Medication Profiles Research Articles

Analysis of Reports Sent to the Portuguese Pharmacovigilance System and Published Literature Regarding the Safety of Metformin in the Elderly.

The first line medication for the treatment of type 2 diabetes is metformin. This study aims to investigate the safety profile of metformin and metformin combination medications in older adults using pharmacovigilance data. A literature search was used to identify published clinical studies reporting safety of metformin in older patients (age ≥ 65 years old), which were then thoroughly evaluated. Additionally, a deep analysis was performed, taking into account suspected adverse drug reaction (ADR) reports submitted to the Portuguese Pharmacovigilance System involving patients with 65 years old or older, with metformin or metformin combination as the suspected drug. The results suggest that metformin is safer when used in combination with other antidiabetics than when used in monotherapy. Metformin prolonged-release tablets have a lower incidence of adverse effects compared to treatment with immediate-release metformin tablets. The analysis of the reports showed that "gastrointestinal disorders" was one of the most common classes reported, and metformin alone was the drug most commonly associated with serious gastrointestinal reactions that resulted in hospitalization. In addition, it was the drug most commonly associated with the lactic acidosis ADR. Even though most ADRs in the reports were serious, the majority progressed to cure. According to the analysis performed, the results suggest that the patient's renal function should be considered in order to prevent ADRs associated with metformin, such as lactic acidosis. Therefore, monitoring the safety profile of metformin remains essential to prevent serious ADRs.

The modern aspects of the optimal therapeutic strategy of hyperemesis gravidarum

Although, nausea and vomiting in early pregnancy is very common, affecting approximately 80% of pregnancies, hyperemesis gravidarum (HG) is a severe form that complicates up to 2.2% of pregnancies. HG is one of the most common indications for hospitalization during pregnancy. In addition to the insufficient nutrition both for the mother and fetus, the severity of HG symptoms causes a serious psychosocial stress, which leads to depression, anxiety and even the development of perinatal pathology. The aim of this meta-analysis was to study available randomized controlled trials about therapeutic strategies by HG, their evaluation based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs.A systematic data search was conducted using the databases MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, Cochrane Database of Systematic Reviews and publications in professional editions of Ukraine for 2013–2023. The search was conducted using the following keywords: pregnancy, nausea and vomiting of pregnant women, excessive vomiting of pregnancy, hyperemesis, antiemetic therapy during pregnancy, infusion therapy and the safety profile of medications prescribed during pregnancy in various combinations.The main outcome was: the effectiveness of therapeutic strategies (reduction or stopping nausea/vomiting); detailing by safety profile of antiemetic drugs; optimization of infusion therapy; additional clinical strategies that help to improve the quality of care for pregnant women; adverse effects and side effects of drugs for HG for the mother/fetus/newborn.The results presented in this meta-analysis can be used in the creation of a national clinical guideline, protocol, consensus or clinical recommendations regarding the clinical management of hyperemesis gravidarum.

Medication histories to identify medication-related problems through the pharmacists' patient care process in a simulated ambulatory care laboratory

Background and purposeAssessment of the Pharmacists' Patient Care Process (PPCP) in pharmacy curricula has been reported in a variety of contexts, but results have not described individual student performance in a controlled ambulatory care skills laboratory to purposefully identify medication-related problems (MRP) and develop plans for resolution. Educational activity and settingOne of five MRPs was embedded within standardized medication profiles to facilitate student completion of three graded ambulatory care medication history encounters in a third-year skills laboratory. Data analysis included student performance in aggregate and according to MRP type from the first to the third medication history encounter. FindingsOne hundred thirty-six students completed three medication histories for 408 encounters. Regardless of MRP, the total and subscale scores for adjusted marginal means were significantly higher in Sessions 2 and 3. Performance on MRP scenarios for drug interactions and adverse effects were significantly lower and higher, respectively. Successful collection of patient history significantly influenced marginal mean scores for respective MRPs. SummaryImprovement in student application of PPCP Steps 1 through 3 may be evident using three simulated ambulatory care medication history patient encounters toward the end of the third professional year, with potential influences by MRP type, MRP repetition, and adequate collection of patient history. Repetition with individualized grading and formative feedback are essential for skill development to identify MRPs in this setting. Confirmation of findings and extension into experiential education with higher complexity are needed to develop consistent and effective application of the PPCP to patient care.

