Mean Initial Dose Research Articles

Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment - A Nationwide Retrospective Cohort Study.

This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

Corticosteroid Prescribing Patterns in the Emergency Department for Acute COPD Exacerbations: A Retrospective Analysis Following an Educational Intervention.

COPD is a progressive lung disease with marked airflow limitation. It has a large global prevalence and is managed with antibiotics, bronchodilators, and corticosteroids. Despite the prevalence, corticosteroid prescribing regimens differ widely amongst providers. This study aims to evaluate baseline corticosteroid prescribing patterns, the ability to change corticosteroid prescribing patterns with the utilization of an educational initiative, and to evaluate the effect of corticosteroid dose on length of stay, 30-day hospital readmission, mortality, and total hospital insulin dosing. This study was conducted via a retrospective observational study. Providers at a single institution answered a baseline questionnaire on COPD corticosteroid prescribing patterns and subsequently received an educational presentation regarding evidence-based corticosteroid recommendations. Data were then retrospectively obtained and analyzed evaluating corticosteroid prescribing patterns both pre- and post-educational intervention. Data were analyzed using IBM SPSS Version 25. The provider survey revealed that most (95.3%) administered 125 mg of methylprednisolone to patients treated for AECOPD. The most common reason a particular dose of corticosteroid was administered was due to previous teaching or practice patterns. The mean initial steroid dose of methylprednisolone decreased following the educational initiative from 114.24 mg to 72.8 mg (p < 0.01). This corresponded to a 69% (n=41) decrease of providers using 125 mg methylprednisolone (p < 0.01), and increased prescribing of 62.5 mg methylprednisolone by 42.6% (n=66). The mean LOS following hospital admission for AECOPD in the pre-intervention group was 5.80 days, while the mean LOS following the targeted educational intervention decreased to 4.82 days (p = 0.01). The implementation of an educational intervention may change provider corticosteroid prescribing patterns. Additionally, lower corticosteroid dose in the Emergency Department may decrease patient length of stay. Keywords: Corticosteroid, COPD, LOS, recommendations, steroid.

Finding individualised treatment in obese needing enoxaparin (FIT ONE): a multicentre study of therapeutic enoxaparin and the role of anti-factor Xa monitoring.

Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aimwasto evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels(P = 0.135). Obesity was not includedin the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95mg/kg twice daily and 1.04mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels.

Examining the Use of Oral Aripiprazole in Patients With Autism Spectrum Disorder: A Study of Retrospective Chart Review at a University Medical Center.

The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at a university medical center in Korea. We retrospectively reviewed the medical records of 164 outpatient children and adolescents diagnosed with ASD by child and adolescent psychiatrists. Patient demographic characteristics, clinical features, age and dose of aripiprazole treatment, associated adverse events, and concomitant medications, etc. were evaluated. Aripiprazole treatment was initiated at a mean age of 7.64 years, at a mean initial dose of 1.15 mg. Methylphenidate was often co-administered with aripiprazole. The most commonly reported adverse effects were increased appetite and weight gain, which in some cases led to discontinuation of medication. A follow-up study is warranted to evaluate the efficacy and safety of aripiprazole treatment in Korean children and adolescents diagnosed with ASD, and it is crucial to consider their clinical characteristics and response to treatment in the evaluation.

The effectiveness of glucocorticoid treatment in post-COVID-19 pulmonary involvement

RationalePersistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited.AimTo evaluate the effects of CS treatment in post-COVID respiratory syndrome patients.Patients and methodsPost-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines.ResultsThe study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894).ConclusionBetter improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.

The Prognostic Power of Preablation Stimulated Thyroglobulin in Children With Differentiated Thyroid Cancer

