Treatment preferences of patients with relapsed and refractory multiple myeloma: a qualitative study.

BMC Cancer. 2019 Mar 25;19(1):264

Authors: Parsons JA, Greenspan NR, Baker NA, McKillop C, Hicks LK, Chan O

Abstract
BACKGROUND: Multiple myeloma is a haematological malignancy characterized by significant morbidity and mortality. This study sought to develop an in-depth understanding of patients' lived experiences of relapsed or refractory multiple myeloma (RRMM) and its treatment, and to identify which features of treatment were most important to them.
METHODS: Qualitative interviews and focus groups (FGs) were conducted with 32 people living with RRMM across Canada. In Phase 1, interviews focused on participants' accounts of their experiences with the disease and its treatment and laid the groundwork for the FGs (Phase 2). The FGs developed a deeper understanding of patients' treatment priorities. Interview and FG transcripts were coded for emergent themes and patterns.
RESULTS: The interviews identified important side effects that had significant impacts on patients' lives, including physical, cognitive, and psychological/emotional side effects. Participants also identified specific treatment features (attributes) that were important to them. These were compiled into a list and used in the FGs to understand patients' priorities. Higher prioritized attributes were: life expectancy, physical and cognitive side effects, and financial impact. Mode of administration, treatment intervals, psychological side effects, and sleep/mood effects were identified as lower priorities.
CONCLUSIONS: RRMM and its treatments impact importantly on patients' quality-of-life across a range of domains. Patients prioritized treatment features that could enhance life expectancy, minimize side effects and offset financial burdens.
IMPLICATIONS FOR CANCER SURVIVORS: A clear articulation of patient priorities can contribute to efforts to design treatment with patients' concerns in mind, thereby promoting a more patient-centered approach to care.

PMID: 30909874 [PubMed - indexed for MEDLINE]

Predictors of gastrointestinal bleeding in older persons taking nonsteroidal anti-inflammatory drugs: Results from the FDA adverse events reporting system.

J Am Assoc Nurse Pract. 2019 03;31(3):214-215

Authors:

PMID: 30839389 [PubMed - indexed for MEDLINE]

A classification framework for exploiting sparse multi-variate temporal features with application to adverse drug event detection in medical records.

BMC Med Inform Decis Mak. 2019 01 10;19(1):7

Authors: Bagattini F, Karlsson I, Rebane J, Papapetrou P

Abstract
BACKGROUND: Adverse drug events (ADEs) as well as other preventable adverse events in the hospital setting incur a yearly monetary cost of approximately $3.5 billion, in the United States alone. Therefore, it is of paramount importance to reduce the impact and prevalence of ADEs within the healthcare sector, not only since it will result in reducing human suffering, but also as a means to substantially reduce economical strains on the healthcare system. One approach to mitigate this problem is to employ predictive models. While existing methods have been focusing on the exploitation of static features, limited attention has been given to temporal features.
METHODS: In this paper, we present a novel classification framework for detecting ADEs in complex Electronic health records (EHRs) by exploiting the temporality and sparsity of the underlying features. The proposed framework consists of three phases for transforming sparse and multi-variate time series features into a single-valued feature representation, which can then be used by any classifier. Moreover, we propose and evaluate three different strategies for leveraging feature sparsity by incorporating it into the new representation.
RESULTS: A large-scale evaluation on 15 ADE datasets extracted from a real-world EHR system shows that the proposed framework achieves significantly improved predictive performance compared to state-of-the-art. Moreover, our framework can reveal features that are clinically consistent with medical findings on ADE detection.
CONCLUSIONS: Our study and experimental findings demonstrate that temporal multi-variate features of variable length and with high sparsity can be effectively utilized to predict ADEs from EHRs. Two key advantages of our framework are that it is method agnostic, i.e., versatile, and of low computational cost, i.e., fast; hence providing an important building block for future exploitation within the domain of machine learning from EHRs.

PMID: 30630486 [PubMed - indexed for MEDLINE]

An anticholinergic burden score for German prescribers: score development.

