Safety and effectiveness of interferon β-1a intramuscular therapy: results of the postmarketing drug surveillance in Japan.

Rinsho Shinkeigaku. 2017 10 27;57(10):553-561

Authors: Makioka H, Nakaya F, Ling Y, Torii S, Saida T, Kira JI

Abstract
To investigate the safety and effectiveness of the interferon β-1a intramuscular injection under clinical conditions in Japan, we conducted an all-case postmarketing surveillance with a 2-year follow-up of patients who were registered during the period between November 2006 (product launch) and December 2010. Case reports were collected from 397 institutions. The safety analysis included 1,476 patients, and the effectiveness analysis included 1,441 patients. Of the patients included in the safety analysis, 86.3% had relapsing-remitting multiple sclerosis. The most common adverse drug reaction was pyrexia (19.24%). Serious adverse events included multiple sclerosis relapse (26 cases) and abnormal hepatic function (10 cases). In the effectiveness analysis, the annualized relapse rate improved significantly from 1.07 to 0.29 (P < 0.001). There was also a significant improvement in in the expanded disability status scale from 3.08 to 2.94 (P < 0.001). The results of the safety and effectiveness profile were consistent with those in previous reports.

PMID: 28966229 [PubMed - indexed for MEDLINE]

Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients.

J Clin Virol. 2017 Mar;88:58-61

Authors: Rodríguez-Osorio I, Cid P, Morano L, Castro Á, Suárez M, Delgado M, Margusino L, Meijide H, Pernas B, Tabernilla A, Pedreira JD, Mena Á, Poveda E

Abstract
BACKGROUND: New direct-acting antivirals agents (DAAs) are very safe and well tolerated.
OBJECTIVES: The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications.
STUDY DESIGN: All HCV-infected patients over 65 years old in clinical follow-up at two Hospitals in Spain who initiated anti-HCV therapy were included (August 2012-October 2015).
RESULTS: A total of 120 HCV mono-infected patients were recorded. Mean age of patients was 72.6±7.4years. There were 53.3% women and GT1b was the most frequent (83.3%); 64.2% had cirrhosis and 42.5% were treatment experienced. Ombitasvir+Paritaprevir/r±Dasabuvir±Ribavirin (RBV) and sofosbuvir/ledipasvir±RBV were the most frequently used regimens. Weight-adjusted dosing of RBV was included in 61.7% and 43.6% of them required a dose reduction. Most of the patients (86.7%) had concomitant chronic medication and in 35.8% adjustment was necessary. Adverse events (AE) were seen in 65% of the patients; more frequent when a protease inhibitor (PI) was being used. The sustained virological response (SVR12) per ITT was 88.3%. Only 3 patients discontinued treatment and 2 patients died.
CONCLUSIONS: High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The presence of AE was frequent (65%). The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. These findings highlight the high rates of response to DAAs in the elderly HCV-population. However, special caution must be taken when using RBV and a PI.

PMID: 28183063 [PubMed - indexed for MEDLINE]

Clinical characteristics of laboratory-confirmed leptospirosis in Okinawa, Japan, 1974-2015: high incidence of Jarisch-Herxheimer reaction.

Trans R Soc Trop Med Hyg. 2016 Sep;110(9):558-565

Authors: Tsuha S, Taniguchi T, Shiiki S, Narita M, Leung DT

Abstract
BACKGROUND: Leptospirosis is a zoonotic disease known to have wide-ranging clinical manifestations. Despite a number of published case series, culture-confirmed series are few and there is a paucity of data on Jarisch-Herxheimer reaction (JHR) associated with treatment of leptospirosis. Our objective was to describe the clinical and epidemiological factors associated with leptospirosis in an endemic area of Japan, with a focus on the occurrence of JHR, an often unrecognized and likely underestimated phenomenon.
METHODS: We performed a retrospective observational study of laboratory-confirmed leptospirosis at a single center over a 40-year period.
RESULTS: We report 100 leptospirosis cases in 99 patients during the period 1974-2015. Seventy-four cases were diagnosed by culture, representing eight different serovars. JHR was seen in 23 (82%) of 28 cases, including 19 (90%) of 21 cases treated with bactericidal antibiotics compared to 4 (57%) of seven cases with bacteriostatic antibiotics (p=0.08).
CONCLUSIONS: We found a wide variety of clinical manifestations, epidemiological exposures, and causative serovars of disease in an endemic region of Japan. We also found that JHR occurs frequently, and its recognition may be important for the diagnosis and management of leptospirosis in the early stage when laboratory confirmation is pending.

