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Cureus Apr 2024Introduction Hypertension (HTN) is considered one of the most frequent life-threatening noncommunicable illnesses. Because HTN has a significant public health impact on...
Introduction Hypertension (HTN) is considered one of the most frequent life-threatening noncommunicable illnesses. Because HTN has a significant public health impact on cardiovascular health status and healthcare systems in India, it is critical to study Indian clinicians' approaches to HTN management. Methodology This was a cross-sectional, multicentric, non-interventional, and single-visit study that aimed to gather data from across India and examine sociodemographic characteristics and clinician treatment choices in the management of HTN in Indian individuals. As a result, building an information platform about HTN is critical to preventing and controlling this growing burden. Results A total of 5298 patients were recruited in the study from 1061 study centers across India. Among the study patients, 66.67% were females with a mean age of 53.95 ± 14.4, and 66.28% of hypertensive patients presented comorbidities. Among the known risk factors for HTN, 2227 (44.5%) were smokers, while 2587 (51.7%) had sedentary lifestyles. A family history of HTN in either one or both parents was seen in 1076 (21.50%) patients. In management, 40.40% of patients were on anti-hypertensive monotherapy. Amlodipine (41.8%) in monotherapy and amlodipine + metoprolol (32.34%) in combination therapy were the most commonly prescribed antihypertensive. Conclusion Management of HTN can be improved by imparting patient education and awareness about the need for medication compliance, lifestyle modifications, and regular follow-up clinic visits.
PubMed: 38699103
DOI: 10.7759/cureus.57435 -
Drugs - Real World Outcomes Sep 2023Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes...
BACKGROUND
Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes β-adrenergic receptor agonists such as mirabegron; however, mirabegron contains a label warning for cytochrome P450 (CYP) 2D6 inhibition, making coadministration with CYP2D6 substrates require monitoring and dose adjustment to avoid unintended increases in substrate concentration.
OBJECTIVE
To understand the codispensing patterns of mirabegron among patients using ten predefined CYP2D6 substrates with and before mirabegron dispensing.
METHODS
This retrospective claims database analysis used the IQVIA PharMetrics Plus Database to assess codispensing of mirabegron with ten predefined CYP2D6 substrate groups identified on the basis of medications most frequently prescribed in the United States, those with high susceptibility to CYP2D6 inhibition, and those with evidence for exposure-related toxicity. Patients had to be ≥ 18 years old before initiation of the CYP2D6 substrate episode that overlapped with mirabegron. The cohort entry period was November 2012 to September 2019, and the overall study period was 1 January 2011 to 30 September 2019. Comparisons of patient profiles at dispensing were made between time periods with and before mirabegron use in the same patient. Descriptive statistics were used to assess the number of exposure episodes, total duration of exposure, and median duration of exposure of CYP2D6 substrate dispensing with and before mirabegron.
RESULTS
CYP2D6 substrate exposure periods totaling ≥ 9000 person-months were available before overlapping exposure to mirabegron for all ten CYP2D6 substrate cohorts. Median codispensing duration for chronically administered CYP2D6 substrates was 62 (interquartile range [IQR] 91) days for citalopram/escitalopram, 71 (105) days for duloxetine/venlafaxine, and 75 (115) days for metoprolol/carvedilol; median codispensing duration for acutely administered CYP2D6 substrates was 15 (33) days for tramadol and 9 (18) days for hydrocodone.
CONCLUSIONS
In this claims database analysis, the dispensing patterns of CYP2D6 substrates with mirabegron displayed frequent overlapping of exposure. Thus, a need exists to better understand the outcomes experienced by patients with OAB who are at increased risk for drug‒drug interactions when taking multiple CYP2D6 substrates concurrently with a CYP2D6 inhibitor.
PubMed: 37219800
DOI: 10.1007/s40801-023-00370-6 -
Clinical Case Reports Sep 2023Ludwig's angina was first described in 1839 by German physician, Wilhelm Frederick Von Ludwig as a rapidly and fatal progressive gangrenous cellulitis and edema of the...
