Dose Of Therapy Research Articles

Projected environmental and public health benefits of extended-interval dosing: an analysis of pembrolizumab use in a US national health system

Health care is a major source of greenhouse gas emissions, leading to climate change and public health harms. Changes are needed to improve the environmental sustainability of health-care practices, but such changes should not sacrifice patient outcomes or financial sustainability. Alternative dosing strategies that reduce the frequency with which specialty drugs are administered, without sacrificing patient outcomes, are an attractive possibility for improving environmental sustainability. We sought to inform environmentally sustainable cancer care by estimating and comparing the environmental and financial effects of alternative, clinically equivalent strategies for pembrolizumab administration. We conducted a retrospective analysis using a cohort of patients from the Veterans Health Administration (VHA) in the USA who received one or more pembrolizumab doses between May 1, 2020, and Sept 30, 2022. Using baseline, real-world administration of pembrolizumab, we generated simulated pembrolizumab use data under three near-equivalent counterfactual pembrolizumab administration strategies defined by combinations of weight-based dosing, pharmacy-level vial sharing and dose rounding, and extended-interval dosing (ie, every 6 weeks). For each counterfactual dosing strategy, we estimated greenhouse gas emissions related to pembrolizumab use across the VHA cohort using a deterministic environmental impact model that estimated greenhouse gas emissions due to patient travel, drug manufacture, and medical waste as the primary outcome measure. We identified 7813 veterans who received at least one dose of pembrolizumab-containing therapy in the VHA during the study period. 59 140 pembrolizumab administrations occurred in the study period, of which 46 255 (78·2%) were dosed at 200 mg every 3 weeks, 12 885 (21·8%) at 400 mg every 6 weeks, and 14 955 (25·3%) were coadministered with infusional chemotherapies. Adoption of weight-based, extended-interval pembrolizumab dosing (4 mg/kg every 6 weeks) and pharmacy-level stewardship strategies (ie, dose rounding and vial sharing) for all pembrolizumab infusions would have resulted in 24·7% fewer administration events than baseline dosing (44 533 events vs 59 140 events) and an estimated 200 metric tons less CO2 emitted per year as a result of pembrolizumab use within the VHA (650 tons vs 850 tons of CO2, a relative reduction of 24%), largely due to reductions in distance travelled by patients to receive treatment. Similar results were observed when weight-based and extended-interval dosing were applied only to pembrolizumab monotherapy and pembrolizumab in combination with oral therapies. Alternative pembrolizumab administration strategies might have environmental advantages over the current dosing and compounding paradigms. Specialty medication dosing can be optimised for health-care spending and environmental sustainability without sacrificing clinical outcomes. None.

Assessment of post-myocardial infarction lipid levels and management: Results from a tertiary care hospital of Pakistan.

Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention. To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan. In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at < 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at < 55 mg/dL. Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% vs 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% vs 11.7%). Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

#284 Risk of dose-dependent methotrexate therapy on renal functions in patients with rheumatoid arthritis

Abstract Background and Aims Methotrexate is often used as first-line therapy for RA because of its proven efficacy, good safety profile, and low cost. The importance of MTX also comes from the fact that in combinatory treatments, the efficacy of bDMARDs or tsDMARDs is always higher when these drugs are combined to MTX, suggesting making MTX at the base of any conventional treatment of RA. Although renal impairment is a major concern in patients taking high-dose MTX for the treatment of malignancy, it has not been fully examined in RA patients treated with low-dose MTX, so we aimed at studying the dose- dependent effects of MTX on renal function and creatinine clearance. Method Three hundred and sixty adult RA patients, regularly attending rheumatology OPC for regular follow up participated in this retrospective cohort study. Young children, patients with any degree of renal impairment and other rhematic diseases were excluded. Serum creatinine and creatinine clearance were followed up at 1 year and 3 years of different doses of MTX therapy, and results were compared to baseline levels. Results Patients’ ages had a mean of 44.60 years, with most being females (80.6%). Range of disease duration was 2-34 years with the mean of 9.93 years. Most of the patients had significant disease activity, where 36.4% had moderate activity and 26.1% of them had high disease activity according to DAS 28 score. We noticed a significant decline of the creatinine clearance at 1 &amp; 3 years follow up regardless the MTX dose used (P-value: ≤0.001 for both). Conclusion We may conclude that MTX therapy has a potential nephrotoxic effect regardless the dose or the duration of therapy, mandating a close monitoring of renal functions for patients maintained on the drug.

