A systematic review of patient values, preferences and expectations for the treatment of recurrent ovarian cancer.

Gynecol Oncol. 2017 Aug;146(2):392-398

Authors: PEBC’s Ovarian Oncology Guidelines Group

Abstract
BACKGROUND AND OBJECTIVES: It is our belief that patient preference should play a significant role in disease management of recurrent ovarian cancer. Since cure is seldom an endpoint in this circumstance, patients' attitudes toward the risks and benefits of chemotherapy versus palliation are relevant.
METHODS: Medline, Embase, CINAHL and PsycINFO from were searched from January 1, 2000 to December 13, 2016 for studies of values, preferences or expectations of women with platinum-sensitive recurrent or refractory ovarian cancer.
RESULTS: Ten studies representing five countries met inclusion criteria. Although there was regional variation in preference for palliation over treatment, certain themes emerged. 1) Patients, even in the context of counselling overestimated the curative capability of chemotherapy. In one study 92% of patients had high expectations of healing after completing an expectation of treatment checklist. Another study observed that patients are often overwhelmed by information provided at diagnosis and there can be a discrepancy between what patients report to have heard and what the clinicians said. 2) Patients who had previously tolerated chemotherapy well were more likely to be accepting of the side-effects of chemotherapy. 3) Patients were more willing to accept chemotherapy and the related side effects when treatment was of curative intent or when overall survival was increased. 4) Patients valued both overall and progression free survival. 5) A significant minority (24%) consistently chose treatment over palliation. 6) Patients were more willing to accept the side effects of chemotherapy than were their health care providers.
CONCLUSIONS: These findings, in aggregate, highlight the importance of communication with patients regarding prognosis, adverse effects and symptom management to help negotiate the decision making process. Chemotherapy in the recurrent setting should be managed on a case by case basis, combining both medical constraints and consideration to patient preferences.

PMID: 28601379 [PubMed - indexed for MEDLINE]

ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish.

Int J Mol Sci. 2017 Apr 19;18(4):

Authors: Cornet C, Calzolari S, Miñana-Prieto R, Dyballa S, van Doornmalen E, Rutjes H, Savy T, D'Amico D, Terriente J

Abstract
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs principles. It Reduces, by up to a third, the number of animals required to assess toxicity in those organs. It Refines the drug toxicity evaluation through novel physiological parameters. Finally, it might allow the Replacement of classical species, such as rodents and larger mammals, thanks to its high predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).

PMID: 28422076 [PubMed - indexed for MEDLINE]

Guided Imagery And Progressive Muscle Relaxation as a Cluster of Symptoms Management Intervention in Patients Receiving Chemotherapy: A Randomized Control Trial.

PLoS One. 2016;11(6):e0156911

Authors: Charalambous A, Giannakopoulou M, Bozas E, Marcou Y, Kitsios P, Paikousis L

Abstract
OBJECTIVE: Patients receiving chemotherapy often experience many different symptoms that can be difficult to alleviate and ultimately negatively influence their quality of life. Such symptoms include pain, fatigue, nausea, vomiting and retching, anxiety and depression. There is a gap in the relevant literature on the effectiveness of cognitive-behavioural and relaxation techniques in symptom clusters. The study reflects this gap in the literature and aimed to test the effectiveness of Guided Imagery (GI) and Progressive Muscle Relaxation (PMR) on a cluster of symptoms experienced by patients undergoing chemotherapy.
METHODS: This was a randomized control trial with 208 patients equally assigned either in the intervention or the control group. Measurements in both groups were collected at baseline and at completion of intervention (4 weeks). Patients were assessed for pain, fatigue, nausea, vomiting and retching, anxiety and depression. The overall management of the cluster was also assessed based on the patients' self-reported health related quality of life-HRQoL. Chi-square tests (X2), independent T-tests and Linear Mixed Models were calculated.
RESULTS: Patients in the intervention group experienced lower levels of Fatigue (p<0.0.0225), and Pain (p = 0.0003) compared to those in the control group and experienced better HRQoL (p<0.0001) [PRE-POST:
INTERVENTION: Pain 4.2(2.5) - 2.5(1.6), Fatigue 27.6(4.1) - 19.3(4.1), HRQoL 54.9(22.7) - 64.5(23), CONTROL: Pain 3.5(1.7) - 4.8(1.5), Fatigue 28.7(4.1) - 32.5(3.8), HRQoL 51.9(22.3)- 41.2(24.1)]. Nausea, vomiting and retching occurred significantly less often in the intervention group [pre-post: 25.4(5.9)- 20.6(5.6) compared to the control group (17.8(6.5)- 22.7(5.3) (F = 58.50 p<0.0001). More patients in the control group (pre:n = 33-post:n = 47) were found to be moderately depressed compared to those in the intervention group (pre:n = 35-post:n = 15) (X2 = 5.93; p = 0.02).
CONCLUSION: This study provided evidence that the combination of GI and PMR can be effective in the management of a cluster of symptoms in cancer patients receiving chemotherapy. These techniques can complement existing management measures to achieve a comprehensive management of this symptom cluster and increase patients HRQoL.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01275872.

