Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Modelling and Design of a Dual Depletion PIN Photodiode as Temperature Sensor.

Nowadays, optical systems play an important role in communications. Dual depletion PIN photodiodes are common devices that can operate in different optical bands, depending on the chosen semiconductors. However, since semiconductor properties vary with the surrounding conditions, some optical devices/systems can act as sensors. In this research work, a numerical model is implemented to analyze the frequency response of this kind of structure. It considers both transit time and capacitive effects, and can be applied to compute photodiode frequency response under nonuniform illumination. The InP-In0.53Ga0.47As photodiode is usually used to convert optical into electrical power at wavelengths around 1300 nm (O-band). This model is implemented considering an input frequency variation of up to 100 GHz. The focus of this research work was essentially the determination of the device's bandwidth from the computed spectra. This was performed at three different temperatures: 275 K, 300 K, and 325 K. The aim of this research work was to analyze if a InP-In0.53Ga0.47As photodiode can act as a temperature sensor, to detect temperature variations. Furthermore, the device dimensions were optimized, to obtain a temperature sensor. The optimized device, for a 6 V applied voltage and an active area of 500 µm2, had a total length of 2.536 µm, in which 53.95% corresponded to the absorption region. In these conditions, if the temperature increases 25 K from the room temperature, one should expect a bandwidth increase of 8.374 GHz, and if it decreases 25 K from that reference, the bandwidth should reduce by 3.620 GHz. This temperature sensor could be incorporated in common InP photonic integrated circuits, which are commonly used in telecommunications.

Epidemiological and clinical characterization of a population-based cohort of cutaneous malignant melanoma patients in the South Region of Portugal.

An historical population-based cohort study was conducted aiming to estimate the incidence of cutaneous malignant melanoma in the South Region of Portugal between Jan 2016 and June 2017; to clinically characterize the diagnosed individuals; to describe instituted treatment; and to estimate survival outcomes. Data were extracted from a cancer registry (ROR-Sul) covering 4,800,000 inhabitants (46% of the Portuguese population) and included a total of 789 individuals meeting eligibility criteria. The crude incidence rate (18 months) of melanoma was 13.36/100,000 inhabitants and the Age-Standardized Incidence Rate per 100,000 World population was 9.65/100,000 inhabitants. The most common histological subtypes identified were superficial extension, followed by malignant melanoma and nodular melanoma. Most cases were diagnosed in stage I (50.39%), equally distributed by sex and with a median age of 65 years. During the study period, 174 recurrence events were recorded (23.45%) and recurrence-free survival rate was significantly lower in more advanced stages. Patients had a two-fold risk of recurrence/death when in presence of ulcerated tumors [adjusted hazard ratio (adj HR) = 2.28; 95% confidence interval (CI) 1.40-3.70]. Overall survival rate at 3-years was 80.54% (95% CI 77.58-83.15), higher than previous national reports, and considerably higher for individuals diagnosed at earlier stages (p < 0.001). We have also identified differential survival outcomes in stages II-III explained by the uptake of sentinel lymph node biopsy. The epidemiologic and clinical characteristics of malignant melanoma patients studied are consistent with international literature. The incidence and rates observed suggests additional public health campaigns are needed to modify behaviours of the Portuguese population and thus reduce their risk.

Nanostructures for Solar Energy Harvesting.

Renewable energy sources are becoming more and more essential to energy production as societies evolve toward a fossil-fuel-free world. Solar energy is one of the most abundant sources of green energy. Nanoantennas can be used to improve and enhance the absorption of light into a photovoltaic cell in order to generate more current. In this study, different nanoantenna structures are analysed in tandem with a silicon solar cell in an effort to improve its output. The nanoantennas studied are metallic aperture nanoantennas made up of either silver, aluminium, gold or copper. The three geometries compared are rectangular, circular and triangular. The maximum field enhancement obtained is for an aluminium rectangular nanoantenna of 50 nm thickness. Despite this, the geometry with more improvements compared with a basic silicon cell was the circle geometry with a 100 nm radius.

Modelling the effect of defects and cracks in solar cells' performance using the d1MxP discrete model.

