Evaluation of weight change and cardiometabolic risk factors in a real-world population of US adults with overweight or obesity.

Whether individuals in real-world settings are able to lose weight and improve cardiometabolic risk factors over time is unclear. We aimed to determine the management of and degree of body weight change over 2 years among individuals with overweight or obesity, and to assess associated changes in cardiometabolic risk factors and clinical outcomes. Using data from 11 large health systems within the Patient-Centered Outcomes Research Network in the U.S., we collected the following data on adults with a recorded BMI ≥25 kg/m2 between January 1, 2016 and December 31, 2016: body-mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), triglycerides and glycated hemoglobin (HbA1c). We found that among 882,712 individuals with BMI ≥25 kg/m2 (median age 59 years; 56% female), 52% maintained stable weight over 2 years and 1.3% utilized weight loss pharmacotherapy. Weight loss of 10% was associated with small but significant lowering of mean SBP (-2.69 mmHg [95% CI -2.88, -2.50]), DBP (-1.26 mmHg [95% CI -1.35, -1.18]), LDL-C (-2.60 mg/dL [95% CI -3.14, -2.05]), and HbA1c (-0.27% [95% CI -0.35, -0.19]) in the same 12 months. However, these changes were not sustained over the following year. In this study of adults with BMI ≥25 kg/m2, the majority had stable weight over 2 years, pharmacotherapies for weight loss were under-used, and small changes in cardiometabolic risk factors with weight loss were not sustained, possibly due to failure to maintain weight loss.

Systematic review of studies investigating ventilator associated pneumonia diagnostics in intensive care.

BACKGROUND: Ventilator-associated pneumonia (VAP) is an important diagnosis in critical care. VAP research is complicated by the lack of agreed diagnostic criteria and reference standard test criteria. Our aim was to review which reference standard tests are used to evaluate novel index tests for suspected VAP. METHODS: We conducted a comprehensive search using electronic databases and hand reference checks. The Cochrane Library, MEDLINE, CINHAL, EMBASE, and web of science were searched from 2008 until November 2018. All terms related to VAP diagnostics in the intensive treatment unit were used to conduct the search. We adopted a checklist from the critical appraisal skills programme checklist for diagnostic studies to assess the quality of the included studies. RESULTS: We identified 2441 records, of which 178 were selected for full-text review. Following methodological examination and quality assessment, 44 studies were included in narrative data synthesis. Thirty-two (72.7%) studies utilised a sole microbiological reference standard; the remaining 12 studies utilised a composite reference standard, nine of which included a mandatory microbiological criterion. Histopathological criteria were optional in four studies but mandatory in none. CONCLUSIONS: Nearly all reference standards for VAP used in diagnostic test research required some microbiological confirmation of infection, with BAL culture being the most common reference standard used.

Skeletal muscle capillary density is related to anaerobic threshold and claudication in peripheral artery disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. Exercise intolerance may result from reduced skeletal muscle capillary density and impaired muscle oxygen delivery. This cross-sectional study tested the hypothesis that capillary density is related to claudication times and anaerobic threshold (AT) in patients with PAD. A total of 37 patients with PAD and 29 control subjects performed cardiopulmonary exercise testing on a treadmill for AT and gastrocnemius muscle biopsies. Skeletal muscle capillary density was measured using immunofluorescence staining. PAD had decreased capillary density (278 ± 87 vs 331 ± 86 endothelial cells/mm2, p = 0.05), peak VO2 (15.7 ± 3.9 vs 24.3 ± 5.2 mL/kg/min, p ⩽ 0.001), and VO2 at AT (11.5 ± 2.6 vs 16.1 ± 2.8 mL/kg/min, p ⩽ 0.001) compared to control subjects. In patients with PAD, but not control subjects, capillary density was related to VO2 at AT (r = 0.343; p = 0.038), time to AT (r = 0.381; p = 0.020), and time after AT to test termination (r = 0.610; p ⩽ 0.001). Capillary density was also related to time to claudication (r = 0.332; p = 0.038) and time after claudication to test termination (r = 0.584; p ⩽ 0.001). In conclusion, relationships between capillary density, AT, and claudication symptoms indicate that, in PAD, exercise limitations are likely partially dependent on limited skeletal muscle capillary density and oxidative metabolism.

