Long-term safety, efficacy, and quality of life outcomes with adjunctive brivaracetam treatment at individualized doses in patients with epilepsy: An up to 11-year, open-label, follow-up trial.

Epilepsia. 2020 Mar 28;:

Authors: O'Brien TJ, Borghs S, He QJ, Schulz AL, Yates S, Biton V

Abstract
OBJECTIVE: To evaluate long-term safety/tolerability of brivaracetam at individualized doses ≤200 mg/d (primary) and maintenance of efficacy over time (secondary) in adults with focal seizures or primary generalized seizures (PGS) enrolled in phase 3, open-label, long-term follow-up trial N01199 (NCT00150800).
METHODS: Patients ≥16 years of age who had completed double-blind, placebo-controlled adjunctive brivaracetam trials NCT00175825, NCT00490035, NCT00464269, or NCT00504881 were eligible. Outcomes included safety, efficacy, and quality of life.
RESULTS: The safety set included 667 patients (focal seizures, 97.8%; PGS, 2.2%); the efficacy set included 648 patients with focal seizures and 15 patients with PGS. Overall, 49.2% of patients had ≥48 months of exposure. Treatment-emergent adverse events (TEAEs) occurred in 91.2% of all patients (91.3% of focal seizures group), brivaracetam discontinuation due to TEAEs in 14.8%, drug-related TEAEs in 56.7%, and serious TEAEs in 22.8%. The most common TEAEs in the focal seizures group (≥15%) were headache (25.3%) and dizziness (21.9%). Mean changes from baseline in Hospital Anxiety and Depression Scale scores at last value during 2-year evaluation were -0.7 (standard deviation [SD] = 4.3) and -0.2 (SD = 4.4) overall. In the focal seizures group, median reduction from baseline in focal seizure frequency/28 days was 57.3%, 50% responder rate was 55.6%, and 6-month and 12-month seizure freedom rates were 30.3% and 20.3%, respectively. Efficacy outcomes improved by exposure duration cohort and then stabilized through the 108-month cohort. Mean improvement from baseline in Patient-Weighted Quality of Life in Epilepsy Inventory total score (efficacy set) was 5.7 (SD = 16.1, Cohen's d = 0.35) at month 12 and 6.5 (SD = 18.0, Cohen's d = 0.36) at month 24.
SIGNIFICANCE: Adjunctive brivaracetam was well tolerated, with a good safety profile in long-term use in adults with epilepsy at individualized doses. Approximately half of the patients remained in the trial at 4 years. Brivaracetam reduced focal seizure frequency versus baseline. Efficacy improved with increasing exposure duration and remained stable through the 9-year cohort.

PMID: 32221987 [PubMed - as supplied by publisher]

Effects of ACE Inhibitors and Angiotensin Receptor Blockers in Normotensive Patients with Diabetic Kidney Disease.

Horm Metab Res. 2020 Mar 27;:

Authors: He D, Zhang Y, Zhang W, Xing Y, Guo Y, Wang F, Jia J, Yan T, Liu Y, Lin S

Abstract
The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing the progression of albuminuria and risk of cardiovascular events in hypertensive patients with diabetic kidney disease (DKD) is well-documented. However, the efficacy and safety of these agents in normotensive patients with DKD are still controversial. MEDLINE, Embase, and Cochrane Library were searched for relevant random controlled trials. The odd risk (OR) reductions were calculated with a random-effects model. Decrease in albuminuria, changes in eGFR, major cardiovascular events, and drug-related adverse events were analyzed. Thirteen RCTs including 1282 patients were retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs significantly decreased albuminuria (MD -80.28 mg/d, 95% CI -104.79 mg/d to -55.77 mg/d), and the efficacy is independent of changes in blood pressure and systolic blood pressure at baseline. The result of subanalysis showed the declining of albuminuria was more significantly in normotensive DKD patients with 2DM (p=0.005). No significant differences were found with regard to the declining of evaluated glomerular filtration rate (eGFR) (MD -0.29 ml/min/1.73 m2, 95% CI -2.99 to 2.41 ml/min/1.73 m2). There were no significant differences in the side effect of the drugs such as hypotension and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can decrease albuminuria to varying degree in normotensive patients with DKD, and better response occurred in patients with 2DM.

