Why policymakers should care about “big data” in healthcare

The term “big data” has gotten increasing popular attention, and there is growing focus on how such data can be used to measure and improve health and healthcare. Analytic techniques for extracting information from these data have grown vastly more powerful, and they are now broadly available. But for these approaches to be most useful, large amounts of data must be available, and barriers to use should be low. We discuss how “smart cities” are beginning to invest in this area to improve the health of their populations; provide examples around model approaches for making large quantities of data available to researchers and clinicians among other stakeholders; discuss the current state of big data approaches to improve clinical care including specific examples, and then discuss some of the policy issues around and examples of successful regulatory approaches, including deidentification and privacy protection.     

C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo

OBJECTIVE: Elevated vascular plasminogen activator inhibitor-1 (PAI-1) levels are associated with atherosclerosis. In vitro, C-type natriuretic peptide (CNP) has anti-proliferative effects and inhibits the production of PAI-1 in cultured vascular cells. Whether CNP can affect PAI-1 in vivo, particularly in the setting of atherosclerosis, has not been reported. METHODS: Using the rabbit carotid arterial collar model of intimal hyperplasia (collar in place for 7 days), PAI-1 protein was compared in normal, vehicle (saline)-collared, and CNP-treated-collared arteries from the same animal. PAI-1 levels were measured by immunohistochemistry and densitometry and by Western blot. CNP was either infused into the peri-arterial space within one collar (10 fmol/h) or infused directly into the arterial lumen under one collar (100 pmol/h). In some rabbits (n=8), superoxide production in collared and normal artery segments was measured in vitro by chemiluminescence. RESULTS: PAI-1 was present throughout the vascular wall. Endothelial PAI-1 was elevated in saline-collared arteries (approximately 16%, P<0.05; n=7 rabbits) compared with normal carotid segments. The collar induced both a neointima that contained PAI-1 and the accumulation of macrophages in the adventitia. Peri-arterial CNP reduced PAI-1 (P<0.05) in the endothelium (33%), adventitia (47%) and neointima (39%), compared with levels in the contralateral, saline-collared carotid artery, while macrophage infiltration was reduced. Elevated superoxide production in collared arteries was not altered by chronic in vivo treatment with CNP (n=8). Peri-arterial CNP treatment did not reduce intimal thickening. Intra-luminal CNP (n=6) reduced endothelial, neointimal and total vessel (Western blot) PAI-1, macrophage accumulation, and intimal thickening (all P<0.05). CONCLUSIONS: CNP treatment of collared carotid arteries in vivo for 1 week suppressed endothelial and neointimal PAI-1, independently of intimal thickening. The CNP effects were not via superoxide. This is the first evidence that CNP inhibits activated PAI-1, in vivo.     

Vascular neutral endopeptidase inhibition improves endothelial function and reduces intimal hyperplasia

OBJECTIVE: Neutral endopeptidase (NEP, EC 3.4.24.11) metabolises endogenous vasoactive peptides that may protect against atherogenesis. Since NEP is found in the adventitia of arteries, we investigated the anti-atherogenic effects of chronic adventitial NEP inhibition. METHODS: Intimal hyperplasia of rabbit carotid arteries was induced by placement of soft, non-occlusive, peri-arterial silastic collars. NEP localisation was studied with autoradiography 7 and 14 days after collar placement. Vascular NEP was inhibited in vivo by local superfusion of one collared carotid artery with Candoxatrilat (50 pmol/h), for 7 days (n = 7). The contralateral collar was filled with saline vehicle. After 7 days, ring segments of collared and normal (proximal to the collar) arteries were obtained and in vitro functional measurements, immunohistochemical determination of the pro-atherogenic factor plasminogen activator inhibitor-1 (PAI-1), localization of macrophages and morphometric analyses were carried out. RESULTS: Vascular NEP radiolabelled substrate binding, mainly in the media, was increased by approximately 50% after 7 days (n = 5; p < 0.05) and by approximately 300% after 14 days of collar placement (n = 5; p < 0.05). Compared with normal artery segments from the same animal, vehicle-filled collared sections displayed significantly impaired vasorelaxation to acetylcholine (endothelium-independent vasodilatation was preserved), increased PAI-1 immunostaining, macrophage accumulation and intimal thickening. In Candoxatrilat-treated collared arteries, vasorelaxation to acetylcholine was improved, along with reductions in PAI-1 levels, macrophage numbers and intimal area (all p < 0.05). CONCLUSION: Enhancing the activity of local, endogenous peptides by adventitial inhibition of vascular NEP may protect against early atherogenesis. This is of particular relevance to using adventitial therapies to prevent intimal hyperplasia leading to restenosis.     

