Dose Reduction and Low-Contrast Detectability Using Iterative CBCT Reconstruction Algorithm for Radiotherapy

Introduction: Several studies have reported the relation between the imaging dose and secondary cancer risk and have emphasized the need to minimize the additional imaging dose as low as reasonably achievable. The iterative cone-beam computed tomography (iCBCT) algorithm can improve the image quality by utilizing scatter correction and statistical reconstruction. We investigate the use of a novel iCBCT reconstruction algorithm to reduce the patient dose while maintaining low-contrast detectability and registration accuracy. Methods: Catphan and anthropomorphic phantoms were analyzed. All CBCT images were acquired with varying dose levels and reconstructed with a Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iCBCT. The low-contrast detectability was subjectively assessed using a 9-point scale by 4 reviewers and objectively assessed using structure similarity index (SSIM). The soft tissue-based registration error was analyzed for each dose level and reconstruction technique. Results: The results of subjective low-contrast detectability found that the iCBCT acquired at two-thirds of a dose was superior to the FDK-CBCT acquired at a full dose (6.4 vs 5.4). Relative to FDK-CBCT acquired at full dose, SSIM was higher for iCBCT acquired at one-sixth dose in head and head and neck region while equivalent with iCBCT acquired at two-thirds dose in pelvis region. The soft tissue-based registration was 2.2 and 0.6 mm for FDK-CBCT and iCBCT, respectively. Conclusion: Use of iCBCT reconstruction algorithm can generally reduce the patient dose by approximately two-thirds compared to conventional reconstruction methods while maintaining low-contrast detectability and accuracy of registration.

Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19

Introduction: Coronavirus disease 2019 is a global health threat often accompanied with coagulopathy. Despite use of thromboprophylaxis in this population, thrombotic event rates are high. Materials and methods: This was a multicenter, retrospective cohort study comparing the safety and effectiveness of thromboprophylaxis strategies at 2 institutions in hospitalized patients with coronavirus disease 2019. Regimen A utilized a higher-than-standard thromboprophylaxis dosage and Regimen B received full-dose anticoagulation for any D-dimer 3 mcg/mL or greater and prophylactic for less than 3 mcg/mL. The primary outcome compared the rate of thrombotic events between treatment groups. Secondary endpoints compared rates of major or clinically relevant non-major bleeding as well as the proportion of patients in each group experiencing thrombotic events within 30 days of discharge. Results: One-hundred fifty-three patients were included in the analysis, 64 receiving Regimen A and 89 receiving Regimen B. Seven (4.6%) thrombotic events occurred, 3 (4.7%) in patients receiving Regimen A, and 4 (4.5%) in Regimen B ( P = 1.0). Twelve patients (13.5%) receiving Regimen B had a bleeding event versus 2 (3.1%) in Regimen A ( P = .04), half of which were major in each group. All patients who bled in either treatment group were receiving mechanical ventilation, and 12 of 14 were receiving full-dose anticoagulation. One patient receiving Regimen A was readmitted with a pulmonary embolism. Conclusions: In this study, the thromboprophylactic regimen impacted bleeding, but no significant difference was seen with thrombotic outcomes. Almost all patients who experienced a bleed were mechanically ventilated and receiving full-dose anticoagulation. The use of full-dose anticoagulation should be cautioned in this population without an additional indication.

Antioxidant Capacity and Nutritional Value of Potato Tubers (Solanum tuberosum L.) as a Dependence of Growing Conditions and Long-Term Storage

The aim of the study was to assess the interactive effect of the use of bio-fertilizer and organic matter brought into the soil, as well as to limit the use of mineral fertilization on the content of bioactive compounds in potato tubers cultivar ‘Satina’. The test results show a positive effect of the applied bio-fertilizer in all tested variants of organic fertilization (straw, fodder pea, manure) on the level of the tested compounds. Comparing the content of crude protein in tubers from plots where half the dose of mineral fertilization was applied, the use of bio-fertilizer increased the content of this component, especially after using straw. After 6 months of storage, organic fertilization had no significant effect on the protein content, while significant differences were found in tubers fertilized with mineral, in favor of the full dose of NPK fertilizers. The storage time increased the content of tyrosine, leucine, lysine, alanine, glutamic acid, and total AA, and also methionine, aspartic acid, and asparagine, while the content of isoleucine and phenyl-alanine decreased. The highest content of total polyphenols was found in tubers where the plots were covered with pea application, a full dose of mineral fertilizer, and the use of bio-fertilizer. Unfortunately, after 6 months of storage, potato tubers from plots fertilized with peas, especially those fertilized with half the dose of mineral fertilization and without the use of biofertilizer, significantly lost the most total polyphenols. Similar relationships were obtained for the level of chlorogenic acid in tubers, which is significantly correlated with the content of polyphenols, but only organic fertilization in the form of peas significantly increased the concentration of chlorogenic acid. On the other hand, the highest post-harvest antioxidant activity was characteristic of tubers from plots fertilized with manure, with a full dose of mineral fertilization and biofertilizer. During the 6-month storage, there was a decrease in the antioxidant capacity, on average 12.4% for the objects. This may indicate the influence of polyphenolic compounds as well as other antioxidants on the assessed trait.

