Longitudinal machine learning uncouples healthy aging factors from chronic disease risks.

To understand human longevity, inherent aging processes must be distinguished from known etiologies leading to age-related chronic diseases. Such deconvolution is difficult to achieve because it requires tracking patients throughout their entire lives. Here, we used machine learning to infer health trajectories over the entire adulthood age range using extrapolation from electronic medical records with partial longitudinal coverage. Using this approach, our model tracked the state of patients who were healthy and free from known chronic disease risk and distinguished individuals with higher or lower longevity potential using a multivariate score. We showed that the model and the markers it uses performed consistently on data from Israeli, British and US populations. For example, mildly low neutrophil counts and alkaline phosphatase levels serve as early indicators of healthy aging that are independent of risk for major chronic diseases. We characterize the heritability and genetic associations of our longevity score and demonstrate at least 1 year of extended lifespan for parents of high-scoring patients compared to matched controls. Longitudinal modeling of healthy individuals is thereby established as a tool for understanding healthy aging and longevity.

Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma.

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

Hospital Revisits Within 30 Days After Conventional and Robotically Assisted Hysterectomy.

OBJECTIVES: To compare the rates of hospital readmissions, emergency department, and outpatient clinic visits after discharge for robotically assisted (RA) versus nonrobotic hysterectomy in women age 30 or more with nonmalignant conditions. DATA SOURCES: Discharges for 2011 for 8 states (CA, FL, GA, IA, MO, NE, NY, TN) (>86,000 inpatient hysterectomies) were drawn from the statewide databases of the Healthcare Cost and Utilization Project. Data from 4 of these states were used to study revisits after 29,000 outpatient hysterectomies. METHODS: Matched pairs of patients were constructed with propensity scores derived from each patient's age group, severity of illness, insurance coverage, and type of procedure. Both the full set of revisits and a set limited to diagnoses for revisits judged in other research to be related to the initial surgery (about 70% of all revisits) were analyzed. The analyses were repeated with an instrumental variables regression design. KEY RESULTS: Using the propensity score matched pairs, revisits, and specifically readmissions, after inpatient hysterectomy were greater for RA versus non-RA patients (relative risk of readmission=124%, P<0.01). Similar results were found for readmissions after outpatient hysterectomy, and readmissions after inpatient hysterectomy for the restricted set of related revisits. In the method with instrumental variables, RA was associated with an increase of 32% in the likelihood of any revisit (P<0.01). CONCLUSIONS: Using 2 different methods to control for selection, this study found higher rates of revisits among women undergoing RA versus non-RA hysterectomy for benign conditions. While selection bias cannot be ruled out completely in an observational study, the study supports broader use of revisits for analyses of outcomes of hysterectomy.

Factors associated with adoption of robotic surgical technology in US hospitals and relationship to radical prostatectomy procedure volume.

OBJECTIVE: Robotic technology has diffused rapidly despite high costs and limited additive reimbursement by major payers. We aimed to identify the factors associated with hospitals' decisions to adopt robotic technology and the consequences of these decisions. METHODS: This observational study used data on hospitals and market areas from 2005 to 2009. Included were hospitals in census-based statistical areas within states in the State Inpatient Database that participated in the American Hospital Association annual surveys and performed radical prostatectomies. The likelihood that a hospital would acquire a robotic facility and the rates of radical prostatectomy relative to the prevalence of robots in geographic market areas were assessed using multivariable analysis. RESULTS: Hospitals in areas where a higher proportion of other hospitals had already acquired a robot were more likely to acquire one (P=0.012), as were those with more than 300 beds (P<0.0001) and teaching hospitals (P<0.0001). There was a significant association between years with a robot and the change in the number of radical prostatectomies (P<0.0001). More radical prostatectomies were performed in areas where the number of robots per 100,000 men was higher (P<0.0001). Adding a single robot per 100,000 men in an area was associated with a 30% increase in the rate of radical prostatectomies. CONCLUSIONS: Local area robot competition was associated with the rapid spread of robot technology in the United States. Significantly more radical prostatectomies were performed in hospitals with robots and in market areas of hospitals with robotic technology.

Hospital preparedness for possible nonconventional casualties: an Israeli experience.

Since 9/11, hospitals and health authorities have been preparing medical response in case of various mass terror attacks. The experience of Tel Aviv Sourasky Medical Center in treating suicide-bombing mass casualties served, in the time leading up to the war in Iraq, as a platform for launching a preparedness program for possible attacks with biological and chemical agents of mass destruction. Adapting Quarantelli's criteria on disaster mitigation to the "microinfrastructure" of the hospital, and including human behavior experts, we attempted to foster an interactive emergency management process that would deal with contingencies stemming from the potential hazards of chemical and biological (CB) weapons. The main objective of our work was to encourage an organization-wide communication network that could effectively address the contingent hazards unique to this unprecedented situation. A stratified assessment of needs, identification of unique dangers to first responders, and assignment of team-training sessions paved the way for program development. Empowerment through leadership and resilience training was introduced to emergency team leaders of all disciplines. Focal subject matters included proactive planning, problem-solving, informal horizontal and vertical communication, and coping through stress-management techniques. The outcome of this process was manifested in an "operation and people" orientation supporting a more effective and compatible emergency management. The aim of article is to describe this process and to point toward the need for a broad-spectrum view in such circumstances. Unlike military units, the civilian hospital staff at risk, expected to deal with CB casualties, requires adequate personal consideration to enable effective functioning. Issues remain to be addressed in the future. We believe that collaboration and sharing of knowledge, information, and expertise beyond the medical realm is imperative in assisting hospitals to expedite appropriate preparedness programs.

Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion.