Effects of Topical Hangeshashinto (TJ-14) on Chemotherapy-Induced Oral Mucositis.

Cancer Manag Res. 2020;12:1069-1078

Authors: Ozawa N, Onda T, Hayashi K, Honda H, Shibahara T

Abstract
Purpose: Hangeshashinto (TJ-14), a Kampo medicine comprising seven types of herbs, has been used in Japan to alleviate the side effects associated with anticancer drug treatments. However, the pharmacological effects of this medicine currently remain unclear. The present study aimed to demonstrate the efficacy of TJ-14 against anticancer drug-induced stomatitis, the pain associated with which may have a negative impact on mastication and swallowing.
Methods: Mucositis was induced in Sprague-Dawley rats by cancer chemotherapy. Changes in body weight, stomatitis grades, histopathological scores, and oral bacterial counts were examined among TJ-14-treated, saline-treated, and Control (no treatment) rats. In vitro studies, including cell proliferation and wound healing assays, using epidermal keratinocyte and fibroblast cell lines were conducted.
Results: The local application of TJ-14 exerted strong antibacterial effects and attenuated oral chemotherapy-induced stomatitis in rats. TJ-14 also increased the viability and invasion of epidermal keratinocytes and fibroblasts.
Conclusion: The present results demonstrated the potential of TJ-14 to attenuate chemotherapy-induced stomatitis.

PMID: 32104087 [PubMed]

A phase II study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with malignant pleural mesothelioma.

Lung Cancer. 2020 Feb 12;:

Authors: Zucali PA, Perrino M, De Vincenzo F, Giordano L, Cordua N, D'Antonio F, Santoro A

Abstract
OBJECTIVES: Second-line chemotherapy is not a standard of care in patients with malignant pleural mesothelioma (MPM) that progresses after first-line treatment with cisplatin and pemetrexed. In pre-clinical models, the combination of gemcitabine (GEM) and imatinib mesylate (IM), compared with GEM alone, led to a further tumor growth inhibition and improved survival. This phase II study evaluates the antitumor activity of a combination of IM and GEM in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-β and/or cKIT by immunohistochemistry (IHC).
PATIENTS AND METHODS: GEM (1000 mg/m2) was given on days 3 and 10; IM (400 mg) was taken orally on days 1-5 and 8-12 of a 21-day cycle. The primary endpoint was the 3-month progression-free survival (PFS) rate. The study follows the optimal two-stage design of Simon. A 3-month PFS target of 75 % was required. With a probability error α = 10 % and a power of 80 %, the calculated sample size was 22 patients. In particular, in the first step, six out of nine patients and globally 14/22 patients free from progressive disease at 3 months were required. Secondary endpoints included response rate, duration of response, toxicity and overall survival (OS).
RESULTS: In total, 23 patients were enrolled (ECOG PS 0-1/2: 9/13; one previous line/≥two previous lines: 10/13). Partial response was achieved in four patients (17.4 %) and stable disease in 11 (47.8 %) with a disease control rate of 65.3 %. After a median follow-up of 34.5 months, median PFS and OS were 2.8 and 5.7 months, respectively. The 3-month PFS rate was 39.1 % (9/23 patients). All-grade drug-related adverse events occurred in 17 (73.9 %) patients. Grade 3 treatment-related adverse events were observed in four (17 %) patients.
CONCLUSIONS: The combination of IM and GEM is well tolerated in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-β and/or cKIT by IHC, but it does not show a significant PFS benefit.

PMID: 32102735 [PubMed - as supplied by publisher]

Polypharmacy among patients with multiple sclerosis: a qualitative systematic review.

