Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose Two-Drug Regimen Versus Continuing a Tenofovir Alafenamide-Based Three- or Four-Drug Regimen for Maintenance of Virologic Suppression in Adults With HIV-1: Phase 3, Randomized, Non-inferiority TANGO Study.

Clin Infect Dis. 2020 Jan 06;:

Authors: van Wyk J, Ajana F, Bisshop F, De Wit S, Osiyemi O, Portilla J, Routy JP, Wyen C, Ait-Khaled M, Nascimento MC, Pappa KA, Wang R, Wright J, Tenorio AR, Wynne B, Aboud M, Gartland MJ, Smith KY

Abstract
BACKGROUND: The 2-drug regimen (2DR) dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with HIV-1. We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals.
METHODS: TANGO is an open-label, multicenter, phase III study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to a once-daily DTG/3TC fixed-dose combination or remain on a tenofovir alafenamide (TAF)-based regimen. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (FDA Snapshot algorithm) in the intention-to-treat-exposed population (4% non-inferiority margin).
RESULTS: 743 adults were enrolled and 741 received ≥1 dose of study drug (DTG/3TC, N=369; TAF-based regimen, N=372). At Week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL treated with DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% CI], -0.3 [-1.2, 0.7]), meeting non-inferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at time of failure. Drug-related grade ≥2 adverse events and adverse events leading to study withdrawal were reported in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively.
CONCLUSIONS: The 2DR DTG/3TC was non-inferior in maintaining virologic suppression vs a TAF-based regimen at Week 48, with no virologic failure or emergent resistance reported in the DTG/3TC group, supporting its use as a simplification strategy for virologically suppressed people living with HIV-1.

PMID: 31905383 [PubMed - as supplied by publisher]

Adverse drug reactions in primary care: a scoping review.

BMC Health Serv Res. 2020 Jan 06;20(1):5

Authors: Khalil H, Huang C

Abstract
BACKGROUND: Medication-related adverse events, or adverse drug reactions (ADRs) are harmful events caused by medication. ADRs could have profound effects on the patients' quality of life, as well as creating an increased burden on the healthcare system. ADRs are one of the rising causes of morbidity and mortality internationally, and will continue to be a significant public health issue with the increased complexity in medication, to treat various diseases in an aging society. This scoping review aims to provide a detailed map of the most common adverse drug reactions experienced in primary healthcare setting, the drug classes that are most commonly associated with different levels/types of adverse drug reactions, causes of ADRs, their prevalence and consequences of experiencing ADRs.
METHODS: We systematically reviewed electronic databases Ovid MEDLINE, Embase, CINAHL Plus, Cochrane Central Register of Controlled Trials, PsycINFO and Scopus. In addition, the National Patient Safety Foundation Bibliography and the Agency for Health Care Research and Quality and Patient Safety Net Bibliography were searched. Studies published from 1990 onwards until December 7, 2018 were included as the incidence of reporting drug reactions were not prevalent before 1990. We only include studies published in English.
RESULTS: The final search yielded a total of 19 citations for inclusion published over a 15-year period that primarily focused on investigating the different types of adverse drug reactions in primary healthcare. The most causes of adverse events were related to drug related and allergies. Idiosyncratic adverse reactions were not very commonly reported. The most common adverse drug reactions reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with adverse events.
CONCLUSION: This scoping review identified that the most causes of ADRs were drug related and due to allergies. Idiosyncratic adverse reactions were not very commonly reported in the literature. This is mainly because it is hard to predict and these reactions are not associated with drug doses or routes of administration. The most common ADRs reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with ADRs.

PMID: 31902367 [PubMed - in process]

Long-Term Kidney Transplant Outcomes: Role of Prolonged-Release Tacrolimus.

