Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review

Baicalin is a natural bioactive compound derived from Scutellaria baicalensis, which is extensively used in traditional Chinese medicine. A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant, anticancer, anti-inflammatory, antimicrobial, cardio-protective, hepatoprotective, renal protective, and neuroprotective properties. Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota, which is further reconverted to baicalin via phase 2 metabolism in the liver. Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis, xenobiotic-induced liver injury, fatty liver disease, viral hepatitis, cholestasis, ulcerative colitis, hepatocellular and colorectal cancer. During in vitro and in vivo examinations, it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B, transforming growth factor beta 1/SMAD3, sirtuin 1, p38/mitogen-activated protein kinase/Janus kinase, and calcium/calmodulin-dependent protein kinase kinaseβ/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways. Furthermore, baicalin also regulates the expression of fibrotic genes such as smooth muscle actin, connective tissue growth factor, β-catenin, and inflammatory cytokines such as interferon gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha, and IL-1β, and attenuates the production of apoptotic proteins such as caspase-3, caspase-9 and B-cell lymphoma 2. However, due to its low solubility and poor bioavailability, widespread therapeutic applications of baicalin still remain a challenge. This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota.     

The HIV care cascade: models,measures and moving forward

Introduction

This article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.

Discussion

Questions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm³; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.

Conclusions

There is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.     

The use of bone morphogenetic protein in thoracolumbar spine procedures: analysis of the MarketScan longitudinal database

Background contextThe use of recombinant human bone morphogenetic protein (BMP) in the thoracolumbar spine remains controversial, with many questioning the risks and benefits of this new biologic.PurposeTo describe national trends, incidence of complications, and revision rates associated with BMP use in thoracolumbar spine procedures.Study design/settingAdministrative database study.Patient sampleA matched cohort of 52,259 patients undergoing thoracolumbar fusion surgery from 2006 to 2010 were identified in the MarketScan database. Patients without BMP treatment were matched 2:1 to patients receiving intraoperative BMP.Outcome measuresRevision rates and postoperative complications.MethodsThe MarketScan database was used to select patients undergoing thoracolumbar fusion procedures, with and without intraoperative BMP. We ascertained outcome measures using either International Classification of Disease, ninth revision, or Current Procedural Terminology coding, and matched groups were evaluated using a bivariate and multivariate analyses. Kaplan-Meier estimates of fusions failure rates were also calculated.ResultsPatients receiving intraoperative BMP underwent fewer refusions, decompressions, posterior and anterior revisions, or any revision procedure (single level 4.53% vs. 5.85%, p<.0001; multilevel 5.02% vs. 6.83%, p<.0001; overall cohort 4.73% vs. 6.09%, p<.0001). After adjusting for comorbidities, demographics, and levels of procedure, BMP was not associated with the postoperative development of cancer (odds ratio 0.92). Bone morphogenetic protein use was associated with an increase in any complication at 30 days (15.8% vs. 14.9%, p=.0065), which is only statistically significant among multilevel procedures (19.74% vs. 18.02%, p=.0013). Thirty-day complications in multilevel procedures associated with BMP use included new dysrhythmia (4.68% vs. 4.01%, p=.0161) and delirium (1.08% vs. 0.69%, p=.0024). A new diagnosis of chronic pain was associated with BMP use in both single-level (2.74% vs. 2.15%, p=.0019) and multilevel (3.7% vs. 2.52%, p<.0001) procedures. Bone morphogenetic protein was negatively associated with infection in single-level procedures (2.12% vs. 2.64%, p=.0067) and wound dehiscence in multilevel procedures (0.84% vs. 1.18%, p=.0167).ConclusionsIn national data analysis of thoracolumbar procedures, we found that BMP was associated with decreased incidence of revision spinal surgery and with a slight increased risk of overall complications at 30 days. Although no BMP-associated increased risk of malignancy was found, lack of long-term follow-up precludes detection of between-group differences in malignancies and other rare events that may not appear until later.     

Patient satisfaction during the administration of local anesthesia using a computer controlled local anesthetic delivery system

Patients undergoing a surgical procedure first must be properly anesthetized prior to the procedure to minimize discomfort. The effectiveness of a Computer Controlled Local Anesthetic Delivery