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Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.
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Objectives: A LSR is a systematic review that is continually updated, incorporating new evidence as it becomes available. They are conducted in research areas where new evidence is constantly emerging on diagnostic methods, treatments, and outcomes. The objective of this study was to understand the current application of LSRs across research areas. Method(s): Embase, MEDLINE, and the Cochrane Database of Systematic Reviews were searched to identify LSRs. Only the most recent update of a LSR was included. Data regarding the indication, intervention, methods, frequency of updates, and funding were extracted. Result(s): Of the 1,243 records identified, 126 LSRs were included for analysis. The first LSR was published in 2015, with a significant increase in the number of LSRs published starting in 2020, coinciding with the COVID-19 pandemic. The most common indication represented by LSRs was COVID-19 (72%), followed by oncology (10%). Other indications with LSRs included chronic pain, traumatic brain injury, and skin disorders, among others. While most oncology LSRs identified interventional randomized-controlled trials (RCTs) (85%), only 54% of COVID-19 LSRs were restricted to interventional studies, including a combination of RCTS and real-world observational studies. Oncology LSRs included common cancers such as prostate, renal, or multiple myeloma. Of the reviews that reported update frequency, 28% planned monthly, 12% yearly, and 12% weekly updates. Only 46% of LSRs were registered. The majority of LSRs were funded by government or research organizations. Objectives of LSRs varied, with most stating the need to maintain up-to-date databases;however, several studies used LSRs to facilitate network meta-analysis or mixed treatment comparisons. Conclusion(s): While LSRs were introduced over five years ago, their frequency increased during the COVID-19 pandemic. Apart from COVID-19, LSRs are commonly used in oncology settings. LSRs provide high-level, relevant, and up-to-date evidence, making them a useful tool for clinical and real-world research.Copyright © 2023
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ContextNorthern Ireland has five health and social care trusts that provide a Urology service. COVID-19 resulted in the cessation of all but the most urgent elective urological cases. As a result there was an immediate need to enhance current facilities to improve care for our patients. Operations for bladder outlet obstruction, such as transurethral resection of the prostate (TURP), were largely on hold. Men with benign prostatic enlargement continued to suffer in terms of quality of life from symptoms and morbidity from their condition, with subsequent costly attendances through unscheduled care.Issue/ChallengeAs one trust, we had over 100 men active on a waiting list for TURP. We had over 100 patients awaiting a review to decide on surgical management. We had over 400 men awaiting routine assessment through our lower urinary tract symptom assessment clinic.Several surgical options now exist for bladder outlet obstruction. Until this project, TURP was the only option offered to men in Northern Ireland, which is out-with NICE guidance. A TURP has traditionally been an inpatient operation requiring a hospital stay of 2-3 days. During the pandemic and looking to the recovery of services, this was not a viable option.Assessment of issue and analysis of its causesA scoping exercise on where to best place any new service was performed. Key stakeholders included our clinical leaders, management colleagues in the trust and the Department of Health. With successful implementation of a traffic light system for COVID-19, a green pathway for elective surgery had been implemented with great success in our main inpatient Ulster Hospital site. Reflecting on what had been learned in this process, and with a clear need to advocate day-case as default for certain procedures, a regional centre out-with our main inpatient operating theatres was delivered – the Regional Day Procedure Centre (DPC), based at Lagan Valley Hospital.ImpactThe impact has been improved individual patient journeys and improved quality of life for men living with benign prostatic obstruction, with their treatment happening much more promptly, as well as increased staff satisfaction and a saving in theatre costs and bed days.InterventionWe learned and implemented novel bladder outlet techniques;namely Rezum steam ablation therapy to the prostate;green light laser treatment of the prostate (GLLP) and hoImium enucleation of the prostate (HoLEP). We arranged simulation-based training for our Consultant and Speciality Doctor team and mock theatre set up training with the theatre staff to include common pitfalls with equipment. We also arranged simulation-based training for postgraduate surgical trainees, enhancing training during the pandemic.Involvement of stakeholders, such as patients, carers or family members:We engaged and had the support of the clinical and managerial teams from the outset. We opened communication with the day-case unit pre-assessment and anaesthetic teams early. We introduced a new co-located outpatient prostate assessment clinic in conjunction with a nurse specialist.Key MessagesOver the last 6 months we have implemented an all options service for bladder outlet obstruction. We have performed more than 50 day-case Rezum cases, introduced day-case GLLP and inpatient HoLEP. All Rezum and GLLP cases have been day-case with the subsequent personal and institutional savings. We will report our clinical outcomes and reflect on lessons learned.Lessons learntThe introduction of novel bladder outlet therapies has led to improved quality of life for men living with bladder outlet obstruction. We have significantly reduced the waiting list and the waiting time for treatment. We have shown that service development and improvement for benign disease is possible even during a pandemic.Measurement of improvementWe are following up these men with validated symptoms and quality of life scores. We get objective measurement of improvement through repeat flow rate and measurement of post void residual urinary volumes. We have kept a database on key patien parameters and self-reported outcomes. Initial results are promising.Strategy for improvementAs an ongoing and ever evolving project, we use multiple PDSA cycles to improve our service. Weekly team briefs at the end of theatre lists allow feedback from all staff. In particular we have learned from our patients. We have introduced local anaesthetic treatment with Rezum in men unfit for other options. We have contacted other units to share their experience and there has been coverage of our work in our regional media.
