Likelihood Of Adverse Drug Reactions Research Articles

Устойчивость к противомикробным препаратам и роль пробиотиков в ее преодолении

The concept of risk management and the ideology of microbiocenosis-oriented therapy can be one of the simple and understandable approaches to the formation of modern ideas about the possibilities of integrated use of antibiotics and probiotics as components of effective antimicrobial therapy. In addition to traditional bacterial probiotics, Saccharomyces boulardii CNCM I-745, which has a number of advantages for the realization of such a therapy strategy, are widely used in real practice. The affiliation of S. boulardii CNCM I-745 to fungi makes it possible to use them in any regimen of complex therapy, including antibacterial drugs. This approach improves treatment compliance, ultimate efficacy of therapy and reduces the likelihood of adverse drug reactions. S. boulardii CNCM I-745 are able to reduce the number of genes encoding antimicrobial resistance (ARG) by modulating the intestinal microbiota and controlling the number of bacteria actively forming the pool of ARG, activation of the immune system, which allows to implement antimicrobial effects against pathogens at early stages of the infectious process, production of saturated fatty acids that have antimicrobial properties and have synergistic effects with other antimicrobial drugs. Key words: antibiotic, antimicrobial resistance, resistome, Saccharomyces boulardii, mycobiome

368 Development of Interactome Network to Understand Adverse Drug Reactions for Antidepressant Medications

OBJECTIVES/GOALS: Patient adherence with antidepressant therapy is a critical aspect of clinical management. Drug molecules often interact with other off-target proteins resulting in adverse events. We utilized an interactome model for predicting the likelihood of adverse drug reactions in order to accurately prescribe antidepressant medications to a patient. METHODS/STUDY POPULATION: We utilized an interactome model to study physical interactions between proteins and biological functions disrupted by major depression to understand how changes in genes alter patient-specific drug efficacy and cause adverse drug-reactions. To study how drugs and diseases propagate through the proteins and biological functions, we harnessed diffusion profiles to represent nodes in the graphical model and used a biased random walks model to illustrate how signals propagate in a heterogeneous biological network. The edge weights were defined for the drug, disease, protein, and biological function node types. The interactions studied included drug-protein, disease-protein, protein-protein, protein-biological function, biological function-biological function. RESULTS/ANTICIPATED RESULTS: Based on previous studies, we anticipate that the genetic variants modulating antidepressant response include 5-HTT, STin2, HTR1A, HTR2A, TPH1 and BDNF. Additionally, genetic variants such as SLC6A4 as well as the HPA pathway may play an important role in antidepressant therapeutic response. With regards to medication drug response, the genes, SLC6A4 and HTR2A, have been known for encoding proteins that affect the synaptic cleft of serotonergic neurons. Also, the gene SLC6A4 has been shown to encode for the serotonin reuptake transporter, which is the main pharmacological target of SSRIs. In female patients with major depression, the polymorphism associated with MAOA gene may be involved in the pharmacological response. DISCUSSION/SIGNIFICANCE: The key to successful depression treatment is early adherence but nearly 60% of patients discontinue antidepressants within three months. By developing a strong understanding of the genes that alter treatment efficacy, we can provide patients with more awareness regarding the most effective treatment plan to minimize adverse events.

Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs) after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion:The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. This retrospective cohort study included patients 18-years or older with solid malignancies receiving active treatment in our hospital who had received the three-dose schedule of the mRNA9 1273 vaccine and whose side effects after each dose were recorded. Patient electronic medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded from the study. Results: A total of 93 patients met the inclusion criteria. Local adverse drug reactions (ADRs) were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic ADRs after the third dose. Cochran-Armitage test showed a statistically significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects. A logistic regression showed that women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion:The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

Exploring elderly patients’ perspectives on deprescribing: a qualitative study interim analysis