ObjectiveTo analyze prognostic factors in children with differentiated thyroid carcinoma (DTC) who have been treated in a single center in the last 27 years. MethodsWe studied 126 children (≤18 years old) who have been treated with near-total thyroidectomy followed by radioiodine therapy and thyroid hormone replacement. Follow-up of the patients was done 2, 6, and 12 months after treatment and then by yearly evaluation. Response to treatment was defined according to the American Thyroid Association guidelines. ResultsPapillary thyroid cancer was the main pathology (93.7%), and 52.4% of the patients had lymph node metastasis at presentation, which was extensive (>5) in 30% of the patients. Distant metastasis was seen in 8.8%. The mean initial dose of I-131 was 74 ± 42.2 MBq/kg. The median follow-up was 59 months and the median time to achieve an excellent response was 29 months. The preablation stimulated thyroglobulin (psTg) level was 202.4 ± 301.8 ng/mL in patients with first-year incomplete response compared with 11.2 ± 17.5 ng/mL in others (P =.001). Furthermore, using logistic regression, the psTg level was found to be the only significant predictor of distant metastasis, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response. Moreover, distant metastasis was more common in boys than in girls, and it took longer time for boys to achieve an excellent response. ConclusionThe psTg level was the only significant predictor of distant metastases in children with DTC, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response.

Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor.

Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib. A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use. Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P < .05) and worst pain NRS (2.7 vs. 5.7, P < .05). Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients' perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.

Continuous Prostanoid Initiation in Severe Pulmonary Hypertension in the Pediatric Cardiac Intensive Care Unit.

Limited data exists regarding prostanoid (PGI2) use in critically ill patients with pulmonary hypertension. (PH) in the pediatric cardiac intensive care unit (CICU) setting. Single center, retrospective study of patients with diagnosis of PH who received continuous PGI2 and were admitted to CICU from January/2015 to April/2022. Data collected included patient demographics and clinical characteristics including diagnosis, etiology of PH, vasoactive and ventilatory support, length of stay, and survival. Type, initial, maximum, and final dose of PGI2 as well as hemodynamic data was obtained. Data reported as mean ± standard deviation. Significance taken p value < 0.05. 24 patients received PGI2 therapy at a mean age of 3.1years, range (0-16.6years). PGI2 was in the form of IV epoprostenol in 12 patients, IV treprostinil in 6, and SQ treprostinil in 6 patients. Mean initial dose was 2.79ng/kg/min, max dose 18.75ng/kg/min, and mean duration of therapy was 38.5days. At PGI2 initiation, 21 (87.5%) were on vasoactive infusions, 19 (79.2%) mechanically ventilated (MV), and 6 (25%) were on extracorporeal membrane oxygenation (ECMO). The in-hospital mortality rate was 37.5% (n = 9). Patients MV and on ECMO support had higher risk of death (p = 0.04, and < 0.01, respectively). PGI2 therapy was tolerated in approximately 50% of patients with the most common side effect being hypotension leading to discontinuation in 1/3rd of patients. Ongoing evaluation of the benefits of PGI2 for patients in the CICU setting will help better identify patient selection, type, and dosing of PGI2.

Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain.

Current guidelines recommend temozolomide as the first-line chemotherapy for aggressive pituitary neuroendocrine tumours. However, no clinical trials have been conducted to date and clinical experience is quite limited. We retrospectively analyzed 28 patients (9 women and 19 men), aged 46.6+16.9, with aggressive pituitary tumours (4 pituitary carcinomas and 24 aggressive adenomas) treated with temozolomide in 10 Spanish pituitary reference centres. Four patients had Cushing's disease, 9 prolactinomas and 15 clinically non-functioning pituitary tumours (seven silent corticotroph, three silent somatotroph, one silent lactotroph, one silent gondotroph and three null-cell tumours). Median size at diagnosis was 10.5 cm3 (IQR 4.7-22.5), with cavernous sinus invasion in 88% and no metastases. Pre-temozolomide treatment, these data were 5.2 cm3 (IQR 1.9-12.3), 89.3% and 14.3% (2 intracranial and 2 spinal metastases). All patients had undergone surgery (1-5 surgeries), 25 (89.3%) had received radiotherapy (7 of them reirradiated) and 13(46.4%) had received cabergoline. One patient interrupted temozolomide prematurely. The remaining 27 patients received a median of 13 cycles (range 3-66) of 5 days every 28 days, with a mean initial dose of 265 ± 73 mg when administered alone and of 133 ± 15 mg when co-administered with radiotherapy. Eight patients (29.6%) had a significant reduction (>30%) in tumour volume and 14 (51.9%) attained tumour stabilization. After a median follow-up of 29 months (IQR 10-55), 8 out of these 22 showed disease progression. A longer progression-free survival was found in the five patients who received concomitant radiotherapy. Seven patients (25%) died (all of them because of tumour progression or complications of treatments) at 77 months (IQR 42-136) after diagnosis and 29 months (IQR 16-55) after the first dose of temozolomide. Adverse effects occurred in 18 patients (14 mild and 4 moderate or severe). In conclusion, temozolomide is an effective medical treatment for aggressive pitNET and pituitary carcinomas but is sometimes followed by tumour progression. Co-administration with radiotherapy may increase progression-free survival.

