Burden of hospitalizations related to adverse drug events in the USA: a retrospective analysis from large inpatient database.

Pharmacoepidemiol Drug Saf. 2017 Jun;26(6):635-641

Authors: Poudel DR, Acharya P, Ghimire S, Dhital R, Bharati R

Abstract
PURPOSE: Adverse drug events (ADEs) represent medication-related patient harm, which is associated with significant patient morbidity and mortality. This study was conducted to determine the rate, specific causes, and outcomes of ADE-related hospitalization in the USA.
METHODS: We used the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample dataset for the years 2008 to 2011. We selected patients with ADE based on 537 Classification of Diseases-9 codes. Main outcome measures included yearly prevalence, cost, length of stay, and mortality of ADE-related hospitalizations. Calculations were performed on weighted samples, and statistical significance was set at p-value <0.05 (two-tailed).
RESULTS: We estimated the total hospitalizations with ADE to be 9 440 757 patients (6.28% of total) from 2008 to 2011. Increasing trend was noted from 2008 (5.97%) to 2011 (6.82%) with an annual percentage change rate of 4.37. Patients with ADE were significantly older (2011: mean age 61.42 vs. 48.65 years) and had more comorbidities. Steroids (14.49%), antineoplastic drugs (13.06%), anticoagulants (11.33%), nonsteroidal anti-inflammatory drugs (8.78%), and opiates/narcotics (6.48%) were the five most common causes of ADE. Patient with ADE stayed 1.89 days [95% confidence interval (CI) (1.79-1.99); p < 0.001] longer, incurred $1851.44 [95%CI ($1613.90-$2088.96), p < 0.001] higher with higher odds of mortality 1.27 [95%CI (1.24-1.29), p < 0.001].
CONCLUSION: Adverse drug event carries a significant burden of inpatient hospital care, incurs more cost, and leads to increased loss of life. Targeted policies to reduce them could potentially help decrease mortality as well as drive down cost. Copyright © 2017 John Wiley & Sons, Ltd.

PMID: 28233421 [PubMed - indexed for MEDLINE]

Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.

Oncologist. 2018 Jan 12;:

Authors: Zhang Z, Zhang Y, Chen G, Hong S, Yang Y, Fang W, Luo F, Chen X, Ma Y, Zhao Y, Zhan J, Xue C, Hou X, Zhou T, Ma S, Gao F, Huang Y, Chen L, Zhou N, Zhao H, Zhang L

Abstract
BACKGROUND: The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear.
MATERIALS AND METHODS: We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed.
RESULTS: Olanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens.
CONCLUSION: Olanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea.
IMPLICATIONS FOR PRACTICE: According to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed-phase nausea control when compared with various neurokinin-1 receptor antagonists-based triple regimens in patients with highly emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms of nausea control and drug price. For cancer patients with HEC, especially those suffering from delayed-phase nausea, olanzapine-based triple regimens should be an optional antiemetic choice.

PMID: 29330211 [PubMed - as supplied by publisher]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

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14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/01/13

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.

Incident adverse drug reactions in geriatric inpatients: a multicentred observational study.

Ther Adv Drug Saf. 2018 Jan;9(1):13-23

Authors: Lavan A, Eustace J, Dahly D, Flanagan E, Gallagher P, Cullinane S, Petrovic M, Perehudoff K, Gudmondsson A, Samuelsson Ó, Sverrisdóttir Á, Cherubin A, Dimitri F, Rimland J, Cruz-Jentoft A, Vélez-Díaz-Pallarés M, Lozano Montoya I, Soiza RL, Subbarayan S, O'Mahony D