Abstract Introduction The ageing population has caused an increase in polypharmacy, multimorbidities and complexity of patients (1). Polypharmacy increases the likelihood of Adverse Drug Reactions, particularly in elderly patients due to functional/cognitive changes (1). Current research investigating views on deprescribing has shown that patients are often willing to undertake deprescribing, however qualitative research in elderly populations is sparse (1). Aim This study aimed to explore elderly patients’ perspectives on deprescribing and pharmaceutical input into their care. Methods Semi-structured interviews were undertaken with a purposive sample of elderly (&amp;gt;65 years) inpatients with multiple morbidities and/or frailty and were taking at least one regular medicine, at two English NHS hospital Trusts. The interview guide was developed with public contributions, aligned with the study aim and informed by the Theoretical Framework of Acceptability (TFA)(2). The TFA was used because it was developed for assessing the acceptability of healthcare interventions (2). The interview guide included a distress protocol because the patient cohort was vulnerable. Interviews were conducted face-to-face, audio-recorded, transcribed verbatim and analysed using the Framework Analysis approach, with a priori categories informed by the TFA. Results Interviews were conducted with 8 participants (2 male,6 female), aged 67-89 and taking 3-9 pre-admission medicines. Most participants seemed to understand that deprescribing may become appropriate and trusted their doctor to initiate discussion when deprescribing is appropriate. However, participants reported wanting to know the rationale for deprescribing (TFA domain: affective attitude): “…why was I taking it in the first place if I don’t need it now?”. Most participants wanted deprescribing discussions to start with the rationale and some said medicines should be stopped gradually with regular reviews (TFA domain: affective attitude, ethicality). Most participants referred to pharmacists having a small role in their healthcare and none mentioned pharmacists stopping medicines (TFA domain: affective attitude): “… they sort all the drugs out don’t they, that they’re ordered…”. Access to GPs was commonly reported as a burden (TFA domain: burden). Some participants reported not feeling confident to ask their GP questions and some said they had not established trust due to not seeing a regular doctor (TFA domain: burden and opportunity costs): “I’ve gotta get my confidence in them…”. Several participants reported having taken medicines for years and said that they thought the medicines were beneficial, whilst other participants said that if they could take fewer medicines they would (TFA domain: ethicality and perceived effectiveness). Some participants understood that deprescribing required weighing up risks and benefits (TFA domain: intervention coherence): “…consider the benefits and the possibility of side effects”. Conclusion This study adds insights from qualitative research, but these may not be widely transferrable. Whilst these are interim analysis findings that may be further refined, they suggest that deprescribing is likely to be acceptable to patients when conducted by healthcare professionals they trust and who provides the rationale for deprescribing. Patients’ awareness of who can deprescribe would benefit from being increased, since participants did not cite pharmacists as experts who can deprescribe. Future research could explore how to do so. References (1) Reeve E, Shakib S, Hendrix I, Roberts MS, Wiese MD. Review of deprescribing processes and development of an evidence-based, patient-centred deprescribing process. Br J Clin Pharmacol. 2014 Oct;78(4):738-47. (2) Sekhon M, Cartwright M, Francis J. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res, 2017; 17: 88.

Use of a consultation service following pharmacogenetic testing in psychiatry.

The emerging discipline of pharmacogenetics(PGx) has the goal of aiding the selection of effective therapies and personalized dosing, decreasing the likelihood of adverse drug reactionsand optimizing resource utilization. Simultaneously, the rapid evolution of economically feasible genetic testing technologies has resulted in a raft of commercial entities that provide genetic data to providers for use with their complex patients. The adoption of pharmacogenomics in psychiatry is growing, but itis limited by severalfactors, including the limitless permutations of drugs, comorbid conditions and concomitant medications and provider understanding of phenomena such as phenoconversion. We established an expert PGx consultation service for psychiatric providers who utilize our commercial PGx assay. To date, this service has provided ∼16,000 consults with extremely high levels of satisfaction; in an anonymous survey, 96% of respondents reported a rating of "very helpful" or "extremely helpful".