Transplant Proc. 2019 Dec 31;:

Authors: Banas B, Krämer BK, Krüger B, Kamar N, Undre N

Abstract
Tacrolimus has significantly improved outcomes for kidney transplant patients and remains the cornerstone of immunosuppressive therapy. While improvements in short-term outcomes in transplantation have been achieved in recent years, maintaining long-term graft survival remains a challenge in kidney transplantation. Minimizing risk factors for poor long-term kidney graft function and survival, and modifying tacrolimus regimens in the early and maintenance phases post-transplantation are essential to maintain long-term kidney transplant outcomes. Tacrolimus has a narrow therapeutic window, resulting in a tightly defined range of optimal drug exposure. Underimmunosuppression is associated with long-term risks, such as the development of donor-specific antibodies and antibody-mediated rejection, with a high possibility of a decline in kidney function and progression to graft failure. Conversely, prolonged overimmunosuppression carries a risk of drug-related adverse events. This review provides an overview of the differences in the formulation, delivery, and pharmacokinetic profiles between immediate- and prolonged-release tacrolimus and evaluates the effect of prolonged-release tacrolimus on the risk factors for poor outcomes in kidney transplantation. Recent evidence is used to provide guidance on target tacrolimus trough levels in the early and maintenance phases post-transplantation, with a view to improving long-term kidney graft function.

PMID: 31901329 [PubMed - as supplied by publisher]

How safe are our studies? Analysis of adverse events in Bayer First-in-Human trials from 2006 to 2016
.

Int J Clin Pharmacol Ther. 2020 Jan;58(1):10-20

Authors: Jung D, Boettcher MF, Wensing G

Abstract
PURPOSE: In regard to the current scientific discussion, this analysis aims to broaden the database for a risk evaluation of First-in-Human (FiH) trials with healthy volunteers.
MATERIALS AND METHODS: Study documents of each FiH study conducted between 2006 and 2016 for Bayer Clinical Pharmacology Cardiovascular were reviewed for inclusion. Study types, treatments, dose steps, study population, number, incidence, and intensity of treatment-emergent adverse events (AEs) were cumulatively analyzed using descriptive statistics. A comparison to a previous similar analysis (period 2000 - 2005) was made.
RESULTS: 22 out of 25 studies were included (20 small molecules, 2 biologics) investigating drugs for cardiovascular (9), hematological (7), pulmonary (3), kidney (2), and metabolic (1) diseases. The mean age of subjects was 34.2 years. 1,250 subjects received treatment (950 active, 300 placebo). 952 AEs occurred (0.76 AEs/treatment, 0.85 AEs/active treatment, 0.49 AEs/placebo treatment). 88.2% (840/952) of AEs were mild, 11.3% (108/952) moderate, and 0.4% (4/952) were severe. 0.4% (5/1250) of subjects had active drug- or procedure-related serious AEs. The most frequent AE was headache (12.9% (123/952)), the mostly affected system organ class was CNS (14.4% of all subjects). The relative risk for an AE was significantly higher under active drug compared to placebo (1.24, 95% LCL >1). The incidence of AEs increased with higher dose steps. A higher incidence of AEs (active and placebo) in recent compared to previous studies was observed.
CONCLUSION: The risk of severe harm for healthy participants was low. The risk to experience any AE was higher under active drug compared to placebo. A trend change towards more frequent reporting of AEs in the recent studies was observed.

PMID: 31746730 [PubMed - indexed for MEDLINE]

Medication prescribing errors among hospitalized pediatric patients at Nekemte Referral Hospital, western Ethiopia: cross-sectional study.

BMC Res Notes. 2019 Jul 16;12(1):421

Authors: Fekadu G, Abdisa E, Fanta K

Abstract
OBJECTIVE: Incidence and clinical outcomes of medication prescribing errors are common and potentially more harmful in the pediatric population than in the adult population. Hence, this study was aimed to assess the prevalence and types of medication prescribing errors in the pediatric wards of Nekemte Referral Hospital (NRH).
RESULTS: Of 384 pediatric patients included in the study, 241 (63%) were males and 116 (30.21%) of them were aged between 1-3 years. About 241 (62.76%) of the patients were treated based on empirical diagnosis and only 10 (2.60%) pediatrics had co-morbid disease. The most category of medication prescribing error was dosing error 251 (48.6%) followed by incorrect drug selection 98 (19.0%). Being critically ill (AOR = 5.31, 95% CI = 1.80-12.31, p = 0.003), route of administration via IV (AOR = 3.98, 95% CI = 1.85-11.15, p = 0.011) and via IV + IM route (AOR = 2.22, 95% CI = 1.05-9.25, p = 0.045) as well as 4-6 medications per patient (AOR = 3.10, 95% CI = 3.43-12.42, p = 0.012) and > 6 medications per patient (AOR = 7.23, 95% CI = 3.91-21.45, p < 0.001) were independent predictors of medication prescribing errors. Antibiotics were the most common classes of drugs responsible for prescribing errors.

