Awareness of medication related falls and preferred interventions among the elderly.

Pak J Pharm Sci. 2018 Mar;31(2):359-364

Authors: Loke MY, Yen Gan LL, Islahudin F

Abstract
Falls are a major problem among the elderly and can lead to serious injury. Adults older than 65 years suffer the greatest number of severe falls. This study aims to evaluate the knowledge and perception of medication related falls as well as preferred medication related fall prevention programs in the local population. A cross-sectional survey was conducted among the elderly patients in a tertiary hospital. A total of 86 patients (n=86) were interviewed. Approximately 23.3% (20 patients) of the elderly had a history of falls over the past 6 months. Majority of the elderly considered falls as a major concern (80 patients, 93%) and is preventable (55 patients, 64%). Patients with a medical condition reported a significantly greater number of falls within the past 6 months (p<0.001). Approximately 69% (59 patients) of the elderly were aware of their medication and associated risk of falls. In patients that were unaware of medication associated risk of falls, 81.5% (22 patients) had a potentially inappropriate medication preferred preventive interventions for medication related falls were related to strength and training programs (37 patients, 43%). The knowledge of falls, medication related falls and intervention strategies in the elderly were minimal.

PMID: 29618421 [PubMed - indexed for MEDLINE]

Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia among Patients with Rheumatoid Arthritis under Methotrexate Therapy.

Tohoku J Exp Med. 2019 07;248(3):209-216

Authors: Sakamoto N, Hara S, Ishimoto H, Nakashima S, Yura H, Miyamura T, Okuno D, Hara A, Kakugawa T, Yamaguchi H, Obase Y, Kushima H, Ishii H, Noguchi S, Kido T, Kobayashi T, Soejima Y, Yoshioka S, Ishimatsu Y, Yatera K, Kadota JI, Mukae H

Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.

PMID: 31366819 [PubMed - in process]

Factors that facilitate reporting of adverse drug reactions by pharmacists in Saudi Arabia.

Expert Opin Drug Saf. 2019 Aug;18(8):745-752

Authors: Aldryhim AY, Alomair A, Alqhtani M, Mahmoud MA, Alshammari TM, Pont LG, Kamal KM, Aljadhey H, Mekonnen AB, Alwhaibi M, Balkhi B, Alhawassi TM

Abstract
Objectives: Adverse drug reactions (ADRs) are a pervasive global problem, and its management is integral to patient safety and healthcare quality. Pharmacists play a pivotal role in monitoring and reporting ADRs, which has a direct impact on patient care. The aim of this study was to identify potential factors that facilitate pharmacists in community and hospital settings to report ADRs. Methods: A cross-sectional, online survey using a validated questionnaire was administered to pharmacists working in community and hospital pharmacies in Saudi Arabia. Results: 1,717 community and 153 hospital pharmacists participated in this study. Only 10.2% and 26.8% of community and hospital pharmacists, respectively, admitted ever reporting an ADR. The most reported factors that may facilitate ADRs reporting have included ongoing improvements in therapeutic knowledge about ADRs, attending educational programs with continuous medical education credits, the seriousness of the experienced ADRs and accessibility to patients' medical profile. The impact of peers by seeing colleagues reporting ADRs and ADRs due to herbal or traditional medicine were the least important factors reported by pharmacists. Conclusion: The study identified factors that can effectively address the under-reporting of ADRs by pharmacists. A multi-stakeholder, multi-pronged approach of ADR reporting is needed to develop greater awareness of this issue among pharmacists.

PMID: 31232612 [PubMed - indexed for MEDLINE]

Severe toxicity in adult patients with lung cancer under treatment with pemetrexed: a prospective cohort study.