Deep Learning Prediction of Adverse Drug Reactions in Drug Discovery Using Open TG–GATEs and FAERS Databases

Machine learning techniques are being increasingly used in the analysis of clinical and omics data. This increase is primarily due to the advancements in Artificial intelligence (AI) and the build-up of health-related big data. In this paper we have aimed at estimating the likelihood of adverse drug reactions or events (ADRs) in the course of drug discovery using various machine learning methods. We have also described a novel machine learning-based framework for predicting the likelihood of ADRs. Our framework combines two distinct datasets, drug-induced gene expression profiles from Open TG–GATEs (Toxicogenomics Project–Genomics Assisted Toxicity Evaluation Systems) and ADR occurrence information from FAERS (FDA [Food and Drug Administration] Adverse Events Reporting System) database, and can be applied to many different ADRs. It incorporates data filtering and cleaning as well as feature selection and hyperparameters fine tuning. Using this framework with Deep Neural Networks (DNN), we built a total of 14 predictive models with a mean validation accuracy of 89.4%, indicating that our approach successfully and consistently predicted ADRs for a wide range of drugs. As case studies, we have investigated the performances of our prediction models in the context of Duodenal ulcer and Hepatitis fulminant, highlighting mechanistic insights into those ADRs. We have generated predictive models to help to assess the likelihood of ADRs in testing novel pharmaceutical compounds. We believe that our findings offer a promising approach for ADR prediction and will be useful for researchers in drug discovery.

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer.

Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum-based chemotherapy. In a placebo-controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous-recombination DNA repair pathways [i.e. homologous-recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight- and platelet count-based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first-line maintenance therapy for advanced ovarian cancer in adults who responded to platinum-based chemotherapy, regardless of homologous-recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-021-00841-2.

Assessment of Potential Drug-Drug Interactions and its Associated Factors in Medical Intensive Care Unit of a Tertiary Care Hospital in Nepal

Drug interaction may cause an increase in the toxicity of a drug, increases the likelihood of adverse drug reactions, or cause a reduction in the efficacy of particular drug therapy, which may worsen the patient’s condition directly or indirectly. This study aims to assess the potential drug-drug interactions (pDDIs) and their associated factors in the Medical Intensive Care Unit (MICU). We carried out a descriptive retrospective study based on the hospital records of 100 MICU patients. Micromedex Interaction application, designed by Truven Health Analytics Inc., was used to screen prescribed medications. We found 219 drug interactions out of 856 drugs prescribed. The average number of drug interactions per patient was 2.19. The frequency of drugs prescribed, the number of days in MICU, and age had a positive correlation with the occurrence of pDDIs. There were 44.7% major pDDIs; pharmacodynamic being the commonest mechanism for it. Most patients in MICU were at the risk of developing pDDIs. A substantial number of interactions had a major severity. Therefore, there is a need for active surveillance for pDDIs to prevent patient harm during particular drug therapy.

Evaluation of pre-chemotherapy antiemetic prescriptions in a hospital unit

Introduction: Antineoplastic drugs, due to their high toxicity, can lead to adverse reactions to drugs, such as emesis, which causes discomfort to the patient. These drugs can be classified according to emetogenic potential and have appropriate treatment protocols. Objectives: The aim of this study is to evaluate whether there is compliance between antiemetic prescription in patients receiving antineoplastic treatment in a hospital unit, according to pre-established emesis prevention protocols. Methods: This is a cross-sectional retrospective study of chemotherapy prescriptions analysis from January to April 2017. Data were analyzed according to the National Comprehensive Cancer Network 2017 Acute Emesis Prevention Protocol. Nonconformities were classified in: wrong medicine; wrong dose; wrong administration frequency and wrong administration route. Results: Of the 919 prescriptions analyzed, 83% did not comply with the protocol. The most common nonconformity found in the study was the wrong dose with the most prevalent scenario being the dexamethasone dose above the required dose. Conclusion: Most of the prescriptions analyzed did not comply with the pre-established protocol. This increases the likelihood of adverse drug reactions, does not effectively prevent emesis, thereby increasing patient weakness, decreasing quality of life, and wasting resources.

