Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States,A Multiple Causes of Death Analysis

ABSTRACT

Chronic obstructive pulmonary disease (COPD) mortality based on the underlying cause of death (UCOD) underestimates disease burden. We aimed to determine the current COPD mortality rate, trends and the distribution of co-morbidities using United States (US) multiple-cause of death (MCOD) records.

All 38,905,575 death certificates of decedents aged ≥45 years in the United States were analyzed for 1999–2015. COPD was defined by ICD–10 codes J40–J44 and J47 based either on the UCOD or up to 20 contributing causes coded. Annual age–standardized COPD death rates were computed by age, gender and race/ethnicity for those with any mention of COPD.

In 2015, COPD was mentioned in 11.59% (292,572 deaths) in MCOD, compared to 11.13% (243,617 deaths) in 1999, a 4% increase. However, it was reported as the UCOD for only 5.56% and 4.97% in 2015 and 1999 respectively, an 11% increase. The most common UCOD in subjects with any mention of COPD was respiratory disorders in 49% of males and 55% of females. The relative change in death rates differed between MCOD and UCOD. For example, among non-Hispanic white females aged 65–74 years the UCOD rate per 100,000 (95% CI) decreased from 163 (160–166) to 147 (145–150), average annual percent decrease (AAPD) –0.26, while the MCOD rate decreased from 308 (304–311) to 263 (260–267), AAPD –0.87.

Statistics based on UCOD understated the burden of COPD in the United States. MCOD rates were twice as high as UCOD rates. The relative change in death percent or rates differed between MCOD and UCOD. MCOD analysis should be repeated periodically to help evaluate the burden of COPD-related mortality.     

Quantifying the relative importance to patients of avoiding symptoms and outcomes of heart failure

Objective: To evaluate heart failure (HF) patients’ disease knowledge and preferences for avoiding different disease outcomes.

Methods: An online survey was administered to 400 individuals with a self-reported diagnosis of HF to elicit relative importance weights (RIWs) for avoiding 11 potential HF symptoms and outcomes using best–worst scaling. The survey also included questions about individuals’ HF knowledge, and demographic and disease-experience characteristics. Differences in RIWs among sub-groups, defined by HF knowledge, caregiver support, age, recent hospitalization or emergency room visit for HF, health-related quality-of-life, and cardiac device experience were examined.

Results: Relative to limitations in usual activities (RIW 1.00), respondents preferred avoiding severe, infrequent cardiovascular events (e.g. stroke [RIW 8.51], heart transplant [RIW 7.84], or heart attack [RIW 5.3]) most, followed by difficulty breathing (RIW 2.55), inability to enjoy life (RIW 1.84), cardiac device implantation (RIW 1.74), and atrial fibrillation (RIW 1.57). Patients preferred avoiding swelling (RIW 0.47) and fatigue (RIW 0.58) least. RIWs for avoiding severe, infrequent events were higher among those with high disease knowledge, those without caregivers, and those without a recent hospitalization or emergency room visit.

Conclusions: Patients’ preferences for avoiding HF outcomes vary across outcomes and by individuals’ knowledge, caregiver status, and age. Healthcare providers should solicit and incorporate insights about patients’ knowledge of HF and their preferences for avoiding HF outcomes into HF education and management planning efforts.     

Relationship between menopausal hormone therapy and mortality after breast cancer The MARIEplus study,a prospective case cohort

