Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

Cancer Chemother Pharmacol. 2019 Aug 19;:

Authors: Esteva FJ, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu AE, Li RK, Rusyn AV, Tiangco B, Lee SJ, Lee SY, Yu SY, Stebbing J

Abstract
PURPOSE: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures.
METHODS: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year.
RESULTS: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs.
CONCLUSION: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.

PMID: 31428820 [PubMed - as supplied by publisher]

A First-in-Human Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics of a Novel Antifungal Drug VL-2397 in Healthy Adults.

Antimicrob Agents Chemother. 2019 Aug 19;:

Authors: Mammen MP, Armas D, Hughes FH, Hopkins AM, Fisher CL, Resch PA, Rusalov D, Sullivan SM, Smith LR

Abstract
VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study was conducted in healthy adults to determine the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (IV) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing cohort prior to recommending the initiation of each subsequent cohort. No serious adverse events (SAEs) occurred; the majority of treatment-emergent adverse events (TEAEs) were mild and self-limited. The most common drug-related TEAEs were infusion site reactions. No clinically-concerning trends were noted in vital signs, electrocardiograms, physical examinations or safety laboratory results. Following single infusions of VL-2397 the overall and maximum exposures rose less than proportionally with increasing doses from 3 mg to 1200 mg as indicated by AUC24 and Cmax No signs of VL-2397 accumulation were observed following IV infusions of 300, 600 and 1200 mg Q24H for 7 days. Renal elimination plays a major role in total body clearance with up to 47% of unmetabolized drug in urine 24 hours after administration at single doses > 30 mg. Overall, VL-2397 dosing in the study appeared to be safe and well tolerated in the healthy subjects. The safety profile, consistent PK and lack of drug accumulation support further development of VL-2397 in patients with invasive aspergillosis.

PMID: 31427299 [PubMed - as supplied by publisher]

[Thinking on safety of "toxic" traditional Chinese medicine for external use].

Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(8):1710-1714

Authors: Xiang LL, Miao MS, Cao LH, Li Y

Abstract
In recent years,the safety of " toxic" traditional Chinese medicine has received great attention. Similarly,the safety of " toxic" Chinese medicines for external use should not be ignored. In this paper,the adverse reactions of toxic Chinese medicine for external use were systematically studied; the causes for adverse reactions were analyzed; and the key problems on the external use of toxic Chinese medicine in modern clinical practice were put forward. For example,usage dosage(time,area),specific efficacy of external use,early warning index of toxicity,toxic dose,adverse effects,toxic symptoms and corresponding treatment measures all had no reference basis,lacking a systematic toxicity evaluation medication criteria for clinical external use of toxic Chinese medicine. Attention shall be paid to the toxicity of toxic Chinese medicine for external use,and the theory of toxicity evaluation should be established for the external use of " toxic" traditional Chinese medicine under specific conditions. The early warning mechanism for toxic and adverse effects were clarified,and relevant early warning sensitive indicators applicable to clinical use were established in this study to control its risk factors. The study on the mechanism of pharmacodynamics and toxicology of " toxic" traditional Chinese medicine for external use was strengthened to clarify the usage and specific effects of external use. On the basis of this,the study of synergism and reduction of toxicity was carried out to maximize the efficacy of external use of traditional Chinese medicine under specific conditions. A toxicity standard of " toxic" Chinese medicines for external use was put forward,which was of great significance to guide clinical safety,rationality,effectiveness as well as the research and development of new dosage forms for external use of traditional Chinese medicine.

PMID: 31090339 [PubMed - indexed for MEDLINE]

Strategies to reduce corticosteroid-related adverse events in asthma.

