Initiation Of Drug Therapy Research Articles

Cardiological monitoring during BTK inhibitor, ICI, and RAF/MEK inhibitor therapy: the single-center prospective registry for cardiovascular events under new cancer therapies (RECENT)

Abstract Background The advent of novel targeted cancer therapies have revolutionized cancer treatment. However, concerns about their impact on cardiovascular health persist and current guidelines recommend cardiac monitoring. Yet, prospective data on incidence rates of cardiovascular events are lacking. The Registry for Cardiovascular Events under new cancer Therapies (RECENT) aims to systematically assess clinical as well as subclinical cardiovascular incidents in patients undergoing these novel therapies to identify baseline risk factors and derive individualized monitoring strategies. Methods This ongoing single-center prospective registry enrolls cancer patients receiving BTK inhibitors, ICI, or RAF/MEK inhibitors. Baseline cardiovascular assessment, risk stratification according to HFA-ICOS risk score, and follow up visits for 12 months at three-monthly intervals (including ECG, biomarkers and echocardiography) during treatment are conducted. Treatment-related events, in particular hypertension, arrhythmias, cancer therapy-related cardiac dysfunction (CTRCD), and (peri-) myocarditis, as defined according to current guideline recommendations, are recorded. Results We report data of the first 85 patients (60.9 ± 14.7 years, 52.9% male) included in this ongoing registry. Of those, 17/85 patients received treatment with BTK inhibitors (20%), 45/85 with ICI (53%) and 23/85 with RAF/MEK inhibitors (27%). Most common treatment indication were dermatological (39/85, 45.9%), hematologic (17/85, 20%), urological (13/85, 15.3%) and head and neck (11/85, 12.9%) cancers. Before treatment, the majority of patients were stratified as low-risk (31/85) or moderate-risk (32/85), and 22/85 (25.9%) as high-risk. 7/85 (8.2%) patients were newly diagnosed with cardiovascular disease at baseline visit, resulting in a change in risk category and subsequent initiation of cardiovascular treatment. This includes 3 patients who had been initially categorized as low-risk and would not have been referred for further cardiac workup due to current guideline recommendations. The six months follow up visit has been completed in 44/85 patients. Among these, 1/20 patients (5%) with ICI developed a perimyocarditis and 2/11 patients (18.2%) with BTK inhibitors developed atrial fibrillation. 1/13 patients (7.7%) with RAF/MEK inhibitor therapy, classified as low-risk at baseline, developed asymptomatic CTRCD, which resolved after initiation of cardioprotective drug therapy. Conclusion This interim analysis of the RECENT registry indicates benefit of a structured baseline cardiac assessment prior to cancer treatment in all patients, irrespective of the initial risk stratification. Contrary to current guidelines, which recommend routine echocardiographic monitoring in patients receiving RAF/MEK inhibitors only in high-risk patients, the current data advocate for extending this also to low-risk patients to detect subclinical deterioration of the cardiovascular status.

Therapeutic inertia and contributing factors among ambulatory patients with hypertension

BackgroundTherapeutic inertia refers to the failure of healthcare providers to initiate or intensify therapy based on current evidence-based guidelines, even when the desired treatment goal is not achieved. Despite poorly controlled hypertension, clinicians often hesitate to intensify treatment. Therapeutic inertia is currently receiving more attention as a significant reason for clinicians’ inability to effectively manage hypertension. However, in our setting, there is limited knowledge about therapeutic inertia and its contributing factors.ObjectivesThe aim of this study was to investigate therapeutic inertia and contributing factors among ambulatory patients with hypertension.MethodA prospective observational study was conducted at the cardiac clinic of Ayder comprehensive specialized hospital in the Tigray region of northern Ethiopia. Patients were recruited into the study during their medication refilling appointments using a simple random sampling technique. All patients were followed for a minimum of 6 months to assess therapeutic inertia, which was defined as the healthcare providers’ failure to initiate or intensify therapy based on current evidence-based guidelines when therapeutic goals were not achieved. Data were collected through patient interviews and review of their medical records. We utilized binary logistic regression analysis to determine factors associated with therapeutic inertia.ResultThe study included 282 participants, with an equal male-to-female ratio. The mean age of the participants was 56.6 ± 12.3 years. Among all participants, a majority (67.4%) had uncontrolled hypertension. The study revealed that 72% of patients with uncontrolled hypertension experienced therapeutic inertia. In response to this issue, we recommended dose escalation for 73% of the patients and the initiation of additional drug therapy for 27% of them. Multivariable analysis indicated that having three or more medications (AOR = 4.74, 95%CI = 1.94–11.61) and having stage II hypertension (AOR = 3.06, 95%CI = 1.32–7.08) were identified as independent predictors of therapeutic inertia.ConclusionThe findings of our study indicated that a large proportion of the patients had poorly controlled hypertension, and a significant number of these patients also demonstrated therapeutic inertia. The number of medications and stage II hypertension were identified as independent predictors of therapeutic inertia. Therefore, it is crucial to prioritize patients at risk of therapeutic inertia and provide them with additional support. Moreover, practice based training should be given to clinicians in order to enhance treatment intensification and overall treatment outcome among ambulatory patients with hypertension.