Expert Opin Drug Saf. 2020 Feb;19(2):139-145

Authors: Frahm N, Hecker M, Zettl UK

Abstract
Objectives: The consequences of polypharmacy (intake of ≥ 5 drugs) are diverse, including drug interactions, rising costs and side effects. Risk groups for polypharmacy are multimorbid and chronically ill people, such as patients with multiple sclerosis (MS). MS is the most common neuroimmunological disease in young adults worldwide. We aimed to provide a systematic overview of the current research status regarding frequency and predictors of polypharmacy in MS patients.Methods: A systematic literature search in the databases PubMed, Cochrane Library and Scopus was carried out according to the PRISMA guidelines. English and German original research articles were included.Results: Seven studies fulfilled the inclusion criteria of this review, while the research objectives and methods were very heterogenous. The polypharmacy rates in these studies ranged from 15% to 59%. Polypharmacy correlated with comorbidities, increased disability, cognitive deficits, increased hospitalization, higher relapse rate and lower quality of life.Conclusions: In MS patients, polypharmacy is common and closely associated with health issues. There is a great need for research in this area, especially regarding longitudinal changes in drug utilization. Effective networks between physicians and pharmacists are needed to optimize medication management for patients and to achieve the best possible therapy results.

PMID: 31965869 [PubMed - indexed for MEDLINE]

A systematic review of natural language processing for classification tasks in the field of incident reporting and adverse event analysis.

Int J Med Inform. 2019 12;132:103971

Authors: Young IJB, Luz S, Lone N

Abstract
CONTEXT: Adverse events in healthcare are often collated in incident reports which contain unstructured free text. Learning from these events may improve patient safety. Natural language processing (NLP) uses computational techniques to interrogate free text, reducing the human workload associated with its analysis. There is growing interest in applying NLP to patient safety, but the evidence in the field has not been summarised and evaluated to date.
OBJECTIVE: To perform a systematic literature review and narrative synthesis to describe and evaluate NLP methods for classification of incident reports and adverse events in healthcare.
METHODS: Data sources included Medline, Embase, The Cochrane Library, CINAHL, MIDIRS, ISI Web of Science, SciELO, Google Scholar, PROSPERO, hand searching of key articles, and OpenGrey. Data items were manually abstracted to a standardised extraction form.
RESULTS: From 428 articles screened for eligibility, 35 met the inclusion criteria of using NLP to perform a classification task on incident reports, or with the aim of detecting adverse events. The majority of studies used free text from incident reporting systems or electronic health records. Models were typically designed to classify by type of incident, type of medication error, or harm severity. A broad range of NLP techniques are demonstrated to perform these classification tasks with favourable performance outcomes. There are methodological challenges in how these results can be interpreted in a broader context.
CONCLUSION: NLP can generate meaningful information from unstructured data in the specific domain of the classification of incident reports and adverse events. Understanding what or why incidents are occurring is important in adverse event analysis. If NLP enables these insights to be drawn from larger datasets it may improve the learning from adverse events in healthcare.

PMID: 31630063 [PubMed - indexed for MEDLINE]

Highlight report: predicting hepatotoxic oral doses of chemicals by in vitro testing and in silico modeling.

Arch Toxicol. 2019 09;93(9):2707-2708

Authors: Hassan R

PMID: 31346659 [PubMed - indexed for MEDLINE]

Serious adverse events in African-American cancer patients with sickle cell trait and inherited haemoglobinopathies in a SEER-Medicare claims cohort.

Br J Cancer. 2019 04;120(8):861-863

Authors: Hoag JR, Andemariam B, Wang X, Gregorio DI, Jones BA, Sporn J, Salner AL, Swede H

Abstract
African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.

PMID: 30890774 [PubMed - indexed for MEDLINE]

Phase 1 trial of dasatinib combined with afatinib for epidermal growth factor receptor- (EGFR-) mutated lung cancer with acquired tyrosine kinase inhibitor (TKI) resistance.