J Chemother. 2019 Apr;31(2):95-104

Authors: Vázquez C, Orlova M, Verzura MA, Minatta JN, Scibona P, Jáuregui EG, Díaz de Arce H, Pallotta MG, Belloso WH

Abstract
Pemetrexed is an antimetabolite approved for treatment of non-small cell lung cancer. Harbouring interindividual variability in both the pharmacokinetic and pharmacogenetic profiles may lead to life-threatening toxicities. A prospective cohort study of adult patients initiating treatment with pemetrexed in combination with platinum between 2013 and 2015 were follow up. Primary exposure were the methylenetetrahydrofolate reductase (MTHFR) single base polymorphisms in exon 4 and 7 and 5'-UTR- thymidylate synthase (TYMS) VNTR genotypes, in addition to baseline clinical and demographic variables. We used a Cox regression model to evaluate patient's survival and toxicity experience and its association with both baseline characteristics, and a-priori determined genetic polymorphisms. Seventy two patients were included, 52.7% developed severe hematologic toxicity during follow-up. None of the tested genotypes were significantly associated with the main outcome on multivariate analysis, nor other basal clinical variables. Overall survival between patients experiencing the outcome was not different from those without it, but hospital admissions were more frequent. MTHFR and 5'-UTR-TYMS genotypes were not useful for predicting high grade toxicity events in patients under treatment with pemetrexed.

PMID: 30739598 [PubMed - indexed for MEDLINE]

Reducing hospital admissions for adverse drug events through coordinated pharmacist care: learning from Hawai'i without a field trip.

BMJ Qual Saf. 2019 02;28(2):91-93

Authors: Steinman MA

PMID: 30472650 [PubMed - indexed for MEDLINE]

Phase 1 study of MEDI3902, an investigational anti-Pseudomonas aeruginosa PcrV and Psl bispecific human monoclonal antibody, in healthy adults.

Clin Microbiol Infect. 2019 May;25(5):629.e1-629.e6

Authors: Ali SO, Yu XQ, Robbie GJ, Wu Y, Shoemaker K, Yu L, DiGiandomenico A, Keller AE, Anude C, Hernandez-Illas M, Bellamy T, Falloon J, Dubovsky F, Jafri HS

Abstract
OBJECTIVES: MEDI3902 is a bivalent, bispecific human immunoglobulin G1κ monoclonal antibody that binds to both the Pseudomonas aeruginosa PcrV protein involved in host cell cytotoxicity and the Psl exopolysaccharide involved in P. aeruginosa colonization and tissue adherence. MEDI3902 is being developed for the prevention of nosocomial P. aeruginosa pneumonia in high-risk patients.
METHODS: This phase 1 dose-escalation study (NCT02255760) evaluated the safety, pharmacokinetics, antidrug antibody (ADA) responses and ex vivo anticytotoxicity and opsonophagocytic killing activities of MEDI3902 after a single intravenous infusion in healthy adults aged 18 to 60 years. Fifty-six subjects were randomized in a 3:1 ratio to receive 250, 750, 1500 or 3000 mg of MEDI3902 or placebo and followed for 60 days afterwards.
RESULTS: Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; no serious TEAEs were observed. The most common TEAEs were infusion-related reactions. MEDI3902 exhibited approximately linear pharmacokinetics across the 250, 750 and 1500 mg doses and nonlinear pharmacokinetics between the 1500 and 3000 mg doses. One subject in the 3000 mg group tested positive for ADA on day 61 and had a lower MEDI3902 serum concentration from days 43 to 61 than ADA-negative subjects. Serum anticytotoxicity antibody concentrations and opsonophagocytic killing activity were correlated with MEDI3902 serum concentrations across all doses.
CONCLUSIONS: Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia.

PMID: 30107283 [PubMed - indexed for MEDLINE]

Cardiovascular Autonomic Dysfunction in Patients with Cancer.

