Predictors of the Onset of Type 1 Diabetes Obtained from Real-World Data Analysis in Cancer Patients Treated with Immune Checkpoint Inhibitors.

Asian Pac J Cancer Prev. 2020 Jun 01;21(6):1697-1699

Authors: Takada S, Hirokazu H, Yamagishi K, Hideki S, Masayuki E

Abstract
Medications that target programmed cell death protein-1 (PD-1) have proven effective. However, blockade of PD-1/Programmed death-ligand 1(PD-L1) causes immune-related adverse events (irAEs). Characteristics of this irAE include many symptom, low in frequency, and difficulty in prevention. The key to a successful ICI-related treatment lies in the management of irAEs resulting from immune checkpoint inhibitor (ICI) treatment. Although it is difficult to predict irAE, we tried to extract features of irAE expression from analysis of real-world database. This study used data extracted from the Japan Adverse Drug Event Report (JADER) database to assess risk factors associated with serious side effects of irAE, type 1 diabetes (T1DM). The analysis targets were nivolumab, atezolizumab, durvalumab, and pembrolizumab, and the study period was from July 2014 to June 2019. Analysis of Japanese population data confirmed that being women and having melanoma were risk factors for developing ICI-related T1DM. Analysis using this database in combination with information on ICI-related T1DM provides information and guidelines that will help in the safer treatment of ICI in the future.

PMID: 32592366 [PubMed - indexed for MEDLINE]

Adherence to ASCO for Prophylaxis of Acute Chemotherapy- Induced Nausea and Vomiting in Iran.

Asian Pac J Cancer Prev. 2020 Jun 01;21(6):1567-1572

Authors: Ebrahimi M, Mehrzad V, Moghaddas A

Abstract
INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the scariest chemotherapy-induced adverse effects. We evaluated the adherence to the 2017 American Society of Clinical Oncology (ASCO), the latest guideline recommendations, for the management of acute CINV at our institute.
METHODS: During a 6-months cross-sectional study on outpatient's cancer patients, we collected data from the prescription documents during temporary hospitalization and compared the results with ASCO guideline recommendations.
RESULTS: The most prescribed prophylactic regimens for the management of CINV were combination of aprepitant, granisetron, and dexamethasone and metoclopramide (51.8%). Regarding prescription compatibility in our center with ASCO guideline recommnedations, selection of different regimens for prophylaxis of acute CINV in our institute was compliant in 0 %, 22%, 4%, and 40% of high, moderate, low, and minimal emetogenic potential of chemotherapy regimen groupss, respectively.
CONCLUSION: Although our hospital is a referral and university-affiliated center, adherence to the ASCO guideline recommendations for prophylaxis of CINV was poor.

PMID: 32592350 [PubMed - indexed for MEDLINE]

Peptide Vaccination against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients.

Vaccines (Basel). 2021 Feb 06;9(2):

Authors: Sommerer C, Schmitt A, Hückelhoven-Krauss A, Giese T, Bruckner T, Wang L, Schnitzler P, Meuer S, Zeier M, Schmitt M

Abstract
INTRODUCTION: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for seronegative end-stage renal disease patients waiting for kidney transplantation.
METHODS: The highly immunogenic nonamer peptide NLVPMVATV derived from CMV phosphoprotein 65(CMVpp65) in a water-in-oil emulsion (Montanide™) plus imiquimod (Aldara™) as an adjuvant was administered subcutaneously four times biweekly. Clinical course as well as immunological responses were monitored using IFN-γ ELISpot assays and flow cytometry for CMV-specific CD8+ T cells.
RESULTS: Peptide vaccination was well tolerated, and no drug-related serious adverse events were detected except for Grade I-II local skin reactions. Five of the 10 patients (50%) mounted any immune response (responders) and 40% of the patients presented CMV-specific CD8+ T cell responses elicited by these prophylactic vaccinations. No responders experienced CMV reactivation in the 18 months post-transplantation, while all non-responders reactivated.
CONCLUSION: CMVpp65 peptide vaccination was safe, well tolerated, and clinically encouraging in seronegative end-stage renal disease patients waiting for kidney transplantation. Further studies with larger patient cohorts are planned.