EVALUATION OF THE USE OF ANTI-NON STEROID INFLAMATION DRUGS ON GERIATRI

Background: Geriatric patients differ from the general patient population. Geriatric differences with other populations include aspects of pharmacokinetics, pharmacodynamics, comorbidities, and the likelihood of adverse drug reactions (ADR). Objective: To determine the accuracy of the dosage and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) in geriatric patients in the Inpatient Installation of Dr.Asmir Salatiga. Methods: The study was conducted non-experimental (observational), using descriptive methods and prospective data collection. Samples were 25 patients with total sampling method. Data analysis included drug use, dose accuracy and evaluation of drug side effects using the Naranjo algorithm. Results: Geriatric patients using the most non-steroidal anti-inflammatory drugs were 18 patients (72%). The largest group of non-steroidal anti-inflammatory drugs is the oxikam group of 12 patients (48%). The exact dosage of non-steroidal anti-inflammatory drugs is 19 cases (76%) on the right dose. Evaluation of drug side effects based on the Naranjo algorithm obtained scores for the "probable / probable category of 6 patients (24%) and the feasible category of 19 patients (76%). Conclusion: The correct dosage of non-steroidal anti-inflammatory drugs is 19 cases (76%) right dose. The evaluation of the side effects of non-steroidal anti-inflammatory drugs was the "probable" category of 6 patients (24%) and the feasible category of 19 patients (76%).

Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed® Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.

A real-world study on adverse drug reactions to Xuebijing injection: hospital intensive monitoring based on 93 hospitals (31,913 cases).

Although we have made tremendous medical advances in recent decades in modern antibiotics and supportive therapies, the treatment of sepsis has not experienced such rapid advancement. Xuebijing injection (XBJ) is a Chinese prescription consisting of Carthamus tinctorius, Radix paeoniae rubra, Ligusticum wallichii, Radix salviae miltiorrhizae and Radix angelicae sinensis. Clinical experience suggests that XBJ may provide a solution in the management of sepsis. However, the safety of this treatment is still controversial. This study aims to detect the occurrence of XBJ-related adverse drug reactions (ADRs) among individuals in clinical practice. From the clinical application of XBJ in a real-world setting, patients in 93 hospitals using XBJ were monitored between August 2013 and August 2016. There was no limit on the treatment course and dosage. From data obtained in interviews or telephone follow-ups with hospitalized patients, the circumstances of patients' adverse events (AEs) during the course of drug treatment and during the 7 days after drug withdrawal were recorded and encoded by MedDRA18.0. The likelihood of ADRs was determined by the criteria of the Uppsala Monitoring Centre. Statistical analyses were performed by SAS9.2 software. In total, 31,913 participants enrolled, and none were lost to follow-up. AEs (suspected ADRs) occurred in 234 participants. ADRs occurred in 96 participants, and the incidence was 0.3%. The ADRs with the top three frequencies were skin pruritus (0.116%), erythra (0.066%) and chest tightness (0.044%). There was no significant relationship between ADRs and solvents (P=0.149), route of administration (P=0.640), unhealthy addiction (P=0.069), allergy (P=0.535), first use of XBJ (P=0.161) or dosage (P=0.743). There was a significant relationship between ADRs and irrigating syringe (P<0.0001) and fluid dripping too quickly (P=0.019). This large-scale survey of hospitalized patients found that the incidence of ADRs was occasional (0.3%), while most of the ADRs were relatively mild or non-serious. XBJ should be administered rationally and according to its instructions to prevent the occurrence of ADRs.

Development of a dosing nomogram for continuous-infusion meropenem in critically ill patients based on a validated population pharmacokinetic model.

Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. A population pharmacokinetic model was developed in NONMEM® 7.3 based on steady-state meropenem concentrations (CSS) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRCG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (CSS ≥8 mg/L) and potentially increased likelihood of adverse drug reactions (CSS >32 mg/L). In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P0.05 - P0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/3940 mg were required to reach a target CSS = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (<0.5%) was associated with these doses. A dosing nomogram was developed for continuous-infusion meropenem based on renal function in a critically ill population.

How to Consider Rare Genetic Variants in Personalized Drug Therapy.

Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune-mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the likelihood of adverse drug reactions (ADRs) are recognized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and are included in the drug labels of the respective medication. They are of particular value in cancer therapy to provide information of use to avoid ADRs and lack of response.

Pattern of adverse drug reactions following anti-tuberculosis therapy in Nigeria: a four year review

Introduction: combined anti-tuberculosis drugs are effective in the management of persons with tuberculosis (TB). These drug combinations have however been documented to increase the likelihood of adverse drug reactions (ADR), poor adherence and treatment failure among patients with TB. This study was therefore conducted to assess and describe the pattern of reported ADR to anti-TB therapy in Nigeria.

Perceptions and attitudes towards off-label dispensing for pediatric patients, a study of hospital based pharmacists in Jordan

BackgroundWith growing responsibility of the pharmacists in ensuring public health and safe medicine use, an understanding of the issues surrounding off-label prescribing is crucial to allow pharmacists to make informed decisions about such practice. The aim of this study is to assess the perceptions and attitudes of hospital based pharmacists toward off-label medicine dispensing to children. MethodsAfter obtaining the required approvals, a validated questionnaire about off-label dispensing to pediatric patients was administered to 250 randomly selected hospital pharmacists. ResultsOne hundred and fifty (150) completed questionnaires were returned. Less than half of the respondents (44%, n = 66) admitted to being familiar with the concept of off-label dispensing, claiming to have obtained this knowledge basically through their dispensing experience rather than education. A minority of respondents (36%, n = 54) reported dispensing off-label medicines within their practice knowingly. The majority of respondents had concerns regarding the efficacy (82%, n = 123) and safety (98%, n = 147) of off-label medicines. The most common reasons given by respondents for a dispensed prescription being off label were younger age than recommended (88%, n = 132). Most of respondents (94%, n = 141) claimed to double check the calculations of doses of medicines before dispensing off-label medicines and 60% (n = 90) of them felt that parents and guardians should be told when an off-label medicine has been prescribed for their children. ConclusionThe majority of respondents were not familiar with the concept of offlabel medicines. While reporting to have gained their knowledge from their professional experience, only a minority of respondents reported knowingly dispensing off-label medicines for pediatric patients. Respondents indicated that manufacturing more appropriate formulations for pediatric patients would reduce such practices in this population. Having concerns regarding the efficacy and safety of off-label medicines used for pediatric patients, respondents felt that the use of off-label medicines would increase the likelihood of adverse drug reactions (ADRs). Finally, respondents felt that such practice of prescribing and dispensing should receive parental consent.

Keep an eye on the SSRI: help avoid possible sight-threatening adverse events.

A recent report in a peer-reviewed UK journal outlines five cases of optic neuropathy thought to be related to long-term treatment with selective serotonin reuptake inhibitors (SSRIs).1 These five were identified over a 2-year period within an island population of 140 000. Each case was assessed using the Naranjo algorithm to indicate likelihood of adverse drug reaction (ADR).2 The Naranjo scores indicated possible ADR in four cases and probable ADR in one case. All five cases presented with visual loss from suspected ischaemic optic neuropathy (ION) and were all extensively investigated for any other possible underlying cause. A ‘non-arteritic’ ischaemic origin was suspected in all cases. Toxicity was felt to be unlikely since three cases were of sudden onset and two cases were unilateral. Two cases …

Use of the Drug Burden Index to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care: a systematic review protocol