Efficacy of Hymecromone in Post-Cholecystectomy Patients

Background. The cholecystectomy is the major cause of sphincter of Oddi dysfunction (SOD), that may be classified as post-cholecystectomy syndrome (PCES). Treatment of PCES requires in most of the cases application of selective antispasmodic drugs.Aim. To evaluate efficacy and safety of hymecromone in patients with post-cholecystectomy SOD, to compare standard and reduced doses of hymecromone.Methods. Overall, 26 patients were enrolled in non-interventional comparative study: 2 males, 24 females, aged from 25 to 74 years. All patients underwent cholecystectomy for symptomatic gallstone disease within 1 to 10 years prior to beginning of the study. All patients were diagnosed to have SOD according to Rome IV Diagnostic Criteria for functional biliary sphincter of Oddi disorder (E1b). All patients underwent hymecromone monotherapy for 3 weeks. Patients were randomized to group A and B to receive full-dose or half-dose of the drug respectively.Results. Abdominal pain completely subsided in 85 % of patients, significant improvement was found for bloating and diarrhea. Mild increase in fasting common bile duct (CBD) diameter after treatment (7.23 ± 0.99 vs 6.78 ± 1.01; p = 0.029) was attributed to choleretic action of hymecromone. Hymecromone resulted in significant improvement of CBD response to fatty meal stimulation (ΔCBD): –1.08 ± 0.46 mm vs –0.10 ± 0.33 mm pretreatment (p = 0.016). Degree of improvement was more pronounced in the group A (full-dose) as compared to group B (half-dose) for abdominal pain (Z = 2.74, p = 0.031), bloating (Z = 2.63, p = 0.035) and constipation (Z = 2.61, p = 0.038)Conclusion. Hymecromone demonstrated itself to be an effective and safe drug, that may be applied both in standard and half dose. However, the efficacy of full-dose is higher both for the treatment of biliary pain and dyspeptic symptoms. Transabdominal ultrasound may be applied as a reliable test for both prediction of treatment efficacy and to monitor patients state during treatment course.

Efficacy and Safety of Afatinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with EGFR Mutations: A Meta-Analysis of Real-World Evidence

Introduction. The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations based on real-world evidence. Materials and Methods. Eligible real-world studies were identified from PubMed, Cochrane Library, and Embase. Cochrane guidelines were used to assess the quality of included studies. Cochran’s Q test and I2 statistics were used for the heterogeneity analysis. Results. Twenty-five studies were included in this meta-analysis; nine studies were included in the qualitative descriptive analysis. The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months. The total incidences of adverse events (AEs) for skin rashes, diarrhea, paronychia, and mucositis were 71.4% (64.4%, 77.9%), 70.4% (60.1%, 79.8%), 52.1% (41.9, 62.3%), and 36.5% (29.5%, 43.8%), respectively. The incidences of severe adverse events (SAEs, Grade ≥3) for diarrhea, skin rashes, paronychia, and mucositis were 9.7% (6.8%, 13.1%), 5.8% (4.5%, 7.2%), 3.8% (2.0%, 6.2%), and 2.1% (1.0%, 3.6%), respectively. Differences in PFS and OS between the afatinib non-full-dose (<40 mg) and full-dose (>40 mg) groups were not significant ( P > 0.05 ). However, the ORR in the full-dose group was 78.5% (66.7%, 88.4%), which was significantly higher than that in the non-full-dose group (67.8% [56.8%, 77.9%]). Conclusion. The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results. In real-world setting, tolerability-guided dose adjustment might not affect the afatinib efficacy.

Failure of a single day metronidazole desensitization protocol, and success of a modified two-day protocol in an outpatient setting

Background True allergy to metronidazole, a common anti-infective in clinical practice, is rarely reported in the literature. In the case of Trichomonas, there are few alternatives to the nitrimidazole class of drugs, and the alternatives that do exist are associated with worse clinical outcomes. Accordingly, for the rare patients with Type 1 hypersensitivity reactions to metronidazole but compelling need, desensitization protocols have been adapted previously. Reactions during these protocols appear common. Patients in previous regimens have required higher level care for observation, which is costly and resource-intensive. Case presentation We report here on a successful outpatient two-day regimen for metronidazole desensitization. Our patient had compelling indication for metronidazole, but reacted after receiving the very first dose of a previously described desensitization protocol. Accordingly, the protocol was adapted further. Despite this, she went on to develop objective hives prior to reaching the full intended dose. With appropriate symptom management and pre-medication on the second day in clinic, she was successfully desensitized and able to complete a week of full-dose metronidazole. No acute care resources were needed. Conclusion We propose this two-day desensitization regimen for patients who react during the previously described desensitization protocols. This regimen was effective and safe, and did not necessitate the use of acute-care resources. Two-day desensitization protocols while relatively uncommon, can be successful.

