Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies.

J Immunol Res. 2018;2018:5376476

Authors: Ng CY, Chen CB, Wu MY, Wu J, Yang CH, Hui RC, Chang YC, Lu CW

Abstract
Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

PMID: 29577050 [PubMed - indexed for MEDLINE]

Automated Screening of Emergency Department Notes for Drug-Associated Bleeding Adverse Events Occurring in Older Adults.

Appl Clin Inform. 2017 10;8(4):1022-1030

Authors: Boyce RD, Jao J, Miller T, Kane-Gill SL

Abstract
Objective To conduct research to show the value of text mining for automatically identifying suspected bleeding adverse drug events (ADEs) in the emergency department (ED). Methods A corpus of ED admission notes was manually annotated for bleeding ADEs. The notes were taken for patients ≥ 65 years of age who had an ICD-9 code for bleeding, the presence of hemoglobin value ≤ 8 g/dL, or were transfused > 2 units of packed red blood cells. This training corpus was used to develop bleeding ADE algorithms using Random Forest and Classification and Regression Tree (CART). A completely separate set of notes was annotated and used to test the classification performance of the final models using the area under the ROC curve (AUROC). Results The best performing CART resulted in an AUROC on the training set of 0.882. The model's AUROC on the test set was 0.827. At a sensitivity of 0.679, the model had a specificity of 0.908 and a positive predictive value (PPV) of 0.814. It had a relatively simple and intuitive structure consisting of 13 decision nodes and 14 leaf nodes. Decision path probabilities ranged from 0.041 to 1.0. The AUROC for the best performing Random Forest method on the training set was 0.917. On the test set, the model's AUROC was 0.859. At a sensitivity of 0.274, the model had a specificity of 0.986 and a PPV of 0.92. Conclusion Both models accurately identify bleeding ADEs using the presence or absence of certain clinical concepts in ED admission notes for older adult patients. The CART model is particularly noteworthy because it does not require significant technical overhead to implement. Future work should seek to replicate the results on a larger test set pulled from another institution.

PMID: 29241242 [PubMed - indexed for MEDLINE]

Effect of prescription medications on erectile dysfunction.

Postgrad Med J. 2018 Mar;94(1109):171-178

Authors: Razdan S, Greer AB, Patel A, Alameddine M, Jue JS, Ramasamy R

Abstract
Erectile dysfunction (ED) affects about 50% of men in the USA and is primarily attributed to physiological (organic) and psychological causes. However, a substantial portion of men suffer from ED due to iatrogenic causes. Common medications such as antihypertensives, non-steroidal anti-inflammatory drugs and antacids may cause ED. Physicians should be aware of the various prescription medications that may cause ED to properly screen and counsel patients on an issue that many may feel too uncomfortable to discuss. In this review, we discuss the physiology, data and alternative therapies for the ED caused by medications.

PMID: 29103015 [PubMed - indexed for MEDLINE]

Chemical toxicity prediction for major classes of industrial chemicals: Is it possible to develop universal models covering cosmetics, drugs, and pesticides?

Food Chem Toxicol. 2018 Feb;112:526-534

Authors: Alves VM, Muratov EN, Zakharov A, Muratov NN, Andrade CH, Tropsha A

Abstract
Computational models have earned broad acceptance for assessing chemical toxicity during early stages of drug discovery or environmental safety assessment. The majority of publicly available QSAR toxicity models have been developed for datasets including mostly drugs or drug-like compounds. We have evaluated and compared chemical spaces occupied by cosmetics, drugs, and pesticides, and explored whether current computational models of toxicity endpoints can be universally applied to all these chemicals. Our analysis of the chemical space overlap and applicability domain (AD) of models built previously for twenty different toxicity endpoints showed that most of these models afforded high coverage (>90%) for all three classes of compounds analyzed herein. Only T. pyriformis models demonstrated lower coverage for drugs and pesticides (38% and 54%, respectively). These results show that, for the most part, historical QSAR models built with data available for different toxicity endpoints can be used for toxicity assessment of novel chemicals irrespective of the intended commercial use; however, the AD restriction is necessary to assure the expected prediction accuracy. Local models may need to be developed to capture chemicals that appear as outliers with respect to global models.

