Mining Patients' Narratives in Social Media for Pharmacovigilance: Adverse Effects and Misuse of Methylphenidate.

Front Pharmacol. 2018;9:541

Authors: Chen X, Faviez C, Schuck S, Lillo-Le-Louët A, Texier N, Dahamna B, Huot C, Foulquié P, Pereira S, Leroux V, Karapetiantz P, Guenegou-Arnoux A, Katsahian S, Bousquet C, Burgun A

Abstract
Background: The Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) have recognized social media as a new data source to strengthen their activities regarding drug safety. Objective: Our objective in the ADR-PRISM project was to provide text mining and visualization tools to explore a corpus of posts extracted from social media. We evaluated this approach on a corpus of 21 million posts from five patient forums, and conducted a qualitative analysis of the data available on methylphenidate in this corpus. Methods: We applied text mining methods based on named entity recognition and relation extraction in the corpus, followed by signal detection using proportional reporting ratio (PRR). We also used topic modeling based on the Correlated Topic Model to obtain the list of the matics in the corpus and classify the messages based on their topics. Results: We automatically identified 3443 posts about methylphenidate published between 2007 and 2016, among which 61 adverse drug reactions (ADR) were automatically detected. Two pharmacovigilance experts evaluated manually the quality of automatic identification, and a f-measure of 0.57 was reached. Patient's reports were mainly neuro-psychiatric effects. Applying PRR, 67% of the ADRs were signals, including most of the neuro-psychiatric symptoms but also palpitations. Topic modeling showed that the most represented topics were related to Childhood and Treatment initiation, but also Side effects. Cases of misuse were also identified in this corpus, including recreational use and abuse. Conclusion: Named entity recognition combined with signal detection and topic modeling have demonstrated their complementarity in mining social media data. An in-depth analysis focused on methylphenidate showed that this approach was able to detect potential signals and to provide better understanding of patients' behaviors regarding drugs, including misuse.

PMID: 29881351 [PubMed]

Memantine induces manic episode in a 73-year-old patient with vascular neurocognitive disorder: a case report.

Neuropsychiatr Dis Treat. 2018;14:1395-1398

Authors: Duan J, Lao C, Chen J, Pan F, Zhang C, Xu W, Zhou W, Hu J, Shang D, Huang M, Xu Y

Abstract
Memantine, an N-methyl-d-aspartate receptor antagonist, is a well-established treatment option for moderate-to-severe cognitive impairment related to Alzheimer disease. Recently, growing evidence has indicated memantine might also be effective in treatment of affective disorders. The common drug-induced adverse events of memantine include confusion, dizziness, drowsiness, headache, insomnia, and agitation. Herein, we presented a case of a 73-year-old female patient with vascular neurocognitive disorder, who developed a manic episode after taking memantine.

PMID: 29881276 [PubMed]

Enteral versus parenteral nutrition and enteral versus a combination of enteral and parenteral nutrition for adults in the intensive care unit.

