A 31-day time to surgery compliant exercise training programme improves aerobic health in the elderly

Background: Over 41,000 people were diagnosed with colorectal cancer (CRC) in the UK in 2011. The incidence of CRC increases with age. Many elderly patients undergo surgery for CRC, the only curative treatment. Such patients are exposed to risks, which increase with age and reduced physical fitness. Endurance-based exercise training programmes can improve physical fitness, but such programmes do not comply with the UK, National Cancer Action Team 31-day time-to-treatment target. High-intensity interval training (HIT) can improve physical performance within 2–4 weeks, but few studies have shown HIT to be effective in elderly individuals, and those who do employ programmes longer than 31 days. Therefore, we investigated whether HIT could improve cardiorespiratory fitness in elderly volunteers, age-matched to a CRC population, within 31 days. Methods: This observational cohort study recruited 21 healthy elderly participants (8 male and 13 female; age 67 years (range 62–73 years)) who undertook cardiopulmonary exercise testing before and after completing 12 sessions of HIT within a 31-day period. Results: Peak oxygen consumption (VO2 peak) (23.9 ± 4.7 vs. 26.2 ± 5.4 ml/kg/min, p = 0.0014) and oxygen consumption at anaerobic threshold (17.86 ± 4.45 vs. 20.21 ± 4.11 ml/kg/min, p = 0.008) increased after HIT. Conclusions: It is possible to improve cardiorespiratory fitness in 31 days in individuals of comparable age to those presenting for CRC surgery

Evaluating short- and long-term impacts of a Medicaid “lock-in” program on opioid and benzodiazepine prescriptions dispensed to beneficiaries

Background Insurance-based “lock-in” programs (LIPs) have become a popular strategy to address controlled substance (CS) (e.g., opioid) misuse. However, little is known about their impacts. We examined changes in CS dispensing to beneficiaries in the 12-month North Carolina Medicaid LIP. Methods We analyzed Medicaid claims linked to Prescription Drug Monitoring Program (PDMP) records for beneficiaries enrolled in the LIP between October 2010 and September 2012 (n = 2702). Outcomes of interest were 1) number of dispensed CS prescriptions and 2) morphine milligram equivalents (MMEs) of dispensed opioids while a) locked-in and b) in the year following release. Results Compared to a period of stable CS dispensed prior to LIP enrollment, numbers of dispensed CS during lock-in and post-release were lower (count difference per person-month: −0.05 (95% CI: −0.11, 0.01); −0.23 (95% CI: −0.31, −0.15), respectively). However, beneficiaries’ average daily MMEs of opioids were elevated during both lock-in and post-release (daily mean difference per person: 18.7 (95% CI: 13.9, 23.6); 11.1 (95% CI: 5.1, 17.1), respectively). Stratification by payer source revealed increases in using non-Medicaid (e.g., out-of-pocket) payment during lock-in that persisted following release. Conclusion While the LIP reduced the number of CS dispensed, the program was also associated with increased acquisition of CS prescriptions using non-Medicaid payment. Moreover, beneficiaries acquired greater dosages of dispensed opioids from both Medicaid and non-Medicaid payment sources during lock-in and post-release. Refining LIPs to increase beneficiary access to substance use disorder screening and treatment services and provider use of PDMPs may address important unintended consequences

On Relativistic Material Reference Systems

This work closes certain gaps in the literature on material reference systems in general relativity. It is shown that perfect fluids are a special case of DeWitt's relativistic elastic media and that the velocity--potential formalism for perfect fluids can be interpreted as describing a perfect fluid coupled to a fleet of clocks. A Hamiltonian analysis of the elastic media with clocks is carried out and the constraints that arise when the system is coupled to gravity are studied. When the Hamiltonian constraint is resolved with respect to the clock momentum, the resulting true Hamiltonian is found to be a functional only of the gravitational variables. The true Hamiltonian is explicitly displayed when the medium is dust, and is shown to depend on the detailed construction of the clocks.Comment: 18 pages, ReVTe

Evidence of heterogeneity in statin-associated type 2 diabetes mellitus risk: A meta-analysis of randomized controlled trials and observational studies

Aims: To conduct a meta-analysis of statin-associated type 2 diabetes mellitus (T2D) risk among randomized controlled trials (RCTs) and observational studies (OBSs), excluding studies conducted among secondary prevention populations. Methods: Studies were identified by searching PubMed (1994-present) and EMBASE (1994-present). Articles had to meet the following criteria: (1) follow-up >one year; (2) >50% of participants free of clinically diagnosed ASCVD; (3) adult participants ≥30 years old; (4) reported statin-associated T2D effect estimates; and (5) quantified precision using 95% confidence interval. Data were pooled using random-effects model. Results: We identified 23 studies (35% RCTs) of n = 4,012,555 participants. OBS participants were on average younger (mean difference = 6.2 years) and had lower mean low-density lipoprotein cholesterol (LDL-C, mean difference = 20.6 mg/dL) and mean fasting plasma glucose (mean difference = 5.2 mg/dL) compared to RCT participants. There was little evidence for publication bias (P > 0.1). However, evidence of heterogeneity was observed overall and among OBSs and RCTs (P Cochran = <0.05). OBS designs, younger baseline mean ages, lower LDL-C concentrations, and high proportions of never or former smokers were significantly associated with increased statin-associated T2D risk. Conclusions: Potentially elevated statin-associated T2D risk in younger populations with lower LDL-C merits further investigation in light of evolving statin guidelines targeting primary prevention populations

