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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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COVID-19, or SARS-CoV-2, is an extremely deadly virus that is responsible for over half a million deaths of people in the world. This virus originated in China in December 2019 and rapidly spread worldwide in 2-3 months, and affected every part of the world. Its life-threatening nature forced governments in all countries to take emergency steps of lockdown that affected the entire world's education, health, social and economic aspects. Due to the implementation of these emergencies, the population is facing psychological, social and financial problems. Additionally, this pandemic has significantly influenced the health care systems as all the resources from governments of all countries were directed to invest funds to discover new diagnostic tests and manage COVID-19 infection. The impact of the COVID-19 pandemic on the education and social life of the population is described in this article. Additionally, the diagnosis, management, and phytoremedia-tion to control the spread of COVID-19 and traditional medicinal plants' role in managing its mild symptoms have been discussed.Copyright © 2023 Bentham Science Publishers.
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Methods: This retrospective study included adults with COVID-19 (ICD-10: U07.1) and pneumonia (ICD-10 subcodes within J11.x - J16.x, J18.x) May 2020-December 2021 in the Premier Healthcare Database, analyzing severity, treatment patterns and clinical outcomes. Result(s): Between May 2020 and December 2021: N=338,930 patients in 856 hospitals 79% of patients received any dexamethasone(DEX);>50% received any remdesivir(RDV) Combination therapy use increased: DEX+RDV only from <1% of patients to 29%;DEX+RDV with baricitinib or tocilizumab from <1% to 19% RDV initiation in the first 2 days of hospitalization increased 41% to 88% Overall all-cause mortality increased 19% to 24% with large differences between severity subgroups: in December 2021, 20%, 32%, 46% and 60%, respectively, in no supplementary oxygen(NSOc), low-flow(LFO), highflow/non-invasive(HFO/NIV) and invasive mechanical ventilation/ECMO(IMV/ECMO) Overall median hospital LOS and ICU LOS remained between 6-10 days, with notable variation by severity subgroup and over time Overall ICU use was 35%-38%, with large differences by severity subgroups: in December 2021, 28%, 47%, 67% and 94%, respectively, in NSOc, LFO, HFO/NIV and IMV/EC Conclusion(s): COVID-19 can result in severe outcomes;understanding treatment and severity trends can improve prognosis.
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Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far;however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs.Copyright © 2020.
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Background: Randomised comparative data is lacking for focal therapy in localised prostate cancer. Imperial Prostate 4 CHRONOS (IP4-CHRONOS) is an RCT designed to reflect patient and physician equipoise to maximise acceptance to randomisation. Methods: Patients and physicians could opt for CHRONOS-A or CHRONOS-B. CHRONOS-A randomised between focal therapy (HIFU/cryotherapy) and radical therapy (radiation/prostatectomy). Using a multi-arm-multistage design, CHRONOS-B randomised between focal and focal combined with neoadjuvant medication (3 months of either finasteride or bicalutamide). We report the pilot phase outcomes on feasibility of randomisation. IP4-CHRONOS had ethics committee approval and was registered (ISRCTN17796995). Results: Due to impact of COVID-19, the target for CHRONOS-A was modified from 60 to 36;36 patients were randomised over 24 months from 7 sites (Nov/2019-Nov/2021). CHRONOS-B randomised 64 patients over 14 months across 6 sites (Dec/2019-Feb/2021). Median (IQR) age and PSA (ng/ml) for CHRONOS-A were 69 (65-72) years and 6 (5-7) and for 66 (60.5-70) years and 6 (4-7) for CHRONOS-B, respectively. 34/36 (94%) and 60/64 (94%) had ISUP Grade Group > / = 2, respectively. 4/18 (22%) randomised to radical in CHRONOS-A withdrew consent;1/22 (5%) randomised to focal withdrew. In CHRONOS-B, only 1/21 (5%) randomised to focal alone, and another randomised to focal with neoadjuvant bicalutamide withdrew. A qualitative recruitment intervention partially improved accrual to CHRONOS-A. Conclusions: IP4-CHRONOS evaluated patient and physician equipoise regarding focal therapy. Randomising between focal and radical therapy is not feasible due to strong patient preferences. A multi-arm, multi-stage RCT investigating the role of neoadjuvant agents combined with focal therapy is feasible.
