With the introduction of Part D drug benefits, Medicare collects information on diagnoses, treatments, and clinical events for millions of beneficiaries. These data are a promising resource for comparative effectiveness research (CER) on treatments, benefit designs, and delivery systems.
We explore the data available for researchers and approaches that could be used to enhance the value of Medicare data for CER.
Challenges and Opportunities
Using currently available Medicare data for CER is challenging; as with all administrative data, it is not possible to capture every factor that contributes to prescribing decisions and patients are not randomly assigned to treatments. In addition, Part D plan selection and switching may influence treatment decisions and contribute to selection bias. Exploiting certain program aspects can help address these limitations. For example, ongoing changes in Medicare or plan policies, and the random assignment of beneficiaries who receive Part D low income subsidies into plans with different formularies could yield natural experiments.
Refining policies around time to data release, provision of additional data elements, and linkage with greater beneficiary-level information would improve the value and usability of these data. Improving the transparency and reproduceability of findings, and potential open access to qualified stakeholders are also important policy considerations. Work is needed to reconcile data needs with current policies and goals.
Medicare data provides a rich resource for CER. Leveraging existing program elements combined with some administrative changes in data availability could create large datasets for evaluating treatment patterns, spending, and coverage decisions.
Comparative effectiveness research; Medicare; prescription drugs
Physicians can receive federal payments for meaningful use of complete certified electronic health records (EHRs). Evidence is limited on how EHR use affects clinical care and outcomes.
To examine the association between use of a commercially available certified EHR and clinical care processes and disease control in patients with diabetes.
Quasi-experimental design with outpatient EHR implementation sequentially across 17 medical centers. Multivariate analyses adjusted for patient characteristics, medical center, time trends, and patient-level clustering.
Kaiser Permanente Northern California, an integrated delivery system.
169 711 patients with diabetes mellitus.
Use of a commercially available certified EHR.
Drug treatment intensification and hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol (LDL-C) testing and values.
Use of an EHR was associated with statistically significant improvements in treatment intensification after HbA1c values of 9% or greater (odds ratio, 1.10 [95% CI, 1.06 to 1.14]) or LDL-C values of 2.6 to 3.3 mmol/L (100 to 129 mg/dL) (odds ratio, 1.06 [CI, 1.03 to 1.09]); increases in 365-day retesting for HbA1c and LDL-C levels among all patients, with the most dramatic change among patients with the worst disease control (HbA1c ≥9% or LDL-C ≥3.4 mmol/L [ ≥130 mg/dL]); and decreased 90-day retesting among patients with HbA1c level less than 7% or LDL-C level less than 2.6 mmol/L (<100 mg/dL). The EHR was also associated with statistically significant reductions in HbA1c and LDL-C levels, with the largest reductions among patients with the worst control (0.06-mmol/L [2.19-mg/dL] reduction among patients with baseline LDL-C ≥3.4 mmol/L [ ≥130 mg/dL]; P < 0.001).
The EHR was implemented in a setting with strong baseline performance on cardiovascular care quality measures.
Use of a commercially available, certified EHR was associated with improved drug treatment intensification, monitoring, and physiologic control among patients with diabetes, with greater improvements among patients with worse control and less testing in patients already meeting guideline-recommended glycemic and lipid targets.
Primary Funding Source
National Institute of Diabetes and Digestive and Kidney Diseases.