#1021 A phase 3 randomized controlled trial of ravulizumab in adult patients with IgA nephropathy

Abstract Background and Aims The pathogenesis of IgA nephropathy (IgAN) includes the deposition of immune complexes in the kidney and activation of the complement system. Complement components, including C5a (anaphylatoxin) and C5b-9 (membrane attack complex), are generated leading to mesangial inflammation and glomerular injury [1]. Ravulizumab, a humanized monoclonal antibody, is a long-acting complement C5 inhibitor that provides immediate, complete, and sustained inhibition of the terminal complement pathway, thereby targeting a key component of the pathophysiology of IgAN. A phase 2 study of ravulizumab (NCT04564339) demonstrated a rapid effect and significant reduction in proteinuria compared with placebo at week 26 (change from baseline in 24-hour urine protein to creatinine ratio [UPCR] –40.3% vs –10.9%), and treatment was well-tolerated [2]. This abstract describes the study design of the planned phase 3 trial of ravulizumab in adult patients with IgAN. Method This phase 3, randomized, double-blind, placebo-controlled trial (I CAN) will evaluate the efficacy and safety of ravulizumab (IV; weight-based dosing Q8W) in adults with IgAN. Eligibility criteria include a diagnosis of primary IgAN based on kidney biopsy at any point, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at screening, and UPCR ≥0.75 g/g or urine protein ≥1.0 g/day (Table 1). The study consists of a 6-week screening period, followed by randomization (1:1) of participants to ravulizumab or placebo and a 2-year blinded treatment period (Fig. 1); all patients receive a stable and maximally tolerated dose of renin-angiotensin system inhibitor therapy. Approximately 450 patients will be randomized, stratified by proteinuria (&amp;lt;2 g/g vs ≥2 g/g), eGFR (&amp;lt;45 vs ≥45 mL/min/1.73 m2), and SGLT2i use (yes/no). The co-primary endpoints are change from baseline to week 34 in 24-hour UPCR evaluated on the log scale and the annualized total eGFR slope over 106 weeks. The sample size for the proteinuria endpoint of n = 204 will provide ∼90% power to detect a 35% relative treatment effect in UPCR at week 34 at a one-sided significance level of 0.005. The total sample size of n = 450 for the eGFR endpoint will provide ∼90% power to detect a difference in total annualized eGFR slope of 2.2 mL/min/1.73 m2 at week 106 at a one-sided significance level of 0.025. An open-label exploratory cohort (n = 20) with eGFR 20-29 mL/min/1.73 m2 and with kidney biopsy within 6 months of or during screening will be enrolled and analyzed separately from the main cohort. At completion of the blinded treatment period, all study participants will have the option to enter an open-label ravulizumab access period for up to 2 years. Results The co-primary endpoints are the change in 24-hour UPCR at week 34 and the annualized total eGFR slope over 106 wks. Secondary and exploratory endpoints include change in 24-hour UPCR at weeks 10, 26, 50, and 106, a composite kidney failure endpoint over 106 weeks, reduction in 24-hour UPCR ≥50% from baseline, time to UPCR &amp;lt;1 g/g and &amp;lt;0.3 g/g, and patient reported outcomes on fatigue, quality of life, and work-related productivity. Safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics will be evaluated. Conclusion Through immediate, complete, and sustained inhibition of C5, ravulizumab targets the pathophysiology of IgAN and has the potential to provide a disease modifying treatment option. This pivotal phase 3 study (I CAN) will evaluate the efficacy of ravulizumab in patients with IgAN who are at high risk of disease progression. The trial will evaluate effects on proteinuria and eGFR that may translate to long term kidney function preservation and provide a rapidly acting treatment option for patients living with IgAN.

