Enhancing Pediatric Adverse Drug Reaction Documentation in the Electronic Medical Record.

J Clin Pharmacol. 2020 Aug 09;:

Authors: Tillman EM, Suppes SL, Feldman K, Goldman JL

Abstract
Adverse drug reactions (ADRs) often go unreported or are inaccurately documented in the electronic medical recorded (EMR), even when they are severe and life-threatening. Incomplete reporting can lead to future prescribing challenges and ADR reoccurrence. The aim of this study was to evaluate the documentation of ADRs within the EMR and determine specific factors associated with appropriate and timely ADR documentation. Retrospective data were collected from a pediatric hospital system ADR reports from October 2010 to November 2018. Data included implicated medication, type, and severity of reaction, treatment location, the presence or absence of ADR documentation in the EMR alert profile within 24 hours of the ADR hospital or clinic encounter discharge, ADR identification method, and the presence or absence of pharmacovigilance oversight at the facility where the ADR was treated. A linear regression model was applied to identify factors contributing to optimal ADR documentation. A total of 3065 ADRs requiring medical care were identified. Of these, 961 ADRs (31%) did not have appropriate documentation added to the EMR alert profile prior to discharge. ADRs were documented in the EMR 87% of the time with the presence of pharmacovigilance oversight and only 61% without prospective pharmacovigilance (P < .01). Severity of ADR was not a predictor of ADR documentation in the EMR, yet the implicated medication and location of treatment did impact reporting. An active pharmacovigilance service significantly improved pediatric ADR documentation. Further work is needed to assure timely, accurate ADR documentation.

PMID: 32776356 [PubMed - as supplied by publisher]

Drug-Induced Interstitial Pneumonia due to Application of FOLFOX as Adjuvant Chemotherapy after Rectal Cancer Surgery: A Case Report and Literature Review.

Case Rep Oncol. 2020 May-Aug;13(2):768-773

Authors: Yanagawa S, Karakuchi N, Mochizuki T, Kodama S, Takeshima Y, Sumimoto K

Abstract
The regimen of oxaliplatin with 5-fluorouracil plus l-leucovorin (FOLFOX) has become one of the most commonly used first-line chemotherapy for patients with advanced colorectal cancer and it provides an increase in disease-free survival as well as an overall survival benefit. Although FOLFOX chemotherapy has helped to improve the clinical outcomes in these patients, the regimen is associated with some therapeutic issues or uncontrolled side effects. Gastrointestinal, neurosensory, and hematological toxicities have frequently been observed in patients treated with FOLFOX, and consequently, some palliative treatment has been established to combat such complications. However, pulmonary toxicities including drug-induced interstitial pneumonia (DI-IP) is rarely observed in these patients and a curative treatment is yet to be established. DI-IP due to chemotherapy is most commonly observed in patients treated with mitomycin, paclitaxel, docetaxel, or gemcitabine. Steroid therapy is mostly used to treat DI-IP, although the efficacy of such treatments is not supported with adequate evidence. FOLFOX-induced interstitial pneumonia (FIIP) is rarely observed, and several case reports of FIIP treated with steroids have been published previously that showed the mortality is extremely high. Here, we present a 74-year-old woman who received modified FOLFOX6 as adjuvant chemotherapy after rectal cancer surgery. The patient experienced FIIP, which improved after application of steroid pulse (high-dose methylprednisolone at 1,000 mg/day for 3 days) and tapering (starting with prednisolone at 40 mg/day) therapy. Our data suggest that such a steroid therapy could represent an effective treatment option for FIIP.

PMID: 32774274 [PubMed - as supplied by publisher]

Commentary: Harm, Truth, and the Nocebo Effect.