Rapid Methadone Induction in a General Hospital Setting: A Retrospective, Observational Analysis.

Outpatient methadone guidelines recommend starting at a low dose and titrating slowly. As fentanyl prevalence and opioid-related mortality increases, there is a need for individuals to rapidly achieve a therapeutic methadone dose. Hospitalization offers a monitored setting for methadone initiation, however dosing practices and safety are not well described. Retrospective, observational analysis of hospitalized patients with opioid use disorder seen by an inpatient addiction consult team in an academic medical center who were newly initiated on methadone between 2016 and 2022. We calculated initial daily dose, maximum daily dose, timing interval of dose escalation, whether patients were connected to an opioid treatment program (OTP) prior to discharge, whether adverse effects or safety events occurred during the hospitalization, and whether such events were definitely or probably related versus possibly related or unrelated to methadone. One hundred twelve patients were included. The mean initial daily methadone dose administered was 32 mg (range: 10-90 mg). The mean maximum dose reached was 76.8 mg (range 30-165 mg). The mean number of days from initial to peak dose was 5.6 days (range 1-19 days). Overall, 30% of patients experienced a safety event, most commonly sedation. Only 4 safety events were deemed probably or definitely related to methadone. In regression analyses, there was no significant difference between starting doses among patients with or without sedation but there was a relationship between last dose and the likelihood of any possibly related event, with those ending at a dose of 100 mg or higher having a higher likelihood event, compared to those ending at lower doses (47.8% vs 12.4%, P < .001). Seventy-six percent were connected to OTP before discharge. Among hospitalized patients initiating methadone, rapid dose titration was infrequently associated with related safety events and most were connected to community-based methadone treatment before discharge.

Evaluation of Activated Clotting Times With a Heparin Reversal Protocol Designed to Conserve Protamine During Drug Shortages: A Retrospective, Cohort Study

To retrospectively evaluate a protamine conservation approach to heparin reversal implemented during times of critical shortages. This approach was aimed at maintaining access to cardiac surgical services. In-patient hospital setting. Eight hundred-one cardiac surgical patients>18 years old. Patients undergoing cardiac surgery who received >30,000 U of heparin were given a single fixed vial protamine dose of 250 mg or a standard 1 mg of protamine to 100 U of heparin ratio-based dose to reverse heparin. The primary endpoint was differences in post-reversal activated clotting times between the 2 groups. The secondary endpoint was differences in the number of protamine vials used between the 2 reversal strategies. The first activated clotting times values measured after initial protamine administration were not different between the Low Dose and Conventional Dose groups (122.3 s v 120.6 s, 1.47 s, 99% CI -1.47 to 4.94, p=0.16). The total amount of protamine administered in the Low Dose group was less than that in the Conventional Dose group (-100.5 mg, 99% CI -110.0 to -91.0, p < 0.0001), as were the number of 250 mg vials used per case (-0.69, 99% CI -0.75 to -0.63, p < 0.0001). The mean initial protamine doses between groups were 250 mg and 352 mg, p < 0.0001. The mean protamine vials used were 1.33 v 2.02, p < 0.0001. When the calculations were based on 50 mg vials, the number of vials used per case in the Low Dose group was even less (-2.16, 99% CI -2.36 to -1.97, p < 0.0001).) CONCLUSIONS: Conservation measures regarding critical medications and supplies during times of shortages can maintain access to important services within a community.

Outcomes in pulmonary sarcoidosis: results of a newly implemented prednisone protocol.