Br J Cancer. 2019 04;120(8):791-796

Authors: Creelan BC, Gray JE, Tanvetyanon T, Chiappori AA, Yoshida T, Schell MJ, Antonia SJ, Haura EB

Abstract
BACKGROUND: Bypass activation of Src family kinases can confer resistance to EGFR tyrosine kinase inhibitors (TKIs) based on preclinical models. We prospectively assessed the safety and clinical activity of dasatinib and afatinib in combination for patients with resistant EGFR-mutant lung cancer.
METHODS: An open-label, dose-escalation phase 1/2 trial (NCT01999985) with 2-stage expansion was conducted with 25 lung cancer patients. Dose expansion required activating EGFR mutations and progression following prior EGFR TKI.
RESULTS: Patients were 72% Caucasian and received median of 2 prior lines of therapy. Maximum-tolerated dose was 30 mg afatinib with 100 mg dasatinib. New or increased pleural effusions were observed in 56% of patients. No radiologic responses were observed, although several EGFR-mutant TKI-resistant patients (26%) had prolonged stable disease over 6 months. The combination reduced the EGFR mutation and T790M variant allele frequency in cell-free DNA (p < .05). Nonetheless, the threshold for futility was met, based on 6-month progression-free survival. For EGFR TKI-resistant patients, median progression-free survival was 3.7 months (95% confidence interval (CI), 2.3-5.0) and overall survival was 14.7 months (95% CI, 8.5-20.9).
CONCLUSIONS: The combination had a manageable toxicity profile and in vivo T790M modulation, but no objective clinical responses were observed.

PMID: 30880334 [PubMed - indexed for MEDLINE]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2020/02/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2020/02/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Evaluation of toxicities related to novel therapy in clinical trials for women with gynecologic cancer.

Cancer. 2020 Feb 25;:

Authors: Lee YC, Wang L, Kohn EC, Rubinstein L, Ivy SP, Harris PJ, Lheureux S

Abstract
BACKGROUND: Women with gynecologic cancer may be at increased risk for adverse events (AEs) due to peritoneal disease burden and prior treatment (surgery, chemotherapy, and pelvic radiotherapy). This study compared the toxicity profiles of patients with and without gynecologic cancer enrolled in phase 1 trials.
METHODS: This was a retrospective analysis of the National Cancer Institute phase 1 database for all trials enrolling 1 or more patients with gynecologic cancer over 2 decades (1995-2015). Clinical parameters collected included demographics, cancer history, trial information, AEs, and responses. AEs (according to the Common Terminology Criteria for Adverse Events) were documented for each patient during treatment, and they were counted once and analyzed on the basis of the highest grade and drug attribution. Multiple regression models were used to compare AEs at the baseline and during treatment.
RESULTS: A total of 4269 patients enrolled in 150 trials were divided into 3 groups: 1) women with gynecologic cancer (n = 685), 2) women with nongynecologic cancer (n = 1698), and 3) men with cancer (n = 1886). The median age was 58 years. The mean number of total AEs reported during treatment was highest for women with gynecologic cancer (17.1 vs 14.7 vs 13.5; P < .001), even though they were similar at the baseline (7.0 vs 7.4 vs 7.0; P = .09). The mean number of drug-related AEs was also highest for women with gynecologic cancer (8.3 vs 6.9 vs 6.2; P < .001). Grade 3 to 5 AEs were similar (2.3 vs 2.3 vs 2.1); however, grade 2 AEs were more frequent in women with gynecologic cancer (4.6 vs 3.9 vs 3.5). Treatment discontinuations due to AEs were similar (9% vs 9% vs 10%).
CONCLUSIONS: Women with gynecologic cancer experienced more frequent low-grade AEs during treatment, and this warrants attention to support their symptom burden. Study dose management should be considered for recurrent grade 2 AEs, particularly during continuous therapy.

PMID: 32097505 [PubMed - as supplied by publisher]

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation: subanalysis by age from a phase III, assessor-blinded study.

