Mortality in Pharmacologically Treated Older Adults with Diabetes: The Cardiovascular Health Study, 1989–2001

BACKGROUND: Diabetes mellitus (DM) confers an increased risk of mortality in young and middle-aged individuals and in women. It is uncertain, however, whether excess DM mortality continues beyond age 75 years, is related to type of hypoglycemic therapy, and whether women continue to be disproportionately affected by DM into older age. METHODS AND FINDINGS: From the Cardiovascular Health Study, a prospective study of 5,888 adults, we examined 5,372 participants aged 65 y or above without DM (91.2%), 322 with DM treated with oral hypoglycemic agents (OHGAs) (5.5%), and 194 with DM treated with insulin (3.3%). Participants were followed (1989–2001) for total, cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD/noncancer mortality. Compared with non-DM participants, those treated with OHGAs or insulin had adjusted hazard ratios (HRs) for total mortality of 1.33 (95% confidence interval [CI], 1.10 to 1.62) and 2.04 (95% CI, 1.62 to 2.57); CVD mortality, 1.99 (95% CI, 1.54 to 2.57) and 2.16 (95% CI, 1.54 to 3.03); CHD mortality, 2.47 (95% CI, 1.89 to 3.24) and 2.75 (95% CI, 1.95 to 3.87); and infectious and renal mortality, 1.35 (95% CI, 0.70 to 2.59) and 6.55 (95% CI, 4.18 to 10.26), respectively. The interaction of age (65–74 y versus ≥75 y) with DM was not significant. Women treated with OHGAs had a similar HR for total mortality to men, but a higher HR when treated with insulin. CONCLUSIONS: DM mortality risk remains high among older adults in the current era of medical care. Mortality risk and type of mortality differ between OHGA and insulin treatment. Women treated with insulin therapy have an especially high mortality risk. Given the high absolute CVD mortality in older people, those with DM warrant aggressive CVD risk factor reduction

Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.

There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Possible photoactivated dermatitis with features of post-inflammatory pigmentary alteration (PIPA) and rosacea

Cutaneous flushing and facial erythema are common dermatologic conditions that elicit a wide differential diagnosis that includes rosacea, seborrheic dermatitis, photodermatitis, connective-tissue diseases, carcinoid syndrome, and mastocytosis. Herein we present an usual case of a mask-like rosacea-PIPA overlap that occurred in a patient with prior history of rectal carcinoid tumor and a negative systemic evaluation

Possible photoactivated dermatitis with features of post-inflammatory pigmentary alteration (PIPA) and rosacea

Cutaneous flushing and facial erythema are common dermatologic conditions that elicit a wide differential diagnosis that includes rosacea, seborrheic dermatitis, photodermatitis, connective-tissue diseases, carcinoid syndrome, and mastocytosis. Herein we present an usual case of a mask-like rosacea-PIPA overlap that occurred in a patient with prior history of rectal carcinoid tumor and a negative systemic evaluation

Prevalence and clinical correlates of aortic dilation in hypertrophic cardiomyopathy

BACKGROUND: Aortic dilation has been associated with various cardiac conditions, although its prevalence and clinical correlates in hypertrophic cardiomyopathy (HCM) remain unclear. OBJECTIVES: The purposes of this study were to define the prevalence of ascending aortic dilation in a large referral population of patients with HCM and to determine clinical and echocardiographic correlates of aortic dilation. METHODS: A total of 1,698 patients with HCM underwent echocardiographic measurement of the tubular ascending aorta (proximal and midlevel) during index evaluation at a tertiary HCM referral center. End-diastolic ascending aorta dimension was indexed to body surface area, with dilation defined for the tubular ascending aorta as 2 SD above the mean (\u3e19 mm/m2) and independently as greater than published age-, sex-, and body surface area- adjusted norms (for the sinus of Valsalva and midlevel). Aortic size and presence of aortic enlargement were correlated with clinical and echocardiographic parameters. RESULTS: Tubular ascending aortic dilation \u3e19 mm/m2 was present in 303 patients with HCM (18%), and dilation above adjusted norms was present in 210 patients with HCM (13%). The median indexed tubular ascending thoracic aortic dimension was 16.5 (interquartile range, 14.8-18.2) mm/m2. Indexed dimension increased linearly with age (R = 0.53, P \u3c .0001). Women and patients with a history of systemic hypertension were more likely to have tubular aortic enlargement \u3e19 mm/m2 (29.8% vs 9.9% and 24.1% vs 10.5%, respectively, P \u3c .0001 for both). Patients with obstructive physiology were more likely to have tubular aortic enlargement \u3e19 mm/m2 than those without resting or provocable obstruction (19.6% vs 14.4%, P = .007). Using adjusted norms, aortic enlargement was more frequent at the midlevel compared with the sinus of Valsalva (71% vs 29%), more common in patients with hypertension (15.4% vs 10.6%, P = .009), and more common in patients with paroxysmal atrial fibrillation (16.3% vs 11.5%, P = .036), but no other relationships remained statistically significant. CONCLUSIONS: In this large cohort of patients with HCM, aortic dilation was common. The key correlate of tubular aortic enlargement \u3e19 mm/m2, and aortic enlargement greater than adjusted norms included a history of systemic hypertension. Given an increased prevalence of aortic dilation in HCM, further study is needed on the clinical impact of aortic dilation