Package Insert Research Articles

Bimekizumab-bkzx for the Treatment of Plaque Psoriasis: A Drug Review.

Bimekizumab is a biologic targeting interleukin (IL)-17A/17F, approved by the Food and Drug Administration (FDA) for moderate-to-severe plaque psoriasis in 2023. A PubMed search was performed using the keywords "bimekizumab," "plaque psoriasis," and "bimekizumab clinical trials," from origin to August 1, 2024. We included phase I to III trials of bimekizumab for plaque psoriasis, studies published post-FDA approval, and information from the package insert. We summarized 1 phase I, 4 phase II, and 4 phase III trials, and 3 real-world studies published post-FDA approval. Bimekizumab was effective; >85% and 70% of patients achieved PASI90 and PASI100, respectively, in phase III trials. Head-to-head, 85% of bimekizumab patients achieved PASI90 versus 50% of ustekinumab patients. The most frequent adverse event was oral candidiasis (4%-10%); serious adverse events were rare (<1%). Long-term studies confirmed sustained efficacy and consistent safety profile. Bimekizumab was more efficacious than other IL-17 inhibitors, ustekinumab, and adalimumab. Real-world data corroborate bimekizumab's efficacy. Bimekizumab had a safety profile like other IL-17 inhibitors, with higher rates of mucocutaneous candidiasis. Many patients who failed other IL-17 inhibitors and switched to bimekizumab experienced clearance. The efficacy of bimekizumab in patients who failed other IL-17 blockers may be attributable to bimekizumab's ability to block multiple IL-17 isoforms. Bimekizumab also outperformed tumor necrosis factor (TNF)-alpha inhibitors. There may be patients who fail previously available drugs, for reasons including nonadherence, antidrug antibodies, or adverse effects; bimekizumab, which targets additional cytokines, may bridge that gap.

Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis.

Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug-drug interactions that complicate modulator therapy have been reported. This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company's summary of product characteristics. A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary.

Adverse events associated with azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. Research design and methods We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. Results A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. Conclusions Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Home blood pressure-lowering effect of esaxerenone versus trichlormethiazide for uncontrolled hypertension: a predefined subanalysis of the EXCITE-HT randomized controlled trial by basal calcium channel blocker versus angiotensin receptor blocker.

This prespecified subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to examine the non-inferiority of esaxerenone to trichlormethiazide as a second-line antihypertensive agent according to the basal antihypertensive agent used (angiotensin receptor blocker [ARB] or calcium channel blocker [CCB]). The primary endpoint, change in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to end of treatment was similar between the two groups (intergroup difference in least squares mean change [95% confidence interval]: -1.3 [-3.8, 1.3]/-0.2 [-1.6, 1.3] mmHg for ARB; -2.7 [-4.2, -1.2]/-0.8 [-1.7, 0.1] mmHg for CCB). The respective incidences of serum potassium levels <3.5 mEq/L and ≥5.5 mEq/L in the ARB subgroup were 3.4% and 4.2% for esaxerenone and 7.9% and 0% for trichlormethiazide; in the CCB subgroup, they were 2.8% and 0.6% for esaxerenone and 13.9% and 1.2% for trichlormethiazide, respectively. The incidence of uric acid level ≥7.0 mg/dL was numerically higher in the trichlormethiazide group than the esaxerenone group in both the ARB and CCB subgroups. The non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP was demonstrated regardless of whether the basal antihypertensive agent was an ARB or CCB. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns. Serum potassium levels tended to be higher when esaxerenone was combined with an ARB than with a CCB, but this can be mitigated if administered according to the package insert. A subgroup analysis of the EXCITE-HT study according to basal antihypertensive agent demonstrated the non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP regardless irrespective of the basal antihypertensive agent. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns.

Advances in Factors Affecting ALDH2 Activity and its Mechanisms.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme primarily involved in the detoxification of alcohol-derived aldehyde and endogenous toxic aldehydes. It exhibits widespread expression across various organs and exerts a broad and significant impact on diverse acute cardiovascular diseases, including acute coronary syndrome, acute aortic dissection, hypoxic pulmonary hypertension, and heart failure. The ALDH2 rs671 variant represents the most prevalent genetic variant in East Asian populations, with carriage rates ranging from 30 to 50% among the Chinese population. Given its widespread presence in the body, the wide range of diseases it affects, and its high rate of variation, it can serve as a crucial tool for the precise prevention and treatment of acute cardiovascular diseases, while offering individualized medication guidance. This review aims to provide a comprehensive overview of the latest advancements in factors affecting ALDH2 activity, encompassing post-transcriptional modifications, modulators of ALDH2, and relevant clinical drugs.