Therap Adv Gastroenterol. 2020;13:1756284820902878

Authors: Hookey L, Bertiger G, Johnson KL, Boules M, Ando M, Dahdal DN

Abstract
Background: The incidence and mortality of colorectal cancer (CRC) increase with age and, therefore, it is recommended that adults undergo regular CRC screening, ideally by colonoscopy, with some new guidelines recommending screening begin at 45 years. Effective bowel preparation is a critical step to a successful colonoscopy. Of concern is that older adults may have poorer quality of bowel preparation or reduced tolerability for the bowel preparation. Here, we performed a post hoc secondary analysis for the effect of age on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation.
Methods: A phase III, randomized, assessor-blinded, multicenter, non-inferiority study was conducted comparing split-dose, low-volume SPMC oral solution with split-dose, low-volume sodium picosulfate, magnesium oxide, and citric acid powder for oral solution. A post hoc secondary analysis was performed to assess efficacy, safety, and tolerability of SPMC oral solution by age group (<50 years, 50-64 years, ⩾65 years). The prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations.
Results: Within age groups, at least 83.9% of participants were responders by the AS, and at least 91.1% of participants were responders by the BBPS in the right colon. On both scales, responder rates were highest in the youngest age group and decreased with increasing age. Greater than 88% of participants in any age group found the preparation 'easy' or 'acceptable' to ingest, with rates of 'easy' being highest in the oldest age group. No new safety signals were seen in any age group. The most commonly reported drug-related, treatment-emergent AEs were, by ascending age group, nausea (7.0%, 3.2%, 0.8%), headache (4.2%, 2.8%, 1.6%) and vomiting (2.8%, 1.2%, 0.8%).
Conclusion: Ready-to-drink SPMC oral solution showed good efficacy of overall colon cleansing and tolerability in adults across different age groups, including those ⩾65 years.ClinicalTrials.gov identifier: NCT03017235.

PMID: 32095161 [PubMed]

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis.

Cancer Invest. 2020 Feb;38(2):130-138

Authors: Sher AF, Golshani GM, Wu S

Abstract
Background: Pembrolizumab as an immune checkpoint inhibitor (ICI) has emerged as an effective treatment for many cancers. It has unique immune-related adverse events (irAE) and little is known about its risk of fatal adverse events (FAEs). We conducted a meta-analysis of clinical trials to determine the incidence and risk of FAEs with pembrolizumab.Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases including PUBMED and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models.Results: A total of 11 clinical trials with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%). The incidence of FAE significantly varied among different tumor types (p = .02), ranging from 0.2% in melanoma to 3.1% in breast cancer, and with its combination with chemotherapy (0.7%, 95% CI: 0.4-1.2% versus 7.0%, 95% CI: 4.9-10%; p<.01). Chemotherapy plus pembrolizumab 7.0% (95%CI: 4.9-10) as compared to pembrolizumab alone 0.7%, (95% CI: 0.4-1.2; p < .001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR = 1.24 (95% CI: 0.8-1.89; p = .31). The most common FAEs were due to infectious complication (26.5%), cardiac toxicity (14.7%) and pneumonitis (13.2%).Conclusions: The risk of FAEs with pembrolizumab may be similar to chemotherapy in cancer patients and may vary with tumor types and its combination with chemotherapy.

PMID: 31985314 [PubMed - indexed for MEDLINE]

Rationalization of a traditional liver medicine using systems biology approach and its evaluation in preclinical trial.

Comput Biol Chem. 2020 Feb;84:107196

Authors: Adhikari A, Darbar S, Das M, Mondal S, Sankar Bhattacharya S, Pal D, Kumar Pal S

