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Aims Methods Results Conclusions Calcium channel blocker (CCB) overdose remains an important poisoning, with increasing availability of dihydropyridines. We aimed to compare the severity and treatment of CCB overdoses.We reviewed CCB overdoses presenting to two toxicology services from 2014 to 2023. We extracted prospectively collected data from a clinical database, including demographics, dose, co‐ingestants, complications, treatments and outcomes, to compare different CCBs.There were 236 overdoses; median age 55 years (interquartile range [IQR]: 41–65 years); 130 (55%) were females. Dihydropyridine overdoses increased significantly: median of nine cases annually (IQR: 8.8–12.3) during the study compared to a median of three cases annually (IQR: 1–4.3; P < 0.001) in the 10 years prior. The commonest agent was amlodipine (147), then lercanidipine (28), diltiazem (27), verapamil (23) and felodipine (11). Median defined daily dose ingested was higher for dihydropyridines, and cardiac co‐ingestants were common except verapamil. Median length of stay was 21 h (IQR: 13–43 h), which was similar except longer for diltiazem (median, 39 h). Fifty‐six patients (24%) were admitted to intensive care, more often for diltiazem (14; 52%) and verapamil (7; 30%). Dysrhythmias occurred in 19 patients (diltiazem [9], verapamil [8], amlodipine [2]), and included 13 junctional dysrhythmias. Hypotension occurred in 91 patients (39%), 62 (26%) received inotropes/vasopressors (adrenaline 32 [52%], noradrenaline 48 [77%]), 21 (9%) high‐dose insulin and 44 (19%) calcium. Adrenaline and high‐dose insulin were more commonly given in diltiazem and verapamil overdoses, compared to vasopressors in dihydropyridine overdoses. Acute kidney injury occurred in 39 patients. Seven (3%) patients died.Dihydropyridines were the commonest CCB overdoses, with amlodipine making up half. More severe toxicity occurred with diltiazem and verapamil. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus is widely used to treat pediatric nephrotic range proteinuria (NRP). Diltiazem, a CYP3A4/5 inhibitor, is often administered with tacrolimus, affecting its pharmacokinetic profile. The impact of this combination on tacrolimus exposure, particularly in CYP3A5*3 genetic polymorphism, remains unclear in pediatric NRP patients. This study aimed to evaluate the effects of diltiazem on tacrolimus pharmacokinetics, focusing on the CYP3A5*3 polymorphism. Methods: We conducted a retrospective clinical study involving pediatric NRP patients, divided into two groups: those receiving tacrolimus with diltiazem and those receiving tacrolimus alone. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. We compared daily dose-adjusted trough concentrations (C0/D) of tacrolimus in both the original and PSM cohorts. The influence of diltiazem on tacrolimus C0/D, stratified by CYP3A5*3 genetic polymorphism, was assessed in a self-controlled case series study. Results: Before PSM, the tacrolimus C0/D in patients taking diltiazem was significantly higher compared to those with tacrolimus alone (75.84 vs. 56.86 ng/mL per mg/kg, P = 0.034). This finding persisted after PSM (75.84 vs. 46.93 ng/mL per mg/kg, P= 0.028). In the self-controlled case study, tacrolimus C0/D elevated about twofold (75.84 vs. 34.76 ng/mL per mg/kg, P < 0.001) after diltiazem administration. CYP3A5 expressers (CYP3A5*1/*1 and *1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3) experienced a 1.8-fold and 1.3-fold increase in tacrolimus C0/D when combined with diltiazem, respectively. Conclusion: Diltiazem significantly increased tacrolimus C0/D, with CYP3A5*3 expressers showing higher elevations than non-expressers among pediatric NRP patients. These findings highlight the importance of personalized tacrolimus therapy based on CYP3A5*3 genotypes in pediatric patients taking diltiazem. [ABSTRACT FROM AUTHOR]

