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]

Antipsychotic Use Among Adult Outpatients and Venous Thromboembolic Disease: A Retrospective Cohort Study.

J Clin Psychopharmacol. 2017 Jun 15;:

Authors: Ferraris A, Szmulewicz AG, Vazquez FJ, Vollmer WM, Angriman F

Abstract
BACKGROUND: Treatment with antipsychotic (AP) agents is associated with incident thromboembolic events. However, the underpinnings of this association remain unknown. We sought to evaluate the effect of AP agents-categorized by their metabolic/sedative and hyperprolactinemia adverse effect profile-on the risk of venous thromboembolic disease during long-term follow-up.
METHODS: A retrospective cohort study of adult patients initiating AP treatment for the first time was conducted. Primary outcome was defined as the time to venous thromboembolism (VTE) (either deep venous thrombosis or acute pulmonary embolism). Antipsychotic agents were categorized by their risk (high vs low) of either drug-induced (a) sedation/metabolic adverse event or (b) hyperprolactinemia. We used a propensity score-adjusted Cox proportional hazards model to control for confounding.
FINDINGS: One thousand eight patients (mean age, 72.4 y) were followed for a median of 36 months. Incident VTE occurred in 6.25% of patients, corresponding to an incidence rate of 184 cases per 10,000 person-years. We found no difference in the hazard of VTE during follow-up between high- and low-risk groups (hazard ratio, 1.23 [95% confidence interval, 0.74-2.04] for drug-induced sedation/metabolic adverse event risk categories, and hazard ratio 0.81 [95% confidence interval, 0.50-1.35] for high versus low hyperprolactinemia risk).
CONCLUSIONS: These results suggest that the risk of thromboembolic events in older adults who started AP treatment for the first time does not seem to be related to these drugs' risk of either sedation/metabolic adverse events or hyperprolactinemia. However, VTE remains a common problem in this subgroup of patients.

PMID: 28622161 [PubMed - as supplied by publisher]

Real-World Efficacy of Daclatasvir and Sofosbuvir, With and Without Ribavirin, in HIV/HCV Coinfected Patients With Advanced Liver Disease in a French Early Access Cohort.

J Acquir Immune Defic Syndr. 2017 May 01;75(1):97-107

Authors: Lacombe K, Fontaine H, Dhiver C, Metivier S, Rosenthal E, Antonini T, Valantin MA, Miailhes P, Harent S, Batisse D, Pageaux GP, Chas J, Aumaitre H, Dominguez S, Allegre T, Lafeuillade A, Billaud E, De Truchis P, Perre P, Leroy V, De Ledinghen V, Sogni P, Dabis F, Zhao Y, Filipovics A, Fedchuk L, Akremi R, Bennai Y, Salmon Ceron D

Abstract
BACKGROUND: Efficacious, well-tolerated, direct antiviral agents have drastically changed the prognosis of hepatitis C virus (HCV) disease, but real-world data for oral treatments are limited in key populations such as HIV/HCV coinfection with advanced liver disease. Daclatasvir (DCV) efficacy and safety was assessed in the French "Autorisation Temporaire d'Utilisation" (ATU) program, providing DCV ahead of market authorization to patients with advanced HCV disease without other treatment options.
METHODS: This was a subanalysis of HIV/HCV coinfected ATU patients treated with DCV plus sofosbuvir (SOF). Recommended duration was 24 weeks; addition of ribavirin (RBV) and/or shorter treatment was at the physician's discretion. The primary efficacy analysis was sustained virologic response at posttreatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting.
RESULTS: The efficacy population (N = 407) was mostly cirrhotic (72%, of whom 18% were decompensated), HCV treatment-experienced (82%), and infected with genotypes 1 (69%), 3 (12%), or 4 (19%). Median CD4 was 555 cells/mm; 95% had HIV RNA <50 copies/mL. Most (74%) were treated for 24 weeks; 14% received RBV. SVR12 was 92% overall (95% confidence interval: 88.6% to 94.0%); 90% (86.4% to 93.2%) in patients with cirrhosis; 95% (88.9% to 97.5%) in patients without cirrhosis. SVR12 was consistent across HCV genotypes and antiretroviral regimens. Among 617 patients with safety data, 7 discontinued for an adverse event and 10 died.
CONCLUSIONS: DCV+SOF±RBV achieved high SVR12 and was well tolerated in this large real-world cohort of HIV/HCV coinfected patients with advanced liver disease.