Abstract
'Bottom-up', i.e., molecule to medicine strategy for the discovery of new drugs takes enormous time and cost. In most of the cases, inherent toxicity and undesired side effects of the developed drug hinder its way beyond the early stages of development. In this regard, the systems pharmacology can play an excellent role by reducing the cost and time of drug development through rationalization and/or repurposing of traditional drugs with known side effects. In the present study, our aim was to develop an integrated systems biology method for the prediction of active ingredients of a traditional medicine and their potential targets inside the body. Further, we evaluated the predictive capacity of the developed method in a preclinical animal model. Here, we have prepared a formulation (SKP17LIV01) from an extract of eight medicinal plants traditionally used as liver medicine and identified the constituents using UHPLC-MS technique. Using systems biology approach, we have rationalized the components of the formulation for potential use in the treatment of heavy metal-induced hepatotoxicity. The active ingredients and potential therapeutic targets were also predicted. A detailed biochemical, histopathological and molecular study on the mice model of lead toxicity confirms the efficacy of the formulation as per prediction by the systems pharmacology approach. The study may open a new frontier for re-discovery of drugs that are already used in traditional medicine.

PMID: 31881525 [PubMed - indexed for MEDLINE]

Acute acetaminophen toxicity in adults.

Nurse Pract. 2019 Nov;44(11):42-47

Authors: Saccomano SJ

Abstract
When taken in the recommended dosage, acetaminophen is a safe and effective analgesic and antipyretic agent. Its wide availability and easy accessibility make accidental or intentional overdose, leading to hepatotoxicity, a common occurrence. To prevent morbidity and mortality, prompt recognition of acetaminophen toxicity is essential. This article covers the stages of acetaminophen toxicity, recommended treatments, and NP considerations, including patient education recommendations.

PMID: 31651762 [PubMed - indexed for MEDLINE]

Effect of Baduanjin Qigong Exercise on Cancer-Related Fatigue in Patients with Colorectal Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

Oncol Res Treat. 2019;42(9):431-439

Authors: Lu Y, Qu HQ, Chen FY, Li XT, Cai L, Chen S, Sun YY

Abstract
BACKGROUND: Cancer-related fatigue (CRF) is one of the most troubling symptoms of cancer patients during chemotherapy, and no gold standard for the treatment of CRF has been established.
OBJECTIVE: This study aimed to examine the effects of the Baduanjin qigong on patients with colorectal cancer and CRF, and to explore its intervention effects.
METHODS: This was an open-label, randomized controlled clinical trial. Ninety patients with chemotherapy-treated colorectal cancer and CRF were randomized to a Baduanjin exercise group or a routine care group. The primary outcome was the Brief Fatigue Inventory (BFI) score at 24 weeks. The secondary outcomes were the Karnofsky Performance Status (KPS) and Pittsburgh Sleep Quality Index (PSQI) scores at 24 weeks.
RESULTS: There were no significant differences between the two groups in CRF level at baseline and 12 weeks. At 24 weeks, the proportion of patients with moderate-to-severe CRF was significantly smaller in the exercise group than in the control group (23.2 vs. 59.1%, p < 0.01). The KPS and PSQI scores were similar in the two groups at baseline and 12 weeks, but they were significantly higher and lower, respectively, at 24 weeks in the exercise group compared with the control group (KPS score: 89.3 ± 8.3 vs. 75.2 ± 11.5, p < 0.01; PSQI score: 4.1 ± 1.1 vs. 6.9 ± 2.0, p < 0.01). Significant time-group interactions were observed for all three scores (all p < 0.01).
CONCLUSIONS: Baduanjin qigong exercise can relieve CRF in patients with colorectal cancer undergoing chemotherapy and can improve their physical activity level and their quality of sleep.

PMID: 31266043 [PubMed - indexed for MEDLINE]

Impact of protocol change on individual factors related to course of adverse reactions to chemotherapy for breast cancer.

