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Goal: This study aimed to examine provincial differences in patient spending for cancer care and reductions in household spending including decisions to forego care in Canada. Methods: Nine-hundred and one patients with cancer, from twenty cancer centers across Canada, completed a self-administered questionnaire (P-SAFE version 7.2.4) (344 breast, 183 colorectal, 158 lung, and 216 prostate) measuring direct and indirect costs and spending changes. Results: Provincial variations showed a high mean out-of-pocket cost (OOPC) of CAD 938 (Alberta) and a low of CAD 280 (Manitoba). Differences were influenced by age and income. Income loss was highest for Alberta (CAD 2399) and lowest for Manitoba (CAD 1126). Travel costs were highest for Alberta (CAD 294) and lowest for British Columbia (CAD 67). Parking costs were highest for Ontario (CAD 103) and lowest for Manitoba (CAD 53). A total of 41% of patients reported reducing spending, but this increased to 52% for families earning

Perspectives of cancer survivors, caregivers, and social workers as key stakeholders on the clinical management of financial toxicity (FT) are critical to identify opportunities for better FT management. Semi-structured interviews (cancer survivors, caregivers) and a focus group (social workers) were undertaken using purposive sampling at a quaternary public hospital in Australia. People with any cancer diagnosis attending the hospital were eligible. Data were analysed using inductive-deductive content analysis techniques. Twenty-two stakeholders (n = 10 cancer survivors of mixed-cancer types, n = 5 caregivers, and n = 7 social workers) participated. Key findings included: (i) genuine concern for FT of cancer survivors and caregivers shown through practical support by health care and social workers; (ii) need for clarity of role and services; (iii) importance of timely information flow; and (iv) proactive navigation as a priority. While cancer survivors and caregivers received financial assistance and support from the hospital, the lack of synchronised, shared understanding of roles and services in relation to finance between cancer survivors, caregivers, and health professionals undermined the effectiveness and consistency of these services. A proactive approach to anticipate cancer survivors' and caregivers' needs is recommended. Future research may develop and evaluate initiatives to manage cancer survivors and families FT experiences and outcomes. [ABSTRACT FROM AUTHOR]

Traditionally, economic evaluations are based on clinical trials with well-defined patient populations that exclude many patient types. By contrast, studies that incorporate general patient populations end up including those in lower income categories, some of whom have significant financial burdens (often described as financial toxicity) related to their care. Consideration of these patient burdens when examining the incremental cost-effectiveness of newer treatments from a clinical trial perspective can result in differing conclusions regarding cost-effectiveness. The challenge is to reliably assess the link between financial toxicity, quality of life and potential decisions to forego or delay care. It is also well-documented that these financial effects are not evenly distributed across populations, with those with low income and of black or Latino decent being most affected. There is a paucity of literature in this space, but some of the early work has suggested that for lung, breast, colorectal and ovarian cancers there are poorer quality-of-life scores and/or shorter overall survival for those experiencing financial toxicity. Hence, we may see both a lower quality of life and a shorter duration of life for these populations. If this is the case, additional considerations include: are the benefits of newer, more-expensive treatment strategies muted by the lack of adherence to these newer treatments due to financial concerns, and, if true, can these effects be effectively quantified as "real-world" outcomes? This rapid review examines these possibilities and the steps that may be required to examine this reliably. [ABSTRACT FROM AUTHOR]

Background: The prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). However, trial conditions do not always reflect the real-world applications of pharmaceutical products; hence, they may not accurately portray the actual risks of ADRs associated with them. The objective of this study is two-fold: (a) demonstrate whether and how post-market and RCT ADR data could lead to different conclusions for a set of drugs of interest, and (b) evaluate the potential economic impact of the post-market ADRs associated with those drugs.Methods: We selected two TNF-α inhibitor biologics, infliximab and adalimumab, and used the Canada Vigilance Adverse Reaction (CVAR) online database as a source of post-market ADR data. Adverse reaction data from RCTs were obtained from ClinicalTrials.gov . Direct healthcare costs associated with adverse reactions were obtained from Canadian Institute for Health Information (CIHI) or Interactive Health Data Application, Alberta. We calculated post-market ADR rates and compared them with those found in the randomized controlled trials of these two drugs. Using the post-market data, we estimated the costs associated with serious ADRs from three perspectives: patient, health system, and societal.Results: For both drugs, the post-market and RCT data exhibited significantly different adverse reaction rates for several different clinical outcomes. As a general trend, more serious adverse reactions, such as death, appeared to have a higher rate in post-market applications compared to the clinical trials. The estimated average annual economic burden of the severe adverse reaction outcomes ranged from $10 million to $20 million for infliximab and $6 million to $19 million for adalimumab.Conclusions: The frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials. Despite possible methodological differences, this is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs. The economic burden of adverse reactions can be substantial, and the cost calculated using post-market data is better reflective of the cost of ADRs in the real-world. [ABSTRACT FROM AUTHOR]

