Neuroreport. 2021 May 5;32(7):555-561. doi: 10.1097/WNR.0000000000001623.

ABSTRACT

l-dopa and dopamine D2 receptor (D2R) agonists are commonly used to relieve the motor deficits of Parkinson's disease. However, long-term treatment with l-dopa or D2R agonists can induce adverse effects such as abnormal involuntary movements (AIMs), which are major limiting factors in achieving long-term control of parkinsonian syndromes. The pathophysiological mechanisms involved in the development of dopaminergic agonist-induced adverse effects are not well understood. Here, we examined the role of two D2R isoforms, D2S and D2L, in l-dopa-induced AIMs using dopamine D2L knockout (D2L KO) mice (expressing purely D2S) and wild-type mice (expressing predominantly D2L). We found that D2L KO mice displayed markedly enhanced AIMs in response to chronic treatment of l-dopa compared to wild-type mice. The l-dopa-induced enhancement of AIMs in D2L KO mice was significantly reduced by the D2R antagonist eticlopride. D2L KO mice also displayed markedly enhanced AIMs in response to chronic treatment with quinpirole, a preferential D2R agonist. These results suggest that D2S contributes more than D2L to dopaminergic agonist-induced AIMs. Our findings may uncover a new factor that contributes to the pathophysiology of dopaminergic drug-induced AIMs, a characteristic manifestation of dyskinesia and also present in psychosis. There is a possibility that the increased ratio of D2S to D2L in the brain plays a significant role in the development of AIM side effects induced by l-dopa or D2R agonists. See Video Abstract, http://links.lww.com/WNR/A622.

PMID:33850083 | DOI:10.1097/WNR.0000000000001623

Drug Ther Bull. 2021 Apr 13:dtb-2021-000017. doi: 10.1136/dtb.2021.000017. Online ahead of print.

NO ABSTRACT

PMID:33849954 | DOI:10.1136/dtb.2021.000017

Lancet Oncol. 2021 Apr 9:S1470-2045(21)00145-5. doi: 10.1016/S1470-2045(21)00145-5. Online ahead of print.

ABSTRACT

BACKGROUND: Copanlisib, an intravenous pan-class I PI3K inhibitor, showed efficacy and safety as monotherapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma who had received at least two therapies. The CHRONOS-3 study aimed to assess the efficacy and safety of copanlisib plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma.

METHODS: CHRONOS-3 was a multicentre, double-blind, randomised, placebo-controlled, phase 3 study in 186 academic medical centres across Asia, Australia, Europe, New Zealand, North America, Russia, South Africa, and South America. Patients aged 18 years and older with an Eastern Cooperative Oncology Group performance status of no more than 2 and histologically confirmed CD20-positive indolent B-cell lymphoma relapsed after the last anti-CD20 monoclonal antibody-containing therapy and progression-free and treatment-free for at least 12 months, or at least 6 months for patients unwilling or unfit to receive chemotherapy, were randomly assigned (2:1) with an interactive voice-web response system via block randomisation (block size of six) to copanlisib (60 mg given as a 1-h intravenous infusion on an intermittent schedule on days 1, 8, and 15 [28-day cycle]) plus rituximab (375 mg/m2 given intravenously weekly on days 1, 8, 15, and 22 during cycle 1 and day 1 of cycles 3, 5, 7, and 9) or placebo plus rituximab, stratified on the basis of histology, progression-free and treatment-free interval, presence of bulky disease, and previous treatment with PI3K inhibitors. The primary outcome was progression-free survival in the full analysis set (all randomised patients) by masked central review. Safety was assessed in all patients who received at least one dose of any study drug. This study is registered with ClinicalTrials.gov, NCT02367040 and is ongoing.

