J Clin Oncol. 2021 Jun 29:JCO2100163. doi: 10.1200/JCO.21.00163. Online ahead of print.

ABSTRACT

PURPOSE: Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC.

PATIENTS AND METHODS: This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients.

RESULTS: Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months (P = .0570). The objective response rate was 4.6% v 2.7% (P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018).

CONCLUSION: Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

PMID:34185551 | DOI:10.1200/JCO.21.00163

Phytother Res. 2021 Jun 28. doi: 10.1002/ptr.7176. Online ahead of print.

ABSTRACT

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

PMID:34184327 | DOI:10.1002/ptr.7176

Eur J Hosp Pharm. 2021 Jun 28:ejhpharm-2021-002739. doi: 10.1136/ejhpharm-2021-002739. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the effect of angiotensin II receptor blocker (ARB) treatment on serum potassium level and hyperkalaemia risk in a clinical setting with inpatients and outpatients using calcium channel blockers (CCBs) as a reference standard.

METHODS: The increased risk of hyperkalaemia associated with ARB treatment is known, however only a few studies have used an active comparator to examine this risk. In this retrospective study at a 320-bed general hospital in Japan, the hospital information system was used to identify patients with at least one prescription for an ARB (819 patients) or a CCB (1015 patients) who were naive to these drugs before study initiation. Serum potassium levels before and after ARB treatment were compared. Additionally, the unadjusted and adjusted hazard ratios for the risk of hyperkalaemia in the ARB and CCB users were estimated.

RESULTS: The serum potassium level was higher in patients receiving ARB treatment (0.05 mEq/L, p=0.02) compared with those on CCB treatment. However, there was no significant association between ARB use and hyperkalaemia (adjusted HR 0.91, 95% CI 0.42 to 1.99, p=0.82).

CONCLUSION: The increase in serum potassium level after ARB initiation makes it necessary to monitor serum potassium levels continuously during ARB treatment; however, the risk of hyperkalaemia appeared to be similar for ARB and CCB treatments.

PMID:34183459 | DOI:10.1136/ejhpharm-2021-002739

BJPsych Open. 2021 Jun 29;7(4):e121. doi: 10.1192/bjo.2021.945.

ABSTRACT

BACKGROUND: Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model.

AIMS: We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia.

METHOD: This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months.

RESULTS: This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients.

CONCLUSION: This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.

PMID:34183088 | DOI:10.1192/bjo.2021.945

JAMA. 2021 Jun 28. doi: 10.1001/jama.2021.9199. Online ahead of print.

ABSTRACT

IMPORTANCE: In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption.

OBJECTIVE: To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020.

INTERVENTIONS: Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA.

MAIN OUTCOME AND MEASURE: Twenty-four-hour urinary excretion of NDMA.

RESULTS: Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, -6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, -1.1 [IQR, -9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported.

CONCLUSIONS AND RELEVANCE: In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04397445.

PMID:34180947 | DOI:10.1001/jama.2021.9199

J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:23247096211028386. doi: 10.1177/23247096211028386.

ABSTRACT

Pancreatitis is inflammation of pancreas associated most commonly with chronic alcoholism and gallstones. Other less common causes of pancreatitis are hyperlipidemia, infections, surgery, trauma, post endoscopic retrograde cholangiopancreatography, and drugs. Drugs are now increasingly recognized as a cause of pancreatitis, and high suspicion and exclusion of other most common causes is required before considering drug-induced pancreatitis. There are few case reports of acute pancreatitis in the literature after statin use, but out of these, only 3 are after starting pravastatin. We are reporting a case of 49-year-old male who presented with nausea, vomiting, and abdominal pain. His laboratory findings were significant for lipase more than 10 000 on admission, and computed tomography scan of abdomen was showing peripancreatic fat stranding and inflammation. After exclusion of most common causes of pancreatitis, pravastatin was found probable culprit for his symptoms, which he started taking 2 weeks ago. We also reviewed the literature on statins-induced acute pancreatitis. With increased uses of statins, physician need to be vigilant to suspect statins as a culprit in cases of pancreatitis with unknown etiology. Prompt discontinuation of statins is required in these cases.

