Drug-treated Patients Research Articles

Common protein networks for various drug regimens of major depression are associated with complement and immunity.

Major depressive disorder (MDD) can present a variety of clinical presentations and has high inter-individual heterogeneity. Multiple studies have suggested various subtype models related to symptoms, etiology, sex, and treatment response. Employing different regimens is common when treating MDD, and identifying effective therapeutics requires time. Frequent treatment attempts and failures can lead to a diagnosis of treatment resistance, and the heterogeneity of treatment responses among individuals makes it difficult to understand and interpret the biological mechanisms underlying MDD. This study explored the differentially expressed proteins and commonly altered protein networks across drug treatments by comparing the serum proteomes of patients with MDD treated with drug regimens (T-MDD, n = 20) and untreated patients (NT-MDD, n = 20). Differentially expressed proteins were profiled in non-drug-treated and drug-treated patients with depression using liquid chromatography-mass spectrometry. The common protein networks affected by different medications were studied. Of the proteins profiled, 12 were significantly differentially expressed between the T-MDD and NT-MDD groups. Commonly altered proteins and networks of various drug treatments for depression were related to the complement system and immunity. Our results provide information on common biological changes across different pharmacological treatments employed for depression and provide an alternative perspective for improving our understanding of the biological mechanisms of drug response in MDD with great heterogeneity in the background of the disease.

Usage pattern of anticoagulants in oncology patients receiving active anticancer therapies in Europe and Asia.

e23297 Background: Risks and benefits associated with use of anticoagulants (ACs) in cancer patients should be carefully assessed due to an increased risk of both thrombotic recurrences and bleeding events. Vitamin K antagonists (AVK) have been the most used ACs for patients with atrial fibrillation and venous thromboembolism for many years. Low molecular weight heparins (LMWH) and direct oral anticoagulants (DOACs) are preferred over AVK for cancer associated thrombosis. To better define the current scenario for ACs in cancer patients we propose to use market research data to describe treatment patterns in Europe and Asia. Methods: This study was conducted using Oncology Dynamics, an online secondary market research survey collecting anonymized patient data, from a representative panel of physicians. Data for 11,568 drug-treated oncology patients (p) (9,178 Europe p; 2,390 Asia p) with active cancer and anticoagulant therapies, collected between Q3 2021 and Q3 2023, from 5 European (France, Spain, Germany, Italy, & UK) and 3 Asian countries (China, Japan, & S. Korea), were analyzed. Patients with Genitourinary (GU) tumors were 36%, Lung 19%, Gastrointestinal (GI) 18%, Hepatobiliary/pancreas 12%, Gynecologic (Gyn) 12%, and Melanoma and Brain < 5%. Results: 94% p were aged > 50 years and 49% > 70 years. 64% p were male and 36% female. 67% p showed advanced/metastatic stage vs 33% local/locally advanced stage. Globally, DOACs use was 55%, LMWH 35%, and AVK < 10%; DOACs were the preferred ACs in Europe (64% p) and LMWH in Asia (59% p). Prescription of AVKs in Asia population was higher (17% p) compared with Europe (7% p). Difference in use of ACs by tumor type in European countries in favor of DOACs vs LMWH was noticeable in GU (75% p vs 13% p), GI (61% vs 34%) and Melanoma (71% vs 22%). In Asia population, predominance of LMWH vs DOACs was observable in Gyn (86% p vs 5% p), GI (57% vs 24%) and Hepatobiliary/pancreas (56% vs 35%). AVK were administered in 53% of GU Asia p and DOACs in 31%. Overall, bleeding was more frequently associated with AVK (32% p), compared to DOACs (15% p) and LMWH (9% p). Conclusions: This research highlights the differences in ACs prescription in oncology patients between Asia and Europe, with a preference for LMWH in former and DOACs in the latter. DOACs are the most common ACs prescribed overall, while AVK, associated with higher incidence of bleeding, are used in a small population. A more comprehensive analysis of the included variables will be shared.

