The application of the Global Trigger Tool: a systematic review.

Int J Qual Health Care. 2016 Dec 01;28(6):640-649

Authors: Hibbert PD, Molloy CJ, Hooper TD, Wiles LK, Runciman WB, Lachman P, Muething SE, Braithwaite J

Abstract
Purpose: This study describes the use of, and modifications and additions made to, the Global Trigger Tool (GTT) since its first release in 2003, and summarizes its findings with respect to counting and characterizing adverse events (AEs).
Data sources: Peer-reviewed literature up to 31st December 2014.
Study selection: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
Data extraction: Two authors extracted and compiled the demographics, methodologies and results of the selected studies.
Results of data synthesis: Of the 48 studies meeting the eligibility criteria, 44 collected data from inpatient medical records and four from general practice records. Studies were undertaken in 16 countries. Over half did not follow the standard GTT protocol regarding the number of reviewers used. 'Acts of omission' were included in one quarter of studies. Incident reporting detected between 2% and 8% of AEs that were detected with the GTT. Rates of AEs varied in general inpatient studies between 7% and 40%. Infections, problems with surgical procedures and medication were the most common incident types.
Conclusion: The GTT is a flexible tool used in a range of settings with varied applications. Substantial differences in AE rates were evident across studies, most likely associated with methodological differences and disparate reviewer interpretations. AE rates should not be compared between institutions or studies. Recommendations include adding 'omission' AEs, using preventability scores for priority setting, and re-framing the GTT's purpose to understand and characterize AEs rather than just counting them.

PMID: 27664822 [PubMed - indexed for MEDLINE]

Evaluation of the types and frequency of drug-related problems and the association with gender in patients with chronic diseases attending a primary health care center in Jordan.

Int Health. 2016 Nov;8(6):423-426

Authors: Al-Azzam SI, Alzoubi KH, Alefan Q, Alzayadeen RN

Abstract
BACKGROUND: Drug-related problems (DRPs) can be defined as any event that is drug related that results in harm or in providing less than optimum medical care to patients. The aim of this study is to determine the types and frequency of each type of DRP in selected outpatient settings in Jordan, with emphasis on gender as a grouping variable.
METHODS: This study was a non-randomized controlled trial, carried out over 3 days, at Alsarih Medical Health Center in the north of Jordan. Clinical pharmacists conducting the research interviewed a randomly selected population, assessed their DRPs, proposed appropriate clinical interventions to physicians and provided appropriate patient counseling.
RESULTS: The study included a total of 258 patients (mean age 54.4±12.1; male ratio 37.6%). The most frequently encountered DRPs in our study were patients' need for counseling and education (83.8%), and life style modifications (80%). This study also revealed that 71.8% of patients required additional and/or more frequent monitoring, and 53% of patients had untreated conditions that required pharmacological and/or non-pharmacological interventions. Gender did not affect the frequency of DRPs among patients.
CONCLUSION: Certain types of DRPs are the most common among outpatient settings. Therefore, measures should be taken to specifically tackle these types of DRPs.

PMID: 27554614 [PubMed - indexed for MEDLINE]

Effect of administration timing of postchemotherapy granulocyte colony-stimulating factor on host-immune cell recovery and CD8(+) T-cell response.

J Immunotoxicol. 2016 Nov;13(6):784-792

Authors: Salem ML, Nassef M, Abdel Salam SG, Zidan A, Mahmoud MH, Badr G, Rubinstein M, Cole D

Abstract
Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a standard supportive therapy given during cancer treatment. It induces acceleration in neutrophil recovery through stimulation of mobilization of hematopoietic progenitors. Given that the latter is also induced by chemotherapy itself, the timing of administration of G-CSF postchemotherapy might impact the resultant overall effects. The present study aimed to determine the optimal timing of G-CSF postchemotherapy to exert its optimal effects on the immune cell recovery and its impact on antigen-specific CD8(+) T-cell response. B6 mice were treated once with cyclophosphamide (4 mg/mouse; CTX) and then daily with G-CSF (5 g/mouse) from Days 1-5, 2-5 or 5-9 post-CTX treatment. The total numbers of various immune cell types were analyzed on Days 7, 9 and 12 post-CTX treatment. To evaluate effects on CD8(+) T-cell response, a pmel-1 transgenic mouse model was used in combination with prime boost peptide vaccination therapy. The total number of white blood cells (WBC), neutrophils, monocytes, lymphocytes, granulocytes and dendritic cells (DC) were significantly increased after G-CSF treatment in particular when G-CSF was administered from Days 2-5 post-CTX treatment. Application of this timing of G-CSF and CTX treatment after adoptive transfer of T-cells followed by prime-boost vaccination with antigenic peptide did not block the expansion of the donor pmel-1 CD8(+) T-cells. In conclusion, adjusting the timing of treatment with G-CSF postchemotherapy can optimize its promoting effects on recovery of myeloid cells without altering the associated antigen-specific immunity.