PMID: 33562163 [PubMed]

Mining and visualizing high-order directional drug interaction effects using the FAERS database.

BMC Med Inform Decis Mak. 2020 03 18;20(Suppl 2):50

Authors: Yao X, Tsang T, Sun Q, Quinney S, Zhang P, Ning X, Li L, Shen L

Abstract
BACKGROUND: Adverse drug events (ADEs) often occur as a result of drug-drug interactions (DDIs). The use of data mining for detecting effects of drug combinations on ADE has attracted growing attention and interest, however, most studies focused on analyzing pairwise DDIs. Recent efforts have been made to explore the directional relationships among high-dimensional drug combinations and have shown effectiveness on prediction of ADE risk. However, the existing approaches become inefficient from both computational and illustrative perspectives when considering more than three drugs.
METHODS: We proposed an efficient approach to estimate the directional effects of high-order DDIs through frequent itemset mining, and further developed a novel visualization method to organize and present the high-order directional DDI effects involving more than three drugs in an interactive, concise and comprehensive manner. We demonstrated its performance by mining the directional DDIs associated with myopathy using a publicly available FAERS dataset.
RESULTS: Directional effects of DDIs involving up to seven drugs were reported. Our analysis confirmed previously reported myopathy associated DDIs including interactions between fusidic acid with simvastatin and atorvastatin. Furthermore, we uncovered a number of novel DDIs leading to increased risk for myopathy, such as the co-administration of zoledronate with different types of drugs including antibiotics (ciprofloxacin, levofloxacin) and analgesics (acetaminophen, fentanyl, gabapentin, oxycodone). Finally, we visualized directional DDI findings via the proposed tool, which allows one to interactively select any drug combination as the baseline and zoom in/out to obtain both detailed and overall picture of interested drugs.
CONCLUSIONS: We developed a more efficient data mining strategy to identify high-order directional DDIs, and designed a scalable tool to visualize high-order DDI findings. The proposed method and tool have the potential to contribute to the drug interaction research and ultimately impact patient health care.
AVAILABILITY AND IMPLEMENTATION: http://lishenlab.com/d3i/explorer.html.

PMID: 32183790 [PubMed - indexed for MEDLINE]

Mouse Embryonic Stem Cell-Derived Ureteric Bud Progenitors Induce Nephrogenesis.

Cells. 2020 01 31;9(2):

Authors: Tan Z, Rak-Raszewska A, Skovorodkin I, Vainio SJ

Abstract
Generation of kidney organoids from pluripotent stem cells (PSCs) is regarded as a potentially powerful way to study kidney development, disease, and regeneration. Direct differentiation of PSCs towards renal lineages is well studied; however, most of the studies relate to generation of nephron progenitor population from PSCs. Until now, differentiation of PSCs into ureteric bud (UB) progenitor cells has had limited success. Here, we describe a simple, efficient, and reproducible protocol to direct differentiation of mouse embryonic stem cells (mESCs) into UB progenitor cells. The mESC-derived UB cells were able to induce nephrogenesis when co-cultured with primary metanephric mesenchyme (pMM). In generated kidney organoids, the embryonic pMM developed nephron structures, and the mESC-derived UB cells formed numerous collecting ducts connected with the nephron tubules. Altogether, our study established an uncomplicated and reproducible platform to generate ureteric bud progenitors from mouse embryonic stem cells.

PMID: 32023845 [PubMed - indexed for MEDLINE]

Potentially inappropriate prescribing in dementia: a state-of-the-art review since 2007.