FINDINGS: Between Aug 3, 2015, and Dec 17, 2019, 652 patients were screened for eligibility. 307 of 458 patients were randomly assigned to copanlisib plus rituximab and 151 patients were randomly assigned to placebo plus rituximab. With a median follow-up of 19·2 months (IQR 7·4-28·8) and 205 total events, copanlisib plus rituximab showed a statistically and clinically significant improvement in progression-free survival versus placebo plus rituximab; median progression-free survival 21·5 months (95% CI 17·8-33·0) versus 13·8 months (10·2-17·5; hazard ratio 0·52 [95% CI 0·39-0·69]; p<0·0001). The most common grade 3-4 adverse events were hyperglycaemia (173 [56%] of 307 patients in the copanlisib plus rituximab group vs 12 [8%] of 146 in the placebo plus rituximab group) and hypertension (122 [40%] vs 13 [9%]). Serious treatment-emergent adverse events were reported in 145 (47%) of 307 patients receiving copanlisib plus rituximab and 27 (18%) of 146 patients receiving placebo plus rituximab. One (<1%) drug-related death (pneumonitis) occurred in the copanlisib plus rituximab group and none occurred in the placebo plus rituximab group.

INTERPRETATION: Copanlisib plus rituximab improved progression-free survival in patients with relapsed indolent non-Hodgkin lymphoma compared with placebo plus rituximab. To our knowledge, copanlisib is the first PI3K inhibitor to be safely combined with rituximab and the first to show broad and superior efficacy in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma.

FUNDING: Bayer.

PMID:33848462 | DOI:10.1016/S1470-2045(21)00145-5

MMW Fortschr Med. 2021 Apr;163(Suppl 4):19-26. doi: 10.1007/s15006-021-9762-5.

ABSTRACT

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is the most common intestinal side effect of an antibiotic therapy. Various probiotics or probiotic combinations are often used preventively while taking antibiotics for the prevention of AAD.

METHOD: This review is based on a systematic literature research in MEDLINE and EMBASE. 7 probiotics are presented with regard to their effectiveness and evidence in the prevention of AAD. Only preparations classified by the World Gastroenerology Organization (WGO) with evidence levels 1-3 for the prevention of AAD were taken into account. 37 clinical studies, including 33 RCTs, were evaluated.

RESULTS: Saccharomyces (S.) boulardii CNCM I-745 is the most extensively studied probiotic regarding the prevention of AAD. It has shown evidence-based efficacy in all patient groups (outpatients and hospitalized children and adults). Lactobacillus rhamnosus GG also has a good evidence regarding the prevention of AAD in children and outpatient adults. The other probiotics and probiotic combinations evaluated in the present study only show efficacy in hospitalized patients or only show very limited evidence regarding their efficacy in the prevention of AAD due to the underlying study design or the small number of patients.

CONCLUSION: The effect of probiotics is strain-specific, no general statement can be made about the efficacy of probiotics in the prevention of AAD. In principle, it is advisable to select a probiotic with an evidence-based effect such as S. boulardii CNCM I-745 or Lactobacillus rhamnosus GG to prevent AAD.

PMID:33844181 | DOI:10.1007/s15006-021-9762-5

Ann Transl Med. 2021 Mar;9(5):430. doi: 10.21037/atm-20-5552.

ABSTRACT

Inhibition of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) has been utilized as a treatment strategy for a variety of immune-mediated inflammatory disorders (IMID), including rheumatoid arthritis, Crohn's disease and psoriasis. A wide array of biologic therapies targeting the TNFα molecule, including etanercept, infliximab, certolizumab, golimumab and adalimumab, are routinely used in the care of patients with these conditions. In addition to their therapeutic potential, anti-TNFα agents commonly induce the formation of autoantibodies such as anti-nuclear antibodies and anti-double stranded DNA antibodies; however, the vast majority of these are of IgM isotype and of unclear clinical significance, uncommonly leading to drug-induced autoimmune disease. For these reasons, TNFα inhibition has been a controversial strategy in the treatment of primary connective tissue disorders (CTDs). However, as new therapeutics continue to be developed for the management of CTDs, the potential utility for anti-TNFα agents has become of great interest, demonstrated in several recent case series and small open-label trials. We review the safety and compatibility of anti-TNFα therapy in the management of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), two well-studied example CTDs, as well as summarize the risks of autoantibody generation, infection, malignancy, and iatrogenic lupus flares as side effects of blocking TNFα in patients with these conditions.

