Long-term follow-up of recovered MPN patients with COVID-19

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Neoplàsies mieloproliferatives cròniquesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Neoplasias mieloproliferativas crónicasCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Chronic myeloproliferative neoplasmsDuring the first wave of SARS-CoV-2 infection a European observational study was launched under the auspices of the European Leukemia Net (ELN), aiming at gathering information about the clinical epidemiology of COVID-19 in patients with chronic myeloproliferative neoplasms (MPN-COVID study).The study was supported by a research grant by the COVID “3×1 project”, BREMBO S.p.A., Bergamo, Italy (TB) and by AIRC 5×1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC). A detailed description of the MYNERVA project is available at https://progettomynerva.it (AMV, PG). The study was also supported by HARMONY PLUS, which is funded through the Innovative Medicines Initiative (IMI), Europe’s largest public-private initiative aiming to speed up the development of better and safer medicines for patients. The HARMONY Alliance has received funding from IMI 2 Joint Undertaking and is listed under grant agreement No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe

Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis

H ydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on followup duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis

Adherence With Antihypertensive Drug Therapy and the Risk of Heart Failure in Clinical Practice

Randomized clinical trials have shown that antihypertensive treatment reduces the risk of heart failure (HF). Limited evidence exists, however, on whether and to what extent this benefit is translated into real-life practice. A nested case–control study was carried out by including the cohort of 76 017 patients from Lombardy (Italy), aged 40 to 80 years, who were newly treated with antihypertensive drugs during 2005. Cases were the 622 patients who experienced hospitalization for HF from initial prescription until 2012. Up to 5 controls were randomly selected for each case. Logistic regression was used to model the HF risk associated with adherence to antihypertensive drugs, which was measured by the proportion of days covered by treatment (PDC). Data were adjusted for several covariates. Sensitivity analyses were performed to account for possible sources of systematic uncertainty. Compared with patients with very low adherence (PDC, ≤25%), low, intermediate, and high adherences were associated with progressively lower risk of HF, reduction in the high-adherence group (>75%) being 34% (95% confidence interval, 17%–48%). Similar effects were observed in younger (40–70 years) and older (71–80 years) patients and between patients treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. There was no evidence that adherence with calcium-channel blockers reduced the HF risk. Antihypertensive treatment lowers the HF risk in real-life practice, but adherence to treatment is necessary for a substantial benefit to take place. This is the case with a variety of antihypertensive drugs

Breakthrough infections in MPN-COVID vaccinated patients

Myeloproliferative diseaseEnfermedad mieloproliferativaMalaltia mieloproliferativaThe study was supported by a research grant by the COVID “3 × 1 project”, BREMBO S.p.A., Bergamo, Italy (T.B.) and by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC). A detailed description of the MYNERVA project is available at https://progettomynerva.it (A.M.V., P.G.). The study was also supported by HARMONY PLUS, which is funded through the Innovative Medicines Initiative (IMI), Europe’s largest public–private initiative aiming to speed up the development of better and safer medicines for patients. The HARMONY Alliance has received funding from IMI 2 Joint Undertaking and is listed under grant agreement No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe

Should methods of correction for multiple comparisons be applied in pharmacovigilance?

Purpose. In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relationship under study are known. To this aim we applied a robust estimation method for the FDR (rFDR) particularly suitable in the pharmacovigilance context. Methods. We exploited the data available for the SAFEGUARD project to apply the rFDR estimation methods to detect potential false positive signals of adverse reactions attributable to the use of non-insulin blood glucose lowering drugs. Specifically, the number of signals generated from the conventional disproportionality measures and after the application of the rFDR adjustment method was compared. Results. Among the 311 evaluable pairs (i.e., drug-event pairs with at least one adverse event report), 106 (34%) signals were considered as significant from the conventional analysis. Among them 1 resulted in false positive signals according to rFDR method. Conclusions. The results of this study seem to suggest that when a restricted number of drug-outcome pairs is considered and warnings about some of them are known, multiple comparisons methods for recognizing false positive signals are not so useful as suggested by theoretical considerations

Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1-6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46-0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35-0.82), and VKA (HR 0.58, 95% CI 0.35-0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37-0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis

Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography Screening Participants

Abstract Introduction The National Lung Screening Trial has achieved a 7% reduction in total mortality with low-dose computed tomography (LDCT) screening as compared with in the chest radiography arm. Other randomized trials are under way, comparing LDCT screening with no intervention. None of these studies was designed to investigate the impact of smoking habits on screening outcome. In the present study, we tested the effect of stopping smoking on the overall mortality of participants undergoing repeated LDCT screening for many years. Methods Between 2000 and 2010, 3381 smokers aged 50 years or older were enrolled in two LDCT screening programs. On the basis of the last follow-up information, subjects were divided into two groups: current smokers throughout the screening period and former smokers. Results With a median follow-up time of 9.7 years and a total of 32,857 person-years (PYs) of follow-up, a total of 151 deaths were observed in the group of 1797 current smokers (17,846 PYs) versus 109 among 1584 former smokers (15,011 PYs), corresponding to mortality rates of 8.46 and 7.26 for every 1000 PYs, respectively. Compared with current smokers, former smokers had an adjusted mortality hazard ratio of 0.61 (95% confidence interval: 0.44–0.83), with a 39% reduction in mortality. A similar reduction in mortality was observed in the subset of 712 late quitters, with a hazard ratio of 0.65 (95% confidence interval: 0.44–0.96). Conclusions Stopping smoking significantly reduces the overall mortality of smokers enrolled in LDCT screening programs. The beneficial effect of stopping smoking on total mortality appears to be threefold to fivefold greater than the one achieved by earlier detection in the National Lung Screening Trial

On Nontrival Equilibria in Finitely Repeated Games

Background: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures.Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates.Results: Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities.Conclusions: Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGI