Triple-drug Therapy Research Articles

Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome.

The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model. We evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in Scn1aA1783V/WT mice. Clobazam, N-desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry for the combinations deemed effective against hyperthermia-induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin. Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in Scn1aA1783V/WT mice. In Scn1aWT/WT mice, brain clobazam and N-desmethyl clobazam concentrations were higher in the triple-drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple-drug therapy than when given alone. A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug-drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.

In Vivo Evaluation of Nose-to-Brain Delivery of Liposomal Donepezil, Memantine, and BACE-1 siRNA for Alzheimer's Disease Therapy.

Our study took an innovative approach by evaluating, in vivo, the efficacy of intranasal (IN) administration of liposomal formulations of donepezil, memantine, and beta-site amyloid precursor protein-cleaving enzyme (BACE-1) siRNA, and their combination as a "triple-drug therapy" in treating Alzheimer's disease (AD). Female APP/PS1 homozygous, transgenic mice were used as an AD model. The spatial short-term memory of the APP/PS1 mice was evaluated by a Y-maze behavioral test. IN-administered formulations demonstrated better short-term memory recovery than oral administration. Triple-drug therapy induced short-term memory recovery and lowered beta-amyloid (Aβ) 40 and 42 peptide levels and BACE-1 mRNA expression. Additionally, inflammatory cytokine mRNA expression was downregulated. This innovative approach opens new possibilities for Alzheimer's disease treatment and nose-to-brain delivery.

Triple-drug therapy with ivermectin, diethylcarbamazine and albendazole for the acceleration of lymphatic filariasis elimination in Kenya: Programmatic implementation and results of the first impact assessment.

The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after the two annual rounds of mass treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic.

Unique EPIYT motif CagA gene Helicobacter pylori Bali 01 isolate as the cause of hematemesis in a male gastric ulcer patient in Wangaya General Teaching Hospital Denpasar Bali: a case report

Background: Helicobacter pylori (H. pylori) infection is related with a number of gastrointestinal disorders, including gastritis, peptic ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This case report aims to present an unique EPIYT motif CagA gene H. pylori Bali 01 isolate as the cause of hematemesis in a male gastric ulcer patient Case Presentation: A 70-year-old male Balinese patient came to the hospital due to hematemesis. Esophagogastroduodenoscopy was performed after stabilizing patient condition with prompt treatment and intravenous proton pump inhibitor. Esophagogastroduodenoscopy revealed a solitary giant ulcer in the gastric antrum. Gastric biopsy was performed and histopathology examination revealed a spherical-like organism, confirmed as H. pylori. Biopsy was sent to the Biomedical Laboratory at West Nusa Tenggara, Mataram, Lombok Island. Culture of biopsy and polymerase chain reaction revealed H. pylori, then named H. pylori Bali 01 isolate. Standard protocol of H. pylori eradication is conducted by administration of triple drug therapy consisting of omeprazole, amoxicillin, and clarithromycin for 14 days. Patient was discharged from hospital in stable condition. Helicobacter pylori was successfully eradicated and revealed completely normal gastric antrum in reperformance of esophagogastroduodenoscopy 3 months later. Conclusion: The EPIYA-ABD motif on this H. pylori Bali 01 isolate is distinctively unique from the EPIYT motif on the second EPIYA sequence.

Multiple recurrent supraventricular tachycardia in infantile tuberous sclerosis complex: management requiring triple-drug therapy.

We report the case of a female neonate admitted to the neonatal ICU with a rapid, narrow-complex tachyarrhythmia determined to be supraventricular tachycardia. Multimodality imaging and genetic testing confirmed a diagnosis of tuberous sclerosis complex with multiple cardiac rhabdomyomas. At 13 days of age, the patient was readmitted, exhibiting recurrent supraventricular tachycardia non-responsive to first-line treatment. Management required triple-drug therapy, whereafter the patient remained stable without recurrences. This is a rare report of supraventricular tachycardia in a functionally normal heart with the occurrence of supraventricular tachycardia due to structural abnormalities, with the possibility of multiple concealed accessory pathways.

Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study

BackgroundAt present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH.MethodsSubjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient.ResultsPCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases.ConclusionsIn NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI’s acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated.Study registrationThis study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings.

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451];p= 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. ClinicalTrials.govNCT03160105.

Effects of Dual and Triple Drug Therapy in Chronic Obstructive Pulmonary Disease Management: An Overview

Effects of Dual and Triple Drug Therapy in Chronic Obstructive Pulmonary Disease Management: An Overview

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

Abstract 6581: DX126-262 combined with chemotherapy (Cisplatin and 5-Fu) demonstrates promising antitumor efficacy in HER2-positive gastric cancer

Abstract Gastric cancer is a common malignant tumor of the digestive system, and its morbidity and mortality rank among the top five in the world. Although significant progress has been made in cytotoxic chemotherapy, immunotherapy and targeted therapy in recent years, the long-term prognosis of patients with advanced or metastatic gastric cancer is still poor. Trastuzumab combined with chemotherapy is the first-line standard of care (SOC) for HER2-positive advanced or metastatic gastric cancer. Two ADC drugs targeting HER2, DS-8201 and RC-48, have also been approved for the treatment of gastric cancer. However, their limited clinical benefits and occurrence of adverse events still present a significant challenge. Therefore, minimizing the off-target toxicity and collateral damage while achieving significant chemotherapy efficacy has become the focus of gastric cancer treatment. DX126-262 is a novel HER2-targeting antibody-drug conjugate (ADC), generated by conjugating a Tubulysin B analogue to a recombinant humanized anti-HER2 monoclonal antibody through a linker containing branched hydrophilic polyethylene glycol, using thiol-maleimide chemistry to achieve drug antibody ratio (DAR) of 3.8. Previous studies have confirmed that DX126-262 monotherapy showed excellent efficacy in HER2-positive gastric cancer NCI-N87 cells in vitro and in vivo. And the efficacy has also been demonstrated in clinical trials (now in phase II, CTR20211871). Based on above results, we intended to further explore whether combination therapy of DX126-262 with Cisplatin and 5-FU can improve the anti-tumor efficacy compared with SOC (Herceptin plus Cisplatin and 5-FU) or DS-8201 monotherapy. The triple-drug combination therapy demonstrated much better therapeutic efficacy than single drug (DX126-262, Cisplatin, 5-FU, Herceptin, or DS-8201) or double-drug combination (Cisplatin plus 5-FU) or SOC (Herceptin plus Cisplatin and 5-FU) on human gastric cancer cells in vitro and in vivo. Meanwhile, triple-drug combination therapy did not exhibit superimposed toxicity, judging by the body weight of mice and hemal biochemistry assays. These results suggested that DX126-262 plus Cisplatin and 5-FU might be a promising strategy for treatment of HER2-positive advanced or metastatic gastric cancer in clinic. Citation Format: Xiaobo Cai, Min Cao, Huihui Guo, Qingliang Yang, Xiangfei Kong, Yong Du, Zhicang Ye, Zhixiang Guo, Lingli Zhang, Lu Bai, Junxiang Jia, Yunxia Zheng, Yongxiang Chen, Miaomiao Chen, Wei Zheng, Jun Zheng, Wenjun Li, Yuanyuan Huang, Mengmeng Liu, Zhongliang Fan, Hangbo Ye, Yifang Xu, Binbin Chen, Meng Dai, Robert Y. Zhao. DX126-262 combined with chemotherapy (Cisplatin and 5-Fu) demonstrates promising antitumor efficacy in HER2-positive gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6581.

Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.

This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE. The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated. The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety. The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.