PMID:33842651 | PMC:PMC8033307 | DOI:10.21037/atm-20-5552

Clin Exp Dermatol. 2021 Apr 10. doi: 10.1111/ced.14674. Online ahead of print.

ABSTRACT

In dermatological practice, removal of macular discoloration in the skin or mucosa is difficult to treat.Topical products often become insufficient to penetrate the skin or mucosa. Surgical removal is also not very reasonable due to the potential risk of scarring. Although patients are generally recommended to receive laser treatment, many of them cannot be treated due to the high cost of these methods. Treatment with liquid nitrogen freezing is a safe, cheap and fast option for various dermatological conditions, including mucosal surfaces with low side effects. (1).

PMID:33837573 | DOI:10.1111/ced.14674

Reg Anesth Pain Med. 2021 Apr 9:rapm-2021-102547. doi: 10.1136/rapm-2021-102547. Online ahead of print.

NO ABSTRACT

PMID:33837138 | DOI:10.1136/rapm-2021-102547

BMJ Evid Based Med. 2021 Apr 9:bmjebm-2020-111648. doi: 10.1136/bmjebm-2020-111648. Online ahead of print.

NO ABSTRACT

PMID:33837110 | DOI:10.1136/bmjebm-2020-111648

Trials. 2021 Apr 9;22(1):262. doi: 10.1186/s13063-021-05236-2.

ABSTRACT

OBJECTIVES: The primary objective is to determine the effect of a daily dose of ivermectin administered in three consecutive days to non-severe COVID-19 patients with no more than 96 hours of symptoms, on the detection of SARS-CoV-2 RNA by PCR from nasopharyngeal swabs at day seven post-treatment initiation. The secondary objectives are: 1. To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab on days 4, 7, 14 and 21 post-treatment initiation 2. To assess the efficacy of ivermectin on the improvement of symptoms 3. To assess the proportion of seroconversions at day 21 4. To assess the safety of ivermectin at the proposed dose 5. To determine the magnitude of the immune response against SARS-CoV-2 6. To assess correlation of the presence of intestinal helminths on participants on baseline and day 14 with COVID-19 progression and treatment.

TRIAL DESIGN: SAINT PERU is a triple-blinded, randomized, placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection.

PARTICIPANTS: The trial is conducted in two national hospitals in Lima-Peru. The study population is patients with a positive PCR test for SARS-CoV-2 in a nasopharyngeal specimen, symptomatic for 96 hours or less, with non-severe COVID-19 disease at baseline, regardless of the presence of risk factors for progression to severity. The study will not include pregnant women or minors (17 years old or younger). Inclusion criteria 1. COVID-19 symptomatology (cough, fever, anosmia, etc.) lasting no more than 96 hours, with a positive nasopharyngeal swab PCR test for SARS-CoV-2. 2. 18 years or older. 3. No use of ivermectin in the month prior to the visit. 4. No known history of ivermectin allergy. 5. Capable to give informed consent. 6. Not current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, cobicistat or critical CYP3A4 substrate drugs such as warfarin. Exclusion criteria 1. COVID-19 pneumonia diagnosed by the attending physician (oxygen saturation < 95% or lung examination) 2. Positive pregnancy test for women at childbearing age. 3. Positive IgG against SARS-CoV-2 by rapid diagnostic test at screening. Participants will be recruited by the investigators at the emergency services of the study sites. They are expected to remain in the trial for a period of 21 days. Follow-up visits will be conducted by the trial medical staff at the participant's home or at a hospital in case of hospitalization. Follow-up visits will assess clinical and laboratory parameters of the patients.

