Initial Regimen Research Articles

Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC). Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS). The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission. The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.

Analysis of panel physician inquiries to U.S. TB Centers of Excellence, 2018-2022.

Applicants seeking entry into the United States are examined overseas for TB by panel physicians and international immigration clinicians guided by Centers for Disease Control and Prevention (CDC) TB Technical Instructions. To support this effort, CDC-funded TB Centers of Excellence (COEs) provide web-based expert consultation, with documentation stored in a medical consultation database (MCD). MCD analysis can reveal inquiry trends among panel physicians worldwide. TB-related queries in the COE MCD from January 1, 2018, to December 31, 2022, were analyzed using a descriptive coding scheme developed through inductive analysis, allowing multiple themes per entry. A total of 215 queries from 126 patients in 28 countries were analyzed. Major themes included evaluating diagnostic criteria, tailoring treatment, and managing comorbidities or adverse reactions. Diagnostic questions (n = 104, 48.4%) included mycobacterial culture, smear, and radiology interpretation. Treatment tailoring inquiries involved optimizing the initial regimen (n = 89, 41.4%) or modifying existing regimens (n = 26, 12.1%). Additionally, 50 consultations (23.2%) mentioned comorbidities, while 47 (21.9%) described adverse reactions. The MCD analysis identified topics where TB expertise was provided in overseas medical evaluation. These topics highlight opportunities for targeted panel physician education to improve the health of individual applicants and advance U.S. TB elimination efforts.

Strengthening and standardizing the preventive treatment for tuberculosis in comprehensive medical facilities

Preventive treatment of high-risk groups for tuberculosis is an important part of tuberculosis prevention and control strategies, and comprehensive medical facilities have an important role to play. This issue of the journal published the "Expert consensus on tuberculosis preventive treatment for individuals at high risk of developing active diseases from latent tuberculosis infection in comprehensive medical facilities". The consensus defined the target population for tuberculosis preventive treatment, recommended the timing of treatment initiation and optional treatment regimens for different groups, and put forward suggestions for the management of preventive treatment. It helped to guide the comprehensive medical facilities to provide more standardized tuberculosis preventive treatment. This article discussed the background and clinical significance of the consensus.

Trends in Initial Antihypertensive Medication Prescribing Among >2.8 Million Veterans Newly Diagnosed With Hypertension, 2000 to 2019.

Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first-line β-blocker use without a compelling condition has fallen out of favor in US guidelines. This serial cross-sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (<140, 140 to <160, and ≥160 mm Hg), as well as trends in subgroups (age, sex, race and ethnicity, and comorbidities warranting β-blocker use). Among 2 832 684 eligible Veterans (average age 61 years, 95% men, 65% non-Hispanic White, and 8% with cardiovascular disease), from 2000-2004 to 2015-2019, initial monotherapy increased across all pretreatment systolic BP levels (<140 mm Hg: 62.1% to 66.4%; 140 to <160 mm Hg: 70.7% to 76.8%; ≥160 mm Hg: 64.2% to 69.7%). Initiation of dual therapy decreased across all pretreatment systolic BP levels (<140 mm Hg: 25.0% to 24.2%; 140 to <160 mm Hg: 20.4% to 17.6%; ≥160 mm Hg: 22.7% to 22.0%). Among 2 521 696 Veterans (89% of overall) without a β-blocker-indicated condition in 2015 to 2019, 20% initiated a β-blocker, most commonly as monotherapy. More than half of US Veterans diagnosed with hypertension with a pretreatment systolic BP ≥160 mm Hg were started on antihypertensive monotherapy. There are disparities between guideline-recommended first-line treatments and the actual regimens initiated for newly diagnosed Veterans with hypertension.

Phototesting for a variety of skin conditions before narrowband (TL-01) Ultraviolet-B

