Prescribed Combination Therapy Research Articles

Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019-2022)

Arterial hypertension (AH) remains the leading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with AH who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all quidelines for the management of AH have recently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness and rationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach to prescribing combinations of specific groups of AHD in different clinical situations. Analyze the real ongoing antihypertensive therapy, including the PCT; international nonproprietary names of drugs and their dosages in RCP; compliance of therapy with clinical recommendations; changing trends in the PCT. An analysis was carried out of the data from the register of AH, the compliance of treatment in different clinical groups of patients and the achievement of BP and low-density lipoprotein cholesterol targets in the sample of 2019-2022 (n=5012). The prescription of AHD and achievement of targets values were assessed in accordance with current clinical guidelines for the management of AH and hypercholesterolemia. Data from 2010 (n=7782) and 2020 (n=3061) were analyzed to assess the dynamics of prescription of monotherapy and PCT. The greatest increase in the number of AHD was observed in patients with hypertension in combination with coronary heart disease, heart failure, and atrial fibrillation. In a small group of patients with hypertension without other CVDs, the recommended combinations of AHD were not prescribed; preference was given to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-adrenoblocker (β-AB). PCT mainly differed from the recommended combinations by the wider use of drugs from the β-AB group. The PCT of recommended drugs was highest in patients with hypertension and coronary artery disease - more than 90%, hypertension and heart failure in 56.2%, hypertension and atrial fibrillation - 33.3%, hypertension and chronic kidney desease - 19.6%. Achievement of BP and low-density lipoprotein cholesterol targets was insufficient in all analyzed groups. Among the international nonproprietary names of drugs, the most frequently prescribed are the following: bisoprolol, metoprolol, lisinopril, perindopril, losartan, spironolactone, amlodipine, torasemide, indapamide, hypochlorothiazide, moxonidine. The prescribed daily dosages were closer to the initial recommended ones. By 2020, the prescription of PCT with β-AB and a more uniform prescription of various combinations will come to the fore, while PCT in 2010 is characterized by the presence of one or two leaders combinations. The described features of prescribing AHD partially reproduce clinical recommendations for the management of AH. Differences in therapy provided in RCP may be associated with an attempt to intensify the treatment of hypertension in patients with other concomitant CVDs. At the same time, analysis of combinations and dosages of prescribed drugs suggests the presence of wide opportunities for further escalation of therapy. The presented data can provide insight into current patterns of antihypertensive therapy prescription in patients in RCP and lay the foundation for optimizing therapy in different categories hypertensive patients.

The choice of optimal therapy for ER+ HER2-metastatic breast cancer (PROMETHEUS): all-Russian analysis of physicians’ preferences – updated survey results

Cyclin-dependent kinase 4/6 inhibitors (iCDK4/6) are the generally accepted standard of care for the treatment of luminal HER2-negative metastatic breast cancer (ER+HER2- mBC). Data from randomized and observational studies have proven the high effectiveness of the combination of iCDK4/6 and endocrine therapy (ET) both in the 1st and in subsequent lines. The use of new drugs in real clinical practice is determined by a number of factors, including the awareness of doctors, their personal experience and subjective preferences, as well as financial support and availability in a particular region. To assess the frequency of prescription of CDK4/6, as well as other types of treatment in the 1st‑2nd line of therapy for ER+ HER2- mBC in real clinical practice in Russia, as well as to determine the factors and preferences of doctors influencing their choice, the National Association of Oncomammologists (NAOM) conducted a survey “Prometheus” of oncology specialists. From February 15 to August 30, 2023, a web survey of healthcare professionals who treat patients with mBC was conducted on the website anketolog.ru. An invitation to survey was sent out through the NAOM database, 112 questionnaires were received and processed. Earlier, in 2020, the “Prometheus” survey was conducted on the territory of the Russian Federation for a similar purpose. In this paper, we present the results of an updated and expanded survey and evaluate changes that have occurred over the past 3 years in actual clinical practice. The results of a 2023 survey conducted in the Russian Federation on the choice of early-line therapy for ER+HER2- mBC showed that, compared with the 2020 survey, the level of “trust” in iCDK4/6 has increased among practicing physicians, and the indications for their use have expanded, including visceral metastases (and even pending visceral crisis), the indications for prescribing chemotherapy in the 1st line have narrowed. When using monoET in the 1st line, the majority of respondents prescribe iCDK4/6 in the 2nd line. Obviously, the wider use of iCDK4/6 is associated not only with the accumulation of clinical knowledge and experience in the use of drugs, but also with improved drug supply. However, the main limitations to the use of iCDK4/6 are still insufficient funding and organizational difficulties. However, it should be noted that 1/5 of the respondents do not face any restrictions and widely prescribe combination therapy.