Cochrane Database Syst Rev. 2018 Jun 08;6:CD012276

Authors: Lewis SR, Schofield-Robinson OJ, Alderson P, Smith AF

Abstract
BACKGROUND: Critically ill people are at increased risk of malnutrition. Acute and chronic illness, trauma and inflammation induce stress-related catabolism, and drug-induced adverse effects may reduce appetite or increase nausea and vomiting. In addition, patient management in the intensive care unit (ICU) may also interrupt feeding routines. Methods to deliver nutritional requirements include provision of enteral nutrition (EN), or parenteral nutrition (PN), or a combination of both (EN and PN). However, each method is problematic. This review aimed to determine the route of delivery that optimizes uptake of nutrition.
OBJECTIVES: To compare the effects of enteral versus parenteral methods of nutrition, and the effects of enteral versus a combination of enteral and parenteral methods of nutrition, among critically ill adults, in terms of mortality, number of ICU-free days up to day 28, and adverse events.
SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase on 3 October 2017. We searched clinical trials registries and grey literature, and handsearched reference lists of included studies and related reviews.
SELECTION CRITERIA: We included randomized controlled studies (RCTs) and quasi-randomized studies comparing EN given to adults in the ICU versus PN or versus EN and PN. We included participants that were trauma, emergency, and postsurgical patients in the ICU.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of evidence with GRADE.
MAIN RESULTS: We included 25 studies with 8816 participants; 23 studies were RCTs and two were quasi-randomized studies. All included participants were critically ill in the ICU with a wide range of diagnoses; mechanical ventilation status between study participants varied. We identified 11 studies awaiting classification for which we were unable to assess eligibility, and two ongoing studies.Seventeen studies compared EN versus PN, six compared EN versus EN and PN, two were multi-arm studies comparing EN versus PN versus EN and PN. Most studies reported randomization and allocation concealment inadequately. Most studies reported no methods to blind personnel or outcome assessors to nutrition groups; one study used adequate methods to reduce risk of performance bias.Enteral nutrition versus parenteral nutritionWe found that one feeding route rather than the other (EN or PN) may make little or no difference to mortality in hospital (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.80 to 1.77; 361 participants; 6 studies; low-certainty evidence), or mortality within 30 days (RR 1.02, 95% CI 0.92 to 1.13; 3148 participants; 11 studies; low-certainty evidence). It is uncertain whether one feeding route rather than the other reduces mortality within 90 days because the certainty of the evidence is very low (RR 1.06, 95% CI 0.95 to 1.17; 2461 participants; 3 studies). One study reported mortality at one to four months and we did not combine this in the analysis; we reported this data as mortality within 180 days and it is uncertain whether EN or PN affects the number of deaths within 180 days because the certainty of the evidence is very low (RR 0.33, 95% CI 0.04 to 2.97; 46 participants).No studies reported number of ICU-free days up to day 28, and one study reported number of ventilator-free days up to day 28 and it is uncertain whether one feeding route rather than the other reduces the number of ventilator-free days up to day 28 because the certainty of the evidence is very low (mean difference, inverse variance, 0.00, 95% CI -0.97 to 0.97; 2388 participants).We combined data for adverse events reported by more than one study. It is uncertain whether EN or PN affects aspiration because the certainty of the evidence is very low (RR 1.53, 95% CI 0.46 to 5.03; 2437 participants; 2 studies), and we found that one feeding route rather than the other may make little or no difference to pneumonia (RR 1.10, 95% CI 0.82 to 1.48; 415 participants; 7 studies; low-certainty evidence). We found that EN may reduce sepsis (RR 0.59, 95% CI 0.37 to 0.95; 361 participants; 7 studies; low-certainty evidence), and it is uncertain whether PN reduces vomiting because the certainty of the evidence is very low (RR 3.42, 95% CI 1.15 to 10.16; 2525 participants; 3 studies).Enteral nutrition versus enteral nutrition and parenteral nutritionWe found that one feeding regimen rather than another (EN or combined EN or PN) may make little or no difference to mortality in hospital (RR 0.99, 95% CI 0.84 to 1.16; 5111 participants; 5 studies; low-certainty evidence), and at 90 days (RR 1.00, 95% CI 0.86 to 1.18; 4760 participants; 2 studies; low-certainty evidence). It is uncertain whether combined EN and PN leads to fewer deaths at 30 days because the certainty of the evidence is very low (RR 1.64, 95% CI 1.06 to 2.54; 409 participants; 3 studies). It is uncertain whether one feeding regimen rather than another reduces mortality within 180 days because the certainty of the evidence is very low (RR 1.00, 95% CI 0.65 to 1.55; 120 participants; 1 study).No studies reported number of ICU-free days or ventilator-free days up to day 28. It is uncertain whether either feeding method reduces pneumonia because the certainty of the evidence is very low (RR 1.40, 95% CI 0.91 to 2.15; 205 participants; 2 studies). No studies reported aspiration, sepsis, or vomiting.
AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether EN is better or worse than PN, or than combined EN and PN for mortality in hospital, at 90 days and at 180 days, and on the number of ventilator-free days and adverse events. We found fewer deaths at 30 days when studies gave combined EN and PN, and reduced sepsis for EN rather than PN. We found no studies that reported number of ICU-free days up to day 28. Certainty of the evidence for all outcomes is either low or very low. The 11 studies awaiting classification may alter the conclusions of the review once assessed.