PMID: 27744340 [PubMed - indexed for MEDLINE]

Old dog begging for new tricks: current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity.

Curr Opin Infect Dis. 2016 Dec;29(6):561-576

Authors: Konvinse KC, Phillips EJ, White KD, Trubiano JA

Abstract
PURPOSE OF REVIEW: Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs.
RECENT FINDINGS: Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge. Although patch and intradermal testing are specific for the diagnosis of immune-mediated ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex-vivo diagnostics, especially enzyme-linked immunospot, has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous immune-mediated ADRs.
SUMMARY: In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct 'allergy label' is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction, is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T cell-mediated ADRs via personalized approaches, including human leukocyte antigen-typing, may pave future pathways to safer antimicrobial prescribing guidelines.

PMID: 27753687 [PubMed - indexed for MEDLINE]

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Dynamic change of fatigue of pemetrexed maintenance treatment in the JMEN trial.

Lung Cancer. 2018 Jan;115:121-126

Authors: Zhang L, Belani CP, Zhang PH, Wang X, Yang L, Orlando M, Wu YL

Abstract
OBJECTIVES: In the JMEN trial, patients with advanced non-squamous non-small cell lung cancer (NSCLC) without progression after platinum-based first-line therapy derived extended survival, delayed disease progression, and maintained overall quality of life (QoL) from pemetrexed maintenance therapy. However, fatigue was the most common physician-reported non-hematological toxicity in the pemetrexed group. This post hoc analysis investigated dynamic change of fatigue.
MATERIALS AND METHODS: Analysis of the overall safety population with squamous and non-squamous NSCLC subgroups included Common Terminology Criteria for Adverse Events to summarize adverse event (AE) rates by cycle and AE investigator-reported severity. Worsening of fatigue, defined as +15mm or more from baseline on a 100mm scale, evaluated QoL using the patient-reported Lung Cancer Symptom Scale. Patients with worsening fatigue and time-to-worsening of fatigue symptoms were also analyzed.
RESULTS: Drug-related fatigue occurred more frequently with pemetrexed than placebo. The drug-related grade 3/4 fatigue was also higher in the overall population on pemetrexed than with placebo. Fatigue incidence during pemetrexed maintenance after induction was not altered with cumulative exposure. Percentage of patients who experienced worsening of fatigue based on patient-reported LCSS scores was comparable between the two arms in cycles 1-10. The time-to-worsening of fatigue was similar between the pemetrexed arm and the placebo arm in the overall population; however, the East Asian subpopulation patients taking pemetrexed experienced a longer median time-to-worsening of fatigue than patients taking placebo.
CONCLUSION: Analyses suggest that despite higher incidence of any grade drug-related fatigue compared with placebo in patients with advanced NSCLC, pemetrexed maintenance does not impair patient-reported QoL.

PMID: 29290253 [PubMed - in process]

Optimising the use of medicines to reduce acute kidney injury in children and babies.

Pharmacol Ther. 2017 Jun;174:55-62

Authors: Oni L, Hawcutt DB, Turner MA, Beresford MW, McWilliam S, Barton C, Park BK, Murray P, Wilm B, Copple I, Floyd R, Peak M, Sharma A, Antoine DJ

Abstract
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs. This may be related to physiological (differential expressions of cytochrome P450 enzymes or variable glomerular filtration rates at different ages for example) and psychological (increasing autonomy and risk perception in teenage years) changes. Increasing numbers of children are surviving life-threatening childhood conditions due to medical advances. This means there is an increasing population who are at risk of the consequences of the long-term, early exposure to nephrotoxic agents. The kidney is an organ that is particularly vulnerable to damage as a consequence of drugs. Drug-induced acute kidney injury (AKI) episodes in children and babies are principally due to non-steroidal anti-inflammatory drugs, antibiotics or chemotherapeutic agents. The renal tubules are vulnerable to injury because of their concentrating ability and high-energy hypoxic environment. This review focuses on drug-induced AKI and the methods to minimise its effect, including general management plus the role of child-specific pharmacokinetic data, the use of pharmacogenomics and early detection of AKI using urinary biomarkers and electronic triggers.

