Inflation, Economic Policy Changes, and Access to Essential Drugs by Retirees in Argentina.

This cross-sectional study investigates whether there are associations between inflation, economic policy changes, and retirees' access to medicines in Argentina.

Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

[Methodological challenges for proactive post-Covid care strategies]. / Opportunità-priorità di innovazione metodologica nel tempo dopo Covid.

. Methodological challenges for proactive post-Covid care strategies. In the present global-national scenarios of healthcare systems obliged to recognise their profound failure in the management of the Covid pandemic, the uncertainties on what could possibly be done to reverse the causes of the failures are the dominant terms of reference. The urgent needs of substantially increasing the investments on the scarce human resources and on the structural inequalities in the access to care are, in fact, in profound contrast with policies obedient mainly to economic sustainability and further exclusion from health rights. An epidemiological agenda explicitly centred on the lives of communities as producers of knowledge (not based on administrative and artificially standardised data), and as real bottom-up partners of the classical top-down actors is illustrated. The above perspective is discussed as a provocative and at the same time realistic opportunity for an innovative promotion of an autonomous role of the nursing professions and research.

[Data as common good.] / I dati come bene comune.

Data are part of language, intelligence, description, knowledge production, politics, economics, medicine: they are the essential quantitative component of any message. The recent transformation of reality into data, however, has made data an economic commodity. But does the raw material of which knowledge is made - data - belong to the universe of the unalienable rights of the individual and of populations or to the global normativity of economy-goods? The transformation of data into proprietary goods has introduced into the rules of research the artificiality and complication of a contractual logic that transforms the qualitative-contextual component of projects into an unwelcome or disturbing guest and turns attention to formal details into a purely administrative exercise. The only possible solution is not to accept the blackmail of obeying the rigidity of rules that prevent a serious and responsible relationship with the problems of patients and real populations.

Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 µg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met. RESULTS: In total, 127 patients were enrolled (ropeg: n=64; standard group: n=63). The primary end point was met in 81% and 51% in the ropeg and standard groups, respectively. Responders continued the assigned treatment until month 24 and maintained response in 83% and 59%, respectively (P=0.02). Ropeg responders less frequently experienced moderate/severe symptoms (33% vs. 67% in the standard group) and palpable splenomegaly (14% vs. 37%) and showed normalization of ferritin levels and blood counts. Nonresponders at 12 months crossed over to the standard (n=9) or ropeg (n=23) group; in patients switched to ropeg only, 7 of 23 met the response criteria in 12 months, and phlebotomy need was high (4.7 per patient per year). Discontinuation because of adverse events occurred in seven patients treated with ropeg. CONCLUSIONS: In this 24-month trial, ropeg was superior to phlebotomy alone in maintaining hematocrit on target. No dose-limiting side effects or toxicities were noted; 9.2% of patients on ropeg and no patients on standard treatment developed neutropenia. (Funded by AOP Health and others; ClinicalTrials.gov number, NCT03003325.)

[What is a statistical genocide? Memo for an active nursing management of the new reform of the national health system]. / Che cosa è uno statistical genocide? Promemoria per una gestione infermieristica attiva del PNRR.

. What is a statistical genocide? Memo for an active nursing management of the new reform of the national health system. A recent editorial note in a journal which is certainly culturally and not only scientifically relevant as The Lancet, underlines how statistics, a discipline and methodology expected to be highly reliable and needed to produce critical evidences for programming and evaluating health issues and interventions, has become in various scenarios a misleading tool, by its capacity of using data to manipulate epidemiological information which coincides with the specific cancellation of situations of violation of human and health rights. As we live in a time and in contexts where data are becoming the protagonists of the decision-making processes from the digitalisation of all information, to the uncontrollable dependence from algorithms in deciding priorities and 'personalised' care the alarm raised deserves attention: not exclusively to avoid misled behaviour, but more importantly to assure better and truly innovative practices. In the present challenging situation, which sees the nursing profession planned to acquire more substantial autonomy in the production of knowledge, the alarm could and should be interpreted as a 'sentinel provocation' (and concrete model scenarios are proposed) to manage and utilise data which focus and made better targeted populations more exposed to conditions of fragility and marginalisation: the dominance of administrative data directed mainly to monitor economic sustainability, must be integrated and re-directed to a care where the human rights to health are the indicators and the measure of outcomes.

A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia.

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

[Measuring strategies and instruments at the uncertain frontiers of quality and quantity]. / Misurare e valutare alle frontiere incerte tra quantità e qualità.

