Loperamide-Induced Torsades de Pointes.

Loperamide is a readily available, over-the-counter medication used to treat diarrhea. At therapeutic doses, loperamide exerts its effects mainly on the intestinal opioid receptors with minimal psychoactive effects; however, at supratherapeutic doses, it reaches central opioid receptors. With tighter regulations on opioid prescriptions, loperamide has emerged as a popular drug of abuse among opioid users. At supratherapeutic doses, loperamide can cause severe cardiac toxicity, resulting in wide QRS rhythms, severe bradycardia, prolonged QTc, polymorphic ventricular tachycardia, and cardiac arrest. We present the case of a 27-year-old female with a history of heroin abuse who suffered torsades de pointes resulting in cardiac arrest in the setting of a loperamide overdose.

An interesting case series of ticagrelor induced long QTc.

This case series explores three patients who underwent percutaneous coronary intervention (PCI) and experienced prolonged QT intervals under treatment with Ticagrelor. The first case was a female who presented with chest pain and received a Xience stent. The second case involved a male patient who received two Xience stents. The third case was that of a male patient with LAD stenosis. All three patients received Ticagrelor and exhibited prolonged QTc intervals on their electrocardiograms (ECGs), which was resolved after switching to Clopidogrel. Thus far, the potential impact of Ticagrelor on QT prolongation has not been adequately addressed in the literature. It is hypothesized that Ticagrelor can block adenosine uptake by red blood cells, which may explain QTc prolongation. The results of this case series indicate that Ticagrelor may prolong QTc intervals. Consequently, it is imperative that clinicians are aware of this previously unlisted side effect and that patients are closely monitored while seeking alternative medications to manage the condition.

A Comparative Analysis of the Effects of Haloperidol and Dexmedetomidine on QTc Interval Prolongation during Delirium Treatment in Intensive Care Units.

Background: Haloperidol and dexmedetomidine are used to treat delirium in the intensive care unit (ICU). The effects of these drugs on the corrected QT (QTc) interval have not been compared before. It was aimed to compare the effects of haloperidol and dexmedetomidine treatment on QTc intervals in patients who developed delirium during ICU follow-up. Method: The study is single-center, randomized, and prospective. Half of the patients diagnosed with delirium in the ICU were treated with haloperidol and the other half with dexmedetomidine. The QTc interval was measured in the treatment groups before and after drug treatment. The study's primary endpoints were maximal QT and QTc interval changes after drug administration. Results: 90 patients were included in the study, the mean age was 75.2±12.9 years, and half were women. The mean time to delirium was 142+173.8 hours, and 53.3% of the patients died during their ICU follow-up. The most common reason for hospitalization in the ICU was sepsis (%37.8.). There was no significant change in QT and QTc interval after dexmedetomidine treatment (QT: 360.5±81.7, 352.0±67.0, p= 0.491; QTc: 409.4±63.1, 409.8±49.7, p=0.974). There was a significant increase in both QT and QTc interval after haloperidol treatment (QT: 363.2±51.1, 384.6±59.2, p=0.028; QTc: 409.4±50.9, 427.3±45.9, p=0.020). Conclusions: Based on the results obtained from the study, it can be concluded that the administration of haloperidol was associated with a significant increase in QT and QTc interval. In contrast, the administration of dexmedetomidine did not cause a significant change in QT and QTc interval.

Hydroxychloroquine-azithromycin, doubase C, and QTc prolongation in congolese patients with COVID-19: Myth or reality?

BACKGROUND: QTc interval prolongation with an increased risk of torsade de pointes (Tsd) has been described in coronavirus disease 2019 (COVID-19) patients treated with hydroxychloroquine (HCQ) and azithromycin (AZI) in Western countries. In the DR Congo, few studies have evaluated the safety of this association or proposed new molecules. AIM: To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C (new molecule). METHODS: In present randomized clinical trial, we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C. Electrocardiogram (ECG) changes on day 14 of randomization were determined based on pretreatment tracing. Prolonged QTc was defined as ≥ 500 ms on day 14 or an increase of ≥ 80 ms compared to pretreatment tracing. Patients with cardiac disease, those undergoing other treatments likely to prolong QTc, and those with disturbed ECG tracings were excluded from the study. RESULTS: The study included 258 patients (mean age 41 ± 15 years; 52% men; 3.4% diabetics, 11.1% hypertensive). Mild and moderate COVID-19 were found in 93.5% and 6.5% of patients, respectively. At baseline, all patients had normal sinus rhythm, a mean heart rate 78 ± 13/min, mean PR space 170 ± 28 ms, mean QRS 76 ± 13 ms, and mean QTc 405 ± 30 ms. No complaints suggesting cardiac involvement were reported during or after treatment. Only four patients (1.5%) experienced QTc interval prolongation beyond 500 ms. Similarly, only five patients (1.9%) had an increase in the QTc interval of more than 80 ms. QTc prolongation was more significant in younger patients, those with high viral load at baseline, and those receiving HCQ-AZI (P < 0.05). None of the patients developed Tsd. CONCLUSION: QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C. The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.