Curr Opin Allergy Clin Immunol. 2019 02;19(1):61-67

Authors: Heffler E, Bagnasco D, Canonica GW

Abstract
PURPOSE OF REVIEW: Severe asthmatics, despite the chronic use of high inhaled corticosteroids (ICS) doses and frequent intake of systemic corticosteroids, remains clinically and/or functionally uncontrolled. These patients are also often affected by rhinitis or chronic rhinosinusitis requiring frequent use of intranasal corticosteroids. Therefore, severe asthmatics are exposed to an overload of corticosteroids that is frequently associated with relevant and costly adverse events. This clinical problem and the strategies to overcome it are here summarized.
RECENT FINDINGS: Different therapeutic options may help in reducing the corticosteroid load in asthmatics, ranging from allergy immunotherapy (nonsuitable for severe uncontrolled patients), immunosuppressant agents like methotrexate or cyclosporine, novel biologic drugs (mainly anti-IgE, anti-IL5 and anti-IL4-receptor-alpha), and aspirin desensitization (for patients with anti-inflammatory drugs exacerbated respiratory disease).
SUMMARY: The evidence of even serious corticosteroid-related adverse events associated with consistent health-care costs, should prompt the entire scientific community and health regulatory authorities to promote actions to increase the use of well tolerated and effective strategies to reduce the corticosteroid need in asthmatics; the most promising option seems to be the add-on use of biologic agents.

PMID: 30407207 [PubMed - indexed for MEDLINE]

Fall-risk increasing drugs and prevalence of polypharmacy in older patients discharged from an Orthogeriatric Unit after a hip fracture.

Aging Clin Exp Res. 2019 Jul;31(7):969-975

Authors: Correa-Pérez A, Delgado-Silveira E, Martín-Aragón S, Rojo-Sanchís AM, Cruz-Jentoft AJ

Abstract
BACKGROUND: Polypharmacy and fall-risk increasing drugs (FRIDS) have been associated with injurious falls. We aimed to estimate the prevalence of polypharmacy and FRIDS in older patients discharged from an Orthogeriatric Unit after a hip fracture surgery.
METHODS: This study describes the baseline findings of a 2-year retrospective cohort study. We included patients older than 80 years discharged from an Orthogeriatric Unit who were able to walk before surgery. Patient's baseline variables, total number of drugs, and FRIDS at hospital discharge were collected.
RESULTS: We included 228 patients. The mean number of drugs and FRIDS prescribed at discharge was 11.6 ± 3.0 and 2.9 ± 1.6, respectively. Polypharmacy was prevalent in all patients except in three: 23.3% (5-9 drugs) and 75.9% (≥ 10 drugs). Only 11 patients had no FRIDS and 35.5% were on > 3 FRIDS. The most prevalent FRIDS were: agents acting on the renin-angiotensin system (43.9%) and anxiolytics (39.9%). The number of FRIDS was higher in patients with extreme polypharmacy (3.4 ± 1.5) than in those on 5-9 drugs (1.5 ± 1.0, p < 0.05). Independent people in performing instrumental activities had lower risk of extreme polypharmacy (≥ 10 drugs) or > 3 FRIDS: OR 0.39 (95% CI 0.18-0.83) and OR 0.41 (95% CI 0.20-0.84), respectively. People living in a nursing home had higher risk of > 3 FRIDS: OR 4.03 (95% CI 1.12-14.53).
CONCLUSIONS: Polypharmacy and fall-risk increasing drugs are prevalent in patients discharged from orthogeriatric care after surgery for a hip fracture. Interventions on drug use at hospital discharge could have a potential impact on falls in this high-risk population.

PMID: 30276631 [PubMed - indexed for MEDLINE]

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

Clin Trials. 2018 08;15(4):386-397

Authors: Muenz DG, Braun TM, Taylor JM

Abstract
Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

PMID: 29779418 [PubMed - indexed for MEDLINE]

Safer Prescribing and Care for the Elderly (SPACE): feasibility of audit and feedback plus practice mail-out to patients with high-risk prescribing.