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Lack of access to cancer prevention education, early screening, and timely treatment, particularly in low socioeconomic, underserved communities, are cited as substantial barriers to improving survivorship. Outreach educational efforts with on-site screenings offered in partnership with community groups are known to be valuable in encouraging community members' uptake of healthy behaviors and adherence to screening recommendation. To create more engaging events, a community-academic partnership, We Engage 4 Health (WE4H), co-created 11 unique 4-panel comic-style stories designed to be read aloud together as attendees visit each event table. These colorful stories are shared on boards that stand on each table and are offered in both English and Spanish at this time. Many tables also have an accompanying hands-on activity. Together, they lead to meaningful "low stakes" discussions which support understanding of seemingly complex health information. Story topics include the cause of cancer (Cells Gone Wrong), cancer risk factors (Reducing Your Risk), the role of primary care in cancer screening (Primary Care for Prevention), the purpose of research (short Research Ready) and details about specific cancer types (Combatting Colon Cancer, Blocking Breast Cancer, Looking for Lung Cancer, Silencing Skin Cancer, Hindering HPV, and Professional Prostate Protection) and COVID-19 (Take Your Best Shot FAQs). A health passport is used to facilitate table visitation and survey collection at each table enables meaningful evaluation of the event as well as provides the community hosts and their partners baseline cancer data to inform future programing. In 2022, WE4H and the University of Cincinnati Cancer Center partnered with three different communities to co-host pilot events that served over 100 adult residents. Community, research interns and university students volunteered to work the tables at the event and received training prior. Post event surveys and discussions indicated that community partners appreciated the different take on a health fair event. Most volunteers indicated that they would enjoy volunteering again. Attendees indicated that they liked the graphic-style story format used and most preferred it to text and text with graphics approaches. Taken together, the data indicates that Reducing Your Risk events are useful in meaningfully engaging hard to reach, at risk attendees. Additional in-person and virtual events are being planned for 2023 as an approach to reach the medically underserved throughout our region.
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Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments and nutrition can influence inflammation, with the intake of certain food items increasing inflammatory biomarkers. The objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched to collect potentially eligible sources that focus on dietary inflammation and cancer outcomes. All sources were uploaded to Covidence software and screened by two independent blinded reviewers. The quality of the sources was assessed using the Newcastle Ottawa scale and relevant data was extracted and transferred to the Comprehensive Meta Analysis software and a random effects model was used to perform meta-analysis. Of the 1444 studies imported into the Covidence software, 13 passed all the screening stages and were included in the final analysis. Eight studies reported on pre-diagnosis diet while five others reported on postdiagnosis diet. Five studies reported on colorectal cancer, four on breast cancer, two on ovarian cancer, one on endometrial cancer and one on prostate cancer. Meta-analysis of the studies found that being in the highest postdiagnosis DII score indicating pro-inflammatory diet significantly increased the risk of all-cause death among cancer survivors by 33.5% (HR = 1.335, 95% CI = 1.049, 1.698, n = 6). Analysis did not show a statistically significant association between DII score and cancer mortality or recurrence (HR = 1.097, 95% CI = 0.939, 1.281, n = 6). Analysis by cancer subtype found a significant correlation between postdiagnosis DII score and all-cause mortality among the breast cancer survivors (HR = 1.335, 95% CI = 1.041, 1.711, n = 3) though there were no significant associations between DII and the outcomes of interest from the other cancer types. The meta-analysis concludes that being in the highest postdiagnosis DII score group significantly increased the risk of all-cause death among cancer survivors. This suggests that risk of all-cause mortality could be reduced for cancer survivors by consuming more anti-inflammatory food components and reducing consumption of pro-inflammatory foods. These findings also warrant more research in this field to clarify the relationship between dietary inflammation as measured by the DII and cancer outcomes, particularly cancer-specific mortality.