PMID: 31311587 [PubMed - indexed for MEDLINE]

Prevalence and recognition of highly significant medication-smoking cessation interactions in a smoke-free hospital.

Drug Alcohol Depend. 2019 07 01;200:78-81

Authors: Chui CY, Taylor SE, Thomas D, George J

Abstract
BACKGROUND: Some medications are more rapidly metabolized by smokers; upon smoking cessation, medication metabolism may be significantly reduced, resulting in medication-related adverse events. Clozapine, olanzapine and theophylline have been deemed to have potentially highly significant interactions with smoking cessation, which could lead to seizures, extrapyramidal effects and tachycardia, respectively. This study examined the period prevalence and characteristics of patients at risk of highly significant medication-smoking cessation interactions when admitted to a smoke-free hospital.
METHODS: A retrospective cross-sectional study was undertaken in an Australian tertiary-referral hospital with a well-established electronic prescribing system. Smokers prescribed clozapine, olanzapine or theophylline prior to and during a hospital admission in 2015 were included. Length of hospital stay, daily doses, and recognition of the potential interaction by treating clinicians were determined from medical records.
RESULTS: The period prevalence of patients at risk of a potentially highly significant medication-smoking cessation interaction was 23/48 (48%), 66/256 (26%) and 1/16 (6%) amongst smokers prescribed clozapine, olanzapine or theophylline, respectively. These interactions were poorly recognized by healthcare professionals during the admission.
CONCLUSIONS: Up to one in two patients receiving medications that have potentially highly significant interactions with smoking cessation may be experiencing clinically significant potential interactions. Such interactions, however, were commonly overlooked by hospital staff. Interventions to improve awareness of this issue are warranted.

PMID: 31108404 [PubMed - indexed for MEDLINE]

Medications and Vocal Function.

Otolaryngol Clin North Am. 2019 Aug;52(4):693-702

Authors: Bock JM

Abstract
Medications can have innumerable direct and indirect effects on laryngeal hydration, vocal fold mucosal integrity, laryngeal muscle function, and laryngeal sensation. Effects, therefore, can be subtle and slowly progressive over time. This article delineates the general classes of medications that are known to cause alterations of vocal function, highlights medical history symptoms that may help raise suspicion for medication-related vocal changes, and presents recommendations for approaches to treatment of these issues.

PMID: 31076163 [PubMed - indexed for MEDLINE]

Idiosyncratic Drug-Induced Acute Liver Failure: A Challenging and Distressing Scenario.

Curr Drug Saf. 2019;14(2):94-101

Authors: Colaci CS, Mendizabal M, Bessone F

Abstract
BACKGROUND: Idiosyncratic Drug Induced Liver Injury (DILI) is a rare adverse event to drugs that occasionally leads to severe liver damage, being one of the leading causes of Acute Liver Failure (ALF) in developed countries. DILI is largely a diagnosis of exclusion.
DISCUSSION AND CONCLUSION: Careful history of drug taking and ruling out other competing etiologies is mandatory given that DILI can present with an extremely variable phenotype. Several prognostic scores have been developed to promptly identify patients with potential risk of developing ALF. New biomarkers to diagnose and predict DILI evolution are under study and hopefully we will benefit from these novel tools in the near future.

PMID: 30767751 [PubMed - indexed for MEDLINE]

Adverse Drug Reactions to Radiographic Contrast Media in a Teaching Hospital in North India: An Observational Study.