INTERVENTION AND COMPARATOR: Ivermectin (300 mcg/kg) or placebo will be administered in one daily dose for three consecutive days. Currently, there is no solid data on the efficacy of ivermectin against the virus in vivo; therefore the use of placebo in the control group is ethically justified.

MAIN OUTCOMES: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1. Mean viral load as determined by PCR cycle threshold (Ct) on days 4, 7, 14, and 21 2. Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial 2. Proportion of patients with a positive rapid diagnostic test at day 21 3. Proportion of drug-related adverse events during the trial 4. Median levels of IgG, IgM, IgA measured by Luminex RANDOMIZATION: Participants will be randomized to receive one dose of 300 mcg/kg ivermectin or placebo daily for three consecutive days. The epidemiologist will generate a list of correlative numbers, in randomized blocks of size 4, with the assignment to the treatment groups (a and b). The randomization list will be kept in an encrypted file accessible only to the trial statistician. This list will be handed directly to the pharmacist. Independently, the principal investigator will randomly assign the intervention (ivermectin) to one of the two groups (a or b) by tossing a coin, and will inform the pharmacist of the result of this process. The pharmacist will prepare and label the treatment vials according to the randomization list prepared by the epidemiologist and the treatment assignment given by the principal investigator. Eligible patients will be allocated in a 1:1 ratio using this randomization list.

BLINDING (MASKING): The clinical trial team, the statistician, and the patients will be blinded as to arm allocation. The vials with placebo will be visibly identical to the ones with the active drug. Treatment will be administered by staff not involved in the clinical care or participant's follow up.

NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The planned sample size is 186 SARS-CoV-2 PCR positive patients: 93 patients to treatment and 93 to the placebo group.

TRIAL STATUS: Current protocol version: 2.0 dated January 15th, 2021. Recruitment started on Aug 29th, 2020. Recruitment is expected to be completed April 30th 2021.

TRIAL REGISTRATION: "Ensayo Clínico aleatorizado de Fase IIa para comparar la efectividad de la ivermectina versus placebo en la negativización del PCR en pacientes en fase temprana de COVID-19" Peru National Health Institute REPEC with number: PER-034-20 , registered July 17th 2020 (National Peruvian Registration before the first participant enrolled). "Randomized Phase IIA Clinical Trial to Evaluate the Efficacy of Ivermectin to Obtain Negative PCR Results in Patients With Early Phase COVID-19" Clinicaltrials.gov: NCT04635943 , retrospectively registered in November 19th 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

PMID:33836826 | DOI:10.1186/s13063-021-05236-2

Drug Ther Bull. 2021 Apr 8:dtb-2021-000018. doi: 10.1136/dtb.2021.000018. Online ahead of print.

ABSTRACT

Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned.

PMID:33832945 | DOI:10.1136/dtb.2021.000018

Eur J Hosp Pharm. 2021 Apr 8:ejhpharm-2020-002667. doi: 10.1136/ejhpharm-2020-002667. Online ahead of print.

ABSTRACT

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

PMID:33832918 | DOI:10.1136/ejhpharm-2020-002667

Eur J Hosp Pharm. 2021 Apr 8:ejhpharm-2020-002610. doi: 10.1136/ejhpharm-2020-002610. Online ahead of print.

ABSTRACT

Hepatotoxicity secondary to exposure of volatile anaesthetics is an exceptional finding, but its clinical interest depends on their frequent use, unpredictable appearance and potential severity. Halothane is the volatile anaesthetic most frequently involved in the development of liver dysfunction, especially after re-exposure. Sevoflurane has rarely been related to this life-threatening complication. We present the case of a 1-year-old girl who had undergone previous surgery for closure of a patent ductus arteriosus, and who developed severe acute hepatitis and died after undergoing surgical repair of an aortic isthmus narrowing by means of general anaesthesia with sevoflurane. Other possible causes of liver failure were excluded. This adverse event was classified as serious and was included in the national and European pharmacovigilance network, with the aim of preventing dangerous effects on patient health in clinical practice, by contributing to the enrichment of the literature.