A novel method to create realistic synthetic medication data.

Synthea is a synthetic patient generator that creates synthetic medical records, including medication profiles. Prior to our work, Synthea produced unrealistic medication data that did not accurately reflect prescribing patterns. This project aimed to create an open-source synthetic medication database that could integrate with Synthea to create realistic patient medication profiles. The Medication Diversification Tool (MDT) created from this study combines publicly available prescription data from the Medical Expenditure Panel Survey (MEPS) and standard medication terminology/classifications from RxNorm/RxClass to produce machine-readable information about medication use in the United States. The MDT was validated using a chi-square goodness-of-fit test by comparing medication distributions from Synthea, Synthea+MDT, and the MEPS. Using a pediatric asthma population, results show that Synthea+MDT had no statistical difference compared to the real-world MEPS with a P value = .84. The MDT is designed to generate realistic medication distributions for drugs and populations. This tool can be used to enhance medication records generated by Synthea by calculating medication-use data at a national level or specific to patient subpopulations. MDT's contributions to synthetic data may enable the acceleration of application development, access to more realistic healthcare datasets for education, and patient-centered outcomes' research. The MDT, when used with Synthea, provides a free and open-source method for making synthetic patient medication profiles that mimic the real world.

Medication Profile of Heart Failure Patients With Reduced Ejection Fraction: The Advara HeartCare Heart Failure Clinic Experience

Medication Profile of Heart Failure Patients With Reduced Ejection Fraction: The Advara HeartCare Heart Failure Clinic Experience

Does needle penetration of the shoulder joint prior to arthroscopy increase infection risk? The effect of preoperative magnetic resonance arthrogram or corticosteroid injection.

Prior literature has associated preoperative corticosteroid shoulder injection (CSI) with infection following shoulder surgery. A recent study found an equally elevated risk of total knee arthroplasty infection with preoperative injection of either CSI or hyaluronic acid. The implication is that violation of a joint prior to surgery, even in the absence of corticosteroid, may pose an elevated risk of infection following orthopedic surgery. The aim of the present study was to determine whether violation of the shoulder joint for magnetic resonance arthrogram (MRA) poses an elevated risk of infection following shoulder arthroscopy, and to compare this risk to that introduced by preoperative CSI. A national, all-payer database was queried to identify patients undergoing shoulder arthroscopy between January 2015 and October 2020. Patients were stratified into the following groups: (1) no CSI or MRA within 6months of surgery (n=5000), (2) CSI within 2weeks of surgery (n=1055), (3) CSI between 2 and 4weeks prior to surgery (n=2575), (4) MRA within 2weeks of surgery (n=414), and (5) MRA between 2 and 4weeks prior to surgery (n=1138). Postoperative infection (septic shoulder or surgical site infection) was analyzed at 90 days, 1 year, and 2 years, postoperatively. Multivariable logistic regression analysis controlled for differences among groups. MRA within 2weeks prior to shoulder surgery was associated with an increased risk of infection at 1year (odds ratio [OR], 2.17; P=.007), while MRA 2-4weeks preceding surgery was not associated with an increased risk of postoperative infection at any time point. By comparison, CSI within 2weeks prior to surgery was associated with an increased risk of postoperative infection at 90 days (OR, 1.72; P=.022), 1 year (OR, 1.65; P=.005), and 2 years (OR, 1.63; P=.002) following surgery. Similarly, CSI 2-4weeks prior to surgery was associated with an increased risk of postoperative infection at 90 days (OR, 1.83; P<.001), 1 year (OR, 1.62; P<.001), and 2 years (OR, 1.79; P<.001). Preoperative CSI within 4weeks of shoulder arthroscopy elevates the risk of postoperative infection. Needle arthrotomy for shoulder MRA elevates the risk of infection in a more limited fashion. Avoidance of MRA within 2weeks of shoulder arthroscopy may mitigate postoperative infection risk. Additionally, the association between preoperative CSI and postoperative infection may be more attributed to medication profile than to needle arthrotomy.