Safety of outpatient commencement of sotalol.

Background: Inpatient monitoring is recommended for sotalol initiation. Objective: The purpose of this study was to assess the safety of outpatient sotalol commencement. Methods: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated. Results: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation (P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy. Conclusion: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol.

Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis, particularly severe ICI-associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis. METHODS: Clinical and electrocardiographic data of 73 cancer patients with ICI-associated myocarditis were retrospectively collected. The severity of ICI-associated myocarditis was graded using the NCCN guidelines for managing immunotherapy-related toxicities. Myocarditis grades 1-2 and grades 3-4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis. RESULTS: Among the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT-proBNP level was associated with severe myocarditis. CONCLUSIONS: ECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI-associated myocarditis.

Comparison of electrocardiogram and blood pressure recording methods in non-rodent toxicology studies: A retrospective analysis.

Our study retrospectively examines 51 non-rodent general toxicology studies conducted over the past 8 years to ascertain the influence of recording methodologies on baseline cardiovascular (CV) parameters and statistical sensitivity. Specifically, our work aims to evaluate the frequency of cardiovascular parameter recording categorized by therapeutic modality and study type, to assess the variability in these parameters based on measurement techniques, and to determine the sample sizes needed for detecting relevant changes in heart rate (HR), blood pressure (BP), and QTc interval in non-human primate (NHP) studies. Results indicate that electrocardiogram (ECG) measurements in dogs and NHP were recorded in 63% of studies, combined with BP recording in 18% of studies, while BP was never recorded alone. Trend analysis reveals a decline in the utilisation of restraint-based methods for ECG measurements post-2017, to the benefit of telemetry-based recordings, particularly Jacketed External Telemetry (JET). There was a marked difference in baseline values, with restraint-based methods showing significantly higher HR and QTc values compared to JET, likely linked to animal stress. Further analysis suggests an unrealistic and unethical sample size requirement in NHP studies for detecting biologically meaningful CV parameter changes using restraint-based methods, while JET methods necessitate significantly smaller sample sizes. This retrospective study indicates a notable shift from snapshots short-duration, restraint-based methods towards telemetry approaches over the recent years, especially with an increased usage of implanted telemetry. The transition contributes to potential consensus within industry or regulatory frameworks for optimal practices in assessing ECG, HR, and BP in general toxicology studies.

Prevalence, Outcomes, and Predictors of Prolonged Corrected QT Interval in Hydroxychloroquine-Naïve Hospitalized COVID-19 Patients.

The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86; P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000; P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality.

Case report: Phosphoinositide 3-kinase inhibitor with fulvestrant in a patient with ER+/HER2- metastatic breast carcinoma induced fatal arrhythmias: a preventable event?

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.

Characterization of ascending dose canine telemetry model supports its use in E14/S7B QT integrated risk assessments.