Support Care Cancer. 2020 Jan;28(1):395-403

Authors: Paula DP, do Brasil Costa VI, Jorge RV, Nobre FF

Abstract
PURPOSE: Asthenia, myalgia, arthralgia, mucositis, abdominal pain, diarrhea, and neutropenia are adverse reactions commonly reported by women undergoing chemotherapy. Traditional approaches do not take into account the effect that chemotherapeutic changes and variable interactions can cause in adverse reactions. We aimed to identify the impact of the change of a chemotherapy protocol within the same treatment in profiles associated with adverse reactions.
METHODS: A total of 166 women admitted to the Brazilian National Institute of Cancer (INCA) were followed. Polymorphisms, clinical variables, and FAC-D protocols (3 cycles of cyclophosphamide, 5-fluorouracil, and doxorubicin followed by 3 cycles of docetaxel) composed the set of independent variables analyzed. Reaction levels were recorded at the end of each chemotherapy cycle via interviews. Marginal models were fitted.
RESULTS: The results of marginal models for non-hematological reactions revealed that the docetaxel phase was associated with increased reaction levels compared with the FAC phase. In addition, the set of factors associated with the reactions changed in each protocol. The post-menopausal status was related to high levels of asthenia in docetaxel protocol whereas CYP2B6 polymorphism (rs3745274) was related to high levels in FAC protocol. Regarding the docetaxel phase, high levels of abdominal pain and mucositis were related to CBR3 gene (rs8133052) polymorphism and diabetes respectively.
CONCLUSION: The results suggest the need for monitoring non-hematological reactions during the docetaxel phase of FAC-D treatment. The factors related to more severe reactions depend on the chemotherapy protocol used.

PMID: 31056713 [PubMed - indexed for MEDLINE]

Safety Profile of Sclerosing Agents: An Analysis From the World Health Organization Pharmacovigilance Database VigiBase.

Dermatol Surg. 2019 12;45(12):1517-1528

Authors: Roselli A, Khouri C, Roustit M, Blaise S, Cracowski JL

Abstract
BACKGROUND: Several sclerosing agents are used to treat chronic venous diseases. Although they do not seem to differ in terms of efficacy, their safety profiles might differ.
OBJECTIVE: To compare the safety profile of sclerosing agents through an analysis of the World Health Organization pharmacovigilance database.
METHODS: The authors performed a disproportionality analysis using the proportional reporting ratio (PRR) method to compare pharmacovigilance signals between each sclerosing agent among 6 adverse event syndromes of interest: hypersensitivity reactions, arterial thromboembolic disorders, venous thromboembolic disorders, cardiac arrhythmias, visual/neurological disturbances, and skin ulcerations. The cutoff for signal detection was defined by a logPRR lower boundary 95% confidence interval (CI) ≥0 and number of cases n ≥3.
RESULTS: Of 1,227 Individual Case Safety Reports (ICSRs) identified, after removal of ICSRs with unselected indications, the authors selected 472 reports for the analysis. The authors found that polidocanol is associated with more reporting of venous embolic/thrombotic events (logPRR = 1.38 [95% CI 1.27-1.49]), ethanolamine with the higher pharmacovigilance disproportionality signal of cardiac arrhythmias (logPRR = 0.80 [95% CI 0.51-1.09]), and STS with more reporting of allergic reactions (logPRR = 1.79 [95% CI 1.59-1.98]).
CONCLUSION: The safety profile of sclerosing agents significantly differs and should guide benefit-risk ratio assessment of such agents.

PMID: 30829775 [PubMed - indexed for MEDLINE]

A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate.

J Clin Rheumatol. 2019 Oct;25(7):284-287

Authors: Stamp LK, OʼDonnell JL, Frampton C, Drake J, Zhang M, Barclay M, Chapman PT