Impact of Visceral Obesity on Clinical Outcome and Quality of Life for Patients with Multiple Myeloma: A Secondary Data Analysis of STaMINA (BMT CTN 0702) Trial

Obesity is a common health problem among multiple myeloma (MM) patients, and it has been linked to poor clinical outcomes and quality of life (QOL). We conducted a secondary analysis of the BMT CTN 0702, a randomized, controlled trial comparing outcomes of three treatment interventions after a single hematopoietic cell transplant (HCT) (N = 758), to investigate the impact of visceral obesity, as measured by waist-to-hip ratio (WHR), on clinical outcomes and QOL in MM patients. A total of 549 MM patients, median age 55.5 years, were enrolled in the study. The majority of patients received triple-drug antimyeloma initial therapy before enrollment, and 29% had high- risk disease according to cytogenetic assessment. The median follow-up time was 6 years. There was no significant association between WHR and progression-free survival (PFS) or overall survival (OS) in MM patients undergoing HCT. Similarly, body mass index (BMI) did not significantly predict PFS or OS. Furthermore, there was no significant correlation between WHR and QOL measures. In conclusion, this study suggests that visceral obesity, as measured by WHR, may not have a significant impact on clinical outcomes in MM patients undergoing HCT. These findings add to the existing literature on the topic and provide valuable information for healthcare professionals and MM patients. Further studies are needed to confirm these results and to investigate other potential factors that may affect clinical outcomes and QOL in this patient population using modern imaging technologies to assess visceral obesity.

Phenotypes and endotypes in asthma-practical approach

Abstract Asthma is a complex heterogeneous inflammatory airway disorder. Inflammation is usually accompanied by an increase in airway smooth muscle mass, thickening of subepithelial lamina reticularis, matrix deposition in the airway walls, an increase in microvessels and neural networks, and mucus metaplasia. Clinical trials are going-on to evaluate the efficacy of biologicals or as an adjunct to allergen immunotherapy in high-T2 inflammation of allergic asthma. Management involves the titration of inhaled triple-drug therapy in a stepwise approach and to address the comorbidities. The targeted use of biological agents in severe diseases needs risk stratification of patients. We need further research on biomarkers and drivers of immune pathways in this era of changing global environment. This review will delve into personalized medicine strategies to treat asthma after phenotypic and endotypic characteristics.

P25 TB or not TB? An unusual case of inflammatory arthritis in an anti-CCP positive patient

P25 TB or not TB? An unusual case of inflammatory arthritis in an anti-CCP positive patient

Efficacy of Fixed-dose Combination of Dapagliflozin and Sitagliptin in Type 2 Diabetes Mellitus Using Continuous Glucose Monitoring: A Real-world Study in India

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial aetiology. Metformin monotherapy is commonly used as the initial treatment, but is often inadequate in achieving optimal glycaemic control, necessitating the need of second and third-line therapies. Fixed dose combination (FDC) of dapagliflozin and sitagliptin in Indian setting is gaining popularity. Time-in-target has become a useful blood glucose indicator that goes "beyond HbA1c" to understand glycaemic control in people with diabetes better. Aims and Objectives: To assess the efficacy of a FDC of dapagliflozin and sitagliptin in Indian T2DM patients. Materials and Methods: This was a single-arm, single-centre, real-world study. Twenty-eight consented T2DM patients age &gt;18 years, either sex, not hospitalized, and estimated glomerular filtration rate &gt;60 ml/min/1.73m2 were administered a continuous glucose monitoring system (CGMS) (Freestyle Libre Pro). Once daily fixed-dose combination (FDC) of dapagliflozin (10mg) and sitagliptin (100mg) was given along with CGMS administration on a background of existing therapy for those who were not to target for glycemic parameters. Since the FDC reaches at its peak concentration after 3-4 days of administration, the efficacy of FDC was considered from 5th day. Hence the baseline was calculated taking the mean of first 4 days after FDC administration. Patients' characteristics, including age (years), sex, weight (kg), body mass index (kg/m2), estimated glycated haemoglobin (%), history of oral hypoglycaemic agents, and dose of insulin were recorded. For efficacy assessment, average daily glucose (ADG), time in target (TIT), time below target (TBT), and time above target (TAT) were recorded at baseline.) and end of the study (day 15th of CGMS administration) from the daily glucose summary of Freestyle Libre Pro CGMS. The percentage improvement of each efficacy parameters were assessed. Results: A statistically significant improvement (p&lt;0.05) in ADG (19.41% decrease), TIT (34.47% increase), and TAT (31.13% decrease) was observed, whereas TBT was increased by 29.23%. Mean age (n=28), weight (n=23), body mass index (n=19) and estimated HbA1c (n=19) was 56.70±9.8 years, 64.67±9.52 Kg, 24.99±4.23 Kg/m2 and 6.84±1.63 % respectively. The majority were on triple drug (n=14; 50%) therapy before CGMS administration than dual (n=5; 17.9%) and monotherapy (2; 7.1%). Fifteen (53.8%) were on insulin with a mean insulin dose of 16.40 IU. Conclusion: Once daily FDC of dapagliflozin and sitagliptin in Indian T2DM patients significantly improves AGD, TIT, and TAT at the end of 15 days.