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COVID-19 mRNA vaccines: COVID-19 pandemic has made an extraordinary impact on global vaccine technology platform developments. Never in human history have there at least 6 vaccine platforms including: inactivated, protein subunit, VLP and other 3 new platforms i.e., mRNA, viral vector, and DNA, with more than 160 vaccine candidates being developed and tested in clinical trials. Nonetheless, among these several vaccine platforms, mRNA vaccine has been proven to be one of the most effective vaccines against COVID-19. There are two mRNA vaccines authorized for emergency use within a year and currently more than 20 mRNA vaccines are in clinical trials. The main advantages of mRNA vaccines are that they are speedily to design and develop, induce strong antibody and T-cell responses, manufacturing faster and at a lower cost. However, one of the major limitations is that it must be stored in cold temperatures. Currently more than billion doses of COVID-19 mRNA vaccines have been given globally. mRNA vaccines will be a key platform for next pandemics preparedness, it is therefore establishing this platform in various regions and LMICs is critical. Beyond COVID-19: A number of viral and cancer mRNA vaccines have been developing even before COVID-19. At least 12 mRNA vaccines against various infectious diseases are now in clinical evaluation, including Chikungunya virus, Cytomegalovirus, Epstein-Barr virus, Human metapneumovirus and parainfluenza virus type3, HIV, Influenza, Nipah, Rabies, Lasa, RSV, Zika, Varicella-zoster virus. Only few are entering phase 3 such as a CMV vaccine, RSV, seasonal influenza. Current mRNA cancer vaccines development, including brain, breast, melanoma, esophagus, lung, ovarian, prostate and solid tumors. Most are aimed for personalized therapy. By 2023, at least 1 viral mRNA vaccine may get approval, whereas a cancer vaccine might take much longer time. Nevertheless, the remaining challenge at the global level is how to truly overcome the vaccine inequity issues in a sustainable way.Copyright © 2023
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Background: coronaviral pandemic (COVID-19) induced by severe acute coronaviral syndrome 2 has imminent consequences for COVID-19 patients. To determine the effect of this pandemic on oncological treatment, Netherlands cancer patients performed a national study . Method(s): From 11 April 2020 to 11 Jan 2021, the oncological care perspective was discussed by an online study. The survey included 20 questions on four topics: patient characteristics, hospital engagement, COVID-19 and COVID-19 problems. Result(s): A total of 2418 (64.53%) patients were female and the remainder (57.5%) were <50 years of age. The most prevalent cancer diagnosis were haematological malignancies (26.1%), breast cancer (22.8%) and other cancers (19.2%). Depending on their illness environment, 34.7% of patients had incurable conditions while 21.6% and 31.8% had curable or healed diseases. The (expected) result of their illness was 'unknown' for 11.9% of patients. According to outpatient environment, 1691 (45.1%) patients have been oncologically examined and have taken follow-up, contrasted with 529 (14.1%) and 1527 (40.8%) patients presently or pending for therapy. Conclusion(s): This is the first research exploring cancer patients' experiences after the COVID-19 pandemic in Iraq. The research indicates the major effect of COVID-19 on oncological treatment, showing the need for psycho-oncological assistance during this pandemic.Copyright © 2020 Ubiquity Press. All rights reserved.
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OBJECTIVE: This study aims to evaluate the lower urinary tract symptoms (LUTS) of the patients with benign prostatic hyperplasia (BPH) who were admitted due to coronavirus disease (COVID-19) and to show the effect of COVID-19 on BPH. METHODS: This prospective study included patients over the age of 45 admitted due to COVID-19 between June 2021 and December 2021 and treated with alpha-blockers for BPH. During admission, the patients were evaluated by prostate volumes, prostate-specific antigen (PSA) values, and International Prostate Symptom Scores (IPSS). Furthermore, treatment duration due to COVID-19, frequency, nocturia, and voided volumes obtained from the voiding diary was recorded. Finally, the sequent IPSS values were compared by inviting the patients to the urology polyclinic in the first month. RESULTS: The mean age of 142 patients was 72.42 ± 10.21 years. The IPSS scores of the patients increased from 10.66 ± 4.46 to 12.99 ± 3.58 1 month after the diagnosis (p < 0.01). Moreover, the IPSS quality of life (QoL) scores were 2.44 ± 0.58 and 2.75 ± 0.51, respectively (p < 0.01). The mean frequency obtained from the voiding diary data increased from 5.10 ± 1.5 to 5.65 ± 1.36 (p < 0.01), mean nocturia count increased from 1.13 ± 0.05 to 1.39 ± 0.66 per day (p < 0.01), and the mean voiding volume decreased from 320.56 ± 46.76 ml to 298.84 ± 39.74 ml (p < 0.01). CONCLUSION: In this study, we detected an increase in LUTS during COVID-19 treatment. Therefore, it should be noted that symptomatic or asymptomatic COVID-19 patients may refer to urology polyclinics due to aggravation of LUTS.