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Introduction COVID-19 has been shown to disproportionately affect patients with metabolic syndrome-associated conditions. Although a few small studies have reported an increased frequency of severe COVID-19 infection in patients with NAFLD, little is known regarding the factors portending adverse outcomes in this group. Given the high and rising prevalence of NAFLD, it is important to identify the predictors of adverse outcomes in this diverse group of patients which was the aim of our study. Study Design We retrospectively studied patients with NAFLD diagnosed with COVID-19 at Community Medical Centers in Fresno, California between March 1 and September 30, 2020. Baseline demographics, medications, laboratory values during COVID-19, and baseline liver fibrosis scores prior to admission along with measured outcomes of severity were collected. Scores studied were NAFLD Fibrosis Score (NFS), AST to Platelet Ratio Index (APRI), fibrosis-4 (FIB-4), and MELD-Na. To assess correlations and associations, Chi-square tests, Independent sample t-tests and Pearson correlation testing were used. Results Patients over 18 years of age with NAFLD and PCR-confirmed COVID-19 were included in the study (n=298). Demographics: 71% Hispanic, 52% male, 72% government insurance, mean age 55 years. Outcomes: 83% hospitalized, 74% required supplemental oxygen, 30% required non-invasive positive pressure ventilation (NIPPV), 25% admitted to the intensive care unit (ICU), 15% required intubation and 13% required vasopressors. COVID-19 related mortality rate was 14%. Risk factors for adverse outcomes: Peak AST, ALT, and total bilirubin levels during COVID-19 had statistically significant positive correlations with ICU admission, intubation, and death. Albumin and platelet levels had statistically significant negative correlations with ICU admission, intubation, and death. Albumin had the strongest correlation of-0.431 to -0.497. Chronic proton pump inhibitor (PPI) use had a statistically significant positive correlation with intubation and ICU admission and chronic ACE-inhibitor use with the outcome of death. (Figure 1). Increasing baseline liver fibrosis scores (NFS, APRI, FIB-4) were associated with worse outcomes for hospitalization, oxygen requirement, NIPPV, ICU admission, intubation and death (Figure 2). Discussion Based on our study, patients with NAFLD with elevated baseline liver fibrosis scores, elevated ALT, AST, total bilirubin, and decreased albumin and platelets during COVID-19 are at a significantly elevated risk for adverse outcomes. NFS, APRI, and FIB-4 scores appeared superior to MELD-Na in predicting outcomes. Chronic PPI and ACEinhibitor use are associated with adverse outcomes, and thus should be used with caution in patients with NAFLD during COVID-19 pandemic. Clinicians should be aware of these risk factors while evaluating patients with COVID-19 and NAFLD. $Φgure
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The varied spectrum of presentation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is intriguing. Multisystem inflammatory syndrome in children (MIS-C) is a well described and documented condition that is associated with the active or recent COVID-19 infection. A similar presentation in adults is termed as Multisystem inflammatory syndrome in Adults (MIS-A). With only very limited cases reported from the west, MIS-A is considered a rare and serious complication of COVID-19. However, it is not as uncommon as we think. Many cases go undiagnosed for lack of COVID -19 like symptoms and unawareness among treating clinicians about this newer clinical entity. Further, antibody testing and inflammatory markers are not easily available in many of the Indian hospitals especially in rural India where the second wave had been intense, thereby making it difficult for the diagnosis of MIS-A. Also, there is no clear treatment guideline for MIS-A unlike MIS-C where the treatment protocol is well laid out. Awareness about MIS-A among treating clinicians can thus help in further evaluation and increased identification of the syndrome at the early stages thereby helping in the early institution of treatment. Our tertiary COVID care hospital in South India which has handled about 5200 cases of COVID-19 is been able to identify 04 cases of MIS-A proving that this clinical entity is not as rare as it is thought but lacks reporting and prompt identification. Here we describe 04 cases of MIS-A and strive to bring in the various aspects of it, including the clinical presentation, laboratory markers, diagnostic criteria and treatment considerations in this post second wave of the COVID-19 pandemic in India. © 2021 Journal of Association of Physicians of India. All rights reserved.