Background and aim Prednisone is used as first-line therapy for patients with pulmonary sarcoidosis. There is however no clear association between prednisone dose and FVC change in patients with pulmonary sarcoidosis. In order to improve our standard of care we introduced a more conservative prednisone protocol. Methods This study is a single centre observational study, applying value-based healthcare (VBHC) and quality improvement (QI) principles. Prednisone intake was reduced from a starting dose of 40 mg to a starting dose of 20 mg. Primary outcomes evaluated were FVC, FEV1 and DLCO % predicted. The secondary outcome measure was BMI. Results 369 patients were included in the old-cohort and 215 in the new-cohort. In the old-cohort, 182 (49.0%) of the patients were treated with prednisone. In total, 114 patients (62.6%) were treated according to the old protocol with a mean initial prednisone dose of 32.1 ±14.2 mg. In the new-cohort, 93 patients (45.0%) were treated with prednisone of which 53 patients (57.0%) received prednisone according to the new protocol. The mean initial prednisone dose in the new-cohort was 21.4 ±9.8 mg. Changes in FVC and FEV1 % predicted did not vary. Change in % predicted DLCO was 2.4 ±9.3 for the old-cohort and -1.3 ±11.4 for the new-cohort (p = 0.01). No statistically significant changes in BMI were observed. Conclusions Our results indicate that in more than half of the patients the new protocol was followed. Data support the observation that a more conservative prednisone regimen might be equally effective, looking at changes in pulmonary function and BMI.

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy

ObjectiveEpidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. MethodsA single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. ResultsOne hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SignificanceEpidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

Cognitive performance of preschoolers with Congenital Hypothyroidism enrolled in a follow-up program

To evaluate the cognitive performance of preschool children with CH incorporated into a follow- up program. Prospective study of 93 patients with a confirmed diagnosis of CH. Intelligence quotient (IQ) was assessed using the Wechsler Preschool and Primary Intelligence Scale (WPPSI) at 4 and 5 years, and the WISC-R at 6 years of age. Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores were analyzed. The study sample was 80 children. The average age at starting hormonal treatment was 42 ± 18 days; treatment started early in 25 patients (24 ± 6 days) and late in 55 patients (50 ± 16 days). The mean initial dose of Levothyroxine was 13.5 ± 1.5µg/kg/day. Children with athyrosis and late initiation of treatment had lower scores on the VIQ (85 ± 14), the PIQ (89 ± 12), and the FSIQ (86 ± 13) scales at 4 years of age, in comparison with patients with early initiation of treatment. These patients scored within the cut-off point for the normal IQ classification (90-109 points). IQ comparison at 6 years of age revealed differences up to 14 points in the PIQ and 11 points in the FSIQ between children with athyrosis and early initiation of treatment, with and without regular attendance to the follow-up program. These results support the importance of early initiation of treatment and the incorporation of children in follow-up programs and early stimulation. The etiology of hypothyroidism and the age at initiation of treatment were the most significant factors that affected cognitive performance.

Four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-associated bleeding: a meta-analysis of fixed versus variable dosing

BackgroundThe optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established. ObjectivesTo evaluate the effectiveness and safety of fixed versus variable 4F-PCC dosing for the management of FXa inhibitor-associated bleeding. MethodsA systematic literature search and meta-analysis of clinical studies was performed using PubMed, Embase, and Cochrane databases from inception to January 2022. The primary outcomes included hemostatic effectiveness, mortality, and thromboembolic events. Secondary outcomes included 4F-PCC usage, total length of stay in hospital and in intensive care units, and time to 4F-PCC administration. The pooled incidence or mean was calculated using a random-effects model and compared between the 2 dosing strategies. ResultsTwenty-five studies were included and data from 1,760 patients (fixed dosing, n = 228; variable dosing, n = 1,532) were analyzed. There were no significant differences in hemostatic effectiveness, thromboembolic events, or mortality rates between the dosing strategies. Hospital length of stay was significantly longer in the fixed-dosing group, with a mean stay of 7.4 days (95% CI: 3.6-11.1) compared to 5.9 days (95% CI: 5.5-6.3) in the variable-dosing group (P < 0.001). The mean initial 4F-PCC dose was significantly higher with variable dosing than fixed dosing (38 IU/kg; 95% CI: 32-44 vs. 27 IU/kg; 95% CI: 26-28, P < 0.001). ConclusionsA fixed-dosing strategy appears to be a safe and effective alternative to variable weight-based dosing and was associated with lower 4F-PCC usage. However, direct comparative studies are needed to confirm these results.

Safety and efficacy of target controlled infusion administration of propofol and remifentanil for moderate sedation in non-hospital dental practice.