Implantable Loop Recorders in patients with Brugada Syndrome: the BruLoop Study

Abstract Aims Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. Aim of this multicentre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients, and to assess the precise arrhythmic cause of syncopal episodes. Methods and Results A total of 370 patients with BrS and ILRs (mean age 43.5±15.9, 33.8% females) from 18 international centers were included. Overall, 274 (74.1%) were implanted due to symptoms (69.3% syncope, 30.7% palpitations). Over a median follow-up of 3 years, an arrhythmic event was recorded in 30.7% of symptomatic patients (18.6% atrial arrhythmias (AAs); 10.2% bradyarrhythmias (BAs) and 7.3% ventricular arrhythmias (VAs)). In patients with recurrent syncope, the etiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of PM in 2.5% and ICD in 8%. At multivariate analysis, the presence of symptoms (HR 2.5, p=0.001) and age >50 years (HR 1.7, p=0.016) were independent predictors of arrhythmic events, while inducibility of VF at EP study (HR 9.0, p<0.001) was predictor of ventricular arrhythmias. Conclusion ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to an appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.General ResultsArrhythmias

P062 Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach

Abstract Background/Aims To evaluate trust-level performance in time to initiation of disease-modifying antirheumatic drug (DMARD) therapy in patients with early inflammatory arthritis (EIA), with identification of change in performance trajectories over time and investigation of trust characteristics associated with this change. Methods We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed-effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics. Results The mean (SD) time to DMARD initiation was 53 (18) days, with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with over 77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worse performance group (OR = 0.69 [95%CI 0.49, 0.93]). Conclusion In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA. Disclosure Z. Yang: None. N. Arumalla: None. M.D. Russell: Honoraria; Lilly, Menarini, Galapagos. Grants/research support; NIHR. Other; Pfizer, Janssen, Biogen, and UCB. K. Bechman: Honoraria; Menarini, Galapagos. Grants/research support; NIHR,Versus Arthritis and Pfizer Global Medical Grants for Quality Improvement in Rheumatology Practice. Other; UCB. E. Alveyn: Other; UCB. S. Gallagher: None. E. Price: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

Prognosis and clinical management of asymptomatic family members with RYR2-mediated catecholaminergic polymorphic ventricular tachycardia: a review.

Despite its low prevalence, the potential diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) should be at the forefront of a paediatric cardiologists mind in children with syncope during exercise or emotions. Over the years, the number of children with a genetic diagnosis of CPVT due to a (likely) pathogenic RYR2 variant early in life and prior to the onset of symptoms has increased due to cascade screening programmes. Limited guidance for this group of patients is currently available. Therefore, we aimed to summarise currently available literature for asymptomatic patients with a (likely) pathogenic RYR2 variant, particularly the history of CPVT and its genetic architecture, the currently available diagnostic tests and their limitations, and the development of a CPVT phenotype - both electrocardiographically and symptomatic - of affected family members. Their risk of arrhythmic events is presumably low and a phenotype seems to develop in the first two decades of life. Future research should focus on this group in particular, to better understand the development of a phenotype over time, and therefore, to be able to better guide clinical management - including the frequency of diagnostic tests, the timing of the initiation of drug therapy, and lifestyle recommendations.

Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan.

Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.

Effect of Antiresorptive Drugs on Osseointegrated Dental Implants: A Systematic Review.

Background: This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). Methods: A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. Results: The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. Conclusions: This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.