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Background: Adjuvant anti-PD1 therapy reduces the risk of recurrence in resected stage III/IV melanoma and is now standard care. Limited data exist beyond registration trials. We sought to explore the use of adjuvant immunotherapy in routine clinical practice. Methods: Patients (pts) from 11 Australian centres who received adjuvant nivolumab (nivo) for resected stage III/IV melanoma were included in this study. Efficacy, toxicity, surveillance, recurrence characteristics, management and further treatment outcomes were examined. Results:471 pts received adjuvant nivo between 8/2018 to 3/2020. 318 (68%) were male, median age 64y (range 17-94), 28 (6%) were AJCC v8 IIIA, 194 (41%) IIIB, 175 (37%) IIIC, 11 (2%) IIID, and 63 (13%) IV. 65 (14%) pts had intransit only disease, 152 (37%) pts were sentinel lymph node biopsy (SLNB+) and only 9 (6%) of these had CLND. 128 (27%) had BRAF mutant (BRAFmt) melanoma. Median time from resection to start of adjuvant nivo was 1.8 months (mo) (range 0.2-4.0). Median FU was 17.5 mo. 256 (54%) pts completed 12 months of nivo, 86 (18%) ceased early for toxicity, 76 (16%) for disease recurrence, 25 (5%) other reasons (COVID-19 8, co-morbidities 7, pt choice 10);28 (6%) pts were still receiving nivo at data cut. Median duration of treatment was 10.4 mo (range 0-16.8). 117 (25%) pts recurred;76 (65%) while ON nivo and 41 (35%) OFF nivo ( > 1 month after last dose, including 20 pts who stopped early for toxicity). 24 mo RFS was 69%. Median time to recurrence was 6.0 mo (95% CI 5.1, 7.5). 56 (48%) had first recurrence with locoregional (LR) disease only and 61 (52%) had distant +/- LR recurrence. Of those who recurred with LR disease only, 46/56 (82%) underwent surgery, 15/46 (33%) then had adjuvant radiotherapy, and 15/46 (33%) had 'second adjuvant' therapy with BRAF/MEK inhibitors (15/21, 71% BRAFmt pts). 10/56 (37%) pts who recurred with LR disease subsequently recurred distantly. 58/80 (73%) pts received systemic therapy at either 1st or subsequent unresectable recurrence. For recurrences ON nivo, 18 pts received combination ipilimumab (ipi) and nivo (ORR 44%), 4 pts had ipi monotherapy (ORR 0%), 7 pts had anti-PD1 + investigational agent (ORR 57%), 11 pts had BRAF/MEK inhibitors (ORR 82%). 1 pt had PD with ongoing PD1 monotherapy. For recurrences OFF nivo, no patients responded to PD1 alone (n = 1) or with an investigational agent (n = 1), ipi+nivo (n = 3), ipi monotherapy (n = 4) or chemotherapy (n = 2);6 pts received BRAF/MEK inhibitors (ORR 50%). 2-year OS was 92%. Conclusions: Despite higher rates of discontinuation due to toxicity compared with clinical trial cohorts, the efficacy data appear similar. Most early recurrences are distant, and many with LR recurrence soon recur distantly thereafter. Second line adjuvant BRAF/MEK inhibitors are frequently used for resected LR recurrence. Both ipi+nivo and BRAF/MEK inhibitors appear to have activity after distant recurrence.