Fearful and anxious patients who find dental treatment intolerable without sedative and analgesic support may benefit from moderate sedation. Target controlled infusion (TCI) pumps are superior to bolus injection in maintaining low plasma and effect-site concentration variability, resulting in stable, steady-state drug concentrations. We evaluated the safety and efficacy of moderate sedation with remifentanil and propofol using TCI pumps in non-hospital dental settings. A prospective chart review was conducted on 101 patients sedated with propofol and remifentanil using TCI pumps. The charts were completed at two oral surgeons and one general dentist's office over 6 months. Hypoxia, hypotension, bradycardia, and over-sedation were considered adverse events and were collected using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS). Furthermore, patient recovery time, sedation length, drug dose, and patient satisfaction questionnaires were used to measure sedation effectiveness. Of the 101 reviewed sedation charts, 54 were of men, and 47 were of women. The mean age of the patients was 40.5 ±18.7 years, and their mean BMI was 25.6 ± 4.4. The patients did not experience hypoxia, bradycardia, and hypotension during the 4694 min of sedation. The average minimum Mean Arterial Pressure (MAP) and heartbeats were 75.1 mmHg and 60.4 bpm, respectively. 98% of patients agreed that the sedation technique met their needs in reducing their anxiety, and 99% agreed that they were satisfied with the sedation 24 hours later. The average sedation time was 46.9 ± 55.6 min, and the average recovery time was 12.4 ± 4.4 min. Remifentanil and propofol had mean initial effect-site concentration doses of 0.96 µ/ml and 1.0 ng/ml respectively. The overall total amount of drug administered was significantly higher in longer sedation procedures compared to shorter ones, while the infusion rate decreased as the procedural stimulus decreased. According to the results of this study, no patients experienced adverse events during sedation, and all patients were kept at a moderate sedation level for a wide range of sedation times and differing procedures. The results showed that TCI pumps are safe and effective for administering propofol and remifentanil for moderate sedation in dentistry.

Age-Dependent Dose Increase During an Acute Electroconvulsive Therapy Series.

Electroconvulsive therapy (ECT) dose is highly relevant for ECT efficacy as well as adverse effects. It is often based on seizure threshold (ST). Studies have shown that ST increases over the course of an ECT series. Clinical observation suggests that this rise might be more pronounced in geriatric patients. Retrospectively, we analyzed ECT dose during the first 20 ECT treatments in 472 patients undergoing ECT. Dose adjustments were assessed in relation to patients' age using generalized least squares regression analysis. Response was defined as Clinical Global Impression Improvement Scale < 4. Dose increased in all patients during the course of the ECT series (mean initial dose, 64.97 ± 68.04 mC; at 10th ECT, 385.46 ± 211.28 mC). Dose was significantly correlated with ECT treatment number, electrode placement, and the interaction between age and ECT treatment number. In other words, dose increase was significantly positively correlated with increasing age, that is dose increased more in older compared with younger patients during the course of an ECT series ( z = 9.47, P < 0.001). Response was not correlated with age-dependent dose increase; however, the length of the ECT series in responders was negatively associated with the dose increase from the first to the seventh ECT session ( F = 5.28, P = 0.0228). Our results indicate that ST increases more rapidly during the course of an ECT series in older compared with younger patients. To ensure high efficacy throughout the course of treatment, attention should be paid to decreasing seizure quality, especially in older patients, and dose should be adjusted accordingly.

Safety and Effectiveness of Ruxolitinib in Real-World Patients with Myelofibrosis: A 2-Year Observational Study from Taiwan