Camb Q Healthc Ethics. 2020 04;29(2):236-245

Authors: Ho D

Abstract
Nocebo effects occur when an individual experiences undesirable physiological reactions caused by doxastic states that are not a treatment's core or characteristic features.1 As Scott Gelfand2 points out, there are numerous studies that have shown that the disclosure of a treatment's side effects to a patient increases the risk of the side effects. From an ethical point of view, nocebo effects caused by the disclosures of side effects present a challenging problem. On the one hand, clinicians' duty to inform patients of the consequences (including possible side effects) of their treatments is critical in ensuring that patients' autonomy is respected. Patients cannot act autonomously if relevant information is withheld from them (without their consent, perhaps). On the other hand, clinicians also ought to minimize harm to patients.

PMID: 32159482 [PubMed - indexed for MEDLINE]

Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients.

J Natl Cancer Inst. 2020 02 01;112(2):123-127

Authors: Joly F, Castel H, Tron L, Lange M, Vardy J

Abstract
A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models.

PMID: 31504664 [PubMed - indexed for MEDLINE]

Epigallocatechin gallate and theaflavin gallate interaction in SARS-CoV-2 spike-protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study.

Drug Dev Res. 2020 Aug 07;:

Authors: Maiti S, Banerjee A

Abstract
SARS-CoV-2 or COVID-19 pandemic global outbreak created the most unstable situation of human health-economy. In the past two decades different parts of the word experienced smaller or bigger outbreak related to human coronaviruses. The spike glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting enzyme (ACE2) and transit over a stabilized open state for the viral internalization to the host cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less sensitive to the protein/nucleic acid based drugs. In this emergent situation, drug-induced destabilization of spike binding to RBD could be a good strategy. In the current study we demonstrated by bioinformatics (CASTp: computed atlas of surface topography of protein, PyMol: molecular visualization) and molecular docking (PatchDock and Autodock) experiments that tea flavonoids catechin products mainly epigallocatechin gallate or other like theaflavin gallate demonstrated higher atomic contact energy (ACE) value, binding energy, Ki value, ligand efficiency, surface area and more amino acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike protein. Moreover, out of three distinct binding sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV-RBD of ACE2 contact), epigallocatechin gallate and theaflavin gallate bind all three sites. As sites I and II are in closer contact with open state location and viral-host contact area, these drugs might have significant effects. Taking into account the toxicity/side effects by chloroquine/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation and so on. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.

PMID: 32770567 [PubMed - as supplied by publisher]

SUPPORT-1 (Subjects Undergoing PCI and Perioperative Reperfusion Treatment): A Prospective, Randomized Trial of CMX-2043 in Patients Undergoing Elective Percutaneous Coronary Intervention.

J Cardiovasc Pharmacol. 2020 Aug;76(2):189-196

Authors: Tcheng JE, Gibson M, Krucoff MW, Patel MR, Ajit M, Hiremath J, Ponde C, Ramsaran E, Clark G, Lader AS, Beeuwkes R

Abstract
OBJECTIVE: The natural molecule α-lipoic acid has been shown to be partially cytoprotective through antioxidant and antiapoptotic mechanisms. To obtain an initial assessment of the safety and potential efficacy of a synthetic derivative, CMX-2043, in preventing ischemic complications of percutaneous coronary intervention (PCI) we conducted the Subjects Undergoing PCI and Perioperative Reperfusion Treatment (SUPPORT-1) trial, the first patient experience with this agent.
METHODS AND RESULTS: SUPPORT-1 was a phase 2a, 6-center, international, placebo-controlled, randomized, double-blind trial. A total of 142 patients were randomized to receive a single intravenous bolus dose of drug or placebo administered 15-60 minutes before PCI. Cardiac biomarker assessments included serial measurements of creatine kinase myocardial band (CK-MB) at 6, 12, 18, and 24 hours after PCI and a single measurement of troponin T (TnT) at 24 hours. Peak concentrations of CK-MB and TnT were significantly reduced in the 2.4 mg/kg group compared with placebo (P = 0.05 and 0.03, respectively). No subject administered 2.4 mg/kg of CMX-2043 had an increase of CK-MB to ≥3X upper limit of normal versus 16% for placebo (P = 0.02); 16% of the 2.4-mg/kg dose group developed an elevation of TnT to ≥3X upper limit of normal versus 39% in the placebo group (P = 0.05). No drug-related serious adverse events were observed in any group.
CONCLUSION: These data suggest that CMX-2043 may reduce PCI periprocedural myonecrosis and support further clinical evaluation of this novel agent for its potential cytoprotective effects.

