The Effects of Pharmacological and Non-Pharmacological Interventions on Symptom Management and Quality of Life among Breast Cancer Survivors Undergoing Adjuvant Endocrine Therapy: A Systematic Review.

Int J Environ Res Public Health. 2020 04 24;17(8):

Authors: Chan CWH, Tai D, Kwong S, Chow KM, Chan DNS, Law BMH

Abstract
Breast cancer survivors need to undergo adjuvant endocrine therapy after completion of curative treatments to prevent disease recurrence. These individuals often experience symptoms which are detrimental to their quality of life (QOL). Implementation of interventions for effective symptom management among these survivors is warranted. This review provides an overview of studies on the effectiveness of the previously developed interventions for breast cancer survivors undergoing adjuvant endocrine therapy on symptom alleviation and enhancement of QOL or health-related QOL (HRQOL). Five electronic databases were employed in the literature search. Study selection, data extraction and critical appraisal of the included studies were conducted by three authors independently. Twenty-four studies were included. Both pharmacological and non-pharmacological interventions are effective in addressing the symptoms associated with adjuvant endocrine therapy among the breast cancer survivors, and in improving their QOL, although discrepancies were noted between the studies in terms of the significance of these effects. Pharmacological and non-pharmacological interventions can be effective for symptom management among breast cancer survivors. Their implementation is recommended for effective survivorship care for these individuals. Further research on intervention development for breast cancer survivors is recommended to provide further evidence for the utility of the explored interventions in survivorship care for these patients.

PMID: 32344759 [PubMed - indexed for MEDLINE]

[Oral cavity as a target and a marker of environmental exposures: diseases diagnosed during adulthood].

Med Sci (Paris). 2020 Mar;36(3):231-234

Authors: Babajko S, Lescaille G, Radoï L, Thu Bui A, Baaroun V, Boyer E, Delbosc S, Chardin H, Barouki R, Coumoul X

Abstract
The oral cavity is one of the main route for environmental contaminations associated to many chronic diseases via alimentation, medications and respiration. Other factors may also impact the oral environment, some of them are endogenous, like microbiota, hormones and saliva, and others are exogenous, like dental materials and pathogens.

PMID: 32228841 [PubMed - indexed for MEDLINE]

Incidence of Adverse Drug Reactions in High-Risk Pregnancy: A Prospective Cohort Study in Obstetric Intensive Care.

Eur J Clin Pharmacol. 2020 Feb;76(2):291-298

Authors: da Costa TX, de Almeida Pimenta Cunha MD, do Vale Bezerra PK, Azeredo FJ, Martins RR, Oliveira AG

Abstract
PURPOSE: To estimate the cumulative incidence of adverse drug reactions (ADRs) in women with high-risk pregnancy hospitalized in an obstetric intensive care unit, then to describe the medicines involved and to identify major risk factors.
METHODS: From June 2016 to December 2017, patients admitted to the ICU with high-risk pregnancy were considered eligible in this observational, longitudinal, prospective study. Patients were investigated daily for the occurrence of ADRs through pharmaceutical anamnesis, active search in medical records and questioning of the health team. Suspected ADRs were classified according to Naranjo's algorithm. Written informed consent was obtained from all patients. Univariate and multivariate logistic regression were used to identify risk factors of ADR.
RESULTS: The study population consisted of 607 high-risk pregnancies from 851 women admitted to the ICU, of whom 244 admitted for non-obstetric conditions, with an ICU stay less than 24 h or readmitted to the ICU were excluded. The mean age was 27.0 ± 7.5 years-old, mean gestational age was 33.8 ± 6.3 weeks. ADR were observed in 165 women (27.2%). No severe ADR was observed and 29.7% were of moderate severity. The most often implicated medicine was magnesium sulphate (25.2%) with 44.5% of patients administered that substance experiencing ADRs consisting of somnolence (68.6%), absent patellar reflex (21.6%) and hypotension (9.8%). Risk factors of ADR were blood pressure (adjusted odds-ratio (aOR) 1.02), haemoglobin level (aOR 1.21) and body temperature (aOR 0.71).
CONCLUSIONS: ADRs affect about one third of high-risk pregnancies, mainly due to magnesium sulphate administrations. High blood pressure, lower body temperature, and high haemoglobin concentration on admission were associated with an increased risk of ADR.

