The Changing Landscape of Parkinson Epidemiologic Research.

J Parkinsons Dis. 2018;8(1):1-12

Authors: Chen H

Abstract
Despite recent successes in understanding the genetics of Parkinson's disease (PD), the causes of late-onset sporadic PD remain elusive. Many of the epidemiologic findings on PD etiology have been challenged by alternative explanations such as reverse causation. This is mainly because PD often takes decades to develop before it can be diagnosed late in life. Convincing evidence shows that this prodromal stage of PD is characterized by various prodromal symptoms such as olfactory impairment and rapid-eye-movement sleep behavior disorder (RBD). As they likely reflect PD pathogenesis years, if not decades, before nigrostriatal involvement, research on these symptoms may represent an unprecedented opportunity to dissect the etiology of PD. Using PD prodromal symptoms as intermediate phenotypes, we may be able to identify factors that contribute to the development of these symptoms and factors that modify their progression to clinical PD. Further, this line of research will also enable examinations of novel etiological hypotheses of PD development such as the microbiome and prion hypotheses. In this article, the author used olfactory impairment and RBD as examples to illustrate the promises and challenges of epidemiologic research on prodromal symptoms to understand PD etiology.

PMID: 29154293 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2019/10/29

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.

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")

These pubmed results were generated on 2019/10/28

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.

A Phase 1 Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer.

Mol Cancer Ther. 2019 Oct 23;:

Authors: Sullivan RJ, Hollebecque A, Flaherty KT, Shapiro GI, Rodon Ahnert J, Millward MJ, Zhang W, Gao L, Sykes A, Willard MD, Yu D, Schade AE, Crowe KJ, Flynn DL, Kaufman MD, Henry JR, Peng SB, Benhadji KA, Conti I, Gordon MS, Tiu RV, Hong DS

Abstract
Mutations in extracellular signal regulated kinase signaling drive a significant percentage of malignancies. LY3009120, a pan-RAF and dimer inhibitor, has preclinical activity in RAS- and BRAF-mutated cell lines including BRAF-mutant melanoma resistant to BRAF inhibitors. This multicenter, open-label, Phase 1 clinical trial (NCT02014116) consisted of Part A (dose escalation) and Part B (dose confirmation) in patients with advanced/metastatic cancer. In Part A, oral LY3009120 was dose escalated from 50 to 700 mg twice daily (BID) on a 28-day cycle. In Part B, 300 mg LY3009120 was given BID. The primary objective was to identify a recommended Phase 2 dose (RP2D). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary efficacy. Identification of pharmacodynamic biomarkers was exploratory. In Parts A and B, 35 and sixteen patients were treated, respectively (N=51). In Part A, six patients experienced eight dose-limiting toxicities. The RP2D was 300 mg BID. Common (>10%) any-grade drug-related treatment-emergent adverse events were fatigue (n=15), nausea (n=12), dermatitis acneiform (n=10), decreased appetite (n=7), and maculopapular rash (n=7). The median duration of treatment was four weeks; 84% of patients completed one or two cycles of treatment. Exposures observed at 300 mg BID were above the preclinical concentration associated with tumor regression. Eight patients had a best overall response of stable disease; there were no complete or partial clinical responses. Despite adequate plasma exposure levels, predicted pharmacodynamic effects were not observed.

PMID: 31645440 [PubMed - as supplied by publisher]

The Emperor's New Clothes: What Randomized Controlled Trials Don't Cover.

J Bone Miner Res. 2018 08;33(8):1394-1396

Authors: Eisman JA, Geusens P, van den Bergh J

PMID: 29953664 [PubMed - indexed for MEDLINE]

Parametric modeling and optimal experimental designs for estimating isobolograms for drug interactions in toxicology.

J Biopharm Stat. 2018;28(4):763-777

Authors: Holland-Letz T, Gunkel N, Amtmann E, Kopp-Schneider A

Abstract
In toxicology and related areas, interaction effects between two substances are commonly expressed through a combination index [Formula: see text] evaluated separately at different effect levels and mixture ratios. Often, these indices are combined into a graphical representation, the isobologram. Instead of estimating the combination indices at the experimental mixture ratios only, we propose a simple parametric model for estimating the underlying interaction function. We integrate this approach into a joint model where both the parameters of the dose-response functions of the singular substances and the interaction parameters can be estimated simultaneously. As an additional benefit, this concept allows to determine optimal statistical designs for combination studies optimizing the estimation of the interaction function as a whole. From an optimal design perspective, finding the interaction parameters generally corresponds to a [Formula: see text]-optimality resp. [Formula: see text]-optimality design problem, while estimation of all underlying dose response parameters corresponds to a [Formula: see text]-optimality design problem. We show how optimal designs can be obtained in either case as well as how combination designs providing reasonable performance in regard to both criteria can be determined by putting a constraint on the efficiency in regard to one of the criteria and optimizing for the other. As all designs require prior information about model parameter values, which may be unreliable in practice, the effect of misspecifications is investigated as well.