Goal: To determine patient-reported financial and family burden associated with treatment of cancer in the previous 28 days across Canada. Methods: A self-administered questionnaire (P-SAFE v7.2.4) was completed by 901 patients with cancer from twenty cancer centres nationally (344 breast, 183 colorectal, 158 lung, 216 prostate) measuring direct and indirect costs related to cancer treatment and foregone care. Monthly self-reported out-of-pocket-costs (OOPCs) included drugs, homecare, homemaking, complementary/ alternative medicines, vitamins/supplements, family care, accommodations, devices, and "other" costs. Travel and parking costs were captured separately. Patients indicated if OOPC, travel, parking, and lost income were a financial burden. Results: Mean 28-day OOPCs were CA$518 (US Purchase Price Parity [PPP] $416), plus CA$179 (US PPP $144) for travel and CA$84 (US PPP $67) for parking. Patients self-reporting high financial burden had total OOPCs (33%), of CA$961 (US PPP $772), while low-burden participants (66%) had OOPCs of CA$300 (US PPP $241). "Worst burden" respondents spent a mean of 50.7% of their monthly income on OOPCs (median 20.8%). Among the 29.4% who took time off work, patients averaged 18.0 days off. Among the 26.0% of patients whose caregivers took time off work, caregivers averaged 11.5 days off. Lastly, 41% of all patients had to reduce spending. Fifty-two per cent of those who reduced spending were families earning < CA$50,000/year. Conclusions: In our Canadian sample, high levels of financial burden exist for 33% of patients, and the severity of burden is higher for those with lower household incomes. [ABSTRACT FROM AUTHOR]

Introduction: Individual acupuncture (AP) is the gold standard method of AP delivery for cancer-related pain; however, costs can be prohibitive. Group AP allows four to six patients to be treated in a single session. This study sought to examine the cost–utility of group AP compared with individual AP from a patient perspective. Materials and Methods: Effectiveness and cost data from a noninferiority randomized trial of group versus individual AP for cancer-related pain were used. In the trial, 74 patients were randomly assigned to individual or group AP treatments twice per week for 6 weeks. The EuroQol five-dimension five level questionnaire (EQ-5D-5L) was used to assess health-related quality of life, and the EQ-5D Utility Index was used as a composite measure constituted of five domains (mobility, self-care, usual activities, anxiety–depression, and pain–discomfort). Linear mixed models were used to compare the change in EQ-5D-5L states pre–post intervention between the two arms. A cost–utility analysis was performed in terms of the incremental costs per additional quality-adjusted life year (QALY) gained. Results: Group AP participants experienced more significant relief in the pain-discomfort subscale of the EQ-5D-5L measure compared with individual AP participants (group × time, F = 6.18; p = 0.02). The effect size on pain-discomfort for group AP (d = 0.80) was higher than that of individual AP (d = 0.34). There were no significant differences between the two study arms for other subscales of the EQ-5D-5L over time. QALYs at 6 weeks were slightly higher for group AP (0.020) compared with individual AP (0.007) leading to an incremental QALY gained by the group arm of 0.013, but this difference was not statistically significant (p = 0.07). The cost of delivering AP treatment for the group arm over 6 weeks ($201.25) was nearly half of the individual arm ($400). Conclusions: Group AP was superior to individual AP in cancer patients. These findings have implications for the use of group AP in low-resource settings and in health care systems where AP for cancer patients is not covered by public health insurance. ClinicalTrials.gov (NCT03641222). Registered July 10, 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03641222 [ABSTRACT FROM AUTHOR]