PMID: 32219798 [PubMed - as supplied by publisher]

Changing Aspects of Male Sexual Functions Accompanying Treatment of Benign Prostatic Hyperplasia With Silodosin 8 mg Per Day.

J Sex Med. 2020 Mar 23;:

Authors: ‘Andrology Study Group of Society of Urologic Surgery-Turkey (SUST)’, Cihan A, Kazaz İO, Yıldırım Ö, Deliktaş H, Ongün Ş, Gül Ü, Şahin B, Üre İ, Özkara H

Abstract
BACKGROUND: Alpha-adrenergic antagonist treatment for benign prostatic hyperplasia (BPH) and drug-related sexual side effects are frequent in aging men.
AIM: To investigate functional changes in erectile and ejaculatory aspects of male sexuality under Silodosin 8 mg per day treatment for BPH.
METHODS: Sexually active patients diagnosed with BPH and who initiated Silodosin treatment were the subjects of the study. The International Prostate Symptom Score, premature ejaculation patient profile (PEP-male) questionnaire, Sexual Health Inventory for Men (SHIM) questionnaire, and estimated intravaginal ejaculation latency time (IELT) values of the participants were used to evaluate sexual functions. Data evaluation was performed in 8 urology clinics retrospectively.
OUTCOMES: Participant ratings for SHIM, PEP, and estimated IELT were the primary outcome measures in the study.
RESULTS: Among 187 recruited patients, data of 98 patients, who completed the trial period in the study, were eligible. The median age of the eligible participants who completed the trial period for 3 months was 59.5 years (range 45-82). 16 patients of 187 (8%) reported a desire for drug withdrawal for anejaculation during the recruitment period. 46 (46.9%) and 49 (50%) patients reported anejaculation in the first and third month of the treatment, respectively. De novo erectile dysfunction was noticed in 15 patients (15.3%). There was a significant increase in the estimated IELT of subjects in both the first (P = .01) and third (P = .002) month. SHIM-1 (P = .008), SHIM-total (P = .009), and PEP scores (P = .008) were also improved in the third month of the treatment. Neither baseline patient characteristics nor changes in the International Prostate Symptom Score after treatment predicted final outcomes with multivariable analysis. The subgroup analysis of participants who reported "anejaculation" also revealed better outcomes compared with participants ejaculating naturally in the third month as per SHIM ratings.
CLINICAL IMPLICATIONS: Despite several male patients having dry orgasms due to Silodosin-induced anejaculation, the majority experienced improved erectile function.
STRENGTHS & LIMITATIONS: The present study demonstrated pioneering results while investigating both erectile and ejaculatory dimensions of the male sexual function during Silodosin treatment for BPH. However, lack of partner evaluation, low follow-up rates, and lack of knowledge about reasons why subjects are lost to follow-up after drug initiation have limited our interpretation.
CONCLUSION: Most patients using Silodosin 8 mg per day for BPH treatment experienced improvement in their erectile function, estimated IELT, and premature ejaculation profile in the third month of the treatment. Underlying mechanisms and reasons for individual differences necessitate further investigation. Cihan A, Kazaz İO, Yıldırım Ö, et al. Changing Aspects of Male Sexual Functions Accompanying Treatment of Benign Prostatic Hyperplasia With Silodosin 8 mg Per Day. J Sex Med 2020;XX:XXX-XXX.

PMID: 32217036 [PubMed - as supplied by publisher]

12 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 2020/03/28

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.

Hemodynamic Collapse Following Therapeutic Plasma Exchange in a Patient Receiving an Angiotensin Receptor Blocker.