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

Summary

Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries.

Purpose

The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications.

Methods

Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year.

Results

Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was ?2.7 (SD 0.89; median ?2.7 [interquartile range, ?3.2, ?2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study.

Conclusions

POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care.     

Erlang could have told you so—A case study of health policy without maths

Little consideration is given to the operational reality of implementing national policy at local scale. Using a case study from Norway, we examine how simple mathematical models may offer powerful insights to policy makers when planning policies. Our case study refers to a national initiative requiring Norwegian municipalities to establish acute community beds (municipal acute units or MAUs) to avoid hospital admissions. We use Erlang loss queueing models to estimate the total number of MAU beds required nationally to achieve the original policy aim. We demonstrate the effect of unit size and patient demand on anticipated utilisation. The results of our model imply that both the average demand for beds and the current number of MAU beds would have to be increased by 34% to achieve the original policy goal of transferring 240 000 patient days to MAUs. Increasing average demand or bed capacity alone would be insufficient to reach the policy goal. Day-to-day variation and uncertainty in the numbers of patients arriving or leaving the system can profoundly affect health service delivery at the local level. Health policy makers need to account for these effects when estimating capacity implications of policy. We demonstrate how a simple, easily reproducible, mathematical model could assist policy makers in understanding the impact of national policy implemented at the local level.     

Paravalvular regurgitation one year after transcatheter aortic valve implantation

Objectives : The aim of this study was to assess the natural history of paravalvular regurgitation at 1 year in patients undergoing TAVI. Background : The immediate incidence of paravalvular regurgitation is estimated to be between 65 and 85% following transcatheter aortic valve implantation (TAVI). There is limited data as to whether this deteriorates during follow‐up. Methods : Forty‐six patients were recruited from a TAVI programme at our institute. All patients underwent an assessment of prosthetic valve function periprocedurally with aortography and immediately postprocedurally with transthoracic echocardiography. Twenty‐one patients with a median age was 83 (66–91) years of whom 14 were male reached 1 year follow‐up, 13 of whom were available for repeat transthoracic echocardiography. Results : The incidence of paravalvular regurgitation immediately following TAVI was 86%. Of them 57% had ≤ mild regurgitation and 29% had > mild regurgitation. At 1 year the incidence of paravalvular regurgitation was 77%. 54% had ≤ mild regurgitation and 34% > mild regurgitation. No patient had severe regurgitation. The degree of regurgitation reduced in 6 (46%), stayed the same in 3 (23%), and increased in 4 (31%) of patients. Conclusions : Patients undergoing TAVI have an immediate postprocedural risk of regurgitation of 86%. In the majority of cases the degree of paravalvular CoreValve® regurgitation is mild, and remains stable in 70% of patients during medium term follow‐up. © 2009 Wiley‐Liss, Inc.     

Application of HPLC and HPTLC for the simultaneous determination of tizanidine and rofecoxib in pharmaceutical dosage form

Two methods are described for the simultaneous determination of tizanidine and rofecoxib in binary mixture. The first method was based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 311 nm. The separation was carried out on Merck HPTLC aluminium sheets of silica gel 60 F254 using toluene:methanol:acetone (7.5:2.5:1.0, v/v/v) as mobile phase. The linear regression analysis data was used for the regression line in the range of 10-100 and 100-1500 ng/spot for tizanidine and rofecoxib, respectively. The second method was based on HPLC separation of the two drugs on the reversed phase kromasil column [C18 (5 microm, 25 cm x 4.6 mm, i.d.)] at ambient temperature using a mobile phase consisting of phosphate buffer pH 5.5 and methanol (45:55, v/v). Flow rate was 1.0 ml/min with an average operating pressure of 180 kg/cm2. Quantitation was achieved with UV detection at 235 nm based on peak area with linear calibration curves at concentration ranges 10-200 and 100-2000 microg/ml for tizanidine and rofecoxib, respectively. Both methods have been successively applied to pharmaceutical formulation. No chromatographic interference from the tablet excipients was found. Both methods were validated in terms of precision, robustness, recovery and limits of detection and quantitation. The analysis of variance (ANOVA) and Student's t-test were applied to correlate the results of tizanidine and rofecoxib determination in dosage form by means of HPTLC and HPLC method.     

Effect of prolonged therapy with neuroleptics on hepatic microsomal enzyme activity in schizophrenic patients

Gamma-glutamyl transpeptidase (GGT) is one of the hepatic microsomal enzymes and is now considered to be a reliable biochemical marker of enzyme induction.