Objective: To seek understanding of financial burden from the perspective of cancer patients, in a largely publicly funded health care system, about the impacts of financial hardship on their lives.Methods: A qualitative descriptive analysis was completed for comments written in response to an open-ended, free-text item on a pan-Canadian survey about costs incurred during cancer treatment and follow-up and the impact of financial difficulties.Results: A total 378 of the 901 survey respondents provided comments about their financial situations during cancer treatment. Forty percent of those individuals indicated experiencing financial struggles and resulting emotional distress. Themes were identified as follows: cost incurred, reduced income and reserves, impact of costs and reduced financial income/reserve, and managing financial distress.Conclusion: Even within a universal health care system, a significant proportion of cancer patients experienced financial struggle and resulting emotional distress.Practice Implications: Regular monitoring of financial and emotional distress and its sources can facilitate the identification of those who are experiencing financial difficulty and the provision of appropriate interventions. [ABSTRACT FROM AUTHOR]

Purpose: Financial toxicity related to cancer diagnosis and treatment is a common issue in developed countries. We seek to systematically summarize the extent of the issue in very high development index countries with publicly funded healthcare. Methods: We identified articles published Jan 1, 2005, to March 7, 2019, describing financial burden/toxicity experienced by cancer patients and/or informal caregivers using OVID Medline Embase and PsychInfo, CINAHL, Business Source Complete, and EconLit databases. Only English language peer-reviewed full papers describing studies conducted in very high development index countries with predominantly publicly funded healthcare were eligible (excluded the USA). All stages of the review were evaluated in teams of two researchers excepting the final data extraction (CJL only). Results: The searches identified 7117 unique articles, 32 of which were eligible. Studies were undertaken in Canada, Australia, Ireland, UK, Germany, Denmark, Malaysia, Finland, France, South Korea, and the Netherlands. Eighteen studies reported patient/caregiver out-of-pocket costs (range US$17–US$506/month), 18 studies reported patient/caregiver lost income (range 17.6–67.3%), 14 studies reported patient/caregiver travel and accommodation costs (range US$8–US$393/month), and 6 studies reported financial stress (range 41–48%), strain (range 7–39%), or financial burden/distress/toxicity among patients/caregivers (range 22–27%). The majority of studies focused on patients, with some including caregivers. Financial toxicity was greater in those with early disease and/or more severe cancers. Conclusions: Despite government-funded universal public healthcare, financial toxicity is an issue for cancer patients and their families. Although levels of toxicity vary between countries, the findings suggest financial protection appears to be inadequate in many countries. [ABSTRACT FROM AUTHOR]

Objective: This research informs existing work by examining the full scope of out-of-pocket costs and lost income, patients' private insurance behaviors, and their overall management of finances during their cancer treatment. The intent was to gain a deeper understanding of patient circumstances and the related costs.Methods: Participant qualitative interviews were conducted in person during outpatient clinic visits or by telephone and were recorded between June 2011 and July 2012. Interviews were transcribed verbatim and subjected to a descriptive qualitative analysis. The research team collaborated early in the process (after three subjects were enrolled) to develop a preliminary coding framework. The coding framework was modified to incorporate additional emerging content until saturation of data was evident. Transcripts were coded using the qualitative software NVivo version 9.0.Results: Fifteen patients agreed to participate in the study and 14 completed the interview (seven breast, three colorectal, two lung, and two prostate). Consistent with existing published work, participants expressed concerns regarding expenses related to medications, complementary/alternative medicines, devices, parking and travel. These concerns were exacerbated if patients did not have insurance or lost insurance coverage due to loss of work. Although many acknowledged in hindsight that additional insurance would have helped, they also recognized that at the time of their diagnoses, it was not a viable option. Previously unidentified categorical costs identified in this study included modifications to housing arrangements or renovations, special clothing, fitness costs and the impact of an altered diet.Conclusion: We confirmed the results of earlier Canadian quantitative work. Additionally, cost categories not previously explored were identified, which will facilitate the development of an improved and more comprehensive quantitative questionnaire for future research. Many patients indicated that supplemental health insurance would have made their cancer journey less stressful, highlighting existing gaps in the government funded health care system. [ABSTRACT FROM AUTHOR]