Missed opportunities: despite improvement in use of cardioprotective medications among patients with lower-extremity peripheral artery disease, underuse remains.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events and benefit from aggressive secondary prevention; however, changes in the use of cardioprotective medications after incident diagnosis of PAD have not been well described. METHODS AND RESULTS: We used Danish nationwide administrative registries (2000-2007) to identify 2 groups with incident PAD: PAD alone (n=34 160) and PAD with history of coronary artery disease (CAD) (n=9570). With the use of a comparator with incident CAD alone (n=154 183), we assessed temporal trends and comparative use of cardioprotective medications. Relative differences in medication use were examined by using multivariable logistic regression. Use of medications improved temporally among both groups: for PAD alone, any antiplatelet use increased from 29% to 59% from 2000 to 2007 (P<0.0001), whereas statin use increased 6-fold (9%-56%; P<0.0001). However, use of these therapies by 18 months after incident diagnosis for both PAD groups remained modest and lower in comparison with CAD alone (any antiplatelet, 53% versus 66%; statins, 40% versus 52%; angiotensin-converting enzyme inhibitors, 20% versus 29%). Relative to CAD alone, patients with PAD alone were less likely to use any antiplatelet (adjusted odds ratio, 0.50; 95% confidence interval, 0.49-0.52), statins (adjusted odds ratio, 0.50; 95% confidence interval, 0.48-0.52), or angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.53) by 18 months. CONCLUSIONS: Despite improvement in the use of cardioprotective medications over time, patients with PAD alone remain less likely than those with CAD alone to use these agents.

Patient Self-Testing of Kidney Function at Home, a Prospective Clinical Feasibility Study in Kidney Transplant Recipients.

Introduction: People with long-term health conditions often attend clinics for kidney function tests. The Self-Testing Own Kidneys (STOK) study assessed feasibility of kidney transplant recipients using hand-held devices to self-test kidney function at home and investigated agreement between home self-test and standard clinic test results. Methods: A prospective, observational, single-center, clinical feasibility study (TRN: ISRCTN68116915), with N = 15 stable kidney transplant recipients, investigated blood potassium and creatinine results agreement between index self-tests at home (patient self-testing of capillary blood, using Abbott i-STAT Alinity analyzers [i-STAT]) and reference tests in clinic (staff sampled venous blood, analyzed with laboratory Siemens Advia Chemistry XPT analyzer) using Bland-Altman and error grid analysis. Results: The mean within-patient difference between index and reference test in creatinine was 2.25 µmol/l (95% confidence interval [CI]: -12.13, 16.81 µmol/l) and in potassium was 0.66 mmol/l (95% CI: -1.47, 2.79 mmol/l). All creatinine pairs and 27 of 40 (67.5%) potassium pairs were judged clinically equivalent. Planned follow-up analysis suggests that biochemical variables associated with potassium measurement in capillary blood were predominant sources of paired test result differences. Paired patient and nurse i-STAT capillary blood test potassium results were not statistically significantly different. Conclusions: This small feasibility study observed that training selected patients to competently use hand-held devices to self-test kidney function at home is possible. Self-test creatinine results showed good analytical and clinical agreement with standard clinic test results. Self-test potassium results showed poorer agreement with standard clinic test results; however, patient self-use of i-STATs at home was not a statistically significant source of difference between paired potassium test results.

Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients.

OBJECTIVE: Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. The mechanism(s) by which exercise training improves functional capacity is not understood. This study tested the hypothesis that in PAD patients who undergo supervised exercise training, increases in capillary density (CD) in calf muscle take place before improvements in peak oxygen uptake (VO(2)). METHODS AND RESULTS: Thirty-five PAD patients were randomly assigned to 12 weeks of directly supervised or home-based exercise training. Peak VO(2) testing and gastrocnemius muscle biopsies were performed at baseline and after training. CD (endothelial cells/mm(2)) was measured using immunofluorescence staining. After 3 weeks of directly supervised training, patients had an increase in CD (216±66 versus 284±77, P<0.01) but no increase in peak VO(2). However, after 12 weeks, peak VO(2) increased (15.3±2.8 versus 16.8±3.8, P<0.01), whereas in muscle, CD remained increased over baseline, but there were no changes in markers of oxidative capacity. Within subjects, CD was related to peak VO(2) before and after directly supervised training. CONCLUSION: Changes in CD in ischemic muscle with training may modulate the response to training, and those changes precede the increase in VO(2).

