Analysis of patient selection and external validity in the Swedish contribution to the COLOR trial

Objective  The colon cancer laparoscopic or open resection (COLOR) trial is an international, randomised controlled trial comparing outcomes of open and laparoscopic surgery for colon cancer. The main purpose of this study was to determine representability by comparing included and nonincluded patients in the participating Swedish centres. Design  At eight centres, which included 391 of the 422 Swedish patients, a local database search was performed to identify retrospectively all patients (n = 2,384) who underwent surgery for colon cancer during the inclusion period, and data was retrieved from medical records. Results  Four hundred fifty-six patients were randomised, 65 of whom were excluded post randomisation (group 2), leaving 391 patients in the study (group 1). For 1,566 patients, valid exclusion criteria were found (group 3). Thus, 362 patients were eligible but not included (group 4). Relative to group 1, patients in group 4 had a significantly higher American Society of Anaesthesiologists (ASA) score, more advanced tumour stage and difference regarding the resections performed. Results showed that 1470 patients (62%) could be calculated as feasible for laparoscopic colon resection (LCR) in a clinical, nontrial situation. Conclusions  The study population in the Swedish part of the COLOR trial was representative of the eligible population with the exception of comorbidity, where those actually included had less severe comorbidity than the nonincluded but eligible patients. In Sweden, 50–60% of colon cancer patients can be operated on by laparoscopy. This work was supported by grants from the Swedish Cancer Society (Project Number 4287-B01-03XCC and Project Number 1921-B03-21XCC), the County Council of Stockholm, Assar Gabrielsson’s Foundation for Clinical Research, Jubileumskliniken Research Foundation, Sahlgrenska University Hospital and the Swedish Society of Medicine. A preliminary version of this paper was previously published in an academic thesis; “Laparoscopic and open surgery for colon cancer. Studies on costs and health related quality of life” by Martin Janson, Karolinska Institutet 2006, ISBN 91-7140-782-0.     

Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".     

Report from the Ready for the Next Round Thought-Leadership Roundtables on Building Resilience in Cancer Care and Control in Canada-Colorectal Cancer Canada; 2021

(1) Background: The COVID-19 pandemic illuminated vulnerabilities in the Canadian health care system and exposed gaps and challenges across the cancer care continuum. Canada is experiencing significant disruptions to cancer-related services, and the impact these disruptions (delays/deferrals/cancellations) have on the health care system and patients are yet to be determined. Given the potential adverse ramifications, how can Canada’s health care systems build resilience for future threats? (2) Methods: To answer this question, CCC facilitated a series of four thought-leadership roundtables, each representing the views of four different stakeholder groups: patients, physicians, health care system leaders, and researchers. (3) Results: Six themes of strength were identified to serve as a springboard for building resilience including, (1) advancing virtual care and digital health technologies to prevent future interruptions in cancer care delivery. (2) developing real-time data metrics, data sharing, and evidence-based decision-making. (3) enhancing public–private-non-profit partnerships to advance research and strengthen connections across the system. (4) advancing patient-centricity in cancer research to drive and encourage precision medicine approaches to care. (5) investing in training and hiring a robust supply of health care human resources. (6) implementing a national strategy and infrastructure to ensure inter-provincial collaborative data sharing (4). Conclusions: A resilient health care system that can respond to shocks and threats is not an emergency system; it is a robust everyday system that can respond to emergencies.     

Eating out of Home: Influence on Nutrition,Health, and Policies: A Scoping Review

Eating out of home (EOH) is a common practice worldwide but research gaps have been identified. The aims of this review were (a) to find a common definition for EOH, (b) to determine the nutritional contribution of EOH, and (c) to analyze the relationship of EOH with health parameters in adults. Fifty-seven articles were finally selected. The definition of EOH was not harmonized between researchers and the comparison between studies was quite difficult. Restaurant and fast food were the terms most used, followed by chain restaurant, à la carte, sit-down restaurant, eating at table, full service, ready to eat, takeaway, buffet and buffet by weight, bar, cafes, and cafeterias, either alone or attached to at least one of the above. The profile of the main EOH participant was a highly educated, high-income, and unmarried young man. EOH was related to a body mass index (BMI) or being overweight in a different way depending on age, sex, or EOH frequency. A high rate of EOH led to poorer diet quality, characterized by higher intakes of energy, total and saturated fats, sugar, and sodium, as well as lower intakes of fiber, dairy, fruit, vegetables, and micronutrients. Regarding beverages, a higher intake of soft drinks, sugar-sweetened beverages, fruit juices, beer, and other alcohol was observed when EOH. There is a need for a methodological consensus for analyzing the impact of EOH on dietary intake and health to avoid bias. Additionally, measures and policies should be utilized to help consumers to make healthier choices when EOH is compatible with business regarding those running EOH establishments.     