J Prim Health Care. 2017 Jun;9(2):145-152

Authors: Wallis K, Tuckey R

Abstract
INTRODUCTION High-risk prescribing in general practice is common and places patients at increased risk of adverse events. AIM The Safer Prescribing and Care for the Elderly (SPACE) intervention, comprising audit and feedback plus practice mail-out to patients with high-risk prescribing, was designed to promote medicines review and support safer prescribing. This study aims to test the SPACE intervention feasibility in general practice. METHODS This feasibility study involved an Auckland Primary Health Organisation (PHO), a clinical advisory pharmacist, two purposively sampled urban general practices, and seven GPs. The acceptability and utility of the SPACE intervention were assessed by semi- structured interviews involving study participants, including 11 patients with high-risk prescribing. Interviews were audio-recorded, transcribed verbatim and analysed using a general inductive approach to identify emergent themes. RESULTS The pharmacist said the SPACE intervention facilitated communication with GPs, and provided a platform for their clinical advisory role at no extra cost to the PHO. GPs said the feedback session with the pharmacist was educational but added to time pressures. GPs selected 29 patients for the mail-out. Some GPs were concerned the mail-out might upset patients, but patients said they felt cared for. Some patients intended to take the letter to their next appointment and discuss their medicines with their GP; others said there were already many things to discuss and not enough time. Some patients were confused by the medicines information brochure. DISCUSSION The SPACE intervention is feasible in general practice. The medicines information brochure needs simplification. Further research is needed to test the effect of SPACE on high-risk prescribing.

PMID: 29530226 [PubMed - indexed for MEDLINE]

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review.

Rev Bras Reumatol Engl Ed. 2017 Nov - Dec;57(6):596-604

Authors: Teles KA, Medeiros-Souza P, Lima FAC, Araújo BG, Lima RAC

Abstract
Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

PMID: 29173694 [PubMed - indexed for MEDLINE]

Discovery and Development of anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication.

Curr Top Med Chem. 2019 Jul 12;:

Authors: Maeda K, Das D, Kobayakawa T, Tamamura H, Takeuchi H

Abstract
The history of human immunodeficiency virus (HIV)/AIDS therapy, which spans over 30 years, is one of the most dramatic stories of science and medicine leading to treatment of a disease. Since the advent of the first AIDS drug, AZT or zidovudine, a number of agents acting on different drug targets, such as HIV enzymes (e.g. reverse transcriptase, protease, and integrase) and host cell factors critical for HIV infection (e.g. CD4 and CCR5), have been added to our armamentarium to combat HIV/AIDS. In this review article, we first discuss the history of the development of anti-HIV drugs, during which several problems such as drug-induced side effects and the emergence of drug-resistant viruses became apparent and had to be overcome. Nowadays, the success of combination antiretroviral therapy (cART), combined with recently-developed powerful but nonetheless less toxic drugs has transformed HIV/AIDS from an inevitably fatal disease into a manageable chronic infection. However, even with such potent cART, it is impossible to eradicate HIV because none of the currently available HIV drugs are effective in eliminating occult "dormant" HIV cell reservoirs. A number of novel unique treatment approaches that should drastically improve the quality of life (QOL) of patients or might actually be able to eliminate HIV altogether has also been discussed later in the review.

PMID: 31424371 [PubMed - as supplied by publisher]

Diabetic ketoacidosis with sodium-glucose cotransporter type 2 inhibitors: a case series.

Med J Aust. 2019 Aug 16;:

Authors: McLachlan G, Keith C, Frauman A

PMID: 31420875 [PubMed - as supplied by publisher]

Nephrotoxicity of iodinated contrast media: From pathophysiology to prevention strategies.