BMJ Open. 2020 01 02;10(1):e029172

Authors: Delgado J, Bowman K, Clare L

Abstract
OBJECTIVES: Dementia frequently occurs alongside comorbidities. Coexisting conditions are often managed with multiple medications, leading to increased risk of potentially inappropriate medication and adverse drug reactions. We aimed to estimate prevalence of, and identify factors reported to be associated with, potentially inappropriate prescribing (PIP) for older individuals diagnosed with dementia.
DESIGN: We used a state-of-the-art review approach, selecting papers written in English and published from 2007 to January 2018. Publications were retrieved from Scopus and Web of Science databases. Inclusion criteria included a formal diagnosis of dementia, a formal classification of PIP and reported prevalence of PIP as an outcome. Random effects models were used to provide a pooled estimate of prevalence of PIP. The Appraisal tool for Cross-Sectional Studies (AXIS tool) was used to assess bias in the included studies.
RESULTS: The bibliographic search yielded 221 citations, with 12 studies meeting the inclusion criteria. The estimates of PIP prevalence for people living with dementia ranged from 14% to 64%. Prevalence was 31% (95% CI 9 to 52) in the community, and 42% (95% CI 30 to 55) in nursing/care homes. PIP included prescribing likely related to dementia (eg, hypnotics and sedative and cholinesterase inhibitors) and prescribing related to treatment of comorbidities (eg, cardiovascular drugs and non-steroidal anti-inflammatory medication). Higher levels of comorbidity were associated with increased risk of PIP; however, only one study investigated associations with specific comorbidities of dementia.
CONCLUSION: PIP remains a significant issue in healthcare management for people living with dementia. Higher levels of comorbidity are associated with increased prevalence of PIP, but the specific conditions driving this increase remain unknown. Further work is necessary to investigate PIP related to the presence of common comorbidities in patients living with dementia.

PMID: 31900263 [PubMed - indexed for MEDLINE]

Predictivity/Translatability of Toxicities Observed in Nonclinical Toxicology Studies to Clinical Safety Outcomes in Drug Development: Case Examples.

Int J Toxicol. 2020 Mar/Apr;39(2):141-150

Authors: Stagg NJ, Ghantous HN, Roth R, Hastings KL

Abstract
Nonclinical toxicology studies are conducted to characterize the potential toxicities and establish a safe starting dose for new drugs in clinical studies, but the question remains as to how predictable/translatable the nonclinical safety findings are to humans. In many cases, there is good concordance between nonclinical species and patients. However, there are cases for which there is a lack of predictivity or translatability that led to early termination of clinical studies due to unanticipated toxicities or early termination of programs before making it to the clinic due to unacceptable nonclinical toxicities assumed to be translatable. A few case examples of safety findings that are translatable versus safety findings that are not translatable and why they are not translateable were presented as a symposium at the 38th Annual Meeting of the American College of Toxicology in Palm Springs, California, and are discussed in this article.

PMID: 31875744 [PubMed - indexed for MEDLINE]

Drug dose and drug choice: Optimizing medical therapy for veterinary cancer.

Vet Comp Oncol. 2020 Jun;18(2):143-151

Authors: Thamm DH, Gustafson DL

Abstract
Although novel agents hold great promise for the treatment of animal neoplasia, there may be room for significant improvement in the use of currently available agents. These improvements include altered dosing schemes, novel combinations, and patient-specific dosing or selection of agents. Previous studies have identified surrogates for "individualized dose intensity,", for example, patient size, development of adverse effects, and pharmacokinetic parameters, as potential indicators of treatment efficacy in canine lymphoma, and strategies for patient-specific dose escalation are discussed. Strategies for treatment selection in individual patients include conventional histopathology, protein-based target assessment (eg, flow cytometry, immunohistochemistry, and mass spectrometry), and gene-based target assessment (gene expression profiling and targeted or global sequencing strategies). Currently available data in animal cancer evaluating these strategies are reviewed, as well as ongoing studies and suggestions for future directions.

PMID: 31487110 [PubMed - indexed for MEDLINE]

Safety profiles of new xanthine oxidase inhibitors: A post-marketing study.