Abstract
Background: Adverse drug reactions (ADRs) are common in older adults and frequently have serious clinical and economic consequences. This study was conducted as a feasibility study for a randomized control trial (RCT) that will investigate the efficacy of a software engine to optimize medications and reduce incident (in-hospital) ADRs. This study's objectives were to (i) establish current incident ADR rates across the six sites participating in the forthcoming RCT and (ii) assess whether incident ADRs are predictable.
Methods: This was a multicentre, prospective observational study involving six European hospitals. Adults aged ⩾ 65 years, hospitalized with an acute illness and on pharmacological treatment for three or more conditions were eligible for inclusion. Adverse events (AEs) were captured using a trigger list of 12 common ADRs. An AE was deemed an ADR when its association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre causality assessment. The proportion of patients experiencing at least one, probable/certain, incident ADR within 14 days of enrolment/discharge was recorded.
Results: A total of 644 patients were recruited, evenly split by sex and overwhelmingly of White ethnicity. Over 80% of admissions were medical. The median number of chronic conditions was five (interquartile range 4-6), with eight or more conditions present in approximately 10%. The mean number of prescribed medications was 9.9 (standard deviation 3.8), which correlated strongly with the number of conditions (r = 0.54, p < 0.0001). A total of 732 AEs were recorded in 382 patients, of which 363 were incident. The majority of events were classified as probably or possibly drug related, with heterogeneity across sites (χ2 = 88.567, df = 20, p value < 0.001). Out of 644 patients, 139 (21.6%; 95% confidence interval 18.5-25.0%) experienced an ADR. Serum electrolyte abnormalities were the most common ADR. The ADRROP (ADR Risk in Older People) and GerontoNet ADR risk scales correctly predicted ADR occurrence in 61% and 60% of patients, respectively.
Conclusion: This feasibility study established the rates of incident ADRs across the six study sites. The ADR predictive power of ADRROP and GerontoNet ADR risk scales were limited in this population.

PMID: 29318003 [PubMed]

Association between ß2-adrenergic receptor gene polymorphisms and adverse events of ritodrine in the treatment of preterm labor: a prospective observational study.

BMC Genet. 2017 Nov 13;18(1):96

Authors: Chung JE, Choi SA, Hwang HS, Park JY, Lee KE, Yee J, Kim YJ, Gwak HS

Abstract
BACKGROUND: Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine.
RESULTS: This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes.
CONCLUSIONS: This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.

PMID: 29132297 [PubMed - indexed for MEDLINE]

Adverse Events Following Vaccination With Bivalent rLP2086 (Trumenba®): An Observational, Longitudinal Study During a College Outbreak and a Systematic Review.

Pediatr Infect Dis J. 2018 Jan;37(1):e13-e19

Authors: Fiorito TM, Baird GL, Alexander-Scott N, Bornschein S, Kelleher C, Du N, Dennehy PH

Abstract
BACKGROUND: In February 2015, two unlinked culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island ("college X") within 3 days. This represented a 489-fold increase in the incidence of MenB disease, and an outbreak was declared. For the first time, bivalent rLP2086 (Trumenba) was selected as a mandatory intervention response. A mass vaccination clinic was coordinated, which provided a unique opportunity to collect safety data in a real-world population of college-age participants. Though the Advisory Committee on Immunization Practices recommends MenB vaccination for college-age individuals (16-23 year olds), there is limited quantifiable safety data available for this population.
METHODS: The Dillman total design survey method was used. Adverse events of bivalent rLP2086 were solicited and quantified retrospectively 2-4 months following each dose of vaccine. Safety data from six clinical trials were used as comparison tools.
RESULTS: The most commonly reported adverse event following vaccination was injection site pain. Reported rates of injection site pain, fatigue, myalgia, fever, and chills were similar than those reported in clinical trials. Reported rates of headache were lower than in clinical trials.
CONCLUSIONS: This study is the first to examine adverse events of bivalent rLP2086 in a real-world setting where more than 90% of a college-age population was vaccinated.

PMID: 28834957 [PubMed - indexed for MEDLINE]

Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer.

Theranostics. 2017;7(5):1360-1372

Authors: Wang Y, Chen X, Tian B, Liu J, Yang L, Zeng L, Chen T, Hong A, Wang X

Abstract
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells. This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in vitro as confirmed with fluorescent microscopic imaging and flow cytometry. Also, intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice and inhibited tumor growth. Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response. Thus, the RNAi nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells both in vitro and in vivo. Our results suggest that the AS1411-EVs have a great potential as drug delivery vehicles to treat cancers.

PMID: 28435471 [PubMed - indexed for MEDLINE]

Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data.