PMID: 28412406 [PubMed - indexed for MEDLINE]

For drug-induced carcinogenesis, the observations are the hypothesis: Invited editorial for the Mini-Symposium on Cancer Pharmacoepidemiology.

Ann Epidemiol. 2016 11;26(11):749-750

Authors: Walker AM

PMID: 27637749 [PubMed - indexed for MEDLINE]

Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study.

Leuk Lymphoma. 2018 Aug 30;:1-10

Authors: Walewski J, Paszkiewicz-Kozik E, Borsaru G, Hellmann A, Janikova A, Warszewska A, Mais A, Ammendola A, Herz T, Krauss B, Henning SW

Abstract
This open-label, single-arm phase II study examined efficacy, safety, pharmacokinetics, and biomarkers of histone deacetylase (HDAC) inhibitor resminostat in patients with relapsed or refractory Hodgkin lymphoma. Thirty-seven heavily pretreated patients received 600 (19 patients) or 800 mg (18 patients) oral resminostat daily for the initial 5 days of 14-day treatment cycles. Objective response rate (ORR) (primary) was 34% reaching disease control in 54% patients. Most patients (69%) showed reduced tumor size and reduced [18F]-FDG uptake in target lesions (71%). Median progression-free survival (PFS) was 2.3 months (95%CI [1.3; 3.3]) and median overall survival (OS) was 12.5 months (95%CI [9.6; 18.6]). Patients who responded or stabilized under resminostat had a 10-month longer OS than patients who progressed. Efficacy assessment, pharmacodynamics, and exploratory biomarker results followed plasma levels, showed target engagement and epigenetic modulations. Common drug-related adverse events (AEs) were nausea, vomiting, anemia, thrombocytopenia, and fatigue, mainly grade 1 or 2.

PMID: 30160566 [PubMed - as supplied by publisher]

Minimal Use of Opioids for Pain Relief in an Internal Medicine Department.

South Med J. 2018 05;111(5):288-292

Authors: Shimoni Z, Varon D, Froom P

Abstract
OBJECTIVES: The objective of the study was to determine if pain control was adequate despite our policy of limited opioid use.
METHODS: In this observational cohort study, we reviewed 300 consecutive patient charts from an internal medicine department. We extracted demographic data, as well as the patients' primary diagnosis, pain on admission, daily pain evaluations (numerical rating score [NRS]), and treatment. Significant pain was defined as a score of ≥3 on the NRS. We determined the incidence of pain and pain control and reviewed the charts of those with an NRS ≥3 for ≥3 days to determine the need for opioid therapy.
RESULTS: Of 1692 total hospitalization days in the 300 consecutive patients with a median age of 80 years (1st-3rd quartiles, 65-87 years) there were 204 days with complaints of pain (12.1%) and 149 days (8.8%) with reports of pain of ≥3 on the NRS. Overall, 28.3% (85 of 300) of the patients had significant pain during their hospitalization. Most of the pain, however, (80.0%, 68 of 85) was short-term (1-2 days) whether or not the patient received pain medication. Pain relief treatment in the hospital included opioids in 17 (5.7%, 95% confidence interval [CI] 3.5-8.9) and dipyrone in 36 (12%, 95% CI 8.8-16) of the 300 patients. Pain control was adequate in the seven patients with prolonged pain who did not receive opioids. There were only two patients discharged with prescriptions for opioids (0.7%, 95% CI 0.2-2.6).
CONCLUSIONS: Significant pain is common in patients hospitalized in an internal medicine department, but the pain is mostly short term and pain control is adequate despite the restricted use of opioid therapy during hospitalization.

PMID: 29767221 [PubMed - indexed for MEDLINE]

Effectiveness and the strategy to treat the side effects of sorafenib administration after transarterial chemoembolization in advanced hepatocellular carcinoma patients.