PMID: 31768575 [PubMed - indexed for MEDLINE]

Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial.

BMJ Sex Reprod Health. 2020 04;46(2):139-146

Authors: Abbe C, Roxby AC

Abstract
INTRODUCTION: There is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs).
METHODS: We examined the frequency of reported AEs by male research participants compared with AEs reported in prescribing information of approved female hormonal contraceptive methods. Published data from trials of the top five most-used female hormonal contraceptives, supplemented by contemporary contraceptive research, were compared with the frequency of AEs reported in a male injectable hormonal contraceptive trial.
RESULTS: We observed similar frequencies of AEs reported by users of male contraceptives compared with those reported by female users. Among quantitatively comparable AEs, compared with men, women reported experiencing higher frequencies of headaches, pelvic pain, and weight gain and similar frequencies of decreased libido. Compared with women, men reported experiencing higher frequencies of acne and mood changes. Men discontinued participation due to AEs at a lower frequency than women.
CONCLUSIONS: Female hormonal methods generally have similar frequencies of AEs to those reported in a recent male hormonal contraceptive trial, and male users had lower rates of discontinuation due to AEs. There were fewer serious AEs of the male contraceptive than reported in contemporary female trials which resulted in FDA licensure. This suggests there may be implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods.

PMID: 31754066 [PubMed - indexed for MEDLINE]

Prevalence and risk factors associated with fatal adverse drug reactions among patients admitted at a Spanish teaching hospital.

Eur J Intern Med. 2019 Dec;70:e14-e16

Authors: Pardo-Cabello AJ, Luna JD, Gómez Jiménez FJ, Del Pozo E, Puche Cañas E

PMID: 31630930 [PubMed - indexed for MEDLINE]

Effectiveness and safety of oral Chinese patent medicines as adjuvant treatment for unstable angina pectoris on the national essential drugs list of China: a protocol for a systematic review and network meta-analysis.

BMJ Open. 2019 09 20;9(9):e026136

Authors: Hua Z, Zhai FT, Tian J, Gao CF, Xu P, Zhang F, Liu SJ, Dong K, Du XF, Zhang Z, Yang G

Abstract
INTRODUCTION: Achieving efficacious and safe treatments for unstable angina pectoris (UAP) is still a challenging clinical problem. The availability of different oral Chinese patent medicines frequently poses a practical challenge to clinicians, namely, which one to choose as first-line regimen for treatment. This study aims to examine the comparative effectiveness and safety of oral Chinese patent medicines for UAP on the national essential drugs list of China.
METHODS AND ANALYSIS: We will conduct a network meta-analysis (NMA) of all randomised controlled trials to evaluate the use of oral Chinese patent medicines as adjuvant for the treatment of UAP. We will explore eight electronic databases from their inception to June 2018 and search for grey literature. Primary outcomes include mortality and the cardiovascular events. Secondary outcomes include: (1) symptom improvement; (2) ECG improvement; (3) frequency of acute angina attack; (4) duration of angina; (5) adverse effects. Two independent authors will screen titles and abstracts, review full texts, extract data, assess the risk of bias using the Cochrane risk of bias tool and assess the quality of evidence and strength of the recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). If adequate data are available, NMA will be performed with Bayesian analysis methods.
ETHICS AND DISSEMINATION: The NMA will help us to reduce the uncertainty of interventions and help clinicians to make optimal and more accurate therapeutic decisions for adults with UAP. Therefore, we will publish the findings of this study in a peer-reviewed journal. No ethics approval is necessary for this study based on the nature of its design.
TRIAL REGISTRATION NUMBER: CRD42018092822.

PMID: 31542734 [PubMed - indexed for MEDLINE]

New oncologic emergencies: What is there to know about inmunotherapy and its potential side effects?