PMID: 27417188 [PubMed - indexed for MEDLINE]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/09/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/09/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Correlation among ocular surface disease, xerostomia, and nasal symptoms in patients with differentiated thyroid carcinoma subjected to radioiodine therapy: A prospective comparative study.

Head Neck. 2017 Sep 25;:

Authors: da Fonseca FL, Yamanaka PK, Mazoti L, Arakawa-Sugueno L, Kato JM, Matayoshi S

Abstract
BACKGROUND: Some complications of radioiodine therapy have been reported, but the involvement of the eyes and adnexa is rarely discussed. The purpose of this study was to determine the correlation among ocular surface changes, xerostomia, and changes in the nasal mucosa associated with radioiodine therapy.
METHODS: Patients subjected to radioiodine therapy (group 1) or not subjected (group 2) were prospectively evaluated by examinations of the ocular surface and tear film, saliva production, and nasal endoscopy. Ocular and nasal symptoms and xerostomia were evaluated using questionnaires.
RESULTS: Evaluation of the ocular surface did not indicate significant differences between the groups. Nasal endoscopy revealed higher mucosal pallor in group 1 and worsening of the endoscopic appearance. Worsening of ocular symptoms and nasal symptoms, xerostomia, and a significant decrease in salivary production was also observed in group 1.
CONCLUSION: Subjective worsening of xerostomia, xerophthalmia, nasal symptoms, and changes in the nasal mucosa in group 1 was observed.

PMID: 28945293 [PubMed - as supplied by publisher]

Thromboembolic adverse event study of combined estrogen-progestin preparations using Japanese Adverse Drug Event Report database.

PLoS One. 2017;12(7):e0182045

Authors: Hasegawa S, Matsui T, Hane Y, Abe J, Hatahira H, Motooka Y, Sasaoka S, Fukuda A, Naganuma M, Hirade K, Takahashi Y, Kinosada Y, Nakamura M

Abstract
Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3-71.4), 29.1 (23.5-35.9), 42.9 (32.3-57.0), 44.7 (32.7-61.1), and 38.6 (26.3-56.7), respectively. The medians (25%-75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3-314.0), 128.0 (27.0-279.0), 204.0 (44.0-660.0), 142.0 (41.3-344.0), and 16.5 (8.8-32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning.

PMID: 28732067 [PubMed - indexed for MEDLINE]

Long-term follow-up of chemoimmunotherapy with rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma: Results of a study of the Mayo Clinic Cancer Center Research Consortium (MCCRC) MC0485 now known as academic and community cancer research united (ACCRU).

Am J Hematol. 2017 Oct;92(10):1004-1010

Authors: Witzig TE, Johnston PB, LaPlant BR, Kurtin PJ, Pederson LD, Moore DF, Nabbout NH, Nikcevich DA, Rowland KM, Grothey A