PMID: 28272163 [PubMed - indexed for MEDLINE]

Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults.

J Acquir Immune Defic Syndr. 2017 May 01;75(1):61-66

Authors: Gallant JE, Thompson M, DeJesus E, Voskuhl GW, Wei X, Zhang H, White K, Cheng A, Quirk E, Martin H

Abstract
OBJECTIVE: To evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase strand transfer inhibitor (INSTI).
DESIGN: Phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study.
METHODS: HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Primary endpoint was time-weighted average change from baseline to day 11 (DAVG11) for plasma HIV-1 RNA. HIV-1 RNA, adverse events (AEs), and laboratory assessments were evaluated through day 17.
RESULTS: Twenty participants were enrolled (n = 4/group). Mean DAVG11 ranged from -0.92 to -1.61 across BIC doses versus -0.01 for placebo. Significant reductions in plasma HIV-1 RNA from baseline at day 11 were observed for all BIC doses compared with placebo (P < 0.001); mean decreases were 1.45-2.43 log10 copies/mL. Increased BIC exposures correlated with increased reduction in plasma HIV-1 RNA from baseline on day 11. Three participants on BIC (50 or 100 mg) achieved plasma HIV-1 RNA <50 copies/mL by end of study. Median Tmax ranged from 1.0 to 1.8 hours (day 1, postdose) and 1.3-2.7 hours (day 10), with median t1/2 ranging from 15.9 to 20.9 hours. No participant developed primary INSTI-R substitution through day 17. BIC was well tolerated, with no discontinuations because of adverse events.
CONCLUSIONS: BIC is a novel, potent, unboosted INSTI that demonstrated rapid, dose-dependent declines in HIV-1 RNA after 10 days of monotherapy. BIC was well tolerated, and displayed rapid absorption and a half-life supportive of once-daily therapy in HIV-infected subjects.

PMID: 28196003 [PubMed - indexed for MEDLINE]

Adverse Reactions to Contrast Material: A Canadian Update.

Can Assoc Radiol J. 2017 May;68(2):187-193

Authors: Morzycki A, Bhatia A, Murphy KJ

Abstract
Imaging techniques frequently employ contrast agents to improve image resolution and enhance pathology detection. These gadolinium- and iodine-based media, although generally considered safe, are associated with a number of adverse effects ranging from mild to severe. Reactions are classified as either anaphylactoid ("anaphylaxis-like") or nonanaphylactoid, depending on a number of elements that will be reviewed. Herein, we have summarized predisposing risk factors for adverse events resulting from the use of contrast, their associated pathophysiological mechanisms as well as known prophylaxis for the antitreatment of high-risk patients. In the unlikely event that a serious adverse reaction does occur, we have provided a comprehensive summary of treatment protocols. Our goal was to thoroughly evaluate the current literature regarding adverse reactions to radiocontrast agents and provide an up to date review for the health care provider.

PMID: 27745988 [PubMed - indexed for MEDLINE]

Implementation of a module to promote competency in adverse drug reaction reporting in undergraduate medical students.

Indian J Pharmacol. 2016 Oct;48(Suppl 1):S69-S73

Authors: Tripathi RK, Jalgaonkar SV, Sarkate PV, Rege NN

Abstract
OBJECTIVES: Underreporting and poor quality of adverse drug reaction (ADR) reports pose a challenge for the Pharmacovigilance Program of India. A module to impart knowledge and skills of ADR reporting to MBBS students was developed and evaluated.
MATERIALS AND METHODS: The module consisted of (a) e-mailing an ADR narrative and online filling of the "suspected ADR reporting form" (SARF) and (b) a week later, practical on ADR reporting was conducted followed by online filling of SARF postpractical at 1 and 6 months. SARF was an 18-item form with a total score of 36. The module was implemented in the year 2012-2013. Feedback from students and faculty was taken using 15-item prevalidated feedback questionnaires. The module was modified based on the feedback and implemented for the subsequent batch in the year 2013-2014. The evaluation consisted of recording the number of students responding and the scores achieved.
RESULTS: A total of 171 students in 2012-2013 batch and 179 in 2013-2014 batch participated. In the 2012-2013 batch, the number of students filling the SARF decreased from basal: 171; 1 month: 122; 6 months: 17. The average scores showed improvement from basal 16.2 (45%) to 26.4 (73%) at 1 month and to 27.3 (76%) at 6 months. For the 2013-2014 batch, the number (n = 179) remained constant throughout and the average score progressively increased from basal 10.5 (30%) to 27.8 (77%) at 1 month and 30.3 (84%) at 6 months.
CONCLUSION: This module improved the accuracy of filling SARF by students and this subsequently will led to better ADR reporting. Hence, this module can be used to inculcate better ADR reporting practices in budding physicians.