Impact of atrial fibrillation ablation in heart failure with reduced ejection fraction

Abstract Introduction Atrial fibrillation (AF) is the most common supraventricular arrhythmia in patients with heart failure (HF) and is associated with a significant increase in morbidity and mortality. Some studies have shown evidence in favor of ablation over pharmacological treatment in patients with AF and reduced ejection fraction (HFrEF). However, little is known about the generalizability of the trial results to routine clinical practice, particularly in a low- and middle-income country. Objective To evaluate whether catheter ablation (CA) of AF reduces morbidity and mortality compared to medical therapy alone in patients with HFrEF and AF in a real-word contemporary cohort from Argentina. Methods We consecutively identified patients with HF with ejection fraction less than 40% associated with paroxysmal or persistent AF who presented to our hospital, either as outpatients or inpatients, between February 2018 and June 2020. Baseline characteristics and outcomes were compared among patients undergoing CA or medical therapy alone. The primary outcome was all-cause mortality and first HF hospitalization until completing a 3-year follow-up. Propensity score overlap weighting was used to balance ablated and drug-treated patients on sex, age, body mass index, hypertension, diabetes, dyslipidemia, smoking, previous atrial fibrillation ablation, use of antiarrhythmic drugs, cardiac resynchronization, cardiac defibrillator, left ventricular ejection fraction, cardiovascular surgery, infarction, stroke, peripheral vascular disease, etiology of heart failure, respiratory disease and renal disease baseline characteristics. Results Data from 6297 patients with AF were analyzed, of whom 430 had ejection fraction ≤ 40%. We excluded 20 patients who were ablated for atrial flutter. 53 patients in the ablation and 357 patients in the medical therapy group were identified. After PS matching, the primary outcome occurred in 9 patients (23,7%) in the ablation group and in 19 patients (50%) in the control group. Catheter ablation was associated with a statistically significant reduction of the primary outcome in a 3-year follow up (Hazard ratio [HR] 0.33 [95%CI, 0.12-0.93]). Conclusion Catheter ablation for atrial fibrillation in patients with HFrEF was associated with decreased risk of mortality and heart failure hospitalisations relative to medical therapy.Kaplan-Meier survival estimates

TCF4 and RBFOX1 as peripheral biomarkers for the differential diagnosis and treatment of major depressive disorder

BackgroundRecent genome-wide association studies on major depressive disorder (MDD) have indicated the involvement of LRFN5 and OLFM4; however, the expression levels and roles of these molecules in MDD remain unclear. The present study aimed to determine the serum levels of TCF4 and RBFOX1 in patients with MDD and to investigate whether these molecules could be used as biomarkers for MDD diagnosis. MethodsThe study included 99 drug-naïve MDD patients, 90 drug-treated MDD patients, and 81 healthy controls (HCs). Serum TCF4 and RBFOX1 levels were measured by ELISA. Pearson's correlation analysis was conducted to determine the association between TCF4/RBFOX1 and clinical variables. Linear support vector machine classifier was used to evaluate the diagnostic capabilities of TCF4 and RBFOX1. ResultsSerum TCF4 and RBFOX1 levels were substantially higher in MDD patients than in HCs and significantly lower in drug-treated MDD patients than in drug-naïve MDD patients. Moreover, serum TCF4 and RBFOX1 levels were associated with the Hamilton Depression Scale score, duration of illness, serum lipids levels, and hepatic function. Thus, both these molecules showed potential as biomarkers for MDD. TCF4 and RBFOX1 combination exhibited a higher diagnostic performance, with the mean area under the curve values of 0.9861 and 0.9936 in the training and testing sets, respectively. LimitationsSmall sample size and investigation of only the peripheral nervous system. ConclusionsTCF4 and RBFOX1 may be involved in the pathogenesis of MDD, and their combination may serve as a diagnostic biomarker panel for MDD.