PMID: 27341675 [PubMed - indexed for MEDLINE]

Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients.

PLoS One. 2016;11(5):e0155649

Authors: Schächtele S, Tümena T, Gaßmann KG, Fromm MF, Maas R

Abstract
BACKGROUND: Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited.
OBJECTIVE: This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs.
METHODS: In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs).
RESULTS: Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions.
CONCLUSION: In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk.

PMID: 27192430 [PubMed - indexed for MEDLINE]

Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists.

PLoS One. 2016;11(5):e0155517

Authors: Yu YM, Lee E, Koo BS, Jeong KH, Choi KH, Kang LK, Lee MS, Choi KH, Oh JM, Shin WG

Abstract
PURPOSE: To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge-attitude-practices and the satisfaction of needs.
METHODS: Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis.
RESULTS: In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06-0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46-16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96-6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23-0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as 'not serious ADR' (77.9%), 'already well known ADR' (81.5%), and 'uncertain about causality' (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p<0.05).
CONCLUSIONS: Findings from our study showed around one in three CPs had ADR reporting experience in Korea, while 87.1% had prior experience with ADR cases. The knowledge of SR, prior experience of ADR, and less concern about the obstacles to SR were contributing factors for reporting levels.

PMID: 27192159 [PubMed - indexed for MEDLINE]

Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

Int J Risk Saf Med. 2016 Mar 16;28(1):13-23

Authors: Awodele O, Ibrahim A, Orhii P

Abstract
BACKGROUND: Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank.
OBJECTIVE: Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals.
METHODS: A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17.
RESULTS: Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia.
CONCLUSION: More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

PMID: 27176753 [PubMed - indexed for MEDLINE]

Illuminating drug action by network integration of disease genes: a case study of myocardial infarction.

Mol Biosyst. 2016 Apr 26;12(5):1653-66

Authors: Wang RS, Loscalzo J

Abstract
Drug discovery has produced many successful therapeutic agents; however, most of these drugs were developed without a deep understanding of the system-wide mechanisms of action responsible for their indications. Gene-disease associations produced by molecular and genetic studies of complex diseases provide great opportunities for a system-level understanding of drug activity. In this study, we focused on acute myocardial infarction (MI) and conducted an integrative network analysis to illuminate drug actions. We integrated MI drugs, MI drug interactors, drug targets, and MI disease genes into the human interactome and showed that MI drug targets are significantly proximate to MI disease proteins. We then constructed a bipartite network of MI-related drug targets and MI disease proteins and derived 12 drug-target-disease (DTD) modules. We assessed the biological relevance of these modules and demonstrated the benefits of incorporating disease genes. The results indicate that DTD modules provide insights into the mechanisms of action of MI drugs and the cardiovascular (side) effects of non-MI drugs.

PMID: 27004607 [PubMed - indexed for MEDLINE]

Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.