PMID: 28031613 [PubMed - indexed for MEDLINE]

The need for a comprehensive medication safety module in medical education.

Indian J Pharmacol. 2016 Oct;48(Suppl 1):S57-S60

Authors: Chandy SJ

Abstract
OBJECTIVE: A rising number of medicines and minimal emphasis on rational prescribing in the medical curriculum may compromise medication safety. There is no focused module in the curriculum dealing with factors affecting safety such as quality, medicines management, rational use, and approach to adverse effects. Creating awareness of these issues would hopefully plant a seed of safe prescribing and encourage pharmacovigilance. A study was therefore done to determine the need for such a module.
METHOD: A quasi-experimental pre-post module study. Medical students (n = 88) completing pharmacology term were recruited after informed consent. A questionnaire containing 20 questions on various themes was administered and scored. Subsequently a module was developed and relevant safety themes taught to the students. After one month, the questionnaire was re-administered.
RESULTS: The pre module score was 9.52/20. Knowledge about the various themes, adverse effects, medication management, quality issues and rational use were similar though poor knowledge was evident in specific areas such as clinical trials, look alike-sound alike medicines (LASA) and medicine storage. The post module score was 12.24/20. The improvement of score was statistically significant suggesting the effectiveness of the module.
CONCLUSION: The relatively poor knowledge and improvement with a specific educational module emphasizes the need of such a module within the medical curriculum to encourage safe use of medicines by Indian Medical Graduates (IMG). It is hoped that the policy makers in medical education will introduce such a module within the medical curriculum.

PMID: 28031610 [PubMed - indexed for MEDLINE]

Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients (The PADR-EC Score).

PLoS One. 2016;11(10):e0165757

Authors: Parameswaran Nair N, Chalmers L, Connolly M, Bereznicki BJ, Peterson GM, Curtain C, Castelino RL, Bereznicki LR

Abstract
BACKGROUND: Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years.
METHODS: ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively.
RESULTS: In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65-0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients' admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56-0.78).
CONCLUSIONS: This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in clinical practice.

PMID: 27798708 [PubMed - indexed for MEDLINE]

Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study.

Occup Environ Med. 2017 Jan;74(1):39-45

Authors: Budnik LT, Scheer E, Burge PS, Baur X

Abstract
OBJECTIVES: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers.
METHODS: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys.
RESULTS: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6).
CONCLUSIONS: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.

PMID: 27655774 [PubMed - indexed for MEDLINE]

Variation in Preventive Care in Children Receiving Chronic Glucocorticoid Therapy.

J Pediatr. 2016 Dec;179:226-232

Authors: Basiaga ML, Burrows EK, Denburg MR, Meyers KE, Grossman AB, Mamula P, Grundmeier RW, Burnham JM

Abstract
OBJECTIVE: To assess preventive care measure prescribing in children exposed to glucocorticoids and identify prescribing variation according to subspecialty and patient characteristics.
STUDY DESIGN: Retrospective cohort study of children initiating chronic glucocorticoids in the gastroenterology, nephrology, and rheumatology divisions at a pediatric tertiary care center. Outcomes included 25-hydroxyvitamin D (25OHD) and lipid testing, pneumococcal polysaccharide (PPV) and influenza vaccination, and stress dose hydrocortisone prescriptions.
RESULTS: A total of 701 children were followed for a median of 589 days. 25OHD testing was performed in 73%, lipid screening in 29%, and PPV and influenza vaccination in 16% and 78%, respectively. Hydrocortisone was prescribed in 2%. Across specialties, 25OHD, lipid screening, and PPV prescribing varied significantly (all P < .001). Using logistic regression adjusting for specialty, 25OHD testing was associated with older age, female sex, non-Hispanic ethnicity, and lower baseline height and body mass index z-scores (all P < .03). Lipid screening was associated with older age, higher baseline body mass index z-score, and lower baseline height z-score (all P < .01). Vaccinations were associated with lower age (P < .02), and PPV completion was associated with non-White race (P = .04).
CONCLUSIONS: Among children chronically exposed to glucocorticoids, 25OHD testing and influenza vaccination were common, but lipid screening, pneumococcal vaccination, and stress dose hydrocortisone prescribing were infrequent. Except for influenza vaccination, preventive care measure use varied significantly across specialties. Quality improvement efforts are needed to optimize preventive care in this high-risk population.