INTRODUCTION: Nonclinical evaluation of the cardiovascular effects of novel chemical or biological entities (NCE, NBEs) is crucial for supporting first-in-human clinical trials. One important aspect of these evaluations is the assessment of potential QT/QTc prolongation risk, as drug-induced QT prolongation can have catastrophic effects. The recent publication of E14/S7B Q&As allows for the situational incorporation of nonclinical QTc data as part of an integrated risk assessment for a Thorough QT (TQT) waiver application provided certain best practice criteria are met. Recent publications provided detailed characterization of nonclinical QTc telemetry data collected from the commonly used Latin square study design. METHODS: To understand whether data from alternate telemetry study designs were sufficient to serve as part of the E14/S7B integrated risk assessment, we report the performance and translational sensitivity to identify clinical risk of QTc prolongation risk for an ascending dose telemetry design. RESULTS: The data demonstrated low variability in QTci interval within animals from day to day, indicating a well-controlled study environment and limited concern for uncontrolled effects across dosing days. Historical study variances of the ascending dose design with n = 4 subjects, measured by least significant difference (LSD) and root mean square error (RMSE) values, were low enough to detect a + 10 ms QTci interval change, and the median minimum detectable difference (MDD) for QTci interval changes was <10 ms. Furthermore, concentration-QTci (C-QTci) assessments to determine +10 ms QTci increases for known hERG inhibitors were comparable to clinical CC values listed in the E14/S7B training materials, supporting the use of the ascending dose design in an E14/S7B integrated risk assessment. DISCUSSION: These findings suggest that the ascending dose design can be a valuable tool in nonclinical evaluation of QT/QTc prolongation risk and the support of TQT waiver applications.

A simple accurate method for concentration-QTc analysis in preclinical animal models.

INTRODUCTION: In preclinical cardiovascular safety pharmacology studies, statistical analysis of the rate corrected QT interval (QTc) is the focus for predicting QTc interval changes in the clinic. Modeling of a concentration/QTc relationship, common clinically, is limited due to minimal pharmacokinetic (PK) data in nonclinical testing. It is possible, however, to relate the average drug plasma concentration from sparse PK samples over specific times to the mean corrected QTc. We hypothesize that averaging drug plasma concentration and the QTc-rate relationship over time provides a simple, accurate concentration-QTc relationship bridging statistical and concentration/QTc modeling. METHODS: Cardiovascular telemetry studies were conducted in non-human primates (NHP; n = 48) and canines (n = 8). Pharmacokinetic samples were collected on separate study days in both species. Average plasma concentrations for specific intervals (CAverage0-X) were calculated for moxifloxacin in canines and NHP using times corresponding to super-intervals for the QTc data statistical analysis. The QTc effect was calculated for each super-interval using a linear regression correction incorporating QT and HR data from the whole super-interval. The concentration QTc effects were then modeled. RESULTS: In NHP, a 10.9 ± 0.06 ms (mean ± 95% CI) change in QTc was detected at approximately 1.5× the moxifloxacin plasma concentration that causes a 10 ms QTc change in humans, based on a 0-24 h super-interval. When simulating a drug without QT effects, mock, no effect on QTc was detected at up to 3× the clinical concentration. Similarly, in canines, a 16.6 ± 0.1 ms change was detected at 1.7× critical clinical moxifloxacin concentration, and a 0.04 ± 0.1 ms change was seen for mock. CONCLUSIONS: While simultaneous PK and QTc data points are preferred, practical constraints and the need for QTc averaging did not prevent concentration-QTc analyses. Utilizing a 0-24 h super-interval method illustrates a simple and effective method to address cardiovascular questions when preclinical drug exposures exceed clinical concentrations.

Optimized J to T peak and T peak to T end measurements in nonclinical species administered moxifloxacin and amiodarone.

INTRODUCTION: Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval. Recent clinical reports suggest that partitioning the QT interval into early (J to T peak; JTp) and late repolarization (T peak to T end; TpTe) components may be valuable for distinguishing low-risk mixed ion channel blockers (hERG plus calcium and/or late sodium currents) from high-risk pure hERG channel blockers. This strategy, if true for nonclinical animal models, could be used to de-risk QT prolonging compounds earlier in the drug development process. METHODS: To explore this, we investigated JTp and TpTe in ECG data collected from telemetered dogs and/or monkeys administered moxifloxacin or amiodarone at doses targeting relevant clinical exposures. An optimized placement of the Tpeak fiducial mark was utilized, and all intervals were corrected for heart rate (QTc, JTpc, TpTec). RESULTS: Increases in QTc and JTpc intervals with administration of the pure hERG blocker moxifloxacin and an initial QTc and JTpc shortening followed by prolongation with the mixed ion channel blocker amiodarone were detected as expected, aligning with clinical data. However, anticipated increases in TpTec by both standard agents were not detected. DISCUSSION: The inability to detect changes in TpTec reduces the utility of these subintervals for prediction of arrhythmias using continuous single­lead ECGs collected from freely moving dogs and monkeys.

Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions.

BACKGROUND: Determination of a drug's potency in blocking the hERG channel is an established safety pharmacology study. Best practice guidelines have been published for reliable assessment of hERG potency. In addition, a set of plasma concentration and plasma protein binding fraction data were provided as denominators for margin calculations. The aims of the current analysis were five-fold: provide data allowing creation of consistent denominators for the hERG margin distributions of the key reference agents, explore the variation in hERG margins within and across laboratories, provide a hERG margin to 10 ms QTc prolongation based on several newer studies, provide information to use these analyses for reference purposes, and provide recommended hERG margin 'cut-off' values. METHODS: The analyses used 12 hERG IC50 'best practice' data sets (for the 3 reference agents). A group of 5 data sets came from a single laboratory. The other 7 data sets were collected by 6 different laboratories. RESULTS: The denominator exposure distributions were consistent with the ICH E14/S7B Training Materials. The inter-occasion and inter-laboratory variability in hERG IC50 values were comparable. Inter-drug differences were most important in determining the pooled margin variability. The combined data provided a robust hERG margin reference based on best practice guidelines and consistent exposure denominators. The sensitivity of hERG margin thresholds were consistent with the sensitivity described over the course of the last two decades. CONCLUSION: The current data provide further insight into the sensitivity of the 30-fold hERG margin 'cut-off' used for two decades. Using similar hERG assessments and these analyses, a future researcher can use a hERG margin threshold to support a negative QTc integrated risk assessment.

Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment.

BACKGROUND: Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD. METHODS: This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included. RESULTS: The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9-25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3-38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study. CONCLUSION: CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Early Screening for Long QT Syndrome and Cardiac Anomalies in Infants: A Comprehensive Study.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20-40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Two Cases of Symptomatic Familial Hypocalciuric Hypercalcemia: Treatment Response to Calcimimetic Therapy.

Familial hypocalciuric hypercalcemia (FHH) is marked by mild to moderate hypercalcemia, normal-elevated serum PTH levels, and relative hypocalciuria. Cinacalcet, a calcimimetic therapy, has been reported to reduce symptom burden and serum calcium levels in FHH. We report 2 adult males with chronic hypercalcemia, with initial concerns for primary hyperparathyroidism. Urine calcium screening and genetic testing confirmed FHH in both patients. Shortened QTc normalized while on cinacalcet in the first patient and reductions in serum calcium and PTH levels without symptomatic hypercalcemia were noted in the second patient. Calcimimetic therapy can potentially be offered to FHH patients, particularly those with hypercalcemia symptoms, serum calcium levels >1 mg/dL (0.25 mmol/L) above normal or at risk of cardiac arrhythmias. Cinacalcet treatment was overall well tolerated and significantly reduced serum calcium and PTH levels in 2 adult FHH patients over time. Calcimimetic therapy has shown promise in managing persistent hypercalcemia and potential adverse events in FHH patients. Potential barriers include indefinite treatment, cost, and possible adverse effects.

QTc interval changes among patients on psychotropic medications: A prospective observational study.

Background: Psychotropic medications are commonly prescribed for the treatment of psychiatric disorders. Various studies have reported QT interval (QTc) prolongation with the use of psychotropics. However, some studies have found no significant risk of QTc changes with these medications. Aim: To assess the effect of psychotropics on QTc in drug-naive psychiatric patients. Materials and Methods: Our study was a prospective observational study, conducted at a tertiary care hospital. Patients aged 18-45 years, drug-naïve, with no medical comorbidity or substance use history, were recruited for the study. ECG to assess QTc was recorded at baseline, second and fourth week after the starting of psychotropic medications. Results: N=8 (4%) patients had QTc prolongation at baseline and were excluded. No clinically significant QTc prolongation was noticed, after 2 weeks and 4 weeks of treatment with any of the psychotropic medications. However, among patients on escitalopram, a significant effect on QTc was noted (P = 0.001) as compared to those on sertraline, risperidone, and olanzapine (P > 0.05). Conclusion: The short-term risk of QTc prolongation with the use of newer psychotropics at optimal doses appears low among young patients with normal baseline QTc and no significant medical or substance use comorbidity.

Determining QTc in acute care settings: What we (don't) know.

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