Nat Biotechnol. 2016 07 12;34(7):697-700

Authors: Sarangdhar M, Tabar S, Schmidt C, Kushwaha A, Shah K, Dahlquist JE, Jegga AG, Aronow BJ

PMID: 27404875 [PubMed - indexed for MEDLINE]

Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study.

Pharmacol Res. 2017 Apr;118:104-110

Authors: Lloret-Linares C, Rollason V, Lorenzini KI, Samer C, Daali Y, Gex-Fabry M, Aubry JM, Desmeules J, Besson M

Abstract
OBJECTIVES: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non-response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting.
METHOD: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations.
RESULTS: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively.
CONCLUSION: When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.

PMID: 27378571 [PubMed - indexed for MEDLINE]

Circadian disruption: New clinical perspective of disease pathology and basis for chronotherapeutic intervention.

Chronobiol Int. 2016;33(8):1101-19

Authors: Smolensky MH, Hermida RC, Reinberg A, Sackett-Lundeen L, Portaluppi F

Abstract
Biological processes are organized in time as innate rhythms defined by the period (τ), phase (peak [Φ] and trough time), amplitude (A, peak-trough difference) and mean level. The human time structure in its entirety is comprised of ultradian (τ < 20 h), circadian (20 h > τ < 28 h) and infradian (τ > 28 h) bioperiodicities. The circadian time structure (CTS) of human beings, which is more complicated than in lower animals, is orchestrated and staged by a brain central multioscillator system that includes a prominent pacemaker - the suprachiasmatic nuclei of the hypothalamus. Additional pacemaker activities are provided by the pineal hormone melatonin, which circulates during the nighttime, and the left and right cerebral cortices. Under ordinary circumstances this system coordinates the τ and Φ of rhythms driven by subservient peripheral cell, tissue and organ clock networks. Cyclic environmental, feeding and social time cues synchronize the endogenous 24 h clocks and rhythms. Accordingly, processes and functions of the internal environment are integrated in time for maximum biological efficiency, and they are also organized and synchronized in time to the external environment to ensure optimal performance and response to challenge. Artificial light at night (ALAN) exposure can alter the CTS as can night work, which, like rapid transmeridian displacement by air travel, necessitates realignment of the Φ of the multitude of 24 h rhythms. In 2001, Stevens and Rea coined the phrase "circadian disruption" (CD) to label the CTS misalignment induced by ALAN and shift work (SW) as a potential pathologic mechanism of the increased risk for cancer and other medical conditions. Current concerns relating to the effects of ALAN exposure on the CTS motivated us to renew our long-standing interest in the possible role of CD in the etiopathology of common human diseases and patient care. A surprisingly large number of medical conditions involve CD: adrenal insufficiency; nocturia; sleep-time non-dipping and rising blood pressure 24 h patterns (nocturnal hypertension); delayed sleep phase syndrome, non-24 h sleep/wake disorder; recurrent hypersomnia; SW intolerance; delirium; peptic ulcer disease; kidney failure; depression; mania; bipolar disorder; Parkinson's disease; Smith-Magenis syndrome; fatal familial insomnia syndrome; autism spectrum disorder; asthma; byssinosis; cancers; hand, foot and mouth disease; post-operative state; and ICU outcome. Poorly conceived medical interventions, for example nighttime dosing of synthetic corticosteroids and certain β-antagonists and cyclic nocturnal enteral or parenteral nutrition, plus lifestyle habits, including atypical eating times and chronic alcohol consumption, also can be causal of CD. Just as surprisingly are the many proven chronotherapeutic strategies available today to manage the CD of several of these medical conditions. In clinical medicine, CD seems to be a common, yet mostly unrecognized, pathologic mechanism of human disease as are the many effective chronotherapeutic interventions to remedy it.

PMID: 27308960 [PubMed - indexed for MEDLINE]

Telbivudine versus lamivudine and entecavir for treatment-naïve decompensated hepatitis B virus-related cirrhosis.