PMID:33832917 | DOI:10.1136/ejhpharm-2020-002610

Eur J Intern Med. 2021 Apr 5:S0953-6205(21)00092-3. doi: 10.1016/j.ejim.2021.03.028. Online ahead of print.

ABSTRACT

OBJECTIVE: To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users.

METHODS: We systematically reviewed randomized controlled trials (RCTs), using MEDLINE (2010-2020) and EMBASE (2010-2020) databases, reporting AE in chloroquine or hydroxychloroquine users during treatment for lupus, rheumatoid arthritis, malaria and COVID-19. The protocol for this systematic review is registered at the PROSPERO database (CRD42020197938). The quality of the included studies was assessed using the Cochrane risk-of-Bias tool and relevant data were extracted though a customized data collection form, independently, by two authors. The IRR of AE was estimated using a random-effect model meta-analysis and heterogeneity was evaluated by T2 and I2. Subgroup analysis was performed, and publication bias was assessed by funnel-plot.

RESULTS: Forty-six RCTs met our eligibility criteria and were included in our analysis (23132 patients). There was not a single death attributed to chloroquine or hydroxychloroquine use in the included RCTs. The IRR of general AE during antimalarial use was 1.15 [CI 95% 1.01-1.31]. COVID-19 patients treated with either antimalarial presented an 83% and 165% higher risk of developing general and gastrointestinal AE, respectively, in comparison with controls. The use of antimalarial increased the risk of developing dermatological AE by 92% in malarial studies and reduced by 65% in lupus studies. We did not find a significatively higher risk of cardiovascular nor ophthalmological AE in antimalarial users.

CONCLUSIONS: Our data reinforces that chloroquine and hydroxychloroquine have a good safety profile though caution is advised when using higher than usual doses in hospitalized COVID-19 patients.

PMID:33832827 | DOI:10.1016/j.ejim.2021.03.028

Scott Med J. 2021 Apr 9:369330211008587. doi: 10.1177/00369330211008587. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to present one-year real-life data of our patients with CD who showed unresponsiveness and/or intolerance to biological agents and then received ustekinumab treatment through an early access program.

MATERIALS AND METHODS: The retrospective study reviewed the 52-week clinical data of 10 patients with moderate or severe CD who underwent ustekinumab therapy.

RESULTS: The 10 patients comprised 7 (70%) men and 3 (30%) women with a mean age of 38 ± 11.3 years. Mean disease duration was 13.5 ± 8.5 years. Mean pretreatment CDAI score was 273.5 ± 92 and mean pretreatment HBI score was 11.6 ± 3.8. At the end of the 8-week intravenous induction treatment, 5 (55%) patients showed clinical remission according to the CDAI and HBI scores. Additionally, 62.5% of the patients were in clinical remission at the end of week 52 according to the CDAI and HBI scores. No drug-related side effects were observed in any patient throughout the treatment.

CONCLUSION: Ustekinumab appears to be effective and safe in the treatment of moderate and severe CD, particularly in cases of unresponsiveness and intolerance to biological agents such as anti-TNF, and in the achievement of clinical remission.

PMID:33832363 | DOI:10.1177/00369330211008587

Drug Chem Toxicol. 2021 Apr 8:1-7. doi: 10.1080/01480545.2021.1908752. Online ahead of print.

