https://journal.chestnet.org/article/S0012-3692(12)60129-9/pdf

Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60937-X.pdf

Maternal and child undernutrition and overweight in low-income and middle-income countries

The use of artificial intelligence, and the deep-learning subtype in particular, has been enabled by the use of labeled big data, along with markedly enhanced computing power and cloud storage, across all sectors. In medicine, this is beginning to have an impact at three levels: for clinicians, predominantly via rapid, accurate image interpretation; for health systems, by improving workflow and the potential for reducing medical errors; and for patients, by enabling them to process their own data to promote health. The current limitations, including bias, privacy and security, and lack of transparency, along with the future directions of these applications will be discussed in this article. Over time, marked improvements in accuracy, productivity, and workflow will likely be actualized, but whether that will be used to improve the patient-doctor relationship or facilitate its erosion remains to be seen.

High-performance medicine: the convergence of human and artificial intelligence

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

https://espace.library.uq.edu.au/view/UQ:284064/UQ284064_OA.pdf

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Hypertension is the leading cause of cardiovascular disease and premature death worldwide. Owing to the widespread use of antihypertensive medications, global mean blood pressure (BP) has remained constant or has decreased slightly over the past four decades. By contrast, the prevalence of hypertension has increased, especially in low- and middle-income countries (LMICs). Estimates suggest that 31.1% of adults (1.39 billion) worldwide had hypertension in 2010. The prevalence of hypertension among adults was higher in LMICs (31.5%, 1.04 billion people) than in high-income countries (28.5%, 349 million people). Variations in the levels of risk factors for hypertension, such as high sodium intake, low potassium intake, obesity, alcohol consumption, physical inactivity and unhealthy diet, may explain some of the regional heterogeneity in hypertension prevalence. Despite the increasing prevalence, the proportions of hypertension awareness, treatment and BP control are low, particularly in LMICs, and few comprehensive assessments of the economic impact of hypertension exist. Future studies are warranted to test implementation strategies for hypertension prevention and control, especially in low-income populations, and to accurately assess the prevalence and financial burden of hypertension worldwide. Hypertension is the leading global cause of cardiovascular disease and premature mortality. In this Review, the authors describe the prevalence, awareness, treatment and control of hypertension worldwide, as well as risk factors for hypertension and the financial burden of this disease.

The global epidemiology of hypertension.

Context.— Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke. Objective.— To estimate the risk of hemorrhagic stroke associated with aspirin treatment. Data Sources.— Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors’ reference files. Study Selection.— All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported. Data Extraction.— Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol. Data Synthesis.— Data from 16 trials with 55 462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10 000 persons (95% confidence interval [CI], 107-167;P,.001) and in ischemic stroke, a reduction of 39 events per 10 000 persons (95% CI, 17-61; P,.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10 000 persons (95% CI, 5-20; P,.001). This risk did not differ by participant or study design characteristics. Conclusions.— These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.

A Meta-analysis of Randomized Controlled Trials

▪Objective:To compare patient and graft survival of recipients of kidneys from living, unrelated donors (LUDs); cadaveric donors; and living, related donors (LRDs) matched for zero (mismat...

Kidney transplantation from living unrelated donors

We evaluated the long-term residual renal function in 64 living related kidney donors. Our main objective was to identify baseline factors, including gender and age, that could predict renal impairment after nephrectomy. Forty-four (69%) of the 64 donors were women. The mean +/- SEM age of those studied was 36 +/- 1.3 years and their mean +/- SEM duration of follow-up was 62 +/- 4.9 months (range, 6 to 174). Overall mean serum creatinine concentration after kidney donation was increased compared to baseline values (1.13 mg/dl vs 0.92 mg/dl, respectively, p < 0.001). At the last follow-up visit, post-nephrectomy mean glomerular filtration rate (GFR) values, adjusted for body surface area, age at donation, baseline serum creatinine and duration of follow-up, measured by 99mTc-DTPA were significantly lower in women than in men (72.11 ml/min vs 87.17 ml/min, respectively, p = 0.02). At follow-up, mean effective renal plasma flow, adjusted for the same variables, measured by 131I-hippuran was also significantly lower in women compared to men (318.07 ml/min vs 400.82 ml/min, respectively, p < 0.01). Eleven of twelve patients with post-nephrectomy GFR values less than 60 ml/min were women. Following nephrectomy, serum creatinine concentration increased significantly as a function of greater age at donation in women but not in men. Similarly, in women but not in men, follow-up GFR measurements decreased significantly as a function of age after adjusting for baseline serum creatinine and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Paul K. Whelton

Papers

A Meta-analysis of Randomized Controlled Trials

Kidney transplantation from living unrelated donors

Effect of age and gender on kidney function in renal transplant donors: a prospective study.