Curr Cardiol Rep. 2018 07 03;20(8):69

Authors: Coumbe BGT, Groarke JD

Abstract
PURPOSE OF REVIEW: Elucidating the mechanisms that contribute to adverse cardiovascular (CV) outcomes and reduce quality of life among patients with cancer is paramount. Cancer, certain cancer drugs, radiation therapy, cancer-associated lifestyle disturbances, and cancer-independent comorbidities combine to predispose oncology patients to autonomic dysfunction (AD). This review will explore the assessment, etiology, and clinical implications of AD in cancer patients and will speculate on therapeutic and research opportunities.
RECENT FINDINGS: AD is particularly prevalent among patients with advanced cancer, but studies suggest increased prevalence across the entire continuum of cancer survivors compared to cancer-free controls. Data on cancer therapy-induced injury to the autonomic nervous system are limited to small studies. AD has been reported after cranial, neck, and mediastinal radiation therapy. Although AD has been shown to confer increased risk of adverse CV outcomes in cancer-free patients, the prognostic relevance of AD in oncology patients is less well investigated. Markers of AD including elevated resting heart rate (HR), reduced HR variability, and abnormal HR recovery have been associated with shorter survival times in various cancer cohorts. Furthermore, AD has been implicated in the etiology of cancer-related fatigue and exercise limitation. Multiple risk factors predispose oncology patients to AD, which is associated with adverse outcomes, including increased mortality, exercise limitation, and fatigue among this cohort. The contribution of AD to overall morbidity and mortality in cancer survivors has largely been overlooked to date. Further investigation is necessary to better understand cancer-treatment specific autonomic injury and to evaluate the role of various pharmacological and non-pharmacological interventions with potential to tackle the sympathovagal imbalance observed in cancer survivors.

PMID: 29971575 [PubMed - indexed for MEDLINE]

Treatment of familial mediterranean fever with canakinumab in patients who are unresponsive to colchicine.

Eur J Rheumatol. 2019 Apr 01;6(2):85-88

Authors: Berdeli A, Şenol Ö, Talay G

Abstract
OBJECTIVE: Familial Mediterranean fever (FMF) is the most common inherited monogenic autoinflammatory disease worldwide. It is caused by loss-of-function mutations in the MEFV gene, mostly affecting Eastern Mediterranean population. It is discussed if it should be considered an autosomal-dominant disease with variable penetrance, because heterozygosis mutations are associated with clinical autoinflammatory manifestations. Colchicine constitutes that the mainstay of FMF treatment should be preventing acute attacks and amyloidosis, and decreasing the chronic inflammation. In colchicine-resistant or intolerant patients, recent insights into the pathogenesis of FMF have made the anti-IL1 treatments important. We aimed to search for the retrospective results of canakinumab treatment in patients with FMF who are unresponsive to colchicine.
METHODS: In this study, 22 (13 males and nine females) patients with FMF with colchicine resistance/intolerance, age ranging from 6 to 18 years, were included in Ege University Department of Pediatric Rheumatology. After clinical and genetic diagnosis, colchicine treatment with standard doses was started. After treatment with canakinumab, complete response to treatment was determined as no acute episodes and normal level of acute phase reactants.
RESULTS: After canakinumab treatment, 22 patients with FMF who were colchicine-resistant were evaluated. After the treatment, no attack was observed in 19 patients, and the values of acute phase reactants were normal in 22 patients. In three patients, disease attack was observed 16 months after the first dose treatment. In all patients, the values of acute phase reactants were found at normal level during treatment. No drug-related side effects were observed in any patient.
CONCLUSION: Canakinumab is an effective and safe anti-IL1 agent to reduce attacks in patients with FMF with no response to colchicine and to reduce the level of high-level laboratory findings associated with FMF.

PMID: 31365342 [PubMed]

Drug-induced interstitial lung disease: role of pharmacogenetics in predicting cytotoxic mechanisms and risks of side effects.