Researchers have long noted an excess of patients with schizophrenia were born during the months of January and March. This winter birth effect has been hypothesized to result either from various causes such as vitamin D deficiency (McGrath, 1999; McGrath et al., 2010), or from maternal infection during pregnancy. Infection with a number of viruses during pregnancy including influenza, and rubella are known to increase the risk of schizophrenia in the offspring (Brown, 2006). Animal models using influenza virus or PolyI:C, a viral mimic, have been able to replicate many of the brain morphological, genetic, and behavioral deficits of schizophrenia (Meyer et al., 2006, 2008a, 2009; Bitanihirwe et al. 2010; Meyer and Feldon, 2010; Short et al., 2010). Using a murine model of prenatal viral infection, our laboratory has shown that viral infection on embryonic days 9, 16, and 18 leads to abnormal expression of brain genes and brain structural abnormalities in the exposed offspring (Fatemi et al., 2005, 2008a,b, 2009a,b). The purpose of the current study was to examine gene expression and morphological changes in the placenta, hippocampus, and prefrontal cortex as a result of viral infection on embryonic day 7 of pregnancy. Pregnant mice were either infected with influenza virus [A/WSN/33 strain (H1N1)] or sham-infected with vehicle solution. At E16, placentas were harvested and prepared for either microarray analysis or for light microscopy. We observed significant, upregulation of 77 genes and significant downregulation of 93 genes in placentas. In brains of exposed offspring following E7 infection, there were changes in gene expression in prefrontal cortex (6 upregulated and 24 downregulated at P0; 5 upregulated and 14 downregulated at P56) and hippocampus (4 upregulated and 6 downregulated at P0; 6 upregulated and 13 downregulated at P56). QRT-PCR verified the direction and magnitude of change for a number of genes associated with hypoxia, inflammation, schizophrenia, and autism. Placentas from infected mice showed a number of morphological abnormalities including presence of thrombi and increased presence of immune cells. Additionally, we searched for presence of H1N1 viral-specific genes for M1/M2, NA, and NS1 in placentas of infected mice and brains of exposed offspring and found none. Our results demonstrate that prenatal viral infection disrupts structure and gene expression of the placenta, hippocampus, and prefrontal cortex potentially explaining deleterious effects in the exposed offspring without evidence for presence of viral RNAs in the target tissues.
placenta; influenza; brain; microarray; schizophrenia; viral genes
Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA) drugs. Therefore, discovery of new agents for treating multiple drug-resistant (MDR) influenza virus infections is important. Here, we propose a parallel screening strategy that simultaneously screens wild-type (WT) and MDR NAs, and identifies inhibitors matching the subsite characteristics of both NA-binding sites. These may maintain their potency when drug-resistant mutations arise. Initially, we analyzed the subsite of the dual H275Y/I223R NA mutant. Analysis of the site-moiety maps of NA protein structures show that the mutant subsite has a relatively small volume and is highly polar compared with the WT subsite. Moreover, the mutant subsite has a high preference for forming hydrogen-bonding interactions with polar moieties. These changes may drive multidrug resistance. Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye), which inhibited WT NA and MDR NA with IC50 values of 3.4 and 4.5 µM, respectively. RB19 comprises a rigid core scaffold and a flexible chain with a large polar moiety. The former interacts with highly conserved residues, decreasing the probability of resistance. The latter forms van der Waals contacts with the WT subsite and yields hydrogen bonds with the mutant subsite by switching the orientation of its flexible side chain. Both scaffolds of RB19 are good starting points for lead optimization. The results reveal a parallel screening strategy for identifying resistance mechanisms and discovering anti-resistance neuraminidase inhibitors. We believe that this strategy may be applied to other diseases with high mutation rates, such as cancer and human immunodeficiency virus type 1.
Small synthetic compounds have been implicated in treatment of human cancers. We have synthesized a small compound, BPR1K0609S1 (hereafter, BP), which inhibits Aurora-A kinase. In the present study, we studied the mechanism of BP suppression of tumorigenesis induced by Aurora-A. Given our previous results that inactivation of p53 accelerates MMTV-Aurora-A-mediated tumorigenesis in vivo, we studied the roles of p53 pathway using the isogenic human colon carcinoma cell lines of HCT116, in which p53, Puma, Bax, p21 or Chk2 is deleted. When these isogenic cell lines are treated with BP for 48 h, accumulation of G2M phase and aneuploidy are commonly observed, and HCT116 p21(-) cells show increase in apoptosis. In xenograft assay, s.c. injection of BP efficiently inhibits tumorigenesis of HCT116 deficient for Chk2 or p21. Re-transplantation of BP-resistant tumors indicates that these resistant cells do not acquire advanced tumor growth. Significantly, 5-FU (5-fluorouracil) treatment further induces apoptosis of BP-resistant HCT116 deficient for Chk2 or Puma. These results demonstrate that p21 deficiency enhances BP-mediated suppression of tumor growth, and that BP and 5-FU can collaborate for tumor regression.