Curr Drug Saf. 2019;14(2):122-126

Authors: Chopra D, Jain A, Garg R, Dhingra S

Abstract
BACKGROUND: Radiocontrast media are used extensively nowadays to visualize internal organs. Currently, non-ionic iodinated contrast media are used which are generally considered to be safe but some adverse reactions have been reported. Thus, the present study was carried out to analyze the nature and incidence of adverse drug reactions (ADRs) to radiographic contrast media in a teaching hospital.
METHODS: An observational study carried out for a period of six months in a teaching hospital. Contrast media induced adverse reactions were analyzed in terms of affected organs, rate, causality assessment, severity and preventability. The treatment and outcomes of adverse events were also recorded. Naranjo Probability Scale was used to evaluate the relationship between the contrast agent used and the suspected ADR. The severity of the suspected ADRs was determined using Hartwig Scale and preventability was assessed using modified Schumock and Thornton criterion.
RESULTS: A total of 15 suspected ADRs occurred in 11 patients with an incidence of 1.4%. It included 5 (45.4%) males and 6 (54.5%) females (p < 05). The highest percentage (72.7 %) of ADRs was seen in adult patients, the mean age being 40.8 years. Vomiting (33.3%) was the most common ADR noted followed by severe nausea and rashes. 64.7 % of ADRs were categorized as probable and 35.3 % were possible. Adverse reactions required treatment in 46.6% patients. There was no fatality reported.
CONCLUSION: The reactions observed were mild to moderate in severity and occurred within 30 minutes of the administration of the contrast.

PMID: 30666915 [PubMed - indexed for MEDLINE]

Regorafenib in Chinese patients with metastatic colorectal cancer: subgroup analysis of the phase 3 CONCUR trial.

J Gastroenterol Hepatol. 2020 Jan 03;:

Authors: Xu J, Xu RH, Qin S, Pan H, Bai Y, Chi Y, Wang L, Bi F, Cheng Y, Liu T, Ma D, Shen L, Ba Y, Liang J, Wang X, Yau TCC, Ma BB, Yeh KH, Lin JK, Kappeler C, Shapiro JA, Kalmus J, Li J

Abstract
BACKGROUND AND AIM: In the phase 3 CONCUR trial (NCT01584830), regorafenib improved overall survival (OS) versus placebo in Asian patients with treatment-refractory metastatic colorectal cancer (mCRC). We conducted a post-hoc subgroup analysis of Chinese patients in CONCUR.
METHODS: Adults with mCRC progressing despite at least two prior treatment regimens and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:1 to regorafenib 160 mg once daily or placebo for the first 3 weeks of each 4-week cycle. Dose modifications were permitted. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective overall response, disease control rate, and safety.
RESULTS: A total of 172 Chinese patients were randomized and treated (regorafenib n=112, placebo n=60). OS was significantly improved with regorafenib versus placebo (8.4 vs 6.2 months, respectively; hazard ratio [HR] 0.56, 95% CI 0.39-0.80; one-sided p=0.000632), as was PFS (HR 0.32, 95% CI 0.22-0.47; one-sided p<0.000001). The most common drug-related grade ≥3 treatment-emergent adverse events (TEAEs; regorafenib, placebo) were hand-foot skin reaction (19%, 0%), hypertension (13%, 3%), hypophosphatemia (7%, 0), increased alanine aminotransferase (6%, 0), and increased aspartate aminotransferase (5%, 0). In patients receiving regorafenib and placebo, respectively, TEAEs led to treatment discontinuation in 14% and 7%, dose reduction in 39% and 0%, and dose interruption in 64% and 20%.
CONCLUSIONS: This retrospective analysis showed that regorafenib provided an OS benefit over placebo for Chinese patients with previously treated mCRC. TEAEs were consistent with the regorafenib safety profile and manageable with treatment modifications.

PMID: 31900959 [PubMed - as supplied by publisher]

Real-world study of direct oral anticoagulant dosing patterns in patients with atrial fibrillation.