Curr Opin Pulm Med. 2019 Sep;25(5):468-477

Authors: Jessurun NT, Drent M, van Puijenbroek EP, Bekers O, Wijnen PA, Bast A

Abstract
PURPOSE OF REVIEW: The diagnosis of drug-induced interstitial lung disease (DI-ILD) is challenging and mainly made by exclusion of other possible causes. Toxicity can occur as a cause of drug(s) or drug-drug interactions. In this review, we summarize the possible role of pharmacogenetics of metabolizing enzymes in DI-ILD.
RECENT FINDINGS: Knowledge of the genetic predispositions of enzymes involved in drug metabolization and their relation with proposed cytotoxic mechanisms of DI-ILD, in particular direct cell toxicity and free oxygen radical production is increasing. The cytochrome P450 enzyme family and other enzymes play an important role in the metabolism of all sorts of ingested, injected, or inhaled xenobiotic substances. The liver is the major site for metabolism. Metabolic cytotoxic mechanisms have however also been detected in lung tissue. Polymorphisms in genes coding for enzymes that influence metabolic activity may lead to localized (toxic) reactions and tissue damage. This knowledge may be helpful in preventing the risk of DI-ILD.
SUMMARY: Drug toxicity can be the consequence of absence or very poor enzyme activity, especially if no other metabolic route is available. In the case of reduced enzyme activity, it is recommended to reduce the dose or to prescribe an alternative drug, which is metabolized by a different, unaffected enzyme system to prevent toxic side effects. However, enhanced enzyme activity may lead to excessive formation of toxic and sometimes reactive metabolites. Therefore, knowing a patient's drug-metabolizing profile before drug prescription is a promising way to prevent or explain DI-ILD.

PMID: 31365381 [PubMed - in process]

A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer.

Gynecol Oncol. 2019 Jul 27;:

Authors: Randall LM, Wenham RM, Low PS, Dowdy SC, Tanyi JL

Abstract
PURPOSE: OTL38 is a folate-indole-cyanine green-like conjugate to folate receptor alpha (FRa). The objectives of this prospective trial were to assess the safety and efficacy (sensitivity and positive predictive value (PPV)) of OTL38 for intraoperative imaging during epithelial ovarian cancer surgery.
METHODS: Patients with suspected ovarian cancer planned for cytoreductive surgery were eligible to receive OTL38. Near-infrared (NIR) imaging was used to visualize target lesions that were evaluated by two blinded pathologists. A modified intent to treat (mITT) population of lesions from all patients who received OTL38-NIR imaging, underwent surgery, and had at least one FRa + target lesion was used to determine sensitivity and PPV. Two generalized linear models, with and without random effects, were employed to estimate sensitivity and PPV.
RESULTS: Forty-four patients were evaluated for safety, and 225 lesions from 29 patients (the mITT population) were evaluated for efficacy. When assuming no correlation of interlesional results within a patient, sensitivity was estimated at 85.93% (95% lower boundary CI = 81.19) and PPV at 88.14% (95% lower boundary CI = 83.59). When controlling for actual correlation of detection among multiple lesions within a single patient (a random effect), sensitivity was estimated at 97.97% (95% lower boundary CI = 87.75) and PPV at 94.93% (95% lower boundary CI = 86.13). A total of 48.3% [14/29, (95% CI 0.29-0.67)] of patients had at least one additional lesion detected by OTL38 alone. Eight patients had mild drug-related adverse events including infusion reaction, nausea, vomiting, and abdominal pain.
CONCLUSIONS: OTL38-NIR was safe and efficacious in this phase II study regardless of folate expression levels and merits phase III evaluation.

PMID: 31362825 [PubMed - as supplied by publisher]

Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Cutaneous Melanoma.