Aurora-A; kinase inhibitors; mice xenograft; cell cycle; apoptosis
One goal of computational anatomy (CA) is to develop tools to accurately segment brain structures in healthy and diseased subjects. In this paper, we examine the performance and complexity of such segmentation in the framework of the large deformation diffeomorphic metric mapping (LDDMM) registration method with reference to atlases and parameters. First we report the application of a multi-atlas segmentation approach to define basal ganglia structures in healthy and diseased kids' brains. The segmentation accuracy of the multi-atlas approach is compared with the single atlas LDDMM implementation and two state-of-the-art segmentation algorithms—Freesurfer and FSL—by computing the overlap errors between automatic and manual segmentations of the six basal ganglia nuclei in healthy subjects as well as subjects with diseases including ADHD and Autism. The high accuracy of multi-atlas segmentation is obtained at the cost of increasing the computational complexity because of the calculations necessary between the atlases and a subject. Second, we examine the effect of parameters on total LDDMM computation time and segmentation accuracy for basal ganglia structures. Single atlas LDDMM method is used to automatically segment the structures in a population of 16 subjects using different sets of parameters. The results show that a cascade approach and using fewer time steps can reduce computational complexity as much as five times while maintaining reliable segmentations.
subcortical segmentation; computational anatomy; brain mapping; LDDMM
There are few studies that have examined the potential of RNA inference (RNAi) to increase protein production in the baculovirus expression vector system (BEVS). Spodoptera frugiperda (fall armyworm) (Sf)-caspase-1-repressed stable cells exhibit resistance to apoptosis and enhancement of recombinant protein production. However, the mechanism of recombinant protein augmentation in baculovirus-infected Caspase-repressed insect cells has not been elucidated.
In the current study, we utilized RNAi-mediated Sf-caspase-1-repressed stable cells to clarify how the resistance to apoptosis can enhance both intracellular (firefly luciferase) and extracellular (secreted alkaline phosphatase [SEAP]) recombinant protein production in BEVS. Since the expression of molecular chaperones is strongly associated with the maximal production of exogenous proteins in BEVS, the differential expression of molecular chaperones in baculovirus-infected stable cells was also analyzed in this study.
The data indicated that the retention of expression of molecular chaperones in baculovirus-infected Sf-caspase-1-repressed stable cells give the higher recombinant protein accumulation.
Apoptosis; Baculovirus; Chaperone; RNA interference; Sf-caspase-1
Identify important organizational elements for providing self-management support (SMS).
Semi-structured qualitative interviews conducted in two healthcare systems.
Kaiser Permanente Northern California and the Danish Health Care System.
36 managers and healthcare professionals in the two healthcare systems.
Main outcome measures
Elements important to providing self-management support to persons with diabetes.
Healthcare professionals’ provision of SMS was influenced by healthcare system organization and their perceptions of SMS, the capability and responsibility of healthcare systems, and their roles in the healthcare organization. Enabling factors for providing SMS included: strong leadership; aligned incentives; use of an integrated health information technology (HIT) system; multidisciplinary healthcare provider teams; ongoing training for healthcare professionals; outreach; and quality goals. Barriers to providing SMS included lack of collaboration between providers and skeptical attitudes towards prevention and outreach.
Conclusions and implications
Implementation of SMS can be improved by an understanding of the elements that enhance its provision: (1) initiatives seeking to improve collaboration and integration between providers; (2) implementation of an integrated HIT system; and (3) ongoing training of healthcare professionals.