Validation of a 5-Year Mortality Prediction Model among U.S. Medicare Beneficiaries

BACKGROUND/OBJECTIVES: A claims-based model predicting 5-year mortality (Lund-Lewis) was developed in a 2008 cohort of North Carolina (NC) Medicare beneficiaries and included indicators of comorbid conditions, frailty, disability, and functional impairment. The objective of this study was to validate the Lund-Lewis model externally within a nationwide sample of Medicare beneficiaries. DESIGN: Retrospective validation study. SETTING: U.S. Medicare population. PARTICIPANTS: From a random sample of Medicare beneficiaries, we created four annual cohorts from 2008 to 2011 of individuals aged 66 and older with an office visit in that year. The annual cohorts ranged from 1.13 to 1.18 million beneficiaries. MEASUREMENTS: The outcome was 5-year all-cause mortality. We assessed clinical indicators in the 12 months before the qualifying office visit and estimated predicted 5-year mortality for each beneficiary in the nationwide sample by applying estimates derived in the original NC cohort. Model performance was assessed by quantifying discrimination, calibration, and reclassification metrics compared with a model fit on a comorbidity score. RESULTS: Across the annual cohorts, 5-year mortality ranged from 24.4% to 25.5%. The model had strong discrimination (C-statistics ranged across cohorts from.823 to.826). Reclassification measures showed improvement over a comorbidity score model for beneficiaries who died but reduced performance among beneficiaries who survived. The calibration slope ranged from.83 to.86; the model generally predicted a higher risk than observed. CONCLUSION: The Lund-Lewis model showed strong and consistent discrimination in a national U.S. Medicare sample, although calibration indicated slight overfitting. Future work should investigate methods for improving model calibration and evaluating performance within specific disease settings

Development and validation of a 5-year mortality prediction model using regularized regression and Medicare data

Purpose: De-implementation of low-value services among patients with limited life expectancy is challenging. Robust mortality prediction models using routinely collected health care data can enhance health care stakeholders' ability to identify populations with limited life expectancy. We developed and validated a claims-based prediction model for 5-year mortality using regularized regression methods. Methods: Medicare beneficiaries age 66 or older with an office visit and at least 12 months of pre-visit continuous Medicare A/B enrollment were identified in 2008. Five-year mortality was assessed through 2013. Secondary outcomes included 30-, 90-, and 180-day and 1-year mortality. Claims-based predictors, including comorbidities and indicators of disability, frailty, and functional impairment, were selected using regularized logistic regression, applying the least absolute shrinkage and selection operator (LASSO) in a random 80% training sample. Model performance was assessed and compared with the Gagne comorbidity score in the 20% validation sample. Results: Overall, 183 204 (24%) individuals died. In addition to demographics, 161 indicators of comorbidity and function were included in the final model. In the validation sample, the c-statistic was 0.825 (0.823-0.828). Median-predicted probability of 5-year mortality was 14%; almost 4% of the cohort had a predicted probability greater than 80%. Compared with the Gagne score, the LASSO model led to improved 5-year mortality classification (net reclassification index = 9.9%; integrated discrimination index = 5.2%). Conclusions: Our claims-based model predicting 5-year mortality showed excellent discrimination and calibration, similar to the Gagne score model, but resulted in improved mortality classification. Regularized regression is a feasible approach for developing prediction tools that could enhance health care research and evaluation of care quality

Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study

Background Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. Methods and findings Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40–75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11–1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13–28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26–2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72–0.94). In addition, females (LHH range: 1.74–2.40) and adults aged 40–50 years (LHH range: 1.00–1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55–3.00) and adults aged 70–75 years (LHH range: 3.95–3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs < 1 for females and adults aged 40–50 years. This study’s primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed

Uncertainty on radiation doses estimated by biological and retrospective physical methods

Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the ‘EURADOS Working Group 10— Retrospective dosimetry’ members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios

Geriatric oncology health services research: Cancer and Aging Research Group infrastructure core

Founded by the late Dr. Arti Hurria, the Cancer and Aging Research Group (CARG) is a collaborative, interdisciplinary team of investigators dedicated to improving the care of older adults with cancer through research, advocacy, and other scholarly initiatives.1 As part of the CARG National Institute on Aging R21/R33 infrastructure grant to harness the available expertise and prioritize the development of high-impact research, the Health Services Research (HSR) Core was developed to foster and advance HSR in geriatric oncology. The mission of the HSR Core is to support clinical investigators to design and conduct highquality HSR focused on older adults with cancer and their caregivers including patterns of care, comparative effectiveness, and care delivery. At the first R21/R33 conference held at City of Hope in October 2018, Dr. Harvey Jay Cohen (Chair, CARG Oversight Board and HSR Core) led the development of this Core. In this perspective paper, we present a review of HSR in geriatric oncology to build a foundation for the Core rationale; proposed Core function, workflow, policies, and procedures; anticipated interactions with other CARG Cores; and proposed plans for sustainabilit

Topological Defects and CMB anisotropies : Are the predictions reliable ?

We consider a network of topological defects which can partly decay into neutrinos, photons, baryons, or Cold Dark Matter. We find that the degree-scale amplitude of the cosmic microwave background (CMB) anisotropies as well as the shape of the matter power spectrum can be considerably modified when such a decay is taken into account. We conclude that present predictions concerning structure formation by defects might be unreliable.Comment: 14 pages, accepted for publication in PR