PMID: 29883514 [PubMed - as supplied by publisher]

Pilot study on the occurrence of multiple cancers following cancer-related therapy at the University of Florida, Jacksonville (2011-2016).

J Investig Med. 2018 Jun 06;:

Authors: Seegobin K, Staggs E, Khawaja R, Maharaj S, Gautam S, Smotherman C, Rana F

Abstract
New primary cancers can occur in patients with a previous cancer. Among the risk factors, therapies such as chemotherapy, radiotherapy, and hormonal therapy have been associated with the development of neoplasms. Second cancers most commonly develop 5-10 years after the initial tumor. We observe the implications of cancer-related therapy in the development of a new tumor. We looked at 602 patients who had their first cancer diagnosed in 2011 and calculated the number of different primary cancers between 2011 and 2016 for each patient. Twenty-four patients had a second cancer within 5 years from the first diagnosis and there were no patients with a third cancer. There was no statically significant difference in the rates of second cancers after exposure to chemotherapy, radiotherapy, hormonal therapy, or any combination of these (p=0.738). Of the second cancers reported after 2011, renal, uterine, cervical, and lung cancers were the most frequently reported. Additionally, there was no statically significant difference among the rates of second cancers in men versus women (p=0.467), as well as among whites versus blacks (p=0.318). We conclude that while new primaries can occur after one cancer, there was no increased risk after exposure to different cancer-related therapies. With increased focus on the primary disease, there is a higher likelihood of missing another primary lesion. This is important as the practical implications of managing multiple primaries are rarely discussed.

PMID: 29880535 [PubMed - as supplied by publisher]

Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

J Biomed Semantics. 2018 Jun 07;9(1):17

Authors: Hur J, Özgür A, He Y

Abstract
BACKGROUND: Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs).
RESULTS: We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems.
CONCLUSIONS: Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

PMID: 29880031 [PubMed - in process]

Peginterferon is preferable to entecavir for prevention of unfavourable events in patients with HBeAg-positive chronic hepatitis B: A five-year observational cohort study.

J Viral Hepat. 2017 Nov;24 Suppl 1:12-20

Authors: Li SY, Li H, Xiong YL, Liu F, Peng ML, Zhang DZ, Ren H, Hu P

Abstract
At present, the long-term effects of pegylated interferon-α (PEG-IFN-α) and entecavir (ETV) are controversial. Studies directly compared the long-term outcomes of these two drugs have not been completed. This study was designed to compare the clinical outcomes of PEG-IFN-α vs ETV therapy in Chinese patients with chronic HBV infection. From September 2008 to December 2016, a large, observational, open-label, prospective cohort study of HBeAg-positive patients with CHB who received PEG-IFN-α or ETV therapy was carried out at the Second Affiliated Hospital of Chongqing Medical University. Cumulative incidences of unfavourable events were calculated with respect to treatment type. Based on the REACH-B model, we compared the observed incidence of hepatocellular carcinoma (HCC) with the expected incidence in each group. PEG-IFN-α-treated patients showed a lower cumulative incidences of unfavourable events and cirrhosis than those treated with ETV (P = .031; P = .044, respectively). Impact factor exploration indicated that treatment type and platelet count are significantly associated with the occurrence of unfavourable events. Based on the REACH-B model, a lower observed cumulative incidence of HCC was observed in PEG-IFN-α-treated patients than predicted (P = .038). However, there was no significant difference of the cumulative HCC incidence between the observed and the predicted cases for ETV-experienced patients (P = .36). Treatment with PEG-INF-α leads to a lower incidence of unfavourable events including cirrhosis and HCC than ETV in patients with HBV. Treatment type and baseline platelet count may be two important factors associated with the long-term clinical outcomes of patients with CHB.

PMID: 29082649 [PubMed - indexed for MEDLINE]

Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort.