ABSTRACT

Carboplatin is amongst the most commonly used anticancer drugs for the management of several human malignancies. However, it has displayed genotoxic properties against normal cells. Evaluation of natural products for their protective effects against chemotherapeutic drug induced toxicity has been growing in recent years. A naturally occurring flavonoid, chrysin, has strong antioxidant abilities and protects against DNA impairment. This study used multiple assays to evaluate the levels of damage to DNA in normal cells and to examine any possible protective role of chrysin against such damage. Male BALB/c mice were administered chrysin orally in two doses of 20 and 40 mg/kg for 10 consecutive days and then a single injection of carboplatin [90 mg/kg body weight (b.w.)] was administered intraperitoneally to induce carboplatin toxicity. 24 h after the carboplatin injection, mice were sacrificed. DNA damage was evaluated using several genotoxicity tests (8-Hydroxydeoxy-guanosine marker, comet assay, micronucleus test, and chromosomal aberration assay) to identify diverse types of damage to the DNA. The results suggest that pretreatment with chrysin significantly decreased the level of DNA damage caused by carboplatin probably due to its potent antioxidant traits. Therefore, chrysin can be considered to be developed as a chemoprotective agent against chemotherapy associated side-effects.

PMID:33829940 | DOI:10.1080/01480545.2021.1908752

Gut Liver. 2021 Apr 7. doi: 10.5009/gnl20338. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: : The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of MucostaⓇ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis.

METHODS: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or MucostaⓇ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; MucostaⓇ, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; MucostaⓇ, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated.

RESULTS: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was -4.01% (95% confidence interval [CI], -13.09% to 5.06%) in the ITT analysis and -4.44% (95% CI, -13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 MucostaⓇ-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates.

CONCLUSIONS: The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (MucostaⓇ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.

PMID:33827990 | DOI:10.5009/gnl20338

Ocul Immunol Inflamm. 2021 Apr 7:1-5. doi: 10.1080/09273948.2021.1887279. Online ahead of print.

ABSTRACT

Purpose: To describe four cases of ocular adverse events resembling intraocular inflammatory and non-inflammatory conditions following yellow fever vaccination (YFV) during a recent yellow fever (YF) outbreak in Brazil.Methods: Charts of patients diagnosed with ocular adverse events after YFV between January 2017 and January 2019 at two tertiary referral centers in Brazil.Results: Four patients (two adults and two children) are reported. Case 1 presented with typical findings of central serous chorioretinopathy which resolved spontaneously; case 2 was diagnosed with acute Vogt-Koyanagi-Harada disease; cases 3 and 4 had bilateral diffuse retinal vasculitis. In the absence of infectious and noninfectious disorders, the temporal association between stand-alone YFV and onset of ocular symptoms within 15 days was interpreted as evidence of causation.Conclusions: Clinicians should be aware of the wide spectrum of possible ocular adverse reactions to stand-alone YFV.

PMID:33826478 | DOI:10.1080/09273948.2021.1887279

Psychooncology. 2021 Apr 6. doi: 10.1002/pon.5654. Online ahead of print.

ABSTRACT

OBJECTIVE: Steroids play an essential role in treating pediatric acute lymphoblastic leukemia (ALL). The downside is that these drugs can cause severe side effects, such as adverse psychological reactions (APRs) and sleep problems, which can compromise health-related quality of life. This study aimed to systematically review literature to identify risk factors for steroid-induced APRs and sleep problems in children with ALL.

METHODS: A systematic search was performed in six databases. Titles/abstracts were independently screened by two researchers. Data from each included study was extracted based on predefined items. Risk of bias and level of evidence were assessed, using the Quality in Prognosis Studies tool and the Grading of Recommendations Assessment, Development and Evaluation tool, respectively.

RESULTS: Twenty-four articles were included. APR measurement ranged from validated questionnaires to retrospective record retrieval, sleep measurement included questionnaires or actigraphy. Overall, quality of evidence was very low. Current evidence suggests that type/dose of steroid is not related to APRs, but might be to sleep problems. Younger patients seem at risk for behavior problems and older patients for sleep problems. No studies describing parental stress or medical history were identified. Genetic susceptibility associations remain to be replicated.

