Оценка клинико-экономической целесообразности применения лекарственных препаратов эзетимиб, алирокумаб, эволокумаб и инклисиран в рамках программы льготного лекарственного обеспечения пациентов очень высокого сердечно-сосудистого риска

Objective: to evaluate the clinical and economic feasibility of expanding the preferential drug provision (PDP) program for adult patients at very high cardiovascular (CV) risk, including those who have not reached lipid targets on statin therapy, by increasing the frequency of use of ezetimibe, alirocumab, evolocumab and inclisiran used in combination with statins, compared with current PDP practice (use of atorvastatin, simvastatin and minimal use of other drugs).Material and methods. A Markov model was constructed to characterize the development of atherosclerotic heart disease in patients with very high CV risk and to suggest a consistent change in hypolipidemic therapy if it is ineffective. The model considered patients' compliance to drug therapy over time and the factor of non-prescription of any treatment. The modeling horizon was 30 years, and the model cycle was 1 year. The outcomes used were quality-adjusted life years (QALY), life years gained (LYG), and probabilities of various individual and combined CV events. The baseline modeling scenario was to increase the frequency of рroprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors’ prescriptions. In addition, alternative scenarios were modeled that included prescription of highly effective lipid-lowering therapy for all patients who had not reached target low-density lipoprotein cholesterol (LDL-C) on statin therapy, and the scenario with 100% compliance to statin therapy.Results. In comparison with current practice of treatment of patients with very high CV risk, clinical and economic modeling showed a decrease in the incidence of combined outcomes (combined CV events – by 8%, extended combined CV events – by 9%) and individual CV events (heart attack – by 4%, stroke – by 3%, unstable angina – by 2%, revascularization – by 3%) in the baseline scenario. In scenarios of prescribing PCSK9 inhibitors and inclisiran to all patients who have not reached target values of LDL-C on statin therapy, the frequency of individual events ranged from 4% to 8%. In the scenario, which also implies 100% drug compliance, the reduction was from 8% to 17% compared with current patient management practices, characterized by lower frequency of hypolipidemic drugs, including PCSK9 inhibitors and inclisiran. The incremental cost-effectiveness ratio (ICER) for QALY in the baseline scenario was 3,598,156 rubles, the ICER for LYG was 1,949,393 rubles. When comparing the ICER with willingness-to-pay (WTP) threshold in the Russian Federation (calculated as three times the gross domestic product per capita and in 2022 amounting to 2.8 million rubles per effect unit) the ICER for LYG did not exceed the WTP in all scenarios, while the ICER for QALY exceeded the WTP by 29–44%, depending on the realized scenario.Conclusion. Expanding the PDP program for high CV risk patients will have a positive impact on their quality of life and life expectancy, as well as significantly reduce the likelihood of acute CV events. Comparison of ICER with estimated WTP suggests that expansion of the PBP program is a cost-effective organizational technology according to LYG criterion, but not according to the QALY criterion.Цель: оценить клинико-экономическую целесообразность расширения программы льготного лекарственного обеспечения (ЛЛО) взрослых пациентов очень высокого сердечно-сосудистого (СС) риска, включая не достигших липидных целей на терапии статинами, за счет увеличения частоты использования лекарственных препаратов (ЛП) эзетимиб, алирокумаб, эволокумаб и инклисиран, применяемых в комбинации со статинами, по сравнению с текущей практикой ЛЛО (использование аторвастатина, симвастатина и минимальное применение других препаратов).Материал и методы. Построена модель Маркова, характеризующая развитие атеросклеротической болезни сердца у пациентов очень высокого СС-риска и предполагающая последовательную смену гиполипидемической терапии при ее неэффективности. Модель учитывала приверженность пациентов лекарственной терапии во времени и фактор неназначения какого-либо лечения. Горизонт моделирования составил 30 лет, цикл модели – 1 год. В качестве исходов были использованы годы жизни с поправкой на качество (англ. quality-adjusted life year, QALY), добавленные годы жизни (англ. life years gained, LYG) без учета ее качества, а также вероятности наступления различных отдельных и комбинированных СС-событий. Базовый сценарий моделирования предполагал увеличение частоты назначения ингибиторов пропротеиновой конвертазы субтилизин-кексинового типа 9 (англ. рroprotein convertase subtilisin/kexin type 9, PCSK9), инклисирана и эзетимиба; дополнительно моделировались альтернативные сценарии расширения ЛЛО, включающие назначение высокоэффективной липидснижающей терапии всем пациентам, не достигшим целевых значений по холестерину липопротеинов низкой плотности (ХС-ЛПНП) на фоне приема статинов, и сценарий, подразумевающий 100% приверженность пациентов приему ЛПРезультаты. По сравнению с текущей практикой лечения пациентов очень высокого СС-риска клинико-экономическое моделирование продемонстрировало снижение частоты комбинированных исходов (комбинированное СС-событие – на 8%, расширенное комбинированное СС-событие – на 9%) и отдельных СС-событий (инфаркт – на 4%, инсульт – на 3%, нестабильная стенокардия – на 2%, реваскуляризация – на 3%) в базовом сценарии. При реализации сценариев назначения ингибиторов PCSK9 и инклисирана всем пациентам, не достигшим целевых значений ХС-ЛПНП на фоне приема статинов, снижение частоты отдельных СС-событий варьировало от 4% до 8%, а в сценарии, подразумевающем также 100% приверженность пациентов приему ЛП, снижение составило от 8% до 17% по сравнению с текущей практикой ведения пациентов, характеризующейся меньшей частотой назначения гиполипидемических ЛП, в т.ч. ЛП группы ингибиторов PCSK9 и инклисирана. Инкрементальный показатель «затраты–эффективность» (англ. incremental cost-effectiveness ratio, ICER) за QALY в базовом сценарии составил 3 598 156 руб., ICER за LYG – 1 949 393 руб. При сопоставлении ICER c расчетным порогом готовности платить (ПГП) в Российской Федерации (рассчитанным как трехкратный размер валового внутреннего продукта на душу населения и в 2022 г. составившим 2,8 млн руб. за единицу эффекта) ICER за LYG не превышал ПГП во всех сценариях, в то время как ICER за QALY превышал ПГП на 29–44% в зависимости от реализуемого сценария.Заключение. Расширение программы ЛЛО пациентов высокого СС-риска окажет позитивное влияние на качество и продолжительность их жизни, а также значительно снизит вероятность острых СС-событий. Сопоставление показателей ICER c расчетным ПГП позволяет заключить, что расширение программы ЛЛО является экономически эффективной организационной технологией по критерию LYG, но не является таковой по критерию QALY