Cureus. 2020 Feb 18;12(2):e7028

Authors: Ashok Kumar P, Paulraj S, Udekwu A

Abstract
Therapeutic plasma exchange (TPE) is a procedure for removal of plasma and its components while leaving behind cellular elements via an apheresis device. It is used in multiple conditions one among which is systemic lupus erythematosus (SLE). Adverse reactions from TPE range from mild hypotension and fever to life-threatening cardiovascular compromise. We report the case of sudden hemodynamic collapse following TPE for a neuropsychiatric lupus flare in a patient on losartan. A 62-year-old Caucasian female with a history of drug-induced lupus presented to the hospital with symptoms of a neuropsychiatric lupus flare. She was initiated on TPE with 5% albumin based on recommendations by her rheumatologist. Shortly after TPE, she became hypotensive with poor response to fluid boluses, requiring pressor support and intubation. These symptoms resolved within 24 hours on supportive measures. This was believed to be due to losartan use on the day of TPE. The medication was discontinued and she had further sessions of TPE with no complications. Angiotensin-converting enzyme (ACE) inhibitors have previously been associated with flushing and hypotension in patients undergoing TPE. Patients undergoing TPE have an activation of the prekallikrein and bradykinin system on contact with the extracorporeal membranes. ACE inhibitors potentiate this reaction by inhibiting bradykinin catabolism. Angiotensin receptor blockers (ARBs) have also been postulated to cause elevated bradykinin levels although data pertaining to the use of ARBs in TPE is limited. We hope to highlight this rare interaction in our case and emphasize the need for further data with regard to the same.

PMID: 32211262 [PubMed]

Comparison of the pain-reducing effects of EMLA cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: A multi-center, open-label, randomized crossover trial.

PLoS One. 2020;15(3):e0230372

Authors: Fujimoto K, Adachi H, Yamazaki K, Nomura K, Saito A, Matsumoto Y, Igarashi K, Uranishi H, Sakaguchi S, Matsuura T, Imura J, Okino K, Mukai K, Okushi Y, Kagaya Y, Tsuruyama Y, Okada K, Miyatake N, Haraguchi T, Iida Y, Yokoyama H

Abstract
Arteriovenous fistula puncture pain is a serious problem for patients undergoing dialysis and a good indication for topical anesthetics. No previous study has compared lidocaine/prilocaine cream (EMLA) with lidocaine tape for pain relief during arteriovenous fistula puncture in patients undergoing maintenance hemodialysis. To this end, we conducted a multicenter randomized crossover study including 66 patients (mean age, 65.8 years; males, 57.6%) undergoing maintenance hemodialysis thrice/week. Subjects were assigned to Sequence EL (EMLA administration followed by lidocaine, with 1-week wash-out) or Sequence LE (reverse administration, first lidocaine then EMLA). All subjects completed the study. At each puncture site, 1 g EMLA (25 mg lidocaine + 25 mg prilocaine) or one sheet of lidocaine tape (18 mg lidocaine) was applied 1 h or 30 min prior to arteriovenous fistula puncture, respectively. The primary endpoint was puncture pain relief, which was measured using a 100-mm visual analog scale. The secondary endpoints included quality of life, which was measured by SF-36, and safety. EMLA produced a 10.1-mm greater visual analog scale improvement than lidocaine tape (P = 0.00001). However, there was no statistically significant difference in the quality of life between the two groups, and no significant carryover/period effect was observed in any analysis. Further, no drug-related adverse events were observed. Taken together, these results suggest that EMLA cream is superior to lidocaine tape for the relief of arteriovenous fistula puncture pain in patients undergoing maintenance hemodialysis. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000027885).

PMID: 32210455 [PubMed - in process]

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid.

Cancers (Basel). 2020 Mar 23;12(3):

Authors: Hoffman MM, Zylla JS, Bhattacharya S, Calar K, Hartman TW, Bhardwaj RD, Miskimins WK, de la Puente P, Gnimpieba EZ, Messerli SM

Abstract
Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC's) and lysine demethylase (LSD1). Here, we investigate the effect of a small molecule epigenetic modulator known as Domatinostat (4SC-202), which inhibits both class I HDAC's and Lysine Demethylase (LSD1), on ATRT cell survival and single cell heterogeneity. Our findings suggest that 4SC-202 is both cytotoxic and cytostatic to ATRT in 2D and 3D scaffold cell culture models and may target cancer stem cells. Single-cell RNA sequencing data from ATRT-06 spheroids treated with 4SC-202 have a reduced population of cells overexpressing stem cell-related genes, including SOX2. Flow cytometry and immunofluorescence on 3D ATRT-06 scaffold models support these results suggesting that 4SC-202 reduces expression of cancer stem cell markers SOX2, CD133, and FOXM1. Drug-induced changes to the systems biology landscape are also explored by multi-omics enrichment analyses. In summary, our data indicate that 4SC-202 has both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and is an important potential cancer therapeutic to be investigated in vivo.