Background: Despite atrial fibrillation guideline recommendations, many patients with heart failure with reduced ejection fraction (EF) continue to receive IV diltiazem for acute rate control. Objective: Our institution recently implemented a clinical decision support system (CDSS)-based tool that recommends against the use of diltiazem in patients with an EF ≤ 40%. The objective of this study was to evaluate outcomes of adherence to the aforementioned CDSS-based tool. Methods: This multi-hospital, retrospective study assessed patients who triggered the CDSS alert and compared those who did and did not discontinue diltiazem. The primary outcome was the occurrence of clinical deterioration. The primary endpoint was compared utilizing a Fisher's Exact Test, and a multivariate logistic regression model was developed to confirm the results of the primary analysis. Results: A total of 246 patients were included in this study with 146 patients in the nonadherent group (received diltiazem) and 100 patients in the adherent group (did not receive diltiazem). There was a higher proportion of patients experiencing clinical deterioration in the alert nonadherence group (33% vs 21%, P = 0.044), including increased utilization of inotropes and vasopressors, and higher rate of transfer to ICU. Conclusion and Relevance: In patients with heart failure with reduced EF, diltiazem use after nonadherence to a CDSS alert resulted in an increased risk of clinical deterioration. This study highlights the need for improved provider adherence to diltiazem clinical decision support systems. [ABSTRACT FROM AUTHOR]

The main goal of cancer treatment is to ensure that the drug reaches the tumor tissue and to reduce the side effects of the drug. This study was conducted to synthesize a novel nanostructured lipid carrier modified with chitosan-folate to deliver diltiazem to cancer cell lines and to evaluate its anticancer effect. Dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectrometer (FTIR) methods were used to characterize the nanoparticles. The cytotoxicity effect on cancer cell lines variants was measured. Flow cytometry was used for cell cycle analysis, and reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the induction of apoptosis. The inflammatory effects were evaluated by molecular analysis, and the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, 2,2-Diphenyl-1-picrylhydrazyl, and Ferric reducing antioxidant power methods were used to measure the antioxidant power of the nanoparticles. The results reported the mean of the real and hydrodynamic diameter of the nanoparticles as 87.7 and 249 nm, respectively, and the encapsulation efficiency of diltiazem was reported to be 86.6%. The cytotoxicity results revealed that the breast cancer cells were more sensitive to treatment, with a median concentration of 33.5µg/ml. Additionally, the nanoparticle treatment led to the arrest of cells in the SubG1 phase while increasing the expression of caspases 3 and 9, which indicates the activation of the internal pathway of apoptosis. Additionally, the increase in the expression of interleukins 6 and 10 suggests an effect of the nanoparticles on inflammation. In addition, the ability to inhibit 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid and 2,2-Diphenyl-1-picrylhydrazyl free radicals with an average concentration of 577, which is more significant than 1000 µg/ml, and the ability of the nanoparticles to reduce iron ions confirmed the antioxidant effect of diltiazem-loaded nanostructured lipid carriers. These results suggest that the nanoparticles have an excellent potential to treat breast cancer.

Owing to its associated advantages such as the generation of two stereocenters in 100% maximum theoretical yield, mild reaction conditions and environmentally friendliness, ketoreductase (KRED)-catalyzed dynamic reductive kinetic resolution (DYRKR) is a versatile and appealing synthetic approach to access valuable chiral alcohols containing two or more stereocenters. Despite the considerable progress that has been made in this research field, previous studies mostly focused on ketone substrates with relatively simple structures. In the present study, ketoreductases YDR368w and YGL039w were identified through enzyme screening and applied to the KRED-catalyzed DYRKR of sterically hindered 2-aryl-1,5-benzothiazepin-3,4(2H,5H)-diones (1). Eleven structurally diverse chiral cis-(2S,3S)-2,3-dihydro-3-hydroxy-2-aryl-1,5-benzothiazepin-4(5H)-ones (cis-(2S,3S)-2), including the critical synthetic intermediates to the calcium channel blockers diltiazem and clentiazem, were prepared in 50–90% isolated yields with excellent stereoselectivities (all >20 : 1 dr and ≥99% ee). Finally, the successful execution of a gram scale synthesis and the demonstrated excellent recyclability of the immobilized ketoreductase (up to 20 cycles) both underscored the good application potential of the currently established DYRKR method. [ABSTRACT FROM AUTHOR]

Background: Fissure-in-Ano is a common condition of the anorectal region. Most of the time, it is managed non-surgically. There are various drugs used for the treatment of anal fissures. Calcium channel blockers are one of them that reduce the tone of sphincter muscles. The present study compares the efficacy of oral diltiazem and topical 2% diltiazem ointment in patients with chronic anal fissures. Methods: Patients were randomized into two groups. Group A (n = 25) received treatment in the form of oral diltiazem, while group B (n = 25) received treatment in the form of 2% (weight/volume) diltiazem ointment for local application in addition to other conservative methods like sitz bath and stool softeners. Outcomes in the form of success of treatment and complications were assessed. Statistical analysis was done using MedCalc software version 14.0. P value of < 0.05 was considered significant. Results: The mean age of patients was 32.00 ± 10.67 years in group A and 30.64 ± 9.53 years in group B. Pain relief was significantly better in group B than in group A at the end of the first week (P = 0.00018), but at the end of 6th week, no significant difference was observed. Fissure healing was more significant in group B than in group A after 6 weeks (P = 0.0152). Conclusion: Local diltiazem ointment is a better option than oral diltiazem for anal fissures with respect to better outcomes and lesser complications. [ABSTRACT FROM AUTHOR]

