Search

Isandra Meirelles,* Carlos Magliano* Health Technology Assessment Unit, Instituto Nacional de Cardiologia, Rio de Janeiro, Rio de Janeiro, Brazil*These authors contributed equally to this workCorrespondence: Isandra Meirelles Email isandrameirelles@gmail.comIntroduction: The different alternatives for non-small-cell lung cancer (NSCLC) treatment can increase survival but cause important adverse events. Therefore, patients’ preference can play a critical role in decision-making. Among stated preference methods, discrete choice experiment (DCE) is the most applied in health care to elicit preferences. This research aims to elicit patients’ preference evaluating the trade-off between the risks (adverse events) and benefits (survival) of systemic treatments, from the perspective of Brazilian patients with locally advanced, metastatic or recurrent NSCLC.Methods: A DCE was performed following the steps of attributes selection; construction of tasks and respondents’ preference elicitation. Patients chose between 2 hypothetical treatments described by the attributes tiredness, hair loss, skin rash, hospitalization, administration mode and survival. A paper-and-pencil survey method was used to elicit the answers from the participants. The statistical data analysis used a mixed logit model to predict the relative importance of the attributes.Results: Most of the 65 patients interviewed were men (53.8%), mean age of 65 (95% confidence interval [CI]: 63– 67) years and lung cancer stage IV (67.7%). Except for hospitalization and administration mode, the attributes coefficients were statistically significant (p < 0.005) for patients’ preferences. Patients would require a minimum survival gain of 11.72 (CI: 10.28– 4.22) months and 19.72 (CI: 17.31‐7.09) months to accept a treatment that causes severe tiredness and severe skin rash, respectively. The market share of the treatments was calculated according to the DCE aggregate-level estimation, considering the impact of each treatment’s side effects. Paclitaxel plus carboplatin had an estimated market share of 31%, followed by gefitinib (27%), erlotinib (24%) and docetaxel (18%).Conclusion: In general, less than a year of survival gain would not suffice for the appearance of severe skin rash or tiredness.Keywords: non-small-cell lung cancer, patient preference

One of the main goals of the NASA Transiting Exoplanet Survey Satellite (TESS) mission is the discovery of Earth-like planets around nearby M-dwarf stars. We present the discovery and validation of three new short-period Earth-sized planets orbiting nearby M dwarfs: TOI-5720 b, TOI-6008 b, and TOI-6086 b. We combined TESS data, ground-based multicolor light curves, ground-based optical and near-infrared spectroscopy, and Subaru/IRD radial velocity data to validate the planetary candidates and constrain the physical parameters of the systems. In addition, we used archival images, high-resolution imaging, and statistical validation techniques to support the planetary validation. TOI-5720 b is an Earth-sized planet with a radius of Rp = 1.09 ± 0.07 R⊕. It orbits a nearby (36 pc) M 2.5 host with an orbital period of P = 1.4344555 ± 0.0000036 days. It has an equilibrium temperature of Teq = 708 ± 19 K (assuming a null albedo) and an incident flux of Sp = 41.7 ± 4.5 S⊕. TOI-6008 b is a short-period planet of P = 0.8574347 ± 0.0000424 day. It has a radius of Rp = 1.03 ± 0.05 R⊕, an equilibrium temperature of Teq = 707 ± 19 K, and an incident flux of Sp = 41.5 ± 4.5 S⊕. The host star (TOI-6008) is a nearby (23 pc) M 5 with an effective temperature of Teff = 3075 ± 75 K. Based on the radial velocity measurements collected with Subaru/IRD, we set a 3σ upper limit of Mp < 4 M⊕, thus ruling out a star or brown dwarf as the transiting companion. TOI-6086 b orbits its nearby (32 pc) M 3 host star (Teff = 3200 ± 75 K) every 1.3888725 ± 0.0000827 days and has a radius of Rp = 1.18 ± 0.07 R⊕, an equilibrium temperature of Teq = 634 ± 16 K, and an incident flux of Sp = 26.8 ± 2.7 S⊕. Additional high-precision radial velocity measurements are needed to derive the planetary masses and bulk densities and to search for additional planets in the systems. Moreover, short-period Earth-sized planets orbiting around nearby M dwarfs are suitable targets for an atmospheric characterization with the James Webb Space Telescope through transmission and emission spectroscopy and phase-curve photometry. [ABSTRACT FROM AUTHOR]