BMC Geriatr. 2018 10 11;18(1):239

Authors: Kiesel EK, Hopf YM, Drey M

Abstract
BACKGROUND: Anticholinergic drugs put elderly patients at a higher risk for falls, cognitive decline, and delirium as well as peripheral adverse reactions like dry mouth or constipation. Prescribers are often unaware of the drug-based anticholinergic burden (ACB) of their patients. This study aimed to develop an anticholinergic burden score for drugs licensed in Germany to be used by clinicians at prescribing level.
METHODS: A systematic literature search in pubmed assessed previously published ACB tools. Quantitative grading scores were extracted, reduced to drugs available in Germany, and reevaluated by expert discussion. Drugs were scored as having no, weak, moderate, or strong anticholinergic effects. Further drugs were identified in clinical routine and included as well.
RESULTS: The literature search identified 692 different drugs, with 548 drugs available in Germany. After exclusion of drugs due to no systemic effect or scoring of drug combinations (n = 67) and evaluation of 26 additional identified drugs in clinical routine, 504 drugs were scored. Of those, 356 drugs were categorised as having no, 104 drugs were scored as weak, 18 as moderate and 29 as having strong anticholinergic effects.
CONCLUSIONS: The newly created ACB score for drugs authorized in Germany can be used in daily clinical practice to reduce potentially inappropriate medications for elderly patients. Further clinical studies investigating its effect on reducing anticholinergic side effects are necessary for validation.

PMID: 30305048 [PubMed - indexed for MEDLINE]

Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients.

Clin Breast Cancer. 2018 10;18(5):e1173-e1179

Authors: Jabir RS, Ho GF, Annuar MABA, Stanslas J

Abstract
PURPOSE: Nonhematologic adverse events (AEs) of docetaxel constitute an extra burden in the treatment of cancer patients and necessitate either a dose reduction or an outright switch of docetaxel for other regimens. These AEs are frequently associated with genetic polymorphisms of genes encoding for proteins involved docetaxel disposition. Therefore, we investigated that association in Malaysian breast cancer patients.
MATERIALS AND METHODS: A total of 110 Malaysian breast cancer patients were enrolled in the present study, and their blood samples were investigated for different single nucleotide polymorphisms using polymerase chain reaction restriction fragment length polymorphism. AEs were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0.
RESULTS: Fatigue, nausea, oral mucositis, and vomiting were the most common nonhematologic AEs. Rash was associated with heterozygous and mutant genotypes of ABCB1 3435C>T (P < .05). Moreover, patients carrying the GG genotype of ABCB1 2677G>A/T reported more fatigue than those carrying the heterozygous genotype GA (P < .05). The presence of ABCB1 3435-T, ABCC2 3972-C, ABCC2 1249-G, and ABCB1 2677-G alleles was significantly associated with nausea and oral mucositis. The coexistence of ABCB1 3435-C, ABCC2 3972-C, ABCC2 1249-G, and ABCB1 2677-A was significantly associated with vomiting (P < .05).
CONCLUSION: The prevalence of nonhematologic AEs in breast cancer patients treated with docetaxel has been relatively high. The variant allele of ABCB1 3435C>T polymorphism could be a potential predictive biomarker of docetaxel-induced rash, and homozygous wild-type ABCB1 2677G>A/T might predict for a greater risk of fatigue. In addition, the concurrent presence of specific alleles could be predictive of vomiting, nausea, and oral mucositis.

PMID: 29885788 [PubMed - indexed for MEDLINE]

Chemotherapy-associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome.