Ludwig's angina was first described in 1839 by German physician, Wilhelm Frederick Von Ludwig as a rapidly and fatal progressive gangrenous cellulitis and edema of the soft tissues of the neck and floor of the mouth with rapid spread to other places like anterior mediastinum. However, Type 2 acute myocardial infarction (MI) due to Ludwig's angina has not been documented. A 62-year-old male presented to the emergency department with visible anterior neck swelling for 1 week, which was preceded by a tooth arch 1 week prior, the patient presented with a high grade fevers, dysphonia, dysphagia, and facial swelling. No history of trauma. He reported in the past 24 h prior to evaluation, a steady progression of pain intensity with rapid progression and anterior neck skin erythema and swelling. The pain was exacerbated by rotation of the neck, tongue protrusion, and speaking. On examination, there was a visible anterior neck swelling measuring 10.0 × 3.0 cm in widest dimensions, exquisitely tender to palpation with a positive temperature gradient, skin hyperpigmentation and firm in consistency, no crepitus, fluctuance, or induration. Tongue appeared elevated with sublingual edema and pooling of secretions. No stridor. A chest and neck ultrasound scan revealed an extensive abscisic mass from the submandibular, neck, sternal notch, and right clavicular region with the largest pockets measuring 2.11 × 0.8 cm, 2.03 × 0.62 cm, 1.50 × 1.1 cm, with noted submandibular, subclavicular and deep and superficial cervical lymph nodes, the largest measuring 1.23 × 1.63 cm in dimensions. A neck-CT scan with contrast revealed a pronounced subcutaneous tissue localized collection extending to both submandibular spaces measuring about 5.5 × 12.5 × 9.5 cm with mural enhancement. The upper chest cuts showed moderate pleural effusions and a paracardial hypodense well-defined lesion measuring 7.5 × 2.5 cm with mild pericardial effusion. The patient was referred to the ear, neck and throat, ENT surgeon for urgent drainage of the abscess, which was done successfully and about 300 mL of hemorrhagic pus was drained. Then transferred to highly dependent unit, (HDU) for IV antibiotic administration and vital observations, prior to that electrocardiogram, ECG showed a normal sinus rhythm. The following day in HDU, the patient started experiencing a chest pain of sudden onset radiating to the upper jaws, left forearm and throbbing in nature, palpitations and started becoming diaphoretic. Blood pressure was 150/70 mmgh and pulse of 120 bpm. ECG readings demonstrated ST-elevation, at lead 11, V2, and V3, cardiac Troponin I and CK-MB were elevated 10.0 ng/mL, (<0.4 ng/mL) and 150.0 IU/L, (5-25 IU/L) respectively. The patient was started on medications to relief acute ischemic pain these included, sublingual nitroglycerin 0.6 mg, morphine 5 mg intravenous slowly, antithrombotic, and beta-adrenergic blockade. He was kept in HDU later with heparin 80 U/kg bolus and 8 U/kg continuous infusion and was taken for coronary angiogram which demonstrated no any coronary artery occlusion. The patient later on started to register improvement and later discharged on medications for follow-up. On follow-up, the subsequent ECG showed persistent atrial fibrillation and patient was discharged on P2Y12 inhibitor, clopidogrel, 75 mg, and beta-blocker, metoprolol 50 mg. Over the past three decades, mortality rates for acute MI have increased significantly, One common subtype, type 2 MI is noted and driven by a myocardial oxygen supply and demand mismatch in the absence of coronary thrombosis. T2MI can occur with or without obstructive coronary disease like in this patients with angiographically normal coronary arteries. T2MI is increasingly recognized because of various septic pathophyisologies that cause increased myocardia oxygen demand. Evidence of myocardial ischemia especially those with sepsis are likely to develop myocardial injury. T2MI is frequent and explains a significant increase in clinical practice. A consensus is needed about how the diagnosis is established, to facilitate evidence-based therapies geared toward improving outcomes.
PubMed: 37636883
DOI: 10.1002/ccr3.7832 -
Molecules (Basel, Switzerland) Feb 2024The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for...
Design of Experimental Approach for Development of Rapid High Performance Liquid Chromatographic Process for Simultaneous Estimation of Metoprolol, Telmisartan, and Amlodipine from Formulation: Greenness and Whiteness Evaluation.
The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10-200 µg/mL for MET and TEL and 5-50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach.
Topics: Humans; Amlodipine; Telmisartan; Metoprolol; Chromatography, High Pressure Liquid; Leukemia, Myeloid, Acute
PubMed: 38474605
DOI: 10.3390/molecules29051087 -
RSC Advances Oct 2023This article presents a solid-phase extraction method combined with a spectrofluorometric method for the extraction/pre-concentration and determination of metoprolol...
This article presents a solid-phase extraction method combined with a spectrofluorometric method for the extraction/pre-concentration and determination of metoprolol (MET) in exhaled breath condensate. The extraction sorbent is an agarose aerogel nanocomposite grafted with graphene oxide (GO) FeO. The size and morphology of the nanosorbent were characterized X-ray crystallography, scanning electron microscopy, Fourier-transform infrared spectrometry, and Brunauer-Emmett-Teller analysis. Factors affecting the extraction/determination of MET were optimized using the one-at-a-time method. Under optimized experimental conditions, the calibration graph was linear in the range of 0.005 to 2.0 μg mL with a detection limit of 0.001 μg mL. The method was successfully applied for the determination of MET in biological samples taken from patients receiving MET.
PubMed: 37860171
DOI: 10.1039/d3ra03883a -
Trials Jan 2024Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial... (Randomized Controlled Trial)
Randomized Controlled Trial
Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial.
BACKGROUND
Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown.
METHODS/DESIGN
A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model.
DISCUSSION
This statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203 .
