High-dose Patients Research Articles

P33 The impact of body mass index on psoriasis area and severity index response in patients treated with adalimumab

Abstract Obesity and psoriasis are bidirectionally linked. Some biologics are given in higher doses in patients >90 kg while others have only one licensed dose. The bioavailability of subcutaneous medication is negatively impacted by fat volume with body mass index (BMI) a potential negative effector on treatment response. Our aim was to assess the impact of baseline BMI on psoriasis area and severity index (PASI) 75 response with adalimumab treatment. Patients recruited to BADBIR with complete datasets in our centre were included. Information was collected from BADBIR records and local electronic care records including age, gender, baseline BMI and PASI at baseline, 6 and 12 months. Statistical analysis was completed using Jamovi v2.0 (Sydney, Australia). We identified 46 patients including 33 males (71.7%) with a median age of 45.5 years [interquartile range (IQR) 35–51]. Most patients were overweight/obese (n = 38, 82.6%) with a median BMI of 29.1 kg/m2 (IQR 25.7–34.6). Disease severity was moderate-to-severe (n = 44, 95.7%) with a median PASI of 12.1 (IQR, 10.3–17.6). Using linear regression analysis, for every 1 standard deviation (SD) increase in baseline PASI, baseline BMI increased by 1.1 kg/m2. Conversely, for every 1 SD increase in baseline BMI, baseline PASI increased by 1.2. Using binomial regression, baseline BMI did not predict PASI75 response at Month 6 (P = 0.786) or Month 12 (P = 0.117). Data regarding the impact of BMI on treatment response in psoriasis are important to predict PASI response on an individualized patient basis. Studies have been conflicting with some suggesting higher weight in treatment-refractory patients and others identifying no difference. We have identified a reciprocal effect between PASI and BMI but fall short of identifying BMI as a predictor of PASI75 response. Large-scale studies including multiple biologic agents are required to further evaluate this.

Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential

Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1–––3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.

The Effectiveness of High versus Low Dose Corticosteroid therapy in Pediatric Patients with Acute Respiratory Distress Syndrome

Abstract Background When the lungs fill with fluid as a result of an infection or injury, acute respiratory distress syndrome ensues. Inflamed and fluid-filled lungs occur. They become rigid as a result, making it difficult for them to breathe fully. Blood oxygen levels will fall, endangering the health of other organs. Patients will require a ventilator to help them breathe while their lungs mend. The aim of this study was: to evaluate safety and efficacy of high dose therapy in acute respiratory distress syndrome pediatric patients and to compare safety and efficacy of high dose versus low dose therapy in Acute respiratory distress syndrome patients. Patients and Methods A Prospective open label randomized trial included 15 patients as group1 received high dose corticosteroid therapy for 3 consequent days, high dose Methyl prednisone 30 mg/kg/day and 15 patients as group 2 received low dose corticosteroid therapy for 3 consequent days, low dose Methyl prednisone 2 mg/kg/day. Clinical and laboratory data chest ultrasound and bronchoalveolar lavage to measured pre collagen peptide were studied in each group before and after corticosteroid therapy. Results In the present study 15(50%) patients received high dose steroid and 15 (50%) patients received low dose steroid, male 23 (70%), female 7 (30%), age 7 (3.0-30.0), weight (9.55 ± 6.63), there was no significant difference in prognosis and total days in pediatric intensive care unit between high and low dose corticosteroid therapy as prognosis improving 17 patients (55%), death 13(45%) and As regards total days in pediatric intensive care unit median in high dose corticosteroid therapy 24.0 (15.50-33.0) and median in low dose corticosteroid therapy 18.50 (11.0-23.50) less days in pediatric intensive care unit in low dose steroid therapy group than high dose steroid therapy group but no significant difference between two groups as regarding decrease in chest ultrasound (BLUE Score) and increase in pre collagen peptide in bronchoalveolar lavage between study groups . Conclusion there was no significant difference in prognosis and total days in pediatric intensive care unit between high and low dose corticosteroid therapy as regarding change in chest ultrasound (BLUE Score) and change in pre collagen peptide in bronchoalveolar lavage between study groups.