Background: For the majority of photo responsive skin disorders, narrowband ultraviolet-B (NBUV-B) phototherapy is currently regarded as the preferred option. The initial dosage of NBUV-B phototherapy is determined as a percentage of the minimal erythema dose (MED) at the majority of dermatology centers that offer phototherapy. This will shorten the time of therapy and lower the chance of burning while optimizing the therapeutic effect. Three times a week is the usual dosage for NBUV-B phototherapy treatment, which takes 18 to 30 sessions on average to clear the condition. For these types of treatment plans, a precise evaluation of the MED is necessary before starting treatment in order to prevent NBUV-B overdoses or underdoses. Aim: The objective of this study is to investigate the MED of 311nm NBUV-B phototherapy in a group of Libyan patients. Methods: For this prospective study, 150 patients with a range of skin conditions who saw the phototherapy unit at Bir Usta Melad Hospital of Dermatology and Venereology in Tripoli, Libya over an 8-month period were enrolled. Skin conditions include vitiligo, atopic dermatitis, and psoriasis are among those being researched. Using Fitzpatrick's questionnaire, skin types were assigned to each patient. Using a MED tester instrument (Dermalight® 80), 311 nm NBUV-B was applied to the right forearm. The test findings were recorded 24 hours later. Results: Of the patients studied, 82 (54.7%) were female and 68 (45.3%) were male. Their ages ranged from 10 to 60 years, with 30% of the sample falling between the ages of 31 and 40. The patients were clinically diagnosed with the following conditions: vitiligo 65(43.3%), psoriasis 61(40.7%), eczema 8(5.3%), pruritus 6(4%), and alopecia areata and lichen planus 5(3.3%) each. According to Fitzpatrick's categorization, the skin prototypes in the included series were 15(10%) patients of skin type III, 118(78.7%) patients of skin type IV, and 17(11.3%) patients of skin type V. Among the enrolled participants, the minimum necessary dose to elicit an erythema for NBUV-B ranged between 300 mJ/cm2 and 750 mJ/cm2, with the mean dosage was 484.7 ± 82.2 mJ/cm2. Conclusions: The average MED to 311nm NBUV-B in Libyan patients was around 500 mJ/cm2, which can be utilized to determine the initial dose and treatment regimen of phototherapy for various skin conditions.

Linking clinical manifestations and causative organisms may provide clues for the treatment of peritoneal dialysis-associated peritonitis

IntroductionDifferent initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection.MethodsPatients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin.ResultsOf 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980–0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580–8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207–0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918–0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749–0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%.ConclusionsCloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment.

OxcarNet: sinc convolutional network with temporal and channel attention for prediction of oxcarbazepine monotherapy responses in patients with newly diagnosed epilepsy

Objective.Monotherapy with antiepileptic drugs (AEDs) is the preferred strategy for the initial treatment of epilepsy. However, an inadequate response to the initially prescribed AED is a significant indicator of a poor long-term prognosis, emphasizing the importance of precise prediction of treatment outcomes with the initial AED regimen in patients with epilepsy.Approach. We introduce OxcarNet, an end-to-end neural network framework developed to predict treatment outcomes in patients undergoing oxcarbazepine monotherapy. The proposed predictive model adopts a Sinc Module in its initial layers for adaptive identification of discriminative frequency bands. The derived feature maps are then processed through a Spatial Module, which characterizes the scalp distribution patterns of the electroencephalography (EEG) signals. Subsequently, these features are fed into an attention-enhanced Temporal Module to capture temporal dynamics and discrepancies. A channel module with an attention mechanism is employed to reveal inter-channel dependencies within the output of the Temporal Module, ultimately achieving response prediction. OxcarNet was rigorously evaluated using a proprietary dataset of retrospectively collected EEG data from newly diagnosed epilepsy patients at Nanjing Drum Tower Hospital. This dataset included patients who underwent long-term EEG monitoring in a clinical inpatient setting.Main results.OxcarNet demonstrated exceptional accuracy in predicting treatment outcomes for patients undergoing Oxcarbazepine monotherapy. In the ten-fold cross-validation, the model achieved an accuracy of 97.27%, and in the validation involving unseen patient data, it maintained an accuracy of 89.17%, outperforming six conventional machine learning methods and three generic neural decoding networks. These findings underscore the model's effectiveness in accurately predicting the treatment responses in patients with newly diagnosed epilepsy. The analysis of features extracted by the Sinc filters revealed a predominant concentration of predictive frequencies in the high-frequency range of the gamma band.Significance. The findings of our study offer substantial support and new insights into tailoring early AED selection, enhancing the prediction accuracy for the responses of AEDs.

Vancomycin in Pediatric Patients with Cystic Fibrosis: Dose Optimization Using Population Pharmacokinetic Approach.