PMID: 27622698 [PubMed - indexed for MEDLINE]

Are proton pump inhibitors really so dangerous?

Dig Liver Dis. 2016 Aug;48(8):851-9

Authors: Savarino V, Dulbecco P, Savarino E

Abstract
For decades, millions of patients with acid-related disorders have had their acid inhibited effectively and safely first with H2-receptor antagonists (H2RAs) and then with proton pump inhibitors (PPI). As with any pharmacological agent, PPIs have been reported to be associated with some adverse events, but several recent large-scale observational studies have evidenced new and serious abnormalities generally linked to their chronic use. However, these studies have often important limitations for their frequent retrospective design and other methodological drawbacks, such as selection biases of the analyzed populations and the presence of various confounding factors. Overall, although the conclusions of these pharmacovigilant investigations must be taken into account and can generate important hypotheses for future research, they do not have to create panic among patients and alarmism among physicians. On considering the weakness of these studies, we suggest physicians should not refrain from continuing to use PPIs, if these drugs are given for medical indications clearly established in the literature and, more importantly, they should not be induced to shift to H2RAs, a class of antisecretory agents that are much less effective than PPIs. A return to the past is potentially dangerous for the patients, taking into account the well-known success of PPIs in the wide spectrum of all acid-related conditions.

PMID: 27321544 [PubMed - indexed for MEDLINE]

Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study.

Respir Med. 2017 Jul;128:50-56

Authors: Halank M, Hoeper MM, Ghofrani HA, Meyer FJ, Stähler G, Behr J, Ewert R, Fletcher M, Colorado P, Nikkho S, Grimminger F

Abstract
BACKGROUND: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study.
METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.5-2.5 mg three times daily). The primary outcome was long-term safety and tolerability of riociguat; secondary outcomes included 6-minute walking distance, World Health Organization functional class, survival, and clinical worsening-free survival.
RESULTS: Sixty-eight patients (inoperable CTEPH, n = 41; PAH, n = 27) entered the long-term extension. Median treatment duration at the final data cut-off was 77 months. The most common adverse events were nasopharyngitis (57%) and peripheral edema (37%). Three patients (4%) experienced serious adverse events of hemoptysis: two moderate, one severe, none fatal or considered drug-related. At Month 48, 6-minute walking distance increased from baseline by 69 ± 105 m, and World Health Organization functional class improved/stabilized/worsened versus baseline in 50/45/5% of patients. Three-year survival and clinical worsening-free survival were 91% and 49%, respectively (with patients censored if they withdrew without experiencing an event). Starting a new PAH treatment was the most frequent clinical worsening event.
CONCLUSIONS: Improvements in exercise and functional capacity were maintained at 4 years in patients remaining on treatment, with no new safety signals identified. These data support riociguat as a long-term treatment option for PAH and inoperable CTEPH.
TRIAL REGISTERED AT: ClinicalTrials.gov.
REGISTRATION NUMBER: NCT00454558.

PMID: 28610669 [PubMed - in process]

Using electronic medical record data to report laboratory adverse events.

Br J Haematol. 2017 Apr;177(2):283-286

Authors: Miller TP, Li Y, Getz KD, Dudley J, Burrows E, Pennington J, Ibrahimova A, Fisher BT, Bagatell R, Seif AE, Grundmeier R, Aplenc R

Abstract
Despite the importance of adverse event (AE) reporting, AEs are under-reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory-based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Children's Oncology Group (COG) trials at one institution were extracted, processed and graded. When compared to gold standard chart data, COG AE report sensitivity and positive predictive values (PPV) were 0-21·1% and 20-100%, respectively. EMR sensitivity and PPV were >98·2% for all AEs. These results demonstrate that EMR-based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.