Abstract
Patients with relapsed aggressive non-Hodgkin lymphoma (NHL) are often treated with platinum-based chemoimmunotherapy regimens in preparation for autologous stem cell transplant. We sought to reduce toxicity and maintain efficacy by using oxaliplatin with rituximab, cytarabine and dexamethasone (ROAD) in a phase II clinical trial in patients who had relapsed after one prior regimen. ROAD was delivered q21 days and consisted of rituximab 375 mg/m(2) IV weekly x 4 doses (cycle 1 only); dexamethasone 40 mg PO/IV d2 - 5; oxaliplatin 130 mg/m(2) IV day 2; cytarabine 2000 mg/m(2) IV × two doses on days 2 to 3; and pegfilgrastim 6 mg SC on day 4. Forty-five eligible patients were accrued between 2006 and 2008. Patient characteristics were a median age of 69 years; 96% had received prior rituximab; 53% were within one year of diagnosis. The median number of cycles received was 2 (range, 1-6). Forty-four % received ROAD as an outpatient. The overall response rate was 71% with 27% (12/45) CR and 44% (20/45) PR. Forty-four % (20/45) of all patients and 69% (18/26) of patients whom responded after 2 cycles proceeded to transplant. Median overall survival was 26 mos (95% CI: 7.3 mos-not reached) and median progression-free survival was 11 mos (95% CI: 6-104 mos). There was no grade 3/4 nephrotoxicity; the rate of grade 3/4 neuropathy was 4%. Forty-two percent of all patients and 69% of patients transplanted remain alive at 5 years. ROAD represents an acceptable salvage therapeutic option for patients with relapsed aggressive NHL.

PMID: 28614905 [PubMed - indexed for MEDLINE]

Impact of comorbidities on outcomes of elderly patients with diffuse large B-cell lymphoma.

Am J Hematol. 2017 Oct;92(10):989-996

Authors: Saygin C, Jia X, Hill B, Dean R, Pohlman B, Smith MR, Jagadeesh D

Abstract
International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II-IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment.

PMID: 28612386 [PubMed - indexed for MEDLINE]

Association of Adverse Events With Antibiotic Use in Hospitalized Patients.

JAMA Intern Med. 2017 Sep 01;177(9):1308-1315

Authors: Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE

Abstract
Importance: Estimates of the incidence of overall antibiotic-associated adverse drug events (ADEs) in hospitalized patients are generally unavailable.
Objective: To describe the incidence of antibiotic-associated ADEs for adult inpatients receiving systemic antibiotic therapy.
Design, Setting, and Participants: Retrospective cohort of adult inpatients admitted to general medicine wards at an academic medical center.
Exposures: At least 24 hours of any parenteral or oral antibiotic therapy.
Main Outcomes and Measures: Medical records of 1488 patients were examined for 30 days after antibiotic initiation for the development of the following antibiotic-associated ADEs: gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic; and 90 days for the development of Clostridium difficile infection or incident multidrug-resistant organism infection, based on adjudication by 2 infectious diseases trained clinicians.
Results: In 1488 patients, the median age was 59 years (interquartile range, 49-69 years), and 758 (51%) participants were female. A total of 298 (20%) patients experienced at least 1 antibiotic-associated ADE. Furthermore, 56 (20%) non-clinically indicated antibiotic regimens were associated with an ADE, including 7 cases of C difficile infection. Every additional 10 days of antibiotic therapy conferred a 3% increased risk of an ADE. The most common ADEs were gastrointestinal, renal, and hematologic abnormalities, accounting for 78 (42%), 45 (24%), and 28 (15%) 30-day ADEs, respectively. Notable differences were identified between the incidence of ADEs associated with specific antibiotics.
Conclusions and Relevance: Although antibiotics may play a critical role when used appropriately, our findings underscore the importance of judicious antibiotic prescribing to reduce the harm that can result from antibiotic-associated ADEs.

PMID: 28604925 [PubMed - indexed for MEDLINE]

Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer.

Expert Opin Pharmacother. 2017 Jun;18(8):825-832

Authors: Clinton TN, Woldu SL, Raj GV

Abstract
INTRODUCTION: Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing hormone-releasing hormone (LHRH) agonist, and more recently, gonadotropin releasing hormone (GnRH) antagonist therapy. Our understanding of the mechanisms and adverse effects of ADT has increased substantially, including the class-specific adverse effects of ADT. Areas covered: This review will summarize the pharmacodynamic and pharmacokinetic properties of the GnRH antagonist degarelix and its role in the management of advanced prostate cancer, the clinical evidence supporting its regulatory approval, as well as potential benefits and disadvantages over traditional LHRH agonist therapy. Expert opinion: Degarelix represents a newer class of ADT that results in a rapid and reliable decline in serum testosterone, a quality that makes it particularly advantageous in men presenting with symptomatic, hormone-sensitive prostate cancer. Due to differences in mechanism of action, there is observational data suggesting a potential cardiovascular and even oncologic benefit over traditional LHRH agonist therapy. Further research is ongoing to more clearly define this potential benefit.