Denmark; diabetes mellitus; general practice; health system; international comparison; patient education; self-management support
Medicare assigns beneficiaries receiving low-income subsidies to plans with premiums below regional benchmarks. The number of these low premium plans fell in 2009, forcing the reassignment of 1.6 million beneficiaries. Using data from Part D plans, we found that CMS’s current risk adjustment scheme does not sufficiently compensate plans for the greater drug spending of low-income subsidy beneficiaries. Since plans can avoid these beneficiaries by raising their premiums above that of their competitors, premiums for all beneficiaries tend to rise over time. Paying more for subsidy and less for non-subsidy beneficiaries, or accounting for past drug use in the risk adjustment scheme could mitigate these perverse incentives.
The aim of this study was to identify the antiviral mechanism of a novel compound, BPR3P0128. From a large-scale screening of a library of small compounds, BPR3P compounds were found to be potent inhibitors of influenza viral replication in Madin–Darby canine kidney (MDCK) cells. BPR3P0128 exhibited inhibitory activity against both influenza A and B viruses. The 50% inhibitory concentrations were in the range of 51 to 190 nM in MDCK cells, as measured by inhibition-of-cytopathic-effect assays. BPR3P0128 appeared to target the viral replication cycle but had no effect on viral adsorption. The inhibition of cap-dependent mRNA transcription by BPR3P0128 was more prominent with a concurrent increase in cap-independent cRNA replication in a primer extension assay, suggesting a role of BPR3P0128 in switching transcription to replication. This reduction in mRNA expression resulted from the BPR3P-mediated inhibition of the cap-dependent endoribonuclease (cap-snatching) activities of nuclear extracts containing the influenza virus polymerase complex. No inhibition of binding of 5′ viral RNA to the viral polymerase complex by this compound was detected. BPR3P0128 also effectively inhibited other RNA viruses, such as enterovirus 71 and human rhinovirus, but not DNA viruses, suggesting that BPR3P0128 targets a cellular factor(s) associated with viral PB2 cap-snatching activity. The identification of this factor(s) could help redefine the regulation of viral transcription and replication and thereby provide a potential target for antiviral chemotherapeutics.
Blood pressure, lipid, and glycemic control are essential for reducing cardiovascular disease (CVD) risk. Many health care systems have successfully shifted aspects of chronic disease management, including population-based outreach programs designed to address CVD risk factor control, to non-physicians. The purpose of this study is to evaluate provision of new information to non-physician outreach teams on need for treatment intensification in patients with increased CVD risk.
Cluster randomized trial (July 1-December 31, 2008) in Kaiser Permanente Northern California registry of members with diabetes mellitus, prior CVD diagnoses and/or chronic kidney disease who were high-priority for treatment intensification: blood pressure ≥ 140 mmHg systolic, LDL-cholesterol ≥ 130 mg/dl, or hemoglobin A1c ≥ 9%; adherent to current medications; no recent treatment intensification). Randomization units were medical center-based outreach teams (4 intervention; 4 control). For intervention teams, priority flags for intensification were added monthly to the registry database with recommended next pharmacotherapeutic steps for each eligible patient. Control teams used the same database without this information. Outcomes included 3-month rates of treatment intensification and risk factor levels during follow-up.
Baseline risk factor control rates were high (82-90%). In eligible patients, the intervention was associated with significantly greater 3-month intensification rates for blood pressure (34.1 vs. 30.6%) and LDL-cholesterol (28.0 vs 22.7%), but not A1c. No effects on risk factors were observed at 3 months or 12 months follow-up. Intervention teams initiated outreach for only 45-47% of high-priority patients, but also for 27-30% of lower-priority patients. Teams reported difficulties adapting prior outreach strategies to incorporate the new information.
Information enhancement did not improve risk factor control compared to existing outreach strategies at control centers. Familiarity with prior, relatively successful strategies likely reduced uptake of the innovation and its potential for success at intervention centers.
ClinicalTrials.gov Identifier NCT00517686
Diabetes mellitus; Hypertension; Hyperlipidemia; Cardiovascular diseases; Clinical inertia
Self-management support is considered to be an essential part of diabetes care. However, the implementation of self-management support within healthcare settings has appeared to be challenging and there is increased interest in “real world” best practice examples to guide policy efforts. In order to explore how different approaches to diabetes care and differences in management structure influence the provision of SMS we selected two healthcare systems that have shown to be comparable in terms of budget, benefits and entitlements. We compared the extent of SMS provided and the self-management behaviors of people living with diabetes in Kaiser Permanente (KP) and the Danish Healthcare System (DHS).