PMID: 32769849 [PubMed - as supplied by publisher]

Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

Neuropsychopharmacol Rep. 2020 Aug 07;:

Authors: Kishi T, Nosaka T, Sakuma K, Okuya M, Iwata N

Abstract
INTRODUCTION: Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random-effect model network meta-analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.
METHODS: The study included the double-blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS-T, primary), positive (PANSS-P), negative (PANSS-N), and general (PANSS-G) subscale scores; and Clinical Global Impression-Severity Scale (CGI-S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.
RESULTS: We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS-T [standardized mean difference (95% credible interval): LUR40 = -0.298 (-0.420, -0.176), LUR80 = -0.170 (-0.320, -0.019)], PANSS-P, and CGI-S scores, LUR40 but not LUR80 outperformed placebo in PANSS-N and PANSS-G scores and response rate. LUR40 outperformed LUR80 regarding PANSS-G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug-Induced Extrapyramidal Symptoms Scale score.
CONCLUSIONS: Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.

PMID: 32767739 [PubMed - as supplied by publisher]

Drugs inducing hearing loss, tinnitus, dizziness and vertigo: an updated guide.

Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):7946-7952

Authors: Altissimi G, Colizza A, Cianfrone G, de Vincentiis M, Greco A, Taurone S, Musacchio A, Ciofalo A, Turchetta R, Angeletti D, Ralli M

Abstract
OBJECTIVE: The awareness of audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo, has widely increased in the recent years. The present guide represents an update of the previous documents published by the authors in 2005 and 2011 on drug-induced ototoxicity and vestibulotoxicity.
MATERIALS AND METHODS: The authors performed a comprehensive analysis of audio-vestibular side effects of commercially available drugs based on the British National Formulary, a pharmaceutical reference book that contains a wide range of useful information and advice on prescription and pharmacology.
RESULTS: Commercially available drugs and their active principles have been classified based on their audio-vestibular side effects, as reported by the pharmaceutical companies and/or health agencies. Drugs have been categorized based on the field of application, the therapeutic indication and the pharmacological properties.
CONCLUSIONS: General practitioners, otolaryngology, neurology and audiology specialists should be aware of possible audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo. The present guide represents a practical tool to rapidly identify potential audio-vestibular side effects of drugs as reported by the pharmaceutical companies and/or health agencies.

PMID: 32767320 [PubMed - as supplied by publisher]

Mechanisms of Beta-Blocker Induced Psoriasis, and Psoriasis De Novo at the Cellular Level.

Cureus. 2020 Jul 02;12(7):e8964

Authors: Awad VM, Sakhamuru S, Kambampati S, Wasim S, Malik BH

Abstract
Beta-blockers are a commonly prescribed medication, but the increase in use goes hand in hand with increasing side effects; one of particular interest lately has been its dermatological reactions. Although rare, beta-blockers can exacerbate pre-existing psoriasis and also cause de novo psoriasis in patients naïve to the disease. The mechanism by which this occurs is still unclear, although numerous articles have been published throughout the years as to how this unusual effect takes place. The most common mechanism suggests that beta-blockers cause intracellular changes in calcium, affecting both keratinocyte proliferation and granulocyte function via decreased cyclic adenosine monophosphate (cAMP) levels. Several inflammatory mediators are known to play a role, as well as reduced expression and desensitization of the beta-adrenergic receptor itself. We discuss these posed pathways in-depth and how each contributes to the worsening or formation of new psoriasis. With this knowledge, future physicians may be more mindful of this side effect should it occur, and why they occur, to better manage our patients on this widely used medication.

