The Two-Sided Residue Interpolation Problem in the Stieltjes Class

The general two-sided directional interpolation problem in the Stieltjes class for matrix functions is solved. An explicit description of all solutions is presented in terms of the original data. The method is based on the reduction of this problem to the solution of homogeneous interpolation problems with symmetries for rationalmatrix functions

The Two-Sided Residue Interpolation Problem in the Stieltjes Class

The general two-sided directional interpolation problem in the Stieltjes class for matrix functions is solved. An explicit description of all solutions is presented in terms of the original data. The method is based on the reduction of this problem to the solution of homogeneous interpolation problems with symmetries for rationalmatrix functions

Treatment Options in Cushing’s Disease

Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease

State-private partnership in the field of medical services: principles, forms and signs

The article explores the features of legal regulation of public-private partnerships in medical services provision. The regulatory legal acts on public-private partnership in provision of medical services should be divided into groups: general and special. The concept of "public-private partnership in the provision of medical services" is proposed, its principles, classification, forms, signs and advantages of their implementation are clarified. The methodology of this study is based on the use of general scientific and special methods of cognition. Comparative legal and comparative methods were used in the study of legislation governing the development of legal relations in the medical services field. The formal logical method helped us to establish the legal structure of such partnerships. The results of this work allowed us to determine the legal problems of legislation that arise during the public-private partnership implementation in the medical services field and the prospects for their elimination. It analyzes the current stage of public-private partnership in the provision of the medical services in Ukraine and the positive experience of individual countries of the European Union and the world, which can bring the quality of their delivery to a higher European level

Riesgo de enfermedades cardiovasculares según categorías de presión arterial en una cohorte argentina

SummaryBackground: Hypertension is a recognized strong risk factor for cardiovascular disease. However, no data was available in our country to quantify the relationship between blood pressure and cardiovascular event.Objective: to quantify the risk of cardiovascular events according to blood pressure categories.Methods: A prospective epidemiological study was conducted in 1526 inhabitants from Rauch City, (Buenos Aires, Argentina) between 1997 and 2012. Subjects were classified into one of these blood-pressure categories: 1-optimal, 2-normal, 3-high-normal, 4-grade 1 hypertension, 5-grade 2 hypertension and 6-grade 3 hypertension. The first CVD event, including unstable angina pectoris, fatal and non-fatal myocardial infarction, myocardial revascularization, and fatal or non-fatal stroke, was defined as the primary endpoint. Multivariable Cox proportional-hazards regression models were used to estimate the relative risk (HR) of CVD according to base-line blood-pressure categories.Results: In 2012, 1124 individuals (73.7% of the baseline sample), 719 women and 405 men (in 1997, aged 45±16 and 46±16 respectively) or their relatives in case of death, could be surveyed again in order to obtain information concerning incident CVD events. Cardiovascular event rates and  HR values increased in a stepwise manner across the blood pressure categories (p for trend across categories &lt;0.001 in both sex); however, in subjects aged ?55 years a j-curve phenomenon was observed, showing the lowest incidence in the high-normal category. In all categories CVD events rates were higher for men.Conclusion: This study quantified relationships between BP and CVD starting from high-normal blood pressure in Argentina.   Resumen Antecedentes: La hipertensión arterial es un reconocido factor de riesgo de enfermedad cardiovascular (ECV). Sin embargo, no hay información en Argentina que cuantifique la relación entre la presión arterial (PA) y ECV.Objetivo: Cuantificar el riesgo de ECV de acuerdo a categorías de PA.Método: Se realizó un estudio epidemiológico prospectivo en 1526 habitantes de la ciudad de Rauch (Buenos Aires, Argentina) entre octubre de 1997 y febrero de 2012. Los individuos fueron clasificados en las categorías de PA: 1-óptima, 2-normal, 3-normal-alta, 4-hipertensión grado 1, 5-hipertensión grado 2 y 6-hipertensión grado 3. Fue definido como punto final el primer evento de ECV (angina de pecho inestable, infarto fatal y no fatal, revascularización, y accidente cerebrovascular fatal y no fatal). El riesgo relativo (HR) de tener un evento fue estimado usando modelos de regresión multivariable de Cox.Resultados: En 2012, fueron re-encuestados 1124 individuos (73,7% de la muestra basal), 719 mujeres y 405 hombres, o sus parientes en caso de muerte (edad en 1997 45±16 y 46±16 años, respectivamente). Las tasas de ECV y los HR se incrementaron para cada categoría de PA por encima de la óptima (p &lt; 0.001 en ambos sexos); sin embargo, en sujetos mayores de 55 años se observó un fenómeno de curva en J, con la incidencia más baja en la categoría normal-alto. En todas las categorías la tasa de eventos fue mayor en hombres.Conclusión: Este estudio demostró y cuantificó la relación entre de PA y ECV a partir de PA normal alta en una población de Argentina. </p

Daratumumab plus lenalidomide and dexamethasone in relapsed/ refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk

Insights on multiple myeloma treatment strategies

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future