The Effect of Initial Anti-tuberculosis Drug Therapy on Transminase Enzymes

Tuberculosis is still a health problem in the world. TB treatment is carried out in 2 phases, namely early and advanced. This study aims to determine changes in serum transaminase enzyme levels (SGOT and SGPT) in pulmonary TB patients before and after initial drug administration. This study was observational with a cohort study design study. Observations were conducted in tuberculosis patients who received initial ATD therapy for 2 months for SGOT and SGPT enzyme levels before and after treatment. The subject of the study was a new case of a pulmonary TB patient aged ?16 years. Subjects received initial therapy in the form of isoniazid, rifampicin, pyrazinamide, and ethambutol. Recruitment of subjects through successive sampling methods with informed consent. Using a spectrophotometer, SGOT and SGPT enzyme tests were performed on the median blood serum cubital vein. Data analysis using the Wilcoxon Test. The study involved 19 subjects (10 men and 9 women) aged 16-65 years. Before ATD, the mean SGOT was 22.84 IU/L, and SGPT was 21.37 IU/L. After ATD, SGOT increased to 58.63 IU/L (p = 0.023), and SGPT to 80.84 IU/L (p = 0.007). Of the 19 subjects, 8 experienced a significant increase in SGOT and 5 SGPT. Five cases showed an increase in SGPT in line with SGOT, and 3 cases showed an increase in SGOT without SGPT. One case saw an increase in SGOT and SGPT of more than 5 times the reference value. This study confirms an increase in transaminase enzymes during initial therapy with first-line ATD.

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

Rapid Detection of M. tuberculosis and Its Resistance to Rifampicin and Isoniazid with the mfloDx™ MDR-TB test.

Rapid detection of tuberculosis (TB) and its resistance are essential for the prompt initiation of correct drug therapy and for stopping the spread of drug-resistant TB. There is an urgent need for increased use of rapid diagnostic tests to control the threat of increased TB and multidrug-resistant TB (MDR-TB). EMPE Diagnostics has developed a multiplex molecular diagnostic platform called mfloDx™ by combining nucleotide-specific padlock probe-dependent rolling circle amplification with sensitive lateral flow biosensors, providing visual signals, similar to a COVID-19 test. The first test kit of this platform, mfloDx™ MDR-TB can identify Mycobacterium tuberculosis (MTB) complex and its clinically significant mutations in the rpoB and katG genes and in the inhA promotor contributing resistance to rifampicin (RIF) and isoniazid (INH), causing MDR-TB. We have evaluated the performance of the mfloDx™ MDR-TB test on 210 sputum samples (110 from suspected TB cases and 100 from TB-negative controls) received from a tertiary care center in India. The clinical sensitivity for detecting MTB compared to acid-fast microscopy and mycobacteria growth indicator tube (MGIT) cultures was 86.4% and 84.9%, respectively. All the 100 control samples were negative indicating excellent specificity. In smear-positive sputum samples, the mfloDx™ MDR-TB test showed a sensitivity of 92.5% and 86.4% against MGIT culture and Xpert MTB/RIF, respectively. The clinical sensitivity for the detection of RIF and INH resistance in comparison with MGIT drug susceptibility testing was 100% and 84.6%, respectively, while the clinical specificity was 100%. From the above evaluation, we find mfloDx™ MDR-TB to be a rapid and efficient test to detect TB and its multidrug resistance in 3 h at a low cost making it suitable for resource-limited laboratories.

Comprehensive analysis of nationwide anticancer drug-related complications in Korea: incidence, types, and cancer-specific considerations in contemporary oncology.

The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking. This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea. Retrospective cohort study. We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects. We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6-12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash. This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease

BackgroundAlpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). ObjectiveThis study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. MethodsNational Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. ResultsA total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77–0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81–0.88]) and in sensitivity analyses. ConclusionPatients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Early-stage diagnosis of bladder cancer using surface-enhanced Raman spectroscopy combined with machine learning algorithms in a rat model

Early diagnosis and accurate assessment of tumor development facilitate early bladder cancer resection and initiation of drug therapy. This study enabled an early, accurate, label-free, noninvasive diagnosis of bladder tumors by analyzing nano-biomarkers in a single drop of urine through surface-enhanced Raman spectroscopy (SERS). In a standard N-butyl-N-4-hydroxybutyl nitrosamine–induced rat model of bladder cancer, cancer stage and polyp tumor development were monitored using a small endoscope with a diameter of 1.2 mm in a minimally invasive manner without the need to kill the rats. Samples were divided into cancer-free, early-stage, and polyp-form cancer. Training data were classified according to micro-cystoscopic 5-aminolevulinic acid fluorescence diagnosis, and specimens were postmortem verified through histopathological analysis. A drop of urine from each sample group was placed on an Au-coated zinc oxide nanoporous chip to filter nano-biomaterials and selectively enhance the Raman signals of nanoscale analytes via SERS. Principal component analysis was used to reduce the dimensionality of the collected Raman spectra, and partial least squares discriminant analysis was used to find diagnostic clusters based on the labeled samples. The combination of SERS and machine learning achieved an accuracy ≥99.6% in diagnosing both early- and polyp-stage bladder tumors. With an area under the receiver operating characteristic curve greater than 0.996, the accuracy of the diagnosis in the rat model suggests that SERS-based diagnostic methods are promising when coupled with machine learning. Low-cost, label-free, and noninvasive surface-enhanced Raman spectra are ideal for developing clinically relevant point-of-care diagnostic techniques.

