A Study of Acute Poisoning Cases Admitted to the University Hospital Emergency Department in Tabriz, Iran.

Drug Res (Stuttg). 2017 Mar;67(3):183-188

Authors: Oraie M, Hosseini MJ, Islambulchilar M, Hosseini SH, Ahadi-Barzoki M, Sadr H, Yaghoubi H

Abstract
Chemical substances have an important threat due to extensive use in medicine, agriculture, industry and environment. In this retrospective study, etiological and demographic characteristics of acute poisoning cases admitted to a hospital in Iran were investigated. We compared these data with those reported from other parts of the country and the international experiences to evaluate any difference if exists. 7 052 poisoned cases admitted to the hospital from April 2006 to March 2013, by data collected from the medical record in poison center section. According to our results there is a predominance of male patients and the majority of the poisoned patients were between 20-30 years old. Drug poisoning was the most common cause of poisonings. The most frequently involved drugs were benzodiazepines and antidepressants. The seasonal distribution of our study showed a peak in summer. To prevent acute poisonings, the social education about the risk assessment of central nervous system-acting drugs and reduction of the exposure period of people to pesticides are recommended. This study suggested a proper educational program for the public and primary care units. Our results provide useful information for preventive strategies.

PMID: 28073114 [PubMed - indexed for MEDLINE]

Disclosure of Adverse Events in Pediatrics.

Pediatrics. 2016 Dec;138(6):

Authors: COMMITTEE ON MEDICAL LIABILITY AND RISK MANAGEMENT, COUNCIL ON QUALITY IMPROVEMENT AND PATIENT SAFETY

Abstract
Despite increasing attention to issues of patient safety, preventable adverse events (AEs) continue to occur, causing direct and consequential injuries to patients, families, and health care providers. Pediatricians generally agree that there is an ethical obligation to inform patients and families about preventable AEs and medical errors. Nonetheless, barriers, such as fear of liability, interfere with disclosure regarding preventable AEs. Changes to the legal system, improved communications skills, and carefully developed disclosure policies and programs can improve the quality and frequency of appropriate AE disclosure communications.

PMID: 27940747 [PubMed - indexed for MEDLINE]

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

PLoS One. 2016;11(11):e0166166

Authors: Elwood PC, Morgan G, Galante J, Chia JW, Dolwani S, Graziano JM, Kelson M, Lanas A, Longley M, Phillips CJ, Pickering J, Roberts SE, Soon SS, Steward W, Morris D, Weightman AL

Abstract
BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin.
METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin.
RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43).
CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.

PMID: 27846246 [PubMed - indexed for MEDLINE]

Eliciting the child's voice in adverse event reporting in oncology trials: Cognitive interview findings from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events initiative.

Pediatr Blood Cancer. 2017 Mar;64(3):

Authors: Reeve BB, McFatrich M, Pinheiro LC, Weaver MS, Sung L, Withycombe JS, Baker JN, Mack JW, Waldron MK, Gibson D, Tomlinson D, Freyer DR, Mowbray C, Jacobs S, Palma D, Martens CE, Gold SH, Jackson KD, Hinds PS

Abstract
BACKGROUND: Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child's voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child's/adolescent's understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity.
PROCEDURE: From seven pediatric research hospitals, children/adolescents ages 7-15 years who were diagnosed with cancer and receiving treatment were eligible, along with their parent-proxies. The Pediatric PRO-CTCAE includes 130 questions that assess 62 symptomatic AEs capturing symptom frequency, severity, interference, or presence. Cognitive interviews with retrospective probing were completed with children in the age groups of 7-8, 9-12, and 13-15 years. The children/adolescents and proxies were interviewed independently.
RESULTS: Two rounds of interviews involved 81 children and adolescents and 74 parent-proxies. Fifteen of the 62 AE terms were revised after Round 1, including refinements to the questions assessing symptom severity. Most participants rated the PRO-CTCAE AE items as "very easy" or "somewhat easy" and were able to read, understand, and provide valid responses to questions. A few AE items assessing rare events were challenging to understand.
CONCLUSIONS: The Pediatric and Proxy PRO-CTCAE performed well among children and adolescents and their proxies, supporting its content validity. Data from PRO-CTCAE may improve symptomatic AE reporting in clinical trials and enhance the quality of care that children receive.

