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2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Marjan Mahdavi-Roshan ◽  
Arsalan Salari ◽  
Eshagh Mohammadyari ◽  
Tofigh Yaghubi Kalurazi ◽  
Aydin Pourkazemi ◽  

Purpose It is argued that COVID-19 patients show various neuropsychiatric symptoms, including fatigue, depression and anxiety. On the other hand, epidemiological and experimental evidence indicated that green tea could potentially have antiviral effects and ameliorate psychiatric disorders. However, there is a lack of clinical evidence. The purpose of this study was to investigate whether drinking green tea can clinically improve psychiatric complications of COVID-19 infection. Design/methodology/approach This study included 40 patients with laboratory confirmed mild-to-moderate COVID-19 disorder in the current randomized open-label controlled trial. Patients were instructed to include three cups/day of green tea (intervention) or black tea (control) to their usual diet for four weeks immediately after diagnosis of the disease. At the study baseline and after the intervention, the enrolled patients’ fatigue, depression and anxiety were assessed by the Chalder Fatigue Scale, Beck Depression Inventory-Fast Screen and State-Trait Anxiety Inventory questionnaires. Findings A total of 19 COVID-19 cases in the intervention group (mean age = 52 years) and 14 cases (mean age = 50 years) in the control group completed the study. Analysis of covariance adjusted for baseline levels, and confounders revealed that those who consumed three cups/day of green tea compared to the patients who received black tea experienced significantly lower fatigue, depression and state and trait anxiety levels (adjusted means for fatigue = 12.3 vs 16.2 (P = 0.03), depression = 0.53 vs 1.8 (P = 0.01), 37.4 vs 45.5 (P < 0.01) and 37.9 vs 45.2 (P < 0.01)). Research limitations/implications The open-label design may bias the evaluation of the self-reported status of fatigue, depression or anxiety as the main outcomes assessed. Moreover, as this study did not include patients with severe COVID-19, this might affect the generalizability of the present results. Thus, the recommendation of daily drinking green tea may be limited to the subjects diagnosed with mild-to-moderate type of infection or those with long-term neuropsychiatric complications owing to COVID-19. Besides, considering the ethical issues, this study could not exclude the drug therapy’s confounding effects; thereby, this point should be considered when interpreting the current results. Besides, it is worth noting that Guilan province in the north of Iran is recognized as a tea (and particularly green tea) producing region; thereby, it is an available and relatively inexpensive product. Considering this issue, the recommendation to consume this medicinal plant in adjunct to the routine treatment approach among patients with mild-to-moderate COVID-19 based on its beneficial effects may be widely accepted. Practical implications Green tea consumption could be considered an option to combat COVID-19 associated psychological complications, including fatigue, depression and anxiety among patients suffering from mild-to-moderate type of this viral infection. Originality/value To the best of the authors’ knowledge, in this study, for the first time, the effects of green tea compared to black tea on COVID-19 associated fatigue, depression and anxiety status within an open-label controlled trial have been investigated.

2021 ◽  
pp. 135965352110422
Franco Maggiolo ◽  
Nicola Gianotti ◽  
Laura Comi ◽  
Elisa Di Filippo ◽  
Laura Fumagalli ◽  

Background Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with HIV. We present efficacy and safety data from the 48-week analysis. Methods PROBE 2 is a randomized, open-label trial. Adults who were on a three-drug therapy and had had <50 HIV-1 RNA copies/mL for at least 6 months were randomly assigned (1:1) to 25 mg rilpivirine plus 800/150 darunavir/cobicistat once daily (early switch group) or to continue their regimen for 24 weeks before switching (late switch group). In the 48-week analysis, the efficacy endpoint was the proportion of participants with <50 copies/mL of HIV-RNA (US Food and Drug Administration snapshot algorithm). The trial is registered with , number NCT04064632. Findings 160 participants were recruited and randomized. At week 48, 70 (87.5%) in the early switch group and 76 (94.8%) in the late switch group maintained HIV-RNA <50 copies/mL. Virological failure (≥50 HIV-RNA copies/mL) was not seen in any patient of the early switch group and in 2 subjects in the late switch group none of which had treatment emergent resistance-associated mutation. Adverse events leading to treatment discontinuation occurred in 7 (8.7%) participants in the early switch group and in none in the late switch group. Interpretation The combination of rilpivirine plus darunavir/cobicistat sustained virological suppression, was associated with a low frequency of virological failure, and had a favorable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and integrase inhibitor-sparing alternative to three-drug regimens.