VA Home Telehealth Program for Initiating and Optimizing Heart Failure Guideline-Directed Medical Therapy.

Heart failure (HF) is a chronic, progressive medical condition. Evidence suggests that guideline-directed medical therapy improves both morbidity and mortality in patients with HF with reduced ejection fraction when properly optimized. Unfortunately, many patients do not receive optimized therapy, highlighting the need to optimize clinicians' methods to more effectively and efficiently initiate and titrate medical therapy. This single-center, retrospective study evaluated the rates of drug interventions prompted by the home telehealth monitoring program for veterans with HF with reduced ejection fraction. Rates of drug interventions were evaluated among those who enrolled and those who did not enroll in the program. There were 20 drug-related interventions in the home telehealth group compared with 11 interventions for the control group. One HF-related hospitalization occurred in the home telehealth program group compared with 6 in the control group. This study demonstrates the potential of home telehealth to optimize veterans' medication regimens and to reduce HF-related hospitalizations. It also provides an additional catalyst to further develop home telehealth services specifically targeted at drug therapy initiation and optimization in patients with HF with reduced ejection fraction.

Osteomyelitis of Jaw Bone due to Aspergillosis in Post-COVID-19 Patients: An Observational Study.

In the second wave of COVID-19 pandemic, there has been an increase in number of cases with Post-COVID-19 fungal osteomyelitis of jaws. Aspergillosis was found to be one of the causes of osteomyelitis of jaw bones in these patients. To evaluate the incidence and pattern of osteomyelitis of jaw due to aspergillosis in post-COVID-19 patients and to discuss the management protocol of the same. Data were obtained at our institution from the period of January 2021 to June 2021. Patients of all age groups with Post-COVID-19 osteomyelitis of jaw due to aspergillosis and those with combined aspergillosis and mucormycosis infection were included. Patients having rhino-orbito-cerebral fungal infection were excluded. A total of 47 patients reported to our center. Demographically the average age of the patients was 49.11years with 72% being males. All 47 patients (N = 100%) had received steroids. 21 of them (N = 44.7%) had diabetes mellitus and 14 (N = 29.8%) patients had other comorbidities. Out of 47 patients, 42 (N = 89.7%) patients were diagnosed with aspergillosis and the remaining 5 (N = 10.3%) cases had a mixed fungal infection of mucormycosis and aspergillosis. On fungal culture Aspergillus flavus was the most common species detected followed by Aspergillus niger and Aspergillus fumigatus. All patients were treated with oral Voriconazole and local surgical debridement. Prompt laboratory testing such as a timely KOH mount, galactomannan test, beta-D-glucan test, histopathology of tissue specimens could help to give an early and definitive diagnosis. The mortality rate we encountered in this study was nil. Early and definitive diagnosis and immediate initiation of antifungal drug therapy and surgical intervention will significantly reduce the rate of morbidity and mortality.

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a German healthcare service payer perspective

Abstract Background Three recent randomized controlled trials demonstrated that, in patients with symptomatic paroxysmal atrial fibrillation (PAF), first-line pulmonary vein isolation (PVI) with cryoballoon ablation reduces atrial arrhythmia recurrence when compared to initial antiarrhythmic drug (AAD) therapy. Purpose To evaluate the cost-effectiveness of initial rhythm control therapy from a German healthcare service payer perspective. Methods The cost-effectiveness model (CEM) structure consisted of a hybrid decision tree and Markov model, where the decision tree informed the initial health state allocation in the first cycle of the Markov model and had a one-year time horizon. The Markov model had a 40-year time horizon using a three-month cycle length. Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% p.a. Individual patient-level data from 703 participants with untreated PAF enrolled into Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518) and EARLY-AF (NCT02825979) were used to estimate efficacy, resource use and health-related quality of life parameters. Cost inputs were sourced from diagnosis-related groups and the Institute for the Hospital Remuneration System (InEK). Where parameters could not be derived, inputs were sourced from available published literature or determined through clinical expert opinion. Probabilistic sensitivity analyses were conducted to explore the impact of any assumptions on model outputs. Results In those treated with cryoablation, the three-month rate of AF recurrence was reduced by 46.7% (p&amp;lt;0.001) on average. Similarly, the average monthly rate of receiving an ablation following initial treatment was reduced by 72.8% (p&amp;lt;0.001). Cryoablation was also associated with a 4.3% (p=0.025) increase in health-related quality of life at 12 months, assessed through the standard EQ-5D-3L instrument. There was no difference in the rate of AF resolution in those who failed initial treatment. CEM results are shown in Table 1. Analysis shows that cryoablation is cost-effective, incurring a cost of ∼€1,000 per patient over a lifetime compared to AADs, while offering an increase in QALYs. Cryoablation attains an average ICER of ∼€5,500, with a 94.1% probability of being cost-effective at a willingness-to-pay threshold of €35,000 per QALY gained. Through 5,000 iterations, the probabilistic sensitivity analysis indicates that cryoablation has ∼20% probability of being cost-saving. Individuals are expected to receive a total of ∼1.2 ablations over a lifetime, regardless of initial treatment. Although, those initially treated with cryoablation as opposed to AADs experience a 45% reduction in time spent in AF health states. Conclusion Initial rhythm control with cryoballoon ablation in PAF is a cost-effective treatment option in a German healthcare setting.Table 1:Key results (per patient)