Self-administered questionnaires were used to collect data from a random sample of 2,536 individuals with DM from KP and the DHS in 2006–2007 to compare the level of SMS provided in the two systems and identify disparities associated with educational attainment. The response rates were 75 % in the DHS and 56 % in KP. After adjusting for gender, age, educational level, and HbA1c level, multiple linear regression analyses determined the level of SMS provided and identified disparities associated with educational attainment.
Receipt of SMS varied substantially between the two systems. More people with diabetes in KP reported receiving all types of SMS and use of SMS tools compared to the DHS (p < .0001). Less than half of all respondents reported taking diabetes medication as prescribed and following national guidelines for exercise.
Despite better SMS support in KP compared to the DHS, self-management remains an under-supported area of care for people receiving care for diabetes in the two health systems. Our study thereby suggests opportunity for improvements especially within the Danish healthcare system and systems adopting similar SMS support strategies.
Self-management support; Type 2 diabetes mellitus; Health system; International comparison
To compare drug costs and adherence among Medicare beneficiaries with the standard Part D coverage gap versus supplemental gap coverage in 2006.
Pharmacy data from Medicare Advantage Prescription Drug (MAPD) plans.
Parallel analyses comparing beneficiaries aged 65+ with diabetes in an integrated MAPD with a gap versus no gap (n=28,780); and in a network-model MAPD with a gap versus generic-only coverage during the gap (n=14,984).
Drug spending was 3 percent (95 percent confidence interval [CI]: 1–4 percent) and 4 percent (CI: 1–6 percent) lower among beneficiaries with a gap versus full or generic-only gap coverage, respectively. Out-of-pocket expenditures were 189 percent higher (CI: 185–193 percent) and adherence to three chronic drug classes was lower among those with a gap versus no gap (e.g., odds ratio=0.83, CI: 0.79–0.88, for oral diabetes drugs). Annual out-of-pocket spending was 14 percent higher (CI: 10–17 percent) for beneficiaries with a gap versus generic-only gap coverage, but levels of adherence were similar.
Among Medicare beneficiaries with diabetes, having the Part D coverage gap resulted in lower total drug costs, but higher out-of-pocket spending and worse adherence compared with having no gap. Having generic-only coverage during the gap appeared to confer limited benefits compared with having no gap coverage.
Medicare; prescription drugs; diabetes
Timely detection of clusters of localized influenza activity in excess of background seasonal levels could improve situational awareness for public health officials and health systems. However, no single data type may capture influenza activity with optimal sensitivity, specificity, and timeliness, and it is unknown which data types could be most useful for surveillance. We compared the performance of ten types of electronic clinical data for timely detection of influenza clusters throughout the 2007/08 influenza season in northern California. Kaiser Permanente Northern California generated zip code-specific daily episode counts for: influenza-like illness (ILI) diagnoses in ambulatory care (AC) and emergency departments (ED), both with and without regard to fever; hospital admissions and discharges for pneumonia and influenza; antiviral drugs dispensed (Rx); influenza laboratory tests ordered (Tests); and tests positive for influenza type A (FluA) and type B (FluB). Four credible events of localized excess illness were identified. Prospective surveillance was mimicked within each data stream using a space-time permutation scan statistic, analyzing only data available as of each day, to evaluate the ability and timeliness to detect the credible events. AC without fever and Tests signaled during all four events and, along with Rx, had the most timely signals. FluA had less timely signals. ED, hospitalizations, and FluB did not signal reliably. When fever was included in the ILI definition, signals were either delayed or missed. Although limited to one health plan, location, and year, these results can inform the choice of data streams for public health surveillance of influenza.
influenza; outbreak detection; spatio-temporal analysis
We have developed a new method to provide a comprehensive quantitative analysis of brain anatomy in cerebral palsy patients, which makes use of two techniques: diffusion tensor imaging and automated 3D whole brain segmentation based on our brain atlas and a nonlinear normalization technique (large-deformation diffeomorphic metric mapping). This method was applied to 13 patients and normal controls. The reliability of the automated segmentation revealed close agreement with the manual segmentation. We illustrate some potential applications for individual characterization and group comparison. This technique also provides a framework for determining the impact of various neuroanatomic features on brain functions.