Comparison of 2 Free Light Chain Assays: Performance of the Free Light Chain Ratio as a Risk Factor for MGUS Progression.

New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS). Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2). There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit. The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay.

A-104 Study of the matrix effect for thyroglobulin and calcitonin in fine-needle aspiration of cervical nodules

Abstract Background Analysis of material from fine needle aspiration of cervical thyroglobulin nodules with Beckman Coulter reagents on the ACCESS equipment and Calcitonin using the Siemens reagent on the Immulite equipment. The matrix effect, linearity and the limit of analytical sensitivity were analyzed. This study aims to analyze the correlation between the serum/plasma results described in the suppliers' package inserts with the results obtained with the puncture matrix. Methods The performance characteristics were tested according to the laboratory's operating procedures, based on the recommendations of ANVISA RDC 166/2017. Such parameters involved doping, which corresponds to the introduction of a calibrator with a known and traceable value into a pool of puncture material that is known to be negative, in order to analyze the behavior of the results obtained, paying attention to the deviations that may eventually occur due to the interference of the characteristics of the puncture material. puncture. After doping the material, dilutions were performed up to the sensitivity limit of the test, also analyzing the functional sensitivity, where ten replicates of the material were dosed, thus obtaining CV%, mean and Standard Deviation values. The same process was carried out and evaluated using the serum material. During the entire process, the materials received and analyzed were centrifuged and always kept in a refrigerated environment. Results The recovery% of the matrix effect study for cervical aspirate puncture showed results within the expected range, ranging from 80% to 120%, as well as the results compared with serum/plasma referenced in the supplier's package insert. The functional sensitivity study for Thyroglobulin showed a CV% of 1.77%, being lower than that recommended by the package insert (2.2%) and for the Calcitonin analyte, the functional sensitivity study showed a CV% of 8.49%, being lower than recommended by the package leaflet (15.7%), in addition to having CV's lower than the 20% recommended by ANVISA. The results obtained with the matrix effect study for serum also showed values between 80% and 120%, both of which agreed. Conclusions The results showed excellent performance for material from fine needle aspiration for both Calcitonin and Thyroglobulin, being consistent with the serum data described by the suppliers' package inserts, thus making the reagent usable for the cervical aspirate puncture matrix.

A-059 Validation of self-collected capillary dried blood spot collection for clinical HbA1c testing

Abstract Background The increased prevalence of diabetes in socially disadvantaged populations requires solutions that are amenable to these communities. Unmanaged diabetes can cause cardiovascular disease, kidney damage, blindness, and limb amputation. Diabetes is traditionally diagnosed using fasting/oral glucose tolerance or hemoglobin A1c (HbA1c) tests; both of which require access to medical and laboratory facilities. Self-collected capillary dried blood spot (DBS) testing for HbA1c could alleviate health disparities by offering access to low cost and minimally invasive remote collection. The objective of this study was to validate self-collected capillary DBS specimens for clinical HbA1c testing. Methods DBS HbA1c was measured using the hemolysate application of the Roche cobas c513 Tina-quant Hemoglobin A1cDx Gen.3 assay. Calibration was performed according to the manufacturer’s package insert. Patient samples were prepared by collecting two 3mm DBS punches. Non-biological standards were prepared by placing two blank 3mm DBS punches into an empty tube and adding 10uL of standard. After 24 hours, samples were resuspended in 750uL of hemolyzing reagent and incubated for 75 minutes at room temperature (RT) while shaking at 800 RPM. Preliminary data showed that non-biological standards spotted onto DBS cards did not behave like real patient samples. A correction factor (CF) was derived (n=134) and challenged (n=20) to account for the systematic bias observed between matched patient DBS and venous specimens. Imprecision was established by running two patient DBS specimens as controls. Accuracy was evaluated using residual College of American Pathologists (CAP) proficiency testing (PT) material (n=32). Linearity was confirmed by running 5 levels of Maine Standards Linearity HbA1c Kit in triplicate. Stability of the DBS specimen and the hemolysate supernatant extracted from the DBS specimen were observed at RT. Results Specimens tested between venous and DBS HbA1c to derive the CF (n=134) had a bias of 0.26% (4.32%) and a linear equation of (y=0.938x +0.631; R=0.996). The resulting CF is: reported HbA1c% = (DBS HbA1c% - 0.631)/0.938. Matched venous and DBS specimens that challenged the CF (n=20) had a bias of -0.10% (-1.83%) and a linear equation of (y=1.06x -0.41; R=0.988). Imprecision was 2.3% and 1.3% for patient DBS control specimens with mean concentrations of 5.3% and 5.9%, respectively. Residual CAP PT samples (n=32) had an average bias of -0.05% (-0.40%). DBS HbA1c concentrations from 4.2-15.5% were linear (y=0.903x +1.15; R=0.999). The DBS specimen is stable for 60 days at RT and the hemolysate supernatant is stable for at least 10 hours at RT. Conclusions Self-collected capillary DBS specimens are acceptable for the clinical measurement of HbA1c, and effectively increase accessibility to diabetes screening and monitoring. Applying a CF to DBS patient samples removes the systematic bias observed between matched venous and DBS samples. Non-biological standards and capillary whole blood do not behave the same on DBS cards. Alternative PT for DBS specimens should be investigated as at-home collection advances.