PMID: 28480768 [PubMed - indexed for MEDLINE]

PDC-SGB: Prediction of effective drug combinations using a stochastic gradient boosting algorithm.

J Theor Biol. 2017 Mar 21;417:1-7

Authors: Xu Q, Xiong Y, Dai H, Kumari KM, Xu Q, Ou HY, Wei DQ

Abstract
Combinatorial therapy is a promising strategy for combating complex diseases by improving the efficacy and reducing the side effects. To facilitate the identification of drug combinations in pharmacology, we proposed a new computational model, termed PDC-SGB, to predict effective drug combinations by integrating biological, chemical and pharmacological information based on a stochastic gradient boosting algorithm. To begin with, a set of 352 golden positive samples were collected from the public drug combination database. Then, a set of 732 dimensional feature vector involving biological, chemical and pharmaceutical information was constructed for each drug combination to describe its properties. To avoid overfitting, the maximum relevance & minimum redundancy (mRMR) method was performed to extract useful ones by removing redundant subsets. Based on the selected features, the three different type of classification algorithms were employed to build the drug combination prediction models. Our results demonstrated that the model based on the stochastic gradient boosting algorithm yield out the best performance. Furthermore, it is indicated that the feature patterns of therapy had powerful ability to discriminate effective drug combinations from non-effective ones. By analyzing various features, it is shown that the enriched features occurred frequently in golden positive samples can help predict novel drug combinations.

PMID: 28099868 [PubMed - indexed for MEDLINE]

Blocking sense-strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA.

EMBO Mol Med. 2016 09;8(9):1082-98

Authors: Michler T, Große S, Mockenhaupt S, Röder N, Stückler F, Knapp B, Ko C, Heikenwalder M, Protzer U, Grimm D

Abstract
Hepatitis B virus (HBV) is a promising target for therapies based on RNA interference (RNAi) since it replicates via RNA transcripts that are vulnerable to RNAi silencing. Clinical translation of RNAi technology, however, requires improvements in potency, specificity and safety. To this end, we systematically compared different strategies to express anti-HBV short hairpin RNA (shRNA) in a pre-clinical immunocompetent hepatitis B mouse model. Using recombinant Adeno-associated virus (AAV) 8 vectors for delivery, we either (i) embedded the shRNA in an artificial mi(cro)RNA under a liver-specific promoter; (ii) co-expressed Argonaute-2, a rate-limiting cellular factor whose saturation with excess RNAi triggers can be toxic; or (iii) co-delivered a decoy ("TuD") directed against the shRNA sense strand to curb off-target gene regulation. Remarkably, all three strategies minimised adverse side effects as compared to a conventional shRNA vector that caused weight loss, liver damage and dysregulation of > 100 hepatic genes. Importantly, the novel AAV8 vector co-expressing anti-HBV shRNA and TuD outperformed all other strategies regarding efficiency and persistence of HBV knock-down, thus showing substantial promise for clinical translation.

PMID: 27473329 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/09/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The importance of pharmacoepidemiology in pregnancy-implications for safety.

Expert Opin Drug Saf. 2017 Oct;16(10):1181-1190

Authors: Benevent J, Montastruc F, Damase-Michel C

Abstract
INTRODUCTION: Prescription of medications to pregnant women is usually a challenge as the drug benefit has to be considered regarding its potential adverse effects. As medication use is common in pregnant women, by chance or necessity, it gives the opportunity to evaluate the consequences of prenatal drug exposure in real life through pharmacoepidemiologic studies. Area covered: Data sources are numerous. Some of them have been created for the particular purpose of assessing medications during pregnancy. Augmented databases enable the study of delayed effects in late childhood and provide information on potential confounders. Each data source exhibits strengths and weaknesses. Several designs can be used to assess the safety of medications during pregnancy. Innovative designs have been developed in order to bypass major limits of classical methods. Expert opinion: An efficient system could follow up each pregnant woman, who had taken a medication, and consider her as a precious information for the knowledge of drug potential adverse actions against the child, who must be followed up to identify long term-effects. The diversity of data sources and approaches of pharmacoepidemiologic studies, the implementation of international networks as well as the improvement of adverse signal detection are the keystones of such an evaluation.

