Drug-drug interaction software in clinical practice: a systematic review.

PURPOSE: Several electronic databases which report the prevalence of drug-drug interactions (DDIs) are used as a tool for evaluation of potentially harmful DDIs. The aim of our review was to evaluate the usability and appropriateness of commercially available electronic databases which assess the prevalence of potential DDIs. METHODS: The systematic electronic literature search was conducted with the following search terms: "database" AND "software," and "drug-drug interactions" AND "database," and the inclusion and exclusion criteria were applied in order to identify the publications of interest. RESULTS: A total of 3766 papers were identified by systematic search. After applying inclusion and exclusion criteria, 38 publications were included in the analysis. The most commonly used software in the included studies was Micromedex® Drug-Reax, for which some authors argue to be the most reliable due to highest sensitivity. It gives information about clinical consequences of DDIs, classifies underlying mechanism and onset of the adverse outcome (either rapid, or delayed) as well as severity (such as minor, moderate, or major), and provides the level of evidence which supports this information. This data is also provided by Drug Interaction Facts®, Lexi-Interact®, and Pharmavista®. A small number of studies which compared assessment of DDIs with electronic database and the clinician's assessment showed large discrepancy in number and relevance of detected DDIs. The overlap was in some cases as low as 11 %. CONCLUSION: The deficiency of clinical relevance of detected DDIs should be addressed in the upcoming research as it would provide more relevant information to the prescribers' in clinical practice.

Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability.

Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3-2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as "typical" EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.

Insights into treatment of complex Crohn's perianal fistulas.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.

Intravenous versus subcutaneous delivery of biotherapeutics in IBD: an expert's and patient's perspective.

Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient.Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients.The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient's role in therapeutical decision-making and how does IBD affect the patient's work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives.The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease.

Therapy modifications during hospitalization in patients with chronic heart failure.

BACKGROUND: Guidelines on suggested pharmacological treatments for heart failure (HF) are not optimally implemented in clinical practice and whether pharmacotherapy adjustment actually happens in daily practice is largely unknown. We aimed to investigate pharmacotherapy modifications during hospitalization. METHODS: This was a prospective observational survey where all admissions were screened for HF; 210 patients were included. The guideline adherence index (GAI) and modified GAI (mGAI, if ≥50% of target dose) were used to grade the pharmacotherapy. RESULTS: Among 198 patients discharged alive (mean age 77years, 51% male), 49% had preserved left ventricular ejection fraction (PLVEF) and 30% had left ventricular systolic dysfunction (LVSD); the echocardiography report was unavailable for 21%. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists were prescribed to 78%, 58% and 20% of patients on admission and 72%, 65% and 23% at discharge, respectively. Overall, 14% of patients met GAI-3, but at discharge only 7% met mGAI-3. One of the key drugs was stopped or down-titrated in 27%. During follow-up, 21% of patients died (25% with LVSD). Patients with LVSD discharged with at least one HF drug had a lower risk of death than patients with none (HR=0.142, 95% CI=0.029-0.683, p=0.015). Patients with PLVEF had better prognosis than LVSD patients when no HF drugs were prescribed at discharge (HR=0.075, 95% CI=0.009-0.627, p=0.017). CONCLUSIONS: The pharmacotherapy of HF patients did not improve significantly during hospitalization, remaining suboptimal. Treatment with key drugs was terminated or reduced in a significant proportion of patients, mostly without specific written justification.

Clinical-pharmacist intervention reduces clinically relevant drug-drug interactions in patients with heart failure: A randomized, double-blind, controlled trial.

BACKGROUND: Incidence of drug-drug interactions (DDIs) increases with complexity of treatment and comorbidities, as in heart failure (HF). This randomized, double-blind study evaluated the intervention of the pharmacist on prevalence of clinically relevant DDIs (NCT01855165). METHODS: Patients admitted with HF were screened for clinically relevant DDIs, and randomized to control or intervention. All attending physicians received standard advice about pharmacological therapy; those in the intervention group also received alerts about clinically relevant DDIs. Primary endpoint was DDI at discharge and secondary were re-hospitalization or death during follow-up. RESULTS: Of 213 patients, 51 (mean age, 79 ± 6 years; male, 47%) showed 66 clinically relevant DDIs and were randomized. For intervention (n=26) versus control (n=25), the number of patients with and the number of DDIs were significantly lower at discharge: 8 vs. 18 and 10 vs. 31; p=0.003 and 0.0049, respectively. Over a 6 month follow-up period, 11 control and 9 intervention patients were re-hospitalized or died (p>0.2 for all). No significant differences were seen between control and intervention for patients with eGFR <60 mL/min/1.73 m(2) (78%) for re-hospitalization or death (10 vs. 7; p=0.74). CONCLUSIONS: Pharmacist intervention significantly reduces the number of patients with clinically relevant DDIs, but not clinical endpoints 6 months from discharge.

Potential drug-drug interactions in hospitalized patients with chronic heart failure and chronic obstructive pulmonary disease.

INTRODUCTION: Polypharmacy is common in patients with chronic heart failure (HF) and/or chronic obstructive pulmonary disease (COPD), but little is known about the prevalence and significance of drug-drug interactions (DDIs). This study evaluates DDIs in hospitalized patients. MATERIAL AND METHODS: We retrospectively screened medical charts over a 6-month period for diagnosis of chronic HF and/or COPD. Potential DDIs were evaluated using Lexi-Interact software. RESULTS: Seven hundred and seventy-eight patients were included in the study (median age 75 years, 61% men). The median number of drugs on admission and discharge was 6 (interquartile range (IQR) 4-9) and 7 (IQR 5-), respectively (p = 0.10). We recorded 6.5 ±5.7 potential DDIs per patient on admission and 7.2 ±5.6 on discharge (p = 0.2). From admission to discharge, type-C and type-X potential DDIs increased (p < 0.05 for both). Type X interactions were rare (< 1%), with the combination of a ß-blocker and a ß2 agonist being the most common (64%). There were significantly more type-C and type-D potential DDIs in patients with chronic HF as compared to patients with COPD (p < 0.001). Patients with concomitant chronic HF and COPD had more type-C and type-X potential DDIs when compared to those with individual disease (p < 0.005). An aldosterone antagonist and ACE inhibitor/ARB were prescribed to 3% of chronic HF patients with estimated glomerular filtration rate < 30 ml/(min × 1.73 m(2)). CONCLUSIONS: The DDIs are common in patients with chronic HF and/or COPD, but only a few appear to be of clinical significance. The increase in potential DDIs from admission to discharge may reflect better guideline implementation rather than poor clinical practice.