Goals

To evaluate provider knowledge, attitudes and barriers to hepatitis B virus (HBV) care and management practices across diverse primary care settings.

Background

Factors influencing adherence to recommended HBV screening and management guidelines are poorly defined.

Materials and methods

Providers across various health care settings in San Francisco were surveyed. Multivariate analyses were used to identify factors associated with recommended HBV screening, vaccination, and disease monitoring.

Results

Of 277 (41.3%) responding providers, 42% reported performing HBV screening in >50% of at-risk patients, and 49%, HBV vaccination in >50% of eligible patients. Most reported appropriate monitoring of a majority of HBV-infected patients with alanine aminotransferase (79%) and HBV viral load (67%) every 6 to 12 months, but performed any hepatocellular carcinoma screening in 49%. Provider factors significantly associated with HBV screening were speaking an Asian language [odds ratio (OR), 3.27], offering HBV treatment (OR, 3.00), having >25% of Asian patients in practice (OR, 2.10), practicing in safety net settings (OR, 7.51) and having higher barrier score (OR, 0.74). Appropriate HBV monitoring was associated with provider speaking an Asian language (OR, 3.43) and provider age (OR, 0.68/decade). Hepatocellular carcinoma screening was associated with having >25% of patients speaking English as a second language (OR, 4.26) and practicing in safety net settings (OR, 0.14).

Conclusions

Rates of adherence to HBV guidelines were suboptimal irrespective of practice setting and were influenced by certain provider, patient and practice factors. This study reinforces the importance of engaging primary care providers in development, dissemination, and implementation of evidence-based HBV practice guidelines.

Objective

To determine the impact on referral patterns of using a Multivariate Index Assay, CA125, modified-American College of Obstetricians and Gynecologists referral guidelines, and clinical assessment among patients undergoing surgery for an adnexal mass after initial evaluation by nongynecologic oncologists.

Study design

Overall, 770 patients were enrolled by nongynecologic oncologists from 2 related, multiinstitutional, prospective trials and analyzed retrospectively. All patients had preoperative imaging and biomarker analysis. The subset of patients enrolled by nongynecologic oncologists was analyzed to determine the projected referral patterns and sensitivity for malignancy based on multivariate index assay (MIA), CA125, modified-American College of Obstetricians and Gynecologists (ACOG) guidelines, and clinical assessment compared with actual practice.

Results

The prevalence of malignancy was 21.3% (n = 164). In clinical practice, 462/770 patients (60.0%) were referred to a gynecologic oncologist for surgery. Triage based on CA125 predicted referral of 157/770 patients (20.4%) with sensitivity of 68.3% (95% confidence interval [CI], 60.8-74.9). Triage based on modified-ACOG guidelines would have resulted in referral of 256/770 patients (33.2%) with a sensitivity of 79.3% (95% CI, 72.4-84.8). Clinical assessment predicted referral of 184/763 patients (24.1%) with a sensitivity of 73.2% (95% CI, 65.9-79.4). Risk stratification using multivariate index assay would have resulted in referral of 429/770 (55.7%) patients, with sensitivity of 90.2% (95% CI, 84.7-93.9). MIA demonstrated statistically significant higher sensitivity (P < .0001) and lower specificity (P < .0001) for detecting malignancy compared with clinical assessment, CA125, and modified-ACOG guidelines.

Conclusion

In this study population, use of MIA as a risk stratification test was associated with referral patterns by nongynecologic oncologists comparable to actual clinical practice and higher sensitivity for malignancy than other adnexal mass triage algorithms.

Background

Hepatitis B (HBV) represents a significant health disparity among medically underserved Asian and Hawaiian/Pacific Islander (API) populations. Studies evaluating adherence to HBV screening and vaccination guidelines in this population are limited.

Objective

The purpose of this study was to evaluate HBV screening and vaccination practices using both provider self-report and patient records.

Design

Medical records for 20,574 API adults were reviewed retrospectively and primary care providers were surveyed to evaluate rates and adherence to HBV screening and vaccination guidelines.

Participants

The study included primary care providers and their adult API patients in the San Francisco safety-net healthcare system.

Main measures

Patient, practice, and provider factors, as well as HBV screening and vaccination practices, were assessed using provider survey constructs and patient laboratory and clinical data. Generalized linear mixed models and multivariate logistic regression analyses were used to identify factors associated with recommended HBV screening and vaccination.