Psychooncology. 2018 08;27(8):1995-2001

Authors: Kim HJ, Barsevick AM, Chan A, Chae JW

Abstract
OBJECTIVE: To identify those experiencing significant self-reported cognitive decline over 2 time points during chemotherapy, examine the risk factors for cognitive decline, and examine differences between those with and without significant decline in functional limitations.
METHODS: This secondary analysis used data from 163 cancer patients, collected from a Korean University hospital. Significant decline was determined by 15% or more reduction from baseline in the Functional Assessment of Cancer Therapy-Cognitive Function. Multivariate logistic regression was performed to estimate risk factors. Repeated-measures ANOVA and t tests tested differences in groups with and without cognitive decline in cognitive impairment and functional limitation.
RESULTS: About 31% (n = 51) experienced significant cognitive decline. Groups with and without decline significantly differed in cognitive-impairment changes over time (F = 238.49, P < .001) and in functional limitations at follow-up (t test, P < .01). Those experiencing increased fatigue over time (odds = 0.94, P < .05) and those who underwent 2 or more cycles between time 1 and 2 (odds = 2.61; P < .05) had higher risk of significant decline over time during chemotherapy.
CONCLUSION: Significant cognitive decline occurred during active chemotherapy; attention to cognitive impairment should be given in the early phase of chemotherapy.

PMID: 29744963 [PubMed - indexed for MEDLINE]

Prevalence of, and factors associated with health supplement use in Dubai, United Arab Emirates: a population-based cross-sectional study.

BMC Complement Altern Med. 2019 Jul 12;19(1):172

Authors: Abdulla NM, Aziz F, Blair I, Grivna M, Adam B, Loney T

Abstract
BACKGROUND: Health supplement (HS) products that are available in the Emirate of Dubai (United Arab Emirates; UAE) contain chemicals that may adversely affect human health. This study aimed to investigate the prevalence of, and factors associated with HS consumption, knowledge, related adverse events, and reporting practices of adverse events amongst the general population in Dubai, UAE.
METHODS: A cross-sectional household telephone survey using a computer-assisted questionnaire was conducted amongst a random representative sample (n = 1203) of the Dubai population that assessed HS use and knowledge. Dependent variables were supplement use and reports of adverse events while independent variables included socio-demographic factors, knowledge, attitudes, and practice. Logistic regression analysis was performed to identify factors independently associated with HS use.
RESULTS: Among the 1203 participants in this study, 455 (37.8%) reported ever using HS. Amongst ever-users, reasons for use were to improve health (66.1%), for bodybuilding (9.9%), disease prevention (6.8%), and weight management (5.3%). The majority of users purchased their HS from pharmacies (88.4%) or were prescribed HS (46.6%). Vitamins were the most commonly used HS (87.9%) followed by minerals (10.5%) and sports nutrition products (10.5%). Only 2.9% of users experienced an adverse event associated with HS use which all resolved when the HS was discontinued. Only three of those affected reported the incident. Multivariate logistic regression analysis revealed that HS use was independently associated with female gender (adjusted odds ratio [AOR]; 3.26, 95% confidence interval [CI]: 2.26-4.70), higher income (AOR 2.41, 95% CI: 1.20-4.83), being a past-smoker (AOR 2.39, 95% CI: 1.27-4.48), having an allergy (AOR 1.75, 95% CI: 1.14-2.66), more frequent doctor visits (AOR 1.86, 95% CI: 1.02-3.39), taking prescribed medications (AOR 1.47, 95% CI: 1.04-2.06), and knowledge about HS (AOR 3.91, 95% CI: 2.26-6.76).
CONCLUSIONS: Our study provides the first population-based estimates of HS use and HS-related adverse events in the Gulf region. Adverse events associated with HS are infrequent and this may be due to the well-developed regulatory framework in Dubai and the high level of knowledge amongst consumers who mainly consume vitamins and minerals on the advice of pharmacists or healthcare professionals.

PMID: 31299957 [PubMed - in process]

Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy.

Eur J Cancer. 2019 Jul 09;118:35-40

Authors: Locati LD, Piovesan A, Durante C, Bregni M, Castagna MG, Zovato S, Giusti M, Ibrahim T, Puxeddu E, Fedele G, Pellegriti G, Rinaldi G, Giuffrida D, Verderame F, Bertolini F, Bergamini C, Nervo A, Grani G, Rizzati S, Morelli S, Puliafito I, Elisei R

Abstract
BACKGROUND: Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)-resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
METHODS: The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
RESULTS: From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval [CI], 7.7-12.6) and 23.8 months (95% CI, 19.7-25.0) respectively.
CONCLUSION: Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.

