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]

Benefits, benefits, once more benefits... with no risk? Stop overlooking the harms of medicines.

Eur J Clin Pharmacol. 2018 Mar;74(3):373-375

Authors: Garattini S, Bertele' V

Abstract
Consideration of drug benefits and harms is asymmetric. Approval of drugs is mainly based on efficacy, while the assessment of their safety is left to post-marketing commitments or spontaneous reporting. Benefits are overestimated as a result of pharmaceutical companies' advertisements, the paucity of independent information, and the scant understanding of the effectiveness of medicines in real life. Polypharmacy in older adults-even during the last period of their life-reflects the tendency to assign priority to efficacy and overlook harms, although nobody knows what happens when three or more drugs are given chronically. Medical journals and public research funding projects do not pay enough attention to drug toxicity. We call for a sense of purpose by all those involved in medicine to tackle this problem. European and national agencies and health authorities should promote and support independent information and experimental and clinical studies on drug toxicity. Information should rely not just on spontaneous reporting but also on active pharmacovigilance. The benefit-harm profile of drugs should be periodically reviewed in the light of toxic effects that come to light over the years. Potential interactions within polytherapies should be sought by re-assessing the pharmacokinetics and pharmacodynamics of their components.

PMID: 29181699 [PubMed - indexed for MEDLINE]

Longitudinal patterns of potentially inappropriate prescribing in early old-aged people.

Eur J Clin Pharmacol. 2018 Mar;74(3):307-313

Authors: Hansen CR, Byrne S, Cullinan S, O'Mahony D, Sahm LJ, Kearney PM

Abstract
PURPOSE: It is contentious whether potentially inappropriate prescribing (PIP) is predominantly a phenomenon of late life or whether it has its origins in early old age. This study examined the pattern of PIP in an early old-aged population over 5 years.
METHODS: Secondary data analysis of a population-based primary care cohort, of patients aged 60-74 years. Medication data were extracted from electronic patient records in addition to information on comorbidities and demographics. Explicit START criteria (PPOs) and STOPP criteria (PIMs) were used to identify PIP. Generalised estimating equations were used to describe trends in PIP over time and adjusted for age, gender and number of medicines.
RESULTS: A total of 978 participants (47.8%) aged 60-74 years were included from the cohort. At baseline, PPOs were detected in 31.2% of patients and PIMs were identified in 35.6% at baseline. Prevalence of PPOs and PIMs increased significantly over time (OR 1.08, 95% CI 1.07; 1.09 and OR 1.04, 95% CI 1.0; 1.06, respectively). A higher number of medicines and new diagnoses were associated with the increasing trend in both PPO and PIM prevalence observed over time, independent of PPOs and PIMs triggered by drug combinations.
CONCLUSIONS: Potentially inappropriate prescribing is highly prevalent among early old-aged people in primary care and increases as they progress to more advanced old age, suggesting that routine application of STOPP/START criteria in this population would significantly improve medication appropriateness.

PMID: 29177646 [PubMed - indexed for MEDLINE]

Inter-rater reliability of STOPPFrail [Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy] criteria amongst 12 physicians.

Eur J Clin Pharmacol. 2018 Mar;74(3):331-338

Authors: Lavan AH, Gallagher P, O'Mahony D

Abstract
PURPOSE: STOPPFrail is an explicit tool, developed by Delphi consensus, to assist physicians with deprescribing medications in frail older adults with poor survival prognosis. This study aimed to determine the inter-rater reliability (IRR), amongst physicians, of STOPPFrail application.
METHODS: Twenty clinical cases were collated to represent frail older patients. Eighteen cases met STOPPFrail inclusion criteria. They had a mean age of 79.5 (SD6) years and a median of 7 (IQR6-8.25) comorbidities and were prescribed a median of 9 (IQR7.75-11.25) medications. Two of the STOPPFrail originators reached complete agreement (gold standard) in determining 91 of 165 medications (55.2%) as inappropriate. Twelve physicians (6 geriatricians, 3 general practitioners and 3 palliative care physicians) independently applied STOPPFrail criteria. IRR between physicians and gold standard (GS) assessment was determined using Cohen's kappa statistic.
RESULTS: Eighteen of the 20 cases that met STOPPFrail inclusion criteria were correctly identified by 9 of 12 physicians (75%). The average time taken per clinical case was 2.7 (SD0.94) minutes. The kappa co-efficient between physicians and GS assessment ranged from 0.71 (substantial) to 0.86 (good), with a mean kappa value of 0.758 (SD0.059). The Fleiss kappa coefficients between GS assessment and geriatricians, GPs and palliative care physicians were 0.80 (SD0.6), 0.77 (SD0.9) and 0.75 (SD0.1), respectively. No significant difference was noted, between groups or between participants within groups, as determined by one-way ANOVA, (df (2, 9) = 0.712, p = 0.516).
CONCLUSIONS: IRR of STOPPFrail criteria between physicians, practising in different specialties, is substantial, despite no prior knowledge of the criteria.