PMID:34180257 | DOI:10.1177/23247096211028386

Front Med (Lausanne). 2021 Jun 4;8:570921. doi: 10.3389/fmed.2021.570921. eCollection 2021.

ABSTRACT

EGFR tyrosine kinase inhibitors (TKIs) are the front-line treatment in EGFR mutation positive advanced non-small cell lung cancer (aNSCLC) patients. Generally, they are well-tolerated but skin toxicity is common (45-100% of patients) and may adversely affect quality of life. Pathogenesis of cutaneous side effects is usually linked to EGFR expression in normal cells of the epidermis and not immune-related. Subacute cutaneous lupus erythematosus (SCLE) is an autoimmune disease and about 40% of SCLE cases are drug related, but no reports are available involving osimertinib. Our report depicts a drug induced-SCLE (DI-SCLE) caused by erlotinib and worsened by osimertinib. The adverse event is characterized by the absence of systemic symptoms. Diagnosis has been performed by skin biopsy and the conditions improved with systemic steroids administration and EGFR-TKIs discontinuation. The report underlines the importance of a complete dermatologic diagnosis of skin lesions induced by EGFR inhibitors, according to symptom severity and timing of improving with standard clinical management. The diagnosis of immune-related skin toxicity in this context affects the treatment and the outcome of skin toxicity and must be taken into account when planning subsequent treatments, potentially including immune checkpoint inhibitors (ICIs).

PMID:34179028 | PMC:PMC8220808 | DOI:10.3389/fmed.2021.570921

J Diabetes Metab Disord. 2021 Jan 19;20(1):271-278. doi: 10.1007/s40200-021-00741-2. eCollection 2021 Jun.

ABSTRACT

AIMS: Diabetic peripheral neuropathy affects up to 60% of individuals and often leads to foot ulceration and eventual amputation. When oral therapy has failed to achieve pain relief, the first line local treatment is the 5% lidocaine-medicated plaster which provides local relief. Capsaicin 8% patch is considered a promising topical treatment for diabetic peripheral neuropathy. The present study investigated the efficacy, safety and tolerability of capsaicin 8% patch vs 5% lidocaine patch treatments over 24 weeks in South Asian male diabetic patients with established peripheral diabetic neuropathy.

METHODS: Analgesic effectiveness was assessed by observing any change in the Numeric Pain Rating Scale (NPRS) score, Brief Pain Inventory (BPI) for painful diabetic peripheral neuropathy (BPI-DPN question 4) and Patient Global Impression of Change (PGIC). All patients received 4% lidocaine gel/cream for 60 min prior to patch application. The trial was probably underpowered, taking into account the smaller than expected number of participants from the calculated 350 sample size required for the whole study. Two hundred ninety-one individuals were divided into three groups based on treatment regimen; Group LL (Lidocaine + Lidocaine), Group LP (Lidocaine + Placebo), Group LC (Lidocaine + Capsaicin). The treatment procedure was conducted once initially and then repeated once at 12 weeks. The patients were followed up on alternate weeks till 24 weeks after the initial treatment.

RESULTS: Group LC experienced a more significant reduction in the average pain intensity (p < 0.05) during the last twenty-four hours. Group LC showed more significant reduction of pain compared to control (p < 0.01), a baseline score of 5.4 ± 1.2 dropped to 3.2 ± 1.5 by week 24 of treatment. The change in mean daily pain intensity was - 2.2 ± 1.5 [95% CI: -2.45, -1.5]. Group LL and LC experienced a significant overall improvement (slightly, much or very much) in the health status during the study. After the second week of the treatment, patient satisfaction scores were 2.1 ± 1.1 in Group LL which increased to 3.2 ± 1.2 by week 24 of treatment. The capsaicin 8% patch appears to be reasonably well tolerated since there were no discontinuations because of serious drug-related treatment emergent adverse event (TEAEs).