PMID: 29173022 [PubMed - indexed for MEDLINE]

Assessing performance of sequential analysis methods for active drug safety surveillance using observational data.

J Biopharm Stat. 2018;28(4):668-681

Authors: Zhou X, Bao W, Gaffney M, Shen R, Young S, Bate A

Abstract
The routine use of sequential methods is well established in clinical studies. Recently, there has been increasing interest in applying these methods to prospectively monitor the safety of newly approved drugs through accrual of real-world data. However, the application to marketed drugs using real-world data has been limited and work is needed to determine which sequential approaches are most suited to such data. In this study, the conditional sequential sampling procedure (CSSP), a group sequential method, was compared with a log-linear model with Poisson distribution (LLMP) through a SAS procedure (PROC GENMOD) combined with an alpha-spending function on two large longitudinal US administrative health claims databases. Relative performance in identifying known drug-outcome associations was examined using a set of 50 well-studied drug-outcome pairs. The study finds that neither method correctly identified all pairs but that LLMP often provides better ability and shorter time for identifying the known drug-outcome associations with superior computational performance when compared with CSSP, albeit with more false positives. With the features of flexible confounding control and ease of implementation, LLMP may be a good alternative or complement to CSSP.

PMID: 29157113 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2019/10/24

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.

Glucocorticosteroid induced cataract – drug-induced damage of vision organ which is worth paying attention in the treatment of inflammatory bowel diseases

Postepy Biochem. 2019 10 01;65(3):227-230

Authors: Caban M

Abstract
Inflammatory bowel diseases (IBD) are a group of diseases which concern an increasing number of patients and are more and more often recognized at a young age. Because of unknown etiology, IBD treatment involves mainly non-specific suppression of inflammatory condition and is based among others on steroids. Glucocorticosteroids display anti-inflammatory action by affecting the course of immune responses, but they also possess several side effects which manifest predominantly during a long-term therapy. These concern, among others the eye and manifest by impaired vision; if left untreated, can lead to blindness. The glucocorticosteroid induced cataract is one of the most common complications of treatment with glucocorticosteroids. In the absence of pharmacological options which have a protective effect, the glucocor­ticosteroid induced cataract is a major problem not only for patients but also clinicians and needs immediate solutions.

PMID: 31643171 [PubMed - in process]

Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis.

BMC Infect Dis. 2019 Oct 22;19(1):882

Authors: Musso M, Mosti S, Gualano G, Mencarini P, Urso R, Ghirga P, Rianda A, Del Nonno F, Goletti D, Palmieri F

Abstract
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective.
CASES PRESENTATION: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB.
CONCLUSIONS: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

PMID: 31640579 [PubMed - in process]

Toxicological pitfalls in ICU practice.

Anaesthesiol Intensive Ther. 2018;50(5):378-383

Authors: Janus T, Pabisiak K

Abstract
Either analgosedation or central nervous system dysfunction may be a side effect of implemented pharmacological treatment, as well as a consequence of intentional or unintentional poisoning. In traumatic lesions or anoxia of the central nervous system, a question arises after a recommended follow-up period about the effects of xenobiotics on nervous system function. Although therapeutic drug monitoring is the gold standard in such cases, usually a single toxicological estimation of "a neurodepressive compound" is performed after treatment discontinuation in order to determine the type and amount of exogenous substances, or their metabolites, in a patient's bodily fluids, which allows for an assessment of its actual effects on central nervous system functions. The aim of this paper was to describe the aspects of diagnostic toxicology which are essential for improved determination of the type and amount of exogenous substances present in biological fluids of intensive care patients. We present examples of clinical cases in order to discuss the most common discrepancies in interpretation related to the ordering of toxicology tests.

PMID: 30615797 [PubMed - indexed for MEDLINE]

A 10-year review of single medication double-dose ingestions in the nation's largest poison control system.