PMID: 28202365 [PubMed - indexed for MEDLINE]

Adverse drug reactions to anticoagulants in Spain: analysis of the Spanish National Hospital Discharge Data (2010-2013).

BMJ Open. 2017 Jan 10;7(1):e013224

Authors: Carrasco-Garrido P, Hernández-Barrera V, Esteban-Hernández J, Jiménez-Trujillo I, Álvaro-Meca A, López de Andrés A, de Miguel Diez J, Rodríguez Barrios JM, Muñoz Robles JA, Jiménez-García R

Abstract
OBJECTIVE: To describe and analyse hospitalisations for adverse drug reactions (ADRs) involving anticoagulants. We also analysed the progress of the reactions over time, the factors related with ADRs.
DESIGN: A retrospective, descriptive, epidemiological study.
SETTING: This study used the Spanish National Hospital Discharge Database (Conjunto Mínimo Básico de Datos, CMBD), over a 4-year period.
PARTICIPANTS: We selected CMBD data corresponding to hospital discharges with a diagnosis of ADRs to anticoagulants (International Classification of Diseases-Ninth Revision, Clinical Modification (ICD-9-CM) code E934.2) in any diagnostic field during the study period.
MAIN OUTCOME MEASURES: We calculated the annual incidence of ADRs to anticoagulants according to sex and age groups. The median lengths of hospital stay and in-hospital mortality (IHM) were also estimated for each year studied. Bivariate analyses of the changes in variables according to year were based on Poisson regression. IHM was analysed using logistic regression models. The estimates were expressed as ORs and their 95% CI.
RESULTS: During the study period, 50 042 patients were hospitalised because of ADRs to anticoagulants (6.38% of all ADR-related admissions). The number of cases increased from 10 415 in 2010 to 13 891 in 2013. Cumulative incidence of ADRs to anticoagulants was significantly higher for men than women and in all age groups. An adjusted multivariate analysis revealed that IHM did not change significantly over time. We observed a statistically significant association between IHM and age, with the highest risk for the ≥85 age group (OR 2.67; 95% CI 2.44 to 2.93).
CONCLUSIONS: The incidence of ADRs to anticoagulants in Spain increased from 2010 to 2013, and was significantly higher for men than women and in all age groups. Older patients were particularly susceptible to being hospitalised with an adverse reaction to an anticoagulant.

PMID: 28073793 [PubMed - indexed for MEDLINE]

Cognitive adverse effects and brain deterioration associated with use of anticholinergic activity medicines in older adults.

Evid Based Med. 2016 12;21(6):235

Authors: Nishtala PS, Salahudeen MS

PMID: 27815304 [PubMed - indexed for MEDLINE]

Systems Toxicology: Systematic Approach to Predict Toxicity.

Curr Pharm Des. 2016;22(46):6911-6917

Authors: Kiani NA, Shang MM, Tegner J

Abstract
Drug discovery is complex and expensive. Numerous drug candidates fail late in clinical trials or even after being released to the market. These failures are not only due to commercial considerations and less optimal drug efficacies but, adverse reactions originating from toxic effects also constitute a major challenge. During the last two decades, significant advances have been made enabling the early prediction of toxic effects using in silico techniques. However, by design, these essentially statistical techniques have not taken the disease driving pathophysiological mechanisms into account. The complexity of such mechanisms in combination with their interactions with drugspecific properties and environmental and life-style related factors renders the task of predicting toxicity on a purely statistical basis which is an insurmountable challenge. In response to this situation, an interdisciplinary field has developed, referred to as systems toxicology, where the notion of a network is used to integrate and model different types of information to better predict drug toxicity. In this study, we briefly review the merits and limitations of such recent promising predictive approaches integrating molecular networks, chemical compound networks, and protein drug association networks.

PMID: 27697024 [PubMed - indexed for MEDLINE]

A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.