PMID: 32210076 [PubMed]

Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Rheumatology (Oxford). 2019 10 01;58(10):1767-1776

Authors: Bechman K, Clarke BD, Rutherford AI, Yates M, Nikiphorou E, Molokhia M, Norton S, Cope AP, Hyrich KL, Galloway JB

Abstract
OBJECTIVE: To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA).
METHODS: The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR 'good response' after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell's C statistic.
RESULTS: The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model.
CONCLUSION: Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.

PMID: 30982886 [PubMed - indexed for MEDLINE]

Abiraterone and spironolactone in prostate cancer: a combination to avoid.

Acta Clin Belg. 2019 Dec;74(6):439-444

Authors: Dhondt B, Buelens S, Van Besien J, Beysens M, De Bleser E, Ost P, Lumen N

Abstract
Objectives: Disease progression in metastatic castration-resistant prostate cancer (mCRPC) is dependent on androgen signaling. This case describes the complex adaptive androgen signaling mechanisms in mCRPC and illustrates that caution should be exercised when treating these patients with drugs influencing the androgen axis.Methods: Single case report and review of the literature.Results: We report the case of an 86-year-old man with mCRPC, treated with the secondary antihormonal agent abiraterone acetate. Following association of spironolactone to deal with symptoms related to mineralocorticoid excess, biochemical and radiographic disease progression occurred. Spironolactone was discontinued and 8 months after withdrawal, the patient continues to show a biochemical response to abiraterone.Conclusions: Although spironolactone generally exerts anti-androgenic effects, experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation. This is supported by the observations described in this case report. Therefore, spironolactone should be avoided in prostate cancer patients suffering from treatment-associated side effects of abiraterone.

PMID: 30477405 [PubMed - indexed for MEDLINE]

When time is of the essence: Managing care in emergency situations in Parkinson's disease.

Parkinsonism Relat Disord. 2019 02;59:49-56

Authors: Prasad S, Pal PK

Abstract
A movement disorder emergency is an acute or sub-acutely evolving neurological illness predominated by a primary movement disorder. Although Parkinson's disease (PD) is a chronic, progressive disorder, patients may present with a variety of acute symptoms. Timely diagnosis and management is crucial to reduce mortality and morbidity. The underlying causes of an emergency in PD may be attributable to either disease related emergencies which occur as a direct consequence of the disease pathophysiology or secondary to anti-parkinsonian medications, such as Parkinsonism-hyperpyrexia syndrome, acute psychosis, etc. Indirect disease related emergencies, are those which not directly associated with the disease but occur secondary to deficits produced by the disease, e.g. falls and pneumonia. Emergencies in patients with PD may also be related to deep brain stimulation or systemic illnesses which are unrelated to PD. Complications may also occur during the surgical management of patients with PD owing to the effects of the disease on cardiovascular and respiratory functions or interactions of PD medication with anesthetic agents. Additionally, although motor complications are expected to form a majority of ER admissions in PD, several studies have reported indirect or non-PD related complications as the predominant primary reason for emergency admissions. The present article aims to review emergencies encountered in patients with PD with focus on the identification and management of these emergencies.

PMID: 30253924 [PubMed - indexed for MEDLINE]

Prevalence of Medication-Dietary Supplement Combined Use and Associated Factors.

Nutrients. 2019 Oct 15;11(10):

Authors: Aznar-Lou I, Carbonell-Duacastella C, Rodriguez A, Mera I, Rubio-Valera M