Clin Exp Med. 2017 May;17(2):233-241

Authors: Yue-Meng W, Li YH, Wu HM, Yang J, Xu Y, Yang LH, Yang JH

Abstract
The long-term effects of telbivudine (TBV) on decompensated hepatitis B virus (HBV)-related cirrhosis were still not established. This study aimed to investigate the efficacy and safety of TBV in such cohort of patients as compared to lamivudine (LAM) and entecavir (ETV). We retrospectively evaluated 130 treatment-naïve patients with HBV-related decompensated cirrhosis who started treatment with TBV (n = 31), LAM (n = 45) or ETV (n = 54). After 24 months of treatment, cumulative virological response (VR) rates (HBV DNA <500 copies/mL) were 83.7, 65.3 and 89.1 % in TBV, LAM and ETV groups, respectively (p = 0.009). Reduction in HBV DNA levels in TBV was -3.66 ± 0.56, significantly higher than LAM (-3.34 ± 0.59; p < 0.05) and lower than ETV group (-3.98 ± 0.52; p < 0.05). The rates of HBeAg loss or seroconversion and normalization of alanine aminotransferase (ALT) were similar among the groups. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease score in TBV were significantly improved compared to at baseline without difference among the groups. TBV resulted in similar cumulative rates of survival and incidence of hepatocellular carcinoma (HCC) to LAM and ETV. Frequencies of complications from cirrhosis, including variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis, were comparable among the groups. Four patients (16.7 %) in TBV displayed virological breakthrough, lower than LAM and higher than ETV (p = 0.004). Cox regression analysis showed that baseline HBV DNA (hazard ratio 0.743; 95 % confidence interval 0.582-949, p = 0.017) was an independent predictor for VR at 24 months. Long-term therapy with TBV was effective and safe in HBV-related decompensated cirrhosis.

PMID: 27094312 [PubMed - indexed for MEDLINE]

Assessment of Adverse Drug Reaction Due to Cancer Chemotherapy in a Teaching Oncology Hospital in Isfahan, Central of Iran.

Rev Recent Clin Trials. 2016;11(3):266-72

Authors: Vaseghi G, Abed A, Jafari E, Eslami N, Eshraghi A

Abstract
INTRODUCTION: Adverse Drug Reactions (ADRs) are common in hospitalized oncology patients. The kinds of ADRs experienced by cancer patients are varied. Therefore, the identification of appropriate manner in order to prevent ADRs may improve patient outcome.
AIMS: The present study evaluated the incidence, frequency and common types of adverse drug reactions among hospitalized oncology patients.
METHODS: Patients hospitalized at a university oncology center (children and adult) during the calendar year 2012 were randomly selected. Data were collected by reviewing of medical records. The outcome measures included the incidence of observed ADRs and ADR-related admissions and achieving strategies to prevent the emergence of chemotherapy side effects.
RESULTS: ADRs frequently occurred in the age group less than 20 years (22%). Prevalence of leukemia (27%), colon cancer (16.5%) and breast cancer (14%) was higher in our region. Most ADRs were recorded in patients receiving cisplatin (44%), doxorubicin (24%) and 5-fluouracil (20%) as chemotherapy. The most frequently observed ADRs were nauseavomiting, neutropenia and constipation in both pediatric and adult population.
CONCLUSION: This study shows that ADRs occur more frequently in the pediatric group compared to adults. Therefore, optimum use of preventative strategy program may contribute to reducing the incidence and severity of ADRs especially in this group.

PMID: 26282897 [PubMed - indexed for MEDLINE]

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

Vet Comp Oncol. 2018 Jan 04;:

Authors: Abma E, Peremans K, De Vos F, Bosmans T, Kitshoff AM, Daminet S, Ni Y, Dockx R, de Rooster H

Abstract
Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients.

PMID: 29314561 [PubMed - as supplied by publisher]

Artemether-lumefantrine for the treatment of Plasmodium malariae, Plasmodium ovale, and mixed Plasmodium malaria: A prospective clinical trial assessing species-specific efficacy in Gabon.