Neurologic music therapy for non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials

IntroductionThe efficacy of neurologic music therapy (NMT) techniques for the treatment of non-fluent aphasia has been widely accepted by the rehabilitation medical community. However, consensus on which dimensions of speech function can be improved by NMT techniques and standardized intervention dosage remains elusive. This study aimed to provide evidence regarding the efficacy of NMT in improving speech function and explore the optimal intervention dose. A systematic review and meta-analysis were conducted to search for randomized clinical trials and open-label trials that evaluated speech functions after NMT.MethodsWe searched all papers and reviews published from database inception to July 2023, including PubMed, Cochrane Library, Web of Science, Embase, and CNKI. Statistical analyses were mainly carried out on RevManV5.4.1 and pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in speech functions, determined by calculating the change in speech functions score from baseline to the primary endpoint in the NMT group versus the control arm.ResultsA total of 11 studies with 329 patients were included. NMT had a positive effect on repetition ability (SMD = 0.37, 95%CI [0.12, 0.62], p &amp;lt; 0.05), but did not lead to significant differences in naming, comprehension, spontaneous speech, or communication. When the intervention time was &amp;gt;20 h, NMT exhibited a significant advantage at improving repetition ability (SMD = 0.43, 95%CI [0.06, 0.79], p &amp;lt; 0.05).DiscussionThis study provides evidence supporting the NMT enhancement of repetition ability in patients with non-fluent aphasia. Future large-sample studies are required to determine the optimal intervention dose of music therapy for different subtypes of non-fluent aphasia.Systematic review registrationPROSPERO, identifier CRD42023470313.

Morphological assessment of the ovarians after single and fractional local electron iradiation

BACKGROUND: When malignant neoplasms of the pelvic organs are irradiated, healthy ovarian tissues can get into the irradiation area. So, among all physico-chemical factors, ionizing radiation is the most common cause of ovarian failure, which has a negative impact on fertility. Conducting research in this area is especially important in connection with the active introduction of electron therapy in the protocols for the treatment of malignant neoplasms of the small pelvis with the need to find ways to prevent and treat post-radiation ovarian lesions. In addition, one of the main tasks of modern radiobiology is the creation of experimental animal models in order to reveal the mechanisms of radiation exposure with subsequent extrapolation of the results obtained to humans in order to level the side effects of radiation therapy and select optimal doses. AIM: The aim of the study was a morphofunctional assessment of the ovaries after local electron irradiation in single and fractional modes. MATERIALS AND METHODS: Wistar rats (n = 30) were divided into three groups: I — control (n = 10); II (n = 10) — subjected to a single local irradiation with electrons at a dose of 2 Gy; III (n = 10) — subjected to fractional local irradiation with electrons in a total dose of 20 Gy. RESULTS: After a single local irradiation with electrons at a dose of 2 Gy, multiple hemorrhages and a decrease in the number of growing follicles with a discontinuous theca layer, which were unevenly distributed over its volume, were noted in the ovary. A statistically significant difference in the number of follicles was revealed: a decrease in the number of primordial, primary, secondary and tertiary follicles and an increase in atretic follicles. The most pronounced difference in the number of follicles between the studied groups was found in the group of fractional electron irradiation at a dose of 20 Gy: the smallest number of primordial and the largest number of atretic follicles with signs of post-radiation fibrosis. CONCLUSIONS: The most profound damage to the ovary develops after exposure to fractional electron irradiation at a total dose of 20 Gy compared with a single exposure to ionizing radiation at a dose of 2 Gy: a reduced number of follicles, a decrease in the area and thickness of the cortical substance, as well as the thickness of the ovarian tunica, in combination with the growth of the connective tissue.

