Drug-Induced Photosensitivity - a Continuing Diagnostic Challenge.

Acta Clin Croat. 2017 Jun;56(2):277-283

Authors: Lugović-Mihić L, Duvančić T, Ferček I, Vuković P, Japundžić I, Ćesić D

Abstract
When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity caused by drugs can appear as phototoxic reactions (which occur more often) or photoallergic reactions (which occur less often and include allergic mechanisms). The following drugs stand out as medications with a high photosensitivity potential: nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular drugs (such as amiodarone), phenothiazines (especially chlorpromazine), retinoids, antibiotics (sulfonamides, tetracyclines, especially demeclocycline and quinolones), etc. In recent years, photosensitive reactions to newer drugs have appeared, e.g., targeted anticancer therapies such as BRAF kinase inhibitors (vemurafenib, dabrafenib), EGFR inhibitors, VEGFR inhibitors, MEK inhibitors, Bcr-Abl tyrosine kinase inhibitors, etc. In patients taking drugs over a longer period of time (e.g., NSAIDs, cardiovascular drugs, etc.), a particular problem arises when an unrecognized drug-induced photosensitivity on the skin manifests in summer months. When taking patient histories, the physician/dermatovenereologist should bear in mind that any drug the patient is currently taking may be the cause of skin reactions. Therefore, patients who use potentially photosensitive drugs and treatments on a long term basis should be warned of the possibility of these side effects on their skin and advised to avoid direct exposure to sunlight and to use adequate photoprotection. If patients carefully protect themselves from the sun, it is often not necessary to stop treatments that include photosensitive drugs. If such reactions appear, anti-inflammatory and antiallergic therapies should be introduced.

PMID: 29485795 [PubMed - in process]

Treatment of Tardive Dyskinesia: A General Overview with Focus on the Vesicular Monoamine Transporter 2 Inhibitors.

Drugs. 2018 Feb 26;:

Authors: Niemann N, Jankovic J

Abstract
Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief. The vesicular monoamine transporter 2 (VMAT2) inhibitors, which include tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with TD. Deutetrabenazine-a deuterated version of tetrabenazine-and valbenazine, the purified parent product of one of the main tetrabenazine metabolites, are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of TD. VMAT2 inhibitors deplete presynaptic dopamine and reduce involuntary movements in many hyperkinetic movement disorders, particularly TD, Huntington disease, and Tourette syndrome. The active metabolites of the VMAT2 inhibitors have high affinity for VMAT2 and minimal off-target binding. Compared with tetrabenazine, deutetrabenazine and valbenazine have pharmacokinetic advantages that translate into less frequent dosing and better tolerability. However, no head-to-head studies have compared the various VMAT2 inhibitors. One of the major advantages of VMAT2 inhibitors over DRBAs, which are still being used by some clinicians in the treatment of some hyperkinetic disorders, including TD, is that they are not associated with the development of TD. We also briefly discuss other treatment options for TD, including amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation. Treatment of TD and other drug-induced movement disorders must be individualized and based on the severity, phenomenology, potential side effects, and other factors discussed in this review.

PMID: 29484607 [PubMed - as supplied by publisher]

Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Eur Arch Otorhinolaryngol. 2017 Jul;274(7):2883-2889

Authors: Rambeau A, Gervais R, De Raucourt D, Babin E, Dugué AE, Florescu C, Blanchard D, Gery B

Abstract
Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

PMID: 28382396 [PubMed - indexed for MEDLINE]

Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis.

Eur Respir J. 2017 Mar;49(3):

Authors: Guglielmetti L, Jaspard M, Le Dû D, Lachâtre M, Marigot-Outtandy D, Bernard C, Veziris N, Robert J, Yazdanpanah Y, Caumes E, Fréchet-Jachym M, French MDR-TB Management Group

Abstract
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.

PMID: 28182570 [PubMed - indexed for MEDLINE]

Can drugs induce or aggravate sleep apneas? A case-noncase study in VigiBase® , the WHO pharmacovigilance database.

Fundam Clin Pharmacol. 2017 Jun;31(3):359-366

Authors: Linselle M, Sommet A, Bondon-Guitton E, Moulis F, Durrieu G, Benevent J, Rousseau V, Chebane L, Bagheri H, Montastruc F, Montastruc JL

Abstract
The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase® , the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case-noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37-year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were 'serious' in around 82% of cases. The case-noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS.

PMID: 28036099 [PubMed - indexed for MEDLINE]

28 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")

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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")

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19 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 2018/02/23

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 2018/02/22

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.

11 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 2018/02/21

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.

Analysis of cocaine adulterants in human brain in cases of drug-related death.

Forensic Sci Int. 2018 Feb 10;285:86-92

Authors: Knuth M, Temme O, Daldrup T, Pawlik E

Abstract
For different reasons, street cocaine is often diluted with pharmacologically active substances, the so-called adulterants such as levamisole or hydroxyzine. A controversial debate exists currently on the uptake of adulterants from cocaine preparations and drug-related death. Previous research convincingly argues that serious adverse side effects that affect the central nervous and cardiovascular systems can be a consequence of adulterated cocaine.
AIMS: Having identified the presence of adulterants in lung tissue and blood, the concentrations of these substances in brain, an important target location, was of interest. This provides an opportunity to assess their role in cases of drug-related deaths.
MATERIALS AND METHODS: We developed and validated a method for the analysis of cocaine, two cocaine metabolites and six adulterants, which can typically be found in cocaine preparations, and one adulterant metabolite in brain tissue by gas chromatography-mass spectrometry (GC-MS)1. Ten brain samples which were tested positive for cocaine were analyzed. The homogenized brain tissue was embedded into drying paper for protein precipitation. During a subsequent solid-phase extraction (SPE), the eluate and one of the wash fractions were collected. After derivatization with N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in pyridine and isooctane, the extracts were analyzed by GC-MS.
RESULTS AND DISCUSSION: The method was fully validated for cocaine (COC), benzoylecgonine (BZE), ecgonine methyl ester (EME), diltiazem (DIL), hydroxyzine (HYD), and levamisole (LEV) and partly validated for cetirizine (CET), lidocaine (LID), phenacetin (PHE), and procaine (PRO) in brain material. By analyzing post-mortem brain tissue of ten cocaine users, LEV, LID, and HYD as well as PHE were identified in contrast to DIL, PRO, and the HYD metabolite CET. HYD and LEV were found in moderate to high concentrations in some cases. Therefore, it cannot be excluded that they have caused adverse side effects.
CONCLUSION: Because adulterants can potentially affect the central nervous and cardiac systems, it is likely that they enhance COC toxicity.

PMID: 29454838 [PubMed - as supplied by publisher]

[Medicaments and oral healthcare 4. Pharmacotherapy in (frail and care dependent) older people].

Ned Tijdschr Tandheelkd. 2017 May;124(5):265-270

Authors: de Baat C, van der Putten GJ, Visser A, Vissink A

Abstract
Polypharmacy is the consequence of multimorbidity. Both phenomena may cause functional limitations and/or frailty and/or care dependency in older people. In the human body, a medicament undergoes at least 3 important actions: absorption, distribution and elimination. These actions may proceed aberrantly in older people. Following interaction with receptors, a medicament triggers a chain reaction in the human body. The receptors and each link of the chain reaction may be subject to changes due to diseases as well as ageing. This, particularly, is the case with regard to medications directed towards the central nervous system and the cardiovascular system. Furthermore, interactions may occur between various medications mutually and between medications on the one hand and on the other hand food and water intake, self-medication with herbs, and diseases. Moreover, older people usually experience more adverse effects of medications when compared to younger people. This is due to altered body actions and reactions, polypharmacy and the many possible interactions. In older people, utilisation and intake of medications often give rise to problems that can be divided into medicament-related, patient-related, care- and care provider-related and other problems.

PMID: 28501881 [PubMed - indexed for MEDLINE]

Clinical research: Inequality in medicine.

Nature. 2017 10 04;550(7674):S18-S19

Authors: Nowogrodzki A

PMID: 28976953 [PubMed - indexed for MEDLINE]

Integrating natural language processing expertise with patient safety event review committees to improve the analysis of medication events.

Int J Med Inform. 2017 Aug;104:120-125

Authors: Fong A, Harriott N, Walters DM, Foley H, Morrissey R, Ratwani RR

Abstract
OBJECTIVES: Many healthcare providers have implemented patient safety event reporting systems to better understand and improve patient safety. Reviewing and analyzing these reports is often time consuming and resource intensive because of both the quantity of reports and length of free-text descriptions in the reports.
METHODS: Natural language processing (NLP) experts collaborated with clinical experts on a patient safety committee to assist in the identification and analysis of medication related patient safety events. Different NLP algorithmic approaches were developed to identify four types of medication related patient safety events and the models were compared.
RESULTS: Well performing NLP models were generated to categorize medication related events into pharmacy delivery delays, dispensing errors, Pyxis discrepancies, and prescriber errors with receiver operating characteristic areas under the curve of 0.96, 0.87, 0.96, and 0.81 respectively. We also found that modeling the brief without the resolution text generally improved model performance. These models were integrated into a dashboard visualization to support the patient safety committee review process.
CONCLUSIONS: We demonstrate the capabilities of various NLP models and the use of two text inclusion strategies at categorizing medication related patient safety events. The NLP models and visualization could be used to improve the efficiency of patient safety event data review and analysis.

PMID: 28529113 [PubMed - indexed for MEDLINE]

Efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel for non-small cell lung cancer patients who have failed at least two prior systemic treatments.

Thorac Cancer. 2017 May;8(3):138-146

Authors: Duan J, Hao Y, Wan R, Yu S, Bai H, An T, Zhao J, Wang Z, Zhuo M, Wang J

Abstract
BACKGROUND: The study was conducted to evaluate the efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) treatment in patients with advanced non-small-cell lung cancer (NSCLC) who have undergone multi-line therapy, and to investigate the association of secreted protein acidic and rich in cysteine (SPARC) expression status with clinical outcome.
METHODS: Sixty-four patients who received NAB-paclitaxel treatment (130 mg/m2 on days 1 and 8 of a 21 day cycle) as third line or further systemic treatment from 1 May 2011 to 30 June 2014 were included in this retrospective analysis. Tumor tissue was available in 28 patients for analysis of SPARC expression by immunohistochemistry.
RESULTS: Sixty-two patients had response evaluation and complete survival follow-up data; 83.9% received the weekly NAB-paclitaxel as fourth-line treatment or beyond. The objective response and disease control rates (n = 62) were 16.1% (10/62) and 64.5% (40/62), respectively. The median progression-free and overall survival rates were 3.7 (95% confidence interval 2.6-4.8) and 9.8 months (95% confidence interval 6.9-12.8), respectively. Previous treatment with taxane did not affect the response to NAB-paclitaxel. The main grade 3-4 toxicities experienced were neutropenia (9.4%) and leukopenia (7.8%). Patients with SPARC expression in tumor stroma but not in cancer cells had poorer progression-free survival compared with those with negative SPARC expression in tumor stroma cells (3.3 vs. 5.0 months, P = 0.036).
CONCLUSION: Weekly NAB-paclitaxel might be effective for heavily pretreated NSCLC patients. SPARC expression in tumor stroma cells might be a potential negative predictor of NAB-paclitaxel.

PMID: 28304139 [PubMed - indexed for MEDLINE]

Comparing the adverse effects of platinum in combination with etoposide or irinotecan in previously untreated small-cell lung cancer patients with extensive disease: A network meta-analyses.

Thorac Cancer. 2017 May;8(3):170-180

Authors: Chen Y, Chen L, Zhong D

Abstract
BACKGROUND: The safety of front-line chemotherapies for the treatment of extensive stage small-cell lung cancer (ED-SCLC) is uncertain. We carried out a network meta-analysis to compare the toxicity of different therapies for ED-SCLC.
METHODS: We searched EMBASE, PubMed, CENTRAL and clinicaltrials.gov. We performed network meta-analysis on hematological (anemia, leukopenia, neutropenia, and thrombocytopenia) and non-hematological toxicities (diarrhea, infection, and nausea and vomiting).
RESULTS: Nine studies with 2317 patients were included. Etoposide with carboplatin (EC) was associated with a higher incidence of anemia (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.13-3.63), leukopenia (OR 2.67, 95% CI 1.25-5.72), neutropenia (OR 12.08, 95% CI 2.13-68.66), and thrombocytopenia (OR 2.73, 95% CI 1.27-5.85) compared with irinotecan with carboplatin (IC). Similarly, etoposide with cisplatin (EP) was associated with a higher incidence of anemia (OR 1.70, 95% CI 1.13-2.56), leukopenia (OR 2.65, 95% CI 1.34-5.28), neutropenia (OR 5.70, 95% CI 2.93-11.10), and thrombocytopenia (OR 3.26, 95% CI 1.66-6.38) compared with irinotecan with cisplatin (IP). EC was associated with a lower incidence of diarrhea (OR 0.26, 95% CI 0.10-0.68) compared with IC, and EP was associated with a lower incidence of diarrhea (OR 0.09, 95% CI 0.03-0.25) and nausea and vomiting (OR 0.53, 95% CI 0.33-0.84) than IP.
CONCLUSIONS: Hematological toxicities were most common in EC-treated patients, while the lowest incidence occurred with IP treatment. The IP regimen was associated with the highest incidence of toxicities of the digestive tract, while the lowest incidence occurred with EC treatment.

PMID: 28263036 [PubMed - indexed for MEDLINE]

Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer.