PMID: 31299580 [PubMed - as supplied by publisher]

Barriers interfering with establishment of Collaborative Drug Therapy Management (CDTM) agreements between clinical pharmacists and physicians.

Saudi Pharm J. 2019 Jul;27(5):713-716

Authors: Alhossan A, Alazba A

Abstract
Purpose: The current level of awareness among health care providers towards working under collaborative agreements, and the barriers that interfere with establishing CDTM agreements between clinical pharmacists and physicians were studied.
Methods: A structured survey was developed after reviewing the literature on CDTM. The questions were validated to assess the level of awareness regarding the role of clinical pharmacists in providing drug therapy management, and to determine the main barriers for not having collaborative agreements with different specialties. In addition to demographic data, physicians' education background, reasons for not having clinical pharmacy services in their clinics, and their perceptions for signing a collaborative agreement were also collected. The sample for the study was obtained from different health specialties in Saudi Arabia. The validated survey was sent and received within approximately two months, Oct-Nov 2017.
Results: We have received 55 responses from different sectors, a 79% response rate. Most physicians had worked before with a clinical pharmacist (76%) and of which 60% valued the services provided by the clinical pharmacist as extremely important and very important (29.1%; 30.9%) respectively. When physicians asked if they have heard about the Collaborative Drug Therapy Management agreement or the term CDTM, 67% of respondents haven't heard that before. Most of the responses, regarding the physicians' awareness of the actual CDTM agreement services, were correct. Only 18% selected incorrect CDTM services. The results showed higher percentages of physicians agreeing with the benefits of CDTM agreement as it can improve overall patient care, reduces risk of drug related adverse events or interactions and allows clinical pharmacists to be part of patient care; 85.5, 83.6 and 83.6 respectively. Physicians who rated the possibility to be involved or to encourage other health care professionals in signing collaborative agreements as high were 76.3 and 74.5 respectively. Based on their specialty, emergency medicine's physicians were most likely to have a CDTM agreement and to encourage others too. On a scale from zero to hundred, the average of the responses rating lack of knowledge about such an agreement as potential barrier on preventing CDTM agreements was 69 ± 0.30. While the gender barrier had the lowest rating with a mean of 15.
Conclusion: There is a huge lack of knowledge and understanding about the role of clinical pharmacists and in CDTM concept. This lack of knowledge affected on having collaborations between clinical pharmacists and physicians in different settings. Educating health care providers and stakeholders about the role of clinical pharmacists in providing drug therapy management and encouraging the concept of CDTM among healthcare providers are the main solutions to enhance clinical pharmacist's role in patient care.

PMID: 31297026 [PubMed]

Risk assessment of patient factors and medications for drug-related problems from a prospective longitudinal study of newborns admitted to a neonatal intensive care unit in Brazil.

