Blood Biochemistry Analysis to Detect Smoking Status and Quantify Accelerated Aging in Smokers.

There is an association between smoking and cancer, cardiovascular disease and all-cause mortality. However, currently, there are no affordable and informative tests for assessing the effects of smoking on the rate of biological aging. In this study we demonstrate for the first time that smoking status can be predicted using blood biochemistry and cell count results andthe recent advances in artificial intelligence (AI). By employing age-prediction models developed using supervised deep learning techniques, we found that smokers exhibited higher aging rates than nonsmokers, regardless of their cholesterol ratios and fasting glucose levels. We further used those models to quantify the acceleration of biological aging due to tobacco use. Female smokers were predicted to be twice as old as their chronological age compared to nonsmokers, whereas male smokers were predicted to be one and a half times as old as their chronological age compared to nonsmokers. Our findings suggest that deep learning analysis of routine blood tests could complement or even replace the current error-prone method of self-reporting of smoking status and could be expanded to assess the effect of other lifestyle and environmental factors on aging.

Population Specific Biomarkers of Human Aging: A Big Data Study Using South Korean, Canadian, and Eastern European Patient Populations.

Accurate and physiologically meaningful biomarkers for human aging are key to assessing antiaging therapies. Given ethnic differences in health, diet, lifestyle, behavior, environmental exposures, and even average rate of biological aging, it stands to reason that aging clocks trained on datasets obtained from specific ethnic populations are more likely to account for these potential confounding factors, resulting in an enhanced capacity to predict chronological age and quantify biological age. Here, we present a deep learning-based hematological aging clock modeled using the large combined dataset of Canadian, South Korean, and Eastern European population blood samples that show increased predictive accuracy in individual populations compared to population specific hematologic aging clocks. The performance of models was also evaluated on publicly available samples of the American population from the National Health and Nutrition Examination Survey (NHANES). In addition, we explored the association between age predicted by both population specific and combined hematological clocks and all-cause mortality. Overall, this study suggests (a) the population specificity of aging patterns and (b) hematologic clocks predicts all-cause mortality. The proposed models were added to the freely-available Aging.AI system expanding the range of tools for analysis of human aging.

Effects of high-frequency chest wall oscillation on pleural pressure and oscillated flow.

The effectiveness of high-frequency chest wall oscillation (HF-CWO) is directly related to the level of oscillated flow (osc) in the airways. We used the Vest system to investigate the effects of HFCWO on chest wall and pleural pressures and we correlated these pressures to the resultant osc. We also compared the latest HFCWO device with it predecessor. Different combinations of vest inflation pressure (background pressure) and oscillation frequency were randomly applied to 10 healthy volunteers. Chest wall pressure was determined using an air-filled bag under the vest and pleural pressure was estimated using an esophageal balloon. Reverse plethysmography was used to measure osc at the mouth and a spirometer was used to measure changes in end-expired lung volume. We found a significant correlation between chest wall and pleural pressure with approximately one-third of the chest wall pressure transmitted into the pleural space. Mean esophageal pressure remained negative at all background pressure/frequency combinations. There was a significant correlation (p<0.0001) between the esophageal pulse pressure and osc, which was highest at 15Hz regardless of the background pressure. The end-expired lung volume correlated with mean chest wall pressure. There was no significant difference between the two Vest systems. Since osc dictates the effectiveness of HFCWO and since osc is dependent on esophageal pulse pressure, which in turn is dependent on chest wall pulse pressure, it follows that the effectiveness of HFCWO is influenced by the ability to generate an effective chest wall pulse pressure.

Approach to outpatient management of adult sleep apnea.

OBJECTIVE: To describe an approach to sleep apnea for family physicians based on a review of current practice limitations for Canadian family physicians, validated risk prediction tools, and ambulatory sleep apnea technologies. SOURCES OF INFORMATION: Published epidemiologic studies focused on family practice management of sleep apnea, clinical practice guidelines, risk prediction tools for sleep apnea, randomized controlled treatment trials, and the author's community practice audit. Evidence was levels I, II, and III. MAIN MESSAGE: Sleep apnea is commonly encountered in family practice, but many family physicians are unfamiliar with sleep medicine. The pretest probability of sleep apnea can be accurately predicted using any one of several simple risk prediction tools. Screening for other common sleep disorders is important, especially when the pretest probability of sleep apnea is low to intermediate; one-third of sleep apnea patients have additional sleep disorders. The use of home-based rather than laboratory-based diagnostic testing and treatment titration is controversial, but the former setting is often used when referral access is limited. CONCLUSION: There are several tools that allow family physicians to make accurate sleep apnea risk assessments. There is growing evidence to guide home- versus laboratory-based diagnosis and treatment of sleep apnea.

The pulse oxygen saturation: inspired oxygen pressure (SpO2:PIO2) diagram: application in the ambulatory assessment of pulmonary vascular disease.