J Cancer Res Ther. 2018 Jan;14(1):196-200

Authors: Zhang K, Sun X, Xie F, Jian W, Li C

Abstract
Objective: The aim is to study the effectiveness and side effects of sorafenib administration after transarterial chemoembolization (TACE) in advanced hepatocellular carcinoma (HCC) patients. To evaluate the safety of the combination of sorafenib and TACE to treat HCC.
Materials and Methods: A total of 36 unresectable HCC patients were enrolled. After TACE, administration of sorafenib was carried out. Follow-up was taken for every 4 weeks. Liver and renal function and alpha-fetoprotein were tested. Modified response evaluation criteria in solid tumors (mRECIST) was used to evaluate the clinical effect. The side effects were recorded.
Results: The median overall survival (mOS) and the median time to progress were 12.5 and 8 months with the range from 6 to 32 and 4-30 months, respectively. The mOS of patients with single tumor was 18 months while that of multiple tumors in liver was 10 months (χ2 = 4.1639, P = 0.0413). According to mRECIST, there were no complete response patients, 2 partial response patients, 10 stable disease patients, and 24 progressive disease patients. Response rate was 5.5% (2/36). Disease control rate (DCR) was 33% (12/36). The main adverse events were hand-foot skin reaction and diarrhea. The frequency of Grade II, III hand-foot-skin reaction was 39%. After treatment, it decreased to 5.6%. Forty-four percentage patients suffered from diarrhea of Grades I and II. After treatment, it decreased to 28%. The mean interval of TACE was 45 days before combination therapy and 120 days after combination therapy.
Conclusion: Administration of sorafenib after TACE could prolong overall survival of advanced HCC patients, keep the stable status longer and extend the interval between TACEs. The side effects are usually treatable, which proves the safety of this combination.

PMID: 29516985 [PubMed - indexed for MEDLINE]

Anticoccidial activity of fruit peel of Punica granatum L.

Microb Pathog. 2018 Mar;116:78-83

Authors: Ahad S, Tanveer S, Malik TA, Nawchoo IA

Abstract
In the interests of food safety and public health, plants and their compounds are now re-emerging as an alternative approach to treat parasitic diseases. Here, we studied the anticoccidial effect of different solvent extracts of the fruit peel of Punica granatum-a commercial waste from pomegranate juice industries. The hope underlying these experiments was to find a sustainable natural product for controlling coccidiosis. The plant extracts were prepared using solvents of different polarity. Acute oral toxicity study was first carried out to see the safety of crude extracts. A high dose of crude extracts (300 mg/kg body weight) was tested for possession of anticoccidial activity against experimentally induced coccidial infection in broiler chicken. Activity was measured in comparison to the reference drug amprolium on the basis of oocyst output reduction, mean weight gain of birds and feed conversion ratio. Oocyst output was measured using Mc-Masters counting technique. Acute oral toxicity study showed that crude extracts of P. granatum are safe up to dosage of 2000 mg/kg body weight. LD50 was not determined as mortalities were not recorded in any of the five groups of chicken. For anticoccidial activity crude methanolic extract (CME) of the fruit peel of P. granatum showed the maximum effect as evident by oocyst output reduction (92.8 ± 15.3), weight gain of birds (1403.0 ± 11.9 g) and feed conversion ratio (1.66 ± 0.04), thereby affirming the presence of alcohol soluble active ingredients in the plant. We also tested different doses (100-400 mg/kg body weight) of the CME of the fruit peel of P. granatum, the most active extract on E. tenella and observed a dose dependent effect. From the present study it can be concluded that alcoholic extract of the fruit peel of P. granatum has significant potential to contribute to the control of coccidian parasites of chicken.

PMID: 29339307 [PubMed - indexed for MEDLINE]

Improving drug allergy management in Australia: education, communication and accurate information.

Med J Aust. 2018 Sep 03;

Authors: Lucas M, Loh RK, Smith WB

PMID: 30157407 [PubMed - as supplied by publisher]

Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Endothelial Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer.