PMID: 27650708 [PubMed - indexed for MEDLINE]

Effect-enhancing and toxicity-reducing activity of usnic acid in ascitic tumor-bearing mice treated with bleomycin.

Int Immunopharmacol. 2017 May;46:146-155

Authors: Su ZQ, Liu YH, Guo HZ, Sun CY, Xie JH, Li YC, Chen JN, Lai XP, Su ZR, Chen HM

Abstract
Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM. UA combined with BLM was significantly more effective than BLM alone in inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, and promoting the cleaved caspase-3 and cleaved caspase-8 activities to induce cancer cellular apoptosis. The mechanism may be associated with the transcriptional regulation of p53/p21/Cyclin pathway. Furthermore, UA effectively moderated the histopathological changes, reduced the content of MDA, HYP, TNF-α, IL-1β, IL-6 and TGF-β1, and increased the level of SOD when combined with BLM in lung tissues of H22-bearing mice, which was believed to be related to the inhibition on the protein level of p-Smad2/3 and enhancement of Smad7 expression. These findings suggested that UA might be a potential effect-enhancing and toxicity-reducing candidate for BLM in the treatment of malignant ascites.

PMID: 28284148 [PubMed - indexed for MEDLINE]

Off-Label Prescribing and Polypharmacy: Minimizing the Risks.

J Psychosoc Nurs Ment Health Serv. 2017 Feb 01;55(2):17-22

Authors: Leahy LG

Abstract
Off-label prescribing and polypharmacy are commonplace in today's health care environment. Patients are treated with multiple medications obtained through multiple providers, and all too frequently, there is no collaboration amongst professionals. Nurses can address these issues by educating themselves and their patients regarding medication indications and uses, side effects, risks, and benefits. By exploring a patient's medication reconciliation, including over-the-counter agents, and identifying the U.S. Food and Drug Administration-approved indications, as well as potential off-label uses and overlapping side effects of the medications prescribed, nurses can facilitate collaboration among prescribers to reduce polypharmacy, minimize medication side effects, and alleviate drug-drug interactions, while improving patient outcomes and quality of life. [Journal of Psychosocial Nursing and Mental Health Services, 55(2), 17-22.].

PMID: 28218925 [PubMed - indexed for MEDLINE]

Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study.

BMC Geriatr. 2017 Jan 26;17(1):35

Authors: Mestres Gonzalvo C, de Wit HA, van Oijen BP, Hurkens KP, Janknegt R, Schols JM, Mulder WJ, Verhey FR, Winkens B, van der Kuy PM

Abstract
BACKGROUND: In the nursing home population, it is estimated that 1 in every 3 patients is polymedicated and given their considerable frailty, these patients are especially prone to adverse drug reactions. Clinical pharmacist-led medication reviews are considered successful interventions to improve medication safety in the inpatient setting. Due to the limited available evidence concerning the benefits of medication reviews performed in the nursing home setting, we propose a study aiming to demonstrate a positive effect that a clinical decision support system, as a health care intervention, may have on the target population. The primary objective of this study is to reduce the number of patients with at least one event when using the clinical decision support system compared to the regular care. These events consist of hospital referrals, delirium, falls, and/or deaths.
METHOD/DESIGN: This study is a multicentre, prospective, randomised study with a cluster group design. The randomisation will be per main nursing home physician and stratified per ward (somatic and psychogeriatric). In the intervention group the clinical decision support system will be used to screen medication list, laboratory values and medical history in order to obtain potential clinical relevant remarks. The remarks will be sent to the main physician and feedback will be provided whether the advice was followed or not. In the control group regular care will be applied.
DISCUSSION: We strongly believe that by using a clinical decision support system, medication reviews are performed in a standardised way which leads to comparable results between patients. In addition, using a clinical decision support system eliminates the time factor to perform medication reviews as the major problems related to medication, laboratory values, indications and/or established patient characteristics will be directly available. In this way, and in order to make the medication review process complete, consultation within healthcare professionals and/or the patient itself will be time effective and the medication surveillance could be performed around the clock.
TRIAL REGISTRATION: The Netherlands National Trial Register NTR5165 . Registered 2nd April 2015.