Antimicrob Agents Chemother. 2018 Jan 08;:

Authors: Groger M, Veletzky L, Lalremruata A, Cattaneo C, Mischlinger J, Zoleko-Manego R, Endamne L, Klicpera A, Kim J, Nguyen T, Flohr L, Remppis J, Matsiegui PB, Adegnika AA, Agnandji ST, Kremsner PG, Mordmüller B, Mombo-Ngoma G, Ramharter M

Abstract
ObjectivesTreatment recommendations for Plasmodium malariae and Plasmodium ovale malaria are largely based on anecdotal evidence. The aim of this study was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated P.malariae or P.ovale mono-infections, or mixed Plasmodium infections.Patients and methodsThis prospective study was conducted in Gabon. Patients with microscopically confirmed P.malariae, P.ovale, or mixed species malaria with at least one of these two Plasmodium species were treated with an oral, fixed dose combination of artemether-lumefantrine for three consecutive days. The primary endpoints were per protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period.Results72 participants (42 male, 30 female) were enrolled, 62.5% of them were PCR corrected mixed Plasmodium infections. Per protocol, PCR corrected ACPR was 96.6% (95%CI 91.9 - 100) on day 28 and 94.2% (95% CI 87.7-100) on day 42. Considering Plasmodium species independently from their co-infecting species, day 42 ACPR was 95.5% (95% CI 89.0-100) for P.falciparum, 100% (exact CI 84.6-100) for P.malariae, 100% (exact CI 76.8-100) for P.ovale curtisi and 90.9% (95% CI 70.7-100) for P.ovale wallikeri Study drug related adverse events were generally mild or moderate.ConclusionThis largest clinical trial assessing the efficacy of an antimalarial against non-falciparum malaria demonstrated satisfying antimalarial activity of artemether-lumefantrine against P.ovale wallikeri, P.ovale curtisi, P.malariae, and mixed Plasmodium infections with per protocol efficacies of 90%-100% without evident tolerability or safety concerns.

PMID: 29311086 [PubMed - as supplied by publisher]

No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy.

AIDS. 2017 May 15;31(8):1137-1141

Authors: Mota TM, Rasmussen TA, Rhodes A, Tennakoon S, Dantanarayana A, Wightman F, Hagenauer M, Roney J, Spelman T, Purcell DFJ, McMahon J, Hoy JF, Prince HM, Elliott JH, Lewin SR

Abstract
OBJECTIVE: To determine the long-term effects of vorinostat on safety and virological parameters in HIV-infected individuals on suppressive antiretroviral therapy (ART).
DESIGN: Prospective longitudinal observational extended follow-up of 20 HIV-infected individuals on ART previously enrolled in a clinical trial of daily vorinostat 400 mg for 14 days. Extended follow-up included visits at 6, 12, 18 and 24 months postenrolment in the initial clinical trial.
METHODS: Cell-associated unspliced HIV RNA, total HIV DNA and plasma HIV RNA were quantified by PCR, and CD4 and CD8 T cells quantified by flow cytometry. Changes over time in each parameter were assessed using the Wilcoxon matched pair signed-rank test and generalized estimating equations for trend modelling.
RESULTS: We recorded a total of 31 adverse events (26 grade 1 and five grade 2) in all study participants (n = 20). There were no significant changes in the number of CD4 or CD8 T cells or plasma HIV RNA over time. In 12 participants for whom baseline samples were available, there were no significant changes in total HIV DNA, cell-associated unspliced HIV RNA, plasma RNA or CD4 and CD8 T cells at 6, 12, 18 or 24 months.
CONCLUSION: Extended follow-up for 24 months did not reveal any long-term toxicity or changes in markers of HIV persistence or transcription in participants on ART who had received 14 days of vorinostat.

PMID: 28301423 [PubMed - indexed for MEDLINE]

Is Hydroxyethyl Starch Safe in Penetrating Trauma Patients?

Mil Med. 2016 May;181(5 Suppl):152-5

Authors: Allen CJ, Ruiz XD, Meizoso JP, Ray JJ, Livingstone AS, Schulman CI, Namias N, Proctor KG