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COVID-19 , Prostatic Hyperplasia , Male , Humans , Aged, 80 and over , Prostatic Hyperplasia/complications , Prospective Studies , Quality of Life , COVID-19 Drug Treatment , COVID-19/complicationsABSTRACT
PURPOSE: This qualitative study aimed to understand the impact of the coronavirus disease 2019 pandemic from March to November 2020 on healthcare delivery and clinical trials for genitourinary (GU) cancers in Australia. METHODS: Annually a pre-conference workshop is hosted by the Australian New Zealand Urogenital and Prostate Cancer Trials Group for supportive care health professionals. In November 2020, those that selected to attend were invited to participate in a focus group. Workshop and focus group discussions were recorded and transcripts were analyzed thematically. RESULTS: Seventy-two individuals involved in GU cancer care and clinical trials took part. Participants described negative changes to GU cancer care and clinical trials from the pandemic due to reduced clinical services and increased wait times. Trial recruitment was paused temporarily during lockdowns, and standard treatment protocols were used to limit hospital visits. Trial process changes included electronic capture of informed consent, home delivery of oral medications, and delegations of assessments. These changes increased administrative activity for clinical trial teams and Human Research Ethics Committees. A transition to telehealth enabled continuity of service delivery and trials but reduced the opportunity for face-to-face patient consultations with increasing concern about the failure to detect supportive care needs. CONCLUSION: The pandemic has prompted a critical review of service delivery and clinical trials for people with GU cancers.
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Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment. Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures. Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells. Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.
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INTRODUCTION AND OBJECTIVE: Research demonstrates the benefits of robotic-assisted prostatectomies (RARP) in regard to blood loss and post-operative recovery, there is a paucity in the literature regarding RARP as an outpatient procedure. With minimal operating room capacity during COVID-19, advances in minimally invasive surgical techniques and a relatively healthy patient population, outpatient RARP may be feasible. The aim of our study was to demonstrate the safety and feasibility of RARP as a same day outpatient procedure. METHOD(S): A retrospective cohort study at a single institution was performed by four fellowship trained surgeons who routinely perform RARP. Patients were identified through billing records who underwent RARP between January 2019 and December 2021. Patients were divided into two cohorts, inpatient (one stay past midnight) and outpatient (defined as same day surgery with no stay past midnight). Individual surgeons admission necessity during COVID-19 limitations. We then extracted data using the electronic health record (EHR). The two groups were then compared using standard statistical methods for cohort studies. Statistical significance was defined as p<0.05. RESULT(S): Over a two-year period, a total of 497 RARP were performed with 139 (28%) outpatient cases. There was no difference in baseline demographics between the cohorts. There was a statistically significant difference in estimated blood loss (142 vs 102 mLs, p>=0.001) and operative time (193 vs 180 mins, p=0.004) in the inpatient vs outpatient cohorts, respectively. There was no significant difference in cancer stage, prostate size, or node/margin positivity between cohorts. There was a higher rate of readmissions (5% vs 0%, p=0.007) and number of ED presentations (0.15 vs 0.05, p=0.019) in the inpatient group. There was no difference in complication rates between the groups. Importantly, there was no significant difference in burden on the clinical staff demonstrated by no difference in number of phone calls to clinic, number of EHR messages, or opioid prescriptions on discharge. CONCLUSION(S): Overall, our data suggests that in a well selected patient group, RARP can safely be performed as an outpatient procedure with no significant differences on clinic staff workload or oncologic outcomes. While there was no pre-defined "algorithm" to determine outpatient vs inpatient surgery, the similarity in demographics and pre-operative characteristics between the groups lends support to performing this procedure as an outpatient with inpatient admission being reserved for select patients.