PMID: 28125977 [PubMed - indexed for MEDLINE]

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

Am J Gastroenterol. 2017 Jan;112(1):120-131

Authors: Casanova MJ, Chaparro M, García-Sánchez V, Nantes O, Leo E, Rojas-Feria M, Jauregui-Amezaga A, García-López S, Huguet JM, Arguelles-Arias F, Aicart M, Marín-Jiménez I, Gómez-García M, Muñoz F, Esteve M, Bujanda L, Cortés X, Tosca J, Pineda JR, Mañosa M, Llaó J, Guardiola J, Pérez-Martínez I, Muñoz C, González-Lama Y, Hinojosa J, Vázquez JM, Martinez-Montiel MP, Rodríguez GE, Pajares R, García-Sepulcre MF, Hernández-Martínez A, Pérez-Calle JL, Beltrán B, Busquets D, Ramos L, Bermejo F, Barrio J, Barreiro-de Acosta M, Roncedo O, Calvet X, Hervías D, Gomollón F, Domínguez-Antonaya M, Alcaín G, Sicilia B, Dueñas C, Gutiérrez A, Lorente-Poyatos R, Domínguez M, Khorrami S, Muñoz C, Taxonera C, Rodríguez-Pérez A, Ponferrada A, Van Domselaar M, Arias-Rivera ML, Merino O, Castro E, Marrero JM, Martín-Arranz M, Botella B, Fernández-Salazar L, Monfort D, Opio V, García-Herola A, Menacho M, Ramírez-de la Piscina P, Ceballos D, Almela P, Navarro-Llavat M, Robles-Alonso V, Vega-López AB, Moraleja I, Novella MT, Castaño-Milla C, Sánchez-Torres A, Benítez JM, Rodríguez C, Castro L, Garrido E, Domènech E, García-Planella E, Gisbert JP

Abstract
OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.
METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.
RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.
CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

PMID: 27958281 [PubMed - indexed for MEDLINE]

Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database.

Fundam Clin Pharmacol. 2017 Apr;31(2):237-244

Authors: Colin O, Favrelière S, Quillet A, Neau JP, Houeto JL, Lafay-Chebassier C, Pérault-Pochat MC, French Pharmacovigilance Network

Abstract
Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period. To assess the association between PML and drug intake, we calculated an adverse drug report odds ratio (ROR) with its 95% confidence interval. We have studied the delay of onset of PML for each drug concerned. Among the 101 cases of PML, 39 drugs were mentioned as suspect. The main therapeutic classes suspected with significant ROR were antineoplastic agents (n = 85), immunosuppressants (n = 67), and corticosteroids. A latent interval from the time of drug initiation to the development of PML is established: the median time to onset was 365 days (123-1095 days). The onset of PML is highly variable and differs among drug classes [from 1 to 96 months (IQR: 39.0-126)]. An association between PML and some immunosuppressant drugs was found as expected, but also with antineoplastic agents and glucocorticoids. An important delay of PML onset after stopping treatment is suspected and should alert prescribers. Prescribers but also patients should be informed about the potential associations with all these drugs. Monitoring could be necessary for many drugs to early detect PML.

PMID: 27736027 [PubMed - indexed for MEDLINE]

Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions.

PLoS One. 2016;11(10):e0164304

Authors: Backenroth D, Chase H, Friedman C, Wei Y

Abstract
Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs.

PMID: 27716785 [PubMed - indexed for MEDLINE]

Short-term recovery of chemotherapy-induced peripheral neuropathy after treatment for pediatric non-CNS cancer.