Cohort studies of breast cancer (BC) patients, but not of disease‐free women at inclusion, have found menopausal hormone therapy (MHT) to be associated with decreased BC specific mortality (BCM). Here, the German population‐based MARIEplus BC cohort was analyzed to further elucidate associations of prediagnostic MHT with BCM (and modification by tumor characteristics), recurrence, and secondarily with other cause and overall mortality. Enrolled 2002–2005, incident invasive BC cases (N = 3,321) were followed up for a median of 6.1 years. Cox proportional hazards models adjusted for tumor characteristics, mammography and lifestyle were applied. Compared with never users of MHT, current users at date of diagnosis had significantly lower BCM (Hazard ratio (HR) 0.72, 95% CI 0.53–0.97) and risk of recurrence (HR 0.61, 95% CI 0.46–0.82). The MHT related reduced BCM was confined to patients with low grade tumors (HR 0.44, 95% CI 0.28–0.70; p_het = 0.01) and not modified by estrogen receptor or nodal status. BCM decreased with MHT duration in current and increased in past users (p_het = 0.015). Mortality due to causes other than BC and overall mortality were also reduced in current MHT users (HR 0.51, 95% CI 0.32–0.81, HR 0.66, 95% CI 0.52–0.86, respectively). Favorable tumor characteristics and mammographic surveillance could not fully explain associations of current MHT use with BCM and recurrence risk. Thus, the study contributes to the evidence that prediagnostic MHT does not have a negative impact on prognosis after BC. The restriction of a reduced BCM to low grade tumors should be confirmed in independent studies.     

Molecular basis of virulence in clinical isolates of Escherichia coli and Salmonella species from a tertiary hospital in the Eastern Cape, South Africa

Background

Apart from localized gastrointestinal infections, Escherichia coli and Salmonella species are major causes of systemic disease in both humans and animals. Salmonella spp. cause invasive infections such as enteric fever, septicemia, osteomyelitis and meningitis while certain types of E. coli can cause systemic infections, including pyelonephritis, meningitis and septicemia. These characteristic requires the involvement of a myriad of virulence factors.

Methods

This study investigated the virulence factors of Escherichia coli and Salmonella species in clinical specimens from patients with diarrhoea presenting to health care centres in Oliver R. Tambo District Municipality, Eastern Cape Province, Republic of South Africa. Microbiology analysis involved the use of cultural and molecular techniques.

Results

Out of a total of 315 samples screened, Salmonella isolates were obtained in 119 (37.8%) of cases and these comprised: S. choleraesuis (6%), S. enteritidis (4%), S. eppendorf (1%), S. hadar (1%), S. isangi (8%), S. panama (1%), S. typhi (52%), S. typhimurium (25%) and untyped Salmonella spp. (2%). Among the Salmonella species 87 (73.1%) were invasive. Using molecular diagnostic methods, diarrheagenic E. coli were detected in 90 cases (28.6%): the greater proportion of this were enteroaggregative E. coli (EAEC) 37 (41.1%), enteropathogenic E. coli (EPEC) 21 (23.3%) and enterohemorrhagic E. coli (EHEC) 21 (23.3%). The predominant virulence gene among the diarrheagenic E. coli was EAEC heat-stable enterotoxin astA genes while the virulence genes identified in the Salmonella strains were 15 (12.6%) flic and 105 (88.2%) inv genes. The amino acid identity of the representative genes showed 95-100% similarity to corresponding blast searched sequence.

Conclusions

This study showed the diversity of virulence gene expression in two major enteric pathogens. S. typhi and enteroaggregative E. coli were the predominant enteropathogens in our study area with an indication that EAEC is endemic within our study population. It was observed among other things that some diarrheagenic E. coli isolated from apparently asymptomatic subjects expressed some virulence genes at frequency as high as seen in diarrheagenic cases. This study underlines the importance of understanding the virulence composition and diversity of pathogens for enhanced clinico-epidemiological monitoring and health care delivery.     