Rehabilitation success after psychosomatic rehabilitation as afunction of psychotherapy dose

Increasing the effectiveness of psychosomatic rehabilitation by prolonging the treatment is a subject of controversial debate. The number of sessions over time defines the dosage in psychotherapy. While the dose-response model assumes an optimal therapy dose, the good-enough level model assumes acorrelation of the rate of change with the total sessions. Arandomized control group study was conducted to investigate the extent to which an adaptive therapy concept with atwo-week intensive phase and early intervention could increase rehabilitation success. A total of 494 rehabilitants between the ages of 21 and 64 (47% women) who completed aclassical or an integrative psychosomatic rehabilitation at the Rehazentrum Oberharz between 2020 and 2022 were analysed. Rehabilitation success was mapped by the Reliable Change Index of individual symptom reduction (depression severity or psychological and somatoform disorders) and as asocio-medical parameter (physician's assessment of potential work ability (WA) after twoweeks). Two-factorial ANOVAs and hierarchical binary logistic regressions were calculated, and sick leave before rehabilitation was statistically controlled. Dosage showed no effect on symptom reduction (p = 0.29) and potential WA after twoweeks (p = 0.90). However, when stratified by disease severity, there was amean effect of dosage (p = 0.05) and twice the probability of WA after twoweeks (odds 2.13; p = 0.01) for those with mild disease at the start of measure (p = 0.05). In the early stages of an affective disorder, early and intensified intervention can counteract the chronification of mental disorders.

Pre-clinical evaluation of clinically relevant iPS cell derived neuroepithelial stem cells as an off-the-shelf cell therapy for spinal cord injury.

Preclinical transplantations using human neuroepithelial stem (NES) cells in spinal cord injury models have exhibited promising results and demonstrated cell integration and functional improvement in transplanted animals. Previous studies have relied on the generation of research grade cell lines in continuous culture. Using fresh cells presents logistic hurdles for clinical transition regarding time and resources for maintaining high quality standards. In this study, we generated a good manufacturing practice (GMP) compliant human iPS cell line in GMP clean rooms alongside a research grade iPS cell line which was produced using standardized protocols with GMP compliant chemicals. These two iPS cell lines were differentiated into human NES cells, from which six batches of cell therapy doses were produced. The doses were cryopreserved, thawed on demand and grafted in a rat spinal cord injury model. Our findings demonstrate that NES cells can be directly grafted post-thaw with high cell viability, maintaining their cell identity and differentiation capacity. This opens the possibility of manufacturing off-the-shelf cell therapy products. Moreover, our manufacturing process yields stable cell doses with minimal batch-to-batch variability, characterized by consistent expression of identity markers as well as similar viability of cells across the two iPS cell lines. These cryopreserved cell doses exhibit sustained viability, functionality, and quality for at least 2 years. Our results provide proof of concept that cryopreserved NES cells present a viable alternative to transplanting freshly cultured cells in future cell therapies and exemplify a platform from which cell formulation can be optimized and facilitate the transition to clinical trials.