The main goal of cancer treatment is to ensure that the drug reaches the tumor tissue and to reduce the side effects of the drug. This study was conducted to synthesize a novel nanostructured lipid carrier modified with chitosan-folate to deliver diltiazem to cancer cell lines and to evaluate its anticancer effect. Dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectrometer (FTIR) methods were used to characterize the nanoparticles. The cytotoxicity effect on cancer cell lines variants was measured. Flow cytometry was used for cell cycle analysis, and reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the induction of apoptosis. The inflammatory effects were evaluated by molecular analysis, and the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid, 2,2-Diphenyl-1-picrylhydrazyl, and Ferric reducing antioxidant power methods were used to measure the antioxidant power of the nanoparticles. The results reported the mean of the real and hydrodynamic diameter of the nanoparticles as 87.7 and 249 nm, respectively, and the encapsulation efficiency of diltiazem was reported to be 86.6%. The cytotoxicity results revealed that the breast cancer cells were more sensitive to treatment, with a median concentration of 33.5µg/ml. Additionally, the nanoparticle treatment led to the arrest of cells in the SubG1 phase while increasing the expression of caspases 3 and 9, which indicates the activation of the internal pathway of apoptosis. Additionally, the increase in the expression of interleukins 6 and 10 suggests an effect of the nanoparticles on inflammation. In addition, the ability to inhibit 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid and 2,2-Diphenyl-1-picrylhydrazyl free radicals with an average concentration of 577, which is more significant than 1000 µg/ml, and the ability of the nanoparticles to reduce iron ions confirmed the antioxidant effect of diltiazem-loaded nanostructured lipid carriers. These results suggest that the nanoparticles have an excellent potential to treat breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Anal fissure, characterized by a painful ulcer in the anal canal, presents a significant medical challenge. While surgical approaches like lateral internal sphincterotomy (LIS) have been the gold standard for chronic anal fissures, they come with potential complications such as incontinence and abscess formation. In contrast, medical treatments, including topical glyceryl trinitrate and diltiazem, have emerged as alternatives, offering non-invasive options with potentially fewer complications. Method: In this retrospective study, we evaluated 136 patients treated for chronic anal fissures between June 2019 and December 2022 at Balikesir University Hospital, comparing surgical and medical interventions. The study encompassed demographic analysis, treatment modalities, complete recovery, recurrence rates, and side effects/complications. Statistical analyses, including logistic regression, were performed to assess the efficacy and risks associated with different treatments. Results: Our findings indicated a higher rate of complete recovery with surgical treatment (86.1%) compared to medical treatments (glyceryl trinitrate: 64.8%, diltiazem: 69.6%). However, no significant difference was observed in recurrence rates between treatment groups. Surgical intervention exhibited a higher incidence of complications such as incontinence and abscess formation, while medical treatments were associated with side effects like headache and gastrointestinal disturbances. Notably, diltiazem therapy showed outcomes comparable to other modalities, indicating its potential as an effective and safer alternative. Conclusion: Despite the favorable outcomes of surgical treatment, considerations of potential complications underscore the importance of tailored approaches. Prospective, randomized controlled trials with larger cohorts are warranted to further elucidate the efficacy and safety profiles of medical treatments in chronic anal fissures, facilitating informed decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objectives. Fissure in ano is one of the most common colorectal diseases seen by surgeons in daily practice. Currently medical management is the first line therapy for treating acute fissure in ano. Apart from general measures, various drugs like nitrates and calcium channel blockers are also used for topical application. Recently topical application of sucralfate and metronidazole are being advocated for in the same way, although there isn't much evidence for their effectiveness. In this study we have compared the efficacy of sucralfate (7% and Metronidazole (1%) ointment to the most commonly used diltiazem (2%) ointment for healing in acute fissure in ano and control of pain. Materials and methods. The present study was a randomized clinical trial with total 96 patients, 47 in the Sucralfate + Metronidazole group and 49 in the Diltiazem group. Both drugs were prescribed for 4 weeks in addition to general measures like sitz bath, laxatives and oral fluids. Patients were followed up at 2 and 4 weeks. Control of symptoms like pain, bleeding and healing of ulcers in both groups were assessed. Frequency or graphs were used for qualitative variables and Mean+/-SD for quantitative variables. Chi-square and t-test was applied for comparison of the two groups, and p-value