Abstract
BACKGROUND/OBJECTIVE: The aim of this study was to determine whether reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis (RA) improved disease control and/or increased MTX-related adverse effects.
METHODS: A randomized double-blind randomized controlled trial comparing 5 mg/wk and 0.8 mg/wk folic acid was undertaken. Rheumatoid arthritis patients on MTX for 3 months or more at a stable dose for 1 month or more were recruited. All participants had DAS28 of 3.2 or greater or required a change in therapy determined by the treating clinician. Disease activity, full blood count, liver function tests, red blood cell (RBC) folate, and RBC MTX polyglutamates were assessed at weeks 0, 4, 8, 16, and 24 along with reports of adverse events.
RESULTS: Forty participants were recruited. The mean (SD) change in RBC folate between week 0 and 24 was +87.9 (57.4) nmol/L in the high-dose group and -113.3 (65.7) nmol/L in the low-dose group (p < 0.05). There was no significant difference in the change in DAS28 between the high- and low-dose groups at 24 weeks (-0.13 [95% confidence interval, -0.69 to 0.43] vs -0.25 [-0.87 to 0.37], respectively [p = 0.78]). There was no significant difference in MTX-related adverse effects between the 2 groups.
CONCLUSIONS: A reduction in RBC folate secondary to reduction in folic acid dose was not associated with a change in RA disease activity or MTX-related adverse effects. The prevention of MTX-related adverse effects remains the primary reason for coprescribing folic acid with MTX.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR12610000739011).

PMID: 30001258 [PubMed - indexed for MEDLINE]

IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial.

Gastroenterology. 2020 Feb 21;:

Authors: Vaezi MF, Fass R, Vakil N, Reasner DS, Mittleman RS, Hall M, Shao JZ, Chen Y, Lane L, Gates AM, Currie MG

Abstract
BACKGROUND AIMS: Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the healthcare system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy.
METHODS: We performed a multicenter, double-blind, placebo-controlled trial from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary end point was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score.
RESULTS: Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 groups (dose-response P=.02). The treatment difference was 11.9% between the 1500-mg IW-3718 and placebo groups (P=.04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500-mg IW-3718 vs placebo groups was a reduction of 17.5% (95% CI, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events.
CONCLUSIONS: In a randomized trial of patients with refractory GERD, adding 1500-mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ClinicalTrials.gov no: NCT02637557.

PMID: 32092310 [PubMed - as supplied by publisher]

A model for an institutional response to the opioid crisis.

J Opioid Manag. 2019 Jan/Feb;16(1):73-83

Authors: Hanna MN, Chambers C, Punyala A, Iqbal A, Singh B, Oruc C, Prakash P, Prajapati Y, Wang Y, Amery Ai Z, Shechter R, Speed TJ, Koch CG, Williams K

Abstract
The use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. Physicians, policymakers, and researchers are focused on finding ways to decrease opioid use and overdose. This crisis calls for a coordinated response that includes the entire healthcare sector. In this work, the authors lay out a blueprint for such a response at the level of the academic medical center. The proposed model is a comprehensive opioid overdose prevention, response, and education program to evaluate, monitor, and address prescription opioid-related adverse events and addiction among all patients within a healthcare system. The approach includes three inter-related elements: (1) creation of an organizational structure that is subdivided into subcommittees to facilitate cross-functional collaboration and implementation. These subcommittees will focus on Research and Design, Implementation, Advisory, and Compliance with the recommendation. (2) Development of an effective communication plan throughout the institution to enable the organization to function seamlessly and efficiently as a single unit, (3) development of a data tracking and reporting system that intended to have a 360° view of all aspects of opioid prescription and downstream patient outcomes. The most effective response system will require an organizational structure that facilitates the ad hoc constitution of cross-functional teams with members drawn from all levels of the organizational hierarchy (executive leadership to frontline staff). Such a structure provides the teams with immediate solutions as developed by the frontline staff and authority to remove institutional barriers that may delay or limit the successful implementation. The model described was developed in our institution by a cross-functional team that included members from the Johns Hopkins School of Medicine and Johns Hopkins University Carey Business School, Department of Operations Management. The multidisciplinary nature of collaboration allowed us to develop a model for an immediate institution-wide response to the opioid crisis, and one that other healthcare organizations could adopt with local modification as a template for execution. The model also meant to serve as a template for an institutional rapid-response that can be seamlessly implemented during any future drug-related crisis or epidemic.

PMID: 32091620 [PubMed - as supplied by publisher]