Abstract
OBJECTIVES: For logistic reasons, a bolus of 6% hydroxyethyl starch (HES 450/0.7 in lactated electrolyte injection) is recommended for battlefield resuscitation even though it has risks of mortality and acute kidney injury (AKI) in certain patient populations. The purpose of this study was to test the hypothesis that victims of penetrating trauma have no increased risks of AKI and/or death when receiving a single bolus of HES during initial fluid resuscitation.
METHODS: 816 consecutive admissions with penetrating trauma were reviewed. Patients who died within 24 hours were excluded. Propensity scores and a 1:1 fixed ratio nearest neighbor matching were used to compare those who received HES to those who did not. Data were expressed as mean ± SD and significance was assessed at p < 0.05.
RESULTS: The cohort was 88% male, age 35 ± 14 years, injury severity score of 10 ± 10, with a 3.8% rate of AKI, and 3.2% rate of mortality. HES was administered to 121 (14.8%) patients. In HES and no HES propensity matched groups, the rate of AKI was 3.8% vs. 4.8% (p = 0.749) and the 90-day mortality rate was 3.8% vs. 4.8% (p = 0.749).
CONCLUSION: An increased risk of mortality or AKI was not observed in penetrating trauma patients who were resuscitated with low volume HES.

PMID: 27168566 [PubMed - indexed for MEDLINE]

En Route Use of Analgesics in Nonintubated, Critically Ill Patients Transported by U.S. Air Force Critical Care Air Transport Teams.

Mil Med. 2016 May;181(5 Suppl):145-51

Authors: Mora AG, Ganem VJ, Ervin AT, Maddry JK, Bebarta VS

Abstract
INTRODUCTION: U.S. Critical Care Air Transport Teams (CCATTs) evacuate critically ill patients with acute pain in the combat setting. Limited data have been reported on analgesic administration en route, and no study has reported analgesic use by CCATTs. Our objective was to describe analgesics used by CCATTs for nonintubated, critically ill patients during evacuation from a combat setting.
METHODS: We conducted an institutional review board-approved, retrospective review of CCATT records. We included nonintubated, critically ill patients who were administered analgesics in flight and were evacuated out of theater (2007-2012). Demographics, injury description, analgesics and anesthetics, and predefined clinical adverse events were recorded. Data were presented as mean ± standard deviation or percentage (%).
RESULTS: Of 1,128 records, we analyzed 381 subjects with the following characteristics: age 26 ± 7.0 years; 98% male; and 97% trauma (70% blast, 17% penetrating, 11% blunt, and 3% burn). The injury severity score was 19 ± 9. Fifty-one percent received morphine, 39% hydromorphone, 15% fentanyl, and 5% ketamine. Routes of delivery were 63% patient-controlled analgesia (PCA), 32% bolus intravenous (IV) administration, 24% epidural delivery, 21% continuous IV infusions, and 9% oral opioids. Patients that were administered local anesthetics (nerve block or epidural delivery) with IV opioids received a lower total dose of opioids than those who received opioids alone. No differences were associated between analgesics and frequency of complications in flight or postflight.
CONCLUSION: About half of nonintubated, critically ill subjects evacuated out of combat by CCATT received morphine and more than half had a PCA. In our study, ketamine was not frequently used and pain scores were rarely recorded. However, we detected an opioid-sparing effect associated with local anesthetics (regional nerve blocks and epidural delivery).

PMID: 27168565 [PubMed - indexed for MEDLINE]

Induction of a Tumor-Metastasis-Receptive Microenvironment as an Unwanted Side Effect After Radio/Chemotherapy and In Vitro and In Vivo Assays to Study this Phenomenon.

Methods Mol Biol. 2016;1516:347-360

Authors: Schneider G, Sellers ZP, Ratajczak MZ

Abstract
Besides surgical removal of tumor tissue, chemotherapy and radiotherapy are the most important and efficient treatment modalities employed to treat therapy-susceptible malignancies. The main aim of this treatment-to destroy tumor cells-is unfortunately usually associated with toxicity to nontumor cells and different degrees of tissue and organ damage. In damaged tissues several chemoattractants are upregulated and released that may attract tumor cells. Moreover, highly migratory radio/chemotherapy treatment may endow cells with several properties of cancer stem cells which survive and respond to these chemoattractants upregulated in collateral tissues. Based on this, one of the unwanted and underappreciated side effects of chemotherapy or radiotherapy is the creation of a metastasis-receptive microenvironment in bones as well as in other organs of the body. Herein we describe methods and assays that can be employed to study migratory properties of cancer cells in in vitro (chemotaxis) and in vivo (seeding efficiency assay) conditions in response to the induction of pro-metastatic microenvironments in various organs and tissues.

PMID: 27032941 [PubMed - indexed for MEDLINE]

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