Mutant Prourokinase with Adjunctive C1-Inhibitor Is an Effective and Safer Alternative to tPA in Rat Stroke

A single-site mutant (M5) of native urokinase plasminogen activator (prouPA) induces effective thrombolysis in dogs with venous or arterial thrombosis with a reduction in bleeding complications compared to tPA. This effect, related to inhibition of two-chain M5 (tcM5) by plasma C1-inhibitor (C1I), thereby preventing non-specific plasmin generation, was augmented by the addition of exogenous C1I to plasma in vitro. In the present study, tPA, M5 or placebo +/− C1I were administered in two rat stroke models. In Part-I, permanent MCA occlusion was used to evaluate intracranial hemorrhage (ICH) by the thrombolytic regimens. In Part II, thromboembolic occlusion was used with thrombolysis administered 2 h later. Infarct and edema volumes, and ICH were determined at 24 h, and neuroscore pre (2 h) and post (24 h) treatment. In Part I, fatal ICH occurred in 57% of tPA and 75% of M5 rats. Adjunctive C1I reduced this to 25% and 17% respectively. Similarly, semiquantitation of ICH by neuropathological examination showed significantly less ICH in rats given adjunctive C1I compared with tPA or M5 alone. In Part-II, tPA, M5, and M5+C1I induced comparable ischemic volume reductions (>55%) compared with the saline or C1I controls, indicating the three treatments had a similar fibrinolytic effect. ICH was seen in 40% of tPA and 50% of M5 rats, with 1 death in the latter. Only 17% of the M5+C1I rats showed ICH, and the bleeding score in this group was significantly less than that in either the tPA or M5 group. The M5+C1I group had the best Benefit Index, calculated by dividing percent brain salvaged by the ICH visual score in each group. In conclusion, adjunctive C1I inhibited bleeding by M5, induced significant neuroscore improvement and had the best Benefit Index. The C1I did not compromise fibrinolysis by M5 in contrast with tPA, consistent with previous in vitro findings

Uptake of Direct Acting Antivirals for Hepatitis C Virus in a New England Medicaid Population, 2014-2017

Introduction Introduction of the direct acting antiviral (DAA) sofosbuvir (SOV) in 2013 offered significant improvement over previous options for hepatitis C virus (HCV) treatment. Initial uptake was low in Medicaid and other populations, perhaps in part due to high drug cost and prior authorization (PA) restrictions related to fibrosis stage, prescribing provider specialty, and sobriety. Both the subsequent introduction of ledipasvir/sofosbuvir (LDV/SOV), an all-oral regimen for most genotypes, and lifting of PA restrictions were expected to increase overall uptake, but little is known about recent prescribing patterns. We examined trends in DAA uptake in a Medicaid population and identified the effect of these two events on treatment initiation. Study Design An interrupted time series (ITS) design utilized enrollment, medical, and pharmacy claims from Medicaid enrollees in three New England states, 12/2013-12/2017. Trends in treatment uptake, defined as 1+ pharmacy claim for a DAA, were examined overall, by demographic characteristics, and prior to and after two time points: 10/2014 (LDV/SOV approval date) and 7/2016 (date PA restrictions affecting two-thirds of members were lifted). Chi-square evaluated demographic differences, segmented regression models examined trends. Study Population The population included members ages 18-64 years with HCV (2+ claims with ICD-9/10 code for HCV or 1+ claim for chronic HCV). Eligible individuals remained in the sample until treatment initiation or Medicaid disenrollment. Findings The analytic sample averaged 30,433 members with HCV per month, mean age 42.9 years, 60% male. In 2014 3.3% of eligible members initiated treatment, increasing to 7.7% in 2017 (p = Conclusion While initial uptake of DAAs was low in this multi-state Medicaid population, treatment initiation among eligible members increased through 2017. Introduction of new medications and lifting of PA restrictions led to an immediate increase in uptake followed by relatively flat monthly utilization. Policy implications Sharp increases in uptake after LDV/SOV introduction may indicate warehousing of members in anticipation of LDV/SOV approval; increases after PA restrictions were lifted indicates demand for treatment among those affected by restrictions. As a large percentage of the Medicaid HCV population remains untreated, planned provider interviews will help to understand barriers and facilitators of treatment for HCV

Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review

Background: There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. Methods: We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. Results: We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening in areas beyond a clinician's primary area of practice was a common strategy for facilitating referral and integrated care, as was joint care planning. Conclusion: Despite considerable limitations and gaps in the literature in terms of the evaluation of integrated care strategies, particularly between AOD services, our review highlights several strategies that could be useful at multiple levels. Given the interconnectedness of integrated care strategies identified, implementation of multi-level strategies rather than single strategies is likely to be preferable

Examining the types and payments of the disabilities of the insurants in the national farmers' health insurance program in Taiwan

<p>Abstract</p> <p>Background</p> <p>In contrast to the considerable body of literature concerning the disabilities of the general population, little information exists pertaining to the disabilities of the farm population. Focusing on the disability issue to the insurants in the Farmers' Health Insurance (FHI) program in Taiwan, this paper examines the associations among socio-demographic characteristics, insured factors, and the introduction of the national health insurance program, as well as the types and payments of disabilities among the insurants.</p> <p>Methods</p> <p>A unique dataset containing 1,594,439 insurants in 2008 was used in this research. A logistic regression model was estimated for the likelihood of received disability payments. By focusing on the recipients, a disability payment and a disability type equation were estimated using the ordinary least squares method and a multinomial logistic model, respectively, to investigate the effects of the exogenous factors on their received payments and the likelihood of having different types of disabilities.</p> <p>Results</p> <p>Age and different job categories are significantly associated with the likelihood of receiving disability payments. Compared to those under age 45, the likelihood is higher among recipients aged 85 and above (the odds ratio is 8.04). Compared to hired workers, the odds ratios for self-employed and spouses of farm operators who were not members of farmers' associations are 0.97 and 0.85, respectively. In addition, older insurants are more likely to have eye problems; few differences in disability types are related to insured job categories.</p> <p>Conclusions</p> <p>Results indicate that older farmers are more likely to receive disability payments, but the likelihood is not much different among insurants of various job categories. Among all of the selected types of disability, a highest likelihood is found for eye disability. In addition, the introduction of the national health insurance program decreases the likelihood of receiving disability payments. The experience in Taiwan can be valuable for other countries that are in an initial stage to implement a universal health insurance program.</p

2013-2015 Connecting Consumers with Care Grant Area Evaluation

This report includes findings from the evaluation of the 2013-2015 Connecting Consumers with Care grant program. The goals of the evaluation were to 1) assess progress made on select outreach and enrollment measures, 2) describe the practices grantees adopted to reach and enroll consumers in health insurance, and 3) characterize efforts and challenges in defining, promoting, and evaluating consumer self-sufficiency