Experience of outpatient follow-up of heart transplant recipients at Shumakov center

Heart transplantation (HT) is considered the optimal therapy for end-stage heart failure. In recent years, the number of operations performed has been growing, which has led to a rise in the number of heart transplant recipients requiring outpatient follow-up.Objective: to evaluate the effectiveness of the model of dual personalized follow-up of heart transplant recipients in the consultative and diagnostic department of Shumakov National Medical Research Center of Transplantology and Artificial Organs.Materials and methods. The study included 1,436 patients under outpatient follow-up from January 2008 to December 2022. Recipient data, results of laboratory and instrumental examination methods, nature and frequency of complications at different follow-up periods were analyzed.Results: At the time of discharge from the hospital, 98.7% of patients had received triple-drug immunosuppressive therapy; 6 months later, methylprednisolone was discontinued in 72.2% of recipients. Mean tacrolimus level during the 1-year follow-up was 8.7 ± 2.7 ng/mL; in the period from 1 to 5 years of followup, the mean was 5.1 ± 2.4 ng/mL. At year 1 after transplantation, 23 (1.7%) recipients had been converted to everolimus; by the end of year 5 of follow-up, the number had increased to 8.6%. The most frequently detected complications during outpatient follow-up were: hypertension (48.65%), post-transplant diabetes mellitus (7.24%), nephropathy (35.97%), and malignant neoplasms (4.2%). Recipient survival, excluding in-hospital mortality, was 96.5%; and 88.0% at year 1 and 5 of follow-up, respectively.Conclusion: The dual personalized approach model for outpatient follow-up and treatment of heart transplant recipients will improve recipient survival and quality of life in the long-term post-HT period.

Comparing Triple Combination Drug Therapy and Traditional Monotherapy for Better Survival in Patients With High-Risk Hypertension: A Systematic Review.

High-risk hypertension patients are more susceptible to cardiovascular disease, stroke, and mortality.Monotherapy and triple combination drug therapy are two different approaches to treating hypertension. Monotherapy involves using a single medication to manage hypertension, whereas triple combination therapy involves the simultaneous use of three different antihypertensive medications from different drug classes. Making a fast switch from monotherapy to combination medication is one method to regulate blood pressure (BP) better. It is widely recognized that a significant proportion of individuals with hypertension require combination therapy to manage their condition effectively. This review aims to evaluate the mortality rates across monotherapy and triple combination drug therapy in high-risk hypertension patients. A systematic literature review was conducted across multiple scientific literature repositories. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for systematic reviews and meta-analyses. Based on the end outcome of each published journal on the effectiveness of triple combination drug therapy as a treatment option for high-risk hypertension patients, there was a notable difference in overall survival, mortality rates, BP reduction, and adherence datasets. Triple combination drug use correlated with increased timeframes for multiple patient survival parameters within the articles shortlisted in this investigation. However, it is crucial for healthcare providers to weigh the risks and benefits of triple combination drug therapy when deciding which treatment approach is best for their patients.