The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care

BackgroundThe evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs.MethodsThe PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention.DiscussionThis trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care.Trial registrationAustralian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

Pharmacogenomic panel testing provides insight and enhances medication management in persons living with HIV.

Our study aimed to assess the impact of pharmacogenomic panel testing in persons living with HIV (PWH). Prospective, observational intervention assessment. One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. Ninety-six participants (median age 53y, 74% white, 84% male, 89% viral load <50 copies/ml) completed panel testing yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in 1 participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.

A systematic review of randomised-controlled trials on deprescribing outcomes in older adults with polypharmacy.

Mixed findings about deprescribing impact have emerged from varied study designs, interventions, outcome measures and targeting sub-categories of medications or morbidities. This systematic review controls for study design by reviewing randomised-controlled trials (RCTs) of deprescribing interventions using comprehensive medication profiles. The goal is to provide a synthesis of interventions and patient outcomes to inform healthcare providers and policy makers about deprescribing effectiveness. This systematic review aims to (1) review RCT deprescribing studies focusing on complete medication reviews of older adults with polypharmacy across all health settings, (2) map patients' clinical and economic outcomes against intervention and implementation strategies and (3) inform research agendas based on observed benefits and best practices. The PRISMA framework for systematic reviews was followed. Databases used were EBSCO Medline, PubMed, Cochrane Library, Scopus and Web of Science. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomised trials. Fourteen articles were included. Interventions varied in setting, preparation, use of interdisciplinary teams, validated guidelines and tools, patient-centredness and implementation strategy. Thirteen studies (92.9%) found deprescribing interventions reduced the number of drugs and/or doses taken. No studies found threats to patient safety in terms of primary outcomes including morbidity, hospitalisations, emergency room use and falls. Four of five studies identifying health quality of life as a primary outcome found significant effects associated with deprescribing. Both studies with cost as their primary outcome found significant effects as did two with cost as a secondary outcome. Studies did not systematically study how intervention components influenced deprescribing impact. To explore this gap, this review mapped studies' primary outcomes to deprescribing intervention components using the Consolidated Framework for Implementation Research. Five studies had significant, positive primary outcomes related to health-related quality of life (HRQOL), cost and/or hospitalisation, with four reporting patient-centred elements in their intervention. RCT primary outcomes found deprescribing is safe and reduces drug number or dose. Five RCTs found a significant deprescribing impact on HRQOL, cost or hospitalisation. Important future research agendas include analysing (1) understudied outcomes like cost, and (2) intervention and implementation components that enhance effectiveness, such as patient-centred elements.

What we need to know and do on sugammadex usage in pregnant and lactating women and those on hormonal contraceptives.

Sugammadex is a chemically modified γ-cyclodextrin that is used as a selective reversal agent for steroidal neuromuscular blockade. The use of sugammadex has greatly increased globally; however, little is known about its potential adverse effects in pregnant and lactating women or those using hormonal contraceptives. There are three important theoretical assumptions. Firstly, pregnancy-related physiological changes involve most organs and affect the pharmacokinetic profiles of medications. Considering the physiological changes in pregnant women and the pharmacokinetic properties of sugammadex, alterations in the dosage and safety profiles of sugammadex may occur during pregnancy. Secondly, very large and polarized sugammadex molecules are expected to have limited placental transfer to the fetus and excretion into breast milk. Finally, sugammadex can bind to steroidal neuromuscular blocking agents as well as other substances with similar structures, such as progesterone. As a result of using sugammadex, progesterone levels can be reduced, causing adverse effects such as early pregnancy cessation and failure of hormonal contraceptives. This narrative review aims to demonstrate the correlations between sugammadex and pregnancy, lactation, and reproductive potential based on previously published preclinical and clinical studies. This will bridge the gap between theoretical assumptions and currently unknown clinical facts. Moreover, this review highlights what anesthesia providers should be aware of and what actions to take while administering sugammadex to such patients.