An increase in Staphylococcus aureus infections has been reported in pediatric patients with cystic fibrosis (CF) over the last few years. This pathogen is commonly treated with vancomycin, an antibiotic for which therapeutic drug monitoring (TDM) is recommended. Updated guidelines were recently published regarding new targets of exposure for the TDM of vancomycin through a Bayesian approach, using population pharmacokinetic (popPK) models. This study aims to assess the predictive performance of vancomycin popPK models in pediatric patients with CF and to recommend optimal initial dosing regimens based on simulations. Patient data were collected from two centers in Canada, and a literature review was conducted to identify all published vancomycin popPK models for pediatric CF patients. External evaluation and simulations were performed according to patient and occasion of treatment. A total of 53 vancomycin concentrations were collected from six pediatric CF patients. Only two popPK models of vancomycin for pediatric CF patients were identified through the literature review. The external evaluation results for both centers combined revealed a population bias of 28.1% and an imprecision of 33.7%. A re-estimation of parameters was performed to improve predictive performance. The optimal initial dosing regimen was 15 mg/kg/dose administered every 6 hours according to the per occasion remodel. The predictive performance and identified optimal initial dosing regimens associated with the model were different depending on the data used, showing external evaluation's importance before implementing a model in clinical practice.

Clinical and economic analysis of the use of dapagliflozin in patients with chronic heart failure with reduced left ventricular ejection fraction in various subgroups of standard therapy in the Russian Federation

To evaluate the clinical and economic effectiveness of dapagliflozin in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (HFrEF) in the Russian Federation in various subgroups of standard therapy for CHF. A clinical and economic analysis of the use of the drug dapagliflozin in addition to standard therapy was carried out in comparison with standard therapy in various subgroups of standard therapy for HFrEF using a modeling method. Cost calculations were carried out in a mathematical model adapted to the healthcare conditions of the Russian Federation by using Russian cost indicators and characteristics of the patient population. The present study demonstrates that the addition of dapagliflozin is beneficial in terms of clinical and cost-effectiveness, regardless of the initial regimen (angiotensin receptor-neprilysin inhibitors [ARNI] or angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]) of standard drug therapy for HFrEF and in all cases leads to an increase in life expectancy, a decrease in the number of hospitalizations and emergency visits due to CHF, as well as cardiovascular mortality. The obtained values of added value per additional year of life in all cases are significantly lower than the willingness-to-pay threshold, which indicates the clinical and economic effectiveness of the strategy of prescribing dapagliflozin as part of standard therapy for patients with HFrEF. In the case of adding dapagliflozin the values of the additional cost of an added year of life in the 3 considered standard therapy options (ARNI or ACEi/ARB, only ACEi/ARB and only ARNI) were 291,256, 279,571 and 338,374 rubles respectively. Thus, the scenario of using dapagliflozin with standard therapy, which included only ACEi/ARB, is characterized by the lowest additional cost and has the best clinical and economic characteristics. At the same time the scenario of use with standard therapy, which included only ARNI, is characterized by the highest value of the additional value of the added year of life.

Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis.

To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach. A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs). The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders. The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.

Peritoneal scintigraphy and SPECT/TC in the diagnosis of leaks in patients on peritoneal dialysis

ObjectiveTo assess the usefulness of peritoneal cavity scintigraphy and the contribution of SPECT/CT in patients on peritoneal dialysis with suspected leak. MethodologyAn observational case series study is carried out. It consists of a longitudinal, retrospective and descriptive study. 11 patients on peritoneal dialysis were studied and it was realiced a peritoneal cavity scintigraphy test and SPECT/CT to evaluate a peritoneal leak. ResultsIn 54,5% of the patients, a positive study of peritoneal leak was obtained. The most frequent localitations were in the abdominal wall at the catheter entry level and the inguinal hernia. In the cases with sintomatology like pain and celullitis of the subcutaneous tract of the cateter the frequent of leak was 100%. There was a change in therapeutic management in patients with a positive study. There was not relevant changes in initial dialysis regimen in patients with a negative study. In this cases, except for one patient who required hemodialysis, all patients experienced clinical improvement. ConclusionsPeritoneal scintigraphy and SPECT/CT study are non-invasive techniques that allow an adequate diagnosis and subsequent management of peritoneal leak.

Interval to Recurrence Affects Survival in Recurrent Head and Neck Squamous Cell Carcinoma.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, with most recurrences occurring within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment is associated with prognosis in patients with HNSCC, further investigation is needed. Patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n=500). Early recurrence (ER) was defined as disease recurrence within six months of radical treatment, whereas late recurrence (LR) was defined as recurrence after more than six months. Continuous variables were assessed using the Mann-Whitney U-test and categorical variables were assessed using Fisher's exact test. A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing ER (recurrence within two to six months) and LR (recurrence after six months), respectively. Multivariate analyses identified two independent risk factors for poor prognosis: ER [hazard ratio (HR)=3.200, 95% confidence interval (CI)=1.570-6.521, p=0.001] and absence of radiotherapy (HR=0.374, 95%CI=0.191-0.733, p=0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in these patients. The selection of treatment for patients with recurrent head and neck squamous cell carcinoma should consider the timing of recurrence, the initial treatment regimen, and the strategy for changing salvage therapy depending on the recurrence status.