Eur J Intern Med. 2019 Aug;66:1-8

Authors: Barquín-García A, Molina-Cerrillo J, Garrido P, Garcia-Palos D, Carrato A, Alonso-Gordoa T

Abstract
Over the last decade anticancer treatment has experienced encouraging changes. One of the latest developments is immunotherapy, which is increasingly becoming a mainstay for the treatment of these malignancies. Unlike conventional chemotherapy, immunotherapy enhances anti-tumor immune response by blocking inhibitory immune checkpoints, and allowing our own immune system to fight against the tumor cells, arising as a new and innovative mechanism of action. Therefore, although well tolerated, these drugs have a unique side effect profile and are known to cause immune-related adverse events (irAEs). Adverse effects of immunotherapy are most commonly observed in the skin, gastrointestinal tract, liver, lung and endocrine systems. Less common toxicities may include neurological, haematological, cardiac, ocular or rheumatologic involvement. As far as we know, cancer patients are frequently seen in the Emergency Department due to treatment related toxicities, thus there is an increasing necessity to learn about this particular side effect profile given that they entail a different and unique management than that of classic chemotherapy drugs.

PMID: 31130304 [PubMed - indexed for MEDLINE]

PRISModegib: the use of the PRISM test to assess the health-related quality of life of patients with locally advanced basal cell carcinoma undergoing Hedgehog pathway inhibitor therapy.

Br J Dermatol. 2019 08;181(2):406-407

Authors: Gualdi G, Moro R, Regina V, Caravello S, Monari P, Calzavara-Pinton PG

PMID: 30737996 [PubMed - indexed for MEDLINE]

Serious Adverse Events Reported with Dietary Supplement Use in the United States: A 2.5 Year Experience.

J Diet Suppl. 2020;17(2):227-248

Authors: Schmitz SM, Lopez HL, Mackay D, Nguyen H, Miller PE

Abstract
Dietary supplement marketers assure the safety of their products by complying with current good manufacturing practices and a host of federal regulations, including those enforced by the Food and Drug Administration (FDA). Post-market surveillance is a key part of identifying safety problems associated with dietary supplement products. FDA requires dietary supplement marketers to provide a domestic address or phone number on product labels for consumers, family members, or health care professionals to report adverse events (AEs) associated with product use and to report all serious adverse events (SAEs) to the agency within 15 business days of receipt. We aimed to evaluate the characteristics of AEs reported with dietary supplement use, including dietary supplement type and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) that occur with reported SAEs. A total of 41,121 unique adverse event cases reported to two large, U.S.-based dietary supplement marketers in a 2.5-year period (March 1, 2014-August 31, 2016) were assessed for seriousness using established criteria. Each SAE was assigned one or more MedDRA preferred terms and system organ classes (SOC). The types of supplements most responsible for SAEs were assessed. Of the 41,121 AE cases reported, 203 (0.48%) were SAEs. SAEs tended to occur with products marketed for weight loss (69.0%) and glycemic control (19.2%). SAEs occurred most commonly in the cardiovascular, gastrointestinal, and nervous system disorder SOCs. The percentage of SAEs reported to dietary supplement marketers is low, predominantly among consumers of two types of supplements. Further study is needed among a larger cohort of supplement users to determine causal associations between types of supplement products and serious adverse events.

PMID: 30513022 [PubMed - indexed for MEDLINE]

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 2020/09/30

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.

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 2020/09/30

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.

21 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 2020/09/29

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

The cooccurrence of heightened media attention and adverse drug reaction reports for hormonal contraception in the United Kingdom between 2014 and 2017.

Br J Clin Pharmacol. 2020 Sep 25;:

Authors: Postma LGM, Donyai P

Abstract
AIM: The aim of this study was to examine the cooccurrence of heightened media attention after the publication of a paper by Skovlund et al. in September 2016 on the link between hormonal contraception and depression or mood on adverse drug reaction (ADR) reports in the UK.
METHODS: A quantitative analysis of relevant newspaper articles published between January 2014 and December 2017 was performed, as well as a content analysis. ADR reports were collected from the Medicines and Healthcare products Regulatory Agency website and via a Freedom of Information request. A quantitative analysis was performed on ADR reports of hormonal contraceptives for all ADRs and for Depressed mood disorders and disturbances.
RESULTS: The publication of the Skovlund et al. paper did not lead to a peak in relevant newspaper articles, but there was a change in the content of the newspaper articles, which focussed more on the link between hormonal contraceptives and depression or mood. There was an overall increase in ADR reports by women relating to hormonal contraceptives between 2016 and 2017, and for combined contraceptives this was due to an increase in ADR reports of Depressed mood disorders and disturbances.
CONCLUSIONS: The content of media attention appears to affect ADR reporting by women for combined contraceptives. In general, patients report the majority of Depressed mood disorders and disturbances ADRs as opposed to health professionals who report other ADRs. Care providers can anticipate to the effect of heightened media attention and help patients when they experience these ADRs.