Oncologist. 2017 03;22(3):245-254

Authors: Vahdat LT, Layman R, Yardley DA, Gradishar W, Salkeni MA, Joy AA, Garcia AA, Ward P, Khatcheressian J, Sparano J, Rodriguez G, Tang S, Gao L, Dalal RP, Kauh J, Miller K

Abstract
BACKGROUND: Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced or metastatic breast cancer.
METHODS: Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m2 orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM + CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR + CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics.
RESULTS: Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1-36.1) weeks on RAM + CAP, 7.3 (6.3-13.0) weeks on ICR + CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p = .1315, RAM + CAP versus CAP; 1.480, p = .0851, ICR + CAP versus CAP). Median OS was 67.4 weeks on RAM + CAP, 62.1 weeks on ICR + CAP, and 71.6 weeks on CAP (HRs: 1.833, p = .0283, RAM + CAP versus CAP; 1.468, p = .1550, ICR + CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥10%) on RAM + CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥10%) on ICR + CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea.
CONCLUSION: Combining RAM or ICR with CAP did not improve PFS in the targeted study population. The Oncologist 2017;22:245-254 IMPLICATIONS FOR PRACTICE: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. VEGFR-1 activation on endothelial and tumor cell surfaces increases tumor vascularization and growth and supports tumor growth via multiple mechanisms, including contributions to angiogenesis and direct promotion of cancer cell proliferation. Strong preclinical and clinical evidence suggests key roles for VEGF and angiogenesis in breast cancer growth, invasion, and metastasis. This randomized phase II study evaluated the efficacy and safety of each antibody in combination with capecitabine in patients with previously treated unresectable, locally advanced or metastatic breast cancer.

PMID: 28220020 [PubMed - indexed for MEDLINE]

Efficacy and Safety of FOLFIRI Regimen in Elderly Versus Nonelderly Patients with Metastatic Colorectal or Gastric Cancer.

Oncologist. 2017 Mar;22(3):293-303

Authors: Kim JW, Lee KW, Kim KP, Lee JH, Hong YS, Kim JE, Kim SY, Park SR, Nam BH, Cho SH, Chung IJ, Park YS, Oh HS, Lee MA, Kang HJ, Park YI, Song EK, Han HS, Lee KT, Shin DB, Kang JH, Zang DY, Kim JH, Kim TW

Abstract
BACKGROUND: Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients.
PATIENTS AND METHODS: Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy.
RESULTS: Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p = .244, and HR, 0.989; 95% CI, 0.774-1.264; p = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p = .479, and HR, 1.188; 95% CI, 0.891-1.585; p = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients.
CONCLUSION: The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status.

PMID: 28209749 [PubMed - indexed for MEDLINE]

OntoADR a semantic resource describing adverse drug reactions to support searching, coding, and information retrieval.

J Biomed Inform. 2016 Oct;63:100-107

Authors: Souvignet J, Declerck G, Asfari H, Jaulent MC, Bousquet C

Abstract
INTRODUCTION: Efficient searching and coding in databases that use terminological resources requires that they support efficient data retrieval. The Medical Dictionary for Regulatory Activities (MedDRA) is a reference terminology for several countries and organizations to code adverse drug reactions (ADRs) for pharmacovigilance. Ontologies that are available in the medical domain provide several advantages such as reasoning to improve data retrieval. The field of pharmacovigilance does not yet benefit from a fully operational ontology to formally represent the MedDRA terms. Our objective was to build a semantic resource based on formal description logic to improve MedDRA term retrieval and aid the generation of on-demand custom groupings by appropriately and efficiently selecting terms: OntoADR.
METHODS: The method consists of the following steps: (1) mapping between MedDRA terms and SNOMED-CT, (2) generation of semantic definitions using semi-automatic methods, (3) storage of the resource and (4) manual curation by pharmacovigilance experts.
RESULTS: We built a semantic resource for ADRs enabling a new type of semantics-based term search. OntoADR adds new search capabilities relative to previous approaches, overcoming the usual limitations of computation using lightweight description logic, such as the intractability of unions or negation queries, bringing it closer to user needs. Our automated approach for defining MedDRA terms enabled the association of at least one defining relationship with 67% of preferred terms. The curation work performed on our sample showed an error level of 14% for this automated approach. We tested OntoADR in practice, which allowed us to build custom groupings for several medical topics of interest.
DISCUSSION: The methods we describe in this article could be adapted and extended to other terminologies which do not benefit from a formal semantic representation, thus enabling better data retrieval performance. Our custom groupings of MedDRA terms were used while performing signal detection, which suggests that the graphical user interface we are currently implementing to process OntoADR could be usefully integrated into specialized pharmacovigilance software that rely on MedDRA.

PMID: 27369567 [PubMed - indexed for MEDLINE]

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases.

Oncotarget. 2016 Dec 13;7(50):82074-82084

Authors: Wu M, Yu Q, Li Q

Abstract
Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products.

PMID: 27738338 [PubMed - indexed for MEDLINE]