Pediatr Blood Cancer. 2017 Jan;64(1):180-187

Authors: Gilchrist LS, Tanner LR, Ness KK

Abstract
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect of pediatric cancer treatment. The presentation of CIPN, trajectory and completeness of recovery over the first 6 months postchemotherapy, and the influence of patient and treatment characteristics on recovery are described.
PATIENTS AND METHODS: Sixty-seven children and adolescents treated for non-CNS cancers were evaluated for CIPN using the pediatric modified total neuropathy score (ped-mTNS) while on treatment and 3 and 6 months postchemotherapy. Differences between diagnostic groups and treatment type were evaluated as well as change in scores over time. Risk factors for on-treatment and persistent CIPN at 6 months were identified.
RESULTS: Overall, ped-mTNSs were in the abnormal range for 86.5% during treatment and scores decreased over time (initial 9.3 ± 0.6, 6 months 4.3 ± 0.4; F = 38.14, P < 0.001). By 6 months posttreatment, mean scores and percentage of children with abnormal scores were reduced to 2.4 ± 0.3 and 11.5%, respectively, in the ALL group, but remained higher at 5.7 ± 0.7 and 57%, respectively, for lymphoma, and 5.2 ± 1.0 and 60%, respectively, for other solid tumors. At 6 months posttreatment, light touch deficits and foot strength deficits remained in 19.4 and 59.7%, respectively, compared with only 4.9 and 9.8% of the control population. Subjects who were older at exposure, female, or who received etoposide in addition to vincristine were at higher risk for on-treatment CIPN. On-treatment sensory abnormalities were associated with increased risk of persistent CIPN.
CONCLUSION: While CIPN improves in most pediatric patients, significant numbers, especially those treated for lymphoma or other solid tumors, have remaining neuropathic signs and symptoms 6 months posttreatment.

PMID: 27567009 [PubMed - indexed for MEDLINE]

[Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists].

Herz. 2016 Dec;41(8):697-705

Authors: Tschöpe C, Kherad B, Spillmann F, Schneider CA, Pieske B, Krackhardt F

Abstract
BACKGROUND: Several studies have indicated that reduction of testosterone levels in patients with prostate cancer undergoing androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists can be associated with an increased risk of cardiovascular events. The GnRH antagonists have a different mode of action compared with GnRH agonists and may be preferred in ADT for patients with cardiovascular disease.
OBJECTIVE: This review article discusses potential mechanisms underlying the development of cardiovascular events associated with ADT when using GnRH agonists and explains the differences in mode of action between GnRH agonists and GnRH antagonists. Additionally, relevant studies are presented and practical recommendations for the clinical practice are provided.
MATERIAL AND METHODS: A literature search was performed. Full publications and abstracts published in the last 10 years up to September 2015 were considered to be eligible.
RESULTS: The GnRH antagonists were associated with a decreased risk of cardiovascular events compared with GnRH agonists in prostate cancer patients undergoing ADT and particularly in patients with cardiovascular risk factors or a history of cardiovascular disease. This decrease may be due to the different mode of action of GnRH antagonists compared with GnRH agonists.
CONCLUSION: Prostate cancer patients with either cardiovascular disease or an increased risk of experiencing a cardiovascular event undergoing ADT should be preferentially treated with GnRH antagonists.

PMID: 27083586 [PubMed - indexed for MEDLINE]

Pharmacokinetic study of bortezomib administered intravenously in Taiwanese patients with multiple myeloma.

Hematol Oncol. 2017 Jun 19;:

Authors: Huang SY, Chang CS, Liu TC, Wang PN, Yeh SP, Ho CL, Kuo MC, Lin HY, de Jong J, Chen JY, Yang YW