. Measuring strategies and instruments at the uncertain frontiers of quality and quantity. As a development of previous contributions in this section on methodology, and with a specific reference to the ongoing discussion in the literature on the reliability and relevance of quantitative measures of qualitative dimensions such as satisfaction, the present comment underlines the need of a 'cultural' approach to the problems which are a mix/crossroad of quality and quantity. Two most recent very brief, didactical, provocative publications, by a woman mathematician and a famous world-renowned economist respectively, are suggested as model examples of the need and potential contribution of a broader, multidisciplinary, culturally contextualized research strategies and instruments.

Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation.

BACKGROUND: Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. OBJECTIVES: To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. METHODS: A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. RESULTS: Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04-1.36], p = 0.026; NT-proBNP: HR:1.19[1.06-1.35], p = 0.016; Ang2: HR:1.07[0.95-1.20], p = 0.283; BMP10: HR:1.09[0.96-1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29-1.90], p < 0.001 1.63], p = 0.097). CONCLUSIONS: The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

Coffee, Atrial Fibrillation, and Circulating Ceramides in Patients with Chronic Heart Failure.

Ceramides are sphingolipids that play roles as structural lipids and as second messengers in biological processes. Circulating ceramides are influenced by diet/food and predict major cardiovascular (CV) events, such as atrial fibrillation (AF). In 1227 patients with symptomatic chronic heart failure (HF), an association between diet and ceramides was found for coffee consumption of ≥3 cups and Cer(d18:1/24:0). Increased Cer(d18:1/24:0) was associated with lower incident AF (24.3% vs 15.4% tertile 1 vs 3, P = 0.016) and lower CV mortality (28.4% vs 12.0% tertile 1 vs 3, P < 0.0001). For coffee consumption, only an association with incident AF was found (24.5% never, 5.2% ≥3 cups). These inverse associations with AF were confirmed in survival analyses corrected for biomarkers (Cer(d18:1/24:0) HR: 0.79, P = 0.018; coffee consumption HR: 0.22, P = 0.001). In conclusion, higher coffee intake was associated with a lower risk of incident AF and with higher concentrations of Cer(d18:1/24:0). Cer(d18:1/24:0) was inversely associated to risk of AF.

[Cultural meta-analysis 2: the after Covid-19]. / Metanalisi culturale 2: il dopo Covid-19.

. Cultural meta-analysis 2: the after Covid-19. Against the background of the promises-expectations of an ethically and ecologically renewed and resilient world (declared needed to compensate and to avoid the repetition of the pandemic tragedy), the same methodology proposed in the heart of the Covid scenario has been applied: a cultural metanalysis - transversal through and comprehensive of the various points of view which have had ( and seem to have) an important role for a period defined as 'some light at the end of the tunnel'. After the mandatory priority of a focus on the most qualified health literature, the survey provides essential elements of information and analysis on scenarios which more closely coincide with the challenges to be faced if and when the imaginary of a 'different-better' world should be translated into reality, specifically in the model area of health. With the obvious limitation of an exercise of methodology (which cannot pretend to a completeness of coverage), both world famous and 'significant' authors are included, as well as Italian voices. The take-home - not easy - message is clear. The pandemic has not been an 'health-disease' event. Its 'syndemic' nature (i.e. its interaction with structural, permanent, economic, social, cultural pandemics) imposes the acceptance and the long-term pursuit of new civilisation paradigms. Health care is definitely one of the areas where this cultural challenge must be met.

[For a visibility of the subjects of health as a human right/common good]. / Per una visibilità concreta dei soggetti della salute come diritto umano/bene comune.

. For a visibility of the subjects of health as a human right/common good. In order to make the many populations of the national health service visible and to produce data that can be used as a guide for health planning, the fragmentation currently present in the databases, prevents the cross-communication and should be overcomed. Social, economical and health indicators should help to shape subgroups of populations and their needs, to render visible the problems (met and unmet) at community level. The critical step is the move from an epidemiology limited to the description of population problems to one that allows to highlight problems' avoidability.

Inequalities in the Universal Right to Health.

Child health inequalities violate children's rights to optimal wellbeing. Different issues worldwide affect children's physical and mental health as well as their development, influencing their future as adults. Inequities are avoidable inequalities. Despite improvements in the past two decades, the ambitious goals of global agendas have, for the most part, remained as expectations with regard to childhood rights, social justice, and health equity in practice. The concept of social determinants of health has become part of the common language in certain settings, but this is still too little to improve health in practice on a global scale, particularly for underprivileged subgroups of the community, as children and adolescents often are. Pediatric health professionals and their organizations are also responsible for guaranteeing children's and adolescents' right to health and better wellbeing, helping to reduce health inequalities.