Medicare bases its risk adjustment method for Medicare Advantage (MA) plan payment on the relative costs of treating various diagnoses in traditional Medicare (TM). But there are many reasons to doubt that the relative cost of treating different diagnoses is similar between MA plans and TM, including the varying applicability of care management methods to different diagnoses and varying degrees of market power among suppliers of services to plans. We use internal cost data from a large health plan to compare its cost of treating various diagnoses with Medicare’s reimbursement. We find substantial variability across diagnoses, implying that the current risk adjustment system creates incentives for MA plans to favor beneficiaries with certain diagnoses, but no consistent relationship between the costliness of the diagnosis and the difference between reimbursement and cost.
As many other European healthcare systems the Danish healthcare system (DHS) has targeted chronic condition care in its reform efforts. Benchmarking is a valuable tool to identify areas for improvement. Prior work indicates that chronic care coordination is poor in the DHS, especially in comparison with care in Kaiser Permanente (KP), an integrated delivery system based in the United States. We investigated population rates of hospitalisation and readmission rates for ambulatory care sensitive, chronic medical conditions in the two systems.
Using a historical cohort study design, age and gender adjusted population rates of hospitalisations for angina, heart failure, chronic obstructive pulmonary disease, and hypertension, plus rates of 30-day readmission and mortality were investigated for all individuals aged 65+ in the DHS and KP.
DHS had substantially higher rates of hospitalisations, readmissions, and mean lengths of stay per hospitalisation, than KP had. For example, the adjusted angina hospitalisation rates in 2007 for the DHS and KP respectively were 1.01/100 persons (95%CI: 0.98-1.03) vs. 0.11/100 persons (95%CI: 0.10-0.13/100 persons); 21.6% vs. 9.9% readmission within 30 days (OR = 2.53; 95% CI: 1.84-3.47); and mean length of stay was 2.52 vs. 1.80 hospital days. Mortality up through 30 days post-discharge was not consistently different in the two systems.
There are substantial differences between the DHS and KP in the rates of preventable hospitalisations and subsequent readmissions associated with chronic conditions, which suggest much opportunity for improvement within the Danish healthcare system. Reductions in hospitalisations also could improve patient welfare and free considerable resources for use towards preventing disease exacerbations. These conclusions may also apply for similar public systems such as the US Medicare system, the NHS and other systems striving to improve the integration of care for persons with chronic conditions.
Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells.
BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats.
Conclusions and Significance
BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments.
Medicare Part D beneficiaries with diabetes are at risk of medication non-adherence and forgoing necessities due to cost pressures. Generic drug coverage during the Part D gap may attenuate these potentially adverse behaviors.
To examine the association between drug coverage during the gap and medication cost-cutting behaviors among insulin users and non-users.
Participants and Setting
2007 survey of Medicare Advantage Part D (MAPD) and Prescription Drug Plan (PDP) beneficiaries within a network-model health system who entered the gap by October 2006 (N=1,468, 57% response rate).
The study was cross-sectional.
The primary predictor variable was no gap coverage versus generic-only gap coverage. We examined seven cost-cutting behaviors as dependent variables, including cost-related non-adherence (CRN) to any medication. Covariates included race/ethnicity, education, health status, income, and comorbidities, as well as generic medication use in the first quarter. We constructed logistic regression models using non-response weights, to generate predicted percentages.
In multivariate analyses, beneficiaries taking insulin were less likely to report CRN if they had generic-only gap coverage compared to no gap coverage (16% vs. 29%, p=0.03). No differences in CRN by type of gap coverage were seen among beneficiaries not taking insulin.