A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer.

Androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, is commonly co-prescribed as combination therapy. To better understand the safety and tolerability profile of relugolix, an oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, in combination with abiraterone acetate (abiraterone) and apalutamide, a phase I study was undertaken. This is an ongoing, 52-week, open-label, parallel cohort study of relugolix in combination with abiraterone in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) [Part 1] and apalutamide in men with mCSPC or non-metastatic castration-resistant prostate cancer (nmCRPC) [Part 2]. Eligible patients treated with leuprolide acetate or degarelix with abiraterone or apalutamide prior to baseline, at which time they were transitioned to relugolix. Assessments included reporting of adverse events, clinical laboratory tests, vital sign measurements, electrocardiogram (ECG) parameters, and testosterone serum concentrations. In this interim report, patients completing ≥12 weeks were included. Overall, 15 men were enrolled in Part 1 and 10 in Part 2. Adverse events were mostly mild-to-moderate in intensity and were consistent with the known safety profiles of the individual medications. No transition (from prior ADT treatment)- or time-related trends in clinical laboratory tests, vital sign measurements, or ECG parameters were observed. Mean testosterone concentrations remained below castration levels. Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs. ClinicalTrials.gov identifier: NCT04666129.

470 Evaluation of cardiovascular risk factor control among people with diabetes in the community pharmacy setting – a cross sectional study

Abstract Introduction Diabetes affects almost 140,000 Irish people and the prevalence is increasing.(1) In Ireland there is no structured programme in place for community pharmacists to provide care to people with diabetes, outside of dispensing medications and supplying medical devices. Research shows that community pharmacists can provide advanced services to people with diabetes that improve glycaemic control, cardiovascular risk, and medication profile.(2) A pharmacist-led intervention among people with diabetes in the Irish community pharmacy setting may be beneficial in addressing these treatment goals. However, baseline data to support this is not available. Aim To assess the cardiovascular risk profile of people with diabetes attending community pharmacy in Ireland. Methods This was a cross-sectional study. Data collection took place in 10 pharmacies, identified by purposeful sampling, in four Irish counties, and was conducted by five pharmacy students. Data collection in each pharmacy lasted between five and six weeks and took place between July 2018 and October 2019. A target sample size was not set. Study participants were aged 18 years and older, with type 1 or type 2 diabetes, attending a participating pharmacy and to whom oral diabetes medicines, insulin or devices for monitoring glycaemic control were dispensed. A data collection form was designed for the study, based on the RxEACH study.(2) Participants were asked their demographics, medical history, and cardiovascular risk factors. Current medications were identified using dispensing software. Data were presented as mean±standard deviation or number (%). Data were analysed in SPSS v28. Results Data were available for 106 participants, 70 (66.0%) male, mean age 63.5±13.7 years. Of these, 90 (84.9%) had type 2 diabetes and 16 (15.1%) had type 1 diabetes. Hypertension and dyslipidaemia were reported by 60 (56.6%) and 59 (55.7%) participants, respectively. This was followed by family history of premature heart disease (N=40, 37.7%), coronary artery disease (N=10, 9.4%), and atrial fibrillation (N=9, 8.5%). Twenty-one participants (19.8%) were current smokers, 31 (29.2%) followed no specific diet, and 44 (41.5%) did not undertake exercise. Oral diabetes medication was prescribed to 85 (80.2%) participants and insulin to 29 (27.4%) participants. Antihypertensive medication was prescribed to 67 (63.2%), lipid-lowering therapy to 53 (50.0%) and an antiplatelet agent to 51 (48.1%) participants. Participants reported that they received education about diabetes medicines from their general practitioner (N=49, 46.2%), endocrinologist (N=21, 19.8%), diabetes nurse (N=28, 26.4%), dietician (N=3, 2.8%), pharmacist (N=17, 16.0%), other source (N=17, 16.0%). Twelve (11.3%) participants reported never receiving medication education. Conclusion Study limitations include being confined to a small number of pharmacies in a geographically limited area and that medical history was based on self-report. Strengths include the use of a robust method of collecting medication data. People with diabetes attending study pharmacies had high rates of behaviours associated with cardiovascular risk including smoking and lack of exercise. Fewer than one-in-six participants reported receiving diabetes medication education from their pharmacist. Pharmacist-led interventions to engage people with diabetes in discussing health behaviours and medication education should be developed and explored as potential future professional services delivered by Irish pharmacists.

Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI).

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student's paired two-sample t-tests and McNamar's tests were performed for continuous and categorical variables between time periods. The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7(12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic. In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

Patient preferences for anti-hyperglycaemic medication for type 2 diabetes mellitus in China: findings from a national survey

ObjectiveThis study aimed to investigate the preferences regarding risks, benefits and other treatment attributes of patients with type 2 diabetes mellitus (T2DM) in China when selecting a second-line anti-hyperglycaemic medicine.MethodsA...

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Real-World Treatment Patterns and Healthcare Resource Utilization in Patients Prescribed Benztropine: A Claims Analysis From 2017-2020

AbstractIntroductionWe sought to examine real-world treatment patterns and healthcare resource utilization (HCRU) for patients receiving an antipsychotic (AP) and subsequently prescribed benztropine.MethodsA retrospective analysis was conducted among patients with evidence of benztropine initiation using claims data from IQVIA’s New Data Warehouse from January 2017–March 2020. Patients were indexed on the date of first pharmacy claim for benztropine and had continuous enrollment in the 6 months prior (pre-index) and minimum 12 months post-index date, up to 24 months. Patients also had ≥1 pharmacy claim for an AP either pre-index or on the index date.ResultsA total of 112,542 patients were included; 59% were female with mean age of 46 years. The most common comorbidities were bipolar disorder (BD; 28.3%), schizophrenia (SCZ; 28.3%), and depression (26.3%). Over half of the cohort (54.1%) had ≥2 comorbid conditions. Nearly 20% of patients had ≥20 medications (median 10–14) and medications with anticholinergic (AC) properties were used by 87.9%. Approximately 80% of patients had mild AC burden at baseline (using AC burden calculator). The median number of benztropine prescription fills was 5 with treatment duration &lt;3 months in 44.3% of patients and &lt;6 months in 61.7%. All-cause mean healthcare costs in the 12-month cohort (24-month cohort) were $11,755 ($23,128), mean costs for pharmacy were $9,229 ($18,148), and mean costs for inpatient stays were $34,669 ($41,280). Emergency room (ER) visits occurred in 47.3% and physician office visits in 78.9% of the cohort. In patients with available inpatient 12-month data (n=33,717), inpatient stays occurred in 4.0% (13.3% when extrapolated to total cohort). In patients with 24-month data (n=73,836), ER visits occurred in 61% of the cohort and inpatient stays in 6.6% (21.9% when extrapolated to the total cohort). Multivariate analyses showed baseline SCZ was associated with a significantly increased risk of ER visit of 30% and inpatient stay of 50%. Similarly, substance abuse was associated with an increased risk of ER visit of 85% and inpatient stay of about 40%. Other significant associations with ER visits included falls/accidents at baseline (148% increased risk), abnormal movement disorders (38% increased risk), and orthostatic hypotension (38% increased risk).ConclusionsIn this real-world analysis of patients initiating benztropine, polypharmacy and AC burden were frequently observed. BD, SCZ, and depression were the most common comorbidities. Healthcare costs and HCRU were high for the entire cohort; inpatient stays contributed to high costs. Baseline SCZ, falls/accidents (ER only), and substance abuse were significantly associated with ER and inpatient admissions. The comorbidity and medication profiles of this cohort may have influenced the high healthcare costs and HCRU observed in the study.FundingNeurocrine Biosciences, Inc.