CONCLUSIONS: The aim of the present study was to assess the efficacy, safety and tolerability of the 8% capsaicin patch in patients with established painful diabetic neuropathy. There was a sustained treatment response to the initial and repeat treatment of the capsaicin 8% patch over the 24 weeks. The study population was very specific so further studies are required to investigate the generalizability of the results for patients experiencing painful diabetic neuropathy. The patch could be considered as an effective long-term treatment option in individuals with painful diabetic neuropathy, particularly those experiencing inadequate pain relief or side effects from systemic therapies.

PMID:34178837 | PMC:PMC8212319 | DOI:10.1007/s40200-021-00741-2

Ther Adv Musculoskelet Dis. 2021 Jun 11;13:1759720X211014020. doi: 10.1177/1759720X211014020. eCollection 2021.

ABSTRACT

BACKGROUND: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) neridronate in CRPS-1 patients.

METHODS: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) neridronate (N = 41) given once daily for 16 consecutive days or placebo control (N = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed.

RESULTS: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients versus placebo (31.9 ± 23.3 mm versus 52.3 ± 27.8 mm, p = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the neridronate group (65.9% versus 29.7%, p = 0.0017). Clinical signs and symptoms were improved significantly in the neridronate group versus placebo for edema (72.5% versus 79.9%, p = 0.03), pain during motion (70% versus 83.3%, p = 0.0009), allodynia (20% versus 63.3%, p = 0.0004), and hyperalgesia (20% versus 56.7%, p = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the neridronate group. No serious drug-related adverse events were reported during the study.

CONCLUSION: In patients with acute CRPS-1, i.m. injections of 25 mg neridronate were associated with clinically relevant benefit compared with placebo controls.

TRIAL REGISTRATION: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28.

PMID:34178124 | PMC:PMC8202309 | DOI:10.1177/1759720X211014020

J Vasc Bras. 2020 Jun 8;19:e20190018. doi: 10.1590/1677-5449.190018.

ABSTRACT

Alopecia is a common complication of anticoagulant therapy that may have important psychological repercussions for patients, especially female patients, and can interfere with the decision to extend anticoagulation. This review aims to describe the mechanisms potentially involved in the genesis of alopecia during anticoagulant therapy, since these are not yet fully understood, and discusses the existing therapies for the most appropriate management.

PMID:34178048 | PMC:PMC8202206 | DOI:10.1590/1677-5449.190018

Front Pharmacol. 2021 Jun 9;12:655605. doi: 10.3389/fphar.2021.655605. eCollection 2021.

ABSTRACT

From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers' Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs. However, the pathogenesis of interstitial lung disease (ILD), a serious drug-induced adverse effect, remains unclear. Moreover, there have been no large-scale evaluations of potential complications associated with currently used antiandrogens, which are commonly employed to treat prostate cancer. Hence, ILD, as an adverse event, remains poorly understood. Therefore, we conducted a survey of reports in the Japanese Adverse Drug Event Report (JADER) database to investigate the potential association between the reporting of ILD and antiandrogen drug use in clinical practice. The occurrence of ILD was investigated by evaluating the relationship between antiandrogen drug use and ILD. Adverse event signals were detected with reporting odds ratios (RORs), using data from the JADER and FDA Adverse Event Reporting System (FAERS) databases, for the analysis of post-marketing adverse event reports. The JADER was used to examine the time profile of adverse event occurrence for each drug, whereas the FAERS was used to screen cases of unknown adverse events and analyze their trends of occurrence. The analysis of data from both databases revealed the 95% confidence interval lower limits of ROR for bicalutamide and flutamide to be > 1, and adverse event signals were detected following the use of either drug. While caution should be exercised for drugs that are new to the market, we conclude that drugs with similar therapeutic effects that have been in use for a long period should also be re-examined for potential adverse events.

PMID:34177574 | PMC:PMC8220081 | DOI:10.3389/fphar.2021.655605

Case Rep Oncol. 2021 May 26;14(2):733-738. doi: 10.1159/000516274. eCollection 2021 May-Aug.