Abstract
This phase 4, single-arm, non-randomized, open-label, post approval commitment study evaluated the pharmacokinetics and safety of bortezomib in Taiwanese patients with multiple myeloma. Patients (≥20 years) with measurable secretory multiple myeloma (serum monoclonal IgG ≥10, IgA/IgE ≥5, IgD ≥0.5 g/L, IgM present [regardless of level], and urine M protein of ≥200 mg/24 h) received intravenous bortezomib 1.3 mg/m(2) , twice weekly for 2 weeks, followed by a 10-day resting phase (days 12 to 21). Pharmacokinetics and safety were assessed at pre-specified time points. All enrolled patients (n = 18, men: 11; women: 7) completed the study. Mean (SD) Cmax (maximum observed plasma concentration) on day 11 was 266 (77.5) ng/mL, approximately 60% higher compared with non-Asian patients receiving a similar bortezomib regimen but with overlapping ranges. Because of the protracted terminal phase, half-life (t1/2 ), area under the plasma concentration-time curve from time 0 to infinity (AUC∞ ), volume of distribution (Vz ), and systemic clearance were not assessable. All patients experienced treatment-emergent adverse events (TEAEs); 78% were drug-related. Most commonly reported TEAEs were thrombocytopenia (n = 11 [61%]), neutropenia (n = 9 [50%]), leukopenia (n = 6 [33%]), and diarrhoea (n = 6 [33%]); the most common serious adverse event was pneumonia (n = 2 [11%]). One patient had a dose reduction due to a TEAE of thrombocytopenia. Overall, bortezomib exposure (AUC) in Taiwanese patients (AUClast [SD]: 230 [147] ng·h/mL) with twice weekly intravenous administration was comparable with non-Asian population (AUClast [SD]: 241 [82] ng·h/mL). Bortezomib treatment was associated with manageable toxicity profile and did not limit the continuity of therapy.

PMID: 28626947 [PubMed - as supplied by publisher]

Clomiphene for the treatment of male infertility: a case report of mood change.

Curr Drug Saf. 2017 Jun 15;:

Authors: Aussedat M, Jean-Louis J, Djahangirian O, Brochet MS

Abstract
BACKGROUND: Clomiphene is normally used in women with ovulatory dysfunction. In men, it is used off label in some cases of infertility. Psychological adverse effects are reported in women but very few in men.
CASE: A 34 year-old man treated with clomiphene for oligoteratospermia presented anxiety, decreased appetite, and depressed mood making him unable to function properly at work, five days after initiation of therapy. Symptoms required reduction followed by discontinuation of treatment four days later because of absence of improvement. Following cessation, the patient noted a gradual then a complete resolution approximately one week later. The patient did not have any psychiatric or other medical condition neither drug nor substance abuse that could explain this clinical presentation. The Naranjo's score was used to prove the clomiphene's imputability.
CONCLUSION: Health care providers should advise patients of the risk of psychological adverse effects when initiating treatment with clomiphene and should provide a close monitoring of mood change, especially during the initial weeks.

PMID: 28625145 [PubMed - as supplied by publisher]

[Icelanders' beliefs about medicines. Use of BMQ].

Laeknabladid. 2017 Februar;103(2):67-72

Authors: Vilhelmsdottir H, Johannsson M

Abstract
OBJECTIVE: To study beliefs held by the general public in Iceland about medicines.
METHODS: The Beliefs about Medicines Questionnaire was used to explore Icelanders' beliefs about medicines. A sample of 1500 Icelandic citizens, aged 18-75, obtained from the Social Science Research Insti-tute was given The Beliefs about Medicines Questionnaire.
RESULTS: The response rate was 61.6%. Most Icelanders have positive beliefs about their medication as well as general trust. Those who suffer from chronic diseases are more positive towards medicines than others and less inclined to view them as excessively used and harmful. Higher level of education predicts more positive beliefs towards medication - and vice versa. Gender and age do not seem to affect such beliefs.
CONCLUSION: Gaining a better understanding of people´s beliefs about medicines and what determines these beliefs can be of considerable value in the search for ways to improve therapy and adherence, espe-cially for those suffering from chronic diseases. Promoting education for the general public about medicines might result in less mis-understanding among patients and subsequently better grounded -beliefs and more adequate therapeutic adherence. Key words: beliefs, medicines, Icelanders, BMQ, survey. Correspondence: Hlif Vilhelmsdottir, hlif84@gmail.com.

PMID: 28489012 [PubMed - indexed for MEDLINE]

Medication governance: preventing errors and promoting patient safety.

