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.

Vocalizations of wild West Indian manatee vary across subspecies and geographic location.

Geographic variation in the vocal behavior of manatees has been reported but is largely unexplored. Vocalizations of wild West Indian manatees (Trichechus manatus) were recorded with hydrophones in Florida from Florida manatees (Trichechus manatus latirostris), and in Belize and Panama from Antillean manatees (Trichechus manatus manatus) to determine if calls varied between subspecies and geographic regions. Calls were visually classified into five categories: squeaks, high squeaks, squeals, squeak-squeals, and chirps. From these five categories, only three call types (squeaks, high squeaks and squeals) were observed in all three populations. Six parameters from the temporal and frequency domains were measured from the fundamental frequency of 2878 manatee vocalizations. A repeated measures PERMANOVA found significant differences for squeaks and high squeaks between each geographic location and for squeals between Belize and Florida. Almost all measured frequency and temporal parameters of manatee vocalizations differed between and within subspecies. Variables that may have influenced the variation observed may be related to sex, body size, habitat and/or other factors. Our findings provide critical information of manatee calls for wildlife monitoring and highlight the need for further study of the vocal behavior of manatees throughout their range.

SIX1+PAX3+ identify a progenitor for myogenic lineage commitment from hPSCs.

The earliest skeletal muscle progenitor cells (SMPCs) derived from human pluripotent stem cells (hPSCs) are often identified by factors expressed by a diverse number of progenitors. An early transcriptional checkpoint that defines myogenic commitment could improve hPSC differentiation to skeletal muscle. Analysis of several myogenic factors in human embryos and early hPSC differentiations found SIX1+PAX3+ co-expression was most indictive of myogenesis. Using dCas9-KRAB hPSCs, we demonstrate that early inhibition of SIX1 alone significantly decreased PAX3 expression, reduced PAX7+ SMPCs, and myotubes later in differentiation. Emergence of SIX1+PAX3+ precursors can be improved by manipulating seeding density, monitoring metabolic secretion and altering the concentration of CHIR99021. These modifications resulted in the co-emergence of hPSC-derived sclerotome, cardiac and neural crest that we hypothesized enhanced hPSC myogenic differentiation. Inhibition of non-myogenic lineages modulated PAX3 independent of SIX1. To better understand SIX1 expression, we compared directed differentiations to fetal progenitors and adult satellite cells by RNA-seq. Although SIX1 continued to be expressed across human development, SIX1 co-factor expression was dependent on developmental timing. We provide a resource to enable efficient derivation of skeletal muscle from hPSCs.

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.

Connectivity conservation at the crossroads: protected areas versus payments for ecosystem services in conserving connectivity for Colombian carnivores.

Protected areas (PAs) constitute one of the main tools for global landscape conservation. Recently, payments for environmental services (PES) have attracted interest from national and regional governments and are becoming one of the leading conservation policy instruments in tropical countries. However, the degree to which areas designated for PES overlap with areas that are critical for maintaining species' landscape connectivity is rarely evaluated. We estimated habitat distributions and connectivity for 16 of the 22 mammalian carnivores occurring in the Caribbean region of Colombia, and identified the overlap between existing PAs and areas identified as being important for connectivity for these species. We also evaluated the potential impact of creation of new PAs versus new PES areas on conserving connectivity for carnivores. Our results show that PAs cover only a minor percentage of the total area that is important for maintaining connectivity ( x = 26.8 % ± 20.2 s . d . ). On the other hand, PES, if implemented extensively, could contribute substantially to mammalian carnivores' connectivity ( x = 45.4 % ± 12.8 s . d . ). However, in a more realistic scenario with limited conservation investment in which fewer areas are set aside, a strategy based on implementing new PAs seems superior to PES. We argue that prioritizing designation of new PAs will be the most efficient means through which to maintain connectivity.

Who Can Debriefing Assessment for Simulation in Healthcare? Different Perspectives on Teledebriefing Assessments.