Improving a regional project on diagnostic reference levels for interventional procedures (OPRIPALC) with the support of a dose management system for the protection of patients and staff

Interventional radiology is a clinical practice with important benefits for patients, but which involves high radiation doses. The optimisation of radiation protection (RP) for paediatric interventional cardiology is a priority for both patients and staff. The use of diagnostic reference levels (DRLs) has been proposed by the International Commission on Radiological Protection to improve RP in imaging procedures. Dose management systems (DMSs) allow the automatic collection of dosimetric, geometric and technical data to assist the optimisation process, with a continuous audit of the procedures, generating alerts to implement corrective actions when necessary. Patient dose indicators may be analysed individually and for different radiation events (fluoroscopy and cine runs). Occupational doses per procedure may be analysed (if electronic dosimeters are available) and linked with patient doses for an integrated approach to RP. Regional optimisation programmes require data collection and processing from several countries to set and periodically update the DRLs. Patient data is anonymised, and each participating hospital has access to their data in a central computer server. Using DMSs may be one of the best ways to support these programs in the collection and analysis of data, raising alerts about high patient and occupational doses and suggesting optimisation actions.

Determinants of radiation exposure during mobile cone-beam CT-guided robotic-assisted bronchoscopy.

Robotic-assisted bronchoscopy (RAB) is an emerging modality to sample pulmonary lesions. Cone-beam computed tomography (CBCT) can be incorporated into RAB. We investigated the magnitude and predictors of patient and staff radiation exposure during mobile CBCT-guided shape-sensing RAB. Patient radiation dose was estimated by cumulative dose area product (cDAP) and cumulative reference air kerma (cRAK). Staff equivalent dose was calculated based on isokerma maps and a phantom simulation. Patient, lesion and procedure-related factors associated with higher radiation doses were identified by logistic regression models. A total of 198 RAB cases were included in the analysis. The median patient cDAP and cRAK were 10.86 Gy cm2 (IQR: 4.62-20.84) and 76.20 mGy (IQR: 38.96-148.38), respectively. Among staff members, the bronchoscopist was exposed to the highest median equivalent dose of 1.48 μSv (IQR: 0.85-2.69). Both patient and staff radiation doses increased with the number of CBCT spins and targeted lesions (p < 0.001 for all comparisons). Patient obesity, negative bronchus sign, lesion size <2.0 cm and inadequate sampling by on-site evaluation were associated with a higher patient dose, while patient obesity and inadequate sampling by on-site evaluation were associated with a higher bronchoscopist equivalent dose. The magnitude of patient and staff radiation exposure during CBCT-RAB is aligned with safety thresholds recommended by regulatory authorities. Factors associated with a higher radiation exposure during CBCT-RAB can be identified pre-operatively and solicit procedural optimization by reinforcing radiation protective measures. Future studies are needed to confirm these findings across multiple institutions and practices.

Abstract 6586: ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models

Abstract Polycomb repressive complex 2 (PRC2) dysregulation occurs in multiple tumor types and is associated with poor prognosis in patients with prostate cancer. In patients treated with androgen receptor pathway inhibitors (ARPI), emergence of tumor cell plasticity is associated with resistance to therapy. Dysregulation of epigenetic reprogramming factors, including PRC2, creates an environment that is permissive for such lineage plasticity. Inhibition of the PRC2 complex therefore may provide an opportunity to overcome or prevent the emergence of plasticity in prostate cancer. Notably, emerging clinical trial data has demonstrated the potential of ARPI and PRC2 inhibitor combination therapy to improve outcomes in patients with metastatic prostate cancer. PRC2 tri-methylates histone H3 at lysine 27 (H3K27me3), leading to long-term transcriptional silencing, a key mechanism regulating cellular functions such as cell growth and differentiation. Three core subunits comprise PRC2: the catalytic subunit enhancer of zeste homolog 2 (EZH2), suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED). EED is essential for the histone methyltransferase activity of PRC2. First-generation PRC2 inhibitors, which target EZH2, exhibit poor drug properties, drug-drug interaction liabilities and short half-life requiring twice daily dosing at high doses in patients. We developed a second generation PRC2 inhibitor, ORIC-944, an allosteric inhibitor of PRC2 that binds the EED subunit. ORIC-944 is a potent, highly selective, orally bioavailable inhibitor with best-in-class properties. ORIC-944 demonstrated single agent tumor growth inhibition in a spectrum of in vivo prostate cancer models, including AR-positive, AR-mutant, ARv7, ARPI-responsive and ARPI-resistant models. In vitro analysis of the combination of ARPIs and ORIC-944 showed synergy in multiple prostate cancer cells, utilizing BLISS and other quantitative methods. In vivo studies revealed that ORIC-944 demonstrated increased efficacy in combination with ARPI, consistent with the in vitro synergy. RNA-seq analysis of transcriptional changes induced by ORIC-944 provided mechanistic insight into the role of PRC2 in prostate cancer lineage plasticity and combination response. These results position ORIC-944 as a best-in-class PRC2 inhibitor for evaluation in combination with ARPI in patients with metastatic prostate cancer. A phase 1b trial of ORIC-944 is ongoing (NCT05413421). Citation Format: Anneleen Daemen, Natalie Yuen, Amber Wang, Aleksandr Pankov, Livia Ulicna, Chelsea Chen, Frank L. Duong, Jason Long, Matthew A. Marx, James G. Christensen, Lori S. Friedman, Melissa R. Junttila. ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6586.

Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity.

Inhibitors of the p53-MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53-MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents.

Has a High Dose of Vitamin D3 Impacted Health Conditions in Older Adults?-A Systematic Review and Meta-Analysis Focusing on Dose 100,000 IU.

Older adults are prone to vitamin D3 (VD3) deficiency, which may impair their health. A high dose of VD3 (HDVD3 = 100,000 IU) could improve their 25-hydroxyvitamin D3 [25(OH)D] level and health outcomes. However, evidence for such a beneficial effect of HDVD3 in older adults coming from clinical trials is mixed. To review the literature on the efficacy of a single dose of 100,000 IU of VD3 in older people. We searched PubMed/Medline, Science Direct, and NIH's clinical trials registry for clinical studies on the effect of a single high dose of VD3 on various health outcomes in older people. We also performed a meta-analysis using the standardized mean difference to assess the effect of VD3 on its blood level. Due to expected high heterogeneity, its amount (i.e., tau2) was estimated using the DerSimonian-Laird estimator. To estimate tau2, the Q-test for heterogeneity and the I2 statistic were calculated. Search results identify 13 studies that reported diverse health outcomes, such as lung and cardiovascular function, skin cancer progression, intensive care unit mortality, immune system response, and bone density. The meta-analysis showed a significant increase in 25(OH)D blood levels after treatment in 10 studies, with an average standardized mean difference of 2.60 ng/mL (95% CI: 2.07 to 3.13). Their results suggested that a single high dose of VD3 may benefit intensive care unit patients and skin cancer patients in remission. However, evidence for other beneficial health effects of HDVD3 was mixed due to high heterogeneity among studies. A single high dose of VD3 may positively affect some health outcomes in older people, possibly due to its pleiotropic and immunomodulatory effects. However, the evidence needs to be more extensive and consistent, and more rigorous studies are required to confirm the benefits and safety of VD3 high doses in older patients.

Appropriate dose of regorafenib based on body weight of colorectal cancer patients: a retrospective cohort study

PurposePrevious randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight.MethodsWe used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups.ResultsWe identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 – 1.39, Table 3) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 – 1.37).ConclusionThe findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.

The Dose Optimization and Evaluation of Image Quality in the Adult Brain Protocols of Multi-Slice Computed Tomography: A Phantom Study.

Computed tomography examinations have caused high radiation doses for patients, especially for CT scans of the brain. This study aimed to optimize the radiation dose and image quality in adult brain CT protocols. Images were acquired using a Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). The image quality was also evaluated using AutoQA Plus v.1.8.7.0 software. CT number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. The modulation transfer function (MTF) showed a higher value in 100 and 120 kVp protocols (p < 0.001), while high-contrast spatial resolution showed a higher value in 80 and 100 kVp protocols (p < 0.001). Low-contrast detectability and the contrast-to-noise ratio (CNR) tended to increase when using high mAs, SNR, and the Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100 and 120 kVp, mAs ranging from 200 to 300 mAs, SNR level within the range of 0.7-1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.

Application of a Contralateral Esophageal-Sparing Technique to Reduce Radiation Esophagitis in Limited-Stage Small Cell Lung Cancer Treated with Twice-Daily Radiotherapy and Concurrent Chemotherapy

Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p<0.001). The CE's median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.

Axial Dose Profile in Head CT Scan Using a 140 kV X-Ray Beam

Computed Tomography (CT) has been widely used in radiological imaging diagnosis, but it generates higher doses in patients. The growing demand for tomography exams has generated concern in the scientific community in increasing the population dose generated by this technique.

Application of a contralateral esophageal-sparing technique to reduce radiation esophagitis in limited-stage small cell lung cancer treated with twice-daily radiotherapy and concurrent chemotherapy.

e20644 Background: Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. Methods: We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. Results: We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p &lt; 0.001). The CE’s median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. Conclusions: By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.