Pharm Pract (Granada). 2019 Oct-Dec;17(4):1709

Authors: Gustafson WL, Saunders J, Vazquez SR, Jones AE, Witt DM

Abstract
Background: Direct oral anticoagulants (DOACs) are preferred for stroke prevention in atrial fibrillation (AF). However, off-label doses have been associated with increased risk of adverse events.
Objective: The objective of this study was to compare the frequency and outcomes of labeled versus off-label DOAC dosing in patients with AF.
Methods: This retrospective cohort study included adults diagnosed with nonvalvular AF (NVAF), discharged from University of Utah Health on DOAC therapy between 7/1/2017 and 9/30/2017. The primary outcome was off-label DOAC dosing frequency, defined as dosing inconsistent with manufacturer labeling. Secondary outcomes included variables associated with off-label dosing and a composite of adverse events (major bleeding, thromboembolism, and all-cause mortality) in the 90 days following the index hospital discharge.
Results: Of 249 included patients, 16.1% were discharged with off-label dosing. Factors associated with off-label dosing included advanced age, lower body mass index, decreased renal function, use of rivaroxaban, and hepatic impairment. The majority of off-label patients (70%) received lower-than-recommended DOAC dosing. Prescriber rationale for off-label prescribing was documented in 25% of patients and included anti-Xa guided dosing, high risk for bleeding or thromboembolism, and prior history of on-therapy adverse events. The rate of adverse events between labeled and off-label DOAC doses was not statistically different (10.0% vs. 6.7%, p=0.299), although this is likely due to small sample size.
Conclusions: Off-label DOAC prescribing for stroke prevention in NVAF at University of Utah Health was consistent or lower than previously published studies. Off-label dosing most often involved under-dosing of rivaroxaban. Future research should investigate the role of provider rationale and insight in optimizing DOAC therapy outcomes.

PMID: 31897264 [PubMed]

A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced esophagogastric cancer.

Invest New Drugs. 2020 Jan 02;:

Authors: Goyal L, Chaudhary SP, Kwak EL, Abrams TA, Carpenter AN, Wolpin BM, Wadlow RC, Allen JN, Heist R, McCleary NJ, Chan JA, Goessling W, Schrag D, Ng K, Enzinger PC, Ryan DP, Clark JW

Abstract
Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2, MET, or FGFR2 or mutations in PIK3CA, EGFR, or BRAF. Ganetespib which is a novel triazolone heterocyclic inhibitor of HSP90, is a potentially biologically rational treatment strategy for advanced EG cancers with these gene amplification. This multicenter, single-arm phase 2 trial enrolled patients with histologically confirmed advanced EG cancer with progression on at least one line of systemic therapy. Patients received Ganetespib 200 mg/m2 IV on Days 1, 8, and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints included: Progression Free Survival (PFS); to correlate the presence of HSP clients with ORR and PFS; evaluating the safety, tolerability and adverse events profile. In this study 26 eligible patients mainly: male 77%, median age 64 years were enrolled. The most common drug-related adverse events were diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response and stayed on treatment for more than seventy (70) months. Median PFS and OS was 61 days (2.0 months), 94 days (3.1 months) respectively. Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single-agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug.

PMID: 31898183 [PubMed - as supplied by publisher]

Interstitial nephritis associated with nivolumab in a patient with hodgkin lymphoma.

Rev Assoc Med Bras (1992). 2019 08 05;65(7):934-936

Authors: Oliveira DS, Mesquita JL, Garcia YDO, Rosales YMZ, Lemes RPG, Rocha Filho FD, Fernandes PFCBC, Duarte PMA, Pitombeira MDS, Duarte FB

PMID: 31389500 [PubMed - indexed for MEDLINE]

"Top ten": another alert on the prescription of proton-pump inhibitors (PPIs) for the elderly.

Rev Assoc Med Bras (1992). 2019 07 22;65(6):742-743

Authors: Manso MEG, Oliveira HSB

PMID: 31340295 [PubMed - indexed for MEDLINE]

Effectiveness of medication reviews in identifying and reducing medication-related problems among people with intellectual disabilities: A systematic review.

J Appl Res Intellect Disabil. 2019 Jul;32(4):750-761

Authors: Nabhanizadeh A, Oppewal A, Boot FH, Maes-Festen D

Abstract
BACKGROUND: Polypharmacy is common in people with intellectual disabilities. Using multiple medication may lead to unintended medication-related problems (MRPs). Medication review may serve as a tool to reduce MRPs. This systematic review assessed the scientific evidence for the effectiveness of medication reviews in identifying and reducing MRPs in people with intellectual disabilities.
METHOD: Literature databases were searched up to August 2017. Studies were selected that included the effect of medication reviews on identifying and/or reducing MRPs in people with intellectual disabilities with no restriction of type of medication, age and level of intellectual disabilities.
RESULTS: The eight studies that fulfilled the inclusion criteria report that systematic medication reviews appear to assist in the identification and reduction of MRPs.
CONCLUSION: There is a lack of studies about the effect of medication reviews on identification and reduction of MRPs, especially health outcomes for people with intellectual disabilities. Further studies with long-term follow-up are needed.