Outcomes of a dexamethasone-prednisone combination treatment course for status asthmaticus

Objectives Dexamethasone has become the standard of care for pediatric patients with status asthmaticus in the emergency department (ED) setting. Inpatient providers often must decide between continuing the second dose of dexamethasone or transitioning to prednisone. The effectiveness of receiving dexamethasone followed by prednisone (combination therapy) compared to only prednisone or dexamethasone remains unclear. This study compares patient characteristics and ED reutilization/hospital readmission outcomes of dexamethasone, prednisone, and combination therapy for inpatient asthma management. Methods A retrospective study was conducted at our tertiary children’s hospital of children aged 2 to 18 years hospitalized between March 2016 and December 2018 with a primary discharge diagnosis of asthma, reactive airway disease, or bronchospasm. The differences between steroid groups were compared using Fisher’s exact or Chi-square tests for categorical variables, and a Kruskal-Wallis test for continuous variables. A multivariable logistic regression was performed to analyze ED reutilization and hospital readmission rates. Results 1697 subjects met inclusion criteria. 115 (6.8%) patients received dexamethasone, 597 (35.2%) received prednisone, and 985 (58.0%) received combination therapy. Patients prescribed combination therapy had a lower exacerbation severity than patients prescribed prednisone, but higher severity than patients prescribed dexamethasone (p < .001, p = .001, respectively). Dexamethasone and combination therapy were not associated with increased 30-day ED reutilization/hospital readmissions compared to prednisone (p > .05). Conclusions In our study, most patients hospitalized for status asthmaticus received combination therapy. Despite the differences in severity between steroid groups, outcomes of combination therapy and dexamethasone monotherapy, as measured by frequency of ED reutilizations/hospital readmissions, are comparable to prednisone monotherapy.

Antidepressant prescription patterns and polypharmacy in outpatient psychiatry: a cross-sectional study.

Background and aim: Prescription patterns of antidepressants have changed over the years with a shift towards newer antidepressants with better tolerability and safety. Polypharmacy is common in psychiatry settings. The study aimed to evaluate the antidepressant drug prescription pattern and polypharmacy in a psychiatry outpatient setting. Investigations: This prospective observational study was conducted in a psychiatric outpatient clinic. The medication use data of eligible patients were collected. In addition, the rationale of antidepressant medication prescription, the defined daily dosage (DDD), the prescribed daily dose (PDD), and the PDD to DDD ratio were assessed. The assessment of prescription polypharmacy was conducted utilizing the framework provided by the National Association of State Mental Health Program Directors. Results: Data from 131 patients was analyzed. Major depressive disorder (32.8%) was the most common disorder for which antidepressants were prescribed. The majority, 91 (69.4%), received monotherapy. Selective serotonin reuptake inhibitors were the most frequently prescribed drugs in 69 (52.7%). Mirtazapine was the most frequently 32(24.4%) prescribed drug. Escitalopram and mirtazapine were the most commonly prescribed combination therapy (4.6%). Antipsychotic medications (37.4%) were the most widely co-prescribed medications, along with antidepressants. The PDD to DDD ratio was less than 1 for mirtazapine and imipramine; they were ≥1 for others. Psychiatric polypharmacy was documented in 87.1% of prescriptions. The total polypharmacy was not significantly (p>0.05) associated with demographic, illness, and treatment-related variables. Conclusion: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressants, monotherapy, and combination therapy. A substantial amount of patients received concomitant administration of antidepressants or psychotropic drugs, warranting careful monitoring.

