Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

BACKGROUND An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20‐expressing B cells, in the primary progressive form of the disease. METHODS In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time‐to‐event analysis. RESULTS The percentage of patients with 12‐week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24‐week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25‐foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2‐weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain‐volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36‐Item Short‐Form Health Survey. Infusion‐related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections. CONCLUSIONS Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long‐term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann–La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570.)
Incidencia de adenocarcinoma en esófago de Barrett, Fundación Santa Fe de Bogotá, 11 años de seguimiento

It has been interesting the understanding of the Barretts Esophagus physiopathology in last 50 years and their association like the more grateful risk factor for Esophagus Adenocarcinoma, whose incidence is increased in a bigger rate that any other cancer type, among 4-10% annually. This retrospective cohort study, seeks to determine Esophagus Adenocarcinoma incidence in Barretts Esophagus and Esophagitis patient in eleven years of pursuit, at La Fundacion Santa Fe de Bogota. There were 49 patients for exposed cohort (Barrett Esophagus) as of not exposed (Esophagitis). The exposed cohort incidence was 4% (2 cases). The confidence intervals (CI) of 95% for a 4% risk in the exposed cohort, included 0, therefore; there was not difference with non exposed cohort, where there were not cases. Both events were detected in routinely endoscopic assay, with average interval between Barrett esophagus diagnosis and adenocarcinoma development 7, 5 year-old. There was not mortality in both cases. This could be the first and only retrospective cohort study that evaluates Barrett Esophagus and Esophagus Adenocarcinoma association that has been carried out in the country, with 11 years to pursuit. The discoveries in general coincide with that referred in the scientific available literature. The pursuit of the patients continues and these results should be considered as an advance report.
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

BACKGROUND Tofacitinib, an oral, small‐molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. METHODS We conducted three phase 3, randomized, double‐blind, placebo‐controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. RESULTS In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5‐mg tofacitinib group and 40.6% in the 10‐mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. CONCLUSIONS In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763, NCT01458951, and NCT01458574, respectively.)
모유수유 지식과 태도 및 태도요인 측정도구의 신뢰도 검증

Diplomová práce se zabývá plánováním inspekčních cest pro car-like robota. Jako model senzoru pro pozorování objektů zájmu byl zvolen model kamery s omezeným úhlem záběru. Pro řešení tohoto problému jsme použili algoritmy Rapidly-exploring Random Trees Star (RRT*) a Random Inspection Tree Algorithm (RITA). Velmi důležitou vlastností obou algoritmů je to, že s narůstajícím výpočetním časem se zlepšuje řešení inspekční cesty (pokud taková cesta existuje) a je dokázáno, že optimální cesta bude nalezena s pravděpodobností jedna v nekonečné iteraci. Další předností algoritmu RITA je to, že nedekomponuje problém inspekčních cest do dvou podproblémů (problém obchodního cestujícího a art gallery problém). Naopak algoritmus RITA řeší problém plánování inspekčních cest jako celek, což znamená, že při hledání inspekčních cest jsou brány v ohled omezující podmínky kinematiky robota. Proto je algoritmus RITA schopen nalézt nejoptimálnější inspekční cestu s ohledem na daného robota. Ačkoliv algoritmus RITA má tyto dvě nezpochybnitelně vynikající vlastnosti, hledání optimální inspekční cesty může být časově náročné. Z tohoto důvodu jsme navrhli dvě vylepšení algoritmu RITA, tak aby jeho původní vlastnosti byly zachovány a přitom se hledání inspekční cesty zrychlilo. Všechny studované a navrhované algoritmy jsme ověřili implementací a na závěr této práce jsme ozkoušeli hledání inspekčních cest algoritmem RITA pro reálného robota.
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia

Background Blinatumomab, a bispecific monoclonal antibody construct that enables CD3‐positive T cells to recognize and eliminate CD19‐positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B‐cell precursor ALL on the basis of single‐group trials that showed efficacy and manageable toxic effects. Methods In this multi‐institutional phase 3 trial, we randomly assigned adults with heavily pretreated B‐cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard‐of‐care chemotherapy. The primary end point was overall survival. Results Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P=0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event‐free survival than that with chemotherapy (6‐month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem‐cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. Conclusions Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B‐cell precursor ALL. (Funded by Amgen; TOWER ClinicalTrials.gov number, NCT02013167.)
The genome gets personal--almost.

T’STHE“YEAROFPERFECTVISION,”2020.AMY,AGE21YEARS, visits with her physician and elects to have complete genomesequencing.Atafollow-upvisit,Amychoosesto learnofhergeneticriskfactorsforheartdisease,diabetes, breastcancer,andcoloncancer.Amy’sphysicianprovidesher with risk scores for those disorders, and with suggestions for lifestylemodifications.Specifically,Amyisalertedtoherparticularlyhighriskofdevelopingtype2diabetes,andherphy
Avaliação das tensões liberadas por elásticos ortodônticos em cadeia: estudo in vitro

INTRODUCTION: Elastomeric materials are considered important sources of orthodontic forces. OBJECTIVE: To assess force degradation over time of four commercially available orthodontic elastomeric chains (Morelli, Ormco, TP and Unitek). METHODS: The synthetic elastics were submerged in 37 oC synthetic saliva and stretched by a force of 150 g (15 mm - Morelli and TP; 16mm - Unitek and Ormco). With a dynamometer, the delivered force was evaluated at different intervals: 30 minutes, 7 days, 14 days and 21 days. The results were subjected to ANOVA and Tukey's test. RESULTS: There was a force decay between 19% to 26.67% after 30 minutes, and 36.67% to 57% after 21 days of activation. CONCLUSIONS: TP elastomeric chains exhibited the smallest percentage of force decay, with greater stability at all time intervals tested. Meanwhile, the Unitek chains displayed the highest percentage of force degradation, and no statically significant difference was found in force decay between Ormco and Morelli elastomeric chains during the study period.
Direct‐acting oral anticoagulants: pharmacology, indications, management, and future perspectives

In recent years, several direct‐acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa®, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto®, Bayer HealthCare), apixaban (Eliquis®, Bristol‐Myers Squibb), and edoxaban (Lixiana®/Savaysa®, Daiichi‐Sankyo). The new compounds have a predictable dose response and few drug–drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

Background Canagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient‐years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal‐replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient‐years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS‐R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754, respectively.)
Obinutuzumab for the First‐Line Treatment of Follicular Lymphoma

BACKGROUND Rituximab‐based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti‐CD20 monoclonal antibody. We compared rituximab‐based chemotherapy with obinutuzumab‐based chemotherapy in patients with previously untreated advanced‐stage follicular lymphoma. METHODS We randomly assigned patients to undergo induction treatment with obinutuzumab‐based chemotherapy or rituximab‐based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator‐assessed progression‐free survival. RESULTS A total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow‐up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab‐based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab‐based chemotherapy (estimated 3‐year rate of progression‐free survival, 80.0% vs. 73.3%; hazard ratio for progression, relapse, or death, 0.66; 95% confidence interval [CI], 0.51 to 0.85; P=0.001). Similar results were seen with regard to independently reviewed progression‐free survival and other time‐to‐event end points. Response rates were similar in the two groups (88.5% in the obinutuzumab group and 86.9% in the rituximab group). Adverse events of grade 3 to 5 were more frequent in the obinutuzumab group than in the rituximab group (74.6% vs. 67.8%), as were serious adverse events (46.1% vs. 39.9%). The rates of adverse events resulting in death were similar in the two groups (4.0% in the obinutuzumab group and 3.4% in the rituximab group). The most common adverse events were infusion‐related events that were considered by the investigators to be largely due to obinutuzumab in 353 of 595 patients (59.3%; 95% CI, 55.3 to 63.2) and to rituximab in 292 of 597 patients (48.9%; 95% CI, 44.9 to 52.9; P<0.001). Nausea and neutropenia were common. A total of 35 patients (5.8%) in the obinutuzumab group and 46 (7.7%) in the rituximab group died. CONCLUSIONS Obinutuzumab‐based immunochemotherapy and maintenance therapy resulted in longer progression‐free survival than rituximab‐based therapy. High‐grade adverse events were more common with obinutuzumab‐based chemotherapy. (Funded by F. Hoffmann–La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968.)
Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005.

CONTEXT Group B streptococcus is a leading infectious cause of morbidity in newborns and causes substantial disease in elderly individuals. Guidelines for prevention of perinatal disease through intrapartum chemoprophylaxis were revised in 2002. Candidate vaccines are under development. OBJECTIVE To describe disease trends among populations that might benefit from vaccination and among newborns during a period of evolving prevention strategies. DESIGN AND SETTING Analysis of active, population-based surveillance in 10 states participating in the Active Bacterial Core surveillance/Emerging Infections Program Network. MAIN OUTCOME MEASURES Age- and race-specific incidence of invasive group B streptococcal disease. RESULTS There were 14,573 cases of invasive group B streptococcal disease during 1999-2005, including 1348 deaths. The incidence of invasive group B streptococcal disease among infants from birth through 6 days decreased from 0.47 per 1000 live births in 1999-2001 to 0.34 per 1000 live births in 2003-2005 (P < .001), a relative reduction of 27% (95% confidence interval [CI], 16%-37%). Incidence remained stable among infants aged 7 through 89 days (mean, 0.34 per 1000 live births) and pregnant women (mean, 0.12 per 1000 live births). Among persons aged 15 through 64 years, disease incidence increased from 3.4 per 100,000 population in 1999 to 5.0 per 100,000 in 2005 (chi2(1) for trend, 57; P < . 001), a relative increase of 48% (95% CI, 32%-65%). Among adults 65 years or older, incidence increased from 21.5 per 100,000 to 26.0 per 100,000 (chi2(1) for trend, 15; P < . 001), a relative increase of 20% (95% CI, 8%-35%). All 4882 isolates tested were susceptible to penicillin, ampicillin, and vancomycin, but 32% and 15% were resistant to erythromycin and clindamycin, respectively. Serotypes Ia, Ib, II, III, and V accounted for 96% of neonatal cases and 88% of adult cases. CONCLUSIONS Among infants from birth through 6 days, the incidence of group B streptococcal disease was lower in 2003-2005 relative to 1999-2001. This reduction coincided with the release of revised disease prevention guidelines in 2002. However, the disease burden in adults is substantial and increased significantly during the study period.
Revisiting the Cataract Surgery Curriculum for Ophthalmology Residents: A Narrative Review

Purpose: To compare the educational model and complication rates of cataract surgery performed by ophthalmology residents in Iran with other countries and present suggestions for improvement Methods: We reviewed a number of studies that investigated the complications of cataract surgery in relation to curriculum modifications from 2009 to 2011. Review: Complication rates are higher in our country compared to others. In Iran, two studies in 2009 and 2011 reported high complication rates among residents. In the USA, the rate of Posterior capsular rupture (PCR) in resident-performed surgeries had a decreasing trend from 2001 to 2011, and the rate of Vitreous loss (VL) reached zero in 2011 after a substantial decrease in 2002 and small variations thereafter. The two Asian and European studies in 2006 and 2009 also reported lower complication rates than Iranian studies. Suggestion: Simulation and wet lab training, exposure to the operating room, providing a portfolio, research shifts, evidence-based discussions with experienced surgeons could improve knowledge and experience of Iranian residents.