The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) ...collaborate to provide annual updates on cancer occurrence and trends in the United States. This Annual Report highlights survival rates. Data were from the CDC- and NCI-funded population-based cancer registry programs and compiled by NAACCR. Trends in age-standardized incidence and death rates for all cancers combined and for the leading cancer types by sex were estimated by joinpoint analysis and expressed as annual percent change. We used relative survival ratios and adjusted relative risk of death after a diagnosis of cancer (hazard ratios HRs) using Cox regression model to examine changes or differences in survival over time and by sociodemographic factors.
Overall cancer death rates from 2010 to 2014 decreased by 1.8% (95% confidence interval CI = -1.8 to -1.8) per year in men, by 1.4% (95% CI = -1.4 to -1.3) per year in women, and by 1.6% (95% CI = -2.0 to -1.3) per year in children. Death rates decreased for 11 of the 16 most common cancer types in men and for 13 of the 18 most common cancer types in women, including lung, colorectal, female breast, and prostate, whereas death rates increased for liver (men and women), pancreas (men), brain (men), and uterine cancers. In contrast, overall incidence rates from 2009 to 2013 decreased by 2.3% (95% CI = -3.1 to -1.4) per year in men but stabilized in women. For several but not all cancer types, survival statistically significantly improved over time for both early and late-stage diseases. Between 1975 and 1977, and 2006 and 2012, for example, five-year relative survival for distant-stage disease statistically significantly increased from 18.7% (95% CI = 16.9% to 20.6%) to 33.6% (95% CI = 32.2% to 35.0%) for female breast cancer but not for liver cancer (from 1.1%, 95% CI = 0.3% to 2.9%, to 2.3%, 95% CI = 1.6% to 3.2%). Survival varied by race/ethnicity and state. For example, the adjusted relative risk of death for all cancers combined was 33% (HR = 1.33, 95% CI = 1.32 to 1.34) higher in non-Hispanic blacks and 51% (HR = 1.51, 95% CI = 1.46 to 1.56) higher in non-Hispanic American Indian/Alaska Native compared with non-Hispanic whites.
Cancer death rates continue to decrease in the United States. However, progress in reducing death rates and improving survival is limited for several cancer types, underscoring the need for intensified efforts to discover new strategies for prevention, early detection, and treatment and to apply proven preventive measures broadly and equitably.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown cause characterized by relentless scarring of the lung parenchyma leading to reduced quality of life and earlier ...mortality. IPF is an age-related disorder, and with the population aging worldwide, the economic burden of IPF is expected to steadily increase in the future. The mechanisms of fibrosis in IPF remain elusive, with favored concepts of disease pathogenesis involving recurrent microinjuries to a genetically predisposed alveolar epithelium, followed by an aberrant reparative response characterized by excessive collagen deposition. Pirfenidone and nintedanib are approved for treatment of IPF based on their ability to slow functional decline and disease progression; however, they do not offer a cure and are associated with tolerability issues. In this review, we critically discuss how cutting-edge research in disease pathogenesis may translate into identification of new therapeutic targets, thus facilitate drug discovery. There is a growing portfolio of treatment options for IPF. However, targeting the multitude of profibrotic cytokines and growth factors involved in disease pathogenesis may require a combination of therapeutic strategies with different mechanisms of action.
Fibrotic interstitial lung diseases (ILDs) are often challenging to diagnose and classify, but an accurate diagnosis has significant implications for both treatment and prognosis. A subset of ...patients with fibrotic ILD experience progressive deterioration in lung function, physical performance, and quality of life. Several risk factors for ILD progression have been reported, such as male sex, older age, lower baseline pulmonary function, and a radiological or pathological pattern of usual interstitial pneumonia. Morphological similarities, common underlying pathobiologic mechanisms, and the consistently progressive worsening of these patients support the concept of a progressive fibrosing (PF)-ILD phenotype that can be applied to a variety of ILD subtypes. The conventional approach has been to use antifibrotic medications in patients with idiopathic pulmonary fibrosis (IPF) and immunosuppressive medications in patients with other fibrotic ILD subtypes; however, recent clinical trials have suggested a favourable treatment response to antifibrotic therapy in a wider variety of fibrotic ILDs. This review summarizes the literature on the evaluation and management of patients with PF-ILD, and discusses questions relevant to applying recent clinicial trial findings to real-world practice.
Background The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated ...with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. Methods Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. Results Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (D lco ) % predicted were declining at a mean rate of 0.12% ( P < .001) and 0.10% ( P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in D lco of 4.2% ( P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% ( P = .103) and D lco increased by 3.9% ( P < .001). Conclusions Treatment with MMF or AZA is associated with improvements in D lco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.
Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease ...(CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different-yet largely unknown-mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.
Abstract Background Context Frailty is defined as a state of decreased reserve and susceptibility to stressors. The relationship between frailty and postoperative outcomes after degenerative spine ...surgery has not been studied. Purpose This study aimed to (1) determine prevalence of frailty in the degenerative spine population; (2) describe patient characteristics associated with frailty; and (3) determine the association between frailty and postoperative complications, mortality, length of stay, and discharge disposition. Study Design This is a retrospective analysis on a prospectively collected cohort from the National Surgical Quality Improvement Program (NSQIP). Patient Sample A total of 53,080 patients who underwent degenerative spine surgery between 2006 and 2012 were included in the study. Outcome Measures A modified frailty index (mFI) with 11 variables derived from the NSQIP dataset was used to determine prevalence of frailty and its correlation with a composite outcome of perioperative complications as well as hospital length of stay, mortality, and discharge disposition. Methods After calculating the mFI for each patient, the prevalence and predictors of frailty were determined for our cohort. The association of frailty with postoperative outcomes was determined after adjusting for known and suspected confounders using multivariate logistic regression. Results Frailty was present in 2,041 patients within the total population (4%) and in 8% of patients older than 65 years. Frailty severity increased with increasing age, male sex, African American race, higher body mass index, recent weight loss, paraplegia or quadriplegia, American Society of Anesthesiologists (ASA) score, and preadmission residence in a care facility. Frailty severity was an independent predictor of major complication (OR 1.15 for every 0.10 increase in mFI, 95%CI 1.09–1.21, p<.0005) and specifically predicted reoperation for postsurgical infection (OR 1.3, 95%CI 1.16–1.46, p<.0005). Prolonged length of stay and discharge to a new facility were also independently predicted by frailty severity (p<.0005). Frailty severity predicted 30-day mortality on unadjusted (OR 2.05, 95%CI 1.70–2.48, p<.0005) and adjusted analyses (OR 1.48, 95%CI 1.18–1.86, p<.0005). Conclusions Frailty is an important predictor of postoperative outcomes following degenerative spine surgery. Preoperative recognition of frailty may be useful for perioperative optimization, risk stratification, and patient counseling.
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