Effect of combined GLP-1 analogue and bupropion/naltrexone on weight loss: a retrospective cohort study.

Little is known about the effect of a multi-drug weight loss strategy in obesity treatment, particularly combining bupropion/naltrexone and glucagon-like peptide 1 (GLP-1) analogue. The purpose of this study was to evaluate if there are any additive effects of prescribing bupropion/naltrexone on top of GLP-1 analogue as weight loss therapy. This was a retrospective cohort study of adult patients with a body mass index (BMI) ≥ 30 kg/m2 prescribed GLP-1 analogue therapy at an obesity specialist clinic in Vancouver, Canada. We compared a 6 and 12-month change in total body weight loss (TBWL) for those receiving monotherapy from the initiation of GLP-1 analogue therapy with those receiving combination therapy from the initiation of bupropion/naltrexone added-on therapy. Patients prescribed combination therapy were stratified into responder (loss of ≥ 5% TBWL) and non-responder (TBWL < 5%) subgroups based on initial response to the GLP-1 analogue alone for any amount of time. The mean weight loss among patients prescribed GLP-1 analogue monotherapy at 12 months was 11.42 kg, SD 9.95 (9.6% TBWL). There was no significant difference between these two treatment strategies overall (HR 0.88, 95% CI 0.68 to 1.14, p = 0.35). However, when stratified by response to initial GLP analogue therapy, the addition of bupropion/naltrexone was associated with a statistically significant reduction in weight in both the responder (4.3% TBWL (p < 0.01)) and non-responder groups (4.0% TBWL (p < 0.01)). GLP-1 analogues are an effective treatment for weight loss, and the addition of bupropion/naltrexone is associated with greater weight loss including in patients who are initially non-responsive to GLP-1 analogues.

Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy

BackgroundScientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AimWe aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). MethodThis nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. ResultsA total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61–75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06 - 2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22–0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). ConclusionThis study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Dynamics of indicators of central hemodynamics and arterial wall rigidity during the background of combination therapy with amlodipine/ valsartan in patients with arterial hypertension

Abstract Aim Assess the impact of antihypertensive therapy of the double fixed combination of amlodipine/valsartan on the parameters of central hemodynamics and elastic properties of arteries in patients with arterial hypertension. Materials and methods During the 3-month follow-up period, 30 patients with arterial hypertension were examined at our cardiology center. Women - 53.3%, men - 46.7%. The average age of the respondents was 54.7±11.3 years. The average duration of AH was 9.5±7.1 years. Patients with previously uncontrolled hypertension were prescribed combination therapy with the inclusion of amlodipine/valsartan, if necessary, the dose was titrated every 2 weeks. All patients initially and 3 months later underwent applanation tonometry using the SphygmoCor device. Central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central pulse pressure (cPP), aortic augmentation (AA), augmentation index (AIx), pulse wave velocity (PWV) were measured, resulting in a conclusion about the state of arterial stiffness . Results are presented as M±SD. Results An analysis of the dynamics of central hemodynamic parameters and vascular stiffness during 3-month combination therapy with amlodipine/valsartan showed a significant decrease in such indicators as cSBP, cDAP, CPD, AA, as well as pulse wave velocity. Thus, the cSBP index initially amounted to 155.2±22.6 mm Hg. and in dynamics - 131.6±18.3 mm Hg. (p&amp;lt;0.001); the cDAP index was 84.2±12.7 mm Hg. vs. 78.4±8.2 mm Hg respectively (p&amp;lt;0.02); the CPP index was 71.0±19.8 mm Hg. vs. 53.2±18.1 mm Hg. respectively (p&amp;lt;0.001); the AA index was 18.3±16.5 mm Hg. vs. 11.9±6.3 mm Hg. respectively (p&amp;lt;0.02); PWV was 9.9±2.7 m/s versus 8.2±2.7 m/s, respectively (p&amp;lt;0.001). Conclusions According to the results of 3-month combination therapy, indicators of central hemodynamics and the state of elastic properties of arteries are significantly improved, which is potentially associated with a decrease in the risk of developing cardiovascular complications in patients with hypertension.