ABSTRACT

Drug-induced interstitial lung disease (DI-ILD) is a rare, yet life-threatening complication associated with tyrosine-kinase inhibitor (TKI) therapy. Third-generation epidermal growth factor receptor-TKI, osimertinib use can be associated with a benign radiological finding called transient asymptomatic pulmonary opacities that can be confused with an infectious pulmonary process resulting in overtreatment with antibiotics or premature treatment withdrawal or severe DI-ILD. In this case, our patient with newly diagnosed metastatic non-small cell lung cancer on treatment with osimertinib developed very early onset severe DI-ILD (grade-IV) with a unique pattern of pulmonary involvement and was treated with high-dose corticosteroids with a response. She was later successfully rechallenged with osimertinib and responded well to the treatment. Our case highlights the importance of being cognizant of the possibility that DI-ILD can rarely occur within a week of treatment initiation with osimertinib and safe reintroduction of the drug is possible in select patients following complete resolution of pulmonary radiographic findings and clinical symptoms even with high-grade adverse events.

PMID:34177523 | PMC:PMC8216030 | DOI:10.1159/000516274

Res Social Adm Pharm. 2021 Jun 19:S1551-7411(21)00230-8. doi: 10.1016/j.sapharm.2021.06.013. Online ahead of print.

ABSTRACT

BACKGROUND: Medication discrepancies at nursing home intake increase the risk of drug-related adverse events. Measuring discrepancy incidence rates and locating the origins of discrepancies can assist in identifying information exchange deficits for high-risk medications.

OBJECTIVE: To determine class-specific discrepancy rates, to determine discordance between medication lists, and to explore patient and system-level factors associated with medication discrepancies discovered between the first and second medication reconciliations conducted at nursing home intake.

METHODS: Medication discrepancy data were prospectively collected from four long-term care facilities over a 9-month period. Medication discrepancies were defined as mismatched prescribing orders between at least two medication history lists. Discrepancy locations were defined as the pairs or triads of facilities between which medication history lists were discordant. Unadjusted logistic regressions were used to identify medication classes with the highest discrepancy rates and patient factors significantly associated with any medication discrepancy.

RESULTS: 40.8% of newly admitted or re-admitted residents and 6.3% of medications reviewed had at least one medication discrepancy discovered during the second medication reconciliation conducted at nursing home intake. Residents prescribed fewer than 14 medications were at less risk of discrepancies. Residents with Charlson Comorbidity Index of 5, COPD, HF, anemia or HTN were at greater risk of discrepancies. Respiratory and analgesic medications were twice as likely as other medication classes to be discrepant (OR = 2.2, 95% CI 1.2-4.4; OR = 2.2, 95% CI 1.3-3.5). Most discrepancies occurred between hospital and nursing home lists (44.9%), or between the hospital, nursing home, and community pharmacy lists (39.3%) CONCLUSIONS: Given the higher risk of discrepancies within respiratory or analgesics, transitions of care teams need to prioritize residents with respiratory conditions or pain. Although re-admitted residents' increased discrepancy risk is likely due to poorer health status, miscommunications across the nursing home, hospital and community pharmacy require further research to clarify system failures.

PMID:34176761 | DOI:10.1016/j.sapharm.2021.06.013

BMJ Case Rep. 2021 Jun 24;14(6):e243079. doi: 10.1136/bcr-2021-243079.

ABSTRACT

Though the prevalence of drug induced allergic interstitial nephritis (AIN) appears to be increasing, the diagnostic and treatment strategies still remain vague. We present a 56-year-old man with a history of hypertension, chronic kidney disease stage IIIa, recent exposure to ciprofloxacin who presented with acute kidney injury. Though the suspicion of AIN was high, his urinary sediment was bland, that is, no leucocytes or leucocyte casts. A renal biopsy subsequently showed features of AIN correlating with a resolving phase of inflammation. Given the resolving nature of the pathology, we chose not to complete a course of corticosteroids despite his need for temporary haemodialysis. He was able to fully recover his renal function. In this report, we emphasise the unreliable nature of the urinary sediment in the diagnosis of AIN, the utility of a renal biopsy in helping to guide treatment, and the controversial data in corticosteroid treatment.

PMID:34167986 | DOI:10.1136/bcr-2021-243079

Front Cardiovasc Med. 2021 Jun 8;8:676771. doi: 10.3389/fcvm.2021.676771. eCollection 2021.