Clin Toxicol (Phila). 2019 01;57(1):31-35

Authors: Correia MS, Whitehead E, Cantrell FL, Lasoff DR, Minns AB

Abstract
BACKGROUND: Most Americans take at least one medication on a daily basis. Inadvertently ingesting a double-dose of a medication with a narrow therapeutic index may lead to adverse effects. When a patient or medical professional contacts the local poison center after an overdose, a poison specialist fields the incoming information and, depending on the caller, provides specific recommendations. We sought to determine which medication classes were most likely to lead to significant adverse outcomes when an extra dose was ingested.
METHODS: This was a retrospective review of all double-dose medication ingestions reported to the California Poison Control System (CPCS) between January 2006 and December 2015. Inclusion criteria were single-instance, single-medication ingestions where the dose was known. All ages and both sexes were included. We evaluated generalized outcomes per AAPCC criteria stratified as no effect, minor, moderate, major or death. We also documented specific symptoms and interventions noted by the poison control specialists.
RESULTS: Out of 1286 cases, 876 ingestions met the inclusion criteria. Medications with antihypertensive and behavior modulating effects each accounted for over a third of all moderate and major effects. The medications/medication classes implicated in the 12 major outcomes included propafenone, beta blockers (βBs), calcium channel blockers (CCBs), bupropion, and tramadol. Of these, vasoactive medications were associated with the most severe effects requiring cardiac pacing and vasopressor drips. Analgesics, antimicrobials, and anti-allergy medications were well tolerated. There were no deaths.
CONCLUSIONS: Major adverse outcomes after a double dose ingestion were rare. Most double dose medication ingestions can be safely monitored at home, albeit with a few exceptions. Vigilance is warranted in cases of βB and CCB ingestion due to the risk of hemodynamic collapse or seizures with tramadol and bupropion.

PMID: 30484705 [PubMed - indexed for MEDLINE]

Relevance of the incubation period in cytotoxicity testing with primary human hepatocytes.

Arch Toxicol. 2018 12;92(12):3505-3515

Authors: Gu X, Albrecht W, Edlund K, Kappenberg F, Rahnenführer J, Leist M, Moritz W, Godoy P, Cadenas C, Marchan R, Brecklinghaus T, Pardo LT, Castell JV, Gardner I, Han B, Hengstler JG, Stoeber R

Abstract
Primary human hepatocytes (PHHs) remain the gold standard for in vitro testing in the field of pharmacology and toxicology. One crucial parameter influencing the results of in vitro tests is the incubation period with test compounds. It has been suggested that longer incubation periods may be critical for the prediction of repeated dose toxicity. However, a study that systematically analyzes the relationship between incubation period and cytotoxicity in PHHs is not available. To close this gap, 30 compounds were tested in a concentration-dependent manner for cytotoxicity in cultivated cryopreserved PHHs (three donors per compound) for 1, 2 and 7 days. The median of the EC50 values of all compounds decreased 1.78-fold on day 2 compared to day 1, and 1.89-fold on day 7 compared to day 1. Median values of EC50 ratios of all compounds at day 2 and day 7 were close to one but for individual compounds the ratio increased up to almost six. Strong correlations were obtained for EC50 on day 1 and day 7 (R = 0.985; 95% CI 0.960-0.994), day 1 and day 2 (R = 0.964; 95% CI 0.910-0.986), as well as day 2 and day 7 (R = 0.981; 95% CI 0.955-0.992). However, compound specific differences also occurred. Whereas, for example, busulfan showed a relatively strong increase on day 7 compared to day 1, cytotoxicity of acetaminophen did not increase during longer incubation periods. To validate the observed correlations, a publicly available data set, containing data on the cytotoxicity of human hepatocytes cultivated as spheroids for incubation periods of 5 and 14 days, was analyzed. A high correlation coefficient of EC50 values at day 5 and day 14 was obtained (R = 0.894; 95% CI 0.798-0.945). In conclusion, the median cytotoxicity of the test compounds increased between 1 and 2 days of incubation, with no or only a minimal further increase until day 7. It remains to be studied whether the different results obtained for some individual compounds after longer exposure periods would correspond better to human-repeated dose toxicity.

PMID: 30317417 [PubMed - indexed for MEDLINE]

Mechanisms of toxic cardiomyopathy.