This cohort study assesses the association of diltiazem with risk of serious bleeding compared with metoprolol in older adults with atrial fibrillation receiving apixaban or rivaroxaban. Key Points: Question: Do patients with atrial fibrillation receiving apixaban or rivaroxaban and concurrently treated for ventricular rate control with diltiazem have greater risk of serious bleeding than those treated with metoprolol? Findings: In this cohort study of 204 155 patients aged 65 years or older, those treated with diltiazem had a significantly greater risk of serious bleeding compared with those treated with metoprolol. Meaning: Among older adults with atrial fibrillation receiving apixaban or rivaroxaban, treatment with diltiazem was associated with increased risk of serious bleeding compared with metoprolol. Importance: Diltiazem, a commonly prescribed ventricular rate–control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation. Objective: To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020. Patients were followed up to 365 days through November 30, 2020. Data were analyzed from August 2023 to February 2024. Exposures: Diltiazem and metoprolol. Main Outcomes and Measures: The primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding. Secondary outcomes were ischemic stroke or systemic embolism, major ischemic or hemorrhagic events (ischemic stroke, systemic embolism, intracranial or fatal extracranial bleeding, or death with recent evidence of bleeding), and death without recent evidence of bleeding. Hazard ratios (HRs) and rate differences (RDs) were adjusted for covariate differences with overlap weighting. Results: The study included 204 155 US Medicare beneficiaries, of whom 53 275 received diltiazem and 150 880 received metoprolol. Study patients (mean [SD] age, 76.9 [7.0] years; 52.7% female) had 90 927 person-years (PY) of follow-up (median, 120 [IQR, 59-281] days). Patients receiving diltiazem treatment had increased risk for the primary outcome (RD, 10.6 [95% CI, 7.0-14.2] per 1000 PY; HR, 1.21 [95% CI, 1.13-1.29]) and its components of bleeding-related hospitalization (RD, 8.2 [95% CI, 5.1-11.4] per 1000 PY; HR, 1.22 [95% CI, 1.13-1.31]) and death with recent evidence of bleeding (RD, 2.4 [95% CI, 0.6-4.2] per 1000 PY; HR, 1.19 [95% CI, 1.05-1.34]) compared with patients receiving metoprolol. Risk for the primary outcome with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 [95% CI, 10.2-20.1] per 1000 PY; HR, 1.29 [95% CI, 1.19-1.39]) was greater than that for lower doses (RD, 6.7 [95% CI, 2.0-11.4] per 1000 PY; HR, 1.13 [95% CI, 1.04-1.24]). For doses exceeding 120 mg/d, the risk of major ischemic or hemorrhagic events was increased (HR, 1.14 [95% CI, 1.02-1.27]). Neither dose group had significant changes in the risk for ischemic stroke or systemic embolism or death without recent evidence of bleeding. When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14 (95% CI, 1.02-1.26). Conclusions and Relevance: In Medicare patients with atrial fibrillation receiving apixaban or rivaroxaban, diltiazem was associated with greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (MI) is a common and severe cardiovascular emergency that requires immediate treatment. Angina pectoris, which typically signals myocardial ischaemia, can appear in MI cases with myriad causes aside from coronary artery disease. However, not all MI patients benefit from invasive revascularisation therapy. We herein report a case involving a 78-year-old female patient with a complex medical history, including non-ST-segment elevation MI and coronary artery bypass grafting, who experienced recurrent chest pain. Instead of a direct result of coronary artery disease, her chest pain was later found to be primarily induced by atrial fibrillation (AF). Consequently, we shifted the focus of management to effective rate control for the AF after careful evaluation and achieved a satisfactory result. This case highlights the successful identification and timely application of intensive heart rate control management in an MI case induced by AF. [ABSTRACT FROM AUTHOR]