Impact of Diabetes Mellitus on Benefit of β-Blocker Therapy After Myocardial Infarction

Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including those with diabetes mellitus (DM). This study assesses the impact of β-blocker type and dosing on survival in patients with DM after MI. A cohort of 6,682 patients in the Outcomes ofBeta-blockerTherapyAfter MyocardialINfarction registry were discharged after MI. In this cohort, 2,137 patients had DM (32%). Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials and reported as percentage. Dosage groups were: no β blocker, >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose. The overall mean discharge β-blocker dose in patients with DM was 42.7 ± 34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Patients with DM were prescribed carvedilol at a higher rate than those without DM (27.8% vs 19.6%). The 3-year mortality estimates were 24.4% and 12.8% for patients with DM versus without DM (p <0.0001), respectively, with an unadjusted hazard ratio=1.820 (confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the >12.5% to 25% dose category had the highest survival rates, whereas patients in the >50% dose had the lowest survival rate among patients discharged on β blockers (p <0.0001). In the multivariable analysis among patients with DM after MI, all β-blocker dose categories demonstrated lower mortality than no therapy; however, only the >12.5% to 25% dose had a statistically significant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907, p=0.025). In patients with DM, there was no statistically significant difference in 3-year mortality among those treated with metoprolol versus carvedilol. In conclusion, our analysis in patients with DM after MI suggested a survival benefit from β-blocker therapy, with no apparent advantage to high- versus low-dose β-blocker therapy; although, physicians tended to prescribe higher doses in patients with DM. There was no survival benefit for carvedilol over metoprolol in patients with DM.

Ginger Extract Reduces Oxidative Stress and Improves the Clinical Outcomes in Patients with Alopecia Areata

Alopecia areata is a common disorder of known autoimmune etiology and mostly treated with oral steroids to stimulate new hair growth with high chances of side effects. The present study was designed to assess the clinical significance of ginger in improving oxidative stress and reducing the dose of prednisolone in patients with alopecia. Forty patients (19 female and 21 male), with different lesions of stable localized on the scalp were enrolled in this pilot prospective open-label clinical study. Exclusion criteria include the use of any medication that may influence the course of the disease. The patients were allocated into two groups and treated with 500 mg of ginger powder once daily for 60 days with either 10 mg or 100 mg/day prednisolone tablets. Blood samples were obtained at zero time, day-30 and day-60 and utilized for the evaluation of the erythrocytes contents of reduced glutathione, and malondialdehyde. The change in body weight, incidence of acne and the hair loss were also monitored. The glutathione and malondialdehyde were compared with those of 20 healthy subjects served as control group. The results revealed that two-month treatment with ginger improved the rate of hair growth probably by attenuating free radicals-induced damage on immune system and addressed the possibility of reducing prednisolone dose from 100 mg to 10 mg administered each other day. In conclusion, the use of ginger may have a role in protecting radical-induced damage and decreasing side effects of high prednisolone dose in patients with alopecia areata.

Variation in opioid filling after same-day breast surgery in Ontario, Canada: a population-based cohort study.

Postoperative pain management practices in breast surgery are variable, with recent evidence that approaches for minimizing or sparing opioids can be successfully implemented. We describe opioid filling and predictors of higher doses in patients undergoing same-day breast surgery in Ontario, Canada. In this retrospective population-based cohort study, we used linked administrative health data to identify patients aged 18 years or older who underwent same-day breast surgery from 2012 to 2020. We categorized procedure types by increasing invasiveness of surgery: partial, with or without axillary intervention (P ± axilla); total, with or without axillary intervention (T ± axilla); radical, with or without axillary intervention (R ± axilla); and bilateral. The primary outcome was filling an opioid prescription within 7 or fewer days after surgery. Secondary outcomes were total oral morphine equivalents (OMEs) filled (mg, median and interquartile range [IQR]) and filling more than 1 prescription within 7 or fewer days after surgery. We estimated associations (adjusted risk ratios [RRs] and 95% confidence intervals [CIs]) between study variables and outcomes in multivariable models. We used a random intercept for each unique prescriber to account for provider-level clustering. Of the 84 369 patients who underwent same-day breast surgery, 72% (n = 60 620) filled an opioid prescription. Median OMEs filled increased with invasiveness (P ± axilla = 135 [IQR 90-180] mg; T ± axilla = 135 [IQR 100-200] mg; R ± axilla = 150 [IQR 113-225] mg, bilateral surgery = 150 [IQR 113-225] mg; p < 0.0001). Factors associated with filling more than 1 opioid prescription were age 30-59 years (v. age 18-29 yr), increased invasiveness (RR 1.98, 95% CI 1.70-2.30 bilateral v. P ± axilla), Charlson Comorbidity Index ≥ 2 versus 0-1 (RR 1.50, 95% CI 1.34-1.69) and malignancy (RR 1.39, 95% CI 1.26-1.53). Most patients undergoing same-day breast surgery fill an opioid prescription within 7 days. Efforts are needed to identify patient groups where opioids may be successfully minimized or eliminated.