Objective: To explore cancer patients' perspective about the impact of financial burden on quality of life. Methods: A qualitative descriptive approach was utilized. In-depth interview transcripts from 14 survivors were subjected to a thematic analysis. Results: All participants experienced reduced income and increased out-of-pocket costs following their diagnosis. None worked during their treatment interval. They described profound impacts on the social, psychological, and spiritual domains of quality of life from the financial challenges. Many were worried about having sufficient funds to support themselves in the long term and felt this added to the burden they were carrying. Most found the financial challenges surprising and unexpected. Additionally, the impact was also experienced by their family members. Implications: Healthcare providers ought to be aware of the potential impact financial challenges can have and the distress they bring about. A discussion about financial concerns needs to occur at the beginning of the cancer journey, with appropriate resources made available, and monitored regularly. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00520-021-06031-0 [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to determine the cost-effectiveness of using transdermal nitroglycerin (GTN) for cases of preterm labor. Methods: The study included 153 women with clinical preterm labor, who were randomly allocated to either a GTN or placebo arm. All randomized cases were included in the final economic analysis. Differences between the two arms in gestational age at delivery, neonatal intensive care unit (NICU) admission, length of NICU stay, and NICU cost were assessed. Costs for non-NICU cases were calculated using Ottawa Hospital data through the Ontario Case Costing Initiative (OCCI). Cost-effectiveness and sensitivity analyses using a hospital perspective were both conducted. Results: In the 153 randomized cases, 55 babies were admitted to NICU (GTN = 24; placebo = 31). We found no significant differences between the two arms in gestational age at delivery, NICU admission rate (32.4% vs. 39.2%), NICU length of stay (42.7 days vs. 52.8 days), or NICU cost (CAN $34,306 vs. CAN $44,326). Overall, (based on all randomized cases) the cost-effectiveness analyses showed that the GTN arm was the dominant strategy, with both lower cost (CAN $13,397 vs. CAN $18,427) and higher NICU admission avoided rate (67.6% vs. 60.8%) compared to the placebo arm. This dominance persisted in all sensitivity analyses. Conclusion: The use of GTN patch for preterm labor could reduce NICU costs, while improving important neonatal outcomes. [Copyright &y& Elsevier]

High-stakes testing has driven the way that educators deliver instruction. Historically, standardized testing has been in existence since the 1800s, but the impact of accountability was not recognized until the late 1970s. Science educators are trying to balance the requirements of state assessments with creative and meaningful curricula. Inquiry-based science instruction has led the way in assisting students in the process of discovering knowledge for themselves instead of simply being asked to recall information. Inquiry learning promotes creativity by increasing motivation, wonderment, and curiosity. The author proposes that inquiry is the key to enhancing creativity, while still meeting the demands of standardized testing. [ABSTRACT FROM AUTHOR]

An abdominal aortic aneurysm (AAA) is a lethal disease. Abdominal ultrasound (US) is used to screen patients for an AAA. Several screening guidelines have recently been released with variable recommendations about whom to screen. It is reasonable to screen patients aged 60 and older, particularly males, women with cardiovascular risk factors, smokers, and patients with a family history of AAA, as these appear to be the major risk factors. Patients with small (<5.5 cm) AAAs should be followed with serial US. Medical management should focus on managing comorbidities, especially those that place patients at risk for other cardiovascular disease, such as smoking and hypertension. Patients with large or symptomatic AAAs should be prepared for surgery, including careful imaging of the abdomen, and placed on a perioperative beta-blocker and a statin to lower LDL cholesterol to less than 70 ng/dL. Endovascular repair has lower short-term mortality and morbidity versus conventional open repair, and trials assessing long-term results are in progress. Basic science and translational research focusing on the underlying pathogenesis of AAAs will likely pave the way for future medical therapies. [ABSTRACT FROM AUTHOR]