‘Inner world’ of luminal HER 2-negative metastatic breast cancer: Efficacy of ribociclib in different intrinsic subtypes

The heterogeneity of breast cancer (BC), which determines various clinical scenarios of the disease, is still inaccessible to our understanding. Heterogeneity is based primarily on intrinsic subtypes of breast cancer, determined using genomic tests. Currently, four intrinsic subtypes are generally recognized: luminal A and B, HER-enriched (HER2-E) and basal-like. HER2-E subtype in luminal HER-negative (ER+HER–) breast cancer accounts for 11–22 per cent of cases. The efficacy of a combination of hormone therapy (HT) and the CDK4/6 inhibitor ribociclib in the HER2-E subtype was evaluated in a large exploratory analysis of MONALEESA-2, -3, and -7 trials. The gain in progression-free survival (PFS) and overall survival (OS) from the addition of ribociclib to HT was observed in all intrinsic subtypes, except for basal-like, and reached maximum in HER2-E subtype: Ribociclib increased the median PFS to 16.4 months from 5.5 months on HT (HR = 0.389; p &lt; 0.0001) and median OS to 40.3 months from 29.4 months (HR = 0.600; p = 0.0180). The significant frequency of occurrence of the HER2-E subtype in ER+HER-BC, the low efficiency of monoHT in this subtype is another argument in favor of prescribing combination therapy in early lines. Information about the intrinsic subtype not only brings us closer to understanding tumor heterogeneity, but may also become a significant factor in determining treatment tactics in the future.

A STUDY OF DRUG UTILIZATION AND COMPARATIVE PHARMACOECONOMIC ANALYSIS OF ANTIDIABETIC DRUGS IN A TERTIARY CARE HOSPITAL

Background: Diabetes Mellitus is a chronic metabolic disorder that is one of the major causes of morbidity and requires lifelong treatment. Aim and Objectives: This study was conducted to determine prescribing pattern and frequency of single and combination antidiabetic drugs prescribed for type 2 DM and to compare their percentage cost variation. Materials and Methods: This was a prospective observational study carried out among in-patients of the general medicine department of a tertiary care hospital for a period of 6 months. Results: A total of 246 subjects were analyzed showing the main age group was between 60-70 years (28.9%). Polypharmacy was evident in the study as 178 (72.4%) prescriptions had greater than 5 drugs. Metformin 500mg in 38 (33.04%), Metformin 500mg + Glimepiride 2mg in 36 (25.35%) subjects and Insulin soluble 30% + Isophane 70% were the most prescribed single, combination, and insulin preparation respectively. The highest percentage cost difference was seen with Vildagliptin 50 mg (72.88%) out of 15 single antidiabetic drugs, Metformin 500mg + Dapagliflozin 10mg (79.93%) out of 20 combination antidiabetic drugs and Insulin soluble 30% + Isophane 70% (28.28%) out of 6 insulin preparations. Conclusion: Oral dosage form was the most prescribed and there is inclination towards prescribing combination therapy. The study concluded that inclusion of generic drugs to the therapy will be economical for the patient, as it can reduce the wider price variation of antidiabetic drugs by different brands available in the hospital pharmacy. KEYWORDS: Type 2 Diabetes mellitus, Anti-diabetic drugs, Drug utilization study, Polypharmacy, Comparative Pharmacoeconomics analysis, Cost analysis.

A Study on Assessment of Pharmacotherapy, Etiology, and Risk Factors in Heart Failure Patients in Tertiary Care Hospital

Abstract: Background: Heart failure is described by the ACC Foundation and AHA as “a complex clinical syndrome resulting from any anatomical or functional impairment of ventricular filling or blood ejection. The main aim was to assess the pharmacotherapy, drug utilization pattern, precipitating factors, and aetiological factors of heart failure. Materials and Methods: The study is a single-centred prospective observational study that was conducted for 6 months. Patients were selected based on study criteria. Results: Out of 155 heart failure, the patient’s most prevalent age group was between 61 and 70 years (33.5%) with a mean of 61.96(±13.72). Out of 155 patients, 86 (55.4%) had a decreased ejection fraction, and the majority of patients were men (53.45%). The most prevalent precipitating variables were found to be anaemia 51(18.68%), hypertension 82(30.03%), and diabetes mellitus 70(25.64%). Cardiomyopathy 70(43.48%) and ischemic heart disease 83(40.88%) were the most often discovered underlying causes in patients with heart failure. The most frequent comorbidities were renal disorders 42(21.53%), hypertension 46(23.58%), and diabetes mellitus 42(23.58%). Around 139(90.25%) prescriptions contained diuretic drugs. Furosemide (69.63%) was the most commonly prescribed diuretic. Followed by antihypertensives 132(85.71%) and digoxin was prescribed to 32 (20.64%) patients. About 36.90% of patients received aspirin and atorvastatin combination drugs. Conclusion: Our study concluded that ischemic heart disease and dilated cardiomyopathy are the core underlying causes of heart failure. Hypertension and diabetes mellitus is considered to be the most common predisposing factors. The most frequent monotherapy prescribed for heart failure includes diuretics, antihypertensives, antiplatelets, and lipid-lowering agents while aspirin and atorvastatin were the most commonly prescribed combination therapy. Keywords: HF patients, Ejection fraction, Hypertension, Hypernatremia, Diuretics.

Should substitution monotherapy or combination therapy be used after failure of the first antiseizure medication? Observations from a 30-year cohort study.

To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy. This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up. During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985 to 1994) to 78% in the last (2005 to 2015) (RR=1.66, 95% CI: 1.17-2.36, corrected-p=0.010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p<0.001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR=1.17, 95% CI: 0.81-1.69, p=0.41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes. The choice of second regimen used based on clinical judgement was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.

A Cardiologists' Survey on the Use of Anticoagulants and Antiplatelets in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Those Undergoing Percutaneous Coronary Intervention in India.

The management of patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) requires appropriate antithrombotic regimens for stroke prevention and in-stent thrombosis. Current practice recommendations are largely based on consensus options as there is limited evidence from randomized clinical trials. Hence, by surveying a group of cardiologists across India, we sought to better understand the current practice patterns of using oral anticoagulants (vitamin K antagonist, VKA or non-vitamin K antagonist oral anticoagulant, NOAC) and antiplatelet therapy in those patients in India. A cross-sectional questionnaire-based survey was conducted across India to better understand the clinical practices in AF management. A total of 151 cardiologists participated in this survey. The most commonly prescribed combination therapy in patients with AF and ACS/undergoing PCI was triple therapy (NOAC + dual antiplatelet [aspirin and P2Y12 inhibitor]) (54.30%) followed by NOAC + single antiplatelet (33.11%).Only 11.26% of cardiologists prescribed VKA + dual antiplatelet therapy. Among anticoagulants, cardiologists prescribed NOACs to 66.11%of patients andVKAs to 25.54%of patients. Among P2Y12 inhibitors, ticagrelor (50.99%) and clopidogrel (47.02%) were the most preferred medication. The physician reported patient adherence rates to NOACs were higher compared to VKAs. Around 41.06% of cardiologists reportedly changed antiplatelet therapy for patients from dual antiplatelet to single antiplatelet therapy in three months; 36.42%, in one month; and 19.21% in six months after PCI. Around 61.59% of cardiologists stopped prescribing antiplatelet therapy for patients by one year. Our survey demonstrated that the majority of cardiologists used triple therapy (NOAC + dual antiplatelet), followed by NOAC + single antiplatelet for managing patients with AF and ACS or undergoing PCI in line with the available guidelines.