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Introduction & Objectives: The incidence of prostate cancer, both in the world and in the Russian Federation, tends to increase. In the Republic of Bashkortostan in 2021, 699 patients with this diagnosis were registered. 19.6% of patients had stage IV disease at the time of diagnosis. 5818 patients were registered, of which 361 died within a year. The effectiveness of hormonal treatment of common prostate cancer has time limitations, after which there is a development of resistance to castration and progression of the disease. To date, drugs such as kabazitaxel, sipuleucel-T vaccine, abiraterone, enzalutamide and radium-223 have been approved for use in metastatic CRPC. The purpose of the work: analysis of the experience of systemic radiotherapyand Radium - 223 patients with mCRPC in the Republic of Bashkortostan in 2021. Material(s) and Method(s): Analysis of patients who received systemic radiotherapy Radium - 223 in the Republic of Bashkortostan according to medical documentation and research data. In 2021, Radiy-223 radiotherapy was performed on 7 patients diagnosed with mCRPC. Median age 63.14 years. All patients met the criteria for treatment, i.e. had castration-resistant prostate cancer with bone metastases, without visceral metastases. All patients had concomitant pathology from the cardiovascular system, respiratory tract, endocrine system. According to the previous surgical treatment, patients were distributed as follows: orchidectomy - 4, prostatectomy - 1 and 2 patients underwent tumor biopsy. By morphology: Glisson 6 - 2 patients, Glisson 7 - 1, Glisson 8 - 3, Glisson 10 - 1. 4 patients were referred to Xofigo for radiologically confirmed progression, 3 patients were progressingin height at PSA levels. Result(s): 1 patient previously received 1 line of systemic therapy, 5 patients received 2 lines, 1 patient received 3 lines of therapy. 6 patients received all 6 courses of radiotherapy, 1 patient did not complete treatment due to COVID 19. He is expected to complete therapy. All patients are currently alive with no signs of disease progression. Serious side effects were not registered. Conclusion(s): The "therapeutic window" for the prescription of radium-223 is the period before the appearance of visceral metastases and decline of the somatic status. To achieve the maximum benefit from the appointment of radium-223, it is necessary to conduct >=5 cycles of therapy, which is possible in 1-2 treatment lines. It is necessary to select patients carefully for radiotherapy - Radium 223.Copyright © 2022 European Association of Urology. Published by Elsevier B.V.
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INTRODUCTION AND OBJECTIVE: Randomised comparative outcomes are unavailable for focal therapy in localised prostate cancer. IP4 CHRONOS is an RCT aimed to optimise recruitment of patients dependent upon clinician and patient equipoise. METHOD(S): Patients with clinically significant localised prostate cancer could opt for IP4-CHRONOS-A or IP4-CHRONOS-B. IP4- CHRONOS-A randomised patients 1:1 between focal therapy(HIFU or cryotherapy) versus radical therapy(radiation or prostatectomy). Using a multi-arm-multistage(MAMS)design, IP4-CHRONOS-B randomised between focal alone(FTA) and focal combined with neoadjuvant medication (12 weeks of finasteride [FTF] or bicalutamide [FTB]). We report the pilot phase outcomes on feasibility of randomisation, early safety outcomes relative to treatment and genito-urinary functional outcomes following over 12 months treatment in IP4-CHRONOS-B. IP4-CHRONOS had ethics committee approval and was registered(ISRCTN17796995). RESULT(S): Following COVID-19 adjustments, IP4-CHRONOSA did not meet its feasibility target. Having randomised 36 patients via10 sites with a recruitment rate (95% CI) of 18% (13-23) & randomisation rate of 97%(86-100). IP4-CHRONOS-B did meet its target, randomising 64 patients across 7 sites with a recruitment rate of 43% (35-52) &randomisation rate of 100%(94-100). The only patients to withdraw were randomised to the radical arm of IP4-CHRONOS-A(4 [22%]) All patients in IP4-CHRONOS-B were compliant with neoadjuvant treatment.Only 1 patient reported CTCAE V4.0 grade>=3 adverse event(AE) in IP4-CHRONOS-A following radical treatment, another patient in each arm reported a serious adverse event(SAE) following treatment. 1 &3 patients reported an AE &SAE following FTB. 2 and 3 patients reported an AE &SAE following FTA. No patients reported any AE or SAE event following FTF. Figure 1 demonstrates generally well preserved genito-urinary function following focal treatment+/-neoadjuvant treatment. CONCLUSION(S): IP4-CHRONOS evaluated patient and physician equipoise regarding focal therapy. Traditional randomisation was not feasible due to strong patient preferences, while a MAMS RCT investigating the role of neoadjuvant agents combined with focal therapy was.