Eur J Radiol. 2019 Jul;116:231-241

Authors: Faucon AL, Bobrie G, Clément O

Abstract
Iodinated contrast media (ICM) induced acute kidney injury (AKI) accounts for 11% of cases of AKI and is its third most common cause in hospitalized patients. However, the pathophysiological mechanisms are not yet completely understood. The nephrotoxicity of ICM is partly the consequence of a direct cytotoxic effect on renal tubular epithelial and endothelial cells. It is also the consequence of impaired intrarenal hemodynamics, these two mechanisms being closely linked. The rheological properties of ICM, the volume infused, and the route of administration increase the intrinsic toxicity generated by the contrast media used. Furthermore, various clinical situations increase the risk of developing AKI. There is no specific treatment. Hydration is the cornerstone of prevention. Preventive measures have reduced the incidence of AKI over the last ten years. After an overview of the pathophysiology of the renal toxicity of ICM, we review risk factors and scores, diagnosis, and means of prevention in the light of the 2018 European Society of Urogenital Radiology and the 2018 American College of Radiology guidelines and recent studies on the subject. In addition, a side-by-side comparison of the updated and less conservative guidelines from the Radiology community and the more cautionary attitude from the Nephrology community are also presented.

PMID: 31054788 [PubMed - indexed for MEDLINE]

[Bronchospasm and flushing after vaccination with 23 serotype pneumococcal polysaccharide in chronic patients].

Rev Esp Quimioter. 2019 Apr;32(2):178-182

Authors: Fernández-Prada M, Martínez-Torrón A, Cuervo-Lage MJ, Ruiz-Salazar J, Martínez-Ortega C, Fernández-Noval F, Huerta-González I

Abstract
OBJECTIVE: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23®). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance.
METHODS: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted.
RESULTS: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found.
CONCLUSIONS: The reactions described do not appear in the PNEUMOVAX23® data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet.

PMID: 30834736 [PubMed - indexed for MEDLINE]

Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly: A systematic review of tools addressing inappropriate prescribing.

J Clin Pharm Ther. 2019 Jun;44(3):349-360

Authors: Aguiar JP, Brito AM, Martins AP, Leufkens HGM, Alves da Costa F

Abstract
WHAT IS KNOWN AND OBJECTIVE: In the last decades, many lists have been developed to screen for inappropriate prescribing. However, information on which potentially inappropriate medications (PIMs) could increase the cardiovascular risk in the elderly is not objectively presented. This review aimed to identify and quantify those PIMs by extracting information from published PIM-lists.
METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), a systematic review of PIM-lists was conducted. The search strategy was run in PubMed, MEDLINE and Google Scholar (1991-09/2017). All PIMs described in those lists were extracted and stratified by their potential cardiovascular risk (including major adverse cardiovascular events-MACE). The number of times each PIM was reported on those lists was also assessed.
RESULTS AND DISCUSSION: We identified 724 papers, and 24 were retained. From those, a total of 17 PIMs to be avoided by the elderly and 21 drug-disease interactions were retrieved. The reporting of PIMs with risk of cardiovascular adverse events was 15.3%, whereas the reporting of those with MACE risk was 7.2%. PIMs most frequently described were tricyclic antidepressants (TCAs; 12/24), centrally acting antiadrenergic agents (11/24), NSAIDs (7/24), antiarrhythmics (Class I and III; 6/24), peripherally acting antiadrenergic agents (6/24) and antithrombotic agents (5/24). Most frequently described PIMs with MACE risk were NSAIDs (7/24), antiarrhythmics (Class I and III) (7/24), selective calcium channel blockers with vascular effects (6/24) and antipsychotics (4/24).
WHAT IS NEW AND CONCLUSION: Data suggest that PIM-lists focus mainly on common adverse events and often poorly describe the potential consequence for MACE occurrence. This systematic review could help healthcare professionals in the identification and deprescribing of these medicines in older patients with high cardiovascular risk during medication review.

PMID: 30746726 [PubMed - indexed for MEDLINE]

Rational drug use analysis of antibiotics in surgical operation with nursing intervention.

