Efficacy of an eConsult service to cure hepatitis C in primary care

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system. We now aim to evaluate its efficacy in curing HCV. In this retrospective cohort study, we describe rates of sustained virologic response 12 weeks after treatment completion (SVR12) for those who received primary care-based HCV treatment through the eConsult system with those who were treated in primary care independent of an eConsult from 2017 to 2019. We found there was no significant difference in the proportion of patients who achieved SVR12 between the two groups. Overall, >90% of patients who received treatment achieved SVR12. Approximately 40% of patients treated for HCV received an eConsult, suggesting utility of the eConsult in expanding access and coordinating treatment for patients within our network.     

Observer error in systolic blood pressure measurement in the elderly. A case for automatic recorders?

Measurement of systolic blood pressure (BP) in the elderly can be inaccurate due to observer errors such as terminal digit preference and expectation bias. Efforts to reduce these errors include use of trained observers, random-zero sphygmomanometers, and automatic BP recorders. To evaluate the value of an infrasonic recorder, the infrasonde, we compared simultaneous systolic BP determinations obtained directly by intra-arterial measurements, and indirectly by a standard cuff-mercury sphygmomanometer using clinic nurses (casual and serial measurements), a trained physician assistant (PA), and the Infrasonde in 36 elderly hypertensive men. All the indirect measurements correlated positively with the direct measurement. A terminal digit preference for zero occurred more frequently in the casual and serial readings compared with the Infrasonde and PA cuff readings: 45% and 51% vs 21% and 22%, respectively. Our data suggest that the Infrasonde is a reliable, alternative device for systolic BP measurement that eliminates observer biases associated with standard cuff BP recordings.     

A prospective trial of colchicine for primary biliary cirrhosis

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.     

Pulmonary hemorrhage in systemic lupus erythematosus.

The clinicopathological features of four patients with systemic lupus erythematosus and pulmonary hemorrhage are described. Our study confirms that pulmonary hemorrhage may be a dominant clinical expression of lung involvement in this disease. Its clinical manifestations are usually quite characteristic. However, hemoptysis may be absent. Radiographically, bilateral alveolar infiltrates resembling pulmonary edema or infection may be seen. Pulmonary hemorrhage was a major contributing factor to the death of three of our patients. The possible pathogenetic mechanisms responsible for pulmonary hemorrhage in our patients and other patients previously recorded in the literature are reviewed. Evidence supporting an immune complex pathogenesis is presented. Our immunopathological and ultrastructural studies demonstrate deposition of immune aggregates in the lungs in the alveolar septa, large blood vessels, and bronchioles in a manner similar to that which has been observed in the experimental serum sickness model of immune complex mediated pulmonary injury. The histological abnormalities, although nonspecific, are consistent with this interpretation, and collectively show diffuse alveolar lining cell and endothelial cell injury. However, an immune complex pathogenesis may not completely explain the occurrence of pulmonary hemorrhage in SLE. Other factors, including bleeding disorders, pulmonary infection, oxygen toxicity, and the "shock lung" syndrome, may also have contributed to lung hemorrhage in some of these patients.     

The effects of varying dietary fat on the nutrient intake in male and female runners

OBJECTIVE: The present study examined the effects of varying dietary fat levels on nutrients in female and male endurance runners. METHODS: Three diets (low, medium and high fat) were designed for each subject using their food preferences and three-day food records. Each diet was eaten for 28 to 31 days. The diets were self-selected from seven-day sample menus. Twelve male and 13 female runners between 18 and 55 years of age who averaged 42 miles/week participated in the study. Daily food intakes, activity records and weekly palatability/hunger scales were completed. RESULTS: Dietary fat intakes, as a percent of total energy intake (%E), averaged 17%E, 31%E, and 44%E on the low, medium and high fat diets, respectively. Energy consumption was less than their estimated energy expenditure (EEE) on all diets. On the low fat diet, the female runners were consuming approximately 60% of their EEE. As dietary fat increased, the difference between calorie intake and estimated energy expenditure became less and the subjects were less hungry on the two higher fat diets. For all subjects, as energy intakes increased, so did carbohydrate intake. Therefore, carbohydrate intake was not different on the two lower fat diets. Irrespective of gender, calcium and zinc intakes, which were below 1989 RDAs, increased with increasing fat intakes, between the low and medium fat diets. Zinc intake was also higher on the highest fat diet. Essential fatty acid intakes for females on the low fat diet were less than 2.5%E. Half of the female runners ate less than the RDA of calcium and zinc on the low fat diet and Fe on the medium fat diet. CONCLUSION: This study suggests that endurance runners may not be consuming enough calories on a low fat diet and that increasing dietary fat increased energy consumption. On the low fat diet, essential fatty acids and some minerals (especially zinc) may be too low. A low fat diet could compromise health and performance.     

Design, synthesis, and activity of 2,6-diphenoxypyridine-derived factor Xa inhibitors.

A novel series of 2,6-diphenoxypyridines has been designed to inhibit factor Xa, a serine protease strategically located in the coagulation cascade. The evolution from the photochemically unstable bisamidine (Z,Z)-BABCH to potent bisamidine compounds with a pyridine heterocycle as the core scaffold has been achieved. The most potent compound in the series, 6h, has a Ki for human factor Xa of 12 nM. The selectivity of 6h against bovine trypsin and human thrombin was greater than 90- and 1000-fold, respectively. Two proposed modes of binding of 6h to factor Xa are made based on the crystal structures of 6h by itself and of 6h bound to bovine trypsin.     

Protein Phosphatase 1 binds strongly to the retinoblastoma protein but not to p107 or p130 in vitro and in vivo

PURPOSE: To identify and characterize retinoblastoma protein (pRb) binding proteins that may influence retinoblast proliferation and retinal pigment epithelial cell survival. METHODS: The yeast two-hybrid system was used to screen a bovine retinal cDNA library and to characterize positive clones. DNA sequencing and site-directed mutagenesis were used for further analysis. Co-immunoprecipitation experiments were used to confirm the results of the two-hybrid system in vivo. RESULTS: In the two-hybrid system, Protein Phosphatase 1alpha1 (PP1alpha1) binds the retinoblastoma protein. Unlike several other pRb binding proteins, PP1alpha1 binds only weakly to the Rb family member p107, and does not demonstrate detectable binding to p130. Confirming the two-hybrid results, endogenous PP1 in a human retinal pigment epithelial (RPE) cell line co-immunoprecipitates with endogenous pRb but not p107 or p130. Site directed mutagenesis of two pRb binding motifs in PP1alpha1 from LXSXE to LXCXE leads to slight increases in its two-hybrid interaction with pRb but does not alter its binding preference for pRb over the other family members. The complete sequence of bovine PP1alpha1 is reported. CONCLUSIONS: The strong two-hybrid interaction between PP1alpha1 and pRb, but not p107 or p130, suggests that the phosphorylation status of members of the pRb family may be regulated by different phosphatases, contributing to fine control of cell cycle progression. Conversely, PP1 activity may be specifically regulated by pRb and not p107 or p130. Mutagenesis studies suggest that PP1alpha1's LXSXE motif is not responsible for its binding preference for pRb over p107 and p130. Disruption of the PP1-pRb interaction may influence retinoblastoma tumorigenesis as well as RPE cell proliferation and survival.