FRI545 Durability Of Treatment Response With VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor, In Patients With Thyroid Eye Disease (TED): Phase 1/2 Clinical Study

Abstract Disclosure: R. Douglas: Consulting Fee; Self; Horizon Therapeutics, Viridian Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. S. Ugradar: Consulting Fee; Self; Viridian Therapeutics Inc. K. Cockerham: Advisory Board Member; Self; Viridian Therapeutics Inc., Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Speaker; Self; Horizon Therapeutics. R.E. Turbin: Advisory Board Member; Self; Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Stock Owner; Self; Viridian Therapeutics Inc. R. Tang: Consulting Fee; Self; Viridian Therapeutics Inc. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. N. Nijhawan: Research Investigator; Self; Viridian Therapeutics Inc. D.J. O’Shaughnessy: Employee; Self; Viridian Therapeutics Inc. R.M. Summerfelt: Employee; Self; Viridian Therapeutics Inc. A. She: Employee; Self; Viridian Therapeutics Inc. B. Katz: Employee; Self; Viridian Therapeutics Inc. Introduction: Clinical and preclinical evidence demonstrate IGF-1 receptor (IGF-1R) antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity, full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 double-masked RCT (NCT05176639) at 3, 10, or 20 mg/kg administered intravenously. Results from the first cohort of TED patients (10 mg/kg) are presented here. Methods: Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy through 12 weeks were assessed. Endpoints included overall responder rate (% of patients with ≥2 mm reduction in proptosis and ≥2 point reduction in CAS), proptosis responder rate (% of patients with ≥2 mm reduction), change from baseline in proptosis and CAS, proportion of patients with CAS decrease to 0 or 1, and diplopia resolution. Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, at 6 weeks, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Mean proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo). MRI analysis of proptosis, available for 4 of 6 drug-treated patients, confirmed proptosis improvement in each; MRI analysis showed slight worsening of proptosis in both placebo patients. CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo), with mean decreases of 4.3 (VRDN-001) and 1.5 (placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). Durability of response in the 5 VRDN-001 treatment responders at 6 weeks persisted through 12 weeks: 80% (4/5) maintained overall responder status and 80% (4/5) maintained proptosis responder status, with mean reduction in proptosis at week 12 of 2.2 mm for all 6 drug-treated patients; MRI analysis confirmed the maintained response for all 4 of the drug-treated patients for whom scans were available. Mean CAS reduction remained consistent (4.2 at Week 12 vs. 4.3 at Week 6) and 80% (4/5) maintained a CAS of 0 or 1. All 4 patients with baseline diplopia had diplopia resolution at Week 12. VRDN-001 was well-tolerated through 12 weeks. AEs were mostly mild, with no severe or serious AEs reported. Conclusions: Two infusions of 10 mg/kg VRDN-001 were well tolerated in this cohort of TED patients, and the rapid, clinically meaningful improvement across all efficacy measures by 6 weeks was sustained through 12 weeks. Further, these results were achieved with a lower dose and fewer treatments than in prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens. Presentation: Friday, June 16, 2023

An Amperometric Biosensor Based on a Bilayer of Electrodeposited Graphene Oxide and Co-Crosslinked Tyrosinase for L-Dopa Detection in Untreated Human Plasma.

L-Dopa, a bioactive compound naturally occurring in some Leguminosae plants, is the most effective symptomatic drug treatment for Parkinson's disease. During disease progression, fluctuations in L-DOPA plasma levels occur, causing motor complications. Sensing devices capable of rapidly monitoring drug levels would allow adjusting L-Dopa dosing, improving therapeutic outcomes. A novel amperometric biosensor for L-Dopa detection is described, based on tyrosinase co-crosslinked onto a graphene oxide layer produced through electrodeposition. Careful optimization of the enzyme immobilization procedure permitted to improve the long-term stability while substantially shortening and simplifying the biosensor fabrication. The effectiveness of the immobilization protocol combined with the enhanced performances of electrodeposited graphene oxide allowed to achieve high sensitivity, wide linear range, and a detection limit of 0.84 μM, suitable for L-Dopa detection within its therapeutic window. Interference from endogenous compounds, tested at concentrations levels typically found in drug-treated patients, was not significant. Ascorbic acid exhibited a tyrosinase inhibitory behavior and was therefore rejected from the enzymatic layer by casting an outer Nafion membrane. The proposed device was applied for L-Dopa detection in human plasma, showing good recoveries.