PMID: 32978837 [PubMed - as supplied by publisher]

A Comprehensive Methodology to Systematically Identify Drug Hypersensitivity and Anaphylactic Reactions in Clinical Trial Databases.

Pharmaceut Med. 2020 Sep 25;:

Authors: Xavier H, Hara I, Ottesen LH, Verheijen RB, Ghiorghiu D, Morgan C

Abstract
BACKGROUND: The incidence of drug hypersensitivity or anaphylactic reactions in clinical trial databases is thought to be underestimated due to variable clinical presentations and lack of clear definitions.
OBJECTIVE: Our objective was to develop a more comprehensive, systematic methodology for retrospectively identifying potential hypersensitivity or anaphylactic reactions reported in patients treated with investigational drugs in clinical trials and to accurately assess and characterise the risk.
METHODS: A three-step approach was developed to identify hypersensitivity or anaphylactic reactions: clinical trial database search, medical review, and adjudication to confirm or rule out cases. The database search strategy consisted of the narrow search for Standardized MedDRA Query (SMQ) Hypersensitivity, a modified MedDRA query based on SMQ Anaphylactic reaction, and pyrexia-related MedDRA Preferred Terms. The cases identified from the search were further medically reviewed taking into consideration the temporal relationship, seriousness, severity, course, and management of the events, action taken, and outcomes of adverse events. Those cases deemed to have potentially drug-related hypersensitivity were then adjudicated to be confirmed or ruled out.
RESULTS: The method was applied to a clinical trial database containing safety data for 421 patients treated with an investigational drug. Application of the methodology led to 19 hypersensitivity cases being identified. Of these, 12 were classified as immediate reactions and 7 as non-immediate reactions.
CONCLUSION: This three-step method provided a thorough and robust way to identify hypersensitivity reactions, including anaphylaxis, in a clinical trial database. This method could be applied to investigational drugs to improve early detection and monitoring of potential safety concerns, subsequent patient safety management strategies, and potentially programme-wide drug development decisions. Algorithmic tools and narrow and/or broad SMQs should be considered when evaluating safety concerns. The authors also recommend a revision of the MedDRA SMQ of Anaphylactic reaction.

PMID: 32975782 [PubMed - as supplied by publisher]

Purified Sika deer antler protein attenuates GM-induced nephrotoxicity by activating Nrf2 pathway and inhibiting NF-κB pathway.

Sci Rep. 2020 Sep 24;10(1):15601

Authors: Wang Z, Wang L, Wang J, Luo J, Ruan H, Zhang J

Abstract
Although gentamicin is widely used as an antibiotic in clinical practice, it also has some side-effects, such as acute kidney injury, which is a common condition caused by the abuse of gentamicin. Sika deer antler protein (SDAPR) can antagonize drug-induced AKI. Since SDAPR is recognized as an effective part of velvet antler, its components were further separated. Two components named SDAP1 and SDAP2 were obtained. The protective effects of SDAPR, SDAP1 and SDAP2 on GM-induced cytotoxicity to HEK293 and its potential mechanisms were studied. MTT and xCELLigence Real-Time cell analysis showed that SDAPR, SDAP1 and SDAP2 could protect HEK293 cells from GM toxicity. Similarly, SDAPR, SDAP1 and SDAP2 can reduce ROS level, reduce oxidative stress and improve inflammation Further studies have shown that SDAPR, SDAP1 and SDAP2 upregulate the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1, and down-regulate the NF-κB pathway by reducing the protein expression of NF-κB. Annexin V/PI flow cytometry and Hoechst 33258 staining showed that SDAPR, SDAP1 and SDAP2 inhibited GM-induced apoptosis in HEK293 cells. Western blot analysis showed SDAPR, SDAP1 and SDAP2 decreased expression level of Bax and Cleaved-caspase-3, and increased the expression level of Bcl-2. In addition, we examined the feasibility of SDAP1 and SDAP1 to avoid kidney injury in a GM mouse model. In conclusion, SDAPR, SDAP1 and SDAP2 can be used to prevent GM-induced HEK293 cytotoxicity, probably because they have strong anti-oxidative stress, anti-inflammatory and anti-apoptotic effects. And SDAP1 and SDAP2 can inhibit GM-induced acute kidney injury in mice.

