Comparative Effectiveness and Safety of Trastuzumab Biosimilars to Herceptin for Adjuvant Treatment of HER2+ Breast Cancer.

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan-Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74-0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72-2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments.

Conventional vs. Sutureless Aortic Valve Bioprosthesis: Is Faster Better?

Purpose: The benefits of sutureless compared to conventional aortic valve prosthesis replacement remain controversial. Supposed advantages of sutureless aortic valve replacement include shortened cross-clamp and implantation time, as well as improved overall safety and good post-operative performance. We aimed to compare the early outcomes and performance of sutureless aortic valve replacement (su-AVR) with the sutureless Perceval (Corcym, Milan, Italy) vs. the conventional AVR with a conventional counterpart, in this case, the Labcor Dokimos Plus (LDP) aortic bioprosthesis. Methods: We compared two types of aortic valve prostheses, the sutureless (Corcym, Milan, Italy) and the conventional valve Labcor Dokimos Plus (LDP), implanted between August 2014 and May 2019 in our Department of Cardiac Surgery at RWTH Aachen University Hospital. Data were collected from 141 patients who received the Perceval (Corcym, Milan, Italy) and 138 who received the Labcor Dokimos Plus (LDP) aortic bioprosthesis. After matching the two groups considering STS mortality risk and pre-operative LDH levels, 201 patients were included in our final study cohort. Seventy-one patients (17 from the Perceval group and 54 from the Dokimos group) were excluded due to the lack of complete data, particularly standardized echocardiographic data (n = 71). Primary endpoints were 30-day mortality, length of hospital stay, and pacemaker implantation. Secondary endpoints were echocardiographic parameters, major adverse cardiovascular events, and prosthesis failure (grade II aortic regurgitation, paravalvular leak with reintervention). Results: Bypass and cross-clamp time proved to be shorter in the Perceval group, while hospital stays were longer. The faster implantation had no effect on the 30-day mortality primary endpoint. Transvalvular gradients were significantly higher in the Perceval group, in addition to a smaller effective orifice area. The LDH values were remarkably higher post-operatively in the Perceval group. Conclusions: Regarding the clinical outcomes, Perceval was equivalent and not superior to the Dokimus bioprosthesis. The suitability of a Perceval prosthesis implantation must be determined on a case-by-case basis and reserved for elderly patients with increased comorbidity.

Conventional Prostheses versus Sutureless Perceval for Aortic Valve Replacement: A Meta-Analysis.

PURPOSE: Perceval sutureless valves have gained popularity. Whether this implant performs superior to the traditional sutured prosthesis remains unclear. This meta- analysis compared the Perceval implants versus the sutured conventional valves for aortic valve replacement (AVR). METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were accessed: PubMed, Google Scholar, Web of Science, Scopus, and EMBASE. All clinical investigations comparing Perceval versus the conventional prostheses for AVR were considered. RESULTS: The Perceval group demonstrated higher rate of pacemaker implantation (P <0.00001). Aortic cross-clamp (ACC) time (P <0.00001) and cardiopulmonary bypass (CPB) time (P <0.00001) were shorter in the Perceval group. Similarity was found in mean and peak pressure gradient (P = 0.8 and P = 0.2, respectively), mean aortic valve area (P = 0.3), length of intensive care unit (P = 0.4) and hospital stay (P = 0.2), rate of revision (P = 0.11), hemorrhages (P = 0.05), paravalvular leak (P = 0.3), cerebrovascular complication (P = 0.7), and early mortality (P = 0.06). CONCLUSION: Given the shorter ACC time and CPB time, Perceval AVR can be an alternative in high-risk patients. The higher rate of pacemaker implantation following Perceval may limit its routine implantation.

Comparison of Use of Neoadjuvant Systemic Treatment for Breast Cancer and Short-term Outcomes Before vs During the COVID-19 Era in Ontario, Canada.

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

Considerations for Developing a Reassessment Process: Report from the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's Reassessment and Uptake Working Group.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.