Clinicians' Perspectives on Barriers and Facilitators for the Adoption of Non-Invasive Liver Tests for NAFLD: A Mixed-Method Study.

(1) Background: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and the limitations of liver biopsies, multiple non-invasive tests (NITs) have been developed to identify non-alcoholic fatty liver disease (NAFLD) patients at-risk of progression. The availability of these new NITs varies from country to country, and little is known about their implementation and adoption in routine clinical practice. This study aims to explore barriers and facilitators that influence the adoption of NAFLD NITs, from healthcare professionals' perspectives. (2) Methods: A cross-sectional study was performed using an exploratory mixed-methods approach. Twenty-seven clinicians from eight different countries with different specialties filled in our questionnaire. Of those, 16 participated in semi-structured interviews. Qualitative and quantitative data were collected and summarized using the recently published Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework for new medical technologies in healthcare organizations. (3) Results: Several factors were reported as influencing the uptake of NITs for NAFLD in clinical practice. Among those: insufficient awareness of tests; lack of practical guidelines and evidence for the performance of tests in appropriate patient populations and care settings; and absence of sufficient reimbursement systems were reported as the most important barriers. Other factors, most notably 'local champions', proper functional payment systems, and sufficient resources in academic hospitals, were indicated as important facilitating factors. (4) Conclusions: Clinicians see the adoption of NITs for NAFLD as a complex process that is modulated by several factors, such as robust evidence, practical guidelines, a proper payment system, and local champions. Future research could explore perspectives from other stakeholders on the adoption of NITs.

Cost Consequences for the NHS of Using a Two-Step Testing Method for the Detection of Clostridium difficile with a Point of Care, Polymerase Chain Reaction Test as the First Step.

Clostridium difficile infection (CDI) is a common healthcare-associated infection. Current practice for diagnosing CDI in the Newcastle upon Tyne Hospitals NHS Foundation Trust involves a three-step, laboratory testing strategy using glutamate dehydrogenase (GDH) enzyme immunoassay (EIA), followed by a polymerase chain reaction (PCR) test then a toxin EIA. However, a PCR point of care test (POCT) for the C. difficile tcdB gene for screening suspected CDI cases, may provide a more efficient way of facilitating an equally effective, two-step, testing strategy with a toxin EIA. This study evaluated the cost consequences of changing from the three-step to a two-step testing strategy. A cost-consequences model was developed to compare the costs and consequences of the two strategies. Uncertainties in the model inputs were investigated with one- and two-way sensitivity analysis. The two-step, POCT strategy was estimated to save £283,282 per 1000 hospitalized NHS patients with suspected infectious diarrhea. Sensitivity analysis indicated that the turnaround time for the POCT was the largest driver for cost savings. Providing the POCT has sufficiently high diagnostic accuracy for detecting C. difficile, the two-step, POCT strategy for CDI identification is likely to be cost saving for NHS hospitals with an offsite laboratory.

How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system. We highlight the importance of articulating the value propositions and documenting the care pathway. We provide guidance on how to conduct care pathway analysis as little has been published on this. We summarize the clinical, economic and qualitative studies to be considered for developing evidence, and provide useful links to relevant software, on-line applications, websites, and give practical advice. We also provide advice on patient and public involvement and engagement (PPIE), and on product management. Our aim is to help device manufacturers to understand the concepts and terminology used in evaluation of in vitro diagnostics (IVDs) so that they can communicate effectively with evaluation methodologists, statisticians, and health economists. Manufacturers of medical tests and devices can use the proposed framework to plan their evidence development strategy in alignment with device development, applications for regulatory approval, and publication.