Distal esophageal spasm is an uncommon esophageal motility disorder presenting with non-cardiac chest pain and dysphagia. The main goal of therapy is symptom relief with pharmacologic, endoscopic, and surgical therapies. Pharmacologic treatment is less invasive and is the preferred method of choice. The purpose of this study was to compare the effectiveness of diltiazem versus fluoxetine in the treatment of distal esophageal spasm. A total of 125 patients with distal esophageal spasm diagnosed using endoscopy, barium esophagogram, and manometry were evaluated. Patients were divided into diltiazem and fluoxetine groups and received a 2-month trial of diltiazem + omeprazole or fluoxetine + omeprazole, respectively. Of 125 patients, 55 were lost to follow up and 70 were eligible for final analysis. Clinical signs and symptoms were assessed before and after therapy using four validated questionnaires: Eckardt score, short form-36, heartburn score, and the hospital anxiety and depression scale. Both regimens significantly relieved symptoms (a decrease in mean Eckardt score of 2.57 and 3.18 for diltiazem and fluoxetine groups, respectively; and a decrease in mean heartburn score by 0.89 and 1.03 for diltiazem and fluoxetine groups, respectively). Patients' quality of life improved based on short form-36 (an increase in mean score of 2.37 and 3.95 for fluoxetine and diltiazem groups, respectively). There was no relationship between patients' improvement and severity of symptoms. Psychological findings based on the hospital anxiety and depression scale were inconsistent (a decrease in mean of 0.143 and 0.57 for fluoxetine and diltiazem groups, respectively; p > 0.05). Fluoxetine and diltiazem were effective for clinical symptom relief in patients with distal esophageal spasm, but were not promising for improving psychological symptoms. Neither regimen was superior in terms of efficacy. Consequently, it is key to consider side effects and comorbidities when choosing a therapy. [ABSTRACT FROM AUTHOR]

This study introduces a practical and cost‐effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one‐pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ‐dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t‐test and F‐test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of competitive flow and diltiazem on postoperative hemodynamics and long-term patency rate in patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective analysis was performed on the clinical records of 98 patients who underwent CABG at Qilu Hospital of Shandong University from March 2018 to September 2020. Among them, 47 patients who underwent CABG alone were assigned to control group, while 51 patients who received additional diltiazem were assigned to study group. The severity of coronary artery stenosis (CAS) was evaluated through preoperative coronary angiography, and bridge vessel flow compared between severe stenosis and non-severe stenosis groups. Changes in hemodynamic parameters between two groups were compared before surgery, as well as 12 and 24 h after surgery. Results: A significantly higher bridge vessel blood flow was found in severe stenosis group compared to non-severe stenosis group (p < 0.05). The CAS severity and bridge vessel blood flow revealed an inverse relationship (r = - 0.792, p < 0.001). At 12 and 24 h post-surgery, the study group exhibited significantly lower central venous pressure (CVP), heart rate (HR) and mean arterial pressure (MAP) than the control group (p < 0.05). There was no significant difference in adverse cardiovascular effects (ACEs), between the two groups after 12 months (p > 0.05). Similarly, there was no significant difference in graft patency rate, mild stenosis rate, severe stenosis rate, complete occlusion rate, and linear signs rate 12 months post-operation (p > 0.05). However, the patency rate was significantly higher in cases with severe stenosis (p < 0.05). Conclusion: Postoperative administration of diltiazem in patients undergoing CABG improves systemic hemodynamic parameters. However, competitive blood flow may potentially decrease the long-term patency rate of bridge vessels in patients. [ABSTRACT FROM AUTHOR]

BACKGROUND Enduring the disease and curing internal sphincter spasm while maintaining continence is the aim of treating the anal fissure. Although they can lead to issues like decreased anal continence, surgical techniques such as lateral internal sphincterotomy or manual anal dilatation have a positive healing impact. We wanted to study the effects of lateral internal sphincterotomy and the application of 2% diltiazem gel. METHODS At Government Vellore Medical College, 100 patients of both sexes, ages 20 to 60, who had recurrent symptoms of fissure in ano for longer than six weeks, participated in this two-year observational study. Patients were chosen at random for either surgery or diltiazem therapy. Patients who were chosen to get diltiazem therapy were told to implant the gel twice daily, up to a 1.5-2 cm length. Spinal anaesthesia was used for the internal sphincterotomy procedure. Post-surgery complications like haemorrhage and hematoma were noted. For a descriptive analysis, the results were tabulated. RESULTS 39% of the sample belonged to the 20-30 age group, and 31% to the 31-40 age group. 17% and 13% of those were between the ages of 41 and 50 and 51 and 60, respectively. 36% of people were female, and 64% of people were male. After four weeks, every patient in the internal sphincterotomy group had totally healed and was pain-free. After three months of follow-up, 10 (20%) patients in the diltiazem group reported having minor pain, while 39 (78%) reported being almost pain-free. Due to inadequate pain alleviation from diltiazem, four patients (8%) had internal sphincterotomies. Eight patients were lost to follow-up after receiving treatment with diltiazem gel, leaving 40 (80%) of the patients with fully healed fissures after 4-8 weeks. Out of the 50 patients who had an internal sphincterotomy, 45 (90%) fully recovered after 4 weeks, with six patients lost to follow-up. Both the internal sphincterotomy group and the diltiazem gel group reported no problems. CONCLUSION In treating chronic anal fissures, internal sphincterotomy works better than topical diltiazem. However, topical diltiazem is safe, simple to use, and has few side effects. It might be taken into consideration for people who are not surgical candidates or who refuse surgery. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic anal fissure is a common health problem related to high morbidity. The chemical option for treating chronic anal fissures is highly preferred. Methods: A clinical prospective comparative study was carried out in the General Surgery Outpatient Department in Rizgary Teaching Hospital, Erbil, KRG, during the period from January 2019 to December 2021,on a sample of 100 patients randomly recruited patients with chronic anal fissures divided into two groups with 50 participants each: the DTZ group, who received 2% diltiazem ointment, and the GTN group, who used 0.2% glyceryl trinitrate ointment twice daily for 6 consecutive weeks. The aim of the study is to compare the efficacy and effects of topical Diltiazem (DTZ) and topical glyceryl trinitrate (GTN) in the management of chronic anal fissures. Results: There was a highly significant association between fissure healing at the 4th week and patients treated with DTZ (P