Validación clínica de enfermería en cicatrización de úlceras venosas con miel nativa chilena suplementada / Clinical validation nursing in healing of venous ulcers with supplemented Chilean native honey / Validação clínica de enfermagem na cicatrização de úlceras venosas com mel nativo chileno suplementado

El objetivo de este estudio longitudinal fue validar clínica y planimétricamente la cicatrización de úlceras venosas con un prototipo de miel médica suplementada, nativa de Chile. La cicatrización de la úlcera venosa, demanda recursos sanitarios y tiempo de enfermería. Las terapias naturales, como la miel, son consideradas cicatrizantes, siendo el enfermero/a el profesional encargado de incorporarlas en la gestión del cuidado de personas con heridas. Participaron 22 pacientes con úlceras venosas, de centros de salud de Padre las Casas, Chile, voluntarios del proyecto CORFO 13IDL2-2329, tratados con un prototipo médico de miel nativa con actividad antibacteriana y suplementada con antioxidantes. Se realizó seguimiento clínico y planimétrico de la disminución del área y perímetro, asociados al uso del producto bajo un protocolo de gestión del cuidado de enfermería. El análisis de imágenes fue con el Software ImageJ®, cuyos datos fueron sometidos a estadística no paramétrica con el Software IBMSPSS-21.0. La reducción del área y perímetro fueron estadísticamente significativos para las úlceras tipo 3 y 4, con una mediana de reducción de área de 95.41 % y 84.40 % para perímetro, ambos entre el segundo y tercer contraste de mediciones. Destacó también la mediana de días de cicatrización en úlceras tipo 4 con 124 días. Se concluyó que la aplicación de miel clínica y un protocolo de gestión del cuidado de enfermería, basado en un tratamiento multifactorial y un criterio uniforme de curación, demostraron reducción de las áreas y perímetros de cicatrización, con énfasis en el desbridamiento.

The objective of the longitudinal study was to validate clinically and planimetrically the healing of venous ulcers with a prototype of upplemented medical honey, native to Chile. Healing of venous ulcer requires health resources and nursing time. Natural therapies, such as honey, are considered healing, and the nurse is responsible for incorporating them in the management of the care of people with injuries. 22 patients with venous ulcers participated, from health centers of Padre las Casas, Chile, volunteers of the CORFO 13IDL2-2329 project, treated with a medical prototype of native honey, supplemented with antioxidants and certified antibacterial activity. Clinical and planimetric follow-up of the area and perimeter decrease, associated with the use of the prototype was carried out under a nursing care management protocol. The analysis of images was with the Software ImageJ® , whose data were subjected to non-parametric statistics with the Software IBMSPSS-21.0. The area and perimeter reduction were statistically significant for type 3 and 4 ulcers, with a median area reduction of 95.41 % and 84.40 % for perimeter, both between the second and third measurements contrast. It also highlighted the median number of days of healing in type 4 ulcers with 124 days. It was concluded that the application of clinical honey and a nursing care management protocol, based on a multifactorial treatment and a uniform cure criterion, demonstrated reduction of the areas and perimeters of healing, with emphasis on debridement.

O objetivo deste estudo longitudinal foi validar clínica e planimetricamente a cicatrização de úlcerações venosas com um protótipo de mel medicinal suplementado, nativo do Chile. A cicatrização da úlcera venosa exige recursos de saúde e tempo de enfermagem. As terapias naturais, como o mel, são consideradas cicatrizantes, e o enfermeiro é o profissional encarregado de incorporá-las ao gerenciamento do cuidado de pessoas com feridas. Participaram 22 pacientes com úlcerações venosas dos centros de saúde de Padre las Casas, Chile, voluntários do projeto CORFO 13IDL2-2329, tratados com um protótipo médico de Mel nativo com atividade antibacteriana e suplementado com antioxidantes. Foi realizado monitoramento clínico e planimétrico da área e diminuição do perímetro, associado ao uso do produto sob um protocolo de gerenciamento de cuidados de enfermagem. A análise das imagens foi realizada com o software ImageJ®, cujos dados foram submetidos a estatística não paramétrica com o software IBMSPSS-21.0. A redução de área e perímetro foi estatisticamente significante para as úlceras tipo 3 e 4, com uma redução mediana da área de 95,41% e 84,40% para o perímetro, ambos entre o segundo e o terceiro contraste da medida. Também se destacaram os dias medianos de cicatrização em úlceras tipo 4 com 124 dias. Concluiu-se que a aplicação do mel clínico e um protocolo de gestão da assistência de enfermagem, baseado em tratamento multifatorial e critério uniforme de cicatrização, demonstraram redução das áreas e perímetros da cicatrização, com ênfase no desbridamento.

Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Forecasting Ontario Oncology Drug Expenditures: A Hybrid Approach to Improving Accuracy.