2021 ◽  
Tomohiro Koga ◽  
Shuntaro Sato ◽  
Naoko Hagimori ◽  
Hiroshi Yamamoto ◽  
Masataka Ishimura ◽  

Abstract Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

2021 ◽  
John Botson ◽  
John RP Tesser ◽  
Ralph Bennett ◽  
Howard M Kenney ◽  
Paul M Peloso ◽  

Abstract Background: Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase+methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.Methods: Uncontrolled gout patients (serum urate [SU]≥6 mg/dL and SU≥6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4-weeks before and during pegloticase therapy. Twelve-month responder rate (SU<6 mg/dL for ≥80% during Month 12), 52-week change from baseline in SU, and extended safety were examined. Efficacy analyses were performed for patients receiving ≥1 pegloticase infusion. PK/anti-drug antibodies (ADAs) were examined and related to efficacy/safety findings. Results: Fourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4 year gout history, pre-therapy SU: 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24-weeks, one patient exited the study per-protocol at 24-weeks (enrolled prior to treatment extension amendment), and 10 remained in study through Week 52. Of the 10, 8 completed 52-weeks of pegloticase+methotrexate and were 12-month responders. The remaining two discontinued pegloticase+methotrexate at Week 24 (met treatment goals) and stayed in study under observation (allopurinol prescribed at physicians’ discretion); one remained a responder at 12-months. At 52-weeks, change from baseline in SU was -8.2 ± 4.1 mg/dL (SU: 1.1 ± 2.4 mg/dL, n=10). Gout flares were common early in treatment but progressively decreased while on therapy (Weeks 1-12: 13/14 [92.9%], Weeks 36-52: 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titres; fewer patients had trough concentrations (Cmin) below quantitation limit (BQL) and median Cmin was higher (1.03 mg/mL vs. BQL) than in pegloticase monotherapy trials.Conclusions: Methotrexate+pegloticase co-therapy was well-tolerated over 12-months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates.Trial registration: NCT03635957, registered 17 August 2018,

2021 ◽  
Patricia Volkow ◽  
Leslie Chavez-Galan ◽  
Lucero Ramon-Luing ◽  
Judith Cruz-Velazquez ◽  
Patricia Cornejo-Juarez ◽  

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with severe Immune reconstitution inflammatory syndrome (S-IRIS-KS), which can occur after initiating cART, and is linked with high mortality particularly in patients with pulmonary involvement. We investigate if valganciclovir initiated before cART decreases HHV-8 VL and assess if it reduces the incidence of S-IRIS-KS and its attributable mortality. Methods: Open-label parallel-group randomized clinical trial in AIDS cART naive patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node or gastrointestinal involvement, lymphedema, or equal or more 30 skin lesions. In the experimental group (EG), patients were randomized to valganciclovir 900 mg BID four weeks before cART and continued until week-48; in the control group (CG), cART was initiated on week-0. Non-severe-IRIS-KS was defined as: increase in the number of lesions plus equal or more than one log10 HIV-VL decrease or equal or more than 50 cells/mm3 increase or equal or more than 2-fold rise in baseline CD4+ cells. S-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia. Results: 40 patients were randomized and 37 completed the study. In the ITT analysis, the overall mortality did not differ between groups. In the per-protocol analyses, the difference showed a trend for higher S-IRIS-KS mortality in the CG 3/19 (15.7%), compared to EG 0/18 (p=0.07). The incidence of S-IRIS KS was significantly lower in the EG; two patients, one each had S-IRIS-KS episode (0.038 per 100 patient-days) compared to CG group, four patients developed 12 S-IRIS-KS episodes (0.21 per 100 patient-days); incidence rate of 0.09 (95% CI 0.02-0.5 p=0.006). Mortality in patients with pulmonary KS was significantly lower in EG, 3/4 in CG vs 0/5 in EG. S-IRIS-KS was associated with higher HHV-8-VL; IL6 and CRP; valganciclovir was protective. Of survivors at week 48, 82% achieved more than 80% remission. No difference was found between groups in the number of non-S-IRIS-KS events. Conclusions: Valganciclovir significantly reduced the episodes of S-IRIS-KS although attributable KS mortality was lower in the EG the difference was not significant (p=0.07). Mortality was significantly lower in EG patients with pulmonary KS.

Lauren E Walker ◽  
Richard FitzGerald ◽  
Geoffrey Saunders ◽  
Rebecca Lyon ◽  
Michael Fisher ◽  

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