Br J Nurs. 2017 Feb 09;26(3):159-165

Authors: Kavanagh C

Abstract
This article highlights the significance of medication errors, identifying potential issues and support systems required. Medication errors involve different health professionals and present at various stages of the medication cycle. Focusing on a collaborative approach and the role of the nurse is necessary. Special groups, particularly older adults, are considered where multiple conditions and multiple medications increase the risk of adverse drug reactions. Nurses' accountability and their knowledge of medications are taken into account along with the role of nurse educators. Reporting errors is crucial; the culture of the organisation significantly contributes to whether errors are reported. Learning arises from near misses and errors, enabling preventive measures to be put in place. There is a need for a culture of safety within organisations where medication governance promotes patient safety and the provision of high-quality care.

PMID: 28185490 [PubMed - indexed for MEDLINE]

Impact of Pharmacists in Optimizing Geriatric Pharmacotherapy in Primary Care Within a Veterans Affairs Medical Center.

Consult Pharm. 2017 Jan 01;32(1):47-62

Authors: Mondiello TB, Stutzman LA

Abstract
OBJECTIVE: To assess pharmacists' impact on optimizing pharmacotherapy among geriatric patients.
DESIGN: Single-site, prospective, quality-improvement project.
SETTING: Primary care at a Veterans Affairs medical center.
PARTICIPANTS: Thirteen males 75 years of age and older were included.
INTERVENTIONS: Recommendations were made by pharmacists to optimize prescribing.
MAIN OUTCOME MEASURES: Differences between specific instances of suboptimal prescribing before and after pharmacists' recommendations, the percentage of pharmacists' recommendations accepted, and the top most commonly prescribed psychotropic medications and their most common indications.
RESULTS: Sixty-three recommendations were made by pharmacists, and 48% of these recommendations were accepted by providers. There was a 27% reduction of the use of high-risk medications, a 44% reduction of omissions of care, and a 74% reduction of incomplete medication monitoring after pharmacists' recommendations. The most commonly prescribed psychotropic medications were zolpidem (31%), lorazepam (23%), and clonazepam and temazepam (each 15%). The most common indications for these medications were anxiety and insomnia (each 46%), with 8% of patients having an indication for both.
CONCLUSION: Pharmacists' recommendations improved geriatric pharmacotherapy by decreasing the overall instances of suboptimal prescribing.

PMID: 28077205 [PubMed - indexed for MEDLINE]

Physician Perceptions of Consultant Pharmacist Services Associated with an Intervention for Adverse Drug Events in the Nursing Facility.

Consult Pharm. 2016 Dec 01;31(12):708-720

Authors: Kane-Gill SL, Hanlon JT, Fine MJ, Perera S, Culley CM, Studenski SA, Nace DA, Boyce RD, Castle NG, Handler SM

Abstract
OBJECTIVE: To assess the importance and performance of consultant pharmacist services delivered before and after an intervention to detect and manage adverse drug events among nursing facility residents.
DESIGN: Before and after intervention survey of physicians participating in a randomized, controlled trial.
SETTING: Four nonprofit, academically affiliated nursing facilities.
PARTICIPANTS: Attending physicians providing nursing facility care who were randomized to intervention or control groups.
INTERVENTIONS: Within the intervention arm, consultant pharmacists provided academic detailing in which trained health care professionals visit practicing physicians in their offices and present the most up-to-date clinical information. Physicians responded to alerts from a medication monitoring system, adjudicated system alerts for adverse drug events (ADEs), and provided structured recommendations about ADE management.
MAIN OUTCOME MEASURES: We compared physicians' assessments of the importance and performance of consultant pharmacist services before and after the trial intervention in the intervention and control groups.
RESULTS: In the intervention group, ratings of importance increased for all 24 survey questions, and 5 of the changes were statistically significant (P < 0.05). In the control group, ratings of importance increased for 16 questions, and none of the changes were statistically significant. In the intervention group, ratings of performance increased for all 24 questions, and 20 of the changes were statistically significant. In the control group, ratings of performance increased for 16 questions, and none of the changes was statistically significant.
CONCLUSION: A multifaceted, consultant pharmacist-led intervention comprising academic detailing, computerized decision support, and structured communication framework can improve physicians' assessment of importance and performance of consultant pharmacist services.
ABBREVIATIONS: ADE = Adverse drug event, M = Statistically significant mean, RCT = Randomized controlled trial, SBAR = Situation, Background, Discussion, Recommendation, SD = Standard deviation.