Use of caffeine for managing apneia of premature

Apnea of prematurity is a common diagnosis in neonatal intensive care units, especially in preterm patients under 35 weeks or patients born with low birth weight (&lt;1500g). From this perspective, the use of caffeine citrate has short and long-term benefits in this pathology, in addition to reducing the incidence of complications. Methodology: A narrative review of the literature was carried out using the PUBMED database, using the following keywords: “Apnea Prematurity”, “Caffeine” and “Treatment”, with a 6-year filter, analyzing 164 articles, of which only 34 were included and 130 were excluded. Results and Discussion: Apnea of prematurity is a common pathology in preterm and extremely preterm infants, with an incidence of 10% of newborns after 34 weeks and 20-85% of newborns born between 30-34 weeks. The pathophysiology of the disease is explained by the immaturity of the central nervous system in maintaining respiratory drive, in addition to impaired sensitivity in response to chemoreceptors and difficulty in maintaining REM sleep, in addition to the chronic losses inherent to chronic hypoxia. Methylxanthines, the active ingredient in caffeine, have the activation mechanism of inhibiting adenosine A1 and A2 receptors coupled to G protein. The recommended initial dose for therapy is 10 mg/kg for apnea of prematurity, but it must be monitored with concentrations serum levels of the drug to a safe therapeutic range, in addition to monitoring side effects in view of the patient's clinical impairment. The main signs of side effects from the use of caffeine are tachycardia, hyperglycemia, reduced growth rate, jaundice, irritability, agitation and convulsions. Conclusion: Apnea of prematurity is a very prevalent pathology in preterm newborns and its therapeutic possibility must be taken into account in view of its possible short and long-term complications, since the use of methylxanthines has different evidence of clinical improvement.

Medium-cumulative dose of cytarabine in consolidation therapy shows the greatest benefit in AML patients

BackgroundHigh-dose cytarabine (HDAC) is commonly used for consolidation therapy in young acute myeloid leukemia (AML) patients, but the dosage of cytarabine is still controversial in the clinic due to its obvious post-chemotherapy adverse effects. The aim of this study was to contrast the efficacy in different dose groups of cytarabine after consolidation therapy in Chinese AML patients.MethodsAML patients treated with cytarabine consolidation at Qilu Hospital, Shandong University from January 2010 to September 2022 were retrospectively analyzed, from which 346 AML patients with relatively complete follow-up data were selected for this study. We compared the patients’ overall survival (OS) rate, relapse-free survival (RFS) rate, and hematologic adverse events in terms of their general characteristics, cytarabine consolidation therapy dose, consolidation course, 2022 European Leukemia Net (ELN) risk stratification, and transplantation.ResultsIn AML patients under 60 years of age, the 5-year RFS rate with high-dose cytarabine consolidation therapy was superior to that of small-dose cytarabine (P = 0.024), while the 5-year RFS rate was comparable in the high-dose and intermediate-dose groups, and there was no obvious difference among the three groups in the 5-year OS rate (P > 0.05). OS and RFS of those given more than 3 courses of cytarabine consolidation therapy were better than those in the 1–2 courses group (P = 0.060, P = 0.040). OS and RFS were better in patients with cumulative dose of cytarabine ≥ 36g than in patients with cumulative dose < 36g (P < 0.05), but cumulative dose ≥ 54g was comparable in OS and RFS with ≥ 36–< 54g group (P > 0.05). There was no significant difference in hematologic adverse effects among the three treatment groups.In the latest ELN risk stratification favorable-risk group, the cumulative dose of cytarabine ≥ 36g had a better 5-year RFS rate than the < 36g group (P = 0.038), and in the intermediate-risk group the 5-year OS rate and RFS rate were better in the ≥ 36g group than the < 36g group (P = 0.012, 0.025). In addition, the prognosis of transplanted patients was better than that of non-transplanted patients, whereas in non-transplanted patients, consolidation therapy with ≥ 36g cytarabine can effectively improve outcomes. Multivariate analysis indicated that age, fibrinogen (FIB) and the cumulative dose of cytarabine of ≥ 36–< 54g were predictors of OS, while age, white blood cell (WBC) and HDAC were predictors of RFS.ConclusionThe results of the study showed that consolidation therapy with cytarabine up to a cumulative dose of ≥ 36–< 54g in AML patients who did not undergo transplantation significantly improved patient prognosis. In the latest ELN risk stratification, cumulative doses of cytarabine ≥ 36g had a better prognosis in favorable and intermediate-risk patients.

Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.

Therapeutic Drug Monitoring and Biomarkers; towards Better Dosing of Antimicrobial Therapy.

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research.

