On the Hardness of SAT with Community Structure

Recent attempts to explain the effectiveness of Boolean satisfiability (SAT) solvers based on conflict-driven clause learning (CDCL) on large industrial benchmarks have focused on the concept of community structure. Specifically, industrial benchmarks have been empirically found to have good community structure, and experiments seem to show a correlation between such structure and the efficiency of CDCL. However, in this paper we establish hardness results suggesting that community structure is not sufficient to explain the success of CDCL in practice. First, we formally characterize a property shared by a wide class of metrics capturing community structure, including "modularity". Next, we show that the SAT instances with good community structure according to any metric with this property are still NP-hard. Finally, we study a class of random instances generated from the "pseudo-industrial" community attachment model of Gir\'aldez-Cru and Levy. We prove that, with high probability, instances from this model that have relatively few communities but are still highly modular require exponentially long resolution proofs and so are hard for CDCL. We also present experimental evidence that our result continues to hold for instances with many more communities. This indicates that actual industrial instances easily solved by CDCL may have some other relevant structure not captured by the community attachment model.Comment: 23 pages. Full version of a SAT 2016 pape

Применение ингаляционных глюкокортикостероидов (ИГКС) во время пандемии COVID-19

The article analyzes 46 publications on the use of ICS for COVID-19. Both research results and their discussion by specialists are presented. The expediency of continuing basic therapy, including ICS, has been demonstrated in the event of COVID-19 in patients with bronchial asthma and chronic obstructive pulmonary disease. The risk of local immunosuppressive action of ICS has been compared with the ability to suppress inflammation in the initial period of COVID-19. Analysis of the publications suggests that it is safe to prescribe ICS to patients with COVID-19 as well as it is advisable to use them in the initial stages of this disease.Представлен анализ 46 публикаций, посвященных применению ИГКС при COVID-19. Представлены как результаты исследований, так и их обсуждение специалистами. Показана целесообразность продолжения базисной терапии, включающей ИГКС, при возникновении COVID-19 у пациентов с бронхиальной астмой и хронической обструктивной болезнью легких. Сопоставлен риск локального иммуносупрессивного действия ИГКС со способностью подавлять воспалительный процесс в начальном периоде COVID-19. Анализ публикаций свидетельствует о безопасности назначения ИГКС пациентам с COVID-19, а также целесообразности их применения на начальных этапах этого заболевания

Применение ингаляционного стероида Ингакорта в комплексной терапии инфильтративного туберкулеза легких

The problem of inhaled steroids administration in respiratory tuberculosis is being discussed whereas systemic prednisolone is a standard component of pathogenic therapy of active lung tuberculosis. This study shows research results for inhaled steroid Ingakort compared with oral prednisolone in lung tuberculosis patients with airway limitation syndrome. The results permit to approve that Ingakort in daily dose of 1000 meg is safe concerning exacerbation of the specific process for the patients studied. Such treatment is accompanied by improvement of bronchial passability and sensitivity to broncholytic drugs.Вопрос о применении ингаляционных стероидов при туберкулезе органов дыхания дискутируется, тогда как системный прием преднизолона является стандартным компонентом патогенетической терапии активного туберкулеза. В работе представлены результаты изучения ингаляционного стероида Ингакорта в сравнении с приемом внутрь преднизолона у больных туберкулезом легких с бронхообструктивным синдромом. Результаты исследования позволяют утверждать, что применение Ингакорта в суточной дозе 1000 мкг в исследованной группе безопасно в плане обострения специфического процесса, а главное – сопровождается улучшением состояния бронхиальной проходимости и чувствительности к ингаляционным бронхолитическим средствам

Клиническое, инструментальное и фармакологическое сопоставление больных хронической обструктивной болезнью легких и бронхиальной астмой в условиях реальной клинической практики