The role of aggressions suffered by healthcare workers as predictors of burnout

Aims and objectives. To examine the prevalence of aggression against healthcare professionals and to determine the possible impact that violent episodes have on healthcare professionals in terms of loss of enthusiasm and involvement towards work. The objective was to analyse the percentage of occupational assault against professionals’ aggression in different types of healthcare services, differentiating between physical and verbal aggression as a possible variable in detecting burnout in doctors and nursing professionals. Background. Leiter and Maslach have explored a double process model of burnout not only based on exhaustion by overload, but also based on personal and organisational value conflicts (community, rewards or values). Moreover, Whittington has obtained conclusive results about the possible relationship between violence and burnout in mental health nurses. Design. A retrospective study was performed in three hospitals and 22 primary care centres in Spain (n = 1·826). Methods. Through different questionnaires, we have explored the relationship between aggression suffered by healthcare workers and burnout. Results. Eleven percent of respondents had been physically assaulted on at least one occasion, whilst 34·4% had suffered threats and intimidation on at least one occasion and 36·6% had been subjected to insults. Both forms of violence, physical and non‐physical aggression, showed significant correlations with symptoms of burnout (emotional exhaustion, depersonalisation and inefficacy). Conclusions. The survey showed evidence of a double process: (1) by which excess workload helps predict burnout, and (2) by which a mismatch in the congruence of values, or interpersonal conflict, contributes in a meaningful way to each of the dimensions of burnout, adding overhead to the process of exhaustion–cynicism–lack of realisation. Relevance to clinical practice. Studies indicate that health professionals are some of the most exposed to disorders steaming from psychosocial risks and a high comorbidity: anxiety, depression, etc. There is a clear need for accurate instruments of evaluation to detect not only the burnout but also the areas that cause it. Professional exhaustion caused by aggression or other factors can reflect a deterioration in the healthcare relationship.     

A mixed method evaluation of a group‐based educational programme for CPAP use in patients with obstructive sleep apnea

Rationale, aims and objectives Continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) has a low long‐term adherence. Educational interventions are few and sparsely described regarding content, pedagogical approach and participants' perceptions. The aim was to describe adherence to CPAP treatment, knowledge about OSA/CPAP, as well as OSA patients' perceptions of participating in a group‐based programme using problem‐based learning (PBL) for CPAP initiation. Educational programme The PBL programme incorporated elements from theories and models concerning motivation and habits. Tutorial groups consisting of four to eight patients met at six sessions during 6 months. Methods A sequential explanatory mixed method design was used on 25 strategically selected patients. Quantitative data regarding, clinical variables, OSA severity, CPAP use, and knowledge were collected at baseline, after 2 weeks and 6 months. Qualitative data regarding patients' perceptions of participation were collected after 6 months by semi‐structured interviews using a phenomenographic approach. Results 72% of the patients were adherent to CPAP treatment after 2 weeks and 6 months. All patients improved their baseline knowledge about OSA and CPAP after 2 weeks and sustained it after 6 months. Anxiety and fear, as well as difficulties and needs were motivational factors for participation. Patients described the difficulties of behavioural change, an awareness that improvements do not occur immediately, a realization of the importance of both technical and emotional support and the need for a healthier lifestyle. Conclusion and practice implications A group‐based programme using PBL seems to facilitate adaptive and developmental learning and result in acceptable CPAP adherence levels.     