A study on appropriate use and stewardship of proton pump inhibitors

Objective: To analyze the prescribing pattern of use of PPI with respect to “FDA-Approved Indications and Doses for PPI Therapy.” Materials and Methods: After obtaining approval from the Institutional Ethics Committee, a cross-sectional study was carried out among 400 inpatients in a tertiary care hospital in Bangalore. The data were collected from the patient case profile and prescriptions and noted in a self-designed data collection form. The statistical analysis of the collected data was performed using SPSS software and Excel. Results: The study, conducted on 400 patients, revealed a male majority (60%) and a female representation of 40%. Proton Pump Inhibitors (PPIs), mainly Pantoprazole (74.70%), were frequently prescribed, notably in General Medicine (220 patients). PPI use was generally appropriate: indication (99%), dose (97%), frequency (92.8%), and duration (91.8%). However, irrational prescriptions were noted: indication (1%), dose (3%), frequency (7.3%), and duration (8.3%). 139 drug interactions were identified, categorized into Major (39.6%), Moderate (46%), and Minor (14.4%). For example, Ondansetron and tramadol exhibited a major interaction. Among PPI combinations, 93.75% could affect CYP2C19 metabolism, and 6.3% had additive/synergistic toxicity potential.

Acute pancreatitis as a manifestation of multisystem inflammatory syndrome among children (MIS-C): A rare case

A multisystem inflammatory syndrome among children (MIS-C) has been linked to COVID-19, and it affects multiple organ systems in the body, including the gastrointestinal system. In present case report, a 14-year-old girl presented with clinico-laboratory and imaging evidence of acute pancreatitis but did not respond to the standard line of management for pancreatitis. Later, the laboratory investigations pointed to the diagnosis of MIS-C. She responded well to a pulse doses of methylprednisolone therapy. Acute pancreatitis as a lone manifestation of MIS-C poses a diagnostic challenge for paediatricians, and one should suspect MIS-C in acute non-responding pancreatitis.

Polyvascular Disease: A Narrative Review of Risk Factors, Clinical Outcomes and Treatment.

Polyvascular disease has a significant global burden and is associated with increased risk of major adverse cardiac events with each additional vascular territory involved. The purpose of this review is to highlight the risk factors, associated outcomes, emerging genetic markers, and evidence for screening and treatment of polyvascular disease. Polyvascular disease is the presence of atherosclerosis in two or more vascular beds. It has a significant global burden, with a prevalence of 30-70% in patients with known atherosclerosis. Patients with polyvascular disease experience elevated rates of cardiovascular death, myocardial infarction and stroke, especially among high-risk subgroups like those with type 2 diabetes mellitus and there is a step-wise increased risk of adverse outcomes with each additional vascular territory involved. Genetic analyses demonstrate that some individuals may carry a genetic predisposition, while others exhibit higher levels of atherogenic lipoproteins and inflammatory markers. Routine screening for asymptomatic disease is not currently recommended by major cardiovascular societies unless patients are high-risk. While there are no established protocols for escalating treatment, existing guidelines advocate for lipid-lowering therapy. Additionally, recent studies have demonstrated benefit from antithrombotic agents, such as P2Y12 inhibitors and low-dose anticoagulation, but the optimal timing and dosage of these agents has not been established, and the ischemic benefit must be balanced against the increased risk of bleeding in the polyvascular population. Due to the high prevalence and risks associated with polyvascular disease, early identification and treatment intensification are crucial to reduce disease progression. Future research is needed to develop screening protocols and determine the optimal timing and dosing of therapy to prevent ischemic events.

Impact of Replacement Therapy on Pregnancy Outcomes in Hemophilia Carriers: A Historical Cohort Study in Saudi Arabia.