Guideline-discordant dosing of direct-acting oral anticoagulants in the veterans health administration

Background Clear guidelines exist to guide the dosing of direct-acting oral anticoagulants (DOACs). It is not known how consistently these guidelines are followed in practice. Methods We studied patients from the Veterans Health Administration (VA) with non-valvular atrial fibrillation who received DOACs (dabigatran, rivaroxaban, apixaban) between 2010 and 2016. We used patient characteristics (age, creatinine, body mass) to identify which patients met guideline recommendations for low-dose therapy and which for full-dose therapy. We examined how often patient dosing was concordant with these recommendations. We examined variation in guideline-concordant dosing by site of care and over time. We examined patient-level predictors of guideline-concordant dosing using multivariable logistic models. Results A total of 73,672 patients who were prescribed DOACS were included. Of 5837 patients who were recommended to receive low-dose therapy, 1331 (23%) received full-dose therapy instead. Of 67,935 patients recommended to receive full-dose therapy, 4079 (6%) received low-dose therapy instead. Sites varied widely on guideline discordant dosing; on inappropriate low-dose therapy, sites varied from 0 to 15%, while on inappropriate high-dose therapy, from 0 to 41%. Guideline discordant therapy decreased by about 20% in a relative sense over time, but its absolute numbers grew as DOAC therapy became more common. The most important patient-level predictors of receiving guideline-discordant therapy were older age and creatinine function being near the cutoff value. Conclusions A substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.

Haemodynamic effects of a prehospital emergency anaesthesia protocol consisting of fentanyl, ketamine and rocuronium in patients with trauma: a retrospective analysis of data from a Helicopter Emergency Medical Service

ObjectivesPrehospital rapid sequence induction (RSI) of anaesthesia is an intervention with significant associated risk. In this study, we aimed to investigate the haemodynamic response over time of a prehospital RSI protocol of fentanyl, ketamine and rocuronium in a heterogeneous population of trauma patients.Design, setting and participantWe performed a retrospective study of all trauma patients who received a prehospital RSI for trauma by a physician staffed Helicopter Emergency Medical Service in the UK between 1 June 2018 and 1 February 2020.Primary outcome measurePrimary outcome was defined as the incidence of clinically relevant hypotensive (systolic blood pressure (SBP) or mean arterial pressure (MAP) >20% below baseline, with an absolute SBP <90 mm Hg or MAP <65 mm Hg) or hypertensive (SBP or MAP >20% above baseline) episodes in the first 10 minutes post-RSI.ResultsIn total, 322 patients were included. 204 patients (63%) received a full-dose induction of 3 μg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium, whereas 128 patients (37%) received a reduced-dose induction. Blood pressures decreased on average 12 mm Hg (95% CI 7 to 16) in the full-dose group and 6 mm Hg (95% CI 1 to 11) in the reduced-dose group, p=0.10). A hypotensive episode (mean SBP drop 53 mm Hg) was noted in 29 patients: 17 (8.3%) receiving a full dose and 12 (10.2%) receiving a reduced-dose induction, p=0.69. The blood pressure nadir was recorded on average 6–8 min after RSI. A hypertensive episode was present in 22 patients (6.8%). The highest blood pressures were recorded in the first 3 min after RSI.ConclusionPrehospital induction of anaesthesia for trauma with fentanyl, ketamine and rocuronium is not related to a significant change in haemodynamics in most patients. However, a (delayed) hypotensive response with a significant drop in SBP should be anticipated in a minority of patients irrespective of the dose regimen chosen.

The Effects of Reduced Mineral Fertilisation Combined with the Foliar Application of Biostimulants and Fertilisers on the Nutrition of Maiden Apple Trees and the Contents of Soil Nutrients

The experiment compared the use of a dose of mineral fertilisation reduced by half in a nursery, which was replaced by foliar treatment with biostimulants and fertilisers. The control combination was a full dose of mineral fertilisation without foliar treatments. The half dose of mineral fertiliser applied into the soil decreased its acidity and salinity. At the same time, it decreased the soil content of macro- and micronutrients, except for calcium and iron. In most cases the simultaneous foliar application of the four biostimulants tested in our experiment reduced the content of macronutrients in the leaves of maiden apple trees, except for calcium. On the other hand, it increased the iron (28.2% average) and manganese (24.8% average) levels in the leaves but reduced the levels of zinc (11.8% average) and copper (25% average). The foliar application of two fertilisers increased the leaf contents of phosphorus (12% average) and calcium (9.3% average). One of the fertilisers also increased the leaf contents of potassium, magnesium, and micronutrients.