Lancet Oncol. 2017 Jul 19;:

Authors: Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T

Abstract
BACKGROUND: Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer.
METHODS: In this ongoing, multicentre, open-label, phase 2 trial, we enrolled adults (aged ≥18 years) with histologically confirmed recurrent or metastatic colorectal cancer locally assessed as dMMR/MSI-H from 31 sites (academic centres and hospitals) in eight countries (Australia, Belgium, Canada, France, Ireland, Italy, Spain, and the USA). Eligible patients had progressed on or after, or been intolerant of, at least one previous line of treatment, including a fluoropyrimidine and oxaliplatin or irinotecan. Patients were given 3 mg/kg nivolumab every 2 weeks until disease progression, death, unacceptable toxic effects, or withdrawal from study. The primary endpoint was investigator-assessed objective response as per Response Evaluation Criteria in Solid Tumors (version 1.1). All patients who received at least one dose of study drug were included in all analyses. This trial is registered with ClinicalTrials.gov, number NCT02060188.
FINDINGS: Of the 74 patients who were enrolled between March 12, 2014, and March 16, 2016, 40 (54%) had received three or more previous treatments. At a median follow-up of 12·0 months (IQR 8·6-18·0), 23 (31·1%, 95% CI 20·8-42·9) of 74 patients achieved an investigator-assessed objective response and 51 (69%, 57-79) patients had disease control for 12 weeks or longer. Median duration of response was not yet reached; all responders were alive, and eight had responses lasting 12 months or longer (event rate 86%, 95% CI 62-95). The most common grade 3 or 4 drug-related adverse events were increased concentrations of lipase (six [8%]) and amylase (two [3%]). 23 (31%) patients died during the study; none of these deaths were deemed to be treatment related by the investigator.
INTERPRETATION: Nivolumab provided durable responses and disease control in pre-treated patients with dMMR/MSI-H metastatic colorectal cancer, and could be a new treatment option for these patients.
FUNDING: Bristol-Myers Squibb.

PMID: 28734759 [PubMed - as supplied by publisher]

Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets.

Sci Rep. 2017 Jul 20;7(1):5962

Authors: Jia X, Jin Q, Liu X, Bian X, Wang Y, Liu L, Ma H, Tan F, Gu M, Chen X

Abstract
Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene sets, while studies about regulatory relationships of TFs, miRNAs and biological processes are very rare. Discovering the complex regulating relations among TFs, gene sets and miRNAs will be helpful for researchers to get a more comprehensive understanding about the mechanism of side reaction. In this study, a framework was proposed to construct the relationship network of gene sets, miRNAs and TFs involved in side effects. Through the construction of this network, the potential complex regulatory relationship in the occurrence process of the side effects was reproduced. The SE-gene set network was employed to characterize the significant regulatory SE-gene set interaction and molecular basis of accompanied side effects. A total of 117 side effects complex modules including four types of regulating patterns were obtained from the SE-gene sets-miRNA/TF complex regulatory network. In addition, two cases were used to validate the complex regulatory modules which could more comprehensively interpret occurrence mechanism of side effects.

PMID: 28729650 [PubMed - in process]

Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study.

Lancet HIV. 2017 Jul 17;:

Authors: Orrell C, Hagins DP, Belonosova E, Porteiro N, Walmsley S, Falcó V, Man CY, Aylott A, Buchanan AM, Wynne B, Vavro C, Aboud M, Smith KY, ARIA study team

Abstract
BACKGROUND: Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1.
METHODS: The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of -12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402.
FINDINGS: Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1-17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor-associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications.
INTERPRETATION: The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women.
FUNDING: ViiV Healthcare.

PMID: 28729158 [PubMed - as supplied by publisher]

Using QR codes to enable quick access to information in acute cancer care.

Br J Nurs. 2017 May 25;26(10):S4-S12

Authors: Upton J, Olsson-Brown A, Marshall E, Sacco J

Abstract
Quick access to toxicity management information ensures timely access to steroids/immunosuppressive treatment for cancer patients experiencing immune-related adverse events, thus reducing length of hospital stays or avoiding hospital admission entirely. This article discusses a project to add a QR (quick response) code to a patient-held immunotherapy alert card. As QR code generation is free and the immunotherapy clinical management algorithms were already publicly available through the trust's clinical network website, the costs of integrating a QR code into the alert card, after printing, were low, while the potential benefits are numerous. Patient-held alert cards are widely used for patients receiving anti-cancer treatment, and this established standard of care has been modified to enable rapid access of information through the incorporation of a QR code.

PMID: 28541108 [PubMed - indexed for MEDLINE]

Pharmacy Educators' Knowledge of Medication Safety and Their Perception Toward Its Integration into the Doctor of Pharmacy Curriculum in Saudi Arabia.