Abstract
INTRODUCTION: The use of medication has increased in recent years in the US while the use of dietary supplements has remained stable but high. Interactions between these two kinds of products may have important consequences, especially in the case of widely used medications such as antihypertensives and antibiotics. The aim of this paper is to estimate the prevalence of potentially serious drug-dietary supplement interactions among tetracyclines, thiazides, and angiotensin II receptor blocker users by means of the NHANES 2013-2014 dataset.
METHODS: Data from 2013-2014 NHANES were obtained. Potential interactions analysed were tetracyclines with calcium, magnesium, and zinc, thiazides with vitamin D, and angiotensin II receptors blockers with potassium. Prevalence was calculated for each potential interaction. Logistic regression was used to assess associated factors.
RESULTS: 864 prescriptions issued to 820 patients were analysed. Overall prevalence of potential interaction was 49%. Older age and higher educational level were strongly associated with being at risk of a potential interaction. Factors such as age, race, civil status, citizenship, country of birth, BMI, and physical activity did not show notable associations.
CONCLUSIONS: Healthcare professionals should be aware of other medical products when they prescribe or dispense a medication or a dietary supplement, especially to the older population and people with a higher educational level.

PMID: 31618867 [PubMed - indexed for MEDLINE]

Using the Self-Controlled Tree-Temporal Scan Statistic to Assess the Safety of Live Attenuated Herpes Zoster Vaccine.

Am J Epidemiol. 2019 07 01;188(7):1383-1388

Authors: Yih WK, Kulldorff M, Dashevsky I, Maro JC

Abstract
The self-controlled tree-temporal scan statistic allows detection of potential vaccine- or drug-associated adverse events without prespecifying the specific events or postexposure risk intervals of concern. It thus opens a promising new avenue for safety studies. The method has been successfully used to evaluate the safety of 2 vaccines for adolescents and young adults, but its suitability to study vaccines for older adults had not been established. The present study applied the method to assess the safety of live attenuated herpes zoster vaccination during 2011-2017 in US adults aged ≥60 years, using claims data from Truven Health MarketScan Research Databases. Counts of International Classification of Diseases diagnosis codes recorded in emergency department or hospital settings were scanned for any statistically unusual clustering within a hierarchical tree structure of diagnoses and within 42 days after vaccination. Among 1.24 million vaccinations, 4 clusters were found: cellulitis on days 1-3, nonspecific erythematous condition on days 2-4, "other complications . . ." on days 1-3, and nonspecific allergy on days 1-6. These results are consistent with local injection-site reactions and other known, generally mild, vaccine-associated adverse events and a favorable safety profile. This method might be useful for assessing the safety of other vaccines for older adults.

PMID: 31062840 [PubMed - indexed for MEDLINE]

Potentially Unsafe Chronic Medication Use Among Older Adult Chronic Opioid Users.

Pharmacotherapy. 2019 02;39(2):140-149

Authors: Silva Almodovar A, Nahata MC

Abstract
STUDY OBJECTIVES: To assess chronic potentially unsafe medication use among older adults using opioids chronically versus those who did not, to assess the likelihood of chronically using medications to treat adverse effects associated with chronic opioid use, and to characterize the differences in chronic potentially unsafe medication use at three morphine equivalent dose (MED) levels/day (less than 50MED, 50-90MED, and more than 90MED).
DESIGN: Retrospective cross-sectional analysis.
DATA SOURCE: Prescription claims data from a national telehealth Medication Therapy Management (MTM) provider for the year 2015.
PATIENTS: All Medicare Part D beneficiaries (65 years and older [older adults]) from one Medicare Part D plan provider in one state who were eligible to receive MTM services.
MEASUREMENTS AND MAIN RESULTS: Medication claims were limited to refills in a 120-day window from one Medicare Part D provider. Chronic medication use was defined as having a total days' medication supply of 84 days or more. Odds ratios (ORs) and χ2 tests were used to compare chronic medication use among beneficiaries who were chronic opioid users versus nonopioid users. Analyses were repeated among chronic opioid users at the less than 50MED, 50-90MED, and more than 90MED levels. Unpaired t tests and Welch's analysis of variance paired with Games-Howell post hoc tests were used for continuous variables. Older adult (mean age 76 years) chronic opioid users were more likely to use muscle relaxants chronically (OR 2.67, 95% confidence interval [CI] 2.20-3.25), benzodiazepines (OR 2.08, 95% CI 1.87-2.31), hypnotics (OR 1.98, 95% CI 1.67-2.34), antidepressants (OR 1.64, 95% CI 1.51-1.77), and nonsteroidal antiinflammatory drugs (OR 1.78, 95% CI 1.59-1.98) versus nonopioid users. Further, chronic opioid users were 3.04 times (95% CI 2.05-4.51) more likely to use muscle relaxants and benzodiazepines concomitantly chronically and also more likely to use medications chronically to treat gastrointestinal reflux disease, constipation, estrogen loss, nausea and vomiting, and edema. Very high-dose (more than 90MED/day) chronic opioid users were more likely than low-dose users (less than 50MED) to use antidepressants (OR 1.51, 95% CI 1.15-1.97, p=0.003).
CONCLUSION: Older adults with chronic opioid use were more likely to use potentially unsafe medications chronically. These data demonstrated discordance between national prescribing guidelines and real-world practice among older adults with chronic pain in one Medicare Part D plan.