Impact of an updated venous thromboembolism prophylaxis guideline in critically ill trauma patients on rates of venous thromboembolisms

IntroductionThe objective of this analysis was to evaluate differences in incidence of venous thromboembolisms (VTE) in critically ill trauma patients between pre- and post-implementation of updated VTE prophylaxis guidelines. MethodsThis was a pre-post analysis of critically ill trauma patients receiving pharmacologic VTE prophylaxis. Trauma patients were included if they had an intensive care unit admission during their hospitalization. The primary outcome was incidence of detected VTE and was analyzed using a Chi-Squared test. A multivariate analysis assessed the effects of guideline implementation on VTE development when controlling for confounders. ResultsThere were 220 patients included. There was a significant increase in low molecular weight heparin use in initial (p ​= ​0.003) and final (p ​= ​0.004) prophylactic regimens between groups. There was no significant difference in VTE incidence between the pre and post groups (6.3% vs 1.9%, p ​= ​0.10). The multivariate analysis showed guideline implementation was independently associated with an 88% reduced odds of VTE (p ​= ​0.04). ConclusionThis analysis suggests the updated VTE prophylaxis guideline implementation was associated with a trend toward reduced VTE development among critically ill trauma patients.

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over β-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. β-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension.

Anticoagulation strategy for patients presenting with ischemic strokes while using a direct oral anticoagulant: A systematic review and meta-analysis.

While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7-2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43-0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25-0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30-0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06-3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. Post-stroke adjustments to anticoagulation therapy-whether altering the drug or its dosage-do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population.

Learning implementation of a guideline based decision support system to improve hypertension treatment in primary care in China: pragmatic cluster randomised controlled trial

ObjectiveTo evaluate the effectiveness of a clinical decision support system (CDSS) in improving the use of guideline accordant antihypertensive treatment in primary care settings in China.DesignPragmatic, open label, cluster randomised...

Factors Associated with Time to Initial Antiretroviral Therapy Discontinuation in the DC Cohort.

When an initial antiretroviral therapy (ART) regimen is effective and well-tolerated, it can be maintained for years as long as the patient adheres. Prior research has revealed that shorter initial ART duration is associated with regimen type, female sex, injection drug use as the HIV transmission category, and lower baseline CD4 count. We examined potential factors associated with initial regimen discontinuation among a subset of newly diagnosed virally unsuppressed PWH in the DC Cohort, an ongoing prospective observation study that uses electronic health record data from clinic sites to collect relevant information, including demographic and clinical information. Participants were excluded from the analysis if they had less than 6 months of follow-up and were virally suppressed at enrollment. There were 479 individuals included in the study. The median age of participants was 33.9 years [interquartile range (IQR) 26-43.9]. The sample was predominantly male (79.1%) and of Black race (70.8%). Over half of the study participants (56.4%) attended community-based clinic sites. The median time to the discontinuation of initial ART was 2.7 years [95% confidence interval (CI): 2.3, 3.4]. Females had a shorter time to ART discontinuation [adjusted hazard ratio (aHR) 1.55, 95% CI: 1.14, 2.11] as did individuals who started on a protease inhibitor-based regimen versus integrase strand transfer inhibitors (aHR 1.87, 95% CI: 1.34, 2.61) and those receiving HIV care at a community-based site (aHR 1.46, 95% CI: 1.11,1.93). Although limited by lack of reason for discontinuation, we demonstrated that ART-naïve women, community clinic attendees, and patients starting on PIs had a shorter duration of initial ART. More anticipatory guidance may be needed to help patients stay on their initial therapy and manage the side effects or to be flexible in trying different regimens.