Int J Clin Pharmacol Ther. 2021 Feb 09;:

Authors: Wakabayashi T, Ueno S, Nakatsuji T, Hirai T, Niinomi I, Oyama S, Inada A, Kambara H, Iwanaga K, Hosohata K

Abstract
INTRODUCTION: The development of new xanthine oxidase (XO) inhibitors, such as febuxostat and topiroxostat, could offer an alternative to treatment with allopurinol. The purpose of this study was to compare safety profiles of new XO inhibitors with allopurinol using a spontaneous reporting system database.
MATERIALS AND METHODS: A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated.
RESULTS: Among 7,305 reports of adverse events associated with XO inhibitors, 64.5% involved males, who were frequently in their 70s (25.9%). A large number of skin-related adverse events were detected with the use of allopurinol, but not with febuxostat or topiroxostat. As for individual XO inhibitors, the signal values showing associations between drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol, drug-induced liver injury and febuxostat, and blood urea increase and topiroxostat were noteworthy.
CONCLUSION: The strength of the associations of XO inhibitors with adverse events is variable, and further studies are required to evaluate the identified signals.

PMID: 33560211 [PubMed - as supplied by publisher]

An unusual case of piperacillin-tazobactam-induced fever, eosinophilia, thrombocytopenia and liver damage.

Eur J Hosp Pharm. 2021 Feb 08;:

Authors: Lv J, Wu G, Zhang F, Su X

Abstract
Piperacillin-tazobactam is a broad-spectrum antimicrobial agent that is commonly used in clinical practice. The development of delayed drug hypersensitivity reaction (DHR) has been reported in several cases previously. Here we describe an unusual case of non-immediate DHR due to a prolonged course of piperacillin-tazobactam. We report a 22-year-old man who developed fever, eosinophilia, thrombocytopenia and elevated hepatic enzymes following 17 days of piperacillin-tazobactam for methicillin-sensitive Staphylococcus aureus (MSSA) pneumonia. These adverse reactions were reversed immediately after antibiotic cessation. Our case highlights that clinicians should be aware of delayed adverse effects in patients receiving long-term piperacillin-tazobactam treatment.

PMID: 33558219 [PubMed - as supplied by publisher]

Risk for Infections During Treatment With Denosumab for Osteoporosis: A Systematic Review and Meta-analysis.

J Clin Endocrinol Metab. 2020 05 01;105(5):

Authors: Diker-Cohen T, Rosenberg D, Avni T, Shepshelovich D, Tsvetov G, Gafter-Gvili A

Abstract
CONTEXT: Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand, an immune system modulator. Safety endpoints including risk for infections were assessed as secondary outcomes in randomized controlled trials (RCTs) of the drug.
OBJECTIVE: To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients.
DATA SOURCES: PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019.
STUDY SELECTION: All RCTs of denosumab (60 mg every 6 months) versus any comparator were included. We excluded trials in cancer patients for prevention of skeletal-related events.
DATA EXTRACTION: Two reviewers independently applied selection criteria and extracted the data. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a fixed effect model. Sensitivity analysis was based on risk of bias.
DATA SYNTHESIS: Thirty-three studies (22 253 patients) were included. There was a higher incidence of SAEI during denosumab treatment versus any comparator (RR, 1.21; 95% CI, 1.04-1.40; I2 = 0%), mainly of ear, nose, and throat (RR, 2.66; 95% CI, 1.20-5.91) and gastrointestinal origin (RR, 1.43; 95% CI, 1.02-2.01). RR was similar in a sensitivity analysis based on adequate allocation concealment. The RR of any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) was comparable between groups.
CONCLUSIONS: A higher incidence of SAEI is demonstrated during treatment with denosumab in an osteoporosis dose. Nevertheless, the overall risk for any infection or related mortality is similar to comparator groups. These findings merit consideration before therapy initiation.

PMID: 31899506 [PubMed - indexed for MEDLINE]

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

J Child Adolesc Psychopharmacol. 2020 02;30(1):38-47

Authors: Mazhar H, Foster BC, Necyk C, Gardiner PM, Harris CS, Robaey P

Abstract
Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

PMID: 31670573 [PubMed - indexed for MEDLINE]

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J Med Chem. 2021 Feb 7. doi: 10.1021/acs.jmedchem.0c01886. Online ahead of print.