PMID: 30636335 [PubMed - indexed for MEDLINE]

Use of a Bioinformatics-Based Toxicity Scoring System to Assess Serotonin Burden and Predict Population-Level Adverse Drug Events from Concomitant Serotonergic Drug Therapy.

Pharmacotherapy. 2019 02;39(2):171-181

Authors: Culbertson VL, Rahman SE, Bosen GC, Caylor ML, Xu D

Abstract
STUDY OBJECTIVE: Numerous medications interact at serotonin (5-hydroxytryptamine [5-HT]) receptors directly or through off-target interactions, causing mild to severe serotonergic adverse drug events (ADEs), particularly among older adults. Our objective was to develop a novel molecular-based toxicity scoring system to assess serotonergic burden resulting from concurrently administered drugs. Quantitative methods to assess serotonergic burden may provide a useful clinical tool for improving pharmacotherapy.
DESIGN: Retrospective cohort study.
DATA SOURCES: PharMetrics Legacy health claims database (January 2001-December 2013) and ChEMBL bioactivity database.
PATIENTS: A 2-serotonergic drug exposure cohort (78,172 patients) and a 3-serotonergic drug exposure cohort (19,900 patients) were generated, and population-level statistics were collected. Nonexposure cohorts were created for each drug exposure cohort and matched in a 4:1 ratio for age, sex, and length of enrollment.
MEASUREMENTS AND MAIN RESULTS: Eight 5-HT medications were screened against multiple bioactivity databases to identify their off-target interactions at 5-HT receptors and serotonin reuptake transporter protein. A computational serotonin burden score (SBS) was derived from the receptor-specific interaction propensities reported from the comprehensive bioactivity screen. Linear regression was used to characterize associations between SBSs and combined total ADE incidence rate detected by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes. A significantly greater incidence of 17 potential 5-HT-related ADEs was seen in exposed serotonergic drug cohorts (p<0.05). A positive correlation between SBS and overall ADE incidence rate in the 2-serotonergic drug exposure cohort (R2  = 0.69, p<0.34) and 3-drug cohort (R2  = 0.85, p<0.01) was observed. When both drug cohorts were combined, total drug SBSs strongly correlated with the composite 5-HT adverse event rate (R2  = 0.92, p<0.0001). Despite an increasing burden of illness, these data suggest that drug combinations with higher SBSs are associated with a higher rate of potential serotonergic ADEs.
CONCLUSION: In this test of concept, positive associations between SBSs and serotonin-related ADEs suggest that it may offer a pharmacologic-based foundation for developing risk assessment tools to assist in optimizing pharmacotherapy.

PMID: 30620414 [PubMed - indexed for MEDLINE]

Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation.

Pharmacotherapy. 2019 02;39(2):196-203

Authors: Martinez BK, Baker WL, Sood NA, Bunz TJ, Meinecke AK, Eriksson D, Coleman CI

Abstract
STUDY OBJECTIVE: Patients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice.
DESIGN: Retrospective claims analysis.
DATA SOURCE: United States Truven MarketScan database (November 2012-March 2017).
PATIENTS: Adults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity-score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group).
MEASUREMENTS AND MAIN RESULTS: Patients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30-day permissible gap), insurance disenrollment, or end of follow-up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12-50) and 40% (95% CI 16-57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92-1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort.
CONCLUSION: This real-world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.

PMID: 30597611 [PubMed - indexed for MEDLINE]

12 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 2020/03/25

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.

11 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 2020/03/25

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.

13 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 2020/03/24

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.