BMJ Open. 2017 Oct 16;7(10):e016627

Authors: Coughtrie AL, Behr ER, Layton D, Marshall V, Camm AJ, Shakir SAW

Abstract
OBJECTIVES: To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases.
SETTING: Suspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected.
PARTICIPANTS: Two expert cardiologists reviewed data for 293 referred cases: 130 were included. Inclusion criteria were new onset or exacerbation of pre-existing ventricular arrhythmias, QTc >500 ms, QTc >450 ms (men) or >470 ms (women) with cardiac syncope, all secondary to drug administration. Exclusion criteria were acute ischaemia and ischaemic polymorphic ventricular tachycardia at presentation, structural heart disease, consent withdrawn or deceased prior to study. Descriptive analysis of Caucasian cases (95% of included cases, n=124) and culpable drug exposures was performed.
RESULTS: Of the 124 Caucasian cases, 95 (77%) were QTc interval prolongation-related; mean age was 62 years (SD 15), and 63% were female. Cardiovascular comorbidities included hypertension (53%) and patient-reported 'heart rhythm problems' (73%). Family history of sudden death (36%) and hypokalaemia at presentation (27%) were common. 165 culpable drug exposures were reported, including antiarrhythmics (42%), of which amiodarone and flecainide were the most common. Sotalol, a beta-blocking agent with antiarrhythmic activity, was also common (15%). 26% reported multiple drugs, of which 84% reported at least one cytochrome (CYP) P450 inhibitor. Potential pharmacodynamics interactions identified were mainly QT prolongation (59%).
CONCLUSIONS: Antiarrhythmics, non-cardiac drugs and drug combinations were found to be culpable in a large cohort of 124 clinically validated proarrhythmia cases. Potential clinical factors that may warn the prescriber of potential proarrhythmia include older women, underlying cardiovascular comorbidity, family history of sudden death and hypokalaemia.

PMID: 29042382 [PubMed - indexed for MEDLINE]

Potentially inappropriate prescribing and its association with health outcomes in middle-aged people: a prospective cohort study in Ireland.

BMJ Open. 2017 Oct 16;7(10):e016562

Authors: Moriarty F, Cahir C, Bennett K, Hughes CM, Kenny RA, Fahey T

Abstract
OBJECTIVES: To determine the prevalence of potentially inappropriate prescribing (PIP) in a cohort of community-dwelling middle-aged people and assess the relationship between PIP and emergency department (ED) visits, general practitioner (GP) visits and quality of life (QoL).
DESIGN: Prospective cohort study.
SETTING: The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study of ageing.
PARTICIPANTS: Individuals aged 45-64 years recruited to TILDA who were eligible for the means-tested General Medical Services scheme and followed up after 2 years.
EXPOSURE: PIP was determined in the 12 months preceding baseline and follow-up TILDA data collection by applying the PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria to participants' medication dispensing data.
OUTCOME MEASURES: At follow-up, the reported rates of ED and GP visits over 12 months (primary outcome) and the CASP-R12 (Control Autonomy Self-realisation Pleasure) measure of QoL (secondary outcome).
ANALYSIS: Multivariate negative binomial (rates) and linear regression (CASP-R12) models controlling for potential confounders.
RESULTS: At 2-year follow-up (n=808), PIP was detected in 42.9% by the PROMPT criteria. An ED visit was reported by 18.7% and 94.4% visited a GP (median 4 visits, IQR 2-6). Exposure to ≥2 PROMPT criteria was associated with higher rates of healthcare utilisation and lower QoL in unadjusted regression. However, in multivariate analysis, the associations between PIP and rates of ED visits (adjusted incidence rate ratio (IRR) 0.92, 95% CI 0.53 to 1.58), and GP visits (IRR 1.06, 95% CI 0.87 to 1.28), and CASP-R12 score (adjusted β coefficient 0.35, 95% CI -0.93 to 1.64) were not statistically significant. Numbers of medicines and comorbidities were associated with higher healthcare utilisation.
CONCLUSIONS: Although PIP was prevalent in this study population, there was no evidence of a relationship with ED and GP visits and QoL. Further research should evaluate whether the PROMPT criteria are related to these and other adverse outcomes in the general middle-aged population.

PMID: 29042380 [PubMed - indexed for MEDLINE]

Prospects and Frontiers of Stem Cell Toxicology.

Stem Cells Dev. 2017 Nov 01;26(21):1528-1539

Authors: Liu S, Yin N, Faiola F

Abstract
The development of stem cell biology has revolutionized regenerative medicine and its clinical applications. Another aspect through which stem cells would benefit human health is their use in toxicology. In fact, owing to their ability to differentiate into all the lineages of the human body, including germ cells, stem cells, and, in particular, pluripotent stem cells, can be utilized for the assessment, in vitro, of embryonic, developmental, reproductive, organ, and functional toxicities, relevant to human physiology, without employing live animal tests and with the possibility of high throughput applications. Thus, stem cell toxicology would tremendously assist in the toxicological evaluation of the increasing number of synthetic chemicals that we are exposed to, of which toxicity information is limited. In this review, we introduce stem cell toxicology, as an emerging branch of in vitro toxicology, which offers quick and efficient alternatives to traditional toxicology assessments. We first discuss the development of stem cell toxicology, and we then emphasize its advantages and highlight the achievements of human pluripotent stem cell-based toxicity research.

PMID: 28874109 [PubMed - indexed for MEDLINE]

Investigation on the incidence of adverse reactions, viraemia and haematological changes following field immunization of cattle using a live attenuated vaccine against lumpy skin disease.

Transbound Emerg Dis. 2018 Feb;65(1):174-185

Authors: Katsoulos PD, Chaintoutis SC, Dovas CI, Polizopoulou ZS, Brellou GD, Agianniotaki EI, Tasioudi KE, Chondrokouki E, Papadopoulos O, Karatzias H, Boscos C

Abstract
The present study was performed to investigate the clinical impact and certain virological and haematological parameters following immunization of cattle against lumpy skin disease (LSD). The study was conducted in a dairy cattle farm (215 animals), immunized with a Neethling strain-based live vaccine. Twenty-seven animals (14 lactating cows, four dry cows and nine calves) were randomly selected for repetitive blood and saliva samplings. An EvaGreen-based real-time PCR was designed to differentiate vaccine from field LSDVs. Vaccinated animals underwent examination for adverse reactions. Nodule samples were collected from two representative cases for histopathological testing and virus identification. Milk yield was calculated based on bulk-tank measurements of all lactating cows (79). Viral DNA was detected between days 6-15 post-vaccination (p.v.) at 63% of the sampled animals (17/27). Saliva and bulk-tank milk samples were LSDV-negative. Pronounced swelling was observed at injection sites of 12% of the immunized animals (26/215), starting at day 6 p.v., and was resolved after 2-4 days. Small-sized (<0.5 cm) cutaneous lumps were developed between days 8-18 p.v. at 9% of the vaccinated animals (19/215). These were observed in adult cows and not in calves/heifers. Resolution was observable 10 days post-development. The vaccine virus was also identified in nodules and injection-site aspirates. Haematological changes (e.g., lower leucocyte counts) were observed in cows and not in calves. Daily milk production was being reduced during the first 12 days p.v. LSD immunization of cows resulted in nodules and low viraemia levels. The fact that nodules and haematological changes were not observed in calves, along with the low viraemia, supports the reduced virulence of the Neethling vaccine strain. The characteristic nodules in vaccinated animals could allow clinical differentiation from those observed in LSD. The developed real-time PCR efficiently differentiates infected from vaccinated cattle, and should be further validated as a tool in LSD surveillance.

PMID: 28391652 [PubMed - indexed for MEDLINE]

Patients' concerns regarding biological agents in rheumatology.

Int J Rheum Dis. 2018 Jun;21(6):1219-1226

Authors: Pehlivan Y, Orucoglu N, Pehlivan S, Kimyon G, Zengin O, Kucuk A, Sahin A, Tomas N, Oksuz MF, Kisacik B, Akar S, Onat AM, Dalkilic E

Abstract
OBJECTIVE: The potential side effects of biological agents may increase the anxiety levels of patients and influence not only their desire to use these therapies but also their concordance to treatment. This study aimed to determine the level and prevalence of drug-related concern in patients treated with biological agents and to acquire additional information regarding the related causes.
MATERIALS AND METHODS: A total of 1134 patients who were using biological agents for at least 3 months with a diagnosis of rheumatic diseases were enrolled. General anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI).
RESULTS: The most common cause for drug-related concerns was the potential side effects of the drugs (59.5%). Among the potential side effects, cancer risk was the most common cause for concern (40.1%), followed by the risk of tuberculosis activation (30.7%). Anxiety levels were higher in patients who experienced side effects than in other patients, and this difference was statistically significant (P < 0.05). STAI trait and state scores were moderately correlated with anxiety levels related to the drug (P < 0.001).
CONCLUSION: Anxiety related to biological agents may significantly affect the patients' anxiety levels. Awareness regarding the patients' concerns and expectations related to the drug is important to ensure drug adherence and concordance to treatment.

PMID: 29879318 [PubMed - in process]

Safe use of vasopressin and angiotensin II for patients with circulatory shock.

Pharmacotherapy. 2018 Jun 07;:

Authors: Bauer SR, Sacha GL, Lam SW

Abstract
Circulatory shock is a medical emergency that requires rapid intervention to optimize patient outcomes. Although catecholamine vasopressors are considered life-sustaining therapy they are associated with adverse reactions and vasopressin and angiotensin II may be utilized to minimize these adverse effects. However, vasopressin and angiotensin II are also associated with adverse reactions that must be known to the clinician in order to mitigate risk for patients. This review focuses on the known adverse drug effects of vasopressin and angiotensin II while offering potential solutions to minimize harm with these agents. Future directions with vasoactive medication safety, including optimization of the electronic medical record, clinical decision support, prediction analytics, and precision medicine for patients with circulatory shock are also discussed. This article is protected by copyright. All rights reserved.

PMID: 29878459 [PubMed - as supplied by publisher]

Cardiovascular Safety of Psychiatric Agents: A Cautionary Tale.

Angiology. 2018 Jan 01;:3319718780145

Authors: Manolis TA, Manolis AA, Manolis AS

Abstract
Psychiatric agents are among the most commonly prescribed medications. Despite the advent of newer generation agents, patients receiving them still experience cardiovascular (CV) side effects. However, these agents may have heterogeneous properties, calling for an individualized approach based on efficacy and also on the particular side effect profile of each specific agent. Proarrhythmic effects arising from drug-induced long-QT syndrome and consequent potentially life-threatening polymorphic ventricular arrhythmias in the form of torsade de pointes, the metabolic syndrome contributing to atherosclerosis and acute coronary syndromes, and drug-induced orthostatic hypotension raise major concerns. Of course, it is also crucial that fear of potential CV adverse effects does not deprive psychiatric patients of appropriate drug therapy. Modification of CV risk factors in psychiatric patients together with optimal management of their CV diseases and appropriate selection of psychotropic agents with greater efficacy and least CV toxicity are of paramount importance in mitigating CV risks and enhancing safety. Identifying patients at high risk of CV complications and close monitoring of all patients receiving these agents are crucial steps to prevent and manage such complications. All these issues are herein reviewed, relevant guidelines are discussed, and schemas are depicted that illustrate the interrelated connections among the psychotropic agents and their CV effects.

PMID: 29874922 [PubMed - as supplied by publisher]

[In process].

Pflege Z. 2017 Apr;70(4):36-8

Authors: Ebbers B

PMID: 29425435 [PubMed - indexed for MEDLINE]

Evaluation of accuracy of IHI Trigger Tool in identifying adverse drug events: a prospective observational study.