Intraoperative Anesthesiology Management and Patient Outcomes for Surgical Revascularization for Moyamoya Disease: A Review and Clinical Experience.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular condition, often presenting as a headache or stroke in adults. Anesthetic management of this illness may challenge providers because it can affect the long-term neurologic outcome and hospital length of stay (LOS) in patients with MMD. MATERIALS AND METHODS: A literature search was conducted to assess etiology and epidemiology, as well as existing reports of intraoperative management of MMD. Due to sparse findings, the search was expanded to include studies of the use of intraoperative anesthetic agents during other neurosurgical procedures. We also retrospectively reviewed all MMD cases from January 1, 2009, to December 31, 2015, at Memorial Hermann Hospital-Texas Medical Center, where intraoperative management involved craniotomy and surgical revascularization. Data were collected primarily on the use of several anesthetic agents. The LOS and any adverse events were also recorded for each case. The data were divided into two equivalent case cohorts: (1) January 1, 2009, to February 18, 2013, and (2) February 19, 2013, to December 31, 2015. RESULTS: Remifentanil use notably increased between the first and second time periods while fentanyl use decreased. Desflurane usage also demonstrated an observed increase when our two cohorts were compared. Additionally, there was a decrease in the mean LOS between the first and second periods of 3.9 and 3.3 days, respectively. CONCLUSION: Increasing use of remifentanil in MMD cases could be attributed to its ability to provide more stable hemodynamics during induction, maintenance, and emergence of anesthesia when compared with fentanyl. Lower systolic pressures, diastolic pressures, and heart rates were reported in patients receiving remifentanil over fentanyl.

Antithrombotic therapy in peripheral artery disease: A review of the EUCLID trial results and current ongoing trials.

In addition to risk-factor modification, antithrombotic therapy is the hallmark of management to reduce cardiovascular ischemic events in patients with peripheral artery disease (PAD). Currently, the guidelines recommend long-term antiplatelet therapy with aspirin or clopidogrel in this patient population to reduce myocardial infarction, stroke, and vascular death. Past outcomes studies have shown some benefit of ticagrelor, another antiplatelet agent, as compared with clopidogrel in patients with coronary disease and concomitant PAD. However, most recently, the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial has shown no additional benefit of ticagrelor over clopidogrel. In this trial, a minority of patients had concomitant coronary artery disease, making it unique to previous studies. The EUCLID trial's evidence of neutrality between clopidogrel and ticagrelor sheds light into the complexity of studying the PAD population and the continued need to meticulously design trials to investigate the optimal therapies. The topics that will be discussed in this review include the role of antiplatelet therapy in the management of patients with PAD, a review of the EUCLID trial results and the important factors to be considered in interpreting the surprising results, and promising recent ongoing clinical trials assessing therapies in the treatment of patients with PAD.

Effects of a 12-Week mHealth Program on FunctionalCapacity and Physical Activity in Patients With PeripheralArtery Disease.

Supervised exercise is beneficial for peripheral artery disease (PAD) patients limited by intermittent claudication (IC). However, supervised exercise for PAD remains widely underutilized. Mobile health (mHealth) provides an intermediate solution between supervised and independent home-based exercise. The purpose of this study was to determine the effects on functional capacity and physical activity patterns of a 12-week mHealth program in PAD patients with IC. Twenty patients were randomized into usual care or a 12-week mHealth intervention consisting of patient education, smartphones, and physical activity trackers. Patient education was disseminated through smartphone and a daily exercise prescription was given based on steps per day. Primary outcomes were 12-week changes in peak VO2 and claudication onset time; and changes in physical activity measured by steps per/day and minutes of exercise per/week. mHealth patients significantly increased peak VO2 from 15.2 ± 4.3 to 18.0 ± 4.8 ml/kg/min (20.3 ± 26.4%; p ≤0.05), while usual care did not change from 14.3 ± 5.4 to 14.5 ± 5.7 ml/kg/min (1.0 ± 6.9%; NS). Comparison of these changes resulted in a significant difference between groups (p ≤0.05) for peak VO2. Claudication onset time significantly increased in mHealth (320 ± 226 to 525 ± 252 seconds; ≤ 0.05), while usual care demonstrated a worsening (252 ± 256 to 231 ± 196 seconds; NS). The comparison of these group changes resulted in a significant difference (p ≤0.05). Neither steps per day or minutes of activity reached significant differences between groups. In conclusion, a 12-week mHealth program in PAD patients with IC can improve peak VO2 and claudication onset time; and mHealth interventions represent a promising alternative therapy for those patients who cannot participate in supervised exercise.