In the article, the authors discuss the history and professional legacy of nursing certification in the U.S. Also cited are the potential benefits of certification like enhanced patient outcomes, improved job satisfaction, and reduced turnover and vacancy rates, and the efforts by groups like the American Nurses Association and the American Association of Critical-Care Nurses Certification Corp. in advancing certification programs.

Background: Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear. Methods: A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 test. Results: A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50–9.04 with I2 = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89–1.80 with I2 = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51–2.45 with I2 = 18%). Conclusion: While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs. [ABSTRACT FROM AUTHOR]

Background and objectives. Fissure in ano is one of the most common colorectal diseases seen by surgeons in daily practice. Currently medical management is the first line therapy for treating acute fissure in ano. Apart from general measures, various drugs like nitrates and calcium channel blockers are also used for topical application. Recently topical application of sucralfate and metronidazole are being advocated for in the same way, although there isn't much evidence for their effectiveness. In this study we have compared the efficacy of sucralfate (7% and Metronidazole (1%) ointment to the most commonly used diltiazem (2%) ointment for healing in acute fissure in ano and control of pain. Materials and methods. The present study was a randomized clinical trial with total 96 patients, 47 in the Sucralfate + Metronidazole group and 49 in the Diltiazem group. Both drugs were prescribed for 4 weeks in addition to general measures like sitz bath, laxatives and oral fluids. Patients were followed up at 2 and 4 weeks. Control of symptoms like pain, bleeding and healing of ulcers in both groups were assessed. Frequency or graphs were used for qualitative variables and Mean+/-SD for quantitative variables. Chi-square and t-test was applied for comparison of the two groups, and p-value <0.05 was taken for statistical significance. Results. Most patients were male and belonged to age group 30-50 years. Most patients in both groups improved on conservative treatment. The difference observed in key outcome parameters like control of pain, bleeding and healing of fissure in both groups weren't found to be statistically significant. Sucralfate and Metronidazole didn't have any incidence of adverse effects and was cheaper in price compared to diltiazem ointment. Conclusions. Sucralfate and Metronidazole was as effective as diltiazem in treating of acute fissure in ano and can be recommended if allergy and adverse reactions to diltiazem are encountered. [ABSTRACT FROM AUTHOR]

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Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600–mutant kinase approved for patients with BRAF‐mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug–drug interactions when co‐administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P‐gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50‐mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUCinf) and maximum plasma concentration (Cmax) geometric mean for encorafenib increased by 183% and 68.4%, respectively, when co‐administered with posaconazole. Apparent encorafenib clearance decreased from 26.0 to 9.2 L/h when coadministered with posaconazole, and plasma terminal half‐life (t½) of encorafenib increased from 4.3 to 7.3 h. The AUCinf and Cmax geometric mean for encorafenib increased by 83.0% and 44.7%, respectively, when co‐administered with diltiazem. Similarly, the apparent encorafenib clearance decreased from 29.0 to 16.0 L/h when co‐administered with diltiazem, and plasma t½ of encorafenib increased from 6.6 to 7.9 h. There were no deaths, serious adverse events (AEs), or patient discontinuations due to AEs in parts 1 or 2. The most frequently reported treatment‐related AEs were erythema (n = 14; 88%) and headache (n = 11; 69%) in part 1 and headache (n = 7; 44%) in part 2. The results of this study indicate that co‐administration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided. [ABSTRACT FROM AUTHOR]