Pak J Pharm Sci. 2018 Sep;31(5(Special)):2263-2269

Authors: Ailing W, Huifang L, Qin H

Abstract
Rational use of antibiotics is an important part of clinical pharmacy in hospitals. In this paper, we compared and analyzed the use of antibiotics in 2016 and 2017, and put forward corresponding interventions. The results showed that the irrational use of drugs after the intervention was significantly reduced (p<0.05). The antibacterials used before the intervention was mainly cephalosporins (45.4%) and quinolones (26.2%). The antibiotics used after intervention was mainly cephalosporins (77.9%) and clindamycin (11.6%). There is no significant difference in the incidence of SSI in combination with a selection of appropriate antimicrobial agents and a variety of antibiotics and an irrational combination of drugs will increase the incidence of adverse drug reactions. Through the implementation of various intervention measures, the clinicians' awareness of the rational application of antimicrobial drugs has been improved significantly, and the rationality of drug use indications, medication course, drug selection, sample delivery rate and so on have been improved to varying degrees.

PMID: 30463822 [PubMed - indexed for MEDLINE]

In response to: fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose.

Clin Toxicol (Phila). 2018 10;56(10):907-908

Authors: Harmouche E, Hoffman RS, Howland MA

PMID: 29575930 [PubMed - indexed for MEDLINE]

Safety and tolerability of lifitegrast ophthalmic solution 5.0%: Pooled analysis of five randomized controlled trials in dry eye disease.

Eur J Ophthalmol. 2019 Jul;29(4):394-401

Authors: Nichols KK, Donnenfeld ED, Karpecki PM, Hovanesian JA, Raychaudhuri A, Shojaei A, Zhang S

Abstract
PURPOSE: Characterize the safety and tolerability of lifitegrast ophthalmic solution 5.0% for the treatment of dry eye disease.
METHODS: Pooled data from five randomized controlled trials were analyzed. Key inclusion criteria were adults with dry eye disease (Schirmer tear test score ⩾1 and ⩽10 mm, eye dryness score ⩾40 (visual analog scale 0-100), corneal staining score ⩾2.0 (0-4 scale)). Participants were randomized to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 or 360 days. Treatment-emergent adverse events and drop comfort scores were assessed.
RESULTS: Overall, 2464 participants (lifitegrast, n = 1287; placebo, n = 1177) were included. Ocular treatment-emergent adverse events occurring in >5% in either group were instillation site irritation (lifitegrast, 15.2%; placebo, 2.8%), instillation site reaction (lifitegrast, 12.3%; placebo, 2.3%), and instillation site pain (lifitegrast, 9.8%; placebo, 2.1%); the most common (> 5%) nonocular treatment-emergent adverse event was dysgeusia (lifitegrast, 14.5%; placebo, 0.3%). The majority of treatment-emergent adverse events were mild to moderate in severity. Discontinuation due to treatment-emergent adverse events occurred in 7.0% (lifitegrast) versus 2.6% (placebo) of participants (ocular: 5.5% vs 1.5%; nonocular: 1.9% vs 1.1%). Drop comfort scores with lifitegrast improved within 3 min of instillation and the score at 3 min improved across visits (12-week trials (both eyes, day 84 vs 0): 2.0 vs 3.3; SONATA (day 360 vs 0): right eye, 1.2 vs 1.7; left eye, 1.2 vs 1.8).
CONCLUSION: Lifitegrast ophthalmic solution 5.0% appeared to be safe and well tolerated for the treatment of dry eye disease. Drop comfort with lifitegrast improved within 3 min of instillation.

PMID: 30112930 [PubMed - indexed for MEDLINE]

Toxic medications in Leber's hereditary optic neuropathy.

Mitochondrion. 2019 05;46:270-277

Authors: Kogachi K, Ter-Zakarian A, Asanad S, Sadun A, Karanjia R

Abstract
Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder characterized by acute bilateral vision loss. The pathophysiology involves reactive oxygen species (ROS), which can be affected by medications. This article reviews the evidence for medications with demonstrated and theoretical effects on mitochondrial function, specifically in relation to increased ROS production. The data reviewed provides guidance when selecting medications for individuals with LHON mutations (carriers) and are susceptible to conversion to affected. However, as with all medications, the proven benefits of these therapies must be weighed against, in some cases, purely theoretical risks for this unique patient population.