Am J Pharm Educ. 2017 Mar 25;81(2):30

Authors: Alkatheri AM, Bustami R, Albekairy AM, Almodaimegh H, Alghamdi S, Alharbi S, Khalidi N, Murphy JE, Qandil AM

Abstract
Objective. To assess pharmacy educators' knowledge of medication safety and their perception toward its integration into the PharmD curriculum in Saudi Arabia. Methods. A survey was administered to pharmacy educators at a college of pharmacy and its affiliate hospital. Knowledge, training, and perception toward integrating medication safety into the PharmD curriculum were evaluated. Results. More than 50% of respondents indicated that medication safety should be covered within selected courses, and 65% indicated that such courses should be mandatory. Pharmacy practice educators had significantly higher levels of knowledge about medication safety than their nonpractice counterparts. Perceptions toward medication safety integration into the curriculum varied significantly by general discipline, academic degree, years of experience, and gender. Conclusion. Pharmacy educators in Saudi Arabia understand the importance of medication safety and its integration into the curriculum. Further studies are needed to guide curricular change to achieve this integration.

PMID: 28381890 [PubMed - indexed for MEDLINE]

Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report.

Indian J Med Res. 2016 Nov;144(5):672-681

Authors: Pai SA, Kshirsagar NA

Abstract
BACKGROUND & OBJECTIVES: With pioglitazone ban and subsequent revoking in India along with varying regulatory decisions in other countries, it was decided to carry out a systematic review on its safety, efficacy and drug utilization in patients with type 2 diabetes mellitus (T2DM) in India and compare with the data from the European Medicines Agency Assessment Report (EMA-AR).
METHODS: Systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching Medline/PubMed, Google Scholar and Science Direct databases using 'pioglitazone AND India AND human' and 'pioglitazone AND India AND human AND patient' and compared with EMA-AR. Spontaneous reports in World Health Organization VigiBase from India were compared with VigiBase data from other countries.
RESULTS: Sixty six publications, 26 (efficacy), 32 (drug utilization) and eight (safety), were retrieved. In India, pioglitazone was used at 15-30 mg/day mostly with metformin and sulphonylurea, being prescribed to 26.7 and 8.4 per cent patients in north and south, respectively. The efficacy in clinical trials (CTs) was similar to those in EMA-AR. Incidence of bladder cancer in pioglitazone exposed and non-exposed patients was not significantly different in an Indian retrospective cohort study. There were two cases and a series of eight cases of bladder cancer published but none reported in VigiBase.
INTERPRETATION & CONCLUSIONS: In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

PMID: 28361819 [PubMed - indexed for MEDLINE]

Type 1 diabetes mellitus caused by treatment with low-dose interferon-α in a melanoma patient.

Melanoma Res. 2017 Jul 19;:

Authors: Sossau D, Kofler L, Eigentler T

Abstract
Interferon-α (INF-α) is used as an adjuvant treatment for high-risk cutaneous melanoma. It has a large variety of potentially severe and irreversible side effects and can contribute toward the development of autoimmune disease. We report a case of a 59-year-old woman who developed type 1 diabetes following the use of low-dose IFN-α for the adjuvant treatment of stage IIB melanoma. Fifteen months after initiating IFN-α, she presented with blood glucose of 1126 mg/dl, hyponatremia, and microalbuminuria. Antibodies to glutamic acid decarboxylase and islet antigen-2 were negative and C-peptide was markedly reduced. There was no personal or family history of any autoimmune conditions. Reinforced insulin treatment and volume substitution with saline and glucose as a counter-regulation was started. To the best of our knowledge, this is the first reported case of low-dose IFN-α-induced type 1 diabetes. Clinicians should closely evaluate the pros and cons of IFN-α treatment in an adjuvant setting and remain mindful of the possibility of drug-induced autoimmune disease.

PMID: 28727675 [PubMed - as supplied by publisher]

Epidural steroid injection-related events requiring hospitalisation or emergency room visits among 52,935 procedures performed at a single centre.