Key results

The mean age of patients was 52 years, and 63.4 % of patients were female. Only 61.5 % underwent HBV testing, and 47.4 % of HBV-susceptible patients were vaccinated. Of 148 (44.8 %) responding providers, most were knowledgeable and had a favorable attitude towards screening, but 43.2 % were unfamiliar with HBV guidelines. HBV screening was positively associated with favorable provider attitude score (OR per unit 1.80, 95 % CI 1.18-2.74) and negatively associated with female patient sex (OR 0.82, 95 % CI 0.73-0.92), a higher number of clinic patients per week (OR per 20 patients 0.46, 95 % CI 0.28-0.76), and provider barrier score (OR per unit 0.45, 95 % CI 0.24-0.87). HBV vaccination was negatively associated with provider barrier score (OR per unit 0.48, 95 % CI 0.25-0.91).

Conclusions

Rates of HBV screening and vaccination of API patients in this safety-net system are suboptimal, and provider factors play a significant role. Efforts to cultivate positive attitudes among providers and expand healthcare system resources to reduce provider barriers to HBV care are warranted.

In a previous study we established forward genetics in the choanoflagellate Salpingoeca rosetta and found that a C-type lectin gene is required for rosette development (Levin et al., 2014). Here we report on critical improvements to genetic screens in S. rosetta while also investigating the genetic basis for rosette defect mutants in which single cells fail to develop into orderly rosettes and instead aggregate promiscuously into amorphous clumps of cells. Two of the mutants, Jumble and Couscous, mapped to lesions in genes encoding two different predicted glycosyltransferases and displayed aberrant glycosylation patterns in the basal extracellular matrix (ECM). In animals, glycosyltransferases sculpt the polysaccharide-rich ECM, regulate integrin and cadherin activity, and, when disrupted, contribute to tumorigenesis. The finding that predicted glycosyltransferases promote proper rosette development and prevent cell aggregation in S. rosetta suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.

Background

Hepatitis B (HBV) is prevalent in certain US populations and regular HBV disease monitoring is critical to reducing associated morbidity and mortality. Adherence to established HBV monitoring guidelines among primary care providers is unknown.

Aims

The purpose of this study was to evaluate HBV disease monitoring patterns and factors associated with adherence to HBV management guidelines in the primary care setting.

Methods

Primary providers within the San Francisco safety net healthcare system were surveyed for HBV management practices, knowledge, attitudes, and barriers to HBV care. Medical records from 1,727 HBV-infected patients were also reviewed retrospectively.

Results

Of 148 (45 %) responding providers, 79 % reported ALT and 44 % reported HBV viral load testing every 6-12 months. Most providers were knowledgeable about HBV but 43 % were unfamiliar with HBV management guidelines. Patient characteristics included: mean age 51 years, 54 % male and 67 % Asian. Within the past year, 75 % had ALT, 24 % viral load, 21 % HBeAg tested, and 40 % of at-risk patients had abdominal imaging for HCC. Provider familiarity with guidelines (OR 1.02, 95 % CI 1.00-1.03), Asian patient race (OR 4.18, 95 % CI 2.40-7.27), and patient age were associated with recommended HBV monitoring. Provider HBV knowledge and attitudes were positively associated, while provider age and perceived barriers were negatively associated with HCC surveillance.

Conclusions

Comprehensive HBV disease monitoring including HCC screening with imaging were suboptimal. While familiarity with AASLD guidelines and patient factors were associated with HBV monitoring, only provider and practice factors were associated with HCC surveillance. These findings highlight the importance of targeted provider education to improve HBV care.

Purpose

Advanced thyroid cancer responds poorly to most therapies. New therapies and combinations are needed. The aim of this study was to examine both in vitro and in vivo activity of two relatively new histone deacetylase inhibitors (HDACIs), belinostat and panobinostat, and a variety of tyrosine kinase inhibitors (TKIs) against a panel of nine human thyroid cancer cell lines.

Methods

The anti-proliferative activity and the effects of HDACIs, TKIs and their combinations on thyroid cancer cells were determined by cytotoxicity assays, microarray and immunoblot analyses. Synergism between HDACIs and TKIs was assessed by the median effects model of Chou-Talalay (Calcusyn(®)).

Results

Belinostat and panobinostat were active against the thyroid cancer cell lines irrespective of their mutational composition, and belinostat was effective in preventing growth of human thyroid cancer xenografts in immunodeficient mice. Further studies showed that both HDACIs induced apoptosis. HDACI also elevated acetylated histone 3, p21(Waf), and PARP, and decreased levels of phosphorylated ERK and AKT (Ser473). RNA assay analysis suggested both HDACIs modulated genes associated with the cell cycle, DNA damage and apoptosis. Most of the TKI (pazopanib, motesanib, sorafenib and dasatinib) were either inactive in vitro or were active only at high doses. However, the novel combinations of either pazopanib or dasatinib TKIs with either belinostat or panobinostat synergistically inhibited cell growth of thyroid cancer cells in vitro.