Medicare beneficiaries using insulin are at high risk of CRN. Generic-only coverage during the gap is associated with an attenuated risk of CRN among insulin users, possibly due to savings on other, generic medications. Future research should evaluate CRN within alternative benefit designs covering selected brand name medications, such as insulin, during the gap.
Medicare Part D; pharmaceutical use; diabetes
Flexor tendon laceration repairs remain challenging despite numerous advances in hand surgery. Although progress on this vital subject matter has been achieved, there continues to be discussion over which surgical technique produces the optimal result. Currently there are several recommended surgical repair options for the lacerated flexor tendon. However, these repairs continue to have possible significant complications including adhesions, decreased range of motion, gapping, and post operative rupture. Stainless steel suture has long been known as an option for flexor tendon repair. Stainless steel suture demonstrates one of the highest tensile strength sutures. However until recently, stainless steel suture placement for flexor tendon repairs was technically problematic. This case study discusses an additional option for repairing lacerated flexor tendons using an advanced stainless steel tendon repair system.
Flexor tendon rupture; Teno Fix; Flexor tendon repair
We evaluated a real-time ambulatory care-based syndromic surveillance system in four metropolitan areas of the United States.
Health-care organizations and health departments in California, Massachusetts, Minnesota, and Texas participated during 2007–2008. Syndromes were defined using International Classification of Diseases, Ninth Revision diagnostic codes in electronic medical records. Health-care organizations transmitted daily counts of new episodes of illness by syndrome, date, and patient zip code. A space-time permutation scan statistic was used to detect unusual clustering. Health departments followed up on e-mailed alerts. Distinct sets of related alerts (”signals”) were compared with known outbreaks or clusters found using traditional surveillance.
The 62 alerts generated corresponded to 17 distinct signals of a potential outbreak. The signals had a median of eight cases (range: 3–106), seven zip code areas (range: 1–88), and seven days (range: 3–14). Two signals resulted from true clusters of varicella; six were plausible but unconfirmed indications of disease clusters, six were considered spurious, and three were not investigated. The median investigation time per signal by health departments was 50 minutes (range: 0–8 hours). Traditional surveillance picked up 124 clusters of illness in the same period, with a median of six ill per cluster (range: 2–75). None was related to syndromic signals.
The system was able to detect two true clusters of illness, but none was of public health interest. Possibly due to limited population coverage, the system did not detect any of 124 known clusters, many of which were small. The number of false alarms was reasonable.
The purpose of this paper is to establish single-participant white matter atlases based on diffusion tensor imaging. As one of the applications of the atlas, automated brain segmentation was performed and the accuracy was measured using Large Deformation Diffeomorphic Metric Mapping (LDDMM). High-quality diffusion tensor imaging (DTI) data from a single-participant were B0-distortion-corrected and transformed to the ICBM-152 atlas or to Talairach coordinates. The deep white matter structures, which have been previously well documented and clearly identified by DTI, were manually segmented. The superficial white matter areas beneath the cortex were defined, based on a population-averaged white matter probability map. The white matter was parcellated into 176 regions based on the anatomical labeling in the ICBM-DTI-81 atlas. The automated parcellation was achieved by warping this parcellation map to normal controls and to Alzheimer’s disease patients with severe anatomical atrophy. The parcellation accuracy was measured by a kappa analysis between the automated and manual parcellation at 11 anatomical regions. The kappa values were 0.70 for both normal controls and patients while the inter-rater reproducibility was 0.81 (controls) and 0.82 (patients), suggesting “almost perfect” agreement. A power analysis suggested that the proposed method is suitable for detecting FA and size abnormalities of the white matter in clinical studies.
Human; White matter; Atlas; Association fiber; Magnetic resonance imaging; Diffusion tensor; Alzheimer’s disease
Little is known about drug cost communications of Medicare Part D beneficiaries with chronic conditions such as diabetes. The purpose of this study is to assess Medicare Part D beneficiaries with diabetes' levels of communication with physicians regarding prescription drug costs; the perceived importance of these communications; levels of prescription drug switching due to cost; and self-reported cost-related medication non-adherence.