CAROTID-FEMORAL PULSE WAVE VELOCITY AND STIFFNESS INDEX MEASURED 5-15 YEARS EARLIER WERE SIGNIFICANTLY HIGHER IN DECEASED THAN IN STILL LIVING TREATED FINNISH HYPERTENSIVE PATIENTS

Objective: To clarify if there is a difference in pulse wave velocity (PWV) measured in the years 2006-2014 (n = 251) comparing in the years 2015-2022 deceased (n = 40) and in the beginning of the year 2023 still living (n = 211) Finnish drug-treated hypertensive patients participating that PWV measurement. Design and method: A Doppler ultrasonography device (Micro Medical PulseTrace PWV and PCA, Micro Medical Ltd, Rochester, Kent, UK) was used to measure carotid-femoral (C-F) PWV and photoplethysmographic transducer of the same machine to measure stiffness index (SI) and resistance index (RI) in 251 Finnish drug-treated hypertensive patients (126 females and 125 males) during the years 2006-2014. At the time of measurement the mean age of the patients was 64.0 (8.3) years. Results: The age at death of the deceased patients was 79.6 (SD 8.14, median 82, range 62-91) years (n = 40). The age in 01Jan2023 living patients was 75.1 (SD 7.6, median 76, range 45-91) years (n = 211), p = 0.0001 between the two groups. The mean C-F PWV was 12.5 (3.6) in deceased and 10.4 (2.2) m/s (p = 0.0001) in living and SI respectively 11.0 (3.4) and 9.6 (2.9) m/s (p = 0.007). No significant difference between the groups was seen in RI. Mean office systolic blood pressure was 150.0 (18.8) mmHg in deceased and 137.5 (14.5) in living (p = 0.003) and respectively mean office diastolic pressure 86.4 (9.2) and 83.4 (9.2) mmHg (p = 0.058). The three most common causes of death were malignancy (n = 13), sudden death (n = 10) and high age (n = 9). Dementia was noticed before death in 13 patients. Conclusions: Carotid-femoral PWV and stiffness index measured 5-15 years earlier were significantly higher in deceased than in still living treated Finnish hypertensive patients Deceased patients were older and their systolic blood pressure was higher which may explain the difference. Malignancies were a common cause of death as also diagnosed dementia in these hypertensive patients. More studies are needed concerning the predictive value of PWV in hypertensive patients.

PS-BPC06-9: THE EFFECT OF COMMON SURGICAL MASKS ON UNATTENDED BLOOD PRESSURE CHANGES IN DRUG TREATED HYPERTENSIVE PATIENTS

Objective: While there are several studies that have focused on the role of face masks in preventing airborne transmission of SARS-CoV-2, few data are available on their effects on physiological measures, and no study has examined their effects on blood pressure (BP). The purpose of our study was to investigate the effect of surgical masks on BP in drug-treated hypertensive patients who had a routine follow-up visit to a university hospital outpatient hypertension clinic. Design and method: The study included already treated hypertensive patients aged > 18 years, while the exclusion criteria were atrial fibrillation or any other arrhythmia affecting the BP measurement, an arm circumference > 42 cm, mental disorders, Parkinson disease, pregnancy, intolerance to the BP measurement method, or unwillingness to participate. A new surgical mask was provided to all participants to replace the face mask that was already in use. After the routine mask-on office BP measurement, patients were left alone and randomized to automated office BP measurement, with measurements taken after first wearing a mask for 10 min, then without wearing the mask for 10 min, and vice versa. Results: A total number of 265 patients were included in the study. Among the participants, 115 were women (43.4%), the mean age was 62 ± 12 years, and the mean office BP was 134 ± 15 / 81 ± 12 mmHg. There was no significant difference between mask-on unattended systolic BP (133 ± 15 mmHg) and mask-off unattended systolic BP (132 ± 15 mmHg) (P = 0.13) or between mask-on unattended diastolic BP (77 ± 13 mmHg) and mask-off unattended diastolic BP (76 ± 13 mmHg) (P = 0.32). Moreover, there was no difference in the heart rate (mask-on first, 69 ± 11 bpm; mask-off first, 69 ± 11 bpm, P = 0.7). Conclusions: Common surgical masks do not affect systolic/diastolic BP levels during unattended BP measurements in treated hypertensive patients.

Brain-clinical signatures for vagus nerve stimulation response.

Vagus nerve stimulation (VNS) is a valuable treatment for drug-resistant epilepsy (DRE) without the indication of surgical resection. The clinical heterogeneity of DRE has limited the optimal indication of choice and diagnosis prediction. The study aimed to explore the correlations of brain-clinical signatures with the clinical phenotype and VNS responsiveness. A total of 89 DRE patients, including VNS- (n= 44) and drug-treated (n= 45) patients, were retrospectively recruited. The brain-clinical signature consisted of demographic information and brain structural deformations, which were measured using deformation-based morphometry and presented as Jacobian determinant maps. The efficacy and presurgical differences between these two cohorts were compared. Then, the potential of predicting VNS response using brain-clinical signature was investigated according to the different prognosis evaluation approaches. The seizure reduction was higher in the VNS-treated group (42.50%) as compared to the drug-treated group (12.09%) (p= 0.11). Abnormal imaging representation, showing encephalomalacia (pcorrected = 0.03), was commonly observed in the VNS-treated group (p= 0.04). In the patients treated with VNS, the mild/subtle brain abnormalities indicated higher seizure frequency (p= 0.03) and worse VNS response (p= 0.04). The partial least square regression analysis showed a moderate prediction potential of brain-clinical signature for VNS response (p< 0.01). The increase in the pre-VNS seizure frequency and structural etiology could indicate a worse prognosis (higher McHugh classification). The brain-clinical signature illustrated its clinical potential in predicting the VNS response, which might allow clinicians to personalize treatment decisions for DRE patients.

Comparing in vivo bioluminescence imaging and the Multi-Cruzi immunoassay platform to develop improved Chagas disease diagnostic procedures and biomarkers for monitoring parasitological cure.

BackgroundChagas disease is caused by the protozoan parasite Trypanosoma cruzi and is a serious public health problem throughout Latin America. With 6 million people infected, there is a major international effort to develop new drugs. In the chronic phase of the disease, the parasite burden is extremely low, infections are highly focal at a tissue/organ level, and bloodstream parasites are only intermittently detectable. As a result, clinical trials are constrained by difficulties associated with determining parasitological cure. Even highly sensitive PCR methodologies can be unreliable, with a tendency to produce “false-cure” readouts. Improved diagnostic techniques and biomarkers for cure are therefore an important medical need.Methodology/Principal findingsUsing an experimental mouse model, we have combined a multiplex assay system and highly sensitive bioluminescence imaging to evaluate serological procedures for diagnosis of T. cruzi infections and confirmation of parasitological cure. We identified a set of three antigens that in the context of the multiplex serology system, provide a rapid, reactive and highly accurate read-out of both acute and chronic T. cruzi infection. In addition, we describe specific antibody responses where down-regulation can be correlated with benznidazole-mediated parasite reduction and others where upregulation is associated with persistent infection. One specific antibody (IBAG39) highly correlated with the bioluminescence flux and represents a promising therapy monitoring biomarker in mice.Conclusions/SignificanceRobust, high-throughput methodologies for monitoring the efficacy of anti-T. cruzi drug treatment are urgently required. Using our experimental systems, we have identified markers of infection or parasite reduction that merit assessing in a clinical setting for the longitudinal monitoring of drug-treated patients.

The impact of comprehensive public hospital reforms on the direct medical cost of inpatients with coronary heart disease.

ObjectivesTo curb the unreasonable growth of medical expenses and reduce the burden of medical treatment, Beijing launched two rounds of comprehensive reform of public hospitals. In the two reforms, the addition of drugs and consumables was canceled successively. This study compared the changes in the direct medical cost of inpatients with coronary heart disease (CHD) in the three stages of two comprehensive public hospital reforms in Beijing and provides data support for health reform policies.SettingCHD diagnosis and treatment data were extracted from the Hospital Information System (HIS) of 33 public hospitals. The total amount and composition of the direct medical expenses of CHD inpatients in the three stages were calculated. Interrupted time series analysis was used to study the instantaneous changes and trend changes in the three stages.ParticipantsThe data were obtained from the HIS system of 33 public hospitals above the second level in Beijing. A total of 66,647 medical and diagnosis records and 24,371,139 charge detail records were included.ResultsAfter the two reforms, the total cost for CHD inpatients with most clinical classifications and treatment methods decreased. The proportion of drug and consumable costs decreased significantly, whereas the proportion of medical consultation service costs increased. Drug-treated patients were mainly affected by the instantaneous reforms, percutaneous coronary intervention-treated patients were simultaneously affected by instantaneous and trending effects, and coronary artery bypass graft-treated patients were mainly affected by the reform trend.ConclusionThe overall change in the direct medical cost of CHD inpatients was consistent with the goal of the comprehensive medical reform of public hospitals in Beijing, which is “total control and structural adjustment.”