Clin Toxicol (Phila). 2019 01;57(1):1-9

Authors: Hantson P

Abstract
BACKGROUND: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins.
OBJECTIVE: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy.
METHODS: The US National Library of Medicine Pubmed database was searched from 1980 to December 2017 utilizing the combinations of the search terms "toxic cardiomyopathy", "drugs", "anticancer drugs", "azidothymidine", "rosiglitazone", "carbon monoxide", "alcohol", "illicit drugs", "cocaine", "metamfetamine", "metals", "venom". A total of 339 articles were screened and papers that dealt with the pathophysiology of toxic cardiomyopathy, either in animal models or in clinical practice were selected, with preference being given to more recently published papers, which left 92 articles. Anticancer drugs: The mechanisms of anthracycline-induced cardiotoxicity are primarily related to their mechanisms of action as anticancer drugs, mainly the inhibition of topoisomerase II β and DNA cleavage. Additional metabolic or oxidative stress factors may play a part, together with interference with iron metabolism. The more recent drugs, trastuzumab and imatinib, also influence stress pathways. Antiretroviral agents: Azidothymidine is cardiotoxic as a result of mitochondrial toxicity. In addition to energy depletion, azidothymidine also increases the production of mitochondrial reactive oxygen species (ROS). Antidiabetic drugs: The cardiotoxicity of thiazolidinedione antidiabetic drugs is still under investigation, though interference with mitochondrial respiration or oxidative stress is suspected. Cocaine: Among the multiple mechanisms involved in cocaine-related cardiotoxicity, excessive sympathetic stimulation with increased myocardial oxygen consumption is well documented in the acute form of left ventricular dysfunction. As for cocaine-related cardiomyopathy, the role of apoptosis and ROS is under investigation. Ethanol: The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. It involves apoptosis, alterations of the excitation-contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium. Metamfetamines: Catecholamine-mediated toxicity is the probable cause, with a possible role for genetic susceptibility. Carbon monoxide: In addition to hypoxic injury, carbon monoxide is also directly toxic to the mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP production. There is no evidence for a delayed dilated cardiomyopathy in survivors of an acute exposure. Metals: Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often required. Antimony may cause lethal oxidative stress and cell death mediated by elevation in intra-cellular calcium. Proposed mechanisms for mercury toxicity include glutathione depletion, production of ROS, and interruption in selenium-dependent endogenous enzymatic reactions. The existence of a lithium-induced cardiomyopathy is still debated. Scorpion venom: Catecholamine release is the probable cause of acute cardiomyopathy following scorpion envenomation.
CONCLUSIONS: The mechanisms behind toxic cardiomyopathy are complex and multifactorial but include interference with myocardial cell bioenergetics and intracellular calcium handling, the generation of ROS, neurohormonal stress, and induction of apoptosis.

PMID: 30260248 [PubMed - indexed for MEDLINE]

Acute poisoning in Shenyang, China: a retrospective and descriptive study from 2012 to 2016.

BMJ Open. 2018 08 29;8(8):e021881

Authors: Zhang Y, Yu B, Wang N, Li T

Abstract
OBJECTIVES: Up-to-date information on the patterns of acute poisoning is crucial for the proper management of poisoning events. The objectives of this study were to analyse the characteristics of patients suffering from acute poisoning admitted to the emergency department (ED) in a tertiary medical centre in Northeast China and to compare these characteristics with those of a previous comparable study.
DESIGN: Retrospective and descriptive study.
SETTING: Data were collected from the hospital information system in Shengjing Hospital, China, from January 2012 to December 2016.
PARTICIPANTS: All cases aged ≥11 years old with a diagnosis of acute poisoning.
RESULTS: In total, 5009 patients aged ≥11 years presented to the ED with acute poisoning during the study period. The average age of the patients was 36.0±15.1 years and over half (52.7%) were in the 20-39age group. The female to male ratio was 1.2:1. Patients with acute poisoning mainly lived in rural areas rather than in urban areas. The majority of patients consumed poison as suicide attempts (56.7%). Men were more commonly poisoned by drug abuse than women, but women outnumbered men in suicidal poisoning. The most common form of poison intake was ingestion (oral intake; 86.2%). The five most common toxic agent groups, in descending order, were therapeutic drugs (32.6%), pesticides (26.9%), alcohol (20.7%), fumes/gases/vapours (11.4%) and chemicals (3.6%). Sedatives/hypnotics in the therapeutic drugs group and paraquat in the pesticides group were the most common toxic agents, respectively. The mortality rate of study participants was 1.3%, with 64 deaths.
CONCLUSIONS: The results of this study indicate the need to strengthen education on the rational and safe use of drugs in Shenyang.

PMID: 30158226 [PubMed - indexed for MEDLINE]

Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

Ann Emerg Med. 2019 01;73(1):79-87

Authors: El Majzoub I, Qdaisat A, Thein KZ, Win MA, Han MM, Jacobson K, Chaftari PS, Prejean M, Reyes-Gibby C, Yeung SJ

Abstract
STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs).
METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death.
RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival.
CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

PMID: 29880440 [PubMed - indexed for MEDLINE]

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.

AIDS. 2018 07 17;32(11):1431-1442

Authors: Eron JJ, Orkin C, Gallant J, Molina JM, Negredo E, Antinori A, Mills A, Reynes J, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Vanveggel S, Opsomer M, AMBER study group

Abstract
OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults.
DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247).
METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin).
RESULTS: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI -1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P < 0.0001 (hip), -0.68 vs. -2.38%, P = 0.004 (lumbar spine), and -0.26 vs. -2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036.
CONCLUSION: D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

PMID: 29683855 [PubMed - indexed for MEDLINE]

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression.

Allergy. 2018 10;73(10):2012-2023

Authors: Blumenthal KG, Li Y, Acker WW, Chang Y, Banerji A, Ghaznavi S, Camargo CA, Zhou L

Abstract
BACKGROUND: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression.
METHODS: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS.
RESULTS: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]).
CONCLUSION: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

PMID: 29574787 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2019/10/23

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.

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

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

These pubmed results were generated on 2019/10/23

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.