Axial Dose Profile in Head CT Scan Using a 140 kV X-Ray Beam

Computed Tomography (CT) has been widely used in radiological imaging diagnosis, but it generates higher doses in patients. The growing demand for tomography exams has generated concern in the scientific community in increasing the population dose generated by this technique.

899: COMPARISON OF CORTICOSTEROID DOSING IN NONINVASIVE POSITIVE PRESSURE VENTILATION COVID-19 PATIENTS

Introduction: High dose corticosteroids decrease ventilator free days in mechanically ventilated COVID-19 patients, however there is limited data on the benefit of higher doses in patients receiving non-invasive positive pressure ventilation. The purpose of this study was to compare high versus low dose corticosteroids’ impact on ventilator free days for COVID-19 patients who received continuous non-invasive positive pressure respiratory support. Methods: This retrospective study included COVID-19 positive patients diagnosed within 14 days of hospital admission, aged 18 years or older, and those who received at least 48 hours of corticosteroids while on continuous non-invasive positive pressure ventilation. Patients were excluded if they were pregnant, had active malignancy, transferred from an on outside facility, used oral corticosteroids within 10 days of hospitalization, and those who died or had comfort care orders placed within 24 hours of admission. The primary objective of this study compared ventilator free days between high dose (dexamethasone 20 mg or methylprednisolone ≥ 120 mg per day) and low dose (dexamethasone 6 mg per day) corticosteroids for patients who received continuous non-invasive positive pressure ventilation. Secondary objectives compared mortality, intensive care unit (ICU) length of stay, and hyperglycemia rates between groups. Results: A total of 72 patients were included in this study with 36 patients in each group. There was a statistically significant difference of 3 ventilator free days between the high and low dose corticosteroid groups (median [IQR], 12 days [8-16] vs 9 days [7-12], p=0.047). No difference was found between groups for ICU length of stay or inpatient mortality. There was an increased incidence of hyperglycemia in the high dose group compared to the low dose group (n [%], 32 patients [89] vs 24 patients [67], p=0.023). Conclusions: Initiating high dose corticosteroids for COVID-19 patients on non-invasive positive pressure ventilation is associated with an increase in ventilator-free days. The use of high dose corticosteroids in this patient population could help to delay or prevent intubation and the complications associated with mechanical ventilation. Future studies should evaluate duration of therapy and additional therapies for COVID-19 patients.

Evaluation of patient doses for routine digital radiography procedures toward establishing an institutional diagnostic reference levels: A case study in Sri Lanka.

The present study was conducted as part of a comprehensive work to establish National Diagnostic Reference Levels (NDRLs) in Sri Lanka for the first time. DRLs can be used as an effective optimization tool for identifying unusually high or low patient doses during X-ray examinations. This study aims to propose institutional DRLs (IDRLs) by measuring the kerma-area product (KAP) of adult patients undergoing routine projection X-ray examinations. The median and the 75th percentile KAP values obtained were compared with that of the single institution KAP values reported from India and Greece. This descriptive cross-sectional study was conducted in a public hospital in Uva province, Sri Lanka, with 400 adult patients aged 18-87 years and weighing 58±20kg. The patient-specific information (age, sex, weight, and height) and corresponding exposure parameters (tube voltage and current-exposure time product) were obtained. The KAP values were measured, and descriptive statistics were utilized for data analysis. The median KAP values obtained were proposed as IDRLs. The IDRLs in Gy.cm2 were 0.23 for cervical spine anterior-posterior (AP), 0.19 for cervical spine lateral (LAT), 0.10 for chest posterior-anterior (PA), 0.06 for knee joint AP, 0.05 for knee joint LAT, 1.47 for KUB AP, 0.85 for lumbar spine AP, 1.97 for lumbar spine LAT, 0.29 for shoulder joint AP, 0.61 for skull PA, and 0.60 for skull LAT examinations. The maximum to minimum ratio of KAP values ranged from 2.4 for KUB AP to 6.3 for the cervical spine AP examinations. The median and the 75th percentile of most of the examinations were comparable to corresponding KAP values reported by the countries mentioned above, except for the skull PA and LAT examinations. Accordingly, interquartile ranges of exposure parameters are recommended for skull examinations to improve the optimization of patient doses.

Primary sclerosing cholangitis-A long night's journey into day.

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