Conclusions

In summary, these HDACIs either alone or combined with selected TKIs may have a role in treatment of aggressive thyroid cancer.

In a previous study we established forward genetics in the choanoflagellate Salpingoeca rosetta and found that a C-type lectin gene is required for rosette development (Levin et al., 2014). Here we report on critical improvements to genetic screens in S. rosetta while also investigating the genetic basis for rosette defect mutants in which single cells fail to develop into orderly rosettes and instead aggregate promiscuously into amorphous clumps of cells. Two of the mutants, Jumble and Couscous, mapped to lesions in genes encoding two different predicted glycosyltransferases and displayed aberrant glycosylation patterns in the basal extracellular matrix (ECM). In animals, glycosyltransferases sculpt the polysaccharide-rich ECM, regulate integrin and cadherin activity, and, when disrupted, contribute to tumorigenesis. The finding that predicted glycosyltransferases promote proper rosette development and prevent cell aggregation in S. rosetta suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.

Objectives

To expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations.

Design

A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats).

Results

Of the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism.

Conclusions

Associations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies.

PURPOSE: We assessed whether Prostate Health Index results improve prediction of grade reclassification for men on active surveillance. METHODS AND MATERIALS: We identified men in Canary Prostate Active Surveillance Study with Grade Group 1 cancer. Outcome was grade reclassification to Grade Group 2+ cancer. We considered decision rules to maximize specificity with sensitivity set at 95%. We derived rules based on clinical data (R1) vs clinical data+Prostate Health Index (R3). We considered an or-logic rule combining clinical score and Prostate Health Index (R4), and a 2-step rule using clinical data followed by risk stratification based on Prostate Health Index (R2). Rules were applied to a validation set, where values of R2-R4 vs R1 for specificity and sensitivity were evaluated. RESULTS: We included 1,532 biopsies (n = 610 discovery; n = 922 validation) among 1,142 men. Grade reclassification was seen in 27% of biopsies (23% discovery, 29% validation). Among the discovery set, at 95% sensitivity, R2 yielded highest specificity at 27% vs 17% for R1. In the validation set, R3 had best performance vs R1 with Δsensitivity = -4% and Δspecificity = +6%. There was slight improvement for R3 vs R1 for confirmatory biopsy (AUC 0.745 vs R1 0.724, ΔAUC 0.021, 95% CI 0.002-0.041) but not for subsequent biopsies (ΔAUC -0.012, 95% CI -0.031-0.006). R3 did not have better discrimination vs R1 among the biopsy cohort overall (ΔAUC 0.007, 95% CI -0.007-0.020). CONCLUSIONS: Among active surveillance patients, using Prostate Health Index with clinical data modestly improved prediction of grade reclassification on confirmatory biopsy and did not improve prediction on subsequent biopsies.

Objective

To establish and compare the repeatability and reproducibility of activated thromboelastography (TEG) and thromboelastometry (ROTEM) assays.

Design

Multicenter in vitro test standardization.

Setting

Veterinary academic centers.

Animals

Test samples were obtained from normal, healthy dogs. Sixty identical 5 mL aliquots of canine platelet-rich plasma collected by apheresis, frozen in 6% dimethyl sulfoxide, were tested initially. Sixty identical 6 mL aliquots of canine fresh frozen plasma with admixed cryoprecipitate were subsequently evaluated.

Interventions

None.

Measurements and main results

Frozen study samples, quality controls, reagents, and consumables were distributed to participating centers (7 TEG and 3 ROTEM). TEG centers analyzed study samples with kaolin and tissue factor activated assays; ROTEM centers ran proprietary ellagic acid activated and tissue factor activated assays. All machines underwent quality control prior to sample analysis. Within- and between-center coefficients of variation (CVs) were calculated and compared using Mann-Whitney tests and calculation of intraclass correlation coefficients. Within and between centers, individual parameters for both TEG and ROTEM assays were comparable. Both within-center and between-center CVs varied markedly (0.7-120.5% and 1.4-116.5%, respectively) with assay type, instrument, and parameter. CVs for equivalent parameters were not significantly different between the 2 platforms. Intraclass correlation coefficients suggested moderate agreement between centers. In general, individual parameter CVs for platelet-rich plasma samples were lower in TEG centers, while CVs for canine fresh frozen plasma with admixed cryoprecipitate samples were lower in ROTEM centers.

Conclusions

More variation within and between centers was identified than anticipated, but some parameters such as alpha angle were repeatable and reproducible. Sample types for future multicenter standardization efforts will require further optimization and may need to be adapted separately to each platform. Individual centers using viscoelastic tests for evaluation and management of clinical patients should take steps to minimize preanalytical and analytical sources of variation.