PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.
Adrenal Cortex Hormones* ; Anti-Asthmatic Agents ; Asthma ; Cohort Studies ; Comparative Effectiveness Research ; Diethylpropion ; Disease Progression ; Gastroesophageal Reflux ; Hospitalization ; Humans ; Odds Ratio ; Prevalence ; Rhinitis

Scrapie is diagnosed antemortem in sheep by detecting misfolded isoforms of prion protein (PrP(Sc)) in lymphoid follicles of the rectal mucosa and nictitating membranes. Assay sensitivity is limited if (a) the biopsy is collected early during disease development, (b) an insufficient number of follicles is collected, or (c) peripheral accumulation of PrP(Sc) is reduced or delayed. A blood test would be convenient for mass live animal scrapie testing. Currently approved techniques, however, have their own detection limits. Novel detection methods may soon offer a non-animal-based, rapid platform with detection sensitivities that rival the prion bioassay. In anticipation, we sought to determine if diseased animals could be routinely identified with a bioassay using B lymphocytes isolated from blood sample volumes commonly collected for diagnostic purposes in small ruminants. Scrapie transmission was detected in five of six recipient lambs intravenously transfused with B lymphocytes isolated from 5~10 mL of blood from a naturally scrapie-infected sheep. Additionally, scrapie transmission was observed in 18 ovinized transgenic Tg338 mice intracerebrally inoculated with B lymphocytes isolated from 5~10 mL of blood from two naturally scrapie-infected sheep. Based on our findings, we anticipate that these blood sample volumes should be of diagnostic value.
Animals ; B-Lymphocytes/*pathology ; Biological Assay/*veterinary ; Mice ; Mice, Transgenic ; Prions/*blood ; Scrapie/blood/*diagnosis/transmission ; Sheep

Methods: Patients undergoing primary, elective 1–3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. Results: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, p =0.022). Conclusions Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.

<b>OBJECTIVEb>A randomized trial of breast self-examination (BSE) program was carried out to evaluate whether the intensive BSE can reduce the death number of women from breast cancer.

<b>METHODSb>A total of 266,064 women (age of 30 to 64 years) associated with 519 textile factories in Shanghai had been randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women) since 1989. Initial instruction in BSE group included demonstration of proper palpation techniques. It was followed by 2 reinforcement sessions during the subsequent 4 years including video shows, BSE instruction sessions and BSE practice under medical supervision. These activities were continued for 5 years. Attendance at all events was recorded. The cohort was followed through July 2000 for development of breast diseases, and the breast cancer cases were followed up through 2001 for vital status. The data analysis methods used included Kaplan-Meier plots, Log-rank test and Cox modeling.

<b>RESULTSb>Among women under instruction, 864 breast cancers were detected and 133 breast cancer deaths occurred, and 896 breast cancers were detected and 130 deaths recorded in the control group. The tumor size (P = 0.07), TNM stage (P = 0.39) and cumulative breast cancer mortality rate (P = 0.72) were not significantly different between the 2 groups. However, more and smaller fibroadenomas were detected in the instruction group than in the control group (P < 0.01).

<b>CONCLUSIONb>Intensive instruction in BSE can not reduce mortality rate of breast cancer, but more and smaller benign breast lumps can be detected.

Adult ; Breast Neoplasms ; diagnosis ; epidemiology ; prevention & control ; Breast Self-Examination ; China ; epidemiology ; Female ; Humans ; Incidence ; Mass Screening ; Middle Aged

Background: and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. Methods: We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). Conclusions Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Background: and Purpose Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse. Methods: INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months. Results: Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9). Conclusions Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.

Background: and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Background: and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Background: and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Background: and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.