J Clin Oncol. 2018 Aug 29;:JCO2018777326

Authors: Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW

Abstract
Purpose Mesenchymal-epithelial transition factor (MET) dysregulation occurs in up to 26% of non-small-cell lung cancers (NSCLCs) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Capmatinib (INC280) is a potent and selective MET inhibitor with preclinical activity in combination with gefitinib in EGFR-mutant, MET-amplified/overexpressing models of acquired EGFR-TKI resistance. This phase Ib/II study investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC who experienced disease progression while receiving EGFR-TKI treatment. Methods Patients in phase Ib received capmatinib 100- to 800-mg capsules once per day or 200- to 600-mg capsules or tablets twice per day, plus gefitinib 250 mg once per day. Patients in phase II received the recommended phase II dose. The primary end point was the overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results Sixty-one patients were treated in phase Ib, and 100 were treated in phase II. The recommended phase II dose was capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. Preliminary clinical activity was observed, with an ORR across phase Ib/II of 27%. Increased activity was seen in patients with high MET-amplified tumors, with a phase II ORR of 47% in patients with a MET gene copy number ≥ 6. Across phases Ib and II, the most common drug-related adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%); the most common drug-related grade 3/4 adverse events were increased amylase and lipase levels (both 6%). No significant drug-drug interactions between capmatinib and gefitinib were evident. Conclusion This study, focused on a predominant EGFR-TKI resistance mechanism in patients with EGFR-mutated NSCLC, shows that the combination of capmatinib with gefitinib is a promising treatment for patients with EGFR-mutated, MET-dysregulated NSCLC, particularly MET-amplified disease.

PMID: 30156984 [PubMed - as supplied by publisher]

Long-term follow up of a phase 1/2 study of ProSavin, a lentiviral vector gene therapy for Parkinson's disease.

Hum Gene Ther Clin Dev. 2018 Aug 29;:

Authors: Palfi S, Gurru J, Le H, Howard K, Ralph GS, Mason S, G G, Domenech P, Buttery P, Hantraye P, Tuckwell N, Barker R, Mitrophanous K

Abstract
Parkinson's disease is typically treated with oral dopamine replacement therapies, however long term use is complicated by motor fluctuations from intermittent stimulation of dopamine receptors and off-target effects. ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a phase 1/2 first-in-human study, with significant improvements in motor behaviour from baseline at 1 year. Here, patients with Parkinson's disease from the open-label trial were followed up in the long term to assess the safety and efficacy of ProSavin after bilateral injection into the putamen. 15 patients who were previously treated with ProSavin have been followed for up for 5 years with some having been seen for 8 years. Eight patients received deep brain stimulation at different time points and their subsequent assessments continued to assess safety. Ninety-six drug-related adverse events were reported (87 mild, 6 moderate, 3 severe) of which more than half occurred in the first year. The most common drug-related events were dyskinesias (33 events, 11 patients) and on-off phenomena (22 events, 11 patients). A significant improvement in the defined "off" UPDRS part III motor scores, compared with baseline, was seen at 2 years (mean score 29·2 vs. 38·4, n=14, p<0.05) and at 4 years in 8 out of 15 patients. ProSavin continued to be safe and well tolerated in patients with Parkinson's disease. Moderate improvements in motor behaviour over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow up.

PMID: 30156440 [PubMed - as supplied by publisher]

Resolution of Crizotinib-Associated Fulminant Hepatitis following Cessation of Treatment.

Case Reports Hepatol. 2018;2018:3413592

Authors: Charville GW, Padda SK, Sibley RK, Puthillath A, Kwo PY

Abstract
Targeted cancer treatments offer the prospect of precise inhibition of tumor growth without the untoward off-target toxicity of traditional chemotherapies. Still, unintended, often idiosyncratic side effects, such as drug-induced liver injury, can occur. We discuss the case of a 26-year-old female with a history of ROS1-rearranged lung adenocarcinoma, undergoing treatment with the tyrosine kinase inhibitor crizotinib, who presented to our hospital with abdominal pain and scleral icterus. Liver chemistries were notable for hyperbilirubinemia (5 mg/dL total) and marked transaminasemia (AST 1736 U/L, ALT >3500 U/L); liver biopsy demonstrated acute hepatitis with extensive necrosis. There was no evidence of an infectious or autoimmune etiology. It was discovered that the patient was taking a 500 mg once daily dose of crizotinib, in lieu of the intended dose of 250 mg twice daily. After immediate cessation of crizotinib therapy upon hospital admission, there was complete biochemical resolution of the hepatitis. This case highlights the potential reversibility of fulminant crizotinib-associated hepatoxicity, possibly related to supratherapeutic dosing, when managed with abrupt stoppage of the drug and initiation of supportive care.