BACKGROUND: The Provincial Drug Reimbursement Program (PDRP) at Cancer Care Ontario (CCO) is responsible for monitoring actual and projected outpatient intravenous cancer drug spending in the province. We developed a hybrid forecasting approach combining automated time-series forecasting with expert-customizable input. OBJECTIVE: Our objectives were to provide a flexible tool in which to incorporate multiple forecasts and to improve the accuracy of the resulting forecast. METHODS: The approach employed linear and non-linear time-series techniques and a combined hybrid model incorporating both approaches. We developed an interactive tool that incorporated the statistical models and identified the best performing forecast according to standard goodness-of-fit measures. Model selection procedures considered both the amount of historical expenditure data available per drug policy and the individual policy contributions to the overall budget. The user was allowed to customize forecasts based on knowledge of external factors related to policy or price changes and new drugs that come to market RESULTS: A comparison of 2016/17 fiscal year expenditures showed that all policies with a significant contribution to the overall budget were forecast with < 4% error. Forecasting error was reduced by at least $Can5 million for the nine most expensive policies compared with expert opinion. This approach to drug budget forecasting was implemented in Ontario for the first time in the 2017/18 fiscal year, where 1% error was observed for the overall budget, corresponding to an overestimate of expenditures by $Can3.0 million. CONCLUSION: We introduced a pragmatic approach for regular forecasting by budget holders in Ontario. Our approach to isolating 'big budget' from 'small budget' drugs using an 80-20 rule and providing multiple forecasts depending on the length of the drug expenditure histories is transferable to other jurisdictions.

Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis.

BACKGROUND: In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC. METHODS: Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population-based databases. Overall survival (OS) was assessed using Kaplan-Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models. RESULTS: For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70-0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia-related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia-related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar. CONCLUSION: In the real world, FFX had longer OS, less frequent all-cause EDV and all-cause hospitalization, but more febrile neutropenia-related hospitalization compared to GnP.

Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?

BACKGROUND: Advanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0-10), in cancer clinics. We explored the association between baseline patient-reported outcomes, via ESAS, and overall survival (OS). METHODS: Advanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan-Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub-cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis. RESULTS: We identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub-cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS. CONCLUSIONS: Higher burden of patient-reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.

Significados de madres y padres mexicanos del mismo género en torno a la crianza / Meanings of Mexican same-sex parents around parenting

Este estudio muestra los significados expresados por tres parejas del mismo género (cuatro mujeres y dos hombres) sobre la crianza de sus hijas e hijos, quienes tenían entre uno y tres años de edad. Desde un enfoque hermenéutico-interpretativo, analizamos entrevistas narrativas, resultando en las siguientes categorías: Importancia de verbalizar y explicar; Reglas, límites y consecuencias; Enseñanza y aprendizaje de valores y habilidades sociales; Mantener una relación cercana; Rasgos/atributos personales valorados (en las y los niños). Encontramos diversas funciones asumidas en su labor como educadores, que se vincularon de forma dinámica con lo que esperaban y valoraban en cuanto a aprendizaje y desarrollo. Fue importante para ellos/as complacer, dar gusto y satisfacer las necesidades de sus niñas y niños, sin que esto significara descuidar una alimentación saludable, establecer y mantener reglas y rutinas, así como enseñar habilidades acordes a su edad. Un significado compartido giró en torno al lenguaje y comunicación, pues para los adultos era importante explicar: desde rutinas, hasta verbalizar sentimientos, o hacer explícito su tipo de familia (tener dos padres o dos madres); siempre considerando lo que puede comprenderse a esa edad. También fue importante para los adultos que sus hijos e hijas fueran alegres y sintieran su amor, manteniendo una relación cercana: cálida, lúdica y afectuosa. Concluimos que estos padres gais y madres lesbianas significaron a la crianza como una tarea amorosa, ardua, permanente y dirigida a formar sujetos con derechos, con quienes se podía negociar y llegar a acuerdos, aun siendo niños y niñas