PMID: 32973191 [PubMed - in process]

DPDDI: a deep predictor for drug-drug interactions.

BMC Bioinformatics. 2020 Sep 24;21(1):419

Authors: Feng YH, Zhang SW, Shi JY

Abstract
BACKGROUND: The treatment of complex diseases by taking multiple drugs becomes increasingly popular. However, drug-drug interactions (DDIs) may give rise to the risk of unanticipated adverse effects and even unknown toxicity. DDI detection in the wet lab is expensive and time-consuming. Thus, it is highly desired to develop the computational methods for predicting DDIs. Generally, most of the existing computational methods predict DDIs by extracting the chemical and biological features of drugs from diverse drug-related properties, however some drug properties are costly to obtain and not available in many cases.
RESULTS: In this work, we presented a novel method (namely DPDDI) to predict DDIs by extracting the network structure features of drugs from DDI network with graph convolution network (GCN), and the deep neural network (DNN) model as a predictor. GCN learns the low-dimensional feature representations of drugs by capturing the topological relationship of drugs in DDI network. DNN predictor concatenates the latent feature vectors of any two drugs as the feature vector of the corresponding drug pairs to train a DNN for predicting the potential drug-drug interactions. Experiment results show that, the newly proposed DPDDI method outperforms four other state-of-the-art methods; the GCN-derived latent features include more DDI information than other features derived from chemical, biological or anatomical properties of drugs; and the concatenation feature aggregation operator is better than two other feature aggregation operators (i.e., inner product and summation). The results in case studies confirm that DPDDI achieves reasonable performance in predicting new DDIs.
CONCLUSION: We proposed an effective and robust method DPDDI to predict the potential DDIs by utilizing the DDI network information without considering the drug properties (i.e., drug chemical and biological properties). The method should also be useful in other DDI-related scenarios, such as the detection of unexpected side effects, and the guidance of drug combination.

PMID: 32972364 [PubMed - in process]

Digoxin therapeutic drug monitoring: age influence and adverse events.

Tunis Med. 2020 Jan;98(1):35-40

Authors: Charfi R, Ben Sassi M, Gaies E, Jebabli N, Daghfous R, Trabelsi S

Abstract
INTRODUCTION: Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. Digoxin has a narrow therapeutic range. So, in the treatment of older patients (≥ 65 years), it is important to set the optimal dose of digoxin to prevent toxicity and therapeutic drug monitoring of digoxin trough plasmatic concentration (C0) may be useful.
AIM: To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin.
METHODS: It consisted in a retrospective study. We included all the patients addressed to the department of clinical pharmacology for digoxin C0 measurement by an automated fluorescence polarization immunoassay. Therapeutic ranges of digoxin C0 were: 1 to 2.5 ng.mL-1 in children, 0.8 to 2 ng.mL-1 in adults and 0.5 to 0.9 ng.mL-1 in older adults (≥ 65 years) in atrial fibrillation and heart failure.
RESULTS: We collected 183 samples from 132 patients. Sex ratio M/W was 0.47. Mean age was 60 years and 57% of patients were older adults. Mean dose of digoxin was 0.3 mg.day-1. In older adults, 45% were administered daily doses over 0.125 mg.day-1. Mean digoxin C0 was 1.6 ng.mL-1. There was more supra-therapeutic C0 in older adults than younger ones (p<0.0001).There was no correlation between C0 and daily dose of digoxin. Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults.
CONCLUSION: TDM is useful to prevent toxicity, mainly in older adults where diagnosis may be difficult to establish.

PMID: 32395775 [PubMed - indexed for MEDLINE]

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors.

BMC Ophthalmol. 2020 Jan 09;20(1):19

Authors: Shin E, Lim DH, Han J, Nam DH, Park K, Ahn MJ, Kang WK, Lee J, Ahn JS, Lee SH, Sun JM, Jung HA, Chung TY

Abstract
BACKGROUND: We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis.
MATERIALS: Retrospective chart review.
RESULTS: Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy.
CONCLUSIONS: EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.
TRIAL REGISTRATION: This study was approved by the institutional review board (IRB) of Samsung Medical Center (IRB no. 2019-04-027) and was conducted according to the principles expressed in the Declaration of Helsinki.