BackgroundAtrial fibrillation is one of the most common arrhythmias. The main thrombotic complication of arterial fibrillation is ischemic stroke, but it can also cause acute renal infarction from embolization. The low incidence and nonspecific clinical manifestations of acute renal infarction make it difficult to diagnose, often leading to either delayed diagnosis or misdiagnosis. Due to its rarity, more efficient treatment guidelines are helpful for the management of acute renal infarction related to the thromboembolic complication of arterial fibrillation.Case reportsWe report a case of acute renal infarction due to underlying arterial fibrillation, where a novel interventional therapeutic method was used. A 66-year-old Chinese man with arterial fibrillation, not on anticoagulation due to the patient's preference, and coronary artery disease post-percutaneous coronary intervention to left anterior descending artery about 1 year ago, was currently on dual antiplatelet therapy. He suddenly developed intermittent and sharp left-sided abdominal pain and was found to have an acute left renal infarction on computed tomography scan. Angiogram showed acute occlusion of the left renal artery due to thromboembolism. For this patient, a combination method of local thrombus aspiration, angioplasty, and infusion of nitroglycerin and diltiazem were used, restoring blood flow to the left kidney. After recovery, the patient was discharged on aspirin, clopidogrel, and warfarin. At 6 months follow-up, there was no residual kidney dysfunction.ConclusionsAcute renal infarction from thromboembolism is a rare but serious complication of arterial fibrillation. More efficient and different options for intervention methods will benefit the treatment of this disease. Here, we report a combination therapeutic method that has not been used in acute renal infarction associated with arterial fibrillation, and which restored renal perfusion and prevented long-term kidney injury.

Ventricular arrhythmias following neurological injury have been attributed to sympathetic surge in subarachnoid hemorrhage and traumatic brain injury. Despite associated risks of bleeding and thrombosis, veno-arterial extracorporeal membrane oxygenation (ECMO) in critically ill, clinically unstable postoperative neurosurgical patients can be lifesaving. In the context of neurological injury and the neurosurgical population, the literature available regarding ECMO utilization is limited, especially in children. We report a case of successful ECMO utilization in a child with malignant ventricular tachycardia after decompressive craniectomy for refractory intracranial hypertension following evacuation of extensive subdural empyema. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem. [ABSTRACT FROM AUTHOR]

PurposePrevious studies evaluating ticagrelor drug-drug interactions have not differentiated intestinal versus systemic mechanisms, which we do here.MethodsUsing recently published methodologies from our laboratory to differentiate metabolic- from transporter-mediated drug-drug interactions, a critical evaluation of five published ticagrelor drug-drug interactions was carried out to investigate the purported clinical significance of enzymes and transporters in ticagrelor disposition.ResultsThe suggested CYP3A4 inhibitors, ketoconazole and diltiazem, displayed unchanged mean absorption time (MAT) and time of maximum concentration (Tmax) values as was expected, i.e., the interactions were mainly mediated by metabolic enzymes. The potential CYP3A4/P-gp inhibitor cyclosporine also showed an unchanged MAT value. Further analysis assuming there was no P-gp effect suggested that the increased AUC and unchanged t1/2 for ticagrelor after cyclosporine administration were attributed to the inhibition of intestinal CYP3A4 rather than P-gp. Rifampin, an inducer of CYP3As after multiple dosing, unexpectedly showed decreased MAT and Tmax values, which cannot be completely explained. In contrast, grapefruit juice, an intestinal CYP3A/P-gp/OATP inhibitor, significantly increased MAT and Tmax values for ticagrelor, which may be due to activation of P-gp or inhibition of OATPs expressed in intestine.ConclusionsThis study provides new insight into the role of transporter pathways in ticagrelor intestinal absorption by examining potential MAT and Tmax changes mediated by drug-drug interactions.

Abstract Background Atrial flutter with 1:1 conduction to the ventricles is a dangerous cardiac arrhythmia. Contemporary guidelines recommend atrioventricular nodal blocking agents should be co-administered with class 1C anti-arrhythmics, as prophylaxis against 1:1 flutter. No guidance is provided on the type or strength of atrioventricular nodal blockade required, and in practice, these agents are frequently prescribed at low dose, or even omitted, due to their side effect profile. Case presentation A 62 year old Caucasian man with a history of paroxysmal atrial fibrillation treated with flecainide, presented with atrial flutter with 1:1 conduction to the ventricles and was cardioverted. Diltiazem was added to prevent this complication and he again presented with atrial flutter with 1:1 conduction to the ventricles, despite prophylaxis with coadministration of diltiazem. Conclusions This case report demonstrates failure of diltiazem to prevent 1:1 flutter in a patient chronically treated with flecainide for paroxysmal atrial fibrillation.