PMID: 29159488 [PubMed - indexed for MEDLINE]

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New insight into organic anion transporters from the perspective of potentially important interactions and drugs toxicity.

J Physiol Pharmacol. 2018 Jun;69(3):

Authors: Mor AL, Kaminski TW, Karbowska M, Pawlak D

Abstract
The family of organic anion transporters (OATs) includes a group of over 10 transmembrane transporting proteins belonging to the solute carrier 22 subfamilies of the major facilitator superfamily. Their function is related to the transport of a great variety of organic anions against the electrical and chemical gradient. OATs are present in most types of human tissues, including the kidneys, liver, placenta, olfactory epithelium, retina, and choroid plexus tissues. The OATs family plays an important role in the cellular uptake, distribution, excretion, and detoxification of many water-soluble drugs, endogenous compounds, nutrition ingredients, environmental contaminants and toxins, and significantly impacts their efficacy, pharmacokinetics and toxicity, both in a preferable and unfavorable way. OATs demonstrated great potential to participate in many potentially relevant interactions, which may lead to unexpected, but not always detrimental, effects. Wider knowledge about their specific functions in the body, role in disease states, pharmacokinetics interactions, and intraindividual response to therapeutic treatment will allow to predict and prevent OAT-related adverse effects or use favorable interactions in pharmacotherapy, as well as to rationally design therapeutics targeted at individual transporter drugs with improved bioavailability, prolonged half-life or reduced toxicity, and improve safety guidelines concerning drug dosage. This review gathers recent reports regarding OAT-related essential interactions involving components of popular therapeutic herbal products, dietary supplements, and clinically important drugs, their significance and potential suitability in modulating the severity of drug-related side effects and toxicity mechanisms.

PMID: 30149367 [PubMed - in process]

Data-Driven Assessment of Potentially Inappropriate Medication in the Elderly.

Stud Health Technol Inform. 2018;253:125-129

Authors: Friedrichs M, Shoshi A, Kleine M

Abstract
Multimorbid patients taking polypharmacy represent a growing population at high risk for inappropriate prescribing. Various lists for identifying potentially inappropriate medication are spread across scientific journals and difficult to access. To address this ongoing need, a new database named PIMBase is developed which integrates these well-known lists and unifies their rating scales. The analysis of the pharmacovigilance data reveals the benefits of combining the lists. PIMBase is meant to be a web-based system and starting point for the data-driven assessment of polypharmacy to identify inappropriate medication and to improve the quality of prescribing. PIMBase is available at https://pimbase.kalis-amts.de.

PMID: 30147056 [PubMed - in process]

Detection and analysis of drug-drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco.

Pan Afr Med J. 2018;29:225

Authors: Fettah H, Moutaouakkil Y, Sefrioui MR, Moukafih B, Bousliman Y, Bennana A, Lamsaouri J, Makram S, Cherrah Y