Recent Pat Anticancer Drug Discov. 2019 Jul 26;:

Authors: Basile D, Lisanti C, Pizzichetta MA, Baldo P, Fornasier G, Re FL, Corona G, Puglisi F

Abstract
BACKGROUND: Malignant melanoma is a skin cancer responsible of 90% of cutaneous cancer related deaths. In recent years, breakthroughs in treatment strategy have revolutionized the prognosis both of early and advanced melanoma patients. In particular, treatment with monoclonal antibodies targeting co-inhibitory checkpoints or specific molecular pathways are pawing the way for a new era of promising options, by prolonging survival time of these patients. Moreover, unlike the chemotherapy that was used until some time ago, these new drugs have a good and more manageable toxicity profile. However, because of the recent introduction in clinical practice of the new agents, there is a learning curve among physicians regarding early recognition and management of the associated side effects.
OBJECTIVES: The analysis of the toxicity profiles of the different agents currently studied for the treatment of early and advanced melanoma, and the description of several relevant recent patents in this field, are the aims of this review.
METHODS: A systematically conducted review, based on current clinical guidelines and on international Pharmacovigilance databases (AERS-Eudravigilance - WHO Vigibase).
RESULTS: Our systematic analysis outlines a comprehensive overview about the pharmacology, clinical application and safety of recent anticancer drugs to treat melanoma, which can be an essential instrument for health professionals and researchers.
CONCLUSION: The new oncological therapies against melanoma are based on increasingly specific biological and immunological targets. For this reason, the potential toxicities that are expected from patients would be less relevant than the systemic &quot;classical&quot; chemotherapy. However, the new therapies are not free from the risk of causing adverse reactions, some of which must be managed promptly and appropriately; moreover the multiplicity of the metabolic pathways exposes the new target therapies to relevant potential interactions. This review can help to understand how important it is not to underestimate potential adverse drug reactions related to new targeted therapies.

PMID: 31362664 [PubMed - as supplied by publisher]

[Drug-drug Interactions You Should Know!]

Pneumologie. 2019 May;73(5):306-318

Authors: Voigt N, Ort K, Sossalla S

Abstract
Drug-drug interactions (DDI) represent a significant problem in modern medicine. The number of patients with multi-morbidity, who take multiple drugs, is constantly increasing (polypharmacy). The related exponential increase in potential DDI is almost incomprehensible. In this article, we review pharmacodynamic DDI and provide clinically relevant examples. In addition, we extensively review pharmakokinetic DDI (e. g. through the cytochrome P450-system or p-glycoproteins) that can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. Finally we provide tools, which may help clinicians in their daily practice to identify and avoid potential DDI. In the context of an ageing society receiving polypharmacy, a better awareness of DDI and of strategies to prevent them is expected to reduce mortality and morbidity.

PMID: 31083751 [PubMed - indexed for MEDLINE]

Drug-induced hypertension: Know the problem to know how to deal with it.

Vascul Pharmacol. 2019 04;115:84-88

Authors: Masi S, Uliana M, Gesi M, Taddei S, Virdis A

Abstract
Arterial hypertension remains the world's leading mortality risk factor and despite overwhelming evidence that blood pressure-lowering strategies greatly reduce the cardiovascular risk, a substantial proportion of hypertensive individuals worldwide fail to achieve an optimal blood pressure control under treatment. Among the causes responsible for the gap existing between blood pressure lowering potential of the different antihypertensive treatments and real-life practice is the presence of drug-induced hypertension. Many therapeutic agents or substances may directly favour an increment of blood pressure values or counteract the blood pressure lowering effects of antihypertensive drugs. Excessive water and sodium retention, direct vasoconstriction or sympathomimetic activation are major mechanisms of action of such substances. The present manuscript will review medications and other substances that may increase blood pressure, also suggesting the choice of the more appropriate antihypertensive agents to employ when withdrawal of the substance or drug causing an elevation of blood pressure values is not possible.