BMJ Open. 2019 Jul 10;9(7):e024377

Authors: Leopoldino RD, Santos MT, Costa TX, Martins RR, Oliveira AG

Abstract
OBJECTIVE: To identify patient factors and medications associated with the occurrence of drug-related problems (DRPs) in neonates admitted to neonatal intensive care units (NICUs).
DESIGN: Prospective, longitudinal study.
SETTING: NICU of a teaching hospital in Brazil.
PARTICIPANTS: Data were collected from the records of the clinical pharmacy service of all neonates admitted between April 2014 and January 2017, excluding neonates with length of stay in the NICU <24 hours or without prescribed drugs.
PRIMARY OUTCOME MEASURES: Occurrence of one or more DRP (conditions interfering in the patient's pharmacotherapy with potential undesired clinical outcomes).
RESULTS: The study observed 600 neonates who had a median length of stay in the NICU of 13 days (range 2-278 days). DRPs were identified in most neonates (60.5%). In a multivariate logistic regression model, the factors independently associated with DRP were gestational age (adjusted OR (AOR) 0.85, 95% CI 0.81 to 0.89), 5 min Apgar <7 (AOR 1.74, 95% CI 1.00 to 3.13), neurological disease (AOR 2.49, 95% CI 1.09 to 5.69), renal disease (AOR 5.75, 95% CI 1.85 to 17.8) and cardiac disease (AOR 2.36, 95% CI 1.31 to 4.24). The medications with greater risk for DRP were amphotericin B (AOR 4.80), meropenem (AOR 4.09), alprostadil (AOR 3.38), vancomycin (AOR 3.34), ciprofloxacin (AOR 3.03), gentamicin (AOR 2.43), cefepime (AOR 1.88), amikacin (AOR 1.82) and omeprazole (AOR 1.66). These medicines represented one-third of all prescribed drugs.
CONCLUSIONS: Gestational age, 5 min Apgar <7, and neurological, cardiac and renal diseases are risk factors for DRP in NICUs. Alprostadil, omeprazole and several anti-infectives were associated with greater risk of DRP.

PMID: 31296505 [PubMed - in process]

[Study and thought on the safety of traditional Chinese medicines under Healthy China strategy].

Zhongguo Zhong Yao Za Zhi. 2018 Mar;43(5):857-860

Authors: Xiao XH

Abstract
As the Healthy China planning has been implemented, traditional Chinese medicine (TCM) has witnessed unprecedented developmental opportunities. However, the safety of TCM has always been like The Sword of Damocles in TCM area, endangering the healthy and sustainable development of TCM. In order to solve the problem of TCM safety in China as soon as possible, the author puts forward that the situation and issues of TCM safety should be considered with the change of the times. At the same time, it is suggested that the research on TCM safety should be listed as the most important project in TCM science and technology field. The safety evaluation and risk control system in line with China national situation and TCM characteristics should be established as soon as possible. The research strategy of TCM safety should be innovated from "five changes". The transition of adverse drug reactions of TCM from "still not clear" to "basically clear" should be tried to realize, which allow TCM inherited from our ancestors to make a greater contribution to human's health.

PMID: 29676078 [PubMed - indexed for MEDLINE]

Knowledge graph prediction of unknown adverse drug reactions and validation in electronic health records.

Sci Rep. 2017 11 27;7(1):16416

Authors: Bean DM, Wu H, Iqbal E, Dzahini O, Ibrahim ZM, Broadbent M, Stewart R, Dobson RJB

Abstract
Unknown adverse reactions to drugs available on the market present a significant health risk and limit accurate judgement of the cost/benefit trade-off for medications. Machine learning has the potential to predict unknown adverse reactions from current knowledge. We constructed a knowledge graph containing four types of node: drugs, protein targets, indications and adverse reactions. Using this graph, we developed a machine learning algorithm based on a simple enrichment test and first demonstrated this method performs extremely well at classifying known causes of adverse reactions (AUC 0.92). A cross validation scheme in which 10% of drug-adverse reaction edges were systematically deleted per fold showed that the method correctly predicts 68% of the deleted edges on average. Next, a subset of adverse reactions that could be reliably detected in anonymised electronic health records from South London and Maudsley NHS Foundation Trust were used to validate predictions from the model that are not currently known in public databases. High-confidence predictions were validated in electronic records significantly more frequently than random models, and outperformed standard methods (logistic regression, decision trees and support vector machines). This approach has the potential to improve patient safety by predicting adverse reactions that were not observed during randomised trials.

PMID: 29180758 [PubMed - indexed for MEDLINE]

Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China.