PMID: 30155324 [PubMed]

Pharmacokinetics and Safety of Single Intravenous Doses of Ceftolozane/Tazobactam in Children with Proven or Suspected Gram-Negative Infection.

Pediatr Infect Dis J. 2018 Aug 27;:

Authors: Bradley JS, Ang JY, Arrieta AC, Larson KB, Rizk ML, Caro L, Yang S, Yu B, Johnson MG, Rhee EG

Abstract
BACKGROUND: Drug-resistant gram-negative bacteria are a growing threat to children, thus new antibiotics are needed to treat infections caused by these pathogens. Ceftolozane/tazobactam is active against many gram-negative pathogens and is approved for treatment of complicated intra-abdominal and urinary tract infections in adults, but has not been evaluated in children.
METHODS: This Phase 1, non-comparative, open-label, multicenter study characterized the pharmacokinetics (by noncompartmental analysis), safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients (birth [7 days postnatal] to <18 years of age) with proven/suspected gram-negative infection or receiving perioperative prophylaxis (clinicaltrials.gov NCT02266706). Patients were enrolled into 1 of 6 age groups to receive a single, age-based ceftolozane/tazobactam dose, with timed blood sample collection for determining plasma concentrations of ceftolozane and tazobactam. Safety and tolerability were also evaluated.
RESULTS: Thirty-seven patients received study drug; 34 were included in the pharmacokinetic population. Ceftolozane and tazobactam pharmacokinetic parameters were generally comparable for patients aged 3 months to <18 years. Patients from birth [7 days postnatal] to <3 months of age had lower clearance than older children, likely due to the immature renal function of these young infants. No deaths, study drug-related serious adverse events, or clinically significant laboratory abnormalities were observed after administration of ceftolozane/tazobactam.
CONCLUSIONS: The doses evaluated in this study yielded ceftolozane/tazobactam exposure levels generally comparable to those in adults. Single doses of ceftolozane/tazobactam were well-tolerated, and no safety concerns were identified. These data informed pharmacokinetic/pharmacodynamic models to derive pediatric dose recommendations for Phase 2 ceftolozane/tazobactam clinical trials.

PMID: 30153232 [PubMed - as supplied by publisher]

Efficacy and safety of rh-endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh-endostatin plus pemetrexed maintenance in non-small cell lung cancer: A retrospective comparison with standard chemotherapy.

Thorac Cancer. 2018 Aug 27;:

Authors: Zhou S, Zuo L, He X, Pi J, Jin J, Shi Y

Abstract
BACKGROUND: Recombinant human endostatin (rh-endostatin) plus standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients has shown improved efficacy; however, it is unclear whether it is effective and safe when added to pemetrexed/cisplatin and used as maintenance therapy.
METHODS: We retrospectively evaluated the data of untreated NSCLC patients administered rh-endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin. The primary endpoint was progression-free survival (PFS).
RESULTS: Fifty-six and 39 patients received rh-endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, and 34 and 29 underwent maintenance treatment, respectively. The median PFS was 10 months (95% confidence interval [CI] 5.85-14.15) in the rh-endostatin and 8.2 months (4.04-12.36) in the chemotherapy group, but the difference was not statistically significant (P = 0.13). In patients administered maintenance treatment, rh-endostatin plus pemetrexed was associated with prolonged PFS compared to single-agent pemetrexed when PFS was calculated from first dosing (13.7 [9.41-17.99] vs. 8.2 [4.16-12.24]; P = 0.032); however, PFS did not differ between the groups (hazard ratio 0.618; 95% CI 0.368-1.038; P = 0.069) after adjusting for clinical factors. No difference was observed in the objective response rate between the groups (48.2% vs. 38.5%; P = 0.346), with the exception of men (62.1% vs. 33.3%; P = 0.032) or in the incidence of drug-related or grade 3-4 adverse events.
CONCLUSION: In previously untreated, advanced-stage NSCLC patients, first-line treatment with pemetrexed/cisplatin plus rh-endostatin did not prolong PFS or overall survival when compared to pemetrexed/cisplatin, but a trend of improved PFS was observed in patients administered maintenance rh-endostatin plus pemetrexed.