Adverse drug reaction prevalence and mechanisms of action of first-line anti-tubercular drugs.

Saudi Pharm J. 2020 Mar;28(3):316-324

Authors: Imam F, Sharma M, Khayyam KU, Al-Harbi NO, Rashid MK, Ali MD, Ahmad A, Qamar W

Abstract
Purpose: Understanding the appearance of anti-tubercular drug-related adverse drug reactions (ADRs) in patients receiving tuberculosis (TB) treatment is important, and may be related to morbidity and mortality if not recognized early. Here, we aimed to characterize the mechanisms underlying adverse drug reactions due to combination anti-tuberculosis therapy of the Revised National Tuberculosis Control Program (RNTCP).
Methods: This was a prospective observational study conducted in 9 DOTS centers of New Delhi, India. All enrolled TB patients receiving first-line tuberculosis treatment as per RNTCP guidelines were monitored for ADRs. All ADRs that appeared during the treatment were recorded and analyzed.
Results: The study included 1011 TB patients on anti-TB treatment under DOTS. According to Naranjo's probability scale, of a total 351 (34.72%) reported adverse events, 102 (10.09%) were definite, 59 (5.83%) probable, 123 (12.17%) possible, and 67 (6.63%) doubtful. On the Hartwig severity scale, of the 351 adverse drug events, 225 (22.26%) were mild, 105 (10.38%) were moderate, and 21 (2.08%) were severe. Out of 102 reported adverse drug reactions, 81 (79.41%) were moderate and 21 (20.59%), while 65.28% did not experience any ADRs.
Conclusions: Directly Observed Treatment (DOT) is effective and safe compared to daily treatment regimens. Patients receiving DOTS therapy needed close monitoring for adverse events. Therefore, a pharmacovigilance program should be added at the National level to accesses the adverse event incidence.

PMID: 32194333 [PubMed]

Comparison of drug safety data obtained from the monitoring system, literature, and social media: An empirical proof from a Chinese patent medicine.

PLoS One. 2019;14(11):e0222077

Authors: Hu R, Golder S, Yang G, Li X, Wang D, Wang L, Xia R, Zhao N, Fang S, Lai B, Liu J, Fei Y

Abstract
OBJECTIVES: To investigate the consistency of adverse events (AEs) and adverse drug reactions (ADRs) reported in the literature, monitoring and social media data.
METHODS: Using one Chinese patent medicine-Cordyceps sinensis extracts (CSE) as an example, we obtained safety data from the national monitoring system (July 2002 to February 2016), literature (up to November 2016) and social media (May 2019). For literature data, we searched the Chinese National Knowledge Infrastructure Database (CNKI), WanFang database, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Embase and the Cochrane Library. Social media data was from the Baidu post bar and Sina micro-blog. Two authors independently screened the literature and extracted data by PRISMA Harms checklist was followed. AEs and ADRs were coded using the World Health Organization Adverse Reaction Terminology (WHO-ART). AEs and ADRs were grouped into thirty-one organ-system classes for comparisons. Frequencies, relative frequencies and rank were used as metrics. Radar chart was used to manifest the features of the distributions and proportions.
RESULTS: 610 AEs reported in CFDA monitoring data were associated with CSE, of which 537 (88.03%) were suspected ADRs (10.49% certain). 5568 AEs were identified from 172 papers (63% RCTs, 37% other types of studies including case series, case reports, ADR monitoring reports and reviews), in which 86 (1.54%) were ADRs (1.54% certain). 15 AEs (0 certain ADR) were identified from social media. AEs, ADRs and their affected system-organ classes, looked largely similar, but different in every aspect when looking at details. Data from RCTs demonstrated the most disparity.
CONCLUSIONS: In our study, the most prevalent AEs and ADRs, mainly gastro-intestinal system disorders including nausea, diarrhea and vomiting, in monitoring system were largely similar with those in literature and social media. But data from different sources varied if looked at details. Multiple data sources (the monitoring system, literature and social media) should be integrated to collect safety information of interventions. The distributions of AEs and ADRs from RCTs were least similar with the data from other sources. Our empirical proof is consistent with other similar studies.

PMID: 31693665 [PubMed - indexed for MEDLINE]