Br J Clin Pharmacol. 2018 Jun 06;:

Authors: das Dores Graciano Silva M, Martins MAP, de Gouvêa Viana L, Passaglia LG, de Menezes RR, de Queiroz Oliveira JA, da Silva JLP, Ribeiro ALP

Abstract
AIMS: Adverse drug events (ADEs) can seriously compromise the safety and quality of care provided to hospitalized patients, requiring the adoption of accurate methods to monitor them. We sought to prospectively evaluate the accuracy of the triggers proposed by the Institute for Healthcare Improvement (IHI) for identifying ADEs.
METHODS: A prospective study was conducted in a public university hospital, in 2015, with patients ≥18 years. Triggers proposed by IHI and clinical alterations suspected to be ADEs were searched daily. The number of days in which the patient was hospitalized was considered as unit of measure to evaluate the accuracy of each trigger.
RESULTS: Three hundred patients were included in this study. Mean age was 56.3 years (standard deviation (SD) 16.0), and 154 (51.3%) were female. The frequency of patients with ADEs was 24.7% and with at least one trigger was 53.3%. From those patients who had at least one trigger, the most frequent triggers were antiemetics (57.5%) and "abrupt medication stop" (31.8%). Triggers' sensitivity ranged from 0.3 to11.8 % and the positive predictive value ranged from 1.2 to 27.3%. Specificity and negative predictive value were greater than 86%. Most patients identified by the presence of triggers did not have ADEs (64.4%). No triggers were identified in 40 (38.5%) ADEs.
CONCLUSIONS: IHI Trigger Tool did not show good accuracy in detecting ADEs in this prospective study. The adoption of combined strategies could enhance effectiveness in identifying patient safety flaws. Further discussion might contribute to improve trigger usefulness in clinical practice.

PMID: 29874704 [PubMed - as supplied by publisher]

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis.

Transplant Proc. 2018 Jun 02;:

Authors: Hwang SD, Lee JH, Lee SW, Kim JK, Kim MJ, Song JH

Abstract
BACKGROUND: Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia.
OBJECTIVE: The purpose of this study was to measure the appropriate dose of valganciclovir required to prevent CMV infection.
METHODS: A systematic review and meta-analysis were performed by using a random effects model. The Cochrane Central Register, MEDLINE, EMBASE, and PubMed databases were searched up to April 15, 2017. We conducted analysis on low-dose (450 mg) and standard-dose (900 mg) valganciclovir groups.
RESULTS: After completion of the research, the analysis revealed that the glomerular filtration rate, graft loss, tacrolimus level, antibody-mediated rejection, and fungal and Candida infection rates did not differ between the 2 groups. However, the incidence of CMV tended to decrease in the low-dose group (0.584 [95% confidence interval [CI], 0.352-0.967]; P = .036). The biopsy-proven rejection rate decreased by 0.427 times in the low-dose group compared with the standard-dose group (95% CI, 0.274-0.667; P = .002). Furthermore, the incidence of leukopenia decreased by 0.371 times in the low-dose group compared with the standard-dose group (95% CI, 0.264-0.523; P = .001).
CONCLUSIONS: The 450-mg dose of valganciclovir effectively prevented post-transplantation CMV infection and decreased drug-induced side effects such as leukopenia. In the future, the lower dose of valganciclovir should be considered to prevent CMV infection and enhance cost-effectiveness.

PMID: 29871773 [PubMed - as supplied by publisher]

Cognitive Effects of Androgen Deprivation Therapy in Men With Advanced Prostate Cancer.

Urology. 2017 05;103:167-172

Authors: Gunlusoy B, Ceylan Y, Koskderelioglu A, Gedizlioglu M, Degirmenci T, Ortan P, Kozacioglu Z

Abstract
OBJECTIVE: To evaluate the prostate cancer effects of androgen deprivation therapy (ADT) by using a systematic set of methods to calculate specific cognitive functions in men with locally advanced or metastatic prostate cancer.
MATERIALS AND METHODS: From April 2014 to February 2016, a prospective, comparative study was done to evaluate the cognitive effects of hormone therapy. Group 1 consisted of 78 patients with locally advanced or metastatic prostate cancer who received complete ADT treatment continuously for 12 months and group 2 (control group) consisted of 78 patients who underwent radical prostatectomy without any additional treatment. The Montreal Cognitive Assessment (MoCA) test and the Frontal Assessment Battery (FAB) test with Turkish language version were used to evaluate multiple domains of cognitive function.
RESULTS: Post-treatment results of both tests revealed that patients in group 1 achieved lower mean total scores than group 2. In MoCA test, the deficits were especially prominent in the areas of language ability and short-term memory capacity (P < .05 and P < .05). No significant differences could be identified between groups in respect to attention, executive functions, visuospatial abilities, abstract thinking, calculating abilities, and orientation. In FAB test, the deficits were especially prominent in the areas of mental flexibility and inhibitory control (P < .05 and P < .05). No significant differences could be identified between groups in conceptualization, motor series, conflicting instructions, and environmental autonomy.
CONCLUSION: ADT affects cognitive functions such as language ability, short-term memory capacity, mental flexibility, and inhibitory control. Urologists should keep in mind these side effects and inform the patients and their families for the early symptoms of cognitive dysfunction.