PMID: 28146330 [PubMed - indexed for MEDLINE]

A Critical Asthma Standardized Clinical and Management Plan Reduces Duration of Critical Asthma Therapy.

Hosp Pediatr. 2017 02;7(2):79-87

Authors: Wong J, Agus MS, Graham DA, Melendez E

Abstract
BACKGROUND AND OBJECTIVE: Reduction of critical asthma management time can reduce intensive care utilization. The goal of this study was to determine whether a Critical Asthma Standardized Clinical Assessment and Management Plan (SCAMP) can decrease length of critical asthma management time.
METHODS: This retrospective study compared critical asthma management times in children managed before and after implementation of a Critical Asthma SCAMP. The SCAMP used an asthma severity score management scheme to guide stepwise escalation and weaning of therapies. The SCAMP guided therapy until continuous albuterol nebulization (CAN) was weaned to intermittent albuterol every 2 hours (q2h). Because the SCAMP was part of a quality improvement initiative in which all patients received a standardized therapy, informed consent was waived. The study was conducted in Medicine ICU and Intermediate Care Units in a tertiary care freestanding children's hospital. Children ≥2 years of age who had CAN initiated in the emergency department and were admitted to the Division of Medicine Critical Care with status asthmaticus were included. The time to q2h dosing from initiation of CAN was compared between the baseline and SCAMP cohorts. Adverse events were compared. The Mann-Whitney test was used for analysis; P values <.05 were considered statistically significant.
RESULTS: There were 150 baseline and 123 SCAMP patients eligible for analysis. There was a decrease in median time to q2h dosing after the SCAMP (baseline, 21.6 hours [interquartile range, 3.2-32.3 hours]; SCAMP, 14.2 hours [interquartile range, 9.0-23.1 hours]; P < .01). There were no differences in adverse events or readmissions.
CONCLUSIONS: A Critical Asthma SCAMP was effective in decreasing time on continuous albuterol.

PMID: 28096296 [PubMed - indexed for MEDLINE]

Changing perceptions and efficacy of generic medicines: An intervention study.

Health Psychol. 2016 Nov;35(11):1246-1253

Authors: Colgan SL, Faasse K, Pereira JA, Grey A, Petrie KJ

Abstract
OBJECTIVE: Generic medicines provide a safe and economical medical treatment and are used routinely throughout the world. However, a significant proportion of individuals view generic medicines as less safe, less effective and of lower quality compared with their equivalent branded medicines. This study aimed to investigate the effect of an educational intervention on improving perceptions and perceived efficacy of generic medicines.
METHOD: Seventy participants who experienced frequent tension headaches were randomized to receive an educational video about generic medicines or a control video. Participants then alternatively took branded and generic ibuprofen to treat their next two consecutive headaches. Changes in perceptions of generic medicines, pain relief and side effects were measured.
RESULTS: The intervention was effective in modifying and improving perceptions of generic medicines in the areas of understanding (p < .05), preference for a generic medicine to treat a serious illness (p < .05), and overall preference for generic medicines (p < .01). However, contrary to predictions, participants in the intervention group reported significantly less pain relief (p = .03) and more symptoms (p = .04) after taking generic ibuprofen compared with branded ibuprofen.
CONCLUSION: This study identified that an educational intervention is effective in modifying and improving perceptions of generic medicines but produced paradoxical effects on drug efficacy and side effects. These findings suggest that complex mechanisms are involved in the relationship between perceptions and drug efficacy and contradict the assumption that improving attitudes toward generic medicines will have a flow-on effect to improving health outcomes. (PsycINFO Database Record

PMID: 27505191 [PubMed - indexed for MEDLINE]

Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015.

PLoS Negl Trop Dis. 2016 Jul;10(7):e0004846

Authors: Moro PL, Woo EJ, Paul W, Lewis P, Petersen BW, Cano M

Abstract
BACKGROUND: In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States.
OBJECTIVE: To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.
METHODS: We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV.
RESULTS: VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination.
CONCLUSIONS: This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies.

PMID: 27410239 [PubMed - indexed for MEDLINE]