CONCLUSIONS: Based on the current evidence, conclusions about risk factors for steroid-induced adverse psychological reactions or sleep problems in children with ALL should be drawn cautiously, since quality of evidence is low and methods of measurement are largely heterogeneous. A standardized registration of steroid-induced APRs/sleep problems and risk factors is warranted for further studies in children with ALL.

PMID:33825231 | DOI:10.1002/pon.5654

J Res Med Sci. 2020 Nov 26;25:109. doi: 10.4103/jrms.JRMS_777_20. eCollection 2020.

ABSTRACT

BACKGROUND: Coronaviruses are major pathogens of respiratory system causing different disorders, including the common cold, Middle East respiratory syndrome, and severe acute respiratory syndrome. Today's global pandemic coronavirus disease 2019 (COVID-19) has high mortality rate, with an approximate of 20% in some studies, and is 30-60 times more fatal than the common annual influenza, However, there is still no gold standard treatment for it. N-acetylcysteine (NAC) is a well-known multi-potential drug with hypothetically probable acceptable effect on COVID-related consequences, which we completely focused in this comprehensive review.

MATERIALS AND METHODS: PubMed, Scopus, Science Direct, and Google Scholar have been searched. Study eligibility criteria: efficacy of NAC in various subclasses of pathogenic events which may occur during COVID-19 infection. Efficacy of NAC for managing inflammatory or any symptoms similar to symptoms of COVID-19 was reviewed and symptom improvements were assessed.

RESULTS: Randomized clinical trials introduced NAC as an antioxidant glutathione analog and detoxifying agent promoted for different medical conditions and pulmonary disorders to alleviate influenza and reduce mortality by 50% in influenza-infected animals. The beneficial effects of NAC on viral disorders, including Epstein-Barr virus, HIV and hepatitis, and well-known vital organ damages were also exist and reported.

CONCLUSION: We classified the probable effects of NAC as oxidative-regulatory and apoptotic-regulatory roles, antiviral activities, anti-inflammatory roles, preventive and therapeutic roles in lung disorders and better oxygenation functions, supportive roles in intensive care unit admitted patients and in sepsis, positive role in other comorbidities and nonpulmonary end-organ damages or failures and even in primary COVID-associated cutaneous manifestations. Based on different beneficial effects of NAC, it could be administered as a potential adjuvant therapy for COVID-19 considering patient status, contraindications, and possible drug-related adverse events.

PMID:33824674 | PMC:PMC8019127 | DOI:10.4103/jrms.JRMS_777_20

J Thorac Oncol. 2021 Apr 3:S1556-0864(21)02067-0. doi: 10.1016/j.jtho.2021.03.012. Online ahead of print.

ABSTRACT

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like protein 3 (DLL3), an atypical Notch ligand expressed in small cell lung cancer (SCLC) tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive stage (ES) SCLC after platinum-based chemotherapy.

METHODS: MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression following 4 cycles of platinum-based front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (q6wk, omitted every third cycle). Primary efficacy endpoints were progression-free survival (PFS) assessed by the Central Radiographic Assessment Committee (CRAC) and overall survival (OS) in DLL3-high patients.

RESULTS: Median age of all randomized patients (N=748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the DLL3-high subset, the hazard ratio (HR) for OS was 1.07 (95% CI: 0.84-1.36) favoring placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 months, HR=0.48; P<0.001). Any-grade adverse events (≥20%) in the Rova-T arm were pleural effusion (27%), decreased appetite (27%), peripheral edema (26%), photosensitivity reaction (25%), fatigue (25%), nausea (22%), and dyspnea (21%).

CONCLUSIONS: Due to the lack of survival benefit in the Rova-T arm, the study did not meet its primary endpoint and was terminated early. As a result, CRAC assessment of PFS was not performed. The frequency of Grade ≥3 and drug-related toxicities were higher with Rova-T vs placebo. Rova-T was associated with unique toxicities such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the ES SCLC population.

PMID:33823285 | DOI:10.1016/j.jtho.2021.03.012