Introduction Ruxolitinib (RUX) is an approved JAK1/JAK2 inhibitor for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PET-MF), but real-world safety and efficacy of RUX in Taiwan are not well understood. This study was conducted to evaluate the safety and efficacy of treatment with RUX with intermediate-2 or high risk PMF, PPV-MF or PET-MF in routine clinical practice. Method This 2-year, single-arm, multicenter, post-marketing surveillance registry collected data on the safety, tolerability, efficacy, and other clinical information of adult patients (pts) aged ≥20 years with a confirmed diagnosis of intermediate-2 or high-risk PMF, PPV-MF, or PET-MF who either received RUX or starting RUX in accordance with the general clinical practice in Taiwan. Primary endpoint included collection of adverse events (AEs), AE of special interest (AESIs; anemia, thrombocytopenia, leukocytosis, hepatitis B virus (HBV) infection or reactivation, tuberculosis (TB) infection, and other infections), and serious adverse events (SAEs) throughout the study. Key secondary endpoints included treatment duration, discontinuation rates, dosage of prescribed RUX, Myeloproliferative Neoplasm symptom assessment form (MPN-10) score after study entry and change in spleen size, specifically in naïve patients who were eligible for spleen response evaluation. Results A total of 99 (51% PMF, 22.4% PPV-MF, and 26.5% PET-MF) pts were recruited, of which 38 (38.4%) pts discontinued due to consent withdrawal (n=11), death (n=10), discontinued prescription of RUX for 3 months (n=4), AEs (n = 2), unsatisfactory therapeutic effect (n=2), administrative problems (n=1), disease progression (n=1), required immediate stem cell transplantation (n=1), and others (n=6). Median age was 68.1 (range: 38.3-87.2) years and gender ratio was balanced, with 97 Taiwanese pts (98.0%). Median disease duration was 13.9 months (range: 0-967.6 months) and 70.7% and 28.3% of pts were identified with the risk of intermediate-2 or high using IPSS/DIPSS risk assessment, respectively. Majority of the recruited pts were RUX pre-treated (n=75; 75.8%) and 24.2% (n=24) pts were RUX-naïve at baseline. During the study, 88 pts (89.8%) had 673 AEs, and 44 (44.9%) experienced 159 SAEs. Half of the pts (55.1%) had moderate or severe SAEs and 39 pts recovered. Over 80% of SAEs (n=131) were not related to RUX. Major AESIs were anemia (29.6%) and thrombocytopenia (20.4%). There were no HBV infection or reactivation reported; 2% of pts had TB while 3% of pts had herpes zoster infections. The major reported infection was pneumonia (20.4%). Key safety data are summarized in Table 1. Most pts had their AEs resolved (77.6%), while 10 deaths occurred due to AEs (10.2%). Majority of the pts (41.8%) received a daily dose of RUX 20 mg at the enrolment, with an average mean daily dose of 22.7±9.2 mg (Figure 1). For naïve pts, mean initial dose was 18.8 ± 8.50 mg and gradually titrated up to 22.3 ± 8.69 mg at 3 months and to 24.0 ± 9.17 mg at 6 months. Among 98 pts, 13.3% pts whose platelet counts between 100-200×103/μL and 21.4% pts whose platelet counts were >200×103/μL were treated with RUX 5-10 mg twice daily. Among 27 RUX pre-treated patients (mean RUX duration before study entry: 17.0 ± 20.98 months), spleen size by palpation was relatively stable throughout the study period. For the 7 RUX naïve pts, the mean spleen size change from baseline was -15.9 %± 28.72 at 12 weeks, -30.8% ± 31.28 at 24 weeks, -54.2% ± 41.93 at 48 weeks and -52.0% ± 36.41 at 96 weeks. However, it should be interpreted with caution due to the small pt pool. A total of 65 pts (65.7%) had >50% improvement in the symptom response by MPN-10 during 2-year study period. . Conclusion This is the first real-world study in Taiwan to evaluate safety and efficacy with RUX in patients with MF. It was observed that physicians employed a conservative strategy for a lower starting dose with gradual titration resulting in comparable safety profile, but lower incidences of thrombocytopenia compared to published clinical trials. The majority of pts reported continuous symptomatic improvement and a small number of RUX naïve pts had pronounced spleen size reduction. Further investigations are required to evaluate whether optimal dose of RUX or titration speed would improve spleen response. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Isolated polymyalgia rheumatica: a cross-sectional, single-center, retrospective cohort study