Eur Radiol. 2017 Jul 19;:

Authors: Lee JW, Lee E, Lee GY, Kang Y, Ahn JM, Kang HS

Abstract
OBJECTIVES: To analyse the incidence and type of epidural steroid injection (ESI)-related adverse events, including procedure-related complications and drug-related systemic effects requiring hospitalisation or emergency room (ER) visits.
METHODS: This study included 52,935 ESI procedures performed in 22,059 patients in our department from March 2004 to February 2016. Of these, we retrospectively reviewed the cases of 1570 patients (1713 procedures) who were hospitalised or visited the ER within 1 month after ESI. ESI-related events were classified as procedure-related complications, drug-related systemic effects, or of uncertain relationship. Descriptive data are provided; no statistical analysis was performed.
RESULTS: There were 244 ESI-related events in 235 patients (males:females = 102:133; mean age: 65.7 years; range: 20-93 years). The incidence of ESI-related events was 0.46% per procedure, including 14 procedure-related complications, 56 drug-related systemic effects, and 174 events of uncertain cause. Of the 52,935 patients, 6 (0.011%) experienced major complications (two spine haematomas and four infections), 1 patient died, and 1 experienced neurological sequelae.
CONCLUSIONS: Although major procedure-related complications and drug-related systemic effects of ESI requiring hospitalisation are very rare, infection and haematoma can occur, resulting in serious outcomes. Hence, ESI should be carefully considered in high-risk patients.
KEY POINTS: • The incidence of ESI-related events requiring hospitalisation was 0.46%. • The incidence of procedure-related complications was 0.026%. • The incidence of drug-related systemic effects was 0.11%. • The incidence of major complication of ESI was 0.011%. • The major complications were spine infection, haematoma, and sepsis.

PMID: 28726118 [PubMed - as supplied by publisher]

Medication Literacy in a Cohort of Chinese Patients Discharged with Acute Coronary Syndrome.

Int J Environ Res Public Health. 2016 Jul 15;13(7):

Authors: Zhong Z, Zheng F, Guo Y, Luo A

Abstract
This study aims at investigating medication literacy of discharged patients with acute coronary syndrome (ACS) in China, and the important determinants of medication literacy among them. For this purpose, we conducted a prospective cohort study. Patient's demographic and clinical data were retrieved from hospital charts and medication literacy was measured by instructed interview using the Chinese version of Medication Literacy Questionnaire on Discharged Patient between 7 and 30 days after the patient was discharged from the hospital. The results show that medication literacy for the surveyed patients was insufficient: >20% did not have adequate knowledge on the types of drugs and the frequency that they need to take the drugs, >30% did not know the name of and the dosage of the drugs they are taking, and >70% did not have adequate knowledge on the effects and side effects of the drugs they are taking. Our research indicated that medication literacy scores decreased with age but increased with education. The number of medicines the discharged patient took with them and days between discharge and interview were not associated with medication literacy levels.

PMID: 27428990 [PubMed - indexed for MEDLINE]

[Decision aids in complex polypharmacy : Medication data bases and counselling by clinical pharmacists].

Z Gerontol Geriatr. 2017 Jul 18;:

Authors: Weinrebe W, Preda R, Bischoff S, Nussbickel D, Humm M, Jeckelmann K, Goetz S

Abstract
The number of older people with polypharmacy (more than six drugs taken simultaneously) is increasing. The greatest proportion consists of guideline drugs, analgesics and psychopharmaceuticals because in many cases of geriatric multimorbidity several underlying main diseases are present which must be treated according to the guidelines. Polypharmacy is a complex and difficult situation for all treating physicians because substantial side effects and intoxication can be induced but it can also be very difficult to recognize which drug was at fault and how a reduction can be safely made. This article describes the exemplary case of a 77-year-old patient with drug-induced delirium and demonstrates the procedure followed. The question of rapid assistance by the utilization of medication data bases is described and the importance of clinical pharmacists is demonstrated. In the future working with medication data bases will possibly become increasingly more important for physicians and hopefully simpler. The case presented here also shows that the effective and justified reduction of drugs can show a very good effect and is possible.

PMID: 28721543 [PubMed - as supplied by publisher]

The efficacy and safety of sugammadex for reversing postoperative residual neuromuscular blockade in pediatric patients: A systematic review.