PMID: 32766006 [PubMed - as supplied by publisher]

Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study.

Mov Disord. 2020 Aug 06;:

Authors: Choi JH, Lee JY, Cho JW, Koh SB, Yang YS, Yoo D, Shin CM, Kim HT

Abstract
OBJECTIVES: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications.
METHODS: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point.
RESULTS: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial.
CONCLUSIONS: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

PMID: 32761955 [PubMed - as supplied by publisher]

Real-World Study of Adding Bevacizumab to Chemotherapy for Ovarian, Tubal, and Peritoneal Cancer as Front-Line or Relapse Therapy (ROBOT): 8-Year Experience.

Front Oncol. 2020;10:1095

Authors: Wu PY, Cheng YM, Shen MR, Chen YC, Huang YF, Chou CY

Abstract
This study aimed to determine the real-world, long-term prognostic impacts, and adverse effects (AEs) of bevacizumab (BEV) in Asian patients with ovarian/tubal/peritoneal cancers. We retrospectively reviewed the medical records of consecutive patients with ovarian/tubal/peritoneal cancer on front-line chemotherapy with or without BEV (Cohort 1) and those who relapsed following chemotherapy and/or BEV (Cohort 2) between 2011 and 2018 in a tertiary medical centre. Patient characteristics, BEV dosages, clinical outcomes, and AEs were analyzed. Hazard ratios for disease progression and death were analyzed using a cox proportional regression model. Benefits of BEV used throughout triweekly, in terms of improved progression-free survival (PFS) and overall survival (OS), were observed at a dosage of 7.5-15 mg/kg among advanced-stage Cohort 1 patients. A progression-free interval of <6 months was the strongest predictor of disease progression and death in advanced-stage patients. BEV throughout and optimal cytoreduction were independent predictors of reduced disease progression. No prognostic advantage was observed between serous and clear cell histologies when BEV was added. Moreover, BEV resulted in improved OS in Cohort 2 patients, especially in the platinum-sensitive subgroup. Most patients had a front-line BEV dosage <10 mg/kg per cycle with <10 treatment cycles. Low rates and grades of BEV-related AEs were observed in both cohorts. BEV used throughout effectively extended PFS and OS in advanced-stage patients with ovarian/tubal/peritoneal cancer. Patients with platinum-sensitive carcinoma, treated with BEV, had a significant improvement in OS and extended PFS. Therefore, BEV can safely be added to chemotherapy for ovarian/tubal/peritoneal cancers.

PMID: 32760668 [PubMed]

In-hospital adverse drug events: analysis of trend in Portuguese public hospitals.

Cad Saude Publica. 2020;36(3):e00056519

Authors: Vitorino M, Aguiar P, Sousa P

Abstract
The objectives of this study were to analyze in-hospital adverse drug events (ADEs) in Portuguese public hospitals, and their association with mortality and the duration of hospitalization. We analyzed an administrative database containing the registration of all hospitalizations occurring in Portuguese public hospitals in 2013-2015. ADEs were identified using the codes E850-858.9 and E930-949.9 from ICD-9-CM. We identified all episodes with registration of in-hospital ADE and we compared them with a random sample of an equal number of episodes with no events recorded. A total of 3,041,443 cases were analyzed, 60,521 presented at least one ADE from which 17,213 occurred in hospital context. The most frequent drug classes associated with ADE were the antineoplastics/immunosuppressant drugs, antibiotics and steroids. Patient characteristics associated with a greater occurrence of in-hospital ADEs (all with p < 0.001) were medical admissions (OR = 1.29), the diagnosis - myeloid leukaemia (OR = 18.63), nephrotic syndrome (OR = 15.75), pneumonia (OR = 1.33) -, a higher number of secondary diagnoses (OR = 1.27), and increased duration of hospital stay (OR = 1.06). Hospitalizations with records of in-hospital ADEs presented a significantly higher mortality (9.6% vs. 4.5) and duration of hospitalization (22.6 vs. 6.4 days). ADEs were shown to be directly associated with an increase in the duration of hospital stay of 8.18 days. This study adds some interesting insights related to the most frequent drug classes and patient characteristics that can influence the frequency of ADEs in Portuguese public hospitals and also the burden of injury resulting from them.