PMID: 30822569 [PubMed - indexed for MEDLINE]

[Postvaccinal complications and management of suspected cases].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2019 Apr;62(4):450-461

Authors: Oberle D, Mentzer D, Rocha F, Streit R, Weißer K, Keller-Stanislawski B

Abstract
In all developed countries there is the possibility to protect oneself from vaccine-preventable diseases. However, not all individuals make use of this option. It is precisely in highly developed countries where a trend to vaccination hesitancy is noticeable, i. e. reluctance to get oneself or one's children vaccinated. The reasons why this is so are many, but the most important reason is the fear of postvaccinal complications, especially of those that imply sequelae or those with fatal outcomes.Whereas there are some proven associations between vaccination and adverse drug reaction, for example febrile seizures after the measles-mumps-rubella (MMR) vaccination, other hypotheses can be refuted, for example autism after the MMR vaccination. On one hand, this article gives an overview of known postvaccinal complications with indication of a causal association with vaccination and on the other hand addresses hypotheses of potential adverse drug reactions that have been refuted by pharmacoepidemiological studies.Only the scientific debate of these hypotheses, which are repeatedly discussed, especially on social media, can contribute to corroborating or refuting a potential causal association. If evidence for a causal association grows, e. g. intussusception, the relevant authorities (e.g. Paul Ehrlich Institute, European Medicines Agency) will take risk-minimizing measures. If studies and meta-analyses do not reveal any evidence of a causal association, a targeted information strategy will be required in order to prevent myths from circulating, vaccination coverages from declining, and infectious diseases from spreading.

PMID: 30820614 [PubMed - indexed for MEDLINE]

Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2.

Cell Immunol. 2018 10;332:121-128

Authors: Che D, Wang J, Ding Y, Liu R, Cao J, Zhang Y, Hou Y, An H, Gao Z, Zhang T

Abstract
BACKGROUND: Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children.
METHODS: MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro.
RESULTS: Mivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, MrgprB2-knockout mice displayed no inflammatory response to mivacurium. Mivacurium induced LAD2 cell degranulation in a dose-dependent manner. Mivacurium stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. However, mivacurium induced the release of only low levels of mediators in LAD2 cells transfected with MRGPRX2-targeted small interfering (si)RNA. Notably, cytokine release was not observed in LAD2 cells even when stimulated with high concentrations of mivacurium.
CONCLUSION: Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.

PMID: 30121125 [PubMed - indexed for MEDLINE]

Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer.

Br J Biomed Sci. 2018 Oct;75(4):169-174

Authors: Abbas M, Kushwaha VS, Srivastava K, Raza ST, Banerjee M

Abstract
BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy.
MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG).
RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038).
CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

PMID: 29909733 [PubMed - indexed for MEDLINE]

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 2019/07/31

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 2019/07/31

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 2019/07/30

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.

Drug interactions in maternal intensive care: prevalence, risk factors, and potential risk medications.

Einstein (Sao Paulo). 2019 May 30;17(3):eAO4521

Authors: Pessoa TL, Clemente Junior WS, Costa TXD, Bezerra PKDV, Martins RR

Abstract
OBJECTIVE: To characterize severe potential drug interactions in maternal intensive care, and to determine their frequency, risk factors and potential risk medications.
METHODS: An observational and longitudinal study conducted between December 2014 and December 2015 in a maternal intensive care unit. Clinical data were collected and severe potential drug interactions were identified on pregnant inpatients. The drug interactions were classified by type, prevalence and exposure rate. A multivariate logistic regression model was used to identify the severe potential drug interactions and the related drugs (p<0.05).
RESULTS: A total of 95.1% of patients were exposed to, at least, one potential drug interaction; in that, 91.7% 33.9% were related to, respectively, moderate and severe potential drug interactions. The patients were exposed, on average, on 69.2% of days they were in the intensive care unit. The main drugs involved in more severe drug interactions were magnesium sulfate, metoclopramide, propranolol and diazepam.
CONCLUSION: The severe potential drug interactions were observed in almost all patients of the study, and, approximately one third of those interactions were related to greater severity and resulted in exposure during long hospital stay. The higher number of prescribed drugs and its previous use of medications at home increase the occurrence of severe potential drug interactions.

PMID: 31166484 [PubMed - indexed for MEDLINE]