PMID: 31918686 [PubMed - indexed for MEDLINE]

Proactive therapeutic drug monitoring (TDM) may be helpful in managing long-term treatment with linezolid safely: findings from a monocentric, prospective, open-label, interventional study.

J Antimicrob Chemother. 2019 12 01;74(12):3588-3595

Authors: Cojutti PG, Merelli M, Bassetti M, Pea F

Abstract
BACKGROUND: Thrombocytopenia may be a dose-dependent adverse effect of linezolid therapy.
OBJECTIVES: To assess whether proactive therapeutic drug monitoring (TDM) could be helpful in preventing and/or in recovering from the occurrence of linezolid-induced thrombocytopenia during long-term treatment.
METHODS: This was a monocentric, prospective, open-label, interventional study conducted between June 2015 and December 2017 among adult patients receiving >10 days of linezolid therapy and undergoing proactive TDM (desired trough level 2-8 mg/L) and platelet count assessment at day 3-5 and then once weekly up to the end of treatment.
RESULTS: Sixty-one patients were included. Twenty-eight (45.9%) always had desired trough level (group A) and 33 (54.1%) experienced linezolid overexposure (group B) [29/33 transiently (subgroup B1) and 4/33 persistently (subgroup B2)]. No patient experienced linezolid underexposure. Median duration of treatment for the different groups ranged between 19 and 54 days. Thrombocytopenia occurred overall in 14.8% of cases (9/61). The incidence rate of thrombocytopenia was significantly lower (P=0.012) in both group A (10.7%; 3/28) and subgroup B1 (10.3%; 3/29) than in subgroup B2 (75.0%; 3/4). Thrombocytopenic patients belonging to both group A and group B1 recovered from thrombocytopenia without the need for discontinuing therapy. Multivariate linear regression analysis revealed that thrombocytopenia was independently associated with baseline platelet count and with median linezolid trough concentrations.
CONCLUSIONS: Proactive TDM of linezolid may be beneficial either in preventing or in recovering from dose-dependent thrombocytopenia, even when treatment lasts for more than 28 days. Larger prospective studies are warranted to confirm our findings.

PMID: 31504570 [PubMed - indexed for MEDLINE]

Monoclonal antibody utilization characteristics in patients with multiple myeloma.

Anticancer Drugs. 2019 09;30(8):859-865

Authors: Ailawadhi S, Sher T, Azzouqa AG, Meghji Z, Jain T, Jani P, Ahmed S, Diehl N, Roy V, Shah V, Hodge D, Ailawadhi M, Alegria VR, Paulus A, Chanan-Khan A, Fonseca R

Abstract
This study analyzed 91 multiple myeloma patients who received two monoclonal antibodies, Daratumumab and Elotuzumab, over a year and report the adverse event profile, infusion practices and utilization of these drugs in the real world. All current reported data on monoclonal antibodies is from clinical trials, without any real-world experience. Patients from Mayo Clinic Florida or Arizona diagnosed with relapsed or refractory multiple myeloma who were treated with Daratumumab or Elotuzumab alone or in combination between 1 January 2016 and 31 December 2016 were included in the analysis. Daratumumab-treated patients (n = 78) were more heavily pre-treated than that in published clinical trials, whereas the elotuzumab patient (n = 13) profile was similar to that published before. Infusion time was on average 2 hours less than the prescribing guidelines and premedication use varied noticeably after the initial monoclonal antibody infusion, with an overall decrease over time. We noted higher than reported haematologic adverse events, especially neutropenia and fewer non-haematologic adverse events. 91.7% infusion-related reactions were observed during the first monoclonal antibody infusion, with a subsequent decrease. All infusion-related reactions were grade 2 or less, and none of the patients discontinued treatment due to infusion-related reactions. Baseline allergy profile or laboratory tests were not associated with the likelihood of developing monoclonal antibody-related infusion-related reactions. The real-world safety profile of monoclonal antibodies showed varying adverse event patterns than those reported in previous clinical trials. The infusion-related reaction patterns were similar to previous reports. Despite changes in premedication regimens safety was maintained in succeeding infusions. Such treatment utilization data is vital to broaden our knowledge of approved therapeutic agents and maximize their benefits for patients.

PMID: 31415286 [PubMed - indexed for MEDLINE]