PMID: 28777918 [PubMed - indexed for MEDLINE]

Exploring the potential for using drug indications to prevent look-alike and sound-alike drug errors.

Expert Opin Drug Saf. 2017 Oct;16(10):1103-1109

Authors: Seoane-Vazquez E, Rodriguez-Monguio R, Alqahtani S, Schiff G

Abstract
BACKGROUND: Look-alike, sound-alike (LASA) drug names are a cause of medication errors with resulting patient harm and healthcare costs. This study assessed to which extent the use of the generic drug name, therapeutic class, health problem, and the U.S. Food and Drug Administration (FDA)-approved indications might be used to differentiate LASA drug pairs.
RESEARCH DESIGN AND METHODS: We collected information about LASA drug pairs reported by the FDA to have look-alike sound-alike similarities. To assess potential for differentiating LASA drug pairs, we compared the following drug characteristics: generic name, therapeutic class, health problem, and FDA-approved indication.
RESULTS: For the 33 FDA reported LASA drug pairs we identified a total of 432 FDA-approved indications. Using the generic name, therapeutic class, health problem and drug indication we were able to differentiate 8 (24.2%), 24 (72.7%), 25 (75.8%) and 26 (78.8%), respectively of the 33 LASA drug pairs. Using the generic name, therapeutic class, and health problem we were able to distinguish 31 (7.2%), 212 (49.1%), and 269 (62.3%), respectively of the 432 FDA-approved indications for the LASA drug pairs.
CONCLUSIONS: Including the FDA-approved indication in the drug prescription may be used to differentiate LASA drug pairs and thus, prevent wrong drug medication errors.

PMID: 28724335 [PubMed - indexed for MEDLINE]

Adverse drug events-Analysis of a decade. A Portuguese case-study, from 2004 to 2013 using hospital database.

PLoS One. 2017;12(6):e0178626

Authors: Scripcaru G, Mateus C, Nunes C

Abstract
PURPOSE: The goal of this study was to characterise adverse drug events (ADE), including both adverse drug reaction (ADR) and accidental poisoning by drugs (AP), considering age, gender, length of stay (LOS), number of deaths and year, during the period 2004-2013. Additionally distributions of the ten's most frequent ADR and AP were characterized, considering age-group and gender.
METHODS: A retrospective descriptive nationwide study was conducted, based on the hospital discharges database in Portugal from 2004 to 2013, using ICD-9. Events were identified based on the following codes: from E930 to E949.9 and from E850 to E858.9.
RESULTS: A total of 9 320 076 patients were discharged within this period, with 133 688 patients (1.46%) having at least one ADE, 4% of them related with AP. The mean age of these patients was 63.79 years (SD 21.31), 54.50% were female and the mean LOS was 14.05 days (SD 22.19). Patient with AP had a mean age of 41.06 years (SD 34.05), 54.70% were female and LOS was 7.15 days (SD 19.42). We have identified 10.691 deaths that represent 8.00% from the total of patients with an ADE. The patients above 65 years were more affected by ADR and children below 18 were more affected by AP.
CONCLUSION: In the last decade an increasing trend of ADR were observed and an AP pattern relatively stable. Elderly people and children were the age groups most affected. Antibiotics (in ADR) and benzodiazepine-based tranquilizers (in AP) were the major problems. This is a huge, increasing and challenging problem. Further research, using individual and contextual risk factors should be developed to understand spatiotemporal variability, promoting tailored interventions, within and across countries.

PMID: 28575013 [PubMed - indexed for MEDLINE]

Assays for Infliximab Drug Levels and Antibodies: A Matter of Scales and Categories.