The objective of this study was to compare demographic, clinical, functional, laboratory data, and therapy in patients with chronic obstructive pulmonary disease (COPD) and asthma who seek for medical aid at medical institutions of Kazan’. Methods. The study involved 153 patients with COPD aged 33 to 89 years and 229 patients with asthma aged 18 to 87 years. Clinical status, rate of exacerbations, spirometric data, treatment and compliance during the previous year were analyzed. Statistical analysis was performed using the SPSS-18 software. Results. COPD patients were older (64.1 ± 0,7 vs 55.4 ± 0,9 years in asthma patients; p < 0,01), more often were males (98.7% vs 1.3%, p < 0.001) and smokers. Coronary heart disease (39.0% vs 25.3%; p < 0.010) and chronic heart failure (35.7% vs 17.5%; p < 0.001) were more common in patients with COPD, while rhinitis (42.4 % vs 3.9%; p < 0.001) and chronic kidney disease (13.1% vs 4.5%; p < 0.001) were more common in asthma patients. Allergic disease was 5-fold more often in asthma patients. Morning symptoms affected daily activity in 77.3% of COPD patients compared to 66.8% of asthma patients (p < 0.05). Generally, daytime activity was impaired in 55.2% of patients with COPD and in 12.7% of patients with asthma (p < 0.05). Excessive use of short-acting bronchodilators was noted at nighttime in 89.6% with COPD and 70.7% with asthma (p < 0.001). Other treatment was in line with guidelines for each the disease. The most convenient inhalational drug delivery device for COPD patients was a metered dosed inhaler, while patients with asthma preferred dry powder inhalers. Compliance of asthma patients was significantly higher than that of COPD patients (57.2% vs 27.8%; p < 0.001). The level of compliance did not change while fixed and free combinations of ICS and LABA or different inhalational devices were used in patients with COPD or asthma. Conclusion. There is a number of clinical signs to distinguish COPD and asthma quite easily in primary care facilities. Excessive use of short-acting bronchodilators and a low compliance of patients are issues requiring to be improved.Целью данного исследования явилась сравнительная оценка демографических, клинических, функциональных и лабораторных данных, характера терапии у больных хронической обструктивной болезнью легких (ХОБЛ) и бронхиальной астмой (БА), обратившихся за медицинской помощью в лечебные учреждения Казани. Материал и методы. Обследованы пациенты (n = 383) с ХОБЛ (n = 153; возраст – 33 года – 89 лет) и БА (n = 229; возраст – 18–87 лет). Предметом оценки явилось состояние больных, частота обострений, данные спирометрии, лечение и комплаентность в течение последнего года. Результаты. Различия пациентов с ХОБЛ и БА заключались в преобладании мужчин (98,7 % vs 1,3 %; p < 0,001), более старшем возрасте (64,1 ± 0,7 года vs 55,4 ± 0,9 года; p < 0,01) и высоком индексе курения соответственно. У больных ХОБЛ чаще встречались ишемическая болезнь сердца (39,0 % vs 25,3 %; p < 0,010) и хроническая сердечная недостаточность (35,7 % vs 17,5 %; p < 0,001); при БА чаще отмечались риниты (42,4 % vs 3,9 %; p < 0,001), хроническая болезнь почек (13,1 % vs 4,5 %; p < 0,001) и в 5 раз чаще – отягощенный аллергологический анамнез. У 77,3 % больных ХОБЛ утренние нарушения состояния здоровья оказывали влияние на дневную активность (при БА – в 66,8 % случаев; p < 0,05). В целом сниженная активность в течение дня наблюдалась у 55,2 % пациентов с ХОБЛ и 12,7 % больных БА (p < 0,05). Избыточное применение короткодействующих бронхолитических препаратов (КДБП) отмечалось ночью: в 89,6 % случаев – при ХОБЛ и в 70,7 % – при БА (p < 0,001), тогда как по остальным признакам лечение соответствовало клиническим рекомендациям по каждой из нозологий. Установлено, что наиболее удобным устройством доставки препаратов для больных ХОБЛ являлись дозированные аэрозольные, при БА – дозированные порошковые ингаляторы. Комплаентность при БА была достоверно выше, чем при ХОБЛ (57,2 % vs 27,8 % соответственно; p < 0,001). При применении фиксированных комбинаций и монотерапии ингаляционными глюкокортикостероидами / длительно действующими β2-адреномиметиками либо различных средств доставки у больных ХОБЛ и БА уровень комплаентности не различался. Заключение. По результатам исследования показано, что при ХОБЛ и БА наблюдается достаточно признаков, позволяющих различать их на уровне врача первичного звена здравоохранения. Среди выявленных проблем, требующих коррекции, установлены избыточное потребление КДБП и низкая комплаентность пациентов.

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

The position of the fixed combination of indacaterol, glycopyrronium, and mometasone furoate in the management of bronchial asthma. The Report of Expert Panel of Russian Respiratory Society

Achieving the control of bronchial asthma (BA) in real clinical practice remains an unresolved problem, despite the expansion of therapeutic options in this area. Guidelines about when and for whom should a particular treatment be used continue to develop. Increasing of inhaled corticosteroid dose (ICS) in combination with a long-acting β2-agonist (LABA) does not always lead to the desired result, although a combined LABA-ICS inhaler could improve the course of asthma and increase adherence. The addition of tiotropium bromide to LABA-ICS requires the use of two inhalers. The targeted biological therapy is associated with the complexity of phenotyping and is possible only in specialized medical centers. Mometasone furoate, indacaterol acetate, and glycopyrronium bromide in fixed doses were combined in Breezhaler® inhaler for asthma maintenance therapy once per day. This way of treatment helps to realize full potential of maintenance inhalation therapy of bronchial asthma and to simplify the achievement of control over the disease in routine clinical practice.Достижение контроля над бронхиальной астмой (БА) в реальной клинической практике остается нерешенной проблемой, несмотря на существенное расширение терапевтических возможностей в этом направлении. Рекомендации о том, когда и для кого должны использоваться те или иные методы лечения, продолжают расширяться. При увеличении дозы ингаляционного глюкокортикостероида (иГКС) в комбинации с длительно действующим β2-агонистом (ДДБА) далеко не всегда достигается желаемый результат, хотя при использовании единого ингалятора иГКС / ДДБА может улучшиться течение БА и повыситься приверженность терапии. При добавлении тиотропия бромида к иГКС / ДДБА требуется использование 2 ингаляторов, а назначение таргетной биологической терапии связано со сложностью фенотипирования и возможно только в специализированных медицинских центрах. Мометазона фуроат, индакатерола ацетат и гликопиррония бромид объединены в фиксированную комбинацию, доставляемую с помощью ингалятора Бризхалер® 1 раз в день для поддерживающей терапии БА. Этот способ лечения помогает реализовать потенциал базисной ингаляционной терапии БА и упростить достижение контроля над заболеванием в повседневной клинической практик

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362