Hepatotoxicity Associated with Immune Checkpoint Inhibitors in Clinical Practice: A Study Leveraging Data from the US Food and Drug Administration's Adverse Event Reporting System

PurposeImmune checkpoint inhibitors (ICIs) are a promising option for the treatment of patients with various cancers. Emerging case reports have raised awareness on hepatotoxicity, a potentially fatal adverse event (AE) that may be associated with the use of ICIs. This study assessed the potential association between ICIs and hepatotoxicity through the mining of data from the US Food and Drug Administration's AE Reporting System (FAERS). MethodsA total of 9,217,181 AEs reported in the period from quarter 1 of 2004 to quarter 3 of 2021 were assessed. Information components (ICs) and reporting odds ratios (RORs) were used to evaluate the association between the use of ICIs and hepatotoxicity. FindingsA total of 52,463 AE reports listed ICIs, used alone or in combination, as a suspected drug. Of these, 1481 cases were related to both ICIs and hepatotoxicity. The use of ICIs was significantly associated with hepatotoxicity compared to all other drugs, making it a safety signal (IC = 1.43 [95% CI, 1.36–1.51]; ROR = 2.78 [95% CI, 2.64–2.93]). With monotherapy, all ICIs, except tremelimumab, were associated with liver damage. The most commonly prescribed combination therapy was nivolumab + ipilimumab (321 cases) with a significant signal detected. Notably, ICI use was significantly associated with hepatic failure (IC = 1.24 [95% CI, 1.06–1.42]; ROR = 2.40 [95% CI, 2.13–2.72]). The risk for ICI-associated hepatotoxicity (including hepatic failure) was greater with ICI combination therapy than with ICI monotherapy. All subgroups by sex and age also showed significant associations between ICI use and hepatotoxicity. ImplicationsA significant association was detected between ICI use and hepatotoxicity. The risk for hepatotoxicity (including hepatic failure) was greater with ICI combination therapy compared with ICI monotherapy.

Prescribing Pattern of Levetiracetam in Epilepsy Patients: A Cross-Sectional Study in a Tertiary Care Centre in Manipur

Objective: The objective is to shed light on the prescribing pattern of levetiracetam, a newer antiepileptic drug, in the treatment of different types of epilepsy. Methods: A record-based cross-sectional study of epilepsy patients who reported to the Therapeutic Drug Monitoring Unit in the Department of Pharmacology, Regional Institute of Medical Sciences, Manipur, was conducted. Case records of patients receiving levetiracetam and reporting from January 2017 to December 2020 were included. The patient’s age, gender, and weight; clinical diagnosis; levetiracetam dose; and other co-administered AEDs were all examined. Findings: Of the 17 cases, the majority of the patients were adults, and 52.9% were males. The patients’ average body weight (kg) was 49.8  9.4. Generalised tonic-clonic seizures (GTCS) constituted the majority of the cases (47.1%), followed by simple partial seizures, complex partial seizures (23.5% of each), and absence seizures (5.9%). 70.11% of the cases received LEV monotherapy, while the remaining cases were prescribed combination therapy. LEV alone was prescribed in 87.5% of GTCS cases. The median daily dose of LEV was 1000 mg (IQR-625). Novelty : The observation that levetiracetam alone is prescribed in the majority of GTCS cases, the commonest type of epilepsy, is an eye-opener for another new monotherapy option for GTCS. Keywords: Prescribing pattern; Levetiracetam; Antiepileptic; Epilepsy; Monotherapy

Expert experience in the management of allergic rhinitis in the Middle East region

Allergic rhinitis (AR), a common atopic disease, is a global health concern causing a significant burden on healthcare resources and is associated with high incidence in the pediatric population. Pharmacotherapy controls the severity of the disease; however, relapsing symptoms challenge the management of AR. A significant AR burden is witnessed in the Middle East region. However, there is a lack of published data on the epidemiology, diagnosis, current treatment options, and preventive measures for AR in the Middle East. The present study, supported by relevant literature, discusses the expert experiences on the epidemiology, diagnosis, current treatment options, and preventive measures for AR in the Middle East. An advisory board meeting involving nine experts in the field of otolaryngology from Saudi Arabia, the United Arab Emirates, Kuwait, and Pakistan was conducted. The experiences of the experts on the epidemiology and diagnosis of AR in the Middle East, including current treatment options, preventive measures, and the management of rhinitis medicamentosa, were combined and supported by a literature review. Based on expert experiences and literature review, Intranasal corticosteroids (INCS) may be considered a more effective treatment option than oral antihistamines. Patients who do not respond within 2-3 weeks of INCS treatment may be prescribed combination therapy with antihistamines and decongestants (limited time and certain cases). These evidence-based expert experiences focusing on the management of AR in the Middle East may provide up-to-date guidance to primary care physicians for the effective management of AR patients in this region.