PMID: 32187293 [PubMed - indexed for MEDLINE]

Perception of side effects associated with anticancer treatment in women with breast or ovarian cancer (KEM-GO-1): a prospective trial.

Support Care Cancer. 2020 Aug;28(8):3605-3615

Authors: Ataseven B, Frindte J, Harter P, Gebers G, Vogt C, Traut A, Breit E, Bluni V, Reinisch M, Heitz F, Kostara A, Kuemmel S, Prader S, Bommert M, Schneider S, du Bois A

Abstract
PURPOSE: Due to advances in anticancer treatment and supportive care, patients increasingly complained about nonphysical side effects of chemotherapy and targeted therapy in recent years. Therefore, continuous assessment of side effects and patients' perceptions is important. The aim of this study was to evaluate the identification and severity of side effects perceived by ovarian cancer (OC) and breast cancer (BC) patients undergoing contemporary anticancer therapy.
METHODS: Between 2015 and 2017, consecutive chemo-naïve OC and BC patients were enrolled in this prospective cohort study. Interviews were performed 12 ± 3 weeks after start of anticancer therapy, and patients were asked to select and rank, according to severity, 72 physical or nonphysical symptoms potentially related to their treatment. Data were analyzed with descriptive statistics.
RESULTS: Forty-five OC patients and 98 BC patients completed the interview. Sleeping difficulties were ranked as the most troublesome symptom, followed by concerns about family or partner, and loss of hair. Alopecia was the most predominant side effect for BC patients, whereas OC patients were highly afflicted by numbness in limbs. Chemotherapy alone or in combination with targeted therapy caused pronounced sleep disturbances. Prolonged taxane treatment led to shortness of breath and numbness in limbs. Vomiting was ranked by one and nausea by eight women among the five most bothersome symptoms.
CONCLUSIONS: Sleep disturbances have lately emerged as the most severe problem in women with OC or BC receiving anticancer therapy. Concerns about family and partner were ranked second in the current study and first in previous investigations.

PMID: 31828488 [PubMed - indexed for MEDLINE]

Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03).

Support Care Cancer. 2020 Aug;28(8):3649-3657

Authors: Hamaguchi R, Tsuchiya T, Miyata G, Sato T, Takahashi K, Miura K, Oshio H, Ohori H, Ariyoshi K, Oyamada S, Iwase S

Abstract
PURPOSE: Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery.
METHODS: A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale.
RESULTS: There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively).
CONCLUSION: This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS.
TRIAL REGISTRATION: UMIN000024784.

PMID: 31811480 [PubMed - indexed for MEDLINE]

Root Cause Analysis Gone Wrong.

AORN J. 2019 10;110(4):468-470

Authors:

PMID: 31560420 [PubMed - indexed for MEDLINE]

The class imbalance problem detecting adverse drug reactions in electronic health records.

Health Informatics J. 2019 12;25(4):1768-1778

Authors: Santiso S, Casillas A, Pérez A

Abstract
This work focuses on adverse drug reaction extraction tackling the class imbalance problem. Adverse drug reactions are infrequent events in electronic health records, nevertheless, it is compulsory to get them documented. Text mining techniques can help to retrieve this kind of valuable information from text. The class imbalance was tackled using different sampling methods, cost-sensitive learning, ensemble learning and one-class classification and the Random Forest classifier was used. The adverse drug reaction extraction model was inferred from a dataset that comprises real electronic health records with an imbalance ratio of 1:222, this means that for each drug-disease pair that is an adverse drug reaction, there are approximately 222 that are not adverse drug reactions. The application of a sampling technique before using cost-sensitive learning offered the best result. On the test set, the f-measure was 0.121 for the minority class and 0.996 for the majority class.

PMID: 30230408 [PubMed - indexed for MEDLINE]

Long-term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open-label extension study.

Asia Pac J Clin Oncol. 2020 Aug 05;:

Authors: Ito T, Fujimori N, Honma Y, Kudo A, Hijioka S, Katsushima S, Kimura Y, Fukutomi A, Hisamatsu S, Nakajima A, Shimatsu A

Abstract
AIM: The aim of this study was to describe the long-term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors.
METHODS: The final analyses of a 48-week open-label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4-weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed.
RESULTS: The median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52-181) and 52.7 (12-181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug-related. Partial response was observed in 2 patients (7.1%; at 60 and 108 weeks), stable disease in 20 (71.4%) and progressive disease in 6 (21.4%). The mean of the greatest change from baseline in the sum of diameters of target lesions was -5.5%. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3% (35.7%)/month and 6.4% (9.6%)/month, respectively.
CONCLUSION: Lanreotide treatment had an acceptable safety profile and was effective over long-term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.

PMID: 32757459 [PubMed - as supplied by publisher]

Granulocyte colony-stimulating factor-associated aortitis in the Japanese Adverse Drug Event Report database.

Cytokine. 2019 07;119:47-51

Authors: Oshima Y, Takahashi S, Tani K, Tojo A

Abstract
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is the standard-of-care therapy for chemotherapy-associated neutropenia in patients with malignancies. Recent case reports have implied that G-CSF treatment may be associated with the development of aortitis, but the precise nature of the relationship is unclear. We investigated the association between G-CSF and risk for aortitis in patients with various malignancies.
METHODS: We performed an observational study of 102,014 subjects with malignant neoplasms documented in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and February 2018. The adjusted odds ratio (OR) and 95% confidence interval (CI) for aortitis in patients treated and not treated with G-CSF were estimated using multivariate logistic regression with R software.
RESULTS: Among the 102,014 subjects, 25 developed aortitis. Of the 3409 and 98,630 subjects treated and not treated with G-CSF, 16 (0.47% [95% CI; 0.27, 0.76]) and 9 (0.01% [0.00, 0.02]) developed aortitis, respectively. Multivariate logistic regression indicated an association between G-CSF and aortitis (adjusted OR 45.87 [19.16, 109.8], p < 0.001). The values for filgrastim, pegfilgrastim, and lenograstim were 0.25% (0.07, 0.63), 1.58% (0.79, 2.81), and 0.24% (0.05, 0.69), respectively.
CONCLUSION: G-CSF treatment was associated with a signal of increased risk for aortitis among patients with malignant neoplasms. Three different G-CSF agents were associated with such risk, implying that it is a class effect. However, we do not recommend changing G-CSF prescriptions, because our results may have been influenced by the limitations of the JADER database and because the benefit of G-CSF treatment outweighs the potential risk.

PMID: 30875590 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Apatinib in Treatment of Unresectable Intrahepatic Cholangiocarcinoma: An Observational Study.

Cancer Manag Res. 2020;12:5345-5351

Authors: Hu Y, Lin H, Hao M, Zhou Y, Chen Q, Chen Z

Abstract
Purpose: Unresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC.
Patients and Methods: A total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The drug-related adverse effects were also monitored.
Results: Based on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded.
Conclusion: Apatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

PMID: 32753952 [PubMed]

The safety profile of favipiravir should not be the first argument to suspend its evaluation in viral hemorrhagic fevers.

PLoS Negl Trop Dis. 2020 06;14(6):e0008259

Authors: Malvy D, Taburet AM, de Lamballerie X, Mentre F, Extramiana F

PMID: 32584817 [PubMed - indexed for MEDLINE]