This study shows the meanings expressed by three Mexican same-gender couples (four women and two men) about the upbringing of their daughters and sons, who were aged between one and three years. From a hermeneutic-interpretative approach, we analysed narrative interviews, resulting in the following categories: Importance of verbalizing and expressing; Rules, limits and consequences; Teaching and learning values and social skills; Maintain a warm relationship; Personal traits/attributes valued (in children). We found that fathers and mothers played different roles in their work as educators, which were linked dynamically with what they expect and value in terms of learning and development. It was important for them to please, to indulge and to satisfy their children's needs, without this neglecting a healthy diet, establishing and maintaining rules and routines, as well as teaching values and skills according to their age. A shared meaning revolved around language and communication: for adults it was important explaining routines, verbalizing feelings, or making explicit their type of family (having two fathers or two mothers); always considering what can be understood at that age. It was also important for our participants that their sons and daughters felt happy and loved through a close, warm, playful and affectionate relationship. We conclude that these gay parents and lesbian mothers meant the upbringing as a loving, arduous and permanent task, committed to forming subjects with rights, with whom they could negotiate and reach agreements

Improved survival in overweight and obese patients with aggressive B-cell lymphoma treated with rituximab-containing chemotherapy for curative intent.

The association between obesity and survival in non-Hodgkin lymphoma is unclear. Using the Ontario Cancer Registry we conducted a retrospective analysis of incident cases of aggressive-histology B-cell lymphoma treated with a rituximab-containing regimen with curative intent between 2008-2016. 6246 patients were included. On multivariable analysis the rate of all-cause mortality was lower for the overweight body mass index (BMI 25-29.9 kg/m2) (HR 0.85; 95%CI 0.77-0.95) and obese BMI (≥30 kg/m2) (HR 0.75; 95%CI 0.67-0.85) groups compared to the normal weight group (18.5-24.9 kg/m2). Binomial logistic regression analysis revealed a lower odds ratio (OR) of admission to hospital during treatment in the overweight (OR 0.84; 95%CI 0.75-0.95) compared to normal weight BMI group. In the largest cohort to date of aggressive-histology B-cell lymphoma patients treated with rituximab, increased BMI is associated with a survival advantage, and the magnitude of this effect increases from overweight to obese BMI.

The flutter-by effect: a comprehensive study of the fluttering cusps of the Perceval heart valve prosthesis.

OBJECTIVES: Sutureless aortic valve prostheses are gaining popularity due to the substantial reduction in cross-clamp time. In this study, we report our observations on the cusp-fluttering phenomenon of the Perceval bioprosthesis (LivaNova, London, UK) using a combination of technical and medical perspectives. METHODS: Between August 2014 and December 2016, a total of 108 patients (69% women) with a mean age of 78 years had aortic valve replacement using the Perceval bioprosthesis (34 combined procedures). All patients underwent transoesophageal echocardiography (TOE) intraoperatively. TOE was performed postoperatively to detect paravalvular leakage and to measure gradients, acceleration time, Doppler velocity indices (Vmax and LVOT/Vmax AV) and effective orifice area indices. In addition, a TOE examination was performed in 21 patients postoperatively. Data were collected retrospectively from our hospital database. RESULTS: The retrospective evaluation of the intraoperative TOE examinations revealed consistent fluttering in all patients with the Perceval bioprosthesis. The echocardiographic postoperative measurements showed a mean effective orifice area index of 0.91 ± 0.12 cm2/m2. The overall mean pressure and peak pressure gradients were in a higher range (13.5 ± 5.1 mmHg and 25.5 ± 8.6 mmHg, respectively), whereas acceleration time (62.8 ± 16.4 ms) and Doppler velocity indices (0.43 ± 0.11) were within the normal range according to the American Society of Echocardiography or european association of echocardiography (EAE) guidelines. The 2-dimensional TOE in Motion Mode (M-Mode) that was performed in patients with elevated lactate dehydrogenase (LDH) levels revealed remarkable fluttering of the cusps of the Perceval bioprosthesis. CONCLUSIONS: In our study cohort, we observed the fluttering phenomenon in all patients who received the Perceval bioprosthesis, which was correlated with elevated LDH levels and higher pressure gradients.

Combined therapy of Ulmo honey (Eucryphia cordifolia) and ascorbic acid to treat venous ulcers / Terapia combinada com mel de Ulmo (Eucryphia cordifolia) e ácido ascórbico para úlceras venosas / Terapia combinada con miel de Ulmo (Eucryphia cordifolia) y ácido ascórbico en úlceras venosas

OBJECTIVE: to assess the clinical effect of topical treatment using Ulmo honey associated with oral ascorbic acid in patients with venous ulcers. METHOD: longitudinal and descriptive quantitative study. During one year, 18 patients were assessed who were clinically diagnosed with venous ulcer in different stages, male and female, adult, with a mean injury time of 13 months. Ulmo honey was topically applied daily. The dressing was applied in accordance with the technical standard for advanced dressings, combined with the daily oral consumptions of 500 mg of ascorbic acid. The monitoring instrument is the assessment table of venous ulcers. RESULTS: full healing was achieved in 100% of the venous ulcers. No signs of complications were observed, such as allergies or infection. CONCLUSION: the proposed treatment showed excellent clinical results for the healing of venous ulcers. The honey demonstrated debriding and non-adherent properties, was easy to apply and remove and was well accepted by the users. The described results generated a research line on chronic wound treatment. .