ABSTRACT

This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 acts on the cytochrome P450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve inflammation, and maintain normal blood pressure. EC5026 is a slow-tight binding transition-state mimic that inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations. The sEH rapidly degrades EpFA; thus, inhibiting sEH increases EpFA in vivo and confers beneficial effects. This mechanism addresses disease states by shifting endoplasmic reticulum stress from promoting cellular senescence and inflammation toward cell survival and homeostasis. We describe the synthesis and optimization of EC5026 and its development through human Phase 1a trials with no drug-related adverse events. Additionally, we outline fundamental work leading to discovery of the analgesic and inflammation-resolving CYP450 branch of the arachidonate cascade.

PMID:33550801 | DOI:10.1021/acs.jmedchem.0c01886

Opioid safety: striking the right balance.

Drug Ther Bull. 2021 Feb 05;:

Authors: Erskine D, Wanklyn S

PMID: 33547173 [PubMed - as supplied by publisher]

Efficacy, Safety, and Tolerability of a Novel Cyclosporine, a Formulation for Dry Eye Disease: a Multicenter Phase II Clinical Study.

Clin Ther. 2021 Feb 02;:

Authors: Peng WY, Chen RX, Dai H, Zhu L, Li Y, Gao ZQ, Li XY, Zhou SY

Abstract
PURPOSE: The purpose of this study was to explore the efficacy, safety, and tolerability of a novel cyclosporine formulation for dry eye disease (DED).
METHODS: This is an exploratory, multicenter, single-blind, randomized, positive-controlled Phase II clinical trial between cyclosporine ophthalmic gel (CyclAGel) and an open-label comparator (Restasis, positive control). A total of 240 eligible patients with moderate to severe DED were randomized to 4 study groups: CyclAGel 0.05%/once daily (QD) (n = 59), CyclAGel 0.05%/BID (n = 60), CyclAGel 0.1%/QD (n = 60), and Restasis 0.05%/BID (n = 61). After receiving BID dosing of hypromellose eye drops during a 2-week run-in period, patients were randomized to the respective treatment group and dosed QD or BID for 12 weeks. Efficacy was assessed based on a number of sign and symptom end points, including eye dryness score (visual analog scale), 6 other parameters of symptoms for dryness (burning/stinging, itching, foreign body sensation, discomfort, sensitivity to light, and pain), and corneal fluorescein staining. The Schirmer test was used to assess dry eye symptoms (visual analog scale severity) at visit 3 (week 2), visit 4 (week 6), and visit 5 (week 12).
FINDINGS: CyclAGel showed a consistent improvement in eye dryness score and the 6 other parameters of symptoms for dryness, corneal fluorescein staining, breakup time, and Schirmer test scores compared with Restasis over the 12-week treatment period. However, there were no statistically significant differences between CyclAGel and Restasis after baseline corrections were made, and the results of the full analysis set remained consistent with those of the per-protocol set (P > 0.05). Moreover, each CyclAGel-treated group (0.05%/QD, 0.05%/BID, and 0.1%/QD) exerted better effects than the Restasis group, and CyclAGel 0.05%/QD showed the most significant improvement. The number of ocular-related treatment-emergent adverse events was low in all treatment groups, with no serious drug-related treatment-emergent adverse events.
IMPLICATIONS: CyclAGel showed excellent safety, tolerability, and comfort profiles at 2 concentrations and frequency in moderate to severe DED.

PMID: 33546885 [PubMed - as supplied by publisher]

Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study.

Anticancer Res. 2021 Feb;41(2):927-936

Authors: Kabadi SM, Byfield SD, LE L, Olufade T

Abstract
BACKGROUND/AIM: Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL). The aim of this retrospective study was to describe treatment patterns, AEs, and associated healthcare costs.
PATIENTS AND METHODS: Patients had two or more claims coded for MCL diagnosis, the first claim date (07/01/2012-05/31/2017) was the index date. Patients with pre-index MCL diagnosis or systemic treatment, or hematopoietic stem cell transplantation were excluded. Cohorts by regimen were followed for up to three lines of therapy.
RESULTS: Patients (n=395; median age 72 years; 31% female) were observed over a total of 576 lines of therapy, the most common being bendamustine plus rituximab; rituximab monotherapy; R-CHOP; and ibrutinib. The most frequent AEs were hypertension (40.5%), anemia (37.7%), and infection (36.1%). However, hepatotoxicity ($19,645), stroke ($18,893), and renal failure ($9,037) were associated with the highest medical costs per patient per month.
CONCLUSION: Among patients receiving common systemic treatments for MCL, AEs occurred frequently; some imposed substantial inpatient care costs.