Extensive level one evidence supports routine abdominal aortic aneurysm (AAA) screening in men aged 65 to 75 years, because AAAs are highly prevalent in this population. Physical examination is an insensitive means of detection. Ruptured AAAs are costly with respect to quality adjusted life years (QALY) lost and medical expenses. Large scale, randomized trials have demonstrated that AAA screening reduces all AAA-related mortality in the screened population and is cost-effective in mid-term follow-up. AAA screening by ultrasound has many advantages over other accepted medical screening programs in its simplicity in structure and the availability of an inexpensive, portable, and reliable means of screening. Additionally, AAA screening almost entirely avoids the negative consequences associated with other screening programs, including the adverse psychological effects and medical costs associated with false-positive examination results. There are subgroups of at-risk women who might benefit from AAA screening, and this issue should be further studied. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the relationship among income and emotional/practical concerns, help‐seeking and unmet needs for cancer survivors aged 18 to 64 years one to three years after treatment. A cross‐sectional survey was mailed in 2016 to 40,790 survivors randomly selected from 10 Canadian provincial cancer registries. Thirty‐three percent responded. A trend analysis was conducted for survivors most likely to be in the workforce exploring the relationship across four income levels and emotional/practical concerns, whether help was sought for identified concerns, and whether help was received. A total of 4,264 respondents, aged 18–64, provided useable data with breast (34.4%) and colo‐rectal (15.0%) accounting for the primary cancer type and 32.0% reporting annual household incomes of <$50,000. More than 94% of respondents indicated having emotional or practical concerns. Between one‐third and one‐half of the respondents sought help for their concerns and, of those, between one‐third and one‐half experienced difficulty finding help or did not obtain assistance. Significant trends across income categories indicated greater percentages of those in lower income categories experienced emotional and practical concerns, rated their concerns as 'big', sought help, and had difficulty finding help to address their concerns. Clearly adult cancer survivors experience emotional and practical concerns. Healthcare professionals have important roles monitoring these concerns and connecting those who desire help to relevant services. Opportunities should be given to individuals, regardless of income level, to indicate if they have concerns and if they would like assistance. [ABSTRACT FROM AUTHOR]

Objective: To estimate the economic burden of bladder cancer due to occupational exposures. Methods: Using a societal perspective, we estimate the lifetime costs of newly diagnosed cases of bladder cancer in Canada that is associated with occupational exposure for the calendar year 2011. The three major categories we consider are direct, indirect, and quality of life costs. Results: There were 199 newly identified cases of bladder cancer. The estimated total cost of bladder cancer for new cases in 2011 was $131 million and an average per-case cost of $658,055 CAD (2011 dollars). Of the total costs, direct costs accounted for 6%, indirect costs 29%, and health-related quality of life costs 65%. Conclusions: The per-case economic burden of bladder cancer due to occupational exposure is substantial which suggests the importance and value of exposure reduction. [ABSTRACT FROM AUTHOR]

Youth shifting to adult mental health services often report experiencing frustrations with accessing care that adequately replaces the youth services they had received. This systematic review assesses the peer reviewed evidence on services/programs aimed at addressing youth to adult transitions in mental health services. Findings suggest little data exists on the effectiveness of transition services/programs. While the available evidence supports meetings between youth and youth caseworkers prior to transitions occurring, it also verifies that this is not common practice. Other identified barriers to effective transitions were categorized as logistical (ineffective system communication), organizational (negative incentives), and related to clinical governance. [ABSTRACT FROM AUTHOR]

Websites are perceived as an additional communication space where public and private institutions and their stakeholders can interact and develop sustainable relationships. Although public relations scholars argue that both companies and consumers may benefit from virtual interactions, the growing online direct-to-consumer advertising and sale of health-related products has raised social and ethical concerns. Our study seeks to clarify the scope and nature of the virtual relationships that are specific to medical devices companies. Through a qualitative analysis of website, we show how four Canadian medical technology companies sought to enroll three types of stakeholders into their innovation development and commercialization strategies: investors, healthcare providers and patients. Our findings show that by reinforcing stereotypical relationships with investors, the websites maintain certain disconnect between the worlds of business and healthcare, and by creating proactive roles for healthcare providers and patients, they contribute to forge ethically convoluted relationships. [ABSTRACT FROM AUTHOR]

A20 is a NF-κB-dependent gene that has dual inflammatory and antiapoptotic functions in endothelial cells (EC). The function of A20 in smooth muscle cells (SMC) is unknown. We demonstrate that A20 is induced in SMC in response to inflammatory stimuli and serves an anti-inflammatory function via blockade of NF-κB and NF-κB-dependent proteins ICAM-1 and MCP-1. A20 inhibits SMC proliferation via increased expression of cyclin-dependent kinase inhibitors p21waf1 and p27kip1. Surprisingly, A20 sensitizes SMC to cytokine- and Fas-mediated apoptosis through a novel NO-dependent mechanism. In vivo, adenoviral delivery of A20 to medial rat carotid artery SMC after balloon angioplasty prevents neointimal hyperplasia by blocking SMC proliferation and accelerating re-endothelialization, without causing apoptosis. However, expression of A20 in established neointimal lesions leads to their regression through increased apoptosis. This is the first demonstration that A20 exerts two levels of control of vascular remodeling and healing. A20 prevents neointimal hyperplasia through combined antiinflammatory and antiproliferative functions in medial SMC. If SMC evade this first barrier and neointima is formed, A20 has a therapeutic potential by uniquely sensitizing neointimal SMC to apoptosis. A20-based therapies hold promise for the prevention and treatment of neointimal disease. [ABSTRACT FROM AUTHOR]