Sci Rep. 2017 10 23;7(1):13819

Authors: Wang L, Li M, Xie J, Cao Y, Liu H, He Y

Abstract
With increased usage of cardiovascular drugs (CVDs) for treating cardiovascular diseases, it is important to analyze CVD-associated adverse events (AEs). In this study, we systematically collected package insert-reported AEs associated with CVDs used in China, and developed and analyzed an Ontology of Cardiovascular Drug AEs (OCVDAE). Extending the Ontology of AEs (OAE) and NDF-RT, OCVDAE includes 194 CVDs, CVD ingredients, mechanisms of actions (MoAs), and CVD-associated 736 AEs. An AE-specific drug class effect is defined to exist when all the drugs (drug chemical ingredients or drug products) in a drug class are associated with an AE, which is formulated as a new proportional class level ratio ("PCR") = 1. Our PCR-based heatmap analysis identified many class level drug effects on different AE classes such as behavioral and neurological AE and digestive system AE. Additional drug-AE correlation tests (i.e., class-level PRR, Chi-squared, and minimal case reports) were also modified and applied to further detect statistically significant drug class effects. Two drug ingredient classes and three CVD MoA classes were found to have statistically significant class effects on 13 AEs. For example, the CVD Active Transporter Interactions class (including reserpine, indapamide, digoxin, and deslanoside) has statistically significant class effect on anorexia and diarrhea AEs.

PMID: 29061976 [PubMed - indexed for MEDLINE]

Long-term luseogliflozin therapy improves histological activity of non-alcoholic steatohepatitis accompanied by type 2 diabetes mellitus.

Clin J Gastroenterol. 2019 Jul 10;:

Authors: Fujimori N, Tanaka N, Kimura T, Sano K, Horiuchi A, Kato N, Takahashi Y, Kuribayashi N, Sugiura A, Yamazaki T, Joshita S, Umemura T, Matsumoto A, Tanaka E

Abstract
A 60-year-old Japanese woman was referred to our hospital for further examination of persistent liver dysfunction. She had been suffering from type 2 diabetes mellitus since the age of 50 years. Her hemoglobin A1c (HbA1c) value was as high as 7.8% despite treatment with dipeptidyl peptidase-4 inhibitor, metformin, and sulfonylurea. After excluding viral hepatitis, alcohol or drug-induced liver injury, and autoimmune liver diseases, liver histology evidence of macrovesicular steatosis, hepatocyte ballooning, and pericellular fibrosis confirmed a diagnosis of non-alcoholic steatohepatitis (NASH). Luseogliflozin (2.5 mg/day), a sodium-glucose cotransporter 2 inhibitor (SGLT2I), was co-administered to strengthen glycemic control. Liver enzymes and HbA1c gradually improved without any adverse events. A second liver biopsy at 15 months after luseogliflozin commencement revealed improvements in steatosis, fibrosis, and overall histological activity score. This case demonstrates that long-term luseogliflozin may be a good therapeutic option for diabetic NAFLD/NASH patients. The merits of persistent SGLT2I administration for NAFLD/NASH patients warrant validation in future studies.

PMID: 31292843 [PubMed - as supplied by publisher]

Anti-cancer drugs-induced arterial injury: risk stratification, prevention, and treatment.

Med Oncol. 2019 Jul 10;36(8):72

Authors: Gara E, Csikó KG, Ruzsa Z, Földes G, Merkely B

Abstract
Vascular side effects of standard chemotherapeutic drugs and novel anti-tumor agents complicate treatment cycles, increase non-cancer-related mortality rates, and decrease the quality of life in cancer survivors. Arterial thromboembolic events (ATEE) are associated with most anti-cancer medications. Previous articles have reported a variety of vascular events including ST-segment elevation myocardial infarction as one of the most severe acute arterial attacks. Cardiologists should play an early role in identifying those at high risk for vascular complications and tailor anti-thrombotic therapies in keeping with thromboembolic and bleeding risks. Early preventive steps and individualized chemotherapy may decrease anti-tumor treatment-related vascular events. Here, we aim to provide an extensive review of anti-tumor drug-induced vascular injury (DIVI), pathomechanisms, and risk stratification underlining arterial events. We give a summary of clinical manifestations, treatment options, and possible preventive measures of DIVI. Additionally, the treatment of modifiable risk factors and tailored choice of chemotherapy must be considered in all oncology patients to prevent DIVI. We propose a complex tool for ATEE risk stratification which is warranted for early prediction leading to less frequent complications in cancer patients.