Placenta for eight sows, 3 in early pregnancy (28 days), 2 in the middle third of gestation (69 days) and 3 at term pregnancy (112 days) were examined by optic microscopy and transmission electron microscopy. The swine placenta, key organ for the success of the pregnancy, is characterised to be diffuse and epitheliochorial. In uterine luminal endometrium attachment of trophoblast fetal with maternal epithelium were observed. In this maternofetal interface of placenta the 28 days pregnancy the spaces between cell and cell were observed; these spaces could be central form of alimentation histiotrophe in this gestational period. The uterine cells contain electron-dense granules connected by narrow cisterns. At the 69-day stage of gestation the epithelial cells have more cell activity because they have nucleolo for cell and this is characteristic of cell division. The maternofetal interface of the placenta at the 69-day stage of gestation is more developed that maternofetal interface at the 28 days of gestation. Placenta at term show trofoblastic cells where it was observed many secretion of proteins and process characteristics of the apoptosis. The knowledge of the architecture and development of the placental areas through the different gestational periods, will allow to understand the immunoendocrine phenomenon that sustains the swine gestation. In this work, ultrastructural placental morphology from different periods of gestation was compared. [ABSTRACT FROM AUTHOR]

Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy., Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis., Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY., Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option., Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil., Competing Interests: ER reports grants and consulting fees from Bayer and Pfizer; grants from the Brazilian Ministry of Science and Technology; and personal fees from Aspen Pharma, Biomm Pharma, and Daiichi-Sankyo, outside the submitted work. LBA reports grants from Bayer, Pfizer and the Brazilian Ministry of Science and Technology. ACS reports consulting fees from Janssen Research & Development LLC, Bayer, Portola, Boehringer Ingelheim, Bristol-Meyers Squibb, ATLAS group and grants from Janssen and Boehringer Ingelheim. AT reports personal fees from Janssen and Recovery Force and grants from Bio Tap, Idorsia, Bristol-Myers Squibb, Novo Nordisk, Janssen, and Doasense. RDL reports grants and personal fees from Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and personal fees from Amgen, Bayer, and Boehringer Ingelheim outside the submitted work. No grants from pharmaceutical companies developing or manufacturing rivaroxaban were involved in this study., (© 2023 Published by Elsevier Ltd.)

Objectives: Several trials have demonstrated the benefit of the CDK 4/6 inhibitors for postmenopausal women with luminal advanced breast cancer. This research aims to compare the cost-utility of the CDK 4/6 inhibitors in patients with no history of resistance to endocrine therapy., Methods: A Markov model was constructed to estimate the incremental cost per quality-adjusted life-years (QALYs) of treatments from the Brazilian public health system perspective over a lifetime horizon (30 years) with 5% annual discount rate for both benefits and costs. Efficacy parameters were extracted from the pivotal studies. Costs were based on open data from the Brazilian Ministry of Health. The utilities were calculated according to the overall population preferences from a British study. Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results., Results: The most cost-effective drug was ribociclib (US$50 748/QALY), followed by abemaciclib (US$64 052/QALY) and palbociclib (US$65 289/QALY). The univariate analysis showed that the incremental cost-utility ratio (ICUR) was mainly sensitive to the overall survival hazard ratio. The one thousand-probabilistic simulation showed that all ICUR values were above classical thresholds such as 1 to 3 gross domestic product (GDP) per capita per QALY., Conclusions: Even though there is no established willingness to pay threshold in Brazil, the estimated ICUR for CDK 4/6 inhibitors is >6 times the Brazilian GDP per capita (GDP per capita = US$5694.73), which might be a barrier to their inclusion in the Brazilian public health system., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the factors associated with survival 20 years after endovascular treatment of an abdominal aortic aneurysm (AAA) in a single center., Methods: Prospective cohort of asymptomatic patients with an infrarenal aortic aneurysm treated with a bifurcated endovascular graft (Talent) between June 1997 and August 2008. Cox proportional hazard multivariable regression was used for analysis of independent risk factors for survival. Kaplan-Meier curves were done with the long-rank test. P < .05 was considered significant., Results: We followed 229 patients, 184 without an endoleak and 45 with an endoleak. Ages ranged between 52 and 89 years, and the mean diameter of the aneurysm was 59.51 ± 14.6 mm. Implantation of the endovascular graft was possible in 99% of the patients. The 30-day mortality rate was 3.4%. In the Cox regression, age <73 years (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.27-0.64), aneurysm size ≤55 mm (HR, 0.62; 95% CI, 0.40-0.95), male sex (HR, 0.17; 95% CI, 0.05-0.52), American Society of Anesthesiologists surgical risk category I and II vs III and IV (HR, 0.51; 95% CI, 0.34-0.75), and aneurysm size reduction ≤3 mm after treatment (HR, 2.23; 95% CI, 1.11-4.51) were significantly correlated with the survival of the patients followed in this long-term case series., Conclusions: This 20-year prospective cohort included patients with an AAA treated with a bifurcated endovascular graft (Talent) at a university hospital in Brazil. This study supports that sex, age, aneurysm size, aneurysm size reduction, and American Society of Anesthesiologists surgical risk category are significantly correlated with patient survival after endovascular treatment of the AAA., (Published by Elsevier Inc.)

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-β-1a-IM) was inferior to the other beta interferons (IFN-βs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-β-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-β-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-β-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-β-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-β-1a-IM was inferior to the other IFN-βs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-β-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-β from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.