THE CHANGE IN QUALITY OF LIFE IN DRUG TREATED HYPERTENSIVE PATIENTS AFTER 10 YEARS OF ANTIHYPERTENSIVE TREATMENT

Objective: To study the change in quality of life in Finnish drug-treated hypertensive patients after ten years of antihypertensive treatment. Design and method: In the beginning the patients participated in a six-month study where their antihypertensive treatment was titrated either by using home or 24 hour ambulatory measurement. Thereafter they have been in the ordinary out-patient care. SF-36 questionnaire was filled out by 44 patients (23 females and 21 males, aged 66.1 (6.1), 55–77 years) in the beginning and after 10.6 (2.9) (6–13) years of antihypertensive treatment. All of them used at least one antihypertensive agent. Results: The mean (SD) SF-36 questionnaire scores after about 10 years of antihypertensive treatment were (maximum 100): Physical functioning 78.5 (19.9), role-physical 72.6 (34.0), bodily pain 68.1 (22.2), general health 64.5 (16.2), vitality 68.6 (15.8), social functioning 90.1 (19.0), role-emotional 76.0 (35.9), mental health 84.5 (14.4) and general health 3.2 (0.7). Compared to the same age Americans social functioning and mental health were higher (better) in our treated hypertensive patients. During 10 years of antihypertensive treatment physical functioning decreased significantly 4.8 (14.4) (p = 0.039). Instead, vitality 6.3 (18.6) (p = 0.032), social functioning 6.1 (17.5) (p = 0.028) and mental health 4.5 (11.7) (p = 0.030) increased significantly. Other parameters did not change significantly. Conclusions: According to our results physical functioning decreased and vitality, social functioning and mental health increased during 10 years of antihypertensive treatment. The decrease in physical functioning is probably explained by aging, because physical function decreases in normal population about 0.5/life year. Perhaps, good antihypertensive treatment explains the increase in those three mental parameters. Thus, it seems that according to the SF 36 questionnaire quality of life in Finnish treated hypertensive patients is quite good and do not decrease significantly during ageing.

SURGICAL MASKS AND UNATTENDED BLOOD PRESSURE CHANGES IN TREATED HYPERTENSIVE PATIENTS

Objective: Although the effect of face masks on preventing airborne transmission of SARS-CoV-2 is well studied, few data are available on their effects on physiological measures and no study has evaluated their effect on blood pressure (BP). The purpose of our study was to investigate the effect of surgical masks on BP in drug-treated hypertensive patients who had a routine follow-up visit to a university hospital outpatient hypertension clinic. Design and method: The study included already treated hypertensive patients aged &gt; 18 years, while the exclusion criteria were atrial fibrillation or any other arrhythmia affecting the BP measurement, an arm circumference &gt; 42 cm, mental disorders, Parkinson’s disease, pregnancy, intolerance to the BP measurement method, or unwillingness to participate. Following the routine mask-on office BP measurement, patients were left alone and randomized to automated office BP measurement, with measurements taken after first wearing a mask for 10 min, then without wearing the mask for 10 min, and vice versa. Results: A total number of 265 patients were included in the study. Among the participants, 115 were women (43.4%), the mean age was 62 ± 12 years, and the mean office BP was 134 ± 15/81 ± 12 mmHg. There was no significant difference between mask-on unattended systolic BP (133 ± 15 mmHg) and mask-off unattended systolic BP (132 ± 15 mmHg) (P = 0.13) or between mask-on unattended diastolic BP (77 ± 13 mmHg) and mask-off unattended diastolic BP (76 ± 13 mmHg) (P = 0.32). Moreover, there was no difference in the heart rate (mask-on, 69 ± 11 bpm; mask-off, 69 ± 11 bpm, P = 0.7). Conclusions: The results of our study indicate that common surgical masks do not affect systolic/diastolic BP levels during unattended BP measurements.

Dynamics of Nigral Iron Accumulation in Parkinson's Disease: From Diagnosis to Late Stage.

Higher nigral iron has been reported in Parkinson's disease (PD). The aim is to understand the dynamics of nigral iron accumulation in PD and its association with drug treatment. Susceptibility magnetic resonance imaging data were obtained from 79 controls and 18 drug-naive (PDDN ) and 87 drug-treated (PDDT ) PD patients. Regional brain iron in basal ganglia and cerebellar structures was estimated using quantitative susceptibility mapping. Nigral iron was compared between PDDN and PDDT subgroups defined by disease duration (early [PDE, <2 years], middle [PDM, 2-6 years], and later [PDL, >6 years]). Associations with both disease duration and types of antiparkinson drugs were explored using regression analysis. Compared to controls, PDDN had lower iron in the substantia nigra (P=0.018), caudate nucleus (P=0.038), and globus pallidus (P=0.01) but not in the putamen or red nucleus. In contrast, PDDT had higher iron in the nigra (P < 0.001) but not in other regions, compared to either controls or PDDN . Iron in the nigra increased with disease duration (PDE > PDDN [P=0.001], PDM > PDE [P=0.045]) except for PDM versus PDL (P=0.226). Levodopa usage was associated with higher (P=0.013) nigral iron, whereas lower nigral iron was correlated with selegiline usage (P=0.030). Nigral iron is lower before the start of dopaminergic medication and then increases throughout the disease until it plateaus at late stages, suggesting increased iron may not be an etiological factor. Interestingly, PD medications may have differential associations with iron accumulation that need further investigation. © 2022 International Parkinson and Movement Disorder Society.

Psychological and Psychopharmacological Interventions in Psychocardiology

Patients with mental disorders have an increased risk to develop cardiovascular disease (CVD), and CVD are frequently comorbid with especially adjustment, anxiety and depressive disorders. Therefore, clinicians need to be aware of effective and safe psychological and pharmacological treatment strategies for patients with comorbid CVD and mental disorders. Cognitive behavioral therapy and third-wave of cognitive-behavioral therapy are effective for patients with CVD and mental disorders. Internet-based psychological treatments may also be considered. In more severe cases, psychopharmacological drugs are frequently used. Although generally well tolerated and efficacious, drug- and dose-dependent side effects require consideration. Among antidepressants, selective serotonin reuptake inhibitors, selective serotonin and noradrenalin reuptake inhibitors, and newer antidepressants, such as mirtazapine, bupropion, agomelatine, and vortioxetine, can be considered, while tricyclic antidepressants should be avoided due to their cardiac side effects. Mood stabilizers have been associated with arrhythmias, and some first- and second-generation antipsychotics can increase QTc and metabolic side effects, although substantial differences exist between drugs. Benzodiazepines are generally safe in patients with CVD when administered short-term, and may mitigate symptoms of acute coronary syndrome. Laboratory and ECG monitoring is always recommended in psychopharmacological drug-treated patients with CVD. Presence of a heart disease should not exclude patients from necessary interventions, but may require careful risk-benefit evaluations. Effectively and safely addressing mental disorders in patients with CVD helps to improve both conditions. Since CVD increase the risk for mental disorders and vice versa, care providers need to screen for these common comorbidities to comprehensively address the patients’ needs.

Nephrotoxicity in cancer treatment: An update.

It has been estimated that nearly 80% of anticancer drug-treated patients receive potentially nephrotoxic drugs, while the kidneys play a central role in the excretion of anticancer drugs. Nephrotoxicity has long been a serious complication that hampers the effectiveness of cancer treatment and continues to influence both mortality and length of hospitalization among cancer patients exposed to either conventional cytotoxic agents or targeted therapies. Kidney injury arising from anticancer drugs tends to be associated with preexisting comorbidities, advanced cancer stage, and the use of concomitant non-chemotherapeutic nephrotoxic drugs. Despite the prevalence and impact of kidney injury on therapeutic outcomes, the field is sorely lacking in an understanding of the mechanisms driving cancer drug-induced renal pathophysiology, resulting in quite limited and largely ineffective management of anticancer drug-induced nephrotoxicity. Consequently, there is a clear imperative for understanding the basis for nephrotoxic manifestations of anticancer agents for the successful management of kidney injury by these drugs. This article provides an overview of current preclinical research on the nephrotoxicity of cancer treatments and highlights prospective approaches to mitigate cancer therapy-related renal toxicity.

Antihypertensive Augmentation: Maximize Dose or Add a New Med?

In drug-treated patients with hypertension whose blood pressure (BP) is inadequately controlled, augmentation strategies include maximizing the dose of

Characterization of Vaginal Microbiota in Women With Recurrent Spontaneous Abortion That Can Be Modified by Drug Treatment.

ObjectiveThe role of vaginal microbiota in recurrent spontaneous abortion (RSA) remains unknown. The purpose of this study was to investigate characteristics of vaginal microbiota and the effects of drug treatment on vaginal microbiota of patients with RSA.MethodsA case-control study was performed, in which non-pregnant patients who experienced RSA were selected and divided into untreated and drug-treated groups. Drug-treated patients were subdivided into the metformin group, metformin plus aspirin group, and other drugs group. Healthy women who had live births and never experienced spontaneous abortion were enrolled in the control group. Characteristics of vaginal microbiomes of patients with RSA and healthy women and the impact of drug treatment on the microbiome was evaluated via 16S rRNA gene sequencing of the V3-V4 region using the Illumina MiSeq platform.ResultsWomen who underwent RSA had lower microbial richness than healthy women. Compared to controls, the relative abundance of seven taxa (Megasphaera, Sneathia sanguinegens, Pseudomonas, Sphingomonas, Rhodococcus, Burkholderia- Caballeronia-Paraburkholderia, and Corynebacterium_1) in the patient’s vaginal microbiota changed significantly, which may be closely related to RSA. The composition of the vaginal microbial community in RSA patients was altered by drug treatment. Metformin combined with aspirin treatment significantly increased the relative abundance of vaginal Lactobacillus spp. in patients.ConclusionAn altered vaginal microbiome composition might be associated with RSA, which could be modified by drug treatment. The effect of metformin combined with aspirin on vaginal Lactobacillus is worthy of attention.

A Virtual Reality Serious Videogame Versus Online Chess Augmentation in Patients with Attention Deficit Hyperactivity Disorder: A Randomized Clinical Trial.

Objective: Serious videogames and virtual reality (VR) have gained increasing interest for treating attention deficit hyperactivity disorder (ADHD). "The Secret Trail of Moon" (TSTM) study is a clinical trial devoted to testing the efficacy of TSTM, a VR serious videogame developed to train in five major cognitive skills usually compromised in patients with ADHD. This study is a three-arm nonequality trial comparing TSTM to online chess training and a control group (CG). This study aims to demonstrate that augmentation with either TSTM or online chess is efficacious in clinically drug-stable patients with ADHD. Materials and Methods: This study is prospective, unicentric, and randomized with a CG. One hundred five patients with ADHD, ages 12-22 years old, and pharmacologically stable were enrolled. Patients were randomized into three groups: TSTM group, online chess group (therapeutic chess [TC]), and CG. Objective and subjective measures of the patient and parents are included. Patient visits differ for each group. TSTM group patients have 15 face-to-face visits: preinclusion visit, inclusion visit, 12 training visits, and final visit. TC and CG patients have 3 face-to-face visits (preinclusion, initial visit, and final visit) and 12 e-mail or phone communications during training (TC) or follow-up (CG group). This study was approved by the local Institutional Review Board (IRB). Results: Not applicable. This is a study protocol. Conclusion: This is the first study testing an augmentation strategy using either a serious videogame or chess in clinically drug-treated patients with ADHD. Using VR serious videogames present with several advantages over traditional videogames. Trial Registration: NCT04355065.

VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function.

Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood–retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.