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider

We have searched in $p \bar{p}$ collisions at $\sqrt{s}$ = 1.8 TeV for events with three charged leptons and missing transverse energy. In the Minimal Supersymmetric Standard Model, we expect trilepton events from chargino-neutralino (\chione \chitwo) pair production, with subsequent decay into leptons. We observe no candidate $e^+e^-e^\pm$, $e^+e^-\mu^\pm$, $e^\pm\mu^+\mu^-$ or $\mu^+\mu^-\mu^\pm$ events in 106 pb$^{-1}$ integrated luminosity. We present limits on the sum of the branching ratios times cross section for the four channels: \sigma_{\chione\chitwo}\cdot BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and M_\chitwo > 82.2 \mgev\sp for $\tan\beta=2$, $\mu =-600$~\mgev\sp and M_\squark= M_\gluino.Comment: 9 pages and 3 figure

Measurement of the Associated γ+μ±\gamma + \mu^\pm Production Cross Section in ppˉp \bar p Collisions at s=1.8\sqrt{s} = 1.8 TeV

We present the first measurement of associated direct photon + muon production in hadronic collisions, from a sample of 1.8 TeV $p \bar p$ collisions recorded with the Collider Detector at Fermilab. Quantum chromodynamics (QCD) predicts that these events are primarily from the Compton scattering process $cg \to c\gamma$, with the final state charm quark producing a muon. Hence this measurement is sensitive to the charm quark content of the proton. The measured cross section of $29\pm 9 pb^{-1}$ is compared to a leading-order QCD parton shower model as well as a next-to-leading-order QCD calculation.Comment: 12 pages, 4 figures Added more detailed description of muon background estimat

Measurement of the top quark mass and top-antitop production cross section from dilepton events at the Collider Detector at Fermilab

We present an analysis of dilepton events originating from top-antitop production in proton-antiproton collisions at sqrt{s}=1.8 TeV at the Fermilab Tevatron Collider. The sample corresponds to an integrated luminosity of 109+-7 pb^{-1}. We observe 9 candidate events, with an estimated background of 2.4+-0.5 events. We determine the mass of the top quark to be M_top = 161+-17(stat.)+-10(syst.) GeV/c^2. In addition we measure a top-antitop production cross section of 8.2+4.4-3.4 pb (where M_top = 175 GeV/c^2 has been assumed for the acceptance estimate).Comment: 6 pages of text, 3 figure

Lifetime history of indoor tanning in young people: a retrospective assessment of initiation, persistence, and correlates

<p>Abstract</p> <p>Background</p> <p>Despite educational and public health campaigns to convey the risks of indoor tanning, many individuals around the world continue to engage in this behavior. Few descriptive studies of indoor tanning have collected information pertaining to the lifetime history of indoor tanning, thereby limiting our ability to understand indoor tanning patterns and potentially target interventions for individuals who not only initiate, but continue to persistently engage in indoor tanning.</p> <p>Methods</p> <p>In-person interviews elicited detailed retrospective information on lifetime history of indoor tanning among white individuals (n = 401) under age 40 seen by a dermatologist for a minor benign skin condition. These individuals were controls in a case-control study of early-onset basal cell carcinoma. Outcomes of interest included ever indoor tanning in both males and females, as well as persistent indoor tanning in females - defined as females over age 31 who tanned indoors at least once in the last three or all four of four specified age periods (ages 11-15, 16-20, 21-30 and 31 or older). Multivariate logistic regression was used to identify sociodemographic and lifestyle correlates of ever and persistent indoor tanning in females.</p> <p>Results</p> <p>Approximately three-quarters (73.3%) of females and 38.3% of males ever tanned indoors, with a median age of initiation of 17.0 and 21.5, respectively. Among indoor tanners, 39.3% of females and 21.7% of males reported being burned while indoor tanning. Female ever indoor tanners were younger, had darker color eyes, and sunbathed more frequently than females who never tanned indoors. Using unique lifetime exposure data, 24.7% of female indoor tanners 31 and older persistently tanned indoors starting as teenagers. Female persistent indoor tanners drank significantly more alcohol, were less educated, had skin that tanned with prolonged sun exposure, and sunbathed outdoors more frequently than non-persistent tanners.</p> <p>Conclusions</p> <p>Indoor tanning was strikingly common in this population, especially among females. Persistent indoor tanners had other high-risk behaviors (alcohol, sunbathing), suggesting that multi-faceted behavioral interventions aimed at health promotion/disease prevention may be needed in this population.</p

Search for Higgs Bosons Produced in Association with a Vector Boson in pp̅ Collisions at √s = 1.8 TeV

We search for Higgs bosons produced in association with a massive vector boson in 91{plus_minus}7 pb{sup {minus}1} of p{ovr p} collisions at {radical} (s) =1.8 TeV recorded by the Collider Detector at Fermilab. We assume the Higgs scalar H{sup 0} decays to a b{ovr b} pair with branching ratio {beta} , and we consider the hadronic decays of the vector boson V (W or Z ). Observations are consistent with background expectations. We place 95{percent} confidence level upper limits on {sigma}(p{ovr p}{r_arrow} H{sup 0}V){beta} as a function of the scalar mass (M{sub H{sup 0}}) over the range 70{lt}M{sub H{sup 0}}{lt}140 GeV /c{sup 2} . When combined with an analysis of the case where V is a leptonically decaying W , these limits vary from 23thinspthinsppb at M{sub H{sup 0}}=70 GeV/c{sup 2} to 17thinspthinsppb at M{sub H{sup 0}}=140 GeV/c{sup 2} . {copyright} {ital 1998} {ital The American Physical Society

Search for a W' Boson via the Decay Mode W' -> mu nu in 1.8 TeV p-pbar Collisions

We report the results of a search for a W' boson produced in p-pbar collisions at a center-of-mass energy of 1.8 TeV using a 107 pb-1 data sample recorded by the Collider Detector at Fermilab. We consider the decay channel W' -> mu nu and search for anomalous production of high transverse mass mu-nu lepton pairs. We observe no excess of events above background and set limits on the rate of W' boson production and decay relative to Standard Model W boson production and decay using a fit of the transverse mass distribution observed. If we assume Standard Model strength couplings of the W' boson to quark and lepton pairs, we exclude a W' boson with invariant mass less than 660 GeV/c**2 at 95% confidence level.Comment: 19 pages, 2 figure