successfully in several common clinical scenarios, including the decision-making process following a diagnosis of nonmetastatic PCa, follow-up care of patients with localized PCa after curative treatments, initial diagnosis of hematuria, management diagnosis and follow-up care of uncomplicated urinary stones and uncomplicated UTIs, and initial evaluation, behavioral therapies, and pelvic floor muscle training in UI patients, as well as follow-up care after surgical treatments of stress urinary incontinence or pelvic organ prolapse. The methodological quality of most of the reports was good. CONCLUSIONS: Telehealth has been implemented successfully in selected patients with PCa, UI, pelvic organ prolapse, uncomplicated urinary stones, and UTIs. Many urological conditions are suitable for telehealth, but more studies are needed on other highly prevalent urological malignant and benign conditions. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine. More robust data on long-term efficacy, safety, and health economics are necessary. PATIENT SUMMARY: The diffusion of coronavirus disease 2019 (COVID-19) infections has recently increased the interest in telehealth, which is the adoption of telecommunication to deliver any health care activity. The available literature indicates that telemedicine has been adopted successfully in selected patients with several common clinical urological conditions, including prostate cancer, uncomplicated urinary stones, uncomplicated urinary infections, urinary incontinence, or pelvic organ prolapse. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine, but more robust data on long-term efficacy, safety, and costs are necessary.

Forecasting the Future of Urology Practice: A Comprehensive Review of the Recommendations by International and European Associations on Priority Procedures During the COVID-19 Pandemic.

CONTEXT: The unprecedented health care scenario caused by the coronavirus disease 2019 (COVID-19) pandemic has revolutionized urology practice worldwide. OBJECTIVE: To review the recommendations by the international and European national urological associations/societies (UASs) on prioritization strategies for both oncological and nononcological procedures released during the current emergency scenario. EVIDENCE ACQUISITION: Each UAS official website was searched between April 8 and 18, 2020, to retrieve any document, publication, or position paper on prioritization strategies regarding both diagnostic and therapeutic urological procedures, and any recommendations on the use of telemedicine and minimally invasive surgery. We collected detailed information on all urological procedures, stratified by disease, priority (higher vs lower), and patient setting (outpatient vs inpatient). Then, we critically discussed the implications of such recommendations for urology practice in both the forthcoming "adaptive" and the future "chronic" phase of the COVID-19 pandemic. EVIDENCE SYNTHESIS: Overall, we analyzed the recommendations from 13 UASs, of which four were international (American Urological Association, Confederation Americana de Urologia, European Association of Urology, and Urological Society of Australia and New Zealand) and nine national (from Belgium, France, Germany, Italy, Poland, Portugal, The Netherlands, and the UK). In the outpatient setting, the procedures that are likely to impact the future burden of urologists' workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia. Finally, some UASs recommended special precautions to perform minimally invasive surgery, while others outlined the potential role of telemedicine to optimize resources in the current and future scenarios. CONCLUSIONS: The expected changes will put significant strain on urological units worldwide regarding the overall workload of urologists, internal logistics, inflow of surgical patients, and waiting lists. In light of these predictions, urologists should strive to leverage this emergency period to reshape their role in the future. PATIENT SUMMARY: Overall, there was a large consensus among different urological associations/societies regarding the prioritization of most urological procedures, including those in the outpatient setting, urological emergencies, and many inpatient surgeries for both oncological and nononcological conditions. On the contrary, some differences were found regarding specific cancer surgeries (ie, radical cystectomy for higher-risk bladder cancer and nephrectomy for larger organ-confined renal masses), potentially due to different prioritization criteria and/or health care contexts. In the future, the outpatient procedures that are likely to impact the burden of urologists' workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia.

Assessing the Burden of Nondeferrable Major Uro-oncologic Surgery to Guide Prioritisation Strategies During the COVID-19 Pandemic: Insights from Three Italian High-volume Referral Centres.

The coronavirus 2019 (COVID-19) pandemic has led to an unprecedented emergency scenario for all aspects of health care, including urology. At the time of writing, Italy was the country with the highest rates of both infection and mortality. A panel of experts recently released recommendations for prioritising urologic surgeries in a low-resource setting. Of note, major cancer surgery represents a compelling challenge. However, the burden of these procedures and the impact of such recommendations on urologic practice are currently unknown. To fill this gap, we assessed the yearly proportion of high-priority major uro-oncologic surgeries at three Italian high-volume academic centres. Of 2387 major cancer surgeries, 32.3% were classified as high priority (12.6% of radical nephroureterectomy, 17.3% of nephrectomy, 33.9% of radical prostatectomy, and 36.2% of radical cystectomy cases). Moreover, 26.4% of high-priority major cancer surgeries were performed in patients at higher perioperative risk (American Society of Anesthesiologists score ≥3), with radical cystectomy contributing the most to this cohort (50%). Our real-life data contextualise ongoing recommendations on prioritisation strategies during the current COVID-19 pandemic, highlighting the need for better patient selection for surgery. We found that approximately two-thirds of elective major uro-oncologic surgeries can be safely postponed or changed to another treatment modality when the availability of health care resources is reduced. PATIENT SUMMARY: We used data from three high-volume Italian academic urology centres to evaluate how many surgeries performed for prostate, bladder, kidney, and upper tract urothelial cancer can be postponed in times of emergency. We found that approximately two-thirds of patients with these cancers do not require high-priority surgery. Conversely, of patients requiring high-priority surgery, approximately one in four is considered at high perioperative risk. These patients may pose challenges in allocation of resources in critical scenarios such as the current COVID-19 pandemic.

Impact of the COVID-19 pandemic on urology residency training in Italy.

In the global emergency scenario caused by COVID-19 pandemic, the Urology residents' training might be critically affected. To provide insights on this issue, a 25-item online Survey was sent to all Italian residents one month after the first case of COVID-19 in Italy, to evaluate their routine involvement in "clinical" (on-call duty, outpatient visits, diagnostic procedures) and "surgical" (endoscopic, open and minimally invasive surgery) training activities before and during the COVID-19 period. Overall, 351 of 577 (60.8%) residents completed the Survey. Before the COVID-19 pandemic, the proportion of residents routinely involved in "clinical" and "surgical" activities ranged from 79.8% to 87.2% and from 49.3% to 73.5%, respectively. In the COVID-19 period, the proportion of residents experiencing a severe reduction (>40%) or complete suppression (>80%) of training exposure ranged between 41.1% and 81.2% for "clinical" activities while between 44.2% and 62.1% for "surgical" activities. This reduction was even more pronounced for residents attending the final year of training. Our study is the first to provide real-life data on how Urology residency training can be impaired during an emergency period. To address this challenge, strategies aiming to increase the use of telemedicine, "smart learning" programs and tele-mentoring of surgical procedures, are warranted.

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 the 11th 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 is 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), a systematic research of the published literature was conducted on 24 April 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 for identifying 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 pre-print 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.