Sci Rep. 2017 Jul 18;7(1):5724

Authors: Liu G, Wang R, Yan Y, Fan L, Xue J, Wang T

Abstract
The aim of this study is to evaluate the efficacy and safety of sugammadex for reversing neuromuscular blockade in pediatric patients. MEDLINE and other three Databases were searched. Randomized clinical trials were included if they compared sugammadex with neostigmine or placebo in pediatric patients undergoing surgery involving the use of rocuronium or vecuronium. The primary outcome was the time interval from administration of reversal agents to train-of-four ratio (TOFr, T4/T1) > 0.9. Incidences of any drug-related adverse events were secondary outcomes. Trial inclusion, data extraction, and risk of bias assessment were performed independently. Mean difference and relative risk were used as summary statistics with random effects models. Statistical heterogeneity was assessed by the I(2) statistic. Funnel plot was used to detect publication bias. Ten studies with 580 participants were included. Although considerable heterogeneity (I(2) = 98.5%) was detected in primary outcome, the results suggested that, compared with placebo or neostigmine, sugammadex can reverse rocuronium-induced neuromuscular blockade more rapidly with lower incidence of bradycardia. No significant differences were found in the incidences of other adverse events. Compared with neostigmine or placebo, sugammadex may reverse rocuronium-induced neuromuscular blockade in pediatric patients rapidly and safely.

PMID: 28720838 [PubMed - in process]

Using constrained information entropy to detect rare adverse drug reactions from medical forums.

Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:2460-2463

Authors: Yi Zheng, Chaowang Lan, Hui Peng, Jinyan Li

Abstract
Adverse drug reactions (ADRs) detection is critical to avoid malpractices yet challenging due to its uncertainty in pre-marketing review and the underreporting in post-marketing surveillance. To conquer this predicament, social media based ADRs detection methods have been proposed recently. However, existing researches are mostly co-occurrence based methods and face several issues, in particularly, leaving out the rare ADRs and unable to distinguish irrelevant ADRs. In this work, we introduce a constrained information entropy (CIE) method to solve these problems. CIE first recognizes the drug-related adverse reactions using a predefined keyword dictionary and then captures high- and low-frequency (rare) ADRs by information entropy. Extensive experiments on medical forums dataset demonstrate that CIE outperforms the state-of-the-art co-occurrence based methods, especially in rare ADRs detection.

PMID: 28268822 [PubMed - indexed for MEDLINE]

Henoch-Schönlein purpura and drug and vaccine use in childhood: a case-control study.

Ital J Pediatr. 2016 Jun 18;42(1):60

Authors: Da Dalt L, Zerbinati C, Strafella MS, Renna S, Riceputi L, Di Pietro P, Barabino P, Scanferla S, Raucci U, Mores N, Compagnone A, Da Cas R, Menniti-Ippolito F, Italian Multicenter Study Group for Drug and Vaccine Safety in Children

Abstract
BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood; nevertheless, its etiology and pathogenesis remain unknown despite the fact that a variety of factors, mainly infectious agents, drugs and vaccines have been suggested as triggers for the disease. The aim of this study was to estimate the association of HSP with drug and vaccine administration in a pediatric population.
METHODS: An active surveillance on drug and vaccine safety in children is ongoing in 11 clinical centers in Italy. All children hospitalized through the local Paediatric Emergency Department for selected acute clinical conditions of interest were enrolled in the study. Data on drug and vaccine use in children before the onset of symptoms leading to hospitalization were collected by parents interview. A case-control design was applied for risk estimates: exposure in children with HSP, included as cases, was compared with similar exposure in children with gastroduodenal lesions, enrolled as controls. HSP cases were validated according to EULAR/PRINTO/PRES criteria. Validation was conducted retrieving data from individual patient clinical record.
RESULTS: During the study period (November 1999-April 2013), 288 cases and 617 controls were included. No increased risk of HSP was estimated for any drug. Among vaccines, measles-mumps-rubella (MMR) vaccine showed an increased risk of HSP (OR 3.4; 95 % CI 1.2-10.0).
CONCLUSIONS: This study provides further evidence on the possible role of MMR vaccine in HSP occurrence.

PMID: 27316345 [PubMed - indexed for MEDLINE]