PMID: 28074750 [PubMed - indexed for MEDLINE]

First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours.

Eur J Cancer. 2017 Jun 15;81:142-150

Authors: Rodon J, Postel-Vinay S, Hollebecque A, Nuciforo P, Azaro A, Cattan V, Marfai L, Sudey I, Brendel K, Delmas A, Malasse S, Soria JC

Abstract
BACKGROUND AND OBJECTIVES: S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule.
MATERIALS AND METHODS: Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD. Pharmacokinetic (PK) parameters were assessed and pharmacodynamic end-points were evaluated in pre- and post-treatment tumour biopsies. Preliminary anti-tumour activity was evaluated as per the Response Evaluation Criteria In Solid Tumours 1.1 criteria.
RESULTS: A total of 103 patients were treated: 79 in the dose-escalation and 24 in the expansion. Doses from 15 to 900 mg were evaluated. Dose-limiting toxicities were reported in 9 patients and occurred at 30, 760 and 900 mg in the qd arm and at 180, 225 and 285 mg in the bid arm. The RD was defined at 600 mg qd. Adverse events (AEs) occurred with similar frequency in both regimens at an equivalent total daily dose. Overall, 83 patients (81.4%) had drug-related AEs, the majority (93%) of which were grade I-II (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) and only 3% led to drug discontinuation. Intratumoural PK analysis at the RD suggested hitting of MET, AXL and FGFR.
CONCLUSION: S49076 demonstrated a tolerable safety profile with limited single-agent activity. PK/pharmacodynamic readouts of S49076 are encouraging for further investigation of S49076 in combination therapies.
TRIAL REGISTRATION NUMBER: ISRCTN00759419.

PMID: 28624695 [PubMed - as supplied by publisher]

Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective Janus kinase 1 inhibitor, after short-term treatment of rheumatoid arthritis: Results of two randomized Phase IIA trials.

Arthritis Rheumatol. 2017 Jun 16;:

Authors: Vanhoutte F, Mazur M, Voloshyn O, Stanislavchuk M, Van der Aa A, Namour F, Galien R, Meuleners L, van 't Klooster G

Abstract
OBJECTIVE: Janus kinase (JAK) inhibitors have shown efficacy in rheumatoid arthritis (RA). We hypothesized that selective inhibition of JAK1 would combine good efficacy with a differentiated safety profile versus less selective JAK inhibitors.
METHODS: In two 4-week exploratory, double-blind, placebo-controlled Phase IIA trials, 127 RA patients with insufficient response to methotrexate received filgotinib (GLPG0634, GS-6034) oral capsules (twice-daily 100 mg, or once-daily 30, 75, 150, 200, or 300 mg) or placebo, added on to a stable regimen of methotrexate, to evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of filgotinib. The primary endpoint was the American College of Rheumatology 20% improvement (ACR20) response rate at Week 4.
RESULTS: Filgotinib (75-300 mg) treatment met the primary endpoint and showed early onset of efficacy. ACR20 response rates progressively increased to Week 4, and DAS28 [CRP] decreased. Marked and sustained improvements in serum CRP and other pharmacodynamic markers were observed. The pharmacokinetic exposure increased dose proportionally within the 30-300 mg dose range. Early side effects observed with other less selective JAK inhibitors were not observed, such as no worsening of anemia (JAK2 related), no effects on liver transaminases and no increase in LDL/cholesterol. A limited decrease in neutrophils, but no neutropenia, was consistent with immunomodulatory effects through JAK1 inhibition. There were no infections. Overall, filgotinib was well tolerated with study drug-related events mild to moderate and transient on therapy, the most common being nausea.
CONCLUSION: Selective inhibition of JAK1 by filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies. This article is protected by copyright. All rights reserved.

PMID: 28622463 [PubMed - as supplied by publisher]