ABSTRACT

Background: Inflammation plays a key role in atherosclerotic plaque destabilization and adverse cardiac remodeling. Recent evidence has shown a promising role of colchicine in patients with coronary artery disease. We evaluated the efficacy and safety of colchicine in post-acute myocardial infarction (MI) patients. Methods: We searched five electronic databases from inception to January 18, 2021, for randomized controlled trials (RCTs) evaluating colchicine in post-acute MI patients. Primary outcomes were cardiovascular mortality and recurrent MI. Secondary outcomes were all-cause mortality, stroke, urgent coronary revascularization, levels of follow-up high-sensitivity C-reactive protein (hs-CRP), and drug-related adverse events. All meta-analyses used inverse-variance random-effects models. Results: Six RCTs involving 6,005 patients were included. Colchicine did not significantly reduce cardiovascular mortality [risk ratio (RR), 0.91; 95% confidence interval (95% CI), 0.52-1.61; p = 0.64], recurrent MI (RR, 0.87; 95% CI, 0.62-1.22; p = 0.28), all-cause mortality (RR, 1.06; 95% CI, 0.61-1.85; p = 0.78), stroke (RR, 0.28; 95% CI, 0.07-1.09; p = 0.05), urgent coronary revascularization (RR, 0.46; 95% CI, 0.02-8.89; p = 0.19), or decreased levels of follow-up hs-CRP (mean difference, -1.95 mg/L; 95% CI, -12.88 to 8.98; p = 0.61) compared to the control group. There was no increase in any adverse events (RR, 0.97; 95% CI, 0.89-1.07; p = 0.34) or gastrointestinal adverse events (RR, 2.49; 95% CI, 0.48-12.99; p = 0.20). Subgroup analyses by colchicine dose (0.5 vs. 1 mg/day), time of follow-up (<1 vs. ≥1 year), and treatment duration (≤30 vs. >30 days) showed no changes in the overall findings. Conclusion: In post-acute MI patients, colchicine does not reduce cardiovascular or all-cause mortality, recurrent MI, or other cardiovascular outcomes. Also, colchicine did not increase drug-related adverse events.

PMID:34169101 | PMC:PMC8217746 | DOI:10.3389/fcvm.2021.676771

BMJ Open. 2021 Jun 24;11(6):e047147. doi: 10.1136/bmjopen-2020-047147.

ABSTRACT

INTRODUCTION: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response.

METHODS AND ANALYSIS: The SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic for Schistosoma mansoni and Schistosoma haematobium, are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial's primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated.

ETHICS AND DISSEMINATION: Ethics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences.

TRIAL REGISTRATION NUMBER: NCT03893097; pre-results.

PMID:34168029 | DOI:10.1136/bmjopen-2020-047147

Ann Coloproctol. 2021 Jun 24. doi: 10.3393/ac.2020.00213.0030. Online ahead of print.

ABSTRACT

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

PMID:34167190 | DOI:10.3393/ac.2020.00213.0030

Phytother Res. 2021 Jun 24. doi: 10.1002/ptr.7180. Online ahead of print.

ABSTRACT

The effects of saffron (Crocus sativus L.) on mood disorders have already been established. More recently, its anti-neoplastic effects have provoked a great attention. This study aims to assess the effects of crocin administration during doxorubicin-based chemotherapy of breast cancer on anxiety, depression, and chemotherapy toxicity profile. Seventy-two patients with non-metastatic Her2/neu positive or triple negative breast cancer were enrolled and randomly assigned to receive either 30 mg/day of crocin or placebo during chemotherapy [2:2]. Beck's Depression and Anxiety Inventories were used at baseline and end of the trial. In addition, the ECOG Common Toxicity Criteria were applied to assess chemotherapy side-effects. After the intervention, the degree of anxiety and depression decreased significantly in the crocin group (p = .001 for both) and increased significantly in the placebo-group (p = .006 and p = .036, respectively). There were significantly higher grade II-IV leukopenia (47.2% vs. 19.4%, p = .012) in the crocin group, and grade II-IV hypersensitivity-reaction (30.6% vs. 5.6%, p = .006) in addition to neurological disorders (66.7% vs. 41.7%, p = .03) in the placebo-group. The results indicate that using crocin during chemotherapy in patients with breast cancer has ameliorated anxiety and depression. Moreover, leucopenia increased whereas hypersensitivity reaction and neurological disorders decreased in the crocin group. In addition, a trend toward survival improvement was observed, which is going to be investigated on longer follow up.