B-120 Reference Interval (RI) Estimation for Pediatric Magnesium using an Indirect Method with Unsupervised Machine Learning Tool and Programming Language

Abstract Background Magnesium is an important intracellular component present in all enzymatic reactions involving Adenosine Triphosphate (ATP) utilization, with the majority stored in bones. In the blood, it exists as a free fraction and another bound to proteins. Regulation occurs through renal processes, and for this reason, hypermagnesemia is associated with renal insufficiency, compromising the central nervous system. On the other hand, hypomagnesemia cases are related to pancreatitis, intestinal malabsorption, childhood malnutrition, among other factors. Following complaints from pediatric doctors that our reference intervals (RI), as suggested by the manufacturer, would yield falsely elevated results in healthy patients, we estimated a new RI in the population served Methods We employed data mining followed by estimation using an indirect method through the LabRI™ algorithm with parametric, non-parametric, and robust statistical treatments for outlier exclusion, implemented in the R language. Latent abnormal values of outpatient pediatric patients were considered. We defined three pediatric partitions for both sexes, aged 0 to 6 years, 7 to 12 years, and above 12 years, using the comparative RI described by the Roche manufacturer. Data were extracted from our Data Lake between January and December 2022 in the Federal District of Brazil, from a laboratory part of a large network. Exclusion criteria included: Potassium &amp;gt; 5.5 and &amp;lt; 3.0 mmol/L; Phosphorus &amp;gt; 8.0 and &amp;lt; 1.5 mg/dL; Total Calcium &amp;gt; 12 mg/dL and &amp;lt; 7 mg/dL; Ionized Calcium &amp;gt; 1.5 mmol/L and &amp;lt; 0.8 mmol/L; Creatinine &amp;gt; 2.0 mg/dL; C-reactive protein (CRP) &amp;gt; 10 mg/dL; Ferritin &amp;gt; 700 ng/mL; A1C &amp;gt; 7.0%; LDL Cholesterol &amp;gt; 200 mg/dL; Magnesium repeated within &amp;lt; 12 months, and samples of hospital origin. Results The evaluated population after exclusion criteria totaled 6,865 children, distributed as follows: 26.0% aged 0 to 6 years, 30.3% aged 7 to 12 years, and 43.7% above 12 years. Outliers were excluded in 1.5%, 0.9%, and 1.0%, respectively. In all partitions, there was a significant discrepancy compared to the reference intervals recommended by Roche. In our estimation, there was an expansion of the upper limit of the reference interval in all partitions, supporting the clinical opinion. The new reference intervals became: 0-6 yrs: from 1.7-2.3 to 2.0-2.7; 7-12 yrs: from 1.7-2.1 to 2.0-2.6; and &amp;gt;12 yrs: from 1.7-2.2 to 1.9-2.6. The standard deviation varied between 0.19 and 0.20, and the median between 2.20 and 2.32 Conclusions The manufacturer states in the package insert that they did not assess the RI for the pediatric population and that each laboratory should verify the RI in the population served. We approve the adoption of the estimated RI for the pediatric population calculated by the LabRI™ tool in the partitions of 0-6 years, 7-12 years, and &amp;gt;12 years, stating in the report “Reference interval established by an indirect method in 6865 children tested in the laboratory, partitioned by age group.”