INTRODUCTION: Virtual debriefing is a cardinal element to achieve the effectiveness of telesimulation. There are different instruments to assess face-to-face debriefing to determine the degree of effectiveness of debriefing; Debriefing Assessment for Simulation in Healthcare (DASH) instrument is one of them. This study aims to describe and compare the evaluation of raters, instructors, and students during a virtual debriefing using the DASH. METHODS: A cross-sectional study was performed evaluating the virtual debriefing of 30 instructors after a heart failure telesimulation scenario. The evaluation was conducted by 30 instructors, 338 undergraduate students in the seventh semester, and 7 simulation raters. The 3 versions of the DASH instrument in Spanish were applied, respectively. RESULTS: Two comparisons were made, student versus instructor and rater versus instructor. Cronbach α was 0.97 for each version. The averages of the results on the DASH instrument were: 6.61 (3.34-7.0), 5.95 (4.65-7.0), and 4.84 (2.68-6.02) for student, rater, and instructor versions, respectively. The size effect between student and debriefer perspectives was 0.42. In contrast, the size effect between instructor and rater was 0.72. All differences were significant. CONCLUSIONS: There are different rates between the persons who use the DASH. In this study, from the perspective of the instructor and rater, the difference was 1 point with a wide range, in contrast with the difference between instructor and student, which is relatively minor. It is necessary to consider the perspectives of experts in the subject to achieve a virtual debriefing of high quality and improve a debriefing by using the DASH.

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.

Implementation Barriers in Telesimulation as an Educational Strategy: An Interpretative Description.

Introduction Telesimulation is one of the different methodologies for distance learning to promote competency in medical trainees. This methodology needs to have professors, students, and standardized patients in one session to perform a teleconsultation. Telesimulation could lead to multiple implementation barriers. This study aims to describe the implementation barriers through the perspective of the professors, students, and standardized patients in a telesimulation scenario in undergraduate medical education. Method We designed and applied a telesimulation scenario in undergraduate medical students. Then we conducted an online questionnaire with the critical incidents technique. The study sample was 18 professors, 26 standardized patients, and 407 students Results We describe a taxonomy with five categories and each one with different subcategories: knowledge (clinical simulation, theoretical over the clinical case, and use of simulators), facilities (access, time of use, and functionality), financing (payment to staff and purchase of equipment), attitude (acceptance and emotion), and participants (communication, collaborative work, and debriefing). Conclusion The description of the implementation barriers through multiple perspectives generates a taxonomy that could improve the quality of the telesimulation. This taxonomy is a proposal to consider the design, implementation, and evaluation when a telesimulation is implemented. The taxonomy could generate a structured plan when the educators implement the telesimulations at their own institutions considering all the barriers proposed.

Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions - New Jersey, February-July 2020.

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.

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

Volumetric polymerization shrinkage and its comparison to internal adaptation in bulk fill and conventional composites: A µCT and OCT in vitro analysis.

OBJECTIVE: To quantify the volumetric polymerization shrinkage (VPS) of different conventional and bulk fill resin composites, through micro-computed tomography (µCT), and qualitative comparison of gap formation through optical coherence tomography (OCT). METHODS: Box-shaped class I cavities were prepared in 30 third-molars and divided into 5 groups (n=6): G1- Filtek Z100 (Z100); G2- Tetric Evoceram Bulk Fill (TEC); G3- Tetric EvoFlow Bulk fill (TEF); G4- Filtek Bulk fill (FBU); and G5- Filtek Bulk fill Flowable (FBF). All groups were treated with Adper Single Bond Plus adhesive and light cured (Bluephase 20i). Each tooth was scanned three times using a µCT apparatus: after cavity preparation (empty scan); after cavity filling (uncured scan) and after light curing of the restorations (cured scan). The µCT images were imported into a three-dimensional rendering software, and volumetric polymerization shrinkage percentage was calculated (%) for each sample. In the same images, interfacial gaps in the pulpal floor were qualitatively evaluated. After µCT evaluation, the pulpal floor from each tooth was polished until a thin tooth structure was obtained and OCT images were obtained by scanning the pulpal portion. Gap formation was observed and qualitatively compared to the µCT images. RESULTS: VPS means ranged from 2.31 to 3.96% for the studied resin composites. The bulk fill materials, either high viscosity or flowable, were not statistically different from each other (p>0.05). The conventional resin composite Z100 presented statistically higher VPS than both high viscosity bulk fill materials studied (p<0.05), although it was statistically similar to the flowable bulk fill materials studied (p>0.05). Both µCT and OCT methodologies enabled gap formation visualization, and images from both technologies could be associated. Gap formation was mostly observed for G1-Z100, G4-FBU, and G5-FBF. VPS% and pulpal gap formation could not be completely associated with each other for all groups and samples. Voids were observed in most of the resin composite fillings, and most VPS were observed in the occlusal area of the samples. SIGNIFICANCE: Volumetric polymerization shrinkage was material-dependent, although bulk fill materials did not differ from each other. Both µCT and OCT enabled interfacial pulpal gap formation visualization. VPS and gap formation cannot be completely associated with one another.