Mov Disord. 2016 Sep;31(9):1373-80

Authors: Tison F, Keywood C, Wakefield M, Durif F, Corvol JC, Eggert K, Lew M, Isaacson S, Bezard E, Poli SM, Goetz CG, Trenkwalder C, Rascol O

Abstract
BACKGROUND: The metabotropic glutamate receptor 5-negative allosteric modulator dipraglurant reduces levodopa-induced dyskinesia in the MPTP-macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa-induced dyskinesia in Parkinson's disease (PD).
METHODS: The study was a phase 2A double-blind, placebo-controlled, randomized (2:1), 4-week, parallel-group, multicenter dose-escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa-induced dyskinesia. Safety and tolerability were assessed based on clinical and biological examination and adverse events recording. Secondary efficacy outcome measures included the modified Abnormal Involuntary Movement Scale, UPDRS, and diaries. Pharmacokinetics were measured at 3 visits following a single dose.
RESULTS: Fifty-two patients were exposed to dipraglurant and 24 to placebo. There were no major safety concerns. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%; P = 0.04) and on day 14 (100 mg, 32%; P =0 .04) and across a 3-hour postdose period on day 14 (P = 0.04). There was no evidence of worsening of parkinsonism. Dipraglurant was rapidly absorbed (tmax = 1 hour). The 100-mg dose led to a mean Cmax of 1844 ng/mL on day 28.
CONCLUSIONS: Dipraglurant proved to be safe and well tolerated in its first administration to PD patients. Its efficacy in reversing levodopa-induced dyskinesia warrants further investigations in a larger number of patients. © 2016 International Parkinson and Movement Disorder Society.

PMID: 27214664 [PubMed - indexed for MEDLINE]

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

J Sex Med. 2017 Dec 27;:

Authors: Tuiten A, van Rooij K, Bloemers J, Eisenegger C, van Honk J, Kessels R, Kingsberg S, Derogatis LR, de Leede L, Gerritsen J, Koppeschaar HPF, Olivier B, Everaerd W, Frijlink HW, Höhle D, de Lange RPJ, Böcker KBE, Pfaus JG

Abstract
BACKGROUND: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available.
AIM: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups.
METHODS: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg).
OUTCOMES: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure.
RESULTS: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%).
CLINICAL IMPLICATIONS: T + S and T + B are promising treatments for women with FSIAD.
STRENGTHS AND LIMITATIONS: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated.
CONCLUSIONS: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2017;XX:XXX-XXX.

PMID: 29289554 [PubMed - as supplied by publisher]

Changing antimalarial agents after inefficacy or intolerance in patients with cutaneous lupus erythematosus: A multicenter observational study.

J Am Acad Dermatol. 2018 Jan;78(1):107-114.e1

Authors: Chasset F, Arnaud L, Jachiet M, Monfort JB, Bouaziz JD, Cordoliani F, Bagot M, Barbaud A, Francès C

Abstract
BACKGROUND: Changing from one antimalarial (AM) agent to another is often recommended in cutaneous lupus erythematosus (CLE) when the first AM agent is ineffective or poorly tolerated.
OBJECTIVE: To evaluate the effect on cutaneous response of a switch from hydroxychloroquine to chloroquine, or the reverse, after failure of the first AM agent.
METHODS: We conducted a retrospective observational study between 1997 and September 2015. The overall cutaneous response rate and reasons for failure of the switch were assessed for up to 48 months. Kaplan-Meier survival curves were used to assess the risk for failure of the second AM agent.
RESULTS: A total of 64 patients with CLE (78% were women) were included; for 48 patients, the switch was for inefficacy, and for 16, it was for adverse events. Median follow-up was 42 months (range, 3-171). Of the patients changed because of inefficacy, 56% were responders at month 3; however, the response decreased over time, with a median duration before failure of the second AM agent of 9 months (95% confidence interval, 6-24). For patients switched because of adverse events, the second AM agent was well tolerated in 69% of cases.
LIMITATIONS: Retrospective design and subjective evaluation of cutaneous response.
CONCLUSION: A change of AM agent should be considered in patients with CLE when the first AM agent is ineffective or poorly tolerated.

PMID: 29061479 [PubMed - indexed for MEDLINE]

Veterinary pharmacovigilance in India: A need of hour.

Indian J Pharmacol. 2017 Jan-Feb;49(1):2-3

Authors: Kumar R, Kalaiselvan V, Verma R, Kaur I, Kumar P, Singh GN

Abstract
Veterinary pharmacovigilance (PV) is important for the Medicine which are used for treating disease in animals. It becomes more important when these animals are further used for producing food. Adverse drug reactions (ADRs) have a direct impact on animals and indirect impact on human beings, for example, through milk products, other animal producing food products. Currently, PV program of India is playing a vital role in assessing the safety of medicines in Indian Population. The safety of medicine in animals can be assessed by veterinary PV. The research institutes involved in animal research and veterinary hospitals can be considered as ADR monitoring centers to assess the safety of medicines on animals.