Comparative analysis of methods for evaluating myocardial hypertrophy in children with arterial hypertension

Relevance: over the past decades, the prevalence of arterial hypertension (AH) in the pediatric population has increased significantly, but there are still many open questions related to the diagnosis and course of the disease, the validity of the choice of antihypertensive therapy and the risks of target organ injury. In clinical practice, patients with hypertension are observed by a team of specialists of various profiles, and a unified approach to managing the disease is not always formed between them. Underestimation of risk factors, late detection of target organ injury and untimely start of antihypertensive therapy significantly increase the risks of an unfavorable, progressive course of the disease, aggravating the further prognosis. Strict adherence to the methods of diagnosing the disease and its potential consequences recommended by the professional community of pediatric cardiologists ensures an adequate initiation of drug therapy, which allows not only to control the course of hypertension, but also to prevent the development of long-term complications. Objective: to analyze the indicators obtained using the formula recommended by pediatric cardiologists compared to the routine method for detecting left ventricular myocardial remodeling in children with AH. Materials and methods: a cross-sectional, cohort, non-randomized study, which included 92 patients with newly diagnosed primary arterial hypertension, who were not receiving antihypertensive therapy at the time of the examination. The standard linear dimensions of the walls and cavities of the heart were assessed during echocardiography. The results were evaluated by the standard Fisher’s test, the xi2 test in the Statistica 9 software. The sample excluded children-athletes, patients with secondary hypertension, overweight, congenital heart disease and cardiomyopathy. All children were tested the same according to the current Federal Clinical Guidelines “Diagnosis and treatment of arterial hypertension in children and adolescents”. Results: the usage of the recommended formula is not only significantly more often allowed to identify the early stages of LV myocardial hypertrophy, but has great sensitivity. The routine method for calculating LV remodeling showed the norm much more often even in case of severe violation of the geometry of the heart. Conclusion: untimely detection of LV myocardial hypertrophy leads to late initiation of antihypertensive therapy, underestimation of risk factors, which increases the risk of an unfavorable course of the disease and the occurrence of long-term cardiovascular complications at a young age.

Kids Mod PAH trial: A multicenter trial comparing mono- versus duo-therapy for initial treatment of pediatric pulmonary hypertension.

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.

Can sPD-1 and sPD-L1 Plasma Concentrations Predict Treatment Response among Patients with Extraparenchymal Neurocysticercosis?

Extraparenchymal neurocysticercosis (EP-NC) is a chronic, potentially life-threatening disease that responds poorly to initial anthelmintic drug therapy. A depressed specific reactivity of peripheral lymphocytes and an increased level of specific Tregs accompanies EP-NC. The immune checkpoint pathway PD-1 and its ligand PD-L1 downregulates effector T cells, causing specific immune suppression in chronic diseases. This study explored whether their soluble forms, sPD-1/sPD-L1, are present in plasma among patients with EP-NC and if their levels could be associated with treatment response. A total of 21 patients with vesicular EP-NC and 22 healthy controls were included. Patients received standard treatment and were followed for six months to assess treatment response by assessing changes in cyst volume determined with 3D MRI. The presence of both sPD-1 and sPD-L1 was more frequently detected among patients with EP-NC than in healthy controls and had higher concentrations. Among patients, higher pre-treatment levels of both markers were associated with a poor treatment response, and the sensitivity and specificity of the sPD-1/sPD-L1 ratio for predicting any response to treatment were high. Our results are consistent with the presence of lymphocyte exhaustion and open new research perspectives to improve the prognosis of patients with this severe disease.