PMID: 33517299 [PubMed - indexed for MEDLINE]

Characterization of drug-induced cutaneous lupus: Analysis of 1994 cases using the WHO pharmacovigilance database.

Autoimmun Rev. 2021 Jan;20(1):102705

Authors: Kawka L, Mertz P, Chasset F, Lebrun-Vignes B, Salem JE, Arnaud L

PMID: 33188917 [PubMed - indexed for MEDLINE]

Impact of pharmacist-led multidisciplinary medication review on the safety and medication cost of the elderly people living in a nursing home: a before-after study.

Expert Rev Pharmacoecon Outcomes Res. 2020 Oct;20(5):481-490

Authors: Leguelinel-Blache G, Castelli C, Rolain J, Bouvet S, Chkair S, Kabani S, Jalabert B, Rouvière S, Choukroun C, Richard H, Kinowski JM

Abstract
Objectives: Adverse drug events (ADE) are a common cause of morbidity and mortality in elderly patients. In this study, we assessed the impact of multidisciplinary medication review (MMR) for nursing home residents on patient safety and costs incurred by the hospital and the national health service. Methods: Medical files of residents were retrospectively assessed for medications prescribed in the previous six months. A pharmacist reviewed the prescriptions and suggested modifications to the patient's medical team. Patients were followed for six months. Trivalle's ADE geriatric risk score was calculated before and after MMR, as were number of potentially inappropriate medications, and economic impact from the perspective of the health care system and the nursing home. Results: Forty-nine patients were recruited. ADE score dropped one risk level (median score of 4 before versus 1 after, p < 0.0001). The number of patients taking at least one potentially inappropriate medication decreased from 30.6% before to 6.1% after MMR (p = 0.005). A mean saving of €232 per patient was made from the nursing home perspective following MMR (p = 0.008). Conclusion: The MMR reduced the iatrogenic drug risk for elderly residents and costs from the nursing home perspective, particularly drug expenditure.

PMID: 31899986 [PubMed - indexed for MEDLINE]

Unveiling the guidance heterogeneity for genome-informed drug treatment interventions among regulatory bodies and research consortia.

Pharmacol Res. 2020 03;153:104590

Authors: Koutsilieri S, Tzioufa F, Sismanoglou DC, Patrinos GP

Abstract
Pharmacogenomics and personalized medicine interventions hold promise to optimize drug treatment modalities and hence, improve the quality of life of the patients by minimizing the occurrence of adverse drug reactions and/or maximizing drug treatment efficacy. To this end, proper guidance for accurately prescribing the correct drug at the right dose is empowered by major regulatory bodies, namely the U.S. Food and Drug Administration (FDA) and the European Medicine Agency (EMA), and well-recognized research consortia, like the Clinical Pharmacogenetics Implementation Consortium (CPIC), that propose therapeutic recommendations after the thorough evaluation of the existing scientific evidence base. In this context, the consistency of these recommendations is crucial for smoothly integrating pharmacogenomics into the clinic. Here, we collected all of the important and clinically actionable pharmacogenomics information provided by the aforementioned renowned sources and documented it in order to assess potential similarities and, most importantly, differences. Our data show that the level of concordance regarding the guidance provided for the same drug-gene association pairs varies significantly, despite the fact that it all derives from a single evidence base. In particular, apart from the expected similarities in a number of association pairs, especially the ones related to cancer genomics, there are still major discrepancies that create confusion as to which guidance should be followed in order to properly inform drug prescribing. This regulatory deficiency calls for the fruitful engagement of the regulatory agencies involved with the contribution of other experts engaged in the field of pharmacogenomics in an effort to harmonize the existing arsenal of guidance for genome-informed drug prescription. The achievement of harmonization would in turn expedite bringing personalized medicine closer to clinical fruition.

PMID: 31830522 [PubMed - indexed for MEDLINE]