Background: To evaluate if there are departures from the WHO Child Growth Standards (WHO-CGS) in postnatal growth of healthy 'Canadian' children in Ontario up to age 2 years, including by infant feeding and ethnicity.Methods: We included data on 9964 healthy, singleton children born in Ontario, Canada. Smoothed weight, length and body mass index (BMI) percentile curves were generated using quantile regression for the Canadian cohort from birth to age 2 years. Differences in percentile values were calculated comparing Canadian children vs. the WHO-CGS.Results: Canadian children under age 2 years were longer than the WHO-CGS at the 10th (0.8 cm), 50th (1.3 cm) and 90th (1.9 cm) percentiles. Canadian children incrementally surpassed the WHO-CGS in weight after age 6 months, and in BMI after 9 months. By age 2 years, the 50th percentile weight of Canadian males was 823 g (95% confidence interval (CI) 680, 965) higher than the WHO-CGS 50th percentile. Weight differences were seen regardless of feeding practice, and were greatest among children of mothers born in Canada and Europe/Western nations, and least for those of East Asian/Pacific or South Asian heritage. Among Canadian breastfed males, 18% (95% CI 16, 19) of newborns and 26% (95% CI 20, 33) toddlers aged 2 years were classified by WHO-CGS as weighing >90th percentile - much higher than the expected rate of 10%. Similarities were seen for differences in BMI.Conclusions: Healthy Canadian infants/toddlers are longer and heavier than the WHO-CGS norms. Explanations for these discrepancies require further elucidation. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents—phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Methods: Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Results: Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). Discussion/Conclusions: Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. Systematic Review Registration: PROSPERO CRD-42016032945 [ABSTRACT FROM AUTHOR]

Abstract: A1/Bfl-1 is a NF-κB dependent, anti-apoptotic Bcl-2 family member that contains four Bcl-2 homology domains (BH) and an amphipathic C-terminal domain, and is expressed in endothelial cells (EC). Based on NF-κB reporter assays in bovine aortic EC, we have previously demonstrated that A1, like Bcl-2 and Bcl-xL, inhibits NF-κB activation. These results, however, do not fully translate when evaluating the cell's own NF-κB machinery in human EC overexpressing A1 by means of recombinant adenovirus (rAd.) mediated gene transfer. Indeed, overexpression of full-length A1 in human umbilical vein EC (HUVEC), and human dermal microvascular EC (HDMEC) failed to inhibit NF-κB activation. However, overexpression of a mutant lacking the C-terminal domain of A1 (A1ΔC) demonstrated a potent NF-κB inhibitory effect in these cells. Disparate effects of A1 and A1ΔC on NF-κB inhibition in human EC correlated with mitochondrial (A1) versus non-mitochondrial (A1ΔC) localization. In contrast, both full-length A1 and A1ΔC protected EC from staurosporine (STS)-induced cell death, indicating that mitochondrial localization was not necessary for A1's cytoprotective function in human EC. In conclusion, our data uncover a regulatory role for the C-terminal domain of A1 in human EC: anchoring A1 to the mitochondrion, which conserves but is not necessary for its cytoprotective function, or by its absence freeing A1 from the mitochondrion and uncovering an additional anti-inflammatory effect. [Copyright &y& Elsevier]

Abstract: Objective: Specific methodological challenges are often encountered during cancer-related economic evaluations. The objective of this study was to provide specific guidance to analysts on the methods for the conduct of high-quality economic evaluations in oncology by building on the Canadian Agency for Drugs and Technologies in Health Guidelines for the Economic Evaluation of Health Technologies (third edition). Methods: Fifteen oncologists, health economists, health services researchers, and decision makers from across Canada identified sections in Canadian Agency for Drugs and Technologies in Health guidelines that would benefit from oncology-specific guidance. Fifteen sections of the guidelines were reviewed to determine whether 1) Canadian Agency for Drugs and Technologies in Health guidelines were sufficient for the conduct of oncology economic evaluations without further guidance specific for oncology products or 2) additional guidance was necessary. A scoping review was conducted by using a comprehensive and replicable search to identify relevant literature to inform recommendations. Recommendations were reviewed by representatives of academia, government, and the pharmaceutical industry in an iterative and formal review of the recommendations. Results: Major adaptations for guidance related to time horizon, effectiveness, modeling, costs, and resources were required. Recommendations around the use of final outcomes over intermediate outcomes to calculate quality-adjusted life-years and life-years gained, the type of evidence, the source of evidence, and the use of time horizon and modeling were made. Conclusions: This article summarizes key recommendations for the conduct of economic evaluations in oncology and describes methods required to ensure that economic assessments in oncology are conducted in a standardized manner. [Copyright &y& Elsevier]

Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation. [ABSTRACT FROM AUTHOR]

The article determines the hospital mortality of patients with severe sepsis in a combination of teaching and community intensive care units in Canada. According to the authors, variables associated with mortality in multivariable analysis included age, acquisition location of severe sepsis, early and late intensive care unit, comorbidity, chronic renal failure, thrombocytopenia and metabolic acidosis. They add that these data confirm that sepsis has high mortality in general ICU populations.

Objective: In this article, we compared the costs of testing meconium for alcohol exposure in newborns with the lifetime benefits of early detection and intervention. Method: A decision analytic model was developed to assess the cost-effectiveness of testing meconium for two scenarios: (1) all infants in the Canadian province of Ontario and (2) infants who have an older sibling diagnosed with fetal alcohol spectrum disorder (FASD). The model incorporated the costs of early screening, early intervention, and the lifetime societal benefits of early intervention. Results: The cost of the meconium test is Can. $150. The lifetime societal cost of the disease is Can. $1.3 million per incident case. The benefit of early intervention is an improvement in literacy, which improves the quality of life parameter by 0.17 and increases adult lifetime earnings by $26,400 per year. The ratio of the incremental cost to the incremental benefits results in an incremental cost-effectiveness ratio for mandating a universal screen of all newborns in Ontario of $65,874 per quality-adjusted life years. When considering targeted screening, there is a cost savings for society and improvements in quality of life. Conclusions: Depending on society's willingness-to-pay threshold for improving infants' lives in a setting of considerable equity concerns, universal screening and targeted screening of infants who have an older sibling diagnosed with FASD both represent policies that are good value for the money. [ABSTRACT FROM AUTHOR]

Background: Apoptotic death of renal proximal tubular epithelial cells (RPTECs) is a feature of acute and chronic renal failure. RPTECs are directly damaged by ischemia, inflammatory, and cytotoxic mediators but also contribute to their own demise by up-regulating proinflammatory nuclear factor-kappaB (NF-kappaB)-dependent proteins. In endothelial cells, the Bcl family member A1 and the zinc finger protein A20 have redundant and dual antiapoptotic and anti-inflammatory effects. We studied the function(s) of A1 and A20 in human RPTECs in vitro. Methods: Expression of A1 [reverse transcription-polymerase chain reaction (RT-PCR) and A20 (Northern and Western blot analysis)] in RPTECs was evaluated. A1 and A20 were overexpressed in RPTECs by recombinant adenoviral-mediated gene transfer. Their effect upon inhibitor of NFkappaB alpha (IkappaBalpha) degradation (Western blot), NF-kappaB nuclear translocation [electrophoretic mobility shift assay (EMSA)], up-regulation of intercellular adhesion molecule-1 (ICAM-1) [fluorescence-activated cell sorter (FACS)] and monocyte chemoattractant protein-1 (MCP-1) (Northern blot) and apoptosis [terminal deoxynucleotiddyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)] and FACS analysis of DNA content) was determined. Results: A1 and A20 were induced in RPTECs as part of the physiologic response to tumor necrosis factor (TNF). A20, but not A1, inhibited TNF-induced NF-kappaB activation by preventing IkappaBalpha degradation, hence subsequent up-regulation of the proinflammatory molecules ICAM-1 and MCP-1. Unexpectedly, A20 did not protect RPTECs from TNF and Fas-mediated apoptosis while A1 protected against both stimuli. Coexpression of A1 and A20 in RPTECs achieved additive anti-inflammatory and antiapoptotic cytoprotection. Conclusion: A1 and A20 exert differential cytoprotective effects in RPTECs. A1 is antiapoptotic. A20 is anti-inflammatory via blockade of NF-kappaB. We propose that A1 and A20 are both required for optimal protection of RPTECs from apoptosis (A1) and inflammation (A20) in conditions leading to renal damage. [ABSTRACT FROM AUTHOR]