PMID: 28458414 [PubMed - indexed for MEDLINE]

Tolerability of central nervous system symptoms among HIV-1 infected efavirenz users: analysis of patient electronic medical record data.

AIDS Care. 2017 08;29(8):1067-1073

Authors: Rosenblatt L, Broder MS, Bentley TGK, Chang E, Reddy SR, Papoyan E, Myers J

Abstract
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor indicated for treatment of HIV-1 infection. Despite concern over EFV tolerability in clinical trials and practice, particularly related to central nervous system (CNS) adverse events, some observational studies have shown high rates of EFV continuation at one year and low rates of CNS-related EFV substitution. The objective of this study was to further examine the real-world rate of CNS-related EFV discontinuation in antiretroviral therapy naïve HIV-1 patients. This retrospective cohort study used a nationally representative electronic medical records database to identify HIV-1 patients ≥12 years old, treated with a 1st-line EFV-based regimen (single or combination antiretroviral tablet) from 1 January 2009 to 30 June 2013. Patients without prior record of EFV use during 6-month baseline (i.e., antiretroviral therapy naïve) were followed 12 months post-medication initiation. CNS-related EFV discontinuation was defined as evidence of a switch to a replacement antiretroviral coupled with record of a CNS symptom within 30 days prior, absent lab evidence of virologic failure. We identified 1742 1st-line EFV patients. Mean age was 48 years, 22.7% were female, and 8.1% had a prior report of CNS symptoms. The first year, overall discontinuation rate among new users of EFV was 16.2%. Ten percent of patients (n = 174) reported a CNS symptom and 1.1% (n = 19) discontinued EFV due to CNS symptoms: insomnia (n = 12), headache (n = 5), impaired concentration (n = 1), and somnolence (n = 1). The frequency of CNS symptoms was similar for patients who discontinued EFV compared to those who did not (10.3 vs. 9.9%; P = .86). Our study found that EFV discontinuation due to CNS symptoms was low, consistent with prior reports.

PMID: 28147708 [PubMed - indexed for MEDLINE]

Polypharmacy in older adults: Association Rule and Frequent-Set Analysis to evaluate concomitant medication use.

Pharmacol Res. 2017 Feb;116:39-44

Authors: Held F, Le Couteur DG, Blyth FM, Hirani V, Naganathan V, Waite LM, Seibel MJ, Handelsman DJ, Cumming RG, Allore HG, Gnjidic D

Abstract
The aim of this study was to apply Association Rule and Frequent-Set analysis, and novel means of data visualisation to ascertain patterns of medication use and medication combinations contributing to medication group clusters according to geriatric syndrome status in older adults. Participants were community-dwelling men (aged ≥70 years, n=1686), Sydney, Australia. Medication exposure was categorised at medication class level and data were analysed according to geriatric syndrome status (presence of at least one syndrome including frailty, falls, cognitive impairment and urinary incontinence). Association Rule and Frequent-Set analysis were performed to identify "interesting" patterns of medication combinations that occur together. This analysis involves advanced computer algorithms that investigated all possible combinations of medications in the dataset in order to identify those which are observed more or much less frequently than expected. Frequent-Set Analysis demonstrated one unexpected medication combination, antiulcer and antidiabetic medications (3.5% of participants) in the overall population (n=1687). Frequency of medication combinations was similar in participants with (n=666) and without (n=1020) geriatric syndromes. Among participants with geriatric syndromes, the most frequent combinations included antigout with lipid-lowering agents (5.7%) followed by angiotensin II and diuretics combination (22%). This novel methodology can be used to detect common medication combinations overall by data visualisation, and against specific adverse drug reactions such as geriatric syndromes. This methodology may be a valuable pharmacovigilance approach to monitor large databases for the safety of medications.

PMID: 27988385 [PubMed - indexed for MEDLINE]

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

Women Health. 2017 Sep;57(8):976-989

Authors: Lin JJ, Chao J, Bickell NA, Wisnivesky JP

Abstract
Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

PMID: 27618729 [PubMed - indexed for MEDLINE]

Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies.