Эффективность различных схем противовирусной терапии у детей с хроническим гепатитом В

Objective. To determine the effectiveness of various interferon therapy regimens in children with chronic hepatitis B (HBV). Patients and methods. The study included 126 children with HBV aged 3 to 17 years, who were treated in the pediatric infectious diseases department of the N.A.Semashko City Clinical Hospital in Samara. The diagnosis of HBV was confirmed by the detection of markers HBsAg, anti-cor IgM, HBeAg, anti-HBe. 88 (69.8%) patients with HBeAg(+) were registered, with HBeAg(‑) – 38 (30,2%). To exclude hepatitis D, total anti-HDVs were determined. Hepatitis B virus DNA was detected by polymerase chain reaction (sensitivity of the method is 10–15 IU/ml). The criterion for inclusion of patients with HBV in the study was the consent of parents and/or patients to antiviral therapy, the exclusion criterion was the presence of anti-HDV. The average age of the patients was 13.4 ± 2.5 years. To receive therapy, the children were divided into two groups. 62 patients of group I were prescribed monotherapy – recombinant interferon α-2b (IFN-α2b) for 24 weeks in a dose of 3 million IU 3 times a week. After 24 weeks patients who had the decrease in viral load (VL) &gt;2 log continued treatment with IFN-a2b, and patients who did not have this were transferred to combination therapy – IFN-a2b 3 million IU 3 times a week every other day together with lamivudine (LV) 3 mg/kg 1 time per day every day.The II group, consisting of 64 patients, was immediately prescribed combination therapy – IFN-a2b + LV – 3 mg / kg 1 time per day daily for 48 weeks. with subsequent evaluation of the effectiveness of therapy. The duration of follow-up after the end of therapy was 12 months. Results. After antiviral therapy in both groups, regardless of the response to therapy, there was a significant decrease in the activity of alanine aminotransferase, aspartate aminotransferase compared with baseline data. In an individual analysis of high blood pressure in both groups before and after antiviral therapy, the number of patients with high blood pressure decreased by half and the proportion of patients with low blood pressure increased. In 15 patients (11.9%), the DNA of the hepatitis B virus stopped being detected. In most children (96.7%), interferon therapy was accompanied by the development of adverse events, most often flu-like (93.5%), asthenic syndromes (96.7%), which were stopped and did not interfere with further treatment. Key words: chronic hepatitis B, children, viral load, antiviral therapy

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A THESIS questionnaire survey of members of the Irish Endocrine Society

BackgroundReplacement of thyroid hormones (TH) with Levothyroxine (LT4) is the treatment of choice for hypothyroidism, however, there are aspects of treatment where uncertainties exist and practice varies. Factors influencing initiation and choice of TH replacement may impact patient satisfaction, safety, and health care costs.MethodsThe aim of the study was to examine the attitudes of Irish endocrinologists regarding the treatment of hypothyroid and euthyroid patients with TH. Members of the Irish Endocrine Society (IES) were invited to participate in an online survey.ResultsForty-eight invitations were sent, and 39 (81.3%) participants responded. All respondents favoured LT4 tablet therapy for treatment of hypothyroidism, but 20.5% prescribed combination therapy (LT4 and liothyronine), and 13% regularly used desiccated thyroid extract. A significant proportion (51%) might prescribe TH in euthyroid patients; 41% for thyroid auto-antibody positive women seeking pregnancy, 18% for goitre and 5% for unexplained fatigue. Many (38%) consider combination therapy in patients with persistent symptoms. Respondents reported seeing LT4 treated patients with persistent symptomatology more frequently and perceive psychosocial factors and comorbidities to be the most common reasons for such symptoms.ConclusionLT4 tablets are the treatment of choice for hypothyroidism in Ireland. Approximately a third of Irish endocrinologists either regularly use, or would consider, liothyronine for hypothyroid patients. A significant proportion would give TH to euthyroid individuals in specific circumstances. The prescription of TH amongst Irish endocrinologists was generally in keeping with recommended practice, and areas where practice deviated from guidance were typically where evidence was conflicting or insufficient.

Prescribing adherence of antihypertensive agents in Chronic Kidney Disease (CKD) patients and its relationship with clinical outcomes

Objectives This study was conducted to evaluate the utilisation of antihypertensive agents, assess prescribing adherence and determine the relationship between guideline adherence indicator (GAI) and clinical outcomes among hypertensive CKD patients. Methods This was a retrospective cohort study involving newly diagnosed CKD patients undergoing follow-up between January to December 2018 at a tertiary Malaysian hospital. The study subjects were screened and recruited using simple random sampling according to inclusion and exclusion criteria. Clinical data was retrieved from the online medical record (eHis system) using a pre-prepared data collection form. Results A total of 74 patients were included in this study with mean (SD) age of 66.86 (10.86) years old. The majority were male (n= 39, 52.7%) and Malay (n= 34, 45.9%). The study results showed that CCB was the drug of choice prescribed, while the most commonly prescribed combination therapy was ACEI + beta-blocker + CCB and ACEI + CCB. The overall adherence to the guideline was moderate (mean (SD) GAI score of 76.25 (17.56) %). There was a significant difference in mean GAI score between subjects with controlled and uncontrolled BP (92.86 (11.11) vs 69.23 (14.88), P &lt;0.05).

Approach to a problem of the progressive muscular dystrophies in children: modern clinic-diagnostic algorithm

Objective — to study the features of clinical symptoms of progressive muscular dystrophies (PMD) in children and to improve their clinical diagnostic algorithm.&#x0D; Methods and subjects. Three groups of children were examined: 33 children with Duchenne PMD aged 2 to 16 years, 7 — with lumbosacral forms of muscular dystrophies aged 3 months to 16 years and 19 — with spinal muscular atrophy aged 3 months to 16 years. The duration of the disease ranged from 3 months to 12 years. Patients underwent clinical and neurological examination to determine the leading clinical syndromes. Motor functions were evaluated on unified scales. Based on the obtained data, the degree of loss of active movements and muscle strength was objectively determined. Assessment of motor dynamics was performed using the NSA (North Star Ambulatory Assessment Worksheet) scale, the 6‑minute gait test, and other functional tests. CHOP — INTEND and HINE2 scales were used in patients with type I spinal muscular atrophy, and Motor Function Measure (MFM), Hammersmith, RULM, etc. scales were used in children with type II and III. Blood biochemical analysis was also performed to determine the level of creatine phosphokinase and lactate dehydrogenase in the blood. Instrumental research methods were used (electroneuromyography, spinal radiography in two projections), in some cases — magnetic resonance imaging was applied. The last stage was molecular genetic diagnosis and verification of clinical diagnosis. After the final diagnosis, patients with Duchenne PMD were prescribed combination therapy (hormonal (corticosteroids) and physiotherapy) according to an international care protocol. Patients are being monitored.&#x0D; Results. Complete history taking, timely detection of the first symptoms of the disease and assessment of their dynamics, analysis of neurological symptoms are important for confirming the diagnosis of PMD. Given the similar clinical symptoms in the onset of various forms of PMD to confirm the diagnosis should follow a certain stage of research. Molecular genetic diagnostics should be performed only after evaluation of the results of general clinical, instrumental and laboratory examination of the child. Timely clarification of the clinical diagnosis of PMD, in particular Duchenne forms, helps to justify the appointment of glucocorticosteroids and disease‑modifying therapy.&#x0D; Conclusions. Treating a patient according to international standards will help stop the process of muscle atrophy with a timely diagnosis.&#x0D;

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Out of 206 members of the DGE's thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p<0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p<0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p<0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p<0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.