PMID: 30793852 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

J Urol. 2020 Jan 02;:101097JU0000000000000738

Authors: Kaplan SA, Herschorn S, McVary KT, Staskin D, Chapple C, Foley S, Cambronero Santos J, Kristy RM, Choudhury N, Hairston J, Schermer CR

Abstract
PURPOSE: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder (OAB) symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS: In this Phase 4 study, a 4-week, tamsulosin 0.4 mg run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received mirabegron 25 mg or placebo add-on therapy. At 4 weeks, doses were titrated to mirabegron 50 mg or placebo equivalent. Efficacy endpoints: changes from baseline to end of treatment in mean number of micturitions/day (primary), mean volume voided (MVV)/micturition, number of urgency episodes/day, Total Urgency and Frequency Score (TUFS), and total International Prostate Symptom Score (IPSS; secondary).
SAFETY: treatment-emergent adverse events (TEAEs) and post-void residual (PVR) volume and maximum urinary flow (Qmax) assessments.
RESULTS: Of 676 men, most were ≥65 years old (380 [56.2%] patients). Tamsulosin plus mirabegron (TAM+MIRA) was statistically superior to tamsulosin plus placebo (TAM+PL) in reducing the mean number of micturitions/day (-2.00 versus -1.62, adjusted difference: -0.39, 95% confidence interval: -0.76, -0.02). Statistically superior results were noted for TAM+MIRA in MVV/micturition, urgency episodes/day, and TUFS (not IPSS). Higher overall TEAE rates were observed with TAM+PL, although higher rates of drug-related TEAEs were noted with TAM+MIRA. Urinary retention rates were higher in the TAM+MIRA group. PVR volume and Qmax results were not clinically meaningful.
CONCLUSIONS: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with OAB symptoms receiving tamsulosin for BPH.

PMID: 31895002 [PubMed - as supplied by publisher]

Inferring Drug-Related Diseases Based on Convolutional Neural Network and Gated Recurrent Unit.

Molecules. 2019 Jul 25;24(15):

Authors: Xuan P, Zhao L, Zhang T, Ye Y, Zhang Y

Abstract
Predicting novel uses for drugs using their chemical, pharmacological, and indication information contributes to minimizing costs and development periods. Most previous prediction methods focused on integrating the similarity and association information of drugs and diseases. However, they tended to construct shallow prediction models to predict drug-associated diseases, which make deeply integrating the information difficult. Further, path information between drugs and diseases is important auxiliary information for association prediction, while it is not deeply integrated. We present a deep learning-based method, CGARDP, for predicting drug-related candidate disease indications. CGARDP establishes a feature matrix by exploiting a variety of biological premises related to drugs and diseases. A novel model based on convolutional neural network (CNN) and gated recurrent unit (GRU) is constructed to learn the local and path representations for a drug-disease pair. The CNN-based framework on the left of the model learns the local representation of the drug-disease pair from their feature matrix. As the different paths have discriminative contributions to the drug-disease association prediction, we construct an attention mechanism at the path level to learn the informative paths. In the right part, a GRU-based framework learns the path representation based on path information between the drug and the disease. Cross-validation results indicate that CGARDP performs better than several state-of-the-art methods. Further, CGARDP retrieves more real drug-disease associations in the top part of the prediction result that are of concern to biologists. Case studies on five drugs demonstrate that CGARDP can discover potential drug-related disease indications.

PMID: 31349692 [PubMed - indexed for MEDLINE]

Antioxidant Properties of Solenostemma argel Effervescent Tablets.