Abstract Background Diltiazem stands out as one of the front-line drugs administered in the emergency department to achieve acute rate control in patients suffering from atrial fibrillation with rapid Ventricular Response. One of the cytochrome enzymes involved in the metabolism of diltiazem is cytochrome P450 2D6 (CYP2D6). Interindividual differences can act on drug metabolism and thus drug efficacy due to the genetic polymorphism induced by the CYP2D6 enzyme. This study explores the association between the efficacy of diltiazem and the genetic polymorphism of CYP2D6 in patients with atrial fibrillation with rapid ventricular response. Results 87 out of 93 individuals with ventricular rate > 120 beats/min constituted the patient cohort. The patients were administered 0.25 mg/kg diltiazem intravenously. As a second dose, 0.35 mg/kg diltiazem was administered to patients who reportedly did not receive adequate drug efficacy. Heart rate control was considered to be achieved in patients whose heart rate fell below 110 beats/min and did not rise above 110 beats/min for 2 h. CYP2D6 *2, *3, *4 and *10 represent allele variants and *1 represents wild type (wt) allele. Achieving rate control after one or two doses of diltiazem in normal allele (wt/wt) carriers proved significantly higher than wt/*2, wt/*4 and wt/*10 heterozygous variant carriers. No significant difference was noted in wt/*3 heterozygous variant carriers. Conclusion The presence of *2, *4 and *10 alleles was observed to significantly compromise the drug efficacy. *3 allele was found to bear no relation to the effect of diltiazem on achieving rate control.

Background: Endotracheal extubation is one of the frequently performed procedure in the practice of Anaesthesia. This study was done to observe the haemodynamic responses during tracheal extubation and to compare the efficacy of IV diltiazem 0.3 mg/kg wih IV Lidocaine 1 mg/kg versus 0.2 mg/kg and 0.1 mg /kg IV Diltiazem with 1mg/kg IV Lignocaine in attenuating the hemodynamic response to tracheal extubation. Methods: 120 patients aged 20 to 60 yrs, belonging to ASA I and II, normotensive were included in the study and they were randomly allocated into 3 groups of 40 each. • Group –I The patient who receive injection Diltiazem 0.1mg/kg and inj Lignocaine 1mg/kg i.v. (n=40) • Grade –II The patients who receive injection Diltiazem 0.2mg/kg and inj. Lignocaine 1mg/kg i.v. (n=40) • Group -III The patients who receive injection Diltiazem 0.3mg/kg and inj.Lignocaine 1mg/kg i.v. (n=40) 2 min before extubation. At the end of the surgery, heart rate (HR), systolic blood pressure (SBP) diastolic blood pressure (DBP) and mean arterial pressure [MAP] were recorded served as base line values. Results: After tracheal extubation, all the haemodynamic parameters increase from base line,0.3 mg/kg inj. Diltiazem along with 1mg/kg inj Lignocaine provide better haemodynamic stability when compared with 0.1 mg/kg and 0.2 mg/kg inj Diltiazem along with inj. Lignocaine 1mg/kg each. 0.2 mg/kg inj. Diltiazem along with 1mg/kg inj Lignocaine provide better haemodynamic stability when compared with 0.1 mg inj Diltiazem with inj. Lignocaine 1mg/kg. Conclusions: Based on the findings of our study, we concluded that combination effect of Inj. Lignocaine and Inj. Diltiazem, Attenuate the hemodynamic response to extubation. 0.3mg/kg Diltiazem with 1mg/kg Lignocaine is superior to 0.2mg/kg and 0.1 mg/kg Diltiazem with 1mg/kg Lignocaine in attenuating the hemodynamic response to extubation. 0.2mg/kg Diltiazem with 1mg/kg Lignocaine is superior to 0.1mg/kg Diltiazem with 1mg /kg lignocaine in attenuating the hemodynamic response to extubation. Further studies are required to evaluate the advantage, beneficial effect and safety of Diltiazem in comparison with other drugs when used for the purpose of attenuating the hemodynamic changes associated with extubation. [ABSTRACT FROM AUTHOR]