The effect of the amount of blocking cue training on blocking of appetitive conditioning in mice.

Conditioning of a target cue is blocked when it occurs in compound with another cue (blocking cue) that has already received conditioning. Although blocking of appetitive conditioning is commonly used in rodents as a test of selective learning, it has been demonstrated rarely in mice. In order to investigate the conditions that result in blocking in mice two studies tested the effect of the extent of prior blocking cue training on blocking of appetitive conditioning. Mice received either 80 or 200 trials of blocking cue training prior to compound conditioning. A control group received only compound training. Experiment 1 assessed the ability of a visual cue to block conditioning to an auditory target cue. Exposure to the context and the unconditioned stimulus, sucrose pellets, was equated across groups. Blocking was evident in mice that received 200, but not 80 training trials with the visual blocking cue. Responding to the blocking cue was similar across groups. Experiment 2 assessed the ability of an auditory cue to block conditioning to a visual target cue. Blocking was evident in mice trained with 80 and 200 auditory blocking cue trials. The results demonstrate that the strength of blocking in mice is dependent on the modality and experience of the blocking cue. Furthermore, prolonged training of the blocking cue after asymptotic levels of conditioned responding have been reached is necessary for blocking to occur under certain conditions suggesting that the strength of conditioned responding is a limited measure of learning.

Peripheral artery disease is a coronary heart disease risk equivalent among both men and women: results from a nationwide study.

AIMS: Lower extremity peripheral artery disease (PAD) has been proposed as a 'coronary heart disease (CHD) risk equivalent'. We aimed to examine whether PAD confers similar risk for mortality as incident myocardial infarction (MI) and whether risk differs by gender. METHODS: Using nationwide Danish administrative registries (2000-2008), we identified patients aged ≥40 years with incident PAD (PAD only, n = 35,628), incident PAD with a history of MI (PAD + MI, n = 7029), and incident MI alone (MI alone, n = 71,115). RESULTS: Patients with PAD only tended to be younger, female, and have less comorbidity than the other groups. During follow up (median 1051 d, IQR 384-1938), we found that MI-alone patients had greater risk of adverse outcomes in the acute setting (first 90 d); however, the PAD-only and PAD + MI groups had higher long-term mortality at 7 years than those with MI alone (47.8 and 60.4 vs. 36.4%, respectively; p < 0.0001). After adjustment, the PAD-only and PAD + MI groups had a higher long-term risk for mortality [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.44-1.51; and HR 1.65, 95% CI 1.58-1.72, respectively], cardiovascular mortality (HR 1.30, 95% CI 1.26-1.34; and HR 1.71, 95% CI 1.62-1.80, respectively), and composite of death, MI, and ischaemic stroke, 95% CI HR, 1.38, 95% CI 1.36-1.42; and HR 1.68, 95% CI 1.61-1.75, respectively). The greater long-term risks of PAD were seen for both women and men. CONCLUSIONS: Both women and men with incident PAD have greater long-term risks of total and cardiovascular mortality vs. those with incident MI. PAD should be considered a CHD risk equivalent, warranting aggressive secondary prevention.

Growth factors for therapeutic angiogenesis in peripheral arterial disease.

PURPOSE OF REVIEW: Peripheral arterial disease is a common disease that has few treatment options. Angiogenesis is defined as the growth of new blood vessels from preexisting vasculature. Therapeutic angiogenesis is an investigational method that uses vascular growth to alleviate disorders of tissue ischemia, such as coronary artery disease and peripheral arterial disease. There have been tremendous changes in the field of therapeutic angiogenesis over the past decade, and there is much promise for the future. RECENT FINDINGS: Initial preclinical work with cytokine growth factor delivery resulted in a great deal of enthusiasm, but larger clinical studies have failed to achieve similar success. With an increased understanding of the complex mechanisms involved in angiogenesis, gene therapy and cell therapy have moved to the forefront of therapeutic angiogenesis. Novel therapies which target multiple different angiogenic pathways are also being developed and tested. SUMMARY: Therapeutic angiogenesis is an exciting field that continues to evolve. This review will focus on the different growth factors being used, their routes of delivery, the results of clinical trials, and some of the novel therapies being developed.