BACKGROUND: The inspired oxygen to pulse saturation (SpO2:PIO2) curve mirrors the oxyhaemoglobin dissociation curve but is shifted to the right by the difference between inspired and alveolar oxygen fractions. Inspection of the curve has been used to discern changes in shunt. AIMS: We aimed to demonstrate the SpO2: PIO2 curve's quantification using readily available software, and its clinical utility in assessing ambulatory patients. METHODS: Six normal and seven hereditary haemorrhagic telangiectasia (HHT) clinic patients have been studied. After measuring barometric pressure, seated subjects were monitored with finger probe pulse oximetry while breathing increasing fractions of humidified oxygen through a Venturi mask until either their SpO2 or PIO2 was 100%. Resulting SpO2 and PIO2 values were plotted, fitted, assessed for goodness-of-fit and compared using the free, open source nonlinear regression extension package drc for the R programming language whose accuracy was also tested against two NIST reference sigmoidal curve datasets. RESULTS: All reference, individual and collected normal results were well fitted by the drc software with highly insignificant goodness-of-fit F tests. The laboratory normal curve was identically fitted by symmetrical Hill and asymmetrical Weibull functions. Although normal and negative HHT screening patient curves did not differ, there were significant differences between normal, pre-treatment (shunt fraction 9.44%), and post-treatment HHT curves. CONCLUSION: Nonlinear regression analysis of the SpO2:PIO2 curve permits valid, simple, safe, noninvasive, sensitive and cheap estimation of shunt in ambulatory patients.

Immunological diagnosis of cutaneous-pulmonary hypersensitivity vasculitis.

A 47-year-old woman had episodic dyspnoea, fatigue, chest radiograph opacifications, and palpable purpura whose biopsy showed leucocytoclastic vasculitis. Negative immunoglobulin A immunofluorescence staining and clinical exclusion of other disorders narrowed her diagnosis to cutaneous pulmonary hypersensitivity vasculitis.

Drotrecogin alpha (activated) in two patients with the hantavirus cardiopulmonary syndrome.

Hantavirus cardiopulmonary syndrome (HCPS) is associated with rapid cardiopulmonary collapse from endothelial injury, resulting in massive capillary leak, shock and severe hypoxemic respiratory failure. To date, treatment remains supportive and includes mechanical ventilation, vasopressors and extracorporeal membrane oxygenation, with mortality approaching 50%. Two HCPS survivors initially given drotrecogin alpha (activated) (DAA) for presumed bacterial septic shock are described. Vasoactive medications were required for a maximum of 52 h, whereas creatinine levels and platelet counts normalized within seven to nine days. Given the similar presentations of HCPS and bacterial septic shock, empirical DAA therapy will likely be initiated before a definitive diagnosis of HCPS is made. Further observations of DAA in HCPS seem warranted.

Improving adherence to a mechanical ventilation weaning protocol for critically ill adults: outcomes after an implementation program.

BACKGROUND: Despite multiple reminders, education sessions, and multidisciplinary team involvement, adherence to an evidence-based mechanical ventilation weaning protocol had been less than 1% in a general systems intensive care unit since implementation. OBJECTIVE: To assess the effectiveness of using an implementation program, the Model for Accelerating Improvement, to improve adherence and clinical outcomes after restarting a mechanical ventilation weaning protocol in an adult general systems intensive care unit. METHODS: A prospective comparative design, before and after implementation of the Model for Accelerating Improvement, was used with a consecutive sample of 129 patients and 112 multidisciplinary team members. Clinical outcomes were rate of unsuccessful extubations, rate of ventilator-associated pneumonia, and duration of mechanical ventilation; practice outcomes were staff's understanding of the mechanical ventilation weaning protocol, perceptions of the practice safety climate, and adherence to the weaning protocol. RESULTS: After the intervention, the rate of unsuccessful extubations decreased, and staff's understanding of and adherence to the weaning protocol increased significantly. The rate of ventilator-associated pneumonia, duration of mechanical ventilation, and staff's perceptions of the practice safety climate did not change significantly. CONCLUSION: Implementing the Model for Accelerating Improvement improved understanding of and adherence to protocol-directed weaning and reduced the rate of unsuccessful extubations.

Pharmacokinetics of rofecoxib: a specific cyclo-oxygenase-2 inhibitor.

Rofecoxib is a commonly used specific cyclo-oxygenase-2 (COX-2) inhibitor. Rofecoxib has high bioavailability, poor aqueous solubility, an elimination half-life suitable for daily administration and a volume of distribution approximating body mass. Species-specific, predominantly hepatic, metabolism occurs, with novel enterohepatic circulation in rats and O-glucuronidation by uridine diphosphate-glucuronosyl transferase (UGT) 2B7 and 2B15 in human liver microsomes. Discrepancies in studies of postoperative analgesia can be putatively explained by known pharmacokinetics. Changes in rofecoxib disposition and pharmacokinetics are evident between races, in elderly patients, in patients with chronic renal insufficiency and in patients with mild to moderate hepatic impairment. Despite the selective action of COX-2 inhibitors, there remains the potential for significant drug interactions. Rofecoxib has been shown to have interactions with rifampicin (rifampin), warfarin, lithium and angiotensin converting enzyme (ACE) inhibitors and theophylline. COX-2 inhibitors represent a major therapeutic advance in terms of gastrointestinal safety; however, long-term safety in other organ systems and with concomitant drug administration still remain to be proven.