PMID: 28188757 [PubMed - indexed for MEDLINE]

A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method.

Sci Rep. 2016 12 09;6:38660

Authors: Tharwat A, Moemen YS, Hassanien AE

Abstract
Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.

PMID: 27934950 [PubMed - indexed for MEDLINE]

Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Evaluations Following Single Oral Doses of GSK2330672 in Healthy Japanese Volunteers.

Clin Pharmacol Drug Dev. 2018 Jun 05;:

Authors: Ino H, Endo A, Wakamatsu A, Ogura H, Numachi Y, Kendrick S

Abstract
GSK2330672 is an inhibitor of the ileal bile acid transporter, designed to have minimal systemic exposure, and is under development as a potential therapeutic for pruritus associated with primary biliary cholangitis and other cholestatic liver diseases. A phase 1, double-blind, placebo-controlled, 4-period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of GSK2330672 in healthy Japanese participants. Sixteen healthy male participants received single oral doses of GSK2330672 (10-180 mg) or placebo in each period. No serious adverse events and no adverse events leading to study discontinuation or withdrawal were reported. Drug-related adverse events reported included gastrointestinal symptoms (mostly diarrhea) and positive fecal occult blood tests, and were all mild and resolved without any interventions. GSK2330672 was undetectable in the majority of participants' plasma. Pharmacodynamic observations included a tendency for total serum bile acids to reduce and for serum 7α-hydroxy-4-cholesten-3-one, a key intermediate of bile acid synthesis, to increase with increasing doses of GSK2330672. In the context of recently published indications of potential efficacy for cholestatic pruritus in non-Japanese populations, these data support further evaluations of GSK2330672 in Japanese patients.

PMID: 29870578 [PubMed - as supplied by publisher]

Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer.

Niger J Clin Pract. 2017 Nov;20(11):1422-1427

Authors: Yang J, Jia B, Yan J, He J

Abstract
PURPOSE: Pancreatic carcinoma is the most lethal cancer, with a 5-year survival rate of <5%. Hyperglycemia is one of the severe adverse drug reactions (ADRs) in cancer treatment. The aim was to analyze the blood glucose-related ADR of antineoplastics in treating pancreatic cancer.
MATERIALS AND METHODS: Antineoplastic drugs were selected from Martindale-The Complete Drug Reference (36th edition). ADR data were extracted from VigiBase, the WHO Uppsala Monitoring Centre, and the WHO's specialist center for drug safety.
RESULTS: Nineteen antineoplastic drugs were selected; VigiBase provided their ADR records including total 235,625 records and 27 heading ADR items, 1348 records of glucose metabolism disorders (GMDs), and 807 records of hyperglycemia. Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; fludarabine and flutamide with high ADR of GMD ratio. All the hyperglycemia ratios of the 9 antineoplastics were more than 50.0%, except pemetrexed and sorafenib. Thoroughly, doxorubicin carried high absolute records and ratios in hyperglycemic conditions.
CONCLUSIONS: Pancreatic carcinoma is an aggressive malignancy typically associated with severe hyperglycemia. Furthermore, hyperglycemia is one of the severe ADRs from antineoplastics, which must be paid special attention to when treating in pancreatic carcinoma, especially doxorubicin, fluorouracil, and gemcitabine. Such real-time monitoring or pretreatment gene test can be suggested.

PMID: 29303126 [PubMed - indexed for MEDLINE]