Diagnostic Utility of Galectin-3 in Thyroid Cancer

Galectin-3 (Gal-3), which has received significant recent attention for its utility as a diagnostic marker for thyroid cancer, represents the most well-studied molecular candidate for thyroid cancer diagnosis. Gal-3 is a protein that binds to β-galactosidase residues on cell surface glycoproteins and has also been identified in the cytoplasmic and nuclear compartment. This marker has been implicated in regulation of normal cellular proliferation and apoptosis, as well as malignant transformation and the metastasis of cancer cells. We here present a mechanistic review of Gal-3 and its role in cancer development and progression. Gal-3 expression studies in thyroid tissue and cytologic tumor specimens and their methodological considerations are also discussed in this article. Despite great variance in their methodology, the majority of immunohistochemical studies found that Gal-3 was differentially expressed in thyroid carcinoma compared with benign and normal thyroid specimens, suggesting that Gal-3 is a good diagnostic marker for thyroid cancer. Recent studies have also demonstrated improved methodological reliability. On the other hand, Gal-3 genomic expression studies have shown inconsistent results for diagnostic utility and are not recommended. Overall, the development of Gal-3 as a diagnostic marker for thyroid cancer represents a promising avenue for future study, and its clinical application could significantly reduce the number of diagnostic thyroid operations performed for cases of indeterminant fine needle aspiration biopsy cytology, and thus positively impact the current management of thyroid nodular disease.Thyroid cancer represents one of the few cancer types that remains a diagnostic dilemma for the clinician. Thyroid nodules are extremely common in the general population, being identified in 5% of patients by palpation and 50% by ultrasound examination.¹ Fine needle aspiration biopsy (FNAB) represents the critical initial diagnostic test used for evaluation of thyroid nodules. However, diagnosis of thyroid cancer still remains uncertain in a large number of cases. In a review of more than 18,000 thyroid FNABs performed at the Mayo Clinic, FNAB had a reported sensitivity of 83%, specificity of 92%, and accuracy of 95%.² Furthermore, in up to 15% of cases, the diagnosis of cancer cannot be definitively determined by FNAB. This occurs in certain histological types of thyroid tumors in which benign and malignant thyroid lesions have overlapping cytomorphologic characteristics. There are also currently no patient or tumor characteristics that can reliably predict the presence of cancer in individuals diagnosed with a thyroid neoplasm of Hurthle cell or follicular subtype.^3,4Thus, when a thyroid tumor with this indeterminate cytology is identified by FNAB, the current recommended approach is a diagnostic operation for removal of either a portion of or the entire thyroid gland.^3,4,5 In addition to the emotional distress experienced by patients who undergo surgery for a possible cancer diagnosis, thyroid resection carries a low but significant risk of permanent injury to associated parathyroid glands and nerves that may lead to the need for life-long calcium supplementation or voice dysfunction, and extremely uncommonly the need for a long term tracheostomy. Indeed, only approximately one in five patients undergoing thyroid resection for indeterminant FNAB cytology will eventually be diagnosed with a thyroid cancer by histopathological evaluation.³Study of the molecular characteristics of thyroid cancer has allowed for the development of potential molecular diagnostic tools. In the largest thyroid cancer diagnostic marker panel study reported to date, we recently found Galectin-3 (Gal-3) to be the most accurate stand-alone marker for differentiated thyroid cancer diagnosis (DTC) when compared with a panel of 56 other molecular markers.⁶ The study used a tissue microarray containing 100 benign and 105 malignant thyroid tumors that was stained for expression of 57 markers. The most useful markers for DTC diagnosis were Gal-3, Cytokeratin 19, vascular endothelial growth factor, androgen receptor, p16, Aurora-A, and Hector Battifora mesothelial antigen-1 (HBME-1). Furthermore, the classification performance of Gal-3 alone (accuracy of 86.9%) was almost as good as the best multimarker panel (accuracy of 91.0%) determined by a Random Forests algorithm using marker combinations from the entire molecular marker panel.Gal-3 is one of the best studied molecular markers for thyroid cancer diagnosis. Numerous studies have elucidated the mechanistic role of Gal-3 in normal physiology and cancer. More than 60 protein expression studies, evaluating more than 6000 thyroid specimens, have been reported in the current literature that investigate the utilization of Gal-3 as a thyroid cancer diagnostic marker. The aim of this review is to present: (1) a mechanistic overview of Gal-3 in thyroid cancer, (2) an evaluation of Gal-3 expression studies with focus on a Gal-3 immunohistochemical (IHC) testing methodologies, and (3) an overview of studies reporting utilization of Gal-3 expression for thyroid cancer diagnosis.