Abstract
Introduction: Drug-drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. Patients with cardiovascular disorders are at higher risk for DDIs because of the types and number of drugs they receive. The aim of the present study was to assess the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco.
Methods: A prospective observational study from June 2016 to September 2016 was carried out in the cardiology department of a hospital in Morocco. Those patients who were taking at least two drugs and had a hospital stay of at least 48 hours were included in the study. The medications of the patients were analysed for possible interactions. All the prescriptions of the study population were screened for drug-drug interactions using a computerized DDI database system (Theriaque®).
Results: During the study period, 138 patients were included; 360 interactions were detected among 94 patients, with an average number of drugs taken of 5.2. The prevalence of DDIs was estimated at 68.11%, the most common of which concerned Kardegic/Plavix (12.22%), Kardegic/Heparin (8.33%), and Lasilix/Spironolactone (5.83%). Among the 726 prescribed drugs, (372 [51.24%]) were drugs of the cardiovascular system, followed by blood and hematopoietic organ drugs (288 [39.67%]) according to the Anatomical Therapeutic Chemical Classification codes. These interactions were categorized on the basis of level of severity: interactions with major severity accounted for 11.11% (40) of the total DDIs while those with moderate and minor severity accounted for 37.22% (134) and 51.66% (186), respectively.
Conclusion: This study reports the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco. This study shows that DDIs are frequent among hospitalized cardiac patients and highlights the need to screen prescriptions of cardiovascular patients for possible DDIs, as this helps in their detection and prevention.Pan African Medical Journal - ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net)Pan African Medical Journal - ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net).

PMID: 30100979 [PubMed - indexed for MEDLINE]

Creating and evaluating an opportunity for medication reconciliation in the adult population of South Africa to improve patient care.

Hosp Pract (1995). 2018 Aug;46(3):110-120

Authors: Naicker P, Schellack N, Godman B, Bronkhorst E

Abstract
OBJECTIVE: Adverse drug events (ADEs) are a major cause of morbidity and mortality, with more than 50% of ADEs being preventable. Adverse Drug Reactions (ADRs) are typically the result of an incomplete medication history, prescribing or dispensing error, as well as over- or under-use of prescribed pharmacotherapy. Medication reconciliation is the process of creating the most accurate list of medications a patient is taking and subsequently comparing the list against the different transitions of care. It is used to reduce medication discrepancies, and thereby ultimately decreasing ADEs. However, little is known about medicine reconciliation activities among public hospitals in South Africa.
METHODS: Prospective quantitative, descriptive design among Internal and Surgical wards in a leading public hospital in South Africa.
RESULTS: 145 study participants were enrolled. Over 1300 (1329) medicines were reviewed of which there was a significant difference (p = 0.006) when comparing the medications that the patient was taking before or during hospitalisation. A total of 552 (41.53%) interventions were undertaken and the majority of patients had at least 3.96 medication discrepancies. The most common intervention upon admission was transcribing the home medication onto the hospital prescription (65.2%) followed by medication duplication (13.44%). During patient's hospital stay, interventions included patient counselling (32.5%) and stopping the previous treatment (37.5%).
CONCLUSION: To ensure continuity of patient care, medication reconciliation should be implemented throughout patients' hospital stay. This involves all key professionals in hospitals.

PMID: 29619837 [PubMed - indexed for MEDLINE]

AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks.

Toxicol Appl Pharmacol. 2018 03 15;343:71-83

Authors: Pittman ME, Edwards SW, Ives C, Mortensen HM

Abstract
The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability to, automatically and on a large scale, integrate AOP knowledge with publically available sources of biological high-throughput data and its derived associations. To support the discovery and development of putative (existing) and potential AOPs, we introduce the AOP-DB, an exploratory database resource that aggregates association relationships between genes and their related chemicals, diseases, pathways, species orthology information, ontologies, and gene interactions. These associations are mined from publically available annotation databases and are integrated with the AOP information centralized in the AOP-Wiki, allowing for the automatic characterization of both putative and potential AOPs in the context of multiple areas of biological information, referred to here as "biological entities". The AOP-DB acts as a hypothesis-generation tool for the expansion of putative AOPs, as well as the characterization of potential AOPs, through the creation of association networks across these biological entities. Finally, the AOP-DB provides a useful interface between the AOP framework and existing chemical screening and prioritization efforts by the US Environmental Protection Agency.

PMID: 29454060 [PubMed - indexed for MEDLINE]

Prevalence and Management of Drug-Related Problems in Chronic Kidney Disease Patients by Severity Level: A Subanalysis of a Cluster Randomized Controlled Trial in Community Pharmacies.

