Research Priorities for Economic Analyses of Prevention: Current Issues and Future Directions

In response to growing interest in economic analyses of prevention efforts, a diverse group of prevention researchers, economists, and policy analysts convened a scientific panel, on “Research Priorities in Economic Analysis of Prevention” at the 19th annual conference of the Society for Prevention Research. The panel articulated four priorities that, if followed in future research, would make economic analyses of prevention efforts easier to compare and more relevant to policymakers and community stakeholders. These priorities are: (1) increased standardization of evaluation methods, (2) improved economic valuation of common prevention outcomes, (3) expanded efforts to maximize evaluation generalizability and impact as well as (4) enhanced transparency and communicability of economic evaluations. In this paper, we define three types of economic analyses in prevention, provide context and rationale for these four priorities as well as related sub-priorities, and discuss the challenges inherent in meeting them.     

Development of Solid Dispersion by Hot Melt Extrusion Using Mixtures of Polyoxylglycerides With Polymers as Carriers for Increasing Dissolution Rate of a Poorly Soluble Drug Model

Various polyoxylglycerides have been researched extensively in the development of solid dispersions (SDs) for bioavailability enhancement of poorly water-soluble drugs. However, because of their low melting points (40°C-60°C), SDs produced are usually soft and semisolid. The objective of present study was to prepare SDs of a Biopharmaceutical Classification System class II drug, carvedilol, in mixtures of stearoyl polyoxylglycerides (Acconon^® C-50; m.p. ～50°C) with polymers by hot melt extrusion to obtain free-flowing powder upon grinding. Miscibility of carvedilol with Kollidon^® VA64, hydroxypropyl methylcellulose acetate succinate, and Klucel^? EXF was first evaluated by film casting, and Kollidon^® VA64 was selected for further study. SDs containing 5%-20% carvedilol, 0%-20% Acconon^® C-50, and the remaining Kollidon^® VA64 were prepared for hot melt extrusion. SDs were characterized by differential scanning calorimetry and powder X-ray diffraction analysis, and dissolution tests were conducted in 250 mL of pH 6.8 phosphate buffer by filling powders in capsules. Carvedilol was miscible with all polymers tested up to 50% and remained amorphous in SDs. The drug release from formulations containing 20% carvedilol and 0, 5%, 10%, and 20% Acconon^® C-50 were 30%, 30%, 70%, and 90%, respectively, in 60 min. SDs containing carvedilol and Acconon^® C-50, up to 20% each, as well as Kollidon^® VA64, were physically stable after 3 months of storage at 25°C/60% relative humidity.     

Hemoglobin levels and coronary heart disease risk by age,race, and sex in the reasons for geographic and racial differences in stroke study (REGARDS)

Higher and lower hemoglobin concentrations are associated with coronary heart disease (CHD), but whether this risk is consistent across age, sex, and race is unclear. The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study is an observational cohort study of 30 239 black, and white, adults aged 45 and older recruited 2003-7. Participants were included if they had hemoglobin measures, were CHD-free at baseline, and had all baseline variables. The primary outcome was incident CHD. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD by hemoglobin concentration. This was expressed as a continuous variable and divided into age-, sex-, and race-specific quintiles. The 16 332 participants were included, contributing 114 362 person-years of follow-up and 915 incident CHD events. The mean age was 63 years, 35% were male, 41% were black, and the mean baseline hemoglobin was 13.6 g/dL (SD 1.4). A significant non-linear association between hemoglobin and CHD was identified (P < .001). This association differed significantly by race (P = .025) but not by sex or age. In whites, the risk for incident CHD was higher in the lowest (HR 2.28, 95% CI 1.61, 3.33) and highest (HR 1.94, 95% CI 1.35, 2.79) hemoglobin quintiles relative to the third quintile. For blacks, only those in the lowest hemoglobin quintile had an increased risk for incident CHD events (HR 1.70, 95% CI 1.20, 2.41). Hemoglobin is an independent risk factor for CHD in whites and blacks but with different hemoglobin concentrations conferring different risks.     

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.     

Resolution of acute lower extremity deep vein thrombosis with rivaroxaban compared to warfarin

Journal of Thrombosis and Thrombolysis - Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown...     

Mannose-binding lectin and ficolin-2 do not influence humoral immune response to hepatitis B vaccine

Background

Host genetics appear to be an important factor in the failure to generate a protective immune response after hepatitis B (HBV) vaccination. Mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway of complement, influence the clinical outcome of HBV, and MBL deficiency has been shown to augment the humoral response to HBV vaccination in several experimental models. Here, we investigated the association of MBL and FCN2 with the humoral response to HBV vaccination in a candidate gene and functional study.

Patients and methods

A post hoc analysis of a prospective, interventional HBV vaccination study among human immunodeficiency virus type 1 (HIV-1) uninfected individuals in Kenya was conducted. Serum levels and polymorphisms of MBL and FCN2 were analysed in relation to the immune response to HBV vaccination.

Results

Protective hepatitis B surface antibody levels (≥10 mIU/mL) were evident in 251/293 (85.7%) individuals. Median MBL and FCN2 levels were similar in responders vs. non-responders with a weak trend towards lower median MBL levels in non-responders (1.0 vs. 1.6 μg/mL, p = 0.1). Similarly, there was no difference in four MBL and six FCN2 polymorphisms analysed in the two groups with the exception of an increased frequency of a homozygous MBL codon 57 mutation in non-responders (4 (9.5%) vs. 8 (3.2%), p = 0.05) corresponding to lower MBL levels. Results were similar after adjusting for age and sex.

Conclusions

Our study does not support a prominent role of the lectin pathway of complement in general and MBL and FCN2 in particular in the humoral immune response to HBV vaccination in African adults.     

Diagnosing skin rejection in vascularized composite allotransplantation: advances and challenges

Refinements in microsurgical techniques coupled with advances in immunosuppressive and immunomodulatory protocols have enabled broader clinical application of vascularized composite allotransplantation (VCA) with encouraging immunological, functional, and esthetic results. However, skin rejection remains a significant obstacle and a serious complication for VCA recipients. Clinical and histopathological features of rejection in VCA have been described in a number of studies, which led to the development of an international consensus on the classification guidelines of rejection in the context of VCA. Nevertheless, currently available diagnostic modalities still have several limitations and shortcomings that can pose a significant diagnostic challenge, particularly when signs of rejection are found to be equivocal. In this review, we provide a critical analysis of these advances and challenges in diagnosing skin rejection. Specifically, we highlight the gaps in understanding of rejection mechanisms, the shortfalls in correlating cellular, molecular, and clinicopathologic markers with rejection grades, deficiencies in defining chronic rejection, and antibody‐mediated rejection after VCA, as well as providing an outlook on novel concepts, such as the utilization of advanced computational analyses and cross‐disciplinary diagnostic approaches.     

Imaging of stress fractures in the athlete

Osseous stress fractures and stress reactions represent the effect of abnormal repetitive stress on normal bone. An accurate and thorough clinical history and sequential radiographs often suffice 40 make the diagnosis especially when the fracture occurs in one of the common locations, such as the tibia, metatarsals, or calcaneus. In cases that are atypical in location or clinical presentation the authors rely more on MR imaging, radionuclide bone scanning, and occasionally CT. MR imaging detects early changes of osseous stress injury and allows precise definition of anatomy and extent of injury, and is the preferred modality for evaluating the continuum of osseous manifestations of stress injury. MR imaging is useful in evaluating shin splints, early osseous stress injuries, and overt stress fracture. In the elite athlete prompt diagnosis and early rehabilitation are the goals.