Different COVID-19 treatments’ impact on hospital length of stay

ImportanceCOVID-19 has adversely affected global healthcare infrastructure since 2019. Currently, there are no large-scale published reports on the efficacy of combination therapy of dexamethasone, remdesivir, and tocilizumab on COVID-19 patients.ObjectivesIs the combination therapy of dexamethasone, remdesivir, and tocilizumab superior to other treatments on hospitalized COVID-19 patients?DesignThis is a retrospective, comparative effectiveness study.SettingSingle-center studyParticipants/interventionsWe analyzed different inpatient COVID-19 treatment options available in the United States and their impact on hospital length of stay (LOS) and mortality. Hospitalized COVID-19 were categorized as “mild,” “moderate” and “severe'' based on the highest level of oxygen required; room air, nasal cannula, or high flow/PAP/intubation, respectively. Patients were treated in accordance with the availability of medications and the latest treatment guidelines.Main outcomesThe endpoints of the study are hospital discharges and death during hospitalization.Results1233 COVID-19 patients were admitted from 2020 to 2021. No treatment combinations showed a statistically significant decrease in hospital LOS in mild COVID-19 patients (p = 0.186). In moderate patients, the combination of remdesivir and dexamethasone slightly decreased LOS by 1 day (p = 0.007). In severe patients, the three-drug combination of remdesivir, dexamethasone, and tocilizumab decreased LOS by 8 days (p = 0.0034) when compared to nonviable treatments, such as hydroxychloroquine and convalescent plasma transfusion. However, it did not show any statistically significant benefit when compared to two-drug regimens (dexamethasone plus remdesivir) in severe COVID-19 (p = 0.116). No treatment arm appeared to show a statistically significant decrease in mortality for severe COVID-19 patients.ConclusionsOur findings suggest that three-drug combination may decrease LOS in severe COVID-19 patients when compared to two-drug therapy. However, the trend was not supported by statistical analysis. Remdesivir may not be clinically beneficial for mild hospitalized COVID-19 patients; considering its cost, one could reserve it for moderate and severe patients. Triple drug therapies, while potentially reducing LOS for severe patients, do not affect overall mortality. Additional patient data may increase statistical power and solidify these findings.

Drug Prescription Patterns and Quality of Life in Rheumatoid Arthritis Patients at a Tertiary Care Teaching Hospital in Central India: A Cross-Sectional Study

Objective: Drug use research’s main goal is to assist patients in using medications responsibly. The chronic inflammatory disease rheumatoid arthritis (RA) is a condition comprising long-term disability. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of therapy preventing joint damage. The study’s aim was to examine the prescription trends for medications used to treat RA. Methodology: In conjunction with the orthopedic department, a cross-sectional observational study was carried out in a tertiary care hospital for 6 months. The current study included 90 patients in total who met the inclusion and exclusion requirements. Data from patients were collected in a case report format and examined to determine the prescription pattern in all 90 patients participated in the study. Female preponderance was seen in the study with 68.8% of female patients compared to 31.1% of male patients affected by the disease. Patients of the age group of 40–60 years (63.3%) were most commonly affected, followed by 61–70 years (26.6%). A combination of two DMARDs, methotrexate and hydroxychloroquine (HCQ), was the most common in 90% of patients. Triple-DMARD combination was required only in 4.4% of patients. Etoricoxib was most the commonly prescribed analgesic in 28.8% of patients, followed by etodolac in 16.6%. Conclusions: RA affects females more often than males. DMARD combination of methotrexate and HCQ was the most commonly used compared to monotherapy and triple-drug therapy. Drug utilization studies give the prescriber feedback and raise their awareness of the proper usage of medications.