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INTRODUCTION AND OBJECTIVE: In 2018, The US Preventive Services Task Force (USPSTF) changed its recommendations for prostate specific antigen (PSA) screening from "non-recommended" to "shared decision-making among men aged 55-69". Thereafter, COVID-19 Pandemic disrupted cancer care with evidence suggesting overall reduced access to and utilization of health care services including preventive screening. We aim to examine the impacts of both events on PSA screening for men aged 55-69. METHOD(S): We analyzed 2013, 2015, 2018, 2019, and 2021 National Health Interview Survey data. Men >54 who reported PSA testing within 12 months preceding survey were considered to have undergone screening. Adjusted difference in differences (DID) analyses were performed to compare changes in screening in men aged 55-69 with reference to men >70 between 2015 and 2019 (pre- and post- 2018 USPSTF recommendation) and between 2019 and 2021 (pre- and post-Pandemic). RESULT(S): A total of 24,308 men were included. PSA screening prevalence was 35.4% (95%CI: 33.7%, 37.1%), 32.1% (95%CI: 30.3%, 33.9%), 33.3% (95%CI: 31.6%, 34.9%), 37.2% (95%CI: 35.7%, 38.8%), and 34.9% (95%CI: 33.3%, 36.5%) respectively for included years. From 2015 to 2019, PSA screening increased 4.6% among men aged 55-69 (95%CI: 1.7, 7.5%) and increased 6.5% among men >70 (95% CI: 2.7, 10.4%). From 2019 to 2021, PSA screening decreased 3.1% among men aged 55-69 (95%CI: 0.58%, 5.8%);PSA screening also decreased 0.8% among older men but did not reach significance (95% CI: -2.6%, 4.2%). DID analysis did not show difference in changes between men aged 55-69 in reference to men >70 from both 2015 to 2019 (DID=-1.9%, 95%CI, -6.7%, 2.9%) and 2019 to 2021 (DID =-2.3%, 95%CI, -6.5%, 1.9%). CONCLUSION(S): We saw an increase in PSA screening after 2018 USPSTF recommendations among its target population e men aged 55-69 and also among older men >70. In contrast, the period from 2019 to 2021 saw a significant decrease in PSA screening in those aged 55-69. The lack of significant DID between groups as well as the downward trend of PSA screening in men >70 together suggest an overall trend of decrease in PSA screening post-Pandemic.
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INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic led to the delay of routine medical care, including cancer screening, beginning in March of 2020. While screening rates for several cancers, including prostate cancer, rapidly recovered after the first wave of the COVID-19 pandemic, the degree to which this recovery was realized in different populations remains unknown. We sought to determine the association of the COVID-19 pandemic with prostate cancer screening, particularly for traditionally underserved patients. METHOD(S): We performed a retrospective cohort study using electronic health records (EHR) data from the Optum EHR database for male patients between the ages of 55-69 eligible for prostate cancer screening from quarter 1 (Q1) of 2016 through Q2 of 2021. We excluded men with a prior diagnosis of prostate cancer. We performed multivariable analysis to estimate screening over time, adjusting for patient age, race, ethnicity, Census division of residence, and insurance status. RESULT(S): A total of 7,361,765 patients were included. After adjusting for patient demographics, the percentage of eligible patients with prostate cancer screening decreased from 2.2% in Q4 of 2019 to 1.3% in Q2 of 2020. There was a rebound in screening to 2.4% in Q3 of 2020, which is similar to baseline levels, and a subsequent decline to 1.6% in Q2 of 2021. This trend was seen even after stratifying based on age, race, ethnicity, division, and insurance status (Figure 1). CONCLUSION(S): A 40% decline in prostate cancer screening in Q2 of 2020 was observed during the first wave of the pandemic. This returned to baseline by Q3 of 2020. Subsequent decline was seen again through Q2 of 2021, which also coincides with the second wave of COVID-19. This trend was unaffected by patient characteristics, such as age, race, insurance status, or division of residence. While these data suggest that the peak of the pandemic impacted prostate cancer screening trends similarly across different patient demographic groups, further study is required to breakdown if this was due to social distancing, decreased clinic volumes, or other factors.