Curr Pharm Biotechnol. 2019;20(8):679-688

Authors: Suliman RS, Ali HS, Alhelal K, Almutairi W, Alnasser S, Omer M, Suliman R, Algebali A

Abstract
OBJECTIVE: In the present study, Solenostemma argel effervescent tablets were prepared from Argel methanolic extract.
METHODS: The tablets were examined for their ability to impede carbon tetrachloride (CCl4)-induced lipid peroxidation in mice liver. The antioxidant activities of the enzymes; super-oxide dismutase (SOD), glutathione peroxidase (GS-PX) along with malondialdehyde level were tested in liver tissues.
RESULTS: The obtained results indicated that the antioxidant enzyme activities were remarkably reduced while the level of Malondialdehyde (MDA), which shows lipid peroxidation, and the activity of alanine aminotransferase (a liver function test) were remarkably intensified following intra-peritoneal i.p injection with the single sub-lethal hepatotoxic dose of CCl4 compared to the control. A necrotic lesion in the liver of mice injected with CCl4 was observed by the histopathological examination. The damaging influence of CCl4 was improved by the retreatment with Argel or BHT, which could also be observed in the normal appearance of the liver tissue.
CONCLUSION: In this study, it was concluded that S. Argel and butylated hydroxytoluene (BHT) could be effective by decreasing lipid peroxidation and increasing the activities of antioxidant enzymes. Therefore, Argel might be applied as a hepatoprotective agent without any side effects.

PMID: 31244420 [PubMed - indexed for MEDLINE]

Recommendations on the Use of Mobile Applications for the Collection and Communication of Pharmaceutical Product Safety Information: Lessons from IMI WEB-RADR.

Drug Saf. 2019 04;42(4):477-489

Authors: Pierce CE, de Vries ST, Bodin-Parssinen S, Härmark L, Tregunno P, Lewis DJ, Maskell S, Van Eemeren R, Ptaszynska-Neophytou A, Newbould V, Dasgupta N, Wisniewski AFZ, Gama S, Mol PGM

Abstract
Over a period of 3 years, the European Union's Innovative Medicines Initiative WEB-RADR (Recognising Adverse Drug Reactions; https://web-radr.eu/ ) project explored the value of two digital tools for pharmacovigilance (PV): mobile applications (apps) for reporting the adverse effects of drugs and social media data for its contribution to safety signalling. The ultimate intent of WEB-RADR was to provide policy, technical and ethical recommendations on how to develop and implement such digital tools to enhance patient safety. Recommendations relating to the use of mobile apps for PV are summarised in this paper. There is a presumption amongst at least some patients and healthcare professionals that information ought to be accessed and reported from any setting, including mobile apps. WEB-RADR has focused on the use of such technology for reporting suspected adverse drug reactions and for broadcasting safety information to its users, i.e. two-way risk communication. Three apps were developed and publicly launched within Europe as part of the WEB-RADR project and subsequently assessed by a range of stakeholders to determine their value as effective tools for improving patient safety; a fourth generic app was later piloted in two African countries. The recommendations from the development and evaluation of the European apps are presented here with supporting considerations, rationales and caveats as well as suggested areas for further research.

PMID: 30911975 [PubMed - indexed for MEDLINE]

Prescribing Antipsychotic Medications to Patients With Dementia: Boxed Warnings and Mitigation of Legal Liability.

Continuum (Minneap Minn). 2019 Feb;25(1):254-259

Authors: Rose RV, Kass JS

Abstract
Clinicians caring for patients with dementia are often at a loss when trying to manage dementia-related behavioral disturbances pharmacologically because no drugs have been proven effective for this indication. Antipsychotics are commonly prescribed for these patients despite a US Food and Drug Administration (FDA)-mandated boxed warning about the heightened risk of death in patients with dementia treated with antipsychotic drugs. This boxed warning does not prevent clinicians from prescribing antipsychotics to patients with dementia. However, it serves as a heightened warning to prescribers to include the specific risks mentioned in the boxed warning in their discussion of risks and benefits of the proposed therapy with their patients or their patients' health care proxy and to document this informed consent conversation in the medical record. By documenting that the risks of the treatment, including those the FDA has deemed serious enough to include in a boxed warning, were discussed and accepted by the medical decision maker, the prescriber also reduces the risk of liability should an adverse event ensue.

PMID: 30707196 [PubMed - indexed for MEDLINE]