Mov Disord. 2016 Jul;31(7):1054-8

Authors: Trenkwalder C, Stocchi F, Poewe W, Dronamraju N, Kenney C, Shah A, von Raison F, Graf A

Abstract
BACKGROUND: Two phase 2 randomized, double-blind studies were designed to evaluate efficacy and safety of immediate-release (study 1) and modified-release (study 2) mavoglurant formulations in PD l-dopa-induced dyskinesia.
METHODS: Patients were randomized to mavoglurant 100-mg or placebo (4:3) groups (study 1) and mavoglurant 200-mg, mavoglurant 150-mg, or placebo (2:1:1) groups (study 2). Primary outcome was antidyskinetic efficacy, as measured by change from baseline to week 12 in modified Abnormal Involuntary Movement Scale total score.
RESULTS: Differences in least-squares mean (standard error) change in modified Abnormal Involuntary Movement Scale total score in week 12 did not reach statistical significance in either study (study 1: mavoglurant 100 mg twice a day versus placebo, 1.7 [1.31]; study 2: mavoglurant 150 mg twice a day (-1.3 [1.16]) and 200 mg twice a day (-0.2 [1.03]) versus placebo). Adverse events incidence was higher with mavoglurant than with placebo.
CONCLUSIONS: Both studies failed to meet the primary objective of demonstrating improvement of dyskinesia with mavoglurant treatment. © 2016 International Parkinson and Movement Disorder Society.

PMID: 27214258 [PubMed - indexed for MEDLINE]

A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia.

Mov Disord. 2016 Jul;31(7):1049-54

Authors: Trenkwalder C, Berg D, Rascol O, Eggert K, Ceballos-Baumann A, Corvol JC, Storch A, Zhang L, Azulay JP, Broussolle E, Defebvre L, Geny C, Gostkowski M, Stocchi F, Tranchant C, Derkinderen P, Durif F, Espay AJ, Feigin A, Houeto JL, Schwarz J, Di Paolo T, Feuerbach D, Hockey HU, Jaeger J, Jakab A, Johns D, Linazasoro G, Maruff P, Rozenberg I, Sovago J, Weiss M, Gomez-Mancilla B

Abstract
BACKGROUND: This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia.
METHODS: Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics.
RESULTS: In total, 67 patients completed the study. AQW051-treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls.
CONCLUSIONS: AQW051 did not significantly reduce dyskinesia or parkinsonian severity. © 2016 International Parkinson and Movement Disorder Society.

PMID: 26990766 [PubMed - indexed for MEDLINE]

Older Adults' Awareness of Deprescribing: A Population-Based Survey.

J Am Geriatr Soc. 2017 Dec;65(12):2691-2696

Authors: Turner JP, Tannenbaum C

Abstract
OBJECTIVES: To determine older adults' awareness of the concept of medication-induced harm and their familiarity with the term "deprescribing." Secondary objectives were to ascertain determinants of self-initiated deprescribing conversations and to identify how older adults seek information on medication harms.
DESIGN: Cross-sectional population-based household telephone survey using random-digit dialling.
SETTING: Canada.
PARTICIPANTS: Community-dwelling adults aged 65 and older (N = 2,665; n = 898 men, n = 1,767 women, mean age 74.9 ± 7.2, range 65-100).
MEASUREMENTS: Information was gathered on age; sex; awareness of the term "deprescribing"; knowledge and information-seeking behaviors related to medication harms; and previous initiation of a deprescribing conversation with a healthcare professional. Three targeted classes of potentially inappropriate prescriptions were asked about: sedative-hypnotics, glyburide, and proton pump inhibitors. Descriptive statistics and regression analyses were used to quantify associations.
RESULTS: Two-thirds (65.2%, 95% confidence interval (CI) = 63.4-67.0%) of participants were familiar with the concept of medication-induced harms. Only 6.9% (95% CI = 5.9-7.8%) recognized the term deprescribing; 48% (95% CI = 46-50%) had researched medication-related harms. Older adults most commonly sought information from the Internet (35.5%, 95% CI = 33.4-37.6%), and from health care professionals (32.2%, 95% CI = 30.1-34.3%). Patient-initiated deprescribing conversations were associated with awareness of medication harms (odds ratio (OR) = 1.74, 95% CI = 1.46-2.07), familiarity with the term deprescribing (OR = 1.55, 95% CI = 1.13-2.12), and information-seeking behaviors (OR = 4.57, 95% CI = 3.84-5.45), independent of age and sex.
CONCLUSION: Healthcare providers can facilitate patient-initiated deprescribing conversations by providing information on medication harms and using the term "deprescribing."

PMID: 28913911 [PubMed - indexed for MEDLINE]