Scand J Immunol. 2017 Sep;86(3):165-170

Authors: Bader LI, Solberg SM, Kaada SH, Bolstad N, Warren DJ, Gavasso S, Gjesdal CG, Vedeler CA

Abstract
Immunogenicity is a frequent cause of secondary non-response to tumour necrosis factor (TNF) inhibitors. Drug level measurement and detection of antidrug antibodies have been shown to be cost effective and clinically relevant, and a large number of assays are available for these purposes. It is, however, difficult to compare assays and translate results into clinical meaningful information due to different methodological approaches and a lack of assay standardization. We have analysed infliximab drug levels and antidrug antibodies in 107 patient samples using enzyme-linked immunoassays (ELISA), immunofluorometric assays (IFMA) and reporter-gene assays (RGA). The RGA gave the lowest results for drug levels, whereas the IFMA detected the highest number of antidrug antibody positive sera. Applying individualized therapeutic ranges to each assay resulted in agreement among all three assays in 74% of samples for drug levels and 98% of samples for antidrug antibodies. We found that TNF inhibitor monitoring assays measure on different scales and that the agreement between quantitative results is limited. However, interassay differences can partially be overcome by assay-individualized translations of quantities into categories, which also is necessary for a meaningful clinical application. Our data demonstrate that assays should not be used interchangeably and that direct comparison of quantitative drug levels obtained with different assays should be avoided.

PMID: 28561325 [PubMed - indexed for MEDLINE]

Influence of CYP2C19*2/*17 genotype on adverse drug reactions of voriconazole in patients after allo-HSCT: a four-case report.

J Cancer Res Clin Oncol. 2017 Jun;143(6):1103-1106

Authors: Beata S, Donata UK, Jarosław D, Tomasz W, Anna WH

Abstract
PURPOSE: Voriconazole (VCZ) is a new-generation triazol antifungal agent. CYP2C19 mutations have been reported to cause variability in VCZ pharmacokinetics, and thus lead to undesirable effects of pharmacotherapy. We observed four Caucasian patients who underwent allogenic hematopoietic stem cell transplantation, treated with voriconazole for prevention of fungal infections, to establish the impact of CYP2C19*2/*17 genotype on side effect occurrence.
METHODS: Genetic testing for CYP2C19 allele*2 and*17 was performed using two PCR-RFLP methods established by Goldstein and Blaisdell, and Sim et al. All four patients presented CYP2C19*2/*17 genotype.
RESULTS: The patients suffered from gastrointestinal, dermatological, neurological, hepatobiliary and renal adverse drug reactions (ADR). ADR could be best described by the use of VCZ. Other drugs potentially causing side effects were also taken into consideration. The presented complications were temporary and did not force dosage regimen adjustments or discontinuation of pharmacotherapy. After 2 months, the patients were discharged from hospital.
CONCLUSIONS: Drug-drug interactions and ADR may occur even if an agent is used for prophylaxis only. We, therefore, should use any available tools for pharmacotherapy optimization-also genetic testing.

PMID: 28247033 [PubMed - indexed for MEDLINE]

The Placebo and Nocebo Phenomena: Their Clinical Management and Impact on Treatment Outcomes.

Clin Ther. 2017 Mar;39(3):477-486

Authors: Chavarria V, Vian J, Pereira C, Data-Franco J, Fernandes BS, Berk M, Dodd S

Abstract
PURPOSE: This overview focuses on placebo and nocebo effects in clinical trials and routine care. Our goal was to propose strategies to improve outcomes in clinical practice, maximizing placebo effects and reducing nocebo effects, as well as managing these phenomena in clinical trials.
METHODS: A narrative literature search of PubMed was conducted (January 1980-September 2016). Systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on placebo or nocebo effects in clinical practice were included in the qualitative synthesis. Search terms included: placebo, nocebo, clinical, clinical trial, clinical setting, placebo effect, nocebo effect, adverse effects, and treatment outcomes. This search was augmented by a manual search of the references of the key articles and the related literature.
FINDINGS: Placebo and nocebo effects are psychobiological events imputable to the therapeutic context. Placebo is defined as an inert substance that provokes perceived benefits, whereas the term nocebo is used when an inert substance causes perceived harm. Their major mechanisms are expectancy and classical conditioning. Placebo is used in several fields of medicine, as a diagnostic tool or to reduce drug dosage. Placebo/nocebo effects are difficult to disentangle from the natural course of illness or the actual effects of a new drug in a clinical trial. There are known strategies to enhance clinical results by manipulating expectations and conditioning.
IMPLICATIONS: Placebo and nocebo effects occur frequently and are clinically significant but are underrecognized in clinical practice. Physicians should be able to recognize these phenomena and master tactics on how to manage these effects to enhance the quality of clinical practice.

PMID: 28237673 [PubMed - indexed for MEDLINE]