Aim: The aim of the study was to review sociodemographic variables, clinical and laboratory findings, disease progression and treatment response of patients with isolated polymyalgia rheumatica and to investigate the effect of initial steroid dose and maintenance treatment on the progression of clinical and laboratory outcome. &#x0D; Material and Method: The medical records of 39 polymyalgia rheumatic patients who followed up between 2001 and 2020 were screened. After excluding patients with overlapped giant cell arteritis and malignancies, 19 polymyalgia rheumatica patients (female:16 and male:3) were included in the study. Demographic data, anthropometric measurements, comorbidities, initial symptom, physical examination, clinical and laboratory (acute phase reactants) findings, medications, changes in treatment status, and cumulative steroid dose were recorded. The medical data of first (1st month), second (4th month), and third (7th month) visits were noted according to the structured form. &#x0D; Results: The mean age was 68±8 years and the mean initial steroid dose was 21.5±8.9 mg. While the complaints regarding polymyalgia rheumatica decreased in 52.6% of patients (n=10) in the first visit, those complaints regressed in 47.4% (n=9) and 73.7% (n=14) of patients in the second and third visit, respectively. In the first visit (1st month), the mean erythrocyte sedimentation rate and C-reactive protein values were 21.7±12.3 mm/h and 5.8±5.1 mg/dl. In the second (4th month) and third visits (7th month), while the mean erythrocyte sedimentation rate was found as 36.5±27.3 mm/h and 27.3±18.6 mm/h, the mean C-reactive protein was 27.2±43.0 mg/dl and 17.6±30.2 mg/dl, respectively. Clinical remission was observed in 47.4% of patients (n=9) in the second visit and in 31.6% of patients (n=6) in the third visit. Median cumulative corticosteroid doses were 600 mg in first visit, 960 mg in second visit, and 1346 mg in the third visit. &#x0D; Conclusion: The clinical characteristics and the initial steroid dose were compatible with the literature. Even though cumulative corticosteroid doses were quite high, lower remission rates were observed in these patients. The possible reason for this was considered to be the non-adherence of the patients to the treatment.

Ultra-fast remote up-titration of heart failure treatment: a safe, efficient and feasible protocol

Abstract Introduction Heart failure (HF) is a common disease with a significant economic burden, mainly caused by HF hospitalisations and significant morbi-mortality. Nevertheless, HF patients are still undertreated due to a clinical inertia that needs to be reversed as soon as possible using new, safe and available methods. Remote up-titrating HF medication might be the solution to rapidly optimize HF treatment to maximal tolerated doses. Purpose Our objective was to describe the safety, efficacy and feasibility of an ultra-fast remote up-titration protocol of HF treatment. Methods Patients with a recent hospitalization due to a HF decompensation and left ventricular ejection fraction &amp;lt;50% were retrospectively included in our database. We collected clinical, biological and treatment data at enrollment and at the end of HF medication optimization. Our protocol consisted in remote consultation (via telephone or video-consultation) every 15 days with a 72h prior blood test. Blood pressure (BP), heart rate (HR) and weight were recorded either by tele-monitoring or self-measurement. Results We evaluated 96 patients, 25% female with a mean LVEF at 29%, main etiology of HF was ischemic (48%) and mean NTproBNP was 2384 pg/mL. Mean BP was 112/70 mmHg, HR was 73 bpm, glomerular filtration rate (GFR) 71 ml/min and potassium concentration was 4,4 mEq/L. Ninety four patients were initially treated with a beta blocker (BB), 29% of our cohort was treated either with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) and 59% was treated with angiotensin receptor neprilysin inhibitor (ARNI). A total of 72 patients were treated with a mineralocorticoid receptor antagonist (MRA) and 58 patients were also treated with an inhibitor of sodium-glucose transport protein 2 (SLGT2i), Figure 1. Median duration of tele-titration consultation was 42 days. We up-titrated BB in 50% of our patients, of which 10% were at maximum dose, making a total of 98% of our cohort under BB treatment. Sixty percent of patients under ACEI or ARB were switched to ARNI. Of the 82% of patients under ARNI, up to 50% achieved the maximal dose. We introduced or up-titrated ARM in 41 patients, reaching the target dose in 37%. Dose variations and mean initial and final doses are shown in Figure 2.1 and 2.2 Minor adverse events that motivated a down-titration or a cessation of treatment were, hyperkalemia 5%, acute renal failure (ARF) 6%, hypotension 3% and bradycardia 2%. Non urgent hospitalization due to ARF with hyperkalemia or HF only occurred in 2 cases. The limiting factors for not reaching the optimal targeted dose were low HR in 20%, hypotension in 11%, high concentration of potassium 10% and chronic renal failure in 9%. Conclusion Remote up-titration of HF medication is a promising tool in the fight against clinical inertia and a fast, feasible, safe (only 2% of major events) and efficient solution to our undertreated patients. Funding Acknowledgement Type of funding sources: None.