PMID: 31292791 [PubMed - in process]

Adverse Drug Events in Patients with Dementia and Neuropsychiatric/Behavioral, and Psychological Symptoms, a One-Year Prospective Study.

Int J Environ Res Public Health. 2019 03 15;16(6):

Authors: Hernández MH, Mestres C, Modamio P, Junyent J, Costa-Tutusaus L, Lastra CF, Mariño EL

Abstract
Older people usually present with adverse drug events (ADEs) with nonspecific symptoms such as cognitive decline, recurrent falls, reduced mobility, and/or major deterioration. The aims of this study were to assess the ADEs of patients with dementia and presenting neuropsychiatric/behavioral, and psychological symptoms in dementia (BPSD) and to categorize and identify the principal factors that allow to prevent ADEs, and separately ADEs that result in falls. To that end, a one-year prospective study in a psychogeriatric ward (July 2015 to July 2016) was performed. All patients admitted to this ward were eligible for enrolment. Patients who met any of the following criteria were excluded from the study: Patients without cognitive impairment, a length of stay under 7 days, and palliative or previous psychiatric pathology. We included 65 patients (60% women, 84.9 years ± 6.7) with mild to moderate cognitive impairment, moderate to severe functional dependence, and a high prevalence of geriatric syndromes and comorbidity. A total of 87.7% were taking five or more drugs (mean 9.0 ± 3.1). ADEs were identified during the interdisciplinary meeting and the follow up by clinical record. Sixty-eight ADEs (81.5% patients) were identified, of which 73.5% were not related to falls. From these, 80% were related to drugs of the nervous system. The Naranjo algorithm determined that 90% of ADEs were probable. The severity of the ADEs was Category E in 34 patients (68%). The number of preventable ADE according to the Schumork⁻Thornton test was 58%. The main ADE was drowsiness/somnolence (27.7%). ADEs related to falls represented a 26.5%. The balance between effective treatment and safety is complex in these patients. A medication review in interdisciplinary teams is an essential component to optimize safety prevention.

PMID: 30875907 [PubMed - indexed for MEDLINE]

[Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature review].

Zhongguo Zhong Yao Za Zhi. 2018 Feb;43(4):820-832

Authors: Wang GQ, Gao Y, Liu FM, Wei RL, Xie YM

Abstract
To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication.

PMID: 29600661 [PubMed - indexed for MEDLINE]

Clinical Laboratory Tests in Some Acute Exogenous Poisonings.

Folia Med (Plovdiv). 2017 Sep 01;59(3):303-309

Authors: Tufkova SG, Yankov IV, Paskaleva DA

Abstract
BACKGROUND: There is no specific toxicological screening of clinical laboratory parameters in clinical toxicology when it comes to acute exogenous poisoning.
AIM: To determine routine clinical laboratory parameters and indicators for assessment of vital functions in patients with acute intoxications.
MATERIALS AND METHODS: One hundred and fifty-three patients were included in the present study. They were hospitalized in the Department of Clinical Toxicology at St. George University Hospital, Plovdiv for cerebral toxicity inducing medication (n = 45), alcohol (n = 40), heroin abuse (n = 33). The controls were 35. The laboratory tests were conducted in compliance with the standards of the clinical laboratory. We used the following statistical analyses: analysis of variance (the ucriterion of normal distribution, the Student's t-test, dispersion analysis based on ANOVA) and non-parametric analysis.
RESULTS AND DISCUSSION: Based on the routine hematological parameters with statistically significant changes in three groups of poisoning are: red blood cells, hematocrit, hemoglobin (except alcohol intoxication) and leukocytes. We found statistically significant changes in serum total protein, sodium and bilirubin. The highest statistical significance is the increased activity of AST and ALT.
CONCLUSION: We present a model for selection of clinical laboratory tests for severe acute poisoning with modern equipment under standardized conditions. The results of the study suggest that the clinical laboratory constellation we used can be used as a mandatory element in the diagnosis of moderate and severe intoxication with the mentioned toxic substances.