A-166 Performance verification of a polyclonal anti-PF4 immunoassay in evaluation of Heparin Induced Thrombocytopenia (HIT)

Abstract Background Heparin-induced thrombocytopenia (HIT) is a severe complication of exposure to heparin that occurs in a small percentage of patients in anticoagulation therapy. HIT could happen regardless of the dose, exposure, schedule, or route of administration. HIT results from an autoantibody directed against endogenous platelet factor 4 (PF4) that forms complex with heparin. This antibody activates platelets and can cause life threatening arterial and venous thrombosis. Untreated HIT has a mortality rate as high as 20%. However, with appropriate screening, diagnosis and early intervention, mortality rates have been reported to be below 2%. The laboratory evidence in evaluating patients for HIT is crucial for early intervention. There are several assays available to diagnose Heparin Induced Thrombocytopenia (i.e., immunoassay and/or functional assay for HIT antibodies; serotonin release assays). The purpose of this study is to establish the measurement criteria and verify performance characteristics of a polyclonal anti-PF4 immunoassay. The test of interest (anti-PF4 immunoassay) is intended for the qualitative detection of the anti-heparin-platelet factor 4 antibodies in plasma or serum by ELISA. Methods The ASSERACHROM Assay (Diagnostica Stago, Inc. USA) was implemented in the automated Dynex DS2 ELISA Processing System (Dynex Technologies Inc USA). Two Dynex DS2 instrument comparisons along with precision, accuracy and measurement range for qualitative positive and negative results were studied. The reference method comparisons with serotonin release assay and other monoclonal anti-PF4 immunoassays were performed. To evaluate performance of the assay, we conducted precision, accuracy, and qualitative method comparison. We compared the assay of interest with two reference lab immunoassays and the gold standard reference method (serotonin release assay). The statistical analysis was carried out in EP Evaluator and GraphPad Prism. Results The negative control precision demonstrated CV of 9.2% (N=20, mean= 0.11, SD= 0.01). The analyte measurement is expressed as optical density (OD). The positive control precision characteristics showed CV of 8.1% (N=20, mean= 1.62, SD= 0.13). The threshold was defined as reference reagent absorbance (R6OD) times the variance factor divided by 100 ((R6OD* variance factor)/100= threshold (X)). This is used for positive (&amp;gt;the X) and negative (&amp;lt; the X) absorbance cut off for patient samples. The R6 reference material precision study resulted in a CV of 7.95% (N=20, mean= 2.1, SD= 0.17). The R6 variance factor per precision statistics at 3SD level was 23.85%. This is comparable to peer group variance provided in the assay package insert (23.5%). The polyclonal anti-PF4 immunoassay versus a reference monoclonal method (N=40) demonstrated agreement of 90.9% with positive agreement of 100% and negative agreement of 89.5%. When compared with gold standard serotonin release assay (N=40), the assay demonstrated agreement of 75% with positive agreement of 90% and negative agreement of 60%. The two instruments demonstrated agreement of 97.5% with positive agreement of 100% and negative agreement of 93.3% (Cohen's Kappa 94.6%; with Kappa &amp;gt; 75% indicates “high” agreement). Conclusions This anti-PF4 immunoassay is precise, accurate and comparable with three different reference methods. The test is best utilized when 4T score based clinical algorithm is used for evaluation of HIT.

Unraveling the Spectrum of Ocular Toxicity with Oxaliplatin: Clinical Feature Analysis of Cases and Pharmacovigilance Assessment of the US Food and Drug Administration Adverse Event Reporting System Database

Ocular adverse events (oAEs) are a class of adverse events associated with oxaliplatin that are realistically observed in real-world settings. Herein, we aim to describe the clinical characteristics of oAEs associated with oxaliplatin through a systematic review of case reports and to assess a potential safety signal. PubMed, Embase, and Cochrane Library databases were used to retrieve case reports. The global disproportionality study was performed leveraging the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2023. Bayesian information component (IC) and reporting odds ratio (ROR) were applied to identify and evaluate potential oAEs associated oxaliplatin. A total of 20 cases from the systematic case review (of 13 screened articles) were reported on oAEs associated with oxaliplatin, with ages between 26 and 76 years. Therein, 16 (84.2%) cases described loss of vision, and the remaining cases presented with bilateral blepharoptosis, papilledema, and optic disc swelling. Insights from the US Food and Drug Administration Adverse Event Reporting System database showed that oAEs accounted for 4.28% (n = 1194) of the overall oxaliplatin-related adverse event reports, of which 1140 (95.48%) had a serious outcome. The median (interquartile range) onset time of oAEs with oxaliplatin was day 1 (0-25; n = 649). Disproportionality analysis revealed that ocular injuries NEC (n = 28, ROR, 22.72; lower limit of the 95% 2-sided CI for IC, 3.12) was the most significant signals detected. Additionally, unexpected significant oAEs, including eyelid ptosis, eyelid edema, eye movement disorder, blepharospasm, periorbital edema, swelling of eyelid, ophthalmoplegia, retinal vein thrombosis, cataract nuclear, blindness cortical, cataract subcapsular, and lacrimation disorder, were also reported disproportionality. Our study systematically described the characteristics and outcomes of oxaliplatin-related ocular toxicity and also uncovered potential oAEs that were not disclosed in the package insert. Further prospective epidemiologic studies to validate these findings are warranted.

Improving diabetes self-management and control through individualized patient counseling: A quasi-experimental study

BACKGROUND: Diabetes is one of the most common chronic diseases, affecting a large proportion of the global population. This study aims to evaluate the effects of individualized patient counseling on diabetes self-management. MATERIALS AND METHODS: This quasi-experimental study utilized a non-randomized two-arm pre-post design. It was conducted at the out-patient clinics of a tertiary care hospital, Gujarat, from February 2023 to August 2023. There were 300 type 2 diabetes patients who belonged to an intervention group receiving 3 monthly 30-minute individualized counseling sessions (n = 150) or a control group continuing usual care (n = 150). Assessments at baseline and 3 months post-intervention compared treatment effects. The outcomes measured were diabetes knowledge, attitudes/beliefs, medication/lifestyle adherence, self-reported quality of life, blood pressure (BP), and HbA1c. The intervention covered medication and lifestyle guidance, self-monitoring skills, barrier identification, and problem-solving with a focus on patient empowerment. The analysis compared within- and between-group changes. RESULTS: At 3 months, counseled patients showed significantly greater improvements in knowledge (difference 13.6 points), self-care abilities (lifestyle adherence difference 6.6 points), 5.9 mmHg extra drop in systolic BP, and 0.6% higher HbA1c reduction versus controls (all P &lt; 0.05). Greater knowledge gain is strongly correlated with improved HbA1c (r = 0.42). Patients reported medication counseling as the most useful and cost and cultural dietary habits as key ongoing barriers. CONCLUSION: Individualized counseling promoted better self-management behaviors, improved clinical measures, and subjective well-being in diabetes patients versus usual care alone. Routine Counseling should be considered to complement medical management in high-risk chronic diseases.

The Awareness of and Adherence to the Pregnancy Prevention Program for Oral Retinoids: A Questionnaire Survey in Denmark.

We aimed to investigate the awareness of oral retinoid teratogenicity and the adherence to the pregnancy prevention program (PPP) related to oral retinoid use by physicians, pharmacists, and patients in Denmark. As part of the multi-country survey, web-based questionnaires were distributed among Danish dermatologists, general practitioners, community pharmacists, and women of childbearing age, who were using or had used oral retinoids within the past 5 years. A total of 62 physicians, 96 pharmacists, and 50 oral retinoid using women responded; 95%, 100%, and 98%, respectively, were aware of the teratogenic risks of oral retinoids. For physicians, the most applied PPP measures were the usage of the patient (44%) and the healthcare professional (19%) guides, while the least applied measure was signing medication risk awareness form (3%). Among the pharmacists, the warning sign on the outer medication package was the most used measure (45%). Among the women, a majority (90%) had read the patient information leaflet included in the medication package and 72% discussed the use of contraception with their healthcare provider, while risk awareness forms and patient cards were seen by only few. In Denmark, physicians, pharmacists, and medicine users were aware about the teratogenic effects of oral retinoids. Adherence to pregnancy preventionmeasures varied, suggesting unwillingness to use the measures that require patients' signatures among physicians and a lack of awareness of pharmacy targeting measures. Accessibility of the latter measures need to be optimized to improve the safety of oral retinoid use.