Review question/objective The aim of this review is to critically appraise, synthesize and present evidence on the use of the Drug Burden Index (DBI) to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care. More specifically, this review seeks to answer the following questions: 1.In which specific settings and patient groups has the Drug Burden Index been applied? 2.Which outcomes have been studied? (E.g. occurrence and incidence of adverse drug reactions, physical functioning, mental functioning, cause of admission to hospital, etc.) 3.Has the use of the Drug Burden Index impacted upon inappropriate prescribing of anticholinergic and sedative agents to elderly patients in institutionalized care? (E.g. cessation of therapy, prescribing altered to other agents, reduction in adverse drug reactions, etc.) Inclusion criteria Types of participants The focus of this review will specifically be on ‘elderly patients’ as described within the studies. If no classification is given within studies, then only those studies reporting on patients aged 65 years and over will be included in the review. Furthermore, patients receiving care within either hospital or care home settings (institutionalized care) will be included in the review. The care of these patients and hence the use of the Drug Burden Index is likely to be markedly different to home dwelling patients. Types of intervention(s) Use of the Drug Burden Index tool to identify and reduce potentially inappropriate prescribing of anticholinergic or sedative medications. Types of comparisons Patients with a score of zero on the Drug Burden Index (i.e. no prescription of anticholinergic or sedative medicines) compared to the Drug Burden Index score; or different levels of Drug Burden Index scores between sub-samples of patients. Most studies will have no comparison. Types of outcomes This review will consider studies that include the following outcome measures: 1.Drug Burden Index scores 2.Physical and mental functioning; adverse effects of anticholinergic and sedative medicines 3.Changes to therapy following application of the Drug Burden Index as a tool to identify potentially inappropriate prescribing

Potential statin-drug interactions: prevalence and clinical significance.

BackgroundStatins are cholesterol-lowering drugs widely used for cardiovascular prevention. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. The exposure of the Bulgarian population to coprescriptions leading to potential statin-drug interactions is currently unknown.ObjectiveThe aim of this study was to investigate the incidence of coprescriptions involving statins and to compare the exposure of outpatients and inpatients to potential statin-drug interactions.SettingA cardiology clinic of the teaching University hospital in Varna, Bulgaria.MethodThis observational retrospective study examined the medical records of hospitalized patients prescribed a statin in combination with potentially interacting drugs. Patients who entered the hospital with a statin coprescription (considered outpatients) were compared with those coprescribed a statin at discharge from hospital (considered inpatients). Potentially interacting drugs included inhibitors and inducers of cytochrome P450 (CYP) enzymes and drugs of narrow safety margin (coumarin anticoagulants, digitalis).Main outcome measureThe proportion of patients exposed to statin coprescriptions with potentially interacting drugs at hospital admission and discharge. Secondary outcome measures: laboratory evidence supporting possible statin-drug interactions.ResultsOut of 1641 hospitalized patients examined, 572 were prescribed a statin, either at hospital admission or discharge. Simvastatin was most commonly prescribed and simvastatin-drug coprescription predominated, especially at discharge. The exposure to all potential statin-drug interactions was similar at hospital admission (26.1%) and discharge (24.4%), as was the exposure to statin combinations with CYP inhibitors, 6.4% and 4%, correspondingly. Overall, more coprescriptions were generated, than were eliminated by hospital physicians. Amiodarone was the CYP inhibitor most frequently coprescribed. Of all interacting drugs acenocoumarol was the most commonly found, the proportions of statin-acenocoumarol coprescriptions being roughly the same at hospital entry (11.5%) and discharge (12.4%). In 7 patients out of 69 exposed to the combination, INR was found to be higher than 3, indicating a risk of over-anticoagulation.ConclusionsPotential statin-drug interactions are common. Although they do not differ between outpatient and inpatient settings, new hazardous coprescriptions are more frequently generated in hospital. Caution is required when acenocoumarol is coprescribed with statins, especially simvastatin.