Renewable energies are increasingly playing an important role in the world's energy supply. Society demands new solutions to solve environmental issues caused by fossil fuels. The importance of photovoltaic technology has been increasing and consequently, the necessity to have more accurate models to characterise the performance of solar cells during their entire lifetime has rose as well. Performance problems may appear during devices' lifetimes associated with factors, such as weather conditions or faulty installation. Cracking might occur, leading to abrupt reductions on the produced power, quite difficult and expensive to fix. The I-V curves of a defected or cracked solar cell might not have the shape imposed by the usual models as 1M5P. In this article, cracked c-Si solar cells are modelled using a novel model: d1MxP. This model is based on the discretisation of the diode's response on models as 1M5P. Instead of imposing a shape and compute some parameters to fit it on experimental data, the proposed model connects every two points. The results suggest a better fit using the proposed model in comparison with the 1M5P, not only in the original curves, but also modelling cracked cells. As consequence of a better fitting, the computation of important figures of merit as maximum power point or fill factor, reveals to be more precise. It is concluded that the proposed model might characterise the performance of a solar cell, even cracked, which is a huge advance aiming the possibility of simulating complex problems during the cells' operation lifetime.

Translation and cross-cultural adaptation of the ABC taxonomy for medication adherence into Portuguese - Updating patients into people.

BACKGROUND: The Ascertaining Barriers to Compliance (ABC) taxonomy for describing medication adherence was created in 2012, aiming to standardize terms and definitions in research and practice. The taxonomy comprises seven terms and definitions. Originally developed in English, subsequently translated into French and German, is currently being translated to Portuguese, Spanish, Czech, Romanian and Italian, aiming to promote its global use and overcome cultural barriers. OBJECTIVES: To cross-culturally translate the ABC taxonomy into Portuguese for Portugal and Brazil. METHODS: A systematic literature search was conducted to identify published taxonomy terms and definitions in Portuguese, and to identify panelists in medication adherence. Initial mapping of terms and definitions retrieved was scrutinized by the research team to build an e-survey. The e-survey was piloted and then sent to panelists in both countries seeking consensus using a three-round Delphi method. Consensus was defined as ≥ 85% for round 1 and ≥ 75% for round 2. Terms with agreement <10% were dropped between rounds. In round 3, terms and definitions reaching agreement between 50 and 75% were classified as moderate consensus,>75-95% as consensus and >95% as strong consensus. RESULTS: A total of 778 studies were identified and 84 included, enabling the extraction of 154 terms and 32 definitions. In round 1, 164 panelists participated, 115 in round 2 and 99 in the round 3. Consensus was achieved in both countries for all seven terms and definitions, although with varying intensity of agreement. The term "Management of adherence" and the definition of "Discontinuation" obtained moderate consensus in both countries. CONCLUSIONS: A unified and unique ABC taxonomy in Portuguese was possible to develop for use in Portugal and in Brazil. Its use will harmonize and standardize the terms and definitions used in clinical practice and research.

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study.

BACKGROUND: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). MATERIALS AND METHODS: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). RESULTS: A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08). CONCLUSION: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.

Identification of a Set of Patient-Related Features to Foster Safe Prescribing of Specific Antipsychotics in the Elderly With Dementia.

Background: Antipsychotics (APs) are widely used to manage behavioral and psychiatric symptoms in dementia, although with a variety of adverse drug reactions. Therefore, it is important to know which patient-related features should be considered to foster a safe prescribing of these medications. Objectives: To compile and validate a set of patient-related features (PRFs) to foster safe prescribing of specific APs in the elderly with dementia; and to evaluate the feasibility of using them in clinical practice by analyzing the exhaustiveness of medical records. Method: A rapid literature review was the starting point, where PRFs were identified through a search in PubMed combined with information from the Summary of Product Characteristics (SmPCs). In the next step, a two-round e-Delphi survey was undertaken, where a total of 450 participants were invited by e-mail, including prescribers and specialists in benefit-risk assessment. Finally, a cross-sectional study was undertaken, where 100 patients were randomly extracted from the psychiatric hospital database. Outcomes were defined as the assessment of the clinical relevance and feasibility of the PRFs, and the level of exhaustiveness of these features in medical records. Data analysis was performed using univariate statistics (IBM SPSS v.23.0). Results: A total of 92 experts participated in the e-Delphi. Forty-seven PRFs obtained consensus, where 12 were applicable to haloperidol, 14 to olanzapine/risperidone, 13 to quetiapine, and 8 to aripiprazole. Age, comorbidities, and co-medications were rated as important features regardless of the prescribed drug. All PRFs were rated as always or frequently available and, if not, they were easy or partially easy to obtain. Age, comorbidities, and co-medications were always available in the medical records, whereas cognitive status (between 41.4 and 78.8%) or hepatic function (between 17.2 and 30.4%) presented a low-level of exhaustiveness. Conclusions: Even though a high number of PRFs were rated as clinically relevant, some of them were identified as frequently missing from medical records. This may suggest that medical records should be complemented with other sources (e.g., nursing and pharmacy records) to ensure a safe prescribing of APs.