Pathophysiology and clinical management of hyperkalemia in chronic kidney disease.

Adaptive increases in kidney and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with chronic kidney disease (CKD) as long as the glomerular filtration rate (GFR) remains >15-20 mL/min. K+ balance is maintained by increased secretion per functioning nephron, which is mediated by elevated plasma K+ concentration, aldosterone, increased flow rate, and enhanced Na+-K+-ATPase activity. Fecal losses of potassium also increase in CKD. These mechanisms are effective in preventing hyperkalemia if urine output is in excess of 600 mL/day and the GFR exceeds 15 mL/min. Development of hyperkalemia with only mild to moderate reductions in GFR should prompt a search for intrinsic disease of the collecting duct, disturbances in mineralocorticoid activity, and/or decreased delivery of sodium to the distal nephron. The initial approach to treatment is to review the patient's medication profile and whenever possible discontinue drugs that impair kidney K+ excretion. Patients should be educated on sources of K+ in the diet and should be strongly encouraged to avoid the use of K+ containing salt substitutes as well as herbal remedies since herbs may be a hidden source of dietary K+. Effective diuretic therapy and correction of metabolic acidosis are effective strategies to minimize the potential for hyperkalemia. Discontinuation or use of submaximal doses of renin-angiotensin blockers should be discouraged given the cardiovascular protective effect these drugs provide. Potassium binding drugs can be useful to enable use of these drugs and potentially allow liberalization of the diet in CKD patients.

The Impact of Substantial Improvements in HbA1c and Weight Loss on the Medication Preferences of People with Type 2 Diabetes.

To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile. Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients' preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited. Participants (N=620) in the US(N=301) and UK(N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants' preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg). HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles.

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients.

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m2 ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m2 ), use of LEV (≥1year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m2 ), LEV use (≥1year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

Prevalence and Correlates of Polypharmacy, and Drug Utilization Pattern in a Semi-urban Population: Results from the Pars Cohort Study.

Although polypharmacy is considered a major predictor of irrational use of drugs, little is known about polypharmacy in developing regions. We aimed to indicate the prevalence and correlates of polypharmacy and to determine the medication profile at the population level in southern Iran. In this cross-sectional study, we analyzed data from participants of the Pars Cohort Study (PCS) (aged above 40 years, N=9269). Polypharmacy was defined as using five or more medications concurrently. A Poisson multivariable model was applied to estimate the adjusted prevalence ratios (APRs) of various risk factors. The Anatomical Therapeutic Chemical (ATC) classification system was used for classifying medications. Prevalence of polypharmacy was 10.4%, (95% CI: 9.75; 11.08) and it was higher among females (15.0%), older adults (age≥65 years) (16.0%), and individuals with more than two chronic conditions (31%). Being female, educated, married, and not having a low socio-economic class were independently associated with a higher likelihood of polypharmacy. The most prevalent medications among female participants were sex hormones and modulators of the genital system (58.4%), drugs for acid-related disorders (14.6%), and anti-anemic preparations (13.6%,). On the other hand, males were using acid-related disorders (14.6%), anti-inflammatory and anti-rheumatic products (7.8%), and beta-blocking agents (6.3%). The prevalence of polypharmacy in our sample was relatively low, especially among males. Cardiovascular drugs, acid suppressants, hormonal contraceptives, and anti-anemic preparations are drug classes with the highest contribution to polypharmacy.