This retrospective cohort study evaluates the safety and efficacy of replacement therapy with regard to pregnancy outcomes in hemophilia carriers. Hemophilia carriers face elevated bleeding risks during pregnancy, necessitating meticulous management, including replacement therapy with clotting factors. This research examines the records of 64 pregnant hemophilia carriers at King Fahad Medical City, Riyadh, from January 2010 to December 2023, analyzing their demographic details, hemophilia type and severity, replacement therapy specifics, and pregnancy outcomes. The study found that 62.5% of the participants had hemophilia A, with 43.8% categorized as severe. Most subjects (87.5%) received recombinant factor VIII at a median dosage of 30 IU/kg weekly. Adverse pregnancy outcomes included gestational hypertension (15.6%), preterm labor (18.8%), and postpartum hemorrhage (12.5%). The cesarean section rate was 28.1%. Neonatal outcomes were generally favorable, with median birth weights at 3100 g and mean Apgar scores of 8.2 and 9.1 at 1 and 5 min, respectively. Logistic regression analysis revealed no significant association between adverse events and therapy type or dosage, though a trend towards significance was noted with once-weekly administration (p = 0.082). The study concludes that replacement therapy is a viable method for managing hemophilia in pregnant carriers, leading to generally favorable maternal and neonatal outcomes. However, it underscores the importance of individualized treatment plans and close monitoring to effectively manage the risks associated with hemophilia during pregnancy.

Intrathecal Baclofen Therapy for Refractory Spasticity: A Case Series

Management of refractory spasticity symptoms remains a challenging task for clinicians. Intrathecal baclofen (ITB) therapy has emerged as a promising option for treating this condition. This study evaluates the effectiveness of ITB therapy in managing refractory spasticity symptoms. A retrospective chart review was conducted on 34 patients with refractory spasticity symptoms who underwent ITB therapy at a single institution. The patients' demographics, clinical characteristics, and dosages were recorded. The primary outcome measures were the reduction in pain, improvement in mobility, decrease in spasm frequency, and alleviation of spasticity. ITB therapy successfully reduced pain, improved mobility, decreased spasm frequency, and alleviated spasticity. The mean daily administered dose was 245μg (range: 88-510μg, standard deviation:104). However, it was observed that the appropriate dosage of ITB therapy was patient-specific and time-sensitive. Moreover, side effects were observed when an incorrect dose was administered. ITB therapy is an effective and safe option for managing refractory spasticity symptoms. However, the appropriate dosage should be individualized and monitored closely to avoid side effects. This study highlights the importance of carefully considering the potential risks and benefits of ITB therapy for each patient.

Phenomena observed in electron EBRT using a pulse-by-pulse radioluminescence dosimetry system with cloud-based analytics

The pulse-by-pulse characteristics of electron beams from a clinical linear accelerator (linac) at high dose rates are crucial for ensuring precise dose delivery in radiation therapy. In this research, we employ a radioluminescence scintillator made from Ge-doped silica optical fiber to analyse electron beams at standard therapy dose rates 600 cGy/min with energy of 15 MeV. The scintillator is combined with a photomultiplier tube (PMT) and a photon-counting setup to achieve microsecond (μs) gating times, providing high temporal resolution. For sub-microsecond (sub-μs) temporal resolution, we utilize a multi-pixel photon counter and a rapid digital oscilloscope. Our study examines the peak time and the time it takes for pulses to return to baseline, uncovering the effects of afterglow at elevated dose rates and its potential implications for dosimetry precision. Our results indicate that monitor chambers, which have lower temporal resolution than the radioluminescence system outlined in this study, may struggle to accurately track high-rate dose delivery, emphasizing the necessity for advanced monitoring methods in FLASH radiotherapy. The dosimetric data was further analysed for deeper analytics on a cloud-based system. The dosimetric data underwent advanced analysis on a cloud-based platform, employing a prototype analytics software system comprised of Dosi-Client and Dosi-Cloud Backend components for real-time data acquisition and processing. This innovative approach revealed significant insights into radiation dosimetry, including the detection of anomalies through a reconstruction convolutional autoencoder, enhancing the precision and reliability of dosimetric measurements.

Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients.

There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals.The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30days, 60days, 180days, and 1year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.