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Introduction & Objectives: In 2020, the COVID-19 pandemic brought innumerous challenges to healthcare systems, with reallocation of professionals and suspension of normal activity. This led to a more difficult patient access to primary care, with postponed routine examinations and delayed referrals to specialized consultations. We are now experiencing the results of such delays, with patients arriving later at specialized outpatient appointments. Our objectives were to compare pathological staging patterns of prostate cancer between pre and post-COVID-19 years. Material(s) and Method(s): At a tertiary center, we gathered all pathological data from prostate biopsies (PB) and radical prostatectomy (RP) from 01-01-2019 to 30-06-2022, and compared pathological specimens between 2019 and post-COVID-19 years (2021 and 2022). Result(s): We collected data from 850 PB and 401 RP. During the first pandemic year (2020), we observed a 34.5% and 24.4% reduction in PB and RP (192 PB in 2020 vs 293 in 2019;96 RP in 2020 vs 127 in 2019), respectively. In 2021 and first semester of 2022, the number of PB and RP returned to pre-pandemic values. In post-pandemic years (2021 and 2022) (PPY) PB resulted in less ISUP1 tumors (20.6% in PPY vs 26.62% in 2019) and more poorly differentiated tumors (21.6% ISUP34 in PPY vs 15.7% in 2019), with a 75% increase in cribriform pattern detection. Regarding RP specimens, we identified a 150% increase in high-grade tumors (ISUP34: 9.9% In PPY vs 3.9% in 2019) and 66% increase in extraprostatic extension (54.3% in PPY vs 36.2% in 2019). Nodal involvement was detected in 4.6% (n=15) in PPY compared to 3.9% (n=5) in 2019. Conclusion(s): We are currently observing a change in prostate cancer disease characteristics compared to pre-pandemic years, with patients arriving with higher-grade tumors and more locally advanced featuresCopyright © 2022 European Association of Urology. Published by Elsevier B.V.
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INTRODUCTION AND OBJECTIVE: COVID-19 led to paradigm shifts in telemedicine due to patient's fear of office visits and travel avoidance. With widespread cancellation of office visits and reduction of diagnostic biopsy procedures in men with elevated PSAs, the need for a non-invasive/non-DRE At Home Collection Kit for assessing risk of aggressive prostate cancer and to prioritize biopsy procedures became apparent. We adapted the existing ExoDx Prostate (EPI) office liquid biomarker kit into an At Home Collection Kit physician/ patient shared decisions for prostate biopsy. METHOD(S): A 2-stage program for an At Home Collection Testing Kit program for the ExoDx Test was initiated in April 2020 at the onset of the COVID-19 pandemic. The Phase 1 Pilot study (100 patients, 6 sites) was completed in June 2020. Based on the findings in the pilot, the program was streamlined based on feedback from physicians, patients, and office mangers before making it available in Phase 2 to all urologists in the US. The utilization of the At Home Collection Kits have been measured. RESULT(S): Extensive feedback from the pilot program led to improvements and streamlining before the Phase 2 rollout. As of October 31st, 2022, >30% of all the ExoDx Prostate Tests are At Home Collection Kits. EPI Score distributions are identical (mean 28.4 and 29.7), (median 23.0 and 24.7) in home or clinic sample collection respectively (Figure 1). CONCLUSION(S): The COVID-19 pandemic accelerated major shifts to telehealth and increased use of At Home Testing. The ExoDx Prostate (EPI) At Home Collection Kit was successfully developed and employed to help men (>50 years old) with elevated PSAs (2-10 ng/ml) considering initial or repeat diagnostic biopsy but with pandemic-related fears of visiting offices/hospitals or wanting to avoid long distance travel from rural areas. As COVID becomes manageable and clinical practices have opened, some pandemicadopted approaches remain relevant: the ExoDxTM Prostate, (EPI) At Home Collection Kit is one such approach.