PMID: 30152052 [PubMed - as supplied by publisher]

Hypothyroidism associated with therapy for multi-drug resistant tuberculosis in Australia.

Intern Med J. 2018 Aug 27;:

Authors: Cheung YM, Van K, Lan L, Barmanray R, Qian SY, Shi WY, Wong J, Hamblin PS, Colman PG, Topliss DJ, Denholm JT, Grossmann M

Abstract
OBJECTIVE: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multidrug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. We aimed to identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia.
DESIGN, SETTING AND PARTICIPANTS: Retrospective multi-centre study including MDR-TB patients from five academic centres covering TB services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if thyroid stimulating hormone (TSH) was elevated, and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions.
MAIN OUTCOME MEASURE: Cumulative proportion of hypothyroidism (at 5 years from treatment initiation).
RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% CI: 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (p=0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication.
CONCLUSIONS: Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement if initiated, may not need to be continued after MDR-TB treatment is completed. This article is protected by copyright. All rights reserved.

PMID: 30151969 [PubMed - as supplied by publisher]

Perspective of Saudi undergraduate pharmacy students on pharmacovigilance and adverse drug reaction reporting: A National Survey.

Curr Pharm Teach Learn. 2017 Sep;9(5):779-785

Authors: Alkayyal N, Cheema E, Hadi MA

Abstract
INTRODUCTION: The purpose of this study was to evaluate Saudi undergraduate pharmacy students' knowledge, attitude, and readiness towards pharmacovigilance and reporting of adverse drug reactions (ADRs).
METHODS: A cross-sectional survey was conducted between January 15, 2016 and February 18, 2016 using a structured, validated and pilot-tested questionnaire among senior (year 4, 5, and 6) undergraduate pharmacy students enrolled at a governmental or private university/college. Students completed an online 27-item questionnaire developed using Google Forms™. The questionnaire consisted of four sections: demographics; knowledge about pharmacovigilance and ADR reporting; attitudes towards ADR reporting; and pharmacy students' readiness towards ADR reporting.
RESULTS: Two hundred and fifty-nine students completed the questionnaire. Most of the participants were females (n=174; 67.2%) and were year 4 (n=128; 49.4%) students. Out of a total possible score of seven, the mean knowledge score (SD) was 4.15 (1.1). Multiple linear regression showed that after adjusting for gender and program of study (BPharm/PharmD), year of the study was found to be an independent predictor (p=0.03) of the total knowledge score. More than half of the respondents (n=166; 64.1%) acknowledged that they do not know how to report ADRs to the relevant authorities in Saudi Arabia. The majority (n=213; 82.2%) of respondents believed that information on how to report ADRs should be taught to senior pharmacy students.

PMID: 29233304 [PubMed - indexed for MEDLINE]

Measuring medication adherence in older community-dwelling patients with multimorbidity.