Data were obtained from a cross-sectional survey (58% response rate) of 1,458 Medicare beneficiaries with diabetes who entered the coverage gap in 2006; adjusted percentages of patients with communication issues were obtained from multivariate regression analyses adjusting for patient demographics and clinical characteristics.
Fewer than half of patients reported discussing the cost of medications with their physicians, while over 75% reported that such communications were important. Forty-eight percent reported their physician had switched to a less expensive medication due to costs. Minorities, females, and older adults had significantly lower levels of communication with their physicians regarding drug costs than white, male, and younger patients respectively. Patients with < $25 K annual household income were more likely than higher income patients to have talked about prescription drug costs with doctors, and to report cost-related non-adherence (27% vs. 17%, p < .001).
Medicare Part D beneficiaries with diabetes who entered the coverage gap have low levels of communication with physicians about drug costs, despite the high perceived importance of such communication. Understanding patient and plan-level characteristics differences in communication and use of cost-cutting strategies can inform interventions to help patients manage prescription drug costs.
A cell culture system for the production of hepatitis C virus (HCV) whole virions has greatly accelerated studies of the virus life cycle and the discovery of anti-HCV agents. However, the quantification of the HCV titers in a whole-virus infection/replication system currently relies mostly on reverse transcription-PCR or immunofluorescence assay, which would be cumbersome for high-throughput drug screening. To overcome this problem, this study has generated a novel cell line, Huh7.5-EG(Δ4B5A)SEAP, that carries a dual reporter, EG(Δ4B5A)SEAP. The EG(Δ4B5A)SEAP reporter is a viral protease-cleavable fusion protein in which the enhanced green fluorescence protein is linked to secreted alkaline phosphatase (SEAP) in frame via Δ4B5A, a short peptide cleavage substrate for NS3/4A viral protease. This study demonstrates that virus replication/infection in the Huh7.5-EG(Δ4B5A)SEAP cells can be quantitatively indicated by measuring the SEAP activity in cell culture medium. The levels of SEAP released from HCV-infected Huh7.5-EG(Δ4B5A)SEAP cells correlated closely with the amounts of HCV in the inocula. The Huh7.5-EG(Δ4B5A)SEAP cells were also shown to be a suitable host for the discovery of anti-HCV inhibitors by using known compounds that target multiple stages of the HCV life cycle. The Z′-factor of this assay ranged from 0.64 to 0.74 in 96-well plates, indicating that this reporter system is suitable for high-throughput screening of prospective anti-HCV agents.
Integration of medical care across clinicians and settings could enhance the quality of care for patients. To date, there is limited data on the levels of integration in practice. Our objective was to compare primary care clinicians' perceptions of clinical integration and three sub-aspects in two healthcare systems: Kaiser Permanente, Northern California (KPNC) and the Danish healthcare system (DHS). Further, we examined the associations between specific organizational factors and clinical integration within each system.
Comparable questionnaires were sent to a random sample of primary care clinicians in KPNC (n = 1103) and general practitioners in DHS (n = 700). Data were analysed using multiple logistic regression models.
More clinicians in KPNC perceived to be part of a clinical integrated environment than did general practitioners in the DHS (OR = 3.06, 95% CI: 2.28, 4.12). Further, more KPNC clinicians reported timeliness of information transfer (OR = 2.25, 95% CI: 1.62, 3.13), agreement on roles and responsibilities (OR = 1.79, 95% CI: 1.30, 2.47) and established coordination mechanisms in place to ensure effective handoffs (OR = 6.80, 95% CI: 4.60, 10.06). None of the considered organizational factors in the sub-country analysis explained a substantial proportion of the variation in clinical integration.
More primary care clinicians in KPNC reported clinical integration than did general practitioners in the DHS. Focused measures of clinical integration are needed to develop the field of clinical integration and to create the scientific foundation to guide managers searching for evidence based approaches.