OBJETIVO: avaliar o efeito clínico de tratamento tópico com mel de Ulmo associado à administração oral de ácido ascórbico em pacientes portadores de úlceras venosas. MÉTODO: estudo quantitativo descritivo longitudinal. Um total de 18 pacientes adultos, ambos os sexos, clinicamente diagnosticados com úlcera venosa em diferentes estágios e com duração de 13 meses em média, foram avaliados pelo período de um ano. A aplicação tópica diária de mel de Ulmo foi realizada de acordo com a norma técnica de tratamento avançado combinada com o consumo diário de 500 mg de ácido ascórbico. O instrumento usado para monitoramento foi a tabela de avaliação de úlceras venosas. RESULTADOS: cicatrização completa foi observada em 100% das úlceras venosas. Não foram observados sinais de complicação tais como alergias ou infecção. CONCLUSÃO: o tratamento proposto apresentou resultados clínicos excelentes na cicatrização das úlceras venosas. Além de favorecer o debridamento, o mel não é aderente, é fácil de aplicar e remover, e é de fácil aceitação por parte dos usuários. Os resultados descritos geraram uma linha investigativa no tratamento de feridas crônicas. .

OBJETIVO: evaluar el efecto clínico del tratamiento con miel de Ulmo tópico asociado a ácido ascórbico oral en pacientes portadores de úlceras venosas. MÉTODO: estudio cuantitativo descriptivo longitudinal. Durante el período de un año se evaluaron 18 pacientes diagnosticados clínicamente de úlcera venosa en sus diferentes estadios, de ambos sexos, adultos, con 13 meses promedio de antigüedad de la lesión. Se realizó la aplicación tópica diaria de miel de Ulmo con curación según la norma técnica de curaciones avanzadas, combinada con el consumo oral diario de 500 mg de ácido ascórbico. El instrumento de seguimiento es la tabla de valoración de úlceras venosas. RESULTADOS: se logró la cicatrización total en el 100% de las úlceras venosas. No se observaron signos de complicación, tales como alergias o infección. CONCLUSIÓN: el tratamiento propuesto mostró excelentes resultados clínicos en la cicatrización de úlceras venosas, presentando la miel propiedades debridantes, no adherentes, fácil de aplicar, remover y aceptación del usuario. Los resultados descritos generaron una línea investigativa en el tratamiento de heridas crónicas. .

Identificación de los niveles de ansiedad y depresión en pacientes con insuficiencia renal crónica de una unidad de hemodiálisis de la ciudad de Armenia - Quindío / Identification of anxiety and depression levels in patients with chronic kidney failure from a hemodialysis unit in the city of Armenia - Quindío

El presente trabajo tuvo como fin identificar los niveles de ansiedad y depresión en pacientes con insuficiencia renal crónica (IRC), de una unidad de hemodiálisis de la ciudad de Armenia. Para ello se realiza una investigación de carácter descriptivo-cuantitativa en una muestra de 12 pacientes con IRC a los que se les aplicó la escala hospitalaria de ansiedad y depresión de Hamilton. Se encontró niveles significativos de ansiedad en el 66% de los encuestados, y depresión significativa en el 28%. Estas altas cifras indican la necesidad de realizar labores de acompañamiento psicológico durante el proceso médico en pro del mejoramiento de las condiciones de vida de las personas con IRC o cualquier otra patología de cronicidad que cause alteraciones en los aspectos psicosociales.

The present Project had as purpose to identify the levels of anxiety and depression in patients with chronic renal failure (CRF) of a hemodialysis unit of the city of Armenia. For that end, a descriptive, quantitative investigation was made in a sample of 12 patients with CRF, who were administered the Hamilton hospital anxiety and depression scale. There were found significant levels of anxiety in 66% of the sample, and significant levels of depression in the 28%. These high figures indicate the necessity to make psychological support work in the medical process to the improvement of life conditions of the people with CRF or any other chronic pathology that causes changes in the psychosocial aspects.