PMID: 30081212 [PubMed - indexed for MEDLINE]

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Adverse symptoms during short-term use of ulipristal acetate in women with uterine myomas and/or adenomyosis.

J Obstet Gynaecol Res. 2019 Apr;45(4):865-870

Authors: Hong YH, Han SJ, Lee D, Kim SK, Jee BC

Abstract
AIM: To evaluate various adverse symptoms during short-term use of ulipristal acetate in women with uterine myomas (n = 90), adenomyosis (n = 3) or both (n = 7).
METHODS: One hundred premenopausal women who received ulipristal acetate for 4-12 weeks during 2016 to 2017 were selected. The medical records were reviewed and the following information was collected; adverse symptoms during medication, presence of menorrhagia or menstrual cramps, blood hemoglobin and liver function test. Adverse symptoms were recorded in the medical records as a checklist form including 76 specific progestin-related symptoms.
RESULTS: Overall, the most frequent adverse symptom was amenorrhea (43%), followed by weight gain (29%), fatigue (27%), abdominal discomfort (21%), decreased menstrual flow (19%) and dizziness (18%). In 89 symptomatic women (with heavy menstrual bleeding and/or menstrual cramping pain and/or anemia), the most frequent adverse symptom was weight gain (27%) and fatigue (27%), followed by abdominal discomfort (21%), dry eye (18%), facial flushing (17%), dizziness (17%), headache (17%) and increased vaginal discharge (15%). Fourteen women stopped the medication due to unwanted adverse symptoms. Of this discontinuation group, major complaint was fatigue (50%), followed by weight gain (36%) and breast discomfort (35.7%).
CONCLUSION: Adverse symptoms were common and discontinuation rate was somewhat higher during short-term course of ulipristal acetate. Information about incidence of various adverse symptoms should be given to women who willing to take ulipristal acetate.

PMID: 30675965 [PubMed - indexed for MEDLINE]

Evaluation of a Novel System to Enhance Clinicians' Recognition of Preadmission Adverse Drug Reactions.

Appl Clin Inform. 2018 04;9(2):313-325

Authors: Smith JC, Chen Q, Denny JC, Roden DM, Johnson KB, Miller RA

Abstract
BACKGROUND: Often unrecognized by providers, adverse drug reactions (ADRs) diminish patients' quality of life, cause preventable admissions and emergency department visits, and increase health care costs.
OBJECTIVE: This article evaluates whether an automated system, the Adverse Drug Effect Recognizer (ADER), could assist clinicians in detecting and addressing inpatients' ongoing preadmission ADRs.
METHODS: ADER uses natural language processing to extract patients' medications, findings, and past diagnoses from admission notes. It compares excerpted information to a database of known medication adverse effects and promptly warns clinicians about potential ongoing ADRs and potential confounders via alerts placed in patients' electronic health records (EHRs). A 3-month intervention trial evaluated ADER's impact on antihypertensive medication ordering behaviors. At the time of patient admission, ADER warned providers on the Internal Medicine wards of Vanderbilt University Hospital about potential ongoing preadmission antihypertensive medication ADRs. A retrospective control group, comprised similar physicians from a period prior to the intervention, received no alerts. The evaluation compared ordering behaviors for each group to determine if preadmission medications changed during hospitalization or at discharge. The study also analyzed intervention group participants' survey responses and user comments.
RESULTS: ADER identified potential preadmission ADRs for 30% of both groups. Compared with controls, intervention providers more often withheld or discontinued suspected ADR-causing medications during the inpatient stay (p < 0.001). Intervention providers who responded to alert-related surveys held or discontinued suspected ADR-causing medications more often at discharge (p < 0.001).
CONCLUSION: Results indicate that ADER helped physicians recognize ADRs and reduced ordering of suspected ADR-causing medications. In hospitals using EHRs, ADER-like systems could improve clinicians' recognition and elimination of ongoing ADRs.

PMID: 29742757 [PubMed - indexed for MEDLINE]