PMID:34164855 | DOI:10.1002/ptr.7180

Int Immunopharmacol. 2021 Jul;96:107755. doi: 10.1016/j.intimp.2021.107755. Epub 2021 May 24.

ABSTRACT

BACKGROUND: Pemphigus is an autoimmune disease that is challenging to treat and has few available therapeutic options. Recently, several studies have demonstrated that rituximab may be an efficacious first-line treatment in newest guidelines.

AIM: To compare the side effect profiles of rituximab administered after a course of immunosuppressant agents versus as a first-line therapy and evaluate the impact of patient characteristics and disease severity indices on occurrence of adverse effects.

METHODS: A retrospective cross-sectional study was conducted on 999 patients with pemphigus vulgaris who received rituximab either as a first-line treatment or after conventional adjuvant therapies. The occurrence of partial or complete remission as well as the incidence of drug-related adverse effects were evaluated and compared between the two groups.

RESULTS: Smoking, pulmonary comorbidity, and mucocutaneous phenotype were associated with an increased risk of developing infectious complications by 12.49, 5.79, and 2.37 fold, respectively. These associations were more prominent among those who received rituximab after immunosuppressant agents.

CONCLUSIONS: Early use of rituximab benefits pemphigus patients, especially those with a mucocutaneous phenotype, pulmonary comorbidity, or history of smoking, and reduces their risk of infectious adverse events.

PMID:34162136 | DOI:10.1016/j.intimp.2021.107755

Medicine (Baltimore). 2021 Jun 25;100(25):e26243. doi: 10.1097/MD.0000000000026243.

ABSTRACT

RATIONALE: Eszopiclone, sold under the brand name Lunesta, is a new type of non-benzodiazepine hypnotic. Eszopiclone is a zopiclone dextrorotation, which is classified as a cyclopyrrolone. It functions by binding gamma-aminobutyric acid (GABA) receptors. Compared with benzodiazepines hypnotics, eszopiclone has higher selectivity for certain subunits of the GABA(A) receptor. So far, there are no reports about the elevation of serum enzymes or severe liver injury caused by eszopiclone. Here, we present a case report of acute liver injury following eszopiclone treatment in a patient with chronic hepatitis B virus (HBV).

PATIENT CONCERNS: The patient was a 53-year-old female with a 36-year history of positive HBV markers. Due to poor sleep, the patient took trazodone hydrochloride orally for 1 year. After hospital admission for positive hepatitis B pathogenic markers, abdominal distension, fatigue, and aggravation, she was treated with eszopiclone under the guidance of the mental health department.

DIAGNOSES: Her transaminase levels increased abnormally after eszopiclone treatment and rapidly decreased after drug withdrawal. This was determined to be an acute liver injury event. liver-protecting treatment was maintained. Considering the patient's anxiety and depression, the patient's family members refused a liver biopsy.

OUTCOMES: Transaminase levels decreased rapidly within one week, and the patient continued to take trazodone hydrochloride after discharge. No adverse events occurred in the follow-up period.

LESSONS: Sleep disorders are more common in patients with chronic diseases, especially patients with chronic liver disease. Recently, it has become common for patients with hepatitis B and C to use antidepressants along with antiviral treatment. Patients with chronic hepatitis B or C may have a threefold risk of liver dysfunction after receiving antituberculosis treatment.[1,2] A proinflammatory environment induced by actively replicating the hepatitis virus may alter the detoxication process and increase drug toxicity.[3] At this time, the safety of other drugs should be reevaluated. Although hepatitis and liver injury are listed as rare adverse reactions of eszopiclone, this case is the first to report the eszopiclone-involved acute liver injury.

PMID:34160387 | DOI:10.1097/MD.0000000000026243