Eur J Clin Pharmacol. 2018 Mar;74(3):357-364

Authors: Kim S, Bennett K, Wallace E, Fahey T, Cahir C

Abstract
PURPOSE: Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on adherence.
METHODS: This is a retrospective cohort study of medication adherence in 855 community-dwelling patients aged ≥ 70 years from 15 practices in Ireland using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. Multimorbidity was measured using the RxRisk-V and by the number of different drug classes. The RxRisk-V algorithm classifies prescription drug fills into 45 chronic disease classes for older populations based on the WHO Anatomical Therapeutic Chemical classification system. Adherence to medications was assessed by: (i) calculating the average medication possession ratio (MPR) per patient and (ii) an MPR< 80%.
RESULTS: The overall median MPR for the cohort was 0.83 (IQR 0.69, 0.91). The conditions with the highest MPRs were hypothyroidism (mean MPR = 0.88, SD = 0.20) and type 2 diabetes (mean MPR = 0.83, SD = 0.19), followed by heart disease. On average, 20-40% of patients were non-adherent (MPR < 80%) across all conditions. There was an inverted U-shaped relationship between the mean MPR and number of morbidities and drug classes. Adherence varied per patients' morbidity burden, with higher adherence for certain combinations of chronic conditions.
CONCLUSION: In total, 31% of older patients with multimorbidity were non-adherent to their medication but adherence levels varied across treatment categories and chronic conditions.

PMID: 29199370 [PubMed - indexed for MEDLINE]

Development and pilot testing of PHARAO-a decision support system for pharmacological risk assessment in the elderly.

Eur J Clin Pharmacol. 2018 Mar;74(3):365-371

Authors: Böttiger Y, Laine K, Korhonen T, Lähdesmäki J, Shemeikka T, Julander M, Edlert M, Andersson ML

Abstract
PURPOSE: The aims of this study are to describe the development of PHARAO (Pharmacological Risk Assessment Online), a decision support system providing a risk profile for adverse events, associated with combined effects of multiple medicines, and to present data from a pilot study, testing the use, functionality, and acceptance of the PHARAO system in a clinical setting.
METHODS: About 1400 substances were scored in relation to their risk to cause any of nine common and/or serious adverse effects. Algorithms for each adverse effect score were developed to create individual risk profiles from the patient's list of medication. The system was tested and integrated to the electronic medical record, during a 4-month period in two geriatric wards and three primary healthcare centers, and a questionnaire was answered by the users before and after the test period.
RESULTS: A total of 732 substances were tagged with one or more of the nine risks, most commonly with the risk of sedation or seizures. During the pilot, the system was used 933 times in 871 patients. The most common signals generated by PHARAO in these patients were related to the risks of constipation, sedation, and bleeding. A majority of responders considered PHARAO easy to use and that it gives useful support in performing medication reviews.
CONCLUSIONS: The PHARAO decision support system, designed as a complement to a database on drug-drug interactions used nationally, worked as intended and was appreciated by the users during a 4-month test period. Integration aspects need to be improved to minimize unnecessary signaling.

PMID: 29198061 [PubMed - indexed for MEDLINE]

Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments.

Eur J Clin Pharmacol. 2018 Mar;74(3):339-347

Authors: Pazan F, Burkhardt H, Frohnhofen H, Weiss C, Throm C, Kuhn-Thiel A, Wehling M

Abstract
PURPOSE: Physicians often face difficulties in choosing appropriate medications for multimorbid older people. The FORTA (Fit for the Aged) classification (A: absolutely, B: beneficial, C: careful, D: don't) was proposed as a clinical tool for improving the quality of drug treatment in the aged. As an implicit tool, FORTA has been shown to aid medication optimization and improve clinical end points in the VALFORTA trial. In this prospective randomized controlled study, 207 older hospitalized patients received standard geriatric treatment and 202 patients received FORTA-guided treatment.
METHODS: Here, changes of drug prescriptions at the anatomical-therapeutic-chemical system (ATC) level were evaluated separately for important diagnoses in descriptive analyses; over- and under-treatment rates were compared between groups.
RESULTS: At the individual drug/drug class level related to all important diagnoses, the application of FORTA significantly improved under-treatments for 12 drugs/drug classes (e.g., ACE inhibitors to treat arterial hypertension) and over-treatments for 7 drugs/drug classes (e.g., proton pump inhibitors to treat gastroesophageal reflux disease).
CONCLUSIONS: FORTA representing the first combined positive/negative labeling approach at the individual drug level aids the optimization of drug treatment in older people as detected for drugs/drug classes at the ATC level in important indications. FORTA is effective in addressing over- and under-treatments even if analyzed for smaller subgroups of VALFORTA.

PMID: 29196825 [PubMed - indexed for MEDLINE]