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INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic placed a significant burden on the US healthcare system. Moreover, many healthcare systems triaged cases based on the severity of disease. Therefore, we assessed the impact of the COVID-19 pandemic on prostate cancer management according to the International Society of Urological Pathology (ISUP) grade groups. METHOD(S): We retrospectively analyzed the National Cancer Database (NCDB) for patients with prostate cancer between 2018- 2020. We divided our cohort into "Pre-Pandemic" (2018/2019) and "Pandemic" (2020) periods. Men were classified according to their ISUP grade group at diagnosis. Hospital characteristics and patient-level clinical and sociodemographic variables were extracted. Our primary outcome was the utilization of definitive treatment (surgery or radiation) versus expectant management (active surveillance, watchful waiting, or no treatment). We performed multivariable logistic regressions to predict the type of management for each ISUP grade group across the two periods adjusting for clinical and socioeconomic covariates. RESULT(S): A total of 398,719 men with a diagnosis of prostate cancer were reported during the "Pre-Pandemic" (70.6%) and "Pandemic" (29.4%) periods. Overall, 24.5% had an ISUP 1, 30.6% an ISUP 2, 18.2% an ISUP 3, 13% ISUP 4, and 13.8% ISUP 5 disease (Table 1). Treatment was less likely during the "Pandemic" compared to the "Pre-Pandemic" period for ISUP grade group 1 (aOR 0.80;95% CI 0.77 - 0.83;p-value <0.001), for ISUP grade group 2 (aOR 0.85;95% CI 0.81 - 0.89;p-value <0.001) and for ISUP grade group 3 (aOR 0.87;95% CI 0.80 - 0.96;p-value <0.003). However, no differences in treatment trends were found for ISUP grade groups 4 and 5 across the two time periods. CONCLUSION(S): During the COVID-19 pandemic, patients with prostate cancers ISUP grade groups 1, 2, and 3 were more likely to receive expectant management than definitive treatment;however, this was not true for patients with more aggressive diseases. This finding suggests a high capacity of facilities to appropriately risk stratify and prioritize higher-risk cases during a public health emergency. A limitation of our study is the inability to assess the treatment trends of men diagnosed in the last 2020 quarter due to the lack of follow-up.
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INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic likely affected the healthcare system's ability to deliver prostate cancer care services. Herein, we sought to evaluate prostate cancer's stage and grade migration resulting from the COVID-19 pandemic. METHOD(S): We retrospectively analyzed the National Cancer Database (NCDB) for men with prostate cancer between 2018-2020. We divided our cohort into the "Pre-Pandemic" (2018/2019) and "Pandemic" (2020) periods. Stage and grade of prostate cancer were stratified according to the severity of disease: PSA value (<=20 vs. >20), clinical T stage (cT1-T2 vs. cT3-T4), clinical M stage (cM0 vs. cM1), International Society of Uropathology (ISUP) grade group (ISUP 1-2-3 vs. ISUP 4-5), and D'Amico risk classification (low risk vs. intermediate & high risk). Pearson's chi-square test was used to assess differences in the distribution of stage and grade across the two periods. We performed multivariable logistic regressions to estimate the effect of the "Pandemic" period on stage and grade distribution adjusting for clinical and socioeconomic covariates. RESULT(S): A total of 398,719 men were diagnosed with prostate cancer during the "Pre-pandemic" (70.6%) and "Pandemic" (29.4%) periods (Table 1). On univariable comparisons, an increase in stage/ grade across the two periods was demonstrated (all p<0.001). After adjusting for covariates, compared to the "Pre-pandemic", the "Pandemic" period was associated with increased odds of PSA >20 levels (aOR 1.06;95% CI 1.03 - 1.08;p-value <0.001), cT3-4 stages (aOR 1.12;95% CI 1.08 - 1.16;p<0.001), cM1 stage (aOR 1.15;95% CI 1.12 - 1.18;p<0.001), ISUP grade group 4 or 5 (aOR 1.03;95% CI 1.01 - 1.05;p=0.003) and D'Amico Intermediate & High risk groups (aOR 1.15;95% CI 1.13 - 1.18;p<0.001). CONCLUSION(S): The COVID-19 pandemic was associated with significant changes in the distribution of both stage and grade of prostate cancer. Possible explanations for this migration include a better selection of patients for prostate biopsy during the pandemic or changes in prostate cancer screening patterns.
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A fundamental challenge in the fight against COVID-19 is the development of reliable and accurate tools to predict disease progression in a patient. This information can be extremely useful in distinguishing hospitalized patients at higher risk for needing UCI from patients with low severity. How SARS-CoV-2 infection will evolve is still unclear. Method(s): A novel pipeline was developed that can integrate RNA-Seq data from different databases to obtain a genetic biomarker COVID-19 severity index using an artificial intelligence algorithm. Our pipeline ensures robustness through multiple cross-validation processes in different steps. Result(s): CD93, RPS24, PSCA, and CD300E were identified as COVID-19 severity gene signatures. Furthermore, using the obtained gene signature, an effective multi-class classifier capable of discrimi-nating between control, outpatient, inpatient, and ICU COVID-19 patients was optimized, achieving an accuracy of 97.5%. Conclusion(s): In summary, during this research, a new intelligent pipeline was implemented to develop a specific gene signature that can detect the severity of patients suffering COVID-19. Our approach to clinical decision support systems achieved excellent results, even when processing unseen samples. Our system can be of great clinical utility for the strategy of planning, organizing and managing human and material resources, as well as for automatically classifying the severity of patients affected by COVID-19.Copyright © 2023 Bentham Science Publishers.