Square-Gaussian random processes and estimators of covariance functions

In this paper inequalities for distributions of quadratic forms from square-Gaussian random variables and distributions of suprema of quadratic forms from square-Gaussian random processes are proved. These inequalities enable us to investigate the jointly distributions of estimators of covariance functions of Gaussian processes

Bladder Cancer: Features of Epidemiology and Indicators of Specialized Care Delivery

The work is based on the materials of official statistical reporting, the analysis of which was carried out for 10 years, divided into two five-year periods (2009-2013 and 2014-2018). Absolute and intensive rates of morbidity and distribution of bladder cancer of the adult population of Ukraine in the regional aspect, taking into account sex were studied, the basic indicators of the prevalence of pathology were analyzed as well. The revealed unfavorable situation is characterized by a steady increase in morbidity and prevalence at a slower pace during 2014-2018. It is noteworthy the high level of morbidity in men, which is growing against the background of its stabilization among women. At the same time, there was noted the tendency in the reduced number of newly diagnosed patients during professional examinations (in 2018-16.9% against 18.0% in 2014) with diagnosis at stages I-II (72.2% vs. 74.79%), wherein every fifth has stage III-IV. With a tendency to increase in the number of registered patients ≥ 5 years (59.1% vs. 56.5%), the death rate did not change significantly within a year from the time of diagnosis (14.7% vs. 15.6%, respectively). In the structure of specialized care, (65% are patients with the first diagnosis), surgical method accounted for 37-40% by years, the combined was second (up to 20% by years), then radiation and chemotherapy, which together did not exceed 5.0%. Areas with high or low relative rates in relation to the average Ukrainian indicators for all parameters studied were identified. In the presence of regional differences, there is a need for in-depth studies of the state of the issue, including the quality and organization of care

Effect of meropenem-vaborbactam vs piperacillin-Tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection the TANGO I randomized clinical trial

IMPORTANCE Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. OBJECTIVE To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. DESIGN, SETTING, AND PARTICIPANTS Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (18 years) with complicated UTI, stratified by infection type and geographic region. INTERVENTIONS Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-Tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. MAIN OUTCOMES AND MEASURES Primary end point for FDA criteriawas overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-To-Treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was 15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95%CIs were calculated. RESULTS Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%]women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-Tazobactam (difference, 4.5%[95%CI, 0.7%to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenemvaborbactam vs 105 of 182 (57.7%) with piperacillin-Tazobactam (difference, 9.0%[95%CI, 0.9%to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9%[95%CI, 4.2%to 16.0%]; P < .001 for noninferiority). Adverse eventswere reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-Tazobactam. CONCLUSIONSANDRELEVANCE Amongpatient swith complicatedUTI,includingacutepyelonephritis andgrowthof a baseline pathogen,meropenem-vaborbactamvs piperacillin-Tazobactamresulted in a compositeoutcomeofcomplete resolution orimprovementof symptomsalongwith microbial eradication thatmet the noninferiority criterion. Further research is needed to understand the spectrum of patients inwhommeropenem-vaborbactam offers a clinical advantage. © 2018 American Medical Association. All rights reserved

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

BACKGROUND The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear. METHODS In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis. RESULTS After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab–axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001). Median progression-free survival was 15.1 months in the pembrolizumab–axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001). The objective response rate was 59.3% (95% CI, 54.5 to 63.9) in the pembrolizumab–axitinib group and 35.7% (95% CI, 31.1 to 40.4) in the sunitinib group (P<0.001). The benefit of pembrolizumab plus axitinib was observed across the International Metastatic Renal Cell Carcinoma Database Consortium risk groups (i.e., favorable, intermediate, and poor risk) and regardless of programmed death ligand 1 expression. Grade 3 or higher adverse events of any cause occurred in 75.8% of patients in the pembrolizumab–axitinib group and in 70.6% in the sunitinib group. CONCLUSIONS Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.

The Seventh International Comparison of Absolute Gravimeters ICAG-2005 at the BIPM. Organization and preliminary results

ICAG-2005, an international comparison of absolute gravimeters, was held in September 2005 at the Bureau International des Poids et Mesures (BIPM), Sèvres, France. Nineteen absolute gravimeters performed measurements of free-fall acceleration g at eleven sites of the BIPM gravity network. Fifteen relative gravimeters were used to measure the vertical gravity gradients and to provide gravity ties between the sites. The maximum g-difference was about 9 mGal. The status of a pilot study was agreed for this comparison by the Consultative Committee for Mass and Related Quantities. For the first time in the ICAG series, a technical protocol specifying the organization, measurement strategy, data processing, calculation of the uncertainties and presentation of the results, was developed for the ICAG 2005. The unweighted mean value of the results of absolute measurements referred to the site A is presented and compared with the similar values obtained in ICAG-1997 and ICAG-2001

Українська версія опитувальника оцінки сімптомів гострого циститу (Acute cystitis symptom score – ACSS) для діагностики та результатів гострого неускладненого циститу, про які повідомляють пацієнтки. Ч. I. Лінгвістична валідація та когнітивна оцінка

The Acute Cystitis Symptom Score (ACSS) was originally developed in Uzbek and Russian language as a self-reporting questionnaire for the clinical diagnosis and follow-up of an acute episode of uncomplicated cystitis (AC) in women based on complains and their effect on the quality of life. After professional forward and backward translations the cognitive assessment of the Ukrainian version of the ACSS was performed in female subjects with different ages and educational levels and in medical professionals treating such patients. After considering all comments of the female subjects and the professionals the final version of the Ukrainian ACSS could be obtained to be further used in clinical studies.Опитувальник оцінки симптомів гострого циститу (ACSS) – це анкета для самозвіту для клінічної діагностики гострого циститу (ГЦ) на основі скарг. Він поєднує поетапну оцінку тяжкості симптомів та їх впливу на якість життя. ACSS складається з двох частин: діагностичної (частина А) та контрольної (частина Б) форм. Обидві частини включають чотири ідентичні домени, що містять: а) шість пунктів для "типових" симптомів ГЦ; б) чотири пункти для диференціальної діагностики; в) три пункти для якості життя та г) п'ять пунктів для додаткових станів. Частина В містить додатково ще один домен, який називається "Динаміка", спрямований на моніторинг змін стану пацієнта під час спостереження