PMID: 28976902 [PubMed - indexed for MEDLINE]

Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials.

J Clin Pharm Ther. 2019 Jul 09;:

Authors: Jeon J, Lee YJ, Lee SY

Abstract
WHAT IS KNOWN AND OBJECTIVE: Angioedema (AE) caused by angiotensin-converting enzyme inhibitors (ACEIs) requires prompt and appropriate management, but current treatment options are limited to symptomatic treatment. Icatibant is a bradykinin receptor antagonist approved for hereditary AE treatment. Some recent studies showed a potential role for icatibant on ACEI-induced AE while others have shown no promising effect. This meta-analysis of randomized controlled trials (RCTs) was conducted to provide evidence for the use of icatibant in the treatment of ACEI-induced AE.
METHODS: Relevant RCTs that examined the effects of icatibant for ACEI-induced AE were retrieved from EMBASE, PubMed and Cochrane Library (Central). Included articles for the meta-analysis were assessed using the Cochrane risk of bias tool. For meta-analysis, the pooled mean differences (MD) with 95% CIs and the pooled relative risk (RR) with 95% CIs were calculated using RevMan 5.3. The systematic review was performed in accordance with the PRISMA statement.
RESULTS AND DISCUSSION: A total of 234 records were identified after searching the databases. In total, three RCTs involving 179 patients were included in the meta-analysis. The three RCTs had a low risk of bias and the characteristics of the participants and the outcome measures were similar among the RCTs. Treatment with icatibant shortened the time to achieve complete resolution of ACEI-induced AE symptoms compared to placebo or conventional treatments. However, the difference was not statistically significant (MD: -7.77 hours; 95% CI: -25.18-9.63 hours). There were no differences between groups in terms of drug-related adverse effects, apart from the reactions at the site of injection (RR: 1.35; 95% CI: 0.53-3.45).
WHAT IS NEW AND CONCLUSION: This meta-analysis evaluated the effectiveness and tolerability of icatibant therapy for ACEI-induced AE, but the benefit of icatibant therapy over placebo or conventional treatment strategies could not be shown.

PMID: 31290163 [PubMed - as supplied by publisher]

Thiopurine Therapy in Patients With Inflammatory Bowel Disease: A Focus on Metabolism and Pharmacogenetics.

Dig Dis Sci. 2019 Jul 09;:

Authors: Chang JY, Cheon JH

Abstract
Thiopurines have been widely used for the maintenance of remission or steroid sparing in patients with inflammatory bowel disease. However, potential drug-related adverse events frequently interfere with their use. Indeed, drug withdrawals associated with adverse reactions have been reported in approximately 25% of patients. To balance the efficacy, safety, and tolerability of thiopurines, regular monitoring of biomarkers (complete blood cell count, liver function test, and metabolic profiles), steady dose escalation, and pretreatment thiopurine S-methyltransferase (TPMT) genotype screening have been routinely recommended. However, the complex thiopurine metabolic pathway and individual differences attributed to pharmacogenetic diversity limit the effectiveness of these strategies in the optimization of thiopurine therapy. Recently, in an effort to facilitate more accurate and personalized prediction of thiopurine response or toxicity, novel genetic markers including NUDT15 and FTO genes were discovered. These discoveries are remarkable because TPMT screening has minimal efficacy for predicting myelosuppression especially in Asian populations, despite the fact that thee populations have a higher frequency of myelosuppression than Western populations. This review focuses on the current understanding of the metabolic pathway and the pharmacogenetics of thiopurines and suggests a personalized preventive strategy against potential adverse drug reactions to optimize their therapeutic application.

PMID: 31290039 [PubMed - as supplied by publisher]