J Manag Care Spec Pharm. 2018 Feb;24(2):173-181

Authors: Quintana-Bárcena P, Lord A, Lizotte A, Berbiche D, Lalonde L

Abstract
BACKGROUND: Drug-related problems (DRPs) are prevalent among chronic kidney disease (CKD) patients. However, little is known about their severity and management by community pharmacists.
OBJECTIVES: To (a) describe the prevalence of DRPs by severity level in CKD patients and (b) assess the effect of a training-and-communication network program in nephrology (ProFiL) on these DRPs.
METHODS: This is a secondary analysis of a cluster randomized controlled trial evaluating the effect of the ProFiL-program. In 6 CKD clinics, patients at CKD stage 3 or 4 and their community pharmacists were recruited and assigned to the ProFiL group or a usual care (UC) group. Using validated criteria, 2 pharmacists identified DRPs and assessed their severity at baseline and after 12 months. The mean annual change in the number of DRPs per patient by severity level was assessed using a 2-level multivariable linear mixed-effects model.
RESULTS: A total of 494 pharmacists and 442 patients participated. At baseline, the prevalence (mean number of DRPs per patient [SD]) of mild DRPs (e.g., requiring dosage adjustment) and moderate DRPs (e.g., drug adherence requiring a monitoring plan) were 0.55 (0.98) and 1.04 (1.51), respectively. After 12 months, an unadjusted incremental annual reduction of 0.34 moderate DRPs (95% CI = -0.66 to -0.01) was observed in the ProFiL group compared with the UC group. After adjustment, no between-group differences were observed.
CONCLUSIONS: Among patients followed in CKD clinics, most DRPs have a moderate severity requiring specific monitoring by pharmacists. The benefit of continuing education programs, such as ProFiL, to reduce moderate DRPs remains to be determined.
DISCLOSURES: This study was supported by the Canadian Institutes of Health Research (grant number: MOP-230207). Part of the study was also funded by Pfizer Canada, Leo Pharma, and Amgen. The authors declare that they have no relevant financial interests. Study concept and design were contributed by Quintana-Bárcena, Lord, and Lalonde. Quintana-Bárcena, Lord, and Lizotte were responsible for the data analysis, and Quintana-Bárcena and Berbiche performed the statistical analysis. The manuscript was written by Quintana-Bárcena and Lalonde and revised by Quintana-Bárcena and Lalonde, along with the other authors.

PMID: 29384023 [PubMed - indexed for MEDLINE]

Important Aspects of Pharmacist-led Medication Reviews in an Acute Medical Ward.

Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):253-261

Authors: Bülow C, Faerch KU, Armandi H, Jensen BN, Sonne J, Christensen HR, Christensen MB

Abstract
In some hospitals, clinical pharmacists review the medication to find drug-related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review (MR) notes, we retrospectively evaluated the clinical implementation and classified (1) timing and communication of the review; (2) DRPs and related suggestions for the physician; and (3) DRPs' potential clinical relevance to patients as 'beneficial', 'somewhat beneficial', 'no relevance' or 'other relevance'. Of 327 DRPs (0-13 DRPs per patient), 42% were implemented. The clinical implementation was higher if the MR note was made prior to (instead of after) the physician's admission, and even higher if the suggestions were communicated verbally (instead of only in writing) to the physicians (44% versus 79%, p < 0.05). The clinical relevance of the DRPs was either 'beneficial' (16%), 'somewhat beneficial' (43%), 'no relevance' (22%) or 'other relevance' (19%). The 'beneficial' DRPs had a higher clinical implementation (53%) than 'no relevance' (34%) (p < 0.05). The most frequently implemented suggestions were based on DRPs concerning 'indication for drug treatment not noticed', 'inappropriate drug form' and 'drug dose too low', with implementation rates of 83%, 67% and 63%, respectively. In our sample, the pharmacist's MR suggestions were only implemented by physicians in 42% of the cases, but review prior to physician contact and verbal communication of the suggestions, higher clinical relevance and specific types of DRPs were associated with a higher implementation rate.

PMID: 28871627 [PubMed - indexed for MEDLINE]