Nutrient and Fiber Intake and Risk of Renal Cell Carcinoma

This study examines the association between nutrient and fiber intake and the risk of renal cell carcinoma (RCC). Between 1994 and 1997 in 8 Canadian provinces, mailed questionnaires were completed by 1,138 incident, histologically confirmed cases of RCC and 5,039 population controls. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios (ORs) and 95% confidence intervals were derived through unconditional logistic regression. Intakes of total fat, saturated fat, monounsaturated fat, trans-fat, and cholesterol were associated with the risk of RCC; the ORs for the highest vs. the lowest quartile were 1.67, 1.53 and 1.46, 1.31, and 1.48, respectively. The positive association was apparently stronger in women, overweight or obese, and never smokers. Sucrose was related to the risk of RCC. High fiber intake was inversely associated with RCC risk. No association was found with intake of total protein and polyunsaturated fat, n-3 and n-6 polyunsaturated fatty acids, and total carbohydrates. The results were consistent across strata of sex, tobacco, and BMI. The findings suggest that a diet low in fats and cholesterol and rich in fiber could favorably affect the risk of RCC.     

High immunogenic potential of p53 mRNA-transfected dendritic cells in patients with primary breast cancer

As pre-existent immunity might be a reflection of an emerging anticancer response, the demonstration of spontaneous T-cell responses against tumor associated antigens (TAAs) in cancer patients may be beneficial before clinical development of dendritic cell (DC)-based cancer vaccines, because it will help to identify likely responders to TAAs among patients who qualify and may benefit from this form of immune therapy. This study aimed to determine pre-existent T-cell reactivity against the tumor suppressor protein p53 in breast cancer patients (BCP) at the time point of primary diagnosis. After a short-term stimulation with autologous wt p53 mRNA-transfected DCs, IFN-γ enzyme-linked immunosorbent spot (ELISPOT) analysis revealed p53-reactive T cells in the peripheral blood of more than 40% (15 of 36) of the tested patients. Both CD4⁺ and CD8⁺ p53-specific T cells secreted IFN-γ after stimulation with p53-transfected DCs. Interestingly, more than 72% (13 of 18) of patients with high p53 (p53^high) expression in tumors were able to mount a p53-specific IFN-γ T-cell response, in contrast to only 10% (1 of 10) of healthy donors and 11% (2 of 18) of patients with low or absent p53 (p53^low) expression in tumors. Furthermore, significantly higher secretion of IL-2 was detected in peripheral blood mononuclear cells after stimulation with p53-transfected DCs from patients with p53^high tumor expression compared to patients with p53^low tumor expression, whereas secretion of IL-10 was predominant in the latter group. The high frequency of spontaneous wt p53-reactive T cells detected in the peripheral blood of primary BCP with accumulation of p53 in tumor provides a rationale to consider DCs transfected with mRNA encoding wt p53 for clinical investigation in these patients.     

Coste económico del paciente asmático en Espa?a (estudio AsmaCost)

ObjectiveThis analysis of the cost of asthma in Spain includes both direct health care costs and indirect costs arising from illness.Patients and MethodsProspective, 12-month observational cohort study of adult patients with asthma diagnosed according to the guidelines of the Global Initiative for Asthma (GINA) and the adapted Spanish criteria (GEMA). We recorded information on health care resources utilized (medications, medical visits, emergency care, hospital admissions, and tests) and indirect costs (patient travel or transfer costs and workdays lost).ResultsA total of 627 patients throughout Spain were studied. Of these, 21.2% had intermittent asthma, 24.6% mild asthma, 27.6% moderate asthma, and 26.6% severe asthma. The total societal cost of asthma (including indirect costs) was €1726 (95% confidence interval [CI], €1314–€2154) per patient annually. Indirect costs accounted for 11.2% of the total. The cost to the National Health Service was €1533 (95% CI, €1133–€1946) per patient annually. The cost of asthma was higher for patients older than 65 years (€2079) and for those with more severe disease (€959 for intermittent asthma; €1598, mild asthma; €1553, moderate asthma; and €2635 severe asthma). Based on these findings, the total annual cost of asthma in Spain is estimated to be €1480 million (95% CI, €382–€2565 million) for patients with demonstrated bronchial hyperreactivity and €3022 million (95% CI, €2472–€3535 million) for patients diagnosed based on symptoms alone.ConclusionsThe average annual cost of asthma in adults in Spain comes to €1726 per patient, considering both direct and indirect costs. The average annual cost per patient to the National Health Service is €1533.