294 Does the Initial Antibiotic Choice Affect the Incidence of Post-Operative Collections in Paediatric Appendicitis?

Abstract Introduction In appendicitis, antibiotics are routinely commenced prior to consideration of operative management. The choice of initial regimen depends on local antimicrobial guidelines. The presence of resistant organisms risks development of post-operative collections. In our tertiary paediatric surgery unit, antimicrobial guidelines were changed in September 2022 to recommend co-amoxiclav instead of cefuroxime/metronidazole. This study compares incidence of post-operative collections before and after the policy change. Method Patients who underwent appendicectomy between September 2021 and October 2023 were identified and contemporaneous data collected. Patients who had initial surgery elsewhere, interval/incidental appendicectomies or penicillin allergy were excluded. Comparison was made between patients receiving cefuroxime/metronidazole (Group 1) or co-amoxiclav (Group 2). Results Over the 26-month period, there were 104 patients in Group 1 (after excluding 47) and 104 in Group 2 (after excluding 46). 4 (3.8%) developed collections in Group 1 versus 13 (12.5%) in Group 2. In Group 1, 2 (50%) were treated with antibiotics alone, 1 (25%) required drain insertion and 1 (25%) had a laparotomy. In Group 2, 7 (54%) were treated with antibiotics alone, 5 (38%) required drain insertion and 1 (8%) had a laparotomy. The relative risk of developing a post-operative collection was 3.3 (p=0.023) in Group 2 versus Group 1. Conclusions The change in antimicrobial policy resulted in a significant increase in post-operative collections in our unit. This provides evidence that a regimen of cefuroxime/metronidazole is more effective at preventing collections and we are liaising with our Microbiology department with a view to amend the guidelines.

Frequency of Human Leukocyte Antigen-B*57:01 Allele Carriers in People Living with HIV/AIDS in Türkiye.

Abacavir is among the first-line initial antiretroviral regimens for most patients living with HIV/AIDS (PLWHA). Although well tolerated, it is associated with hypersensitivity reaction (HSR), which is treatment-limiting and potentially life-threatening. HSR was shown to be associated with the class I MHC allele, HLA-B*57:01. In this study, we aimed to evaluate the prevalence of HLA-B*57:01 in PLWHA in Istanbul, Türkiye. Five HIV treatment centers in Istanbul included all sequential treatmentnaïve, ≥ 18 years adult PLWHA, between December 2017- December 2021. Demographic, clinical, and laboratory data were collected at baseline and during treatment. HLA-B* 57:01 genotyping was determined with PCR-SSP. Eight hundred sixty-seven PLWHA were included (male:91%, mean age 39.6±11.1 years). 1.6% of patients were found to be HLA-B*57:01 positive. Among HLA-B*57:01 positive patients, 4 were initially given abacavir-containing treatment; they were switched to non-abacavir treatment upon the allele found to be positive. Although previous studies reported the HLA-B*57:01 prevalence of PLWHA in Türkiye as 3-3.6%, we have found the prevalence to be 1.6%. The current study includes higher numbers of patients than the previous studies. Furthermore, patients from all over the country apply to the centers in Istanbul; compared to the other studies, which involve patients limited to the relevant regions. It can be assumed that the number in our cohort is more representative of the country. In conclusion, the prevalence of the HLA-B*57:01 allele in PLWHA in this study is relatively low. With evident benefit in preventing abacavir HSR, HLA-B*57:01 should be screened in planning antiretroviral therapy.

Metformin in Combination with Standard Therapy in Patients with Diffuse Large B-Cell Lymphoma: A Randomized Phase II Clinical Trial.

Metformin has been shown to have antitumor activity in different tumor types. In DLBCL (Diffuse large B cell lymphoma), using metformin with front-line chemotherapy & immunotherapy resulted in improved clinical outcomes. To assess the effectiveness of incorporating metformin into the standard initial treatment regimen of R-CHOP for patients with DLBCL. The evaluation metrics included response rate, toxicity, progression-free survival (PFS), and overall survival (OS). This prospective phase 2 trial included 100 adult patients with histopathological evidence of DLBCL, eligible for first-line treatment with R-CHOP, life expectancy of at least 6 months, and performance status (PS) ≤ 2. Patients were randomized to receive either metformin plus R-CHOP or R-CHOP alone. Each group included 50 patients. The metformin arm had more females than the standard arm (p=0.016). Nausea was significantly higher in the test arm than the standard arm (p=0.008). Metformin group had higher rates of complete remission (CR) at the end of treatment (92% vs 74%; p=0.017), lower rates of relapse/progression (10% vs 36%; p=0.002), and lower rates of overall mortality (4% vs 20%; p=0.014). The mean disease-free survival (DFS) was 24.5 months in the metformin group versus 20.2 months in the control arm (p=0.023). Likewise, the mean progression-free survival (PFS) was 25.91 versus 19.81 months and the mean overall survival (OS) was 27.39 versus 23.8 months (p-values= 0.002, and 0.013 respectively). By multivariate analysis of response and relapse, the use of metformin was an independent prognostic factor of CR and relapse. The addition of metformin to standard R-CHOP could improve clinical outcomes in patients with DLBCL with a tolerable safety profile.