Topics: Humans; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Double-Blind Method; Drug Combinations; Hypertension; Irbesartan; Treatment Outcome
PubMed: 38218924
DOI: 10.1186/s13063-023-07803-1 -
Cureus Dec 2023A 56-year-old female presented with a diagnosis of iron deficiency anemia over three years prior (on oral iron supplementation) and presented with altered mental status....
A 56-year-old female presented with a diagnosis of iron deficiency anemia over three years prior (on oral iron supplementation) and presented with altered mental status. She was admitted to the Coronary Care Unit for troponinemia and T-wave inversions. Two-dimensional echocardiography revealed hypokinesia of the left ventricle (LV) anterior wall with reduced ejection fraction. The patient was stabilized on metoprolol and heparin infusions, but heparin was discontinued after iron studies revealed overload (iron: 159 ug/dL, 100% saturation, ferritin: 1480 ng/mL). Cardiac MRI revealed mixed concentric-eccentric LV hypertrophy, raising concern for severe iron overload. Mutation analysis of the (homeostatic iron regulator) gene responsible for hereditary hemochromatosis was negative for a homozygous mutation. Hematology was consulted to establish outpatient follow-up and consider treatments for the acquired hemochromatosis. Acquired hemochromatosis typically occurs in the setting of multiple blood product transfusions. Oral supplementation is typically mitigated by limited bioavailability. Follow-up was needed to track the patient's iron deficiency anemia and identify resolution and potential toxicity. Further research into predisposing factors for hemochromatosis in patients on oral supplementation without mutations is indicated.
PubMed: 38186413
DOI: 10.7759/cureus.50166 -
Cell Death & Disease Feb 2024Phosphodiesterase 2A (Pde2A) is a dual-specific PDE that breaks down both cAMP and cGMP cyclic nucleotides. We recently highlighted a direct relationship between Pde2A...
Phosphodiesterase 2A (Pde2A) is a dual-specific PDE that breaks down both cAMP and cGMP cyclic nucleotides. We recently highlighted a direct relationship between Pde2A impairment, a consequent increase of cAMP, and the appearance of mouse congenital heart defects (CHDs). Here we aimed to characterize the pathways involved in the development of CHDs and in their prevention by pharmacological approaches targeting cAMP and cGMP signaling. Transcriptome analysis revealed a modulation of more than 500 genes affecting biological processes involved in the immune system, cardiomyocyte development and contractility, angiogenesis, transcription, and oxidative stress in hearts from Pde2A embryos. Metoprolol and H89 pharmacological administration prevented heart dilatation and hypertabeculation in Pde2A embryos. Metoprolol was also able to partially impede heart septum defect and oxidative stress at tissue and molecular levels. Amelioration of cardiac defects was also observed by using the antioxidant NAC, indicating oxidative stress as one of the molecular mechanisms underpinning the CHDs. In addition, Sildenafil treatment recovered cardiac defects suggesting the requirement of cAMP/cGMP nucleotides balance for the correct heart development.
Topics: Mice; Animals; Cyclic Nucleotide Phosphodiesterases, Type 2; Metoprolol; Signal Transduction; Cyclic GMP; Heart Defects, Congenital; Oxidative Stress
PubMed: 38395995
DOI: 10.1038/s41419-024-06549-1 -
Journal of Healthcare Engineering 2023[This retracts the article DOI: 10.1155/2022/7340992.].
[This retracts the article DOI: 10.1155/2022/7340992.].
PubMed: 37829361
DOI: 10.1155/2023/9790631 -
Critical Care and Resuscitation :... Jun 2022Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label"....
Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label". Critical illness makes seeking consent for off-label medication use impractical. We aimed to characterise the extent of off-label medication use in a tertiary medical- surgical intensive care unit (ICU) by auditing the electronic health records of all patients admitted over a one-month period. We found 25.4% of 2292 prescriptions made for 142 patients were off-label. Eighty-one (37.2%) of the total of 218 different prescribed medications were used at least once for an off-label indication. Medications commonly prescribed off-label included antacids (pantoprazole, esomeprazole), analgesics (fentanyl, morphine, ketamine, pregabalin), anticonvulsants (levetiracetam), antibiotics (cefazolin, erythromycin), antipsychotics (quetiapine, haloperidol), and cardiovascular agents (metoprolol, clonidine). Nearly all patients (88.0%) received at least one off-label medication during their ICU stay. Most off- label medications were used for conventional (albeit not licensed) reasons, but nine out of 81 (11.1%) were not; for example, acetazolamide for hypertension, aminophylline for oliguria, and dexmedetomidine for seizures. Recognising the challenges of formally registering an indication with the Therapeutic Goods Administration, but also the value of reducing the incidence of medications used for potentially incorrect purposes, we suggest guideline endorsement of what constitutes standard critical care practice as an alternative to regulatory control.
PubMed: 38045597
DOI: 10.51893/2022.2.OA8