Self-Medication of Medical Students at Erzincan Binali Yıldırım University in Turkey: A Cross-Sectional Study.

Responsible self-medication (SM) can save time, money, reduce the number of visits to the doctor, and alleviate pressure on health services. However, while there are clear benefits, SM also carries significant risks, such as increased drug side effects, inappropriate use of prescription drugs, drug interactions, misdiagnosis, drug dependence, masking of medical conditions, and antibiotic resistance. This study aimed to investigate the practices of medical students at a public university in Türkiye towards SM, as well as to determine the factors influencing such practices. The population of this cross-sectional study included first-, fourth-, and sixth-year medical students. As the goal was to reach the entire population (375 students), no sample selection was made. A total of 332 students (88.5%) participated in the study.The relevant literature was used for the basis of the questionnaire used in the study. In the statistical evaluation, percentages, means, standard deviations, medians, minimum, and maximum values were used to present the descriptive data, while factors influencing SM were analyzed using the chi-square test and bivariate and multivariate logistic regression analysis. The overall rate of SM among the participants was found to be 96.1%. No statistically significant difference was observed in SM rates based on the year of study (p>0.05). The rate of students using antibiotics without a prescription was 19.3%. Additionally, 82.5% of the students reported reading the package insert before using a drug. The most common symptoms leading to SM were headaches (83.1%) and the common cold (63.6%). The most frequently self-administered medications were analgesics (86.1%), common cold medicines (54.8%), and vitamins (34.0%). Furthermore, 79.3% of the participants indicated that they self-medicate because they perceive their condition as a simple illness, 64.6% because they had experienced a similar illness before, and 28.2% because they believed they had sufficient knowledge of medications.In multivariate regression analysis, keeping medicines at home/in the dormitory for later use and not having a chronic disease were found to be effective factors in students' practice of SM. It is important to plan educational interventions to promote the development of responsible SM behaviors. Starting these educational programs in the first year of medical school is thought to contribute significantly to the fostering of responsible SM practices.

The Pharmacokinetic Interaction of Tirabrutinib with Voriconazole, Itraconazole, and Fluconazole in SD Rats by UPLC-MS/MS.

Tirabrutinib is an orally effective, approved, and highly selective second-generation Bruton's tyrosine kinase (BTK) inhibitor for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL). This study aimed to develop an ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) method for the determination of tirabrutinib concentration in rat plasma, where zanubrutinib was used as an internal standard (IS). This method was also applied to study whether tirabrutinib would interact with voriconazole, itraconazole, and fluconazole in rats, providing a reference value for clinical medication guidance. In the current study, the organic solvent protein precipitation method was used to treat plasma samples, which is simple and reproducible. Tirabrutinib (m/z 455.32 → 320.21) and zanubrutinib (m/z 472.13 → 455.04) were separated on a Waters Acquity BEH C18 column (2.1 × 50 mm, 1.7 μm) and detected by multiple reaction monitoring (MRM) in positive ionization mode. The method showed good linearity in the range of 5-3000 ng/mL for tirabrutinib with the lower limit of quantification (LLOQ) of 5 ng/mL. The recovery and matrix effects were 85.7-91.0% and 102.0-113.3%, respectively. The accuracy, precision, stability, and carry-over effect were also acceptable. The method could also be used for determining the pharmacokinetic interaction of tirabrutinib in rats. The results showed AUC0→∞ of tirabrutinib to be increased by 139.3% and 83.9% in the presence of voriconazole and fluconazole, respectively, while itraconazole had little effect. It is necessary to monitor the concentration of tirabrutinib in patients when it is combined with voriconazole and fluconazole to achieve a better therapeutic effect and reduce the risk of adverse reaction. Further research should be conducted in the future.

통신판매 관련 헌법재판소 결정의 비판적 검토 - 의약품의 약국외 판매 제한과 도수 있는 안경 및 콘택트렌즈의 통신판매 제한을 중심으로

This paper aims to examine the constitutional limits on the laws of non face-to-face sales(this concept includes not only online sales but also all other sales methods that do not involve ‘real’ face-to-face interaction), focusing on the jurisprudence of the Constitutional Court. In case of pharmaceuticals, with a excessively limited exception, sales are only permitted in pharmacies(the place itself). Since a temporary allowance during the COVID-19 period, non face-to-face sales have been permitted only under very exceptional conditions. In contrast, many foreign countries generally allow the non face-to-face sales of pharmaceuticals. For instance, Japan, which has a legal system similar to ours, has actively permitted non face-to-face sales to maximize Consumer’s Right to Self-determination, especially after the Supreme Court's ruling that declared the ban on non face-to-face sales unconstitutional. On the other hand, the Constitutional Court of Korea has ruled that the relevant regulations do not infringe basic rights, citing reasons such as the need for thorough medication guidance, prevention of pharmaceutical contamination, clarification of accountability, enough exceptional allowance for sales outside pharmacies, enough medical services by public health centers, difficulties in assuming the necessity of non face-to-face sales, various problems associated with allowing sales outside pharmacies, and the insignificance of the business disadvantages to pharmacists and other sellers. In the case of prescription eyeglasses and contact lenses, non face-to-face sales are completely restricted. The Constitutional Court has justified the restriction using logic similar to that applied to pharmaceuticals. However, considering that the constitutional freedom of occupation for sellers is intended to protect the freedom of economic activity rather than the occupation itself, and that it is necessary to recognize the distinct interests of consumer self-determination in guaranteeing it practically—distinguishing it from the freedom of occupation and including it within the protection scope of the Constitution while assessing the degree of restriction in actual judgment—the series of Constitutional Court rulings may not necessarily be based on sound jurisprudence. Specifically, regarding general pharmaceuticals, the primary issue is that access to relatively low-risk medications that require minimal knowledge is not allowed through more accessible means. For prescription drugs, remote methods such as video consultations could be equivalent to face-to-face guidance based on a doctor's prescription, and the complete lack of exceptions for individuals, such as those with chronic diseases, and the elderly, the physically disabled and residents of remote areas who need improved medical accessibility, is problematic. In case of prescription eyeglasses and contact lenses, considering the several distinctions from pharmaceuticals, a critical review of the Constitutional Court's stance of not recognizing the unconstitutionality of such regulations is inevitable.

Community Specialist Team for Older Adults - Who Do You Think We Are? Co-Design Of A Patient Information Leaflet

Abstract Background Navigating care pathways can be challenging and confusing for patients and caregivers. With the emergence of several new clinical specialist teams, we identified the need for accurate, clear and relevant information, provided as a printed leaflet and available at referral stage for both older adults and referring practitioners. Methods A draft Patient Information Leaflet (PIL) was developed with contributions from all members of the Community Specialist Team for Older Adults (CSTOA) explaining the purpose of the service. A review of referral sources was undertaken to identify those key stakeholders from whom feedback should be sought to ensure content validity. The draft PIL and a feedback questionnaire were distributed to patients and their caregivers who have had intervention from the CSTOA in addition to General Practitioners and Community Health Network colleagues. Results There were 27/35 responses to the questionnaire. Data was collated and analysed. All respondents reported that from reading the PIL, they understood clearly what the service provides, and all agreed that the leaflet accurately describes the service. Details such as what to expect from intervention of the team and advice to bring a family member to the initial appointment were mentioned as particularly useful content. Supplementary feedback commended the co-location and accessibility of the service compared to a hospital setting. It was suggested that other services should be included in the CSTOA. Based on survey responses, minor edits were made to the PIL to meet stakeholder satisfaction. Conclusion Feedback from this survey helped endorse the provision of a printed PIL to be provided at referral stage. Additional commentary gathered, re-enforces the need for continuous interaction and information sharing with service stakeholders. Next steps include making this PIL available electronically to allow for real time updates and translating to other languages to ensure inclusivity.

The Challenges for EU User Testing Policies for Patient Information Leaflets.

Patient information leaflets (PILs) are essential tools in healthcare, providing crucial information about medication use. In the European Union, the European Medicines Agency (EMA) oversees the regulation and standardisation of PILs to ensure their readability and accessibility. However, challenges persist in ensuring these documents are comprehensible and user-friendly. This study employs a qualitative analytical approach, reviewing existing literature and regulatory documents to identify gaps in the EU user testing policies for PILs. It focuses on the diversity of participant samples, the independence of the testing process, and the robustness of user testing protocols. Findings indicate that current user testing practices often lack diversity and may be biased when pharmaceutical companies conduct their own tests. Additionally, there is a lack of user testing protocols for translated PILs, potentially compromising their accuracy and cultural relevance. To improve the efficacy of PILs, it is essential to include diverse and representative samples in user testing, mandate independent third-party evaluations, implement protocols for user testing on translated PILs, and ensure continuous updates to guidelines based on the latest best practices in health communication. These measures will enhance patient safety and understanding of medication information.

A Quality Improvement Project On The Introduction Of A Nurse-Led, Patient Self-Monitored Blood Pressure Telehealth Platform

Abstract Background Telehealth is a strategy for health and wellbeing promotion. Hypertension is a modifiable risk factor in vascular health. Timely, reliable and accessible identification of this risk is important. Working within an interdisciplinary ambulatory neurovascular hub, a nurse-led model of service provided the opportunity to effectively identify and modify this risk through the secondary prevention measure of hypertension management. Methods An interdisciplinary neurovascular service quality improvement group, the “Stroke Big Room”, evaluated service models and telehealth platforms for patient-self monitoring of hypertension. The telehealth “Florence” platform was introduced. An accompanying Patient Information Leaflet was developed with the Communications Team within the Trust. Patients with a blood pressure of 130/80mmHg and a confirmed diagnosis of minor stroke or transient ischaemic attack were offered the “Flo” platform. Results A 20-patient sample found: 50% required no treatment change, 30% were commenced on antihypertensive treatment and 20% required antihypertensive dose increase. In the 2023/24 financial year, 285 patients participated in the Flo platform. Conclusion Timely identification and modification of hypertension is a reversible risk factor for neurovascular disease. A nurse-led service for the provision of, education on and support in use of a telehealth monitoring platform is an effective approach. This service model allows for effective secondary prevention treatment in a rapid and accessible way. The telehealth platform “Flo” was accessible to patients on the basis of patient reported outcome measures. As a result of the use of the platform, pharmacotherapeutic interventions occurred in 50% of participants in this telehealth programme.

A SADMAN With No Plan; Medication Management and Adherence To SADMAN Guidelines In Ambulatory Geriatric Care

Abstract Background Medication side effects are common causes of ill health, with ‘SADMAN’ medications identified as frequent offenders- sulphonylureas, angiotensin-converting enzyme inhibitors (ACEi), diuretics, metformin, angiotensin-receptor blockers, nonsteroidal anti-inflammatories and sodium/glucose cotransporter-2 inhibitors. Recent consensus recommendation published in the American Journal of Kidney Diseases is that patients on these should omit them if unwell1. We examined SADMAN usage within our Day Hospital, knowledge of this guidance and patients’ confidence in managing their medications. Methods All patients presenting for review in one week in our Day Hospital were included. Data collected included age, gender and number of medications including SADMAN. Patients were asked had they been advised to stop SADMAN medications if unwell, whether medications were blister packed and if they would be confident identifying and stopping a particular medication. Results 27 patients were included. 56% male, mean age 80 years old and mean number of medications 9 (range 0-22). 67% had medications blister-packed. 48% were prescribed one or more SADMAN medications and 15% more than one. Most commonly prescribed were ACEi (30%) and diuretics (19%). No patients had been advised to stop taking a SADMAN medication if they became unwell. Only 19% of patients (31% on SADMAN medications) were confident they could identify/stop a particular medication. Conclusion Despite clear guidelines to stop SADMAN medications if unwell, we found that no patients attending our Day Hospital were aware of this. Even if patients were appropriately educated, there was a lack of confidence in medication management. Polypharmacy and blister packing of medications pose significant barriers, leading us to question the feasibility of SADMAN guideline implementation in an Ambulatory Geriatric Care setting. Reference 1. Watson KE et al. Consensus Recommendations for Sick Day Medication Guidance for People With Diabetes, Kidney, or Cardiovascular Disease: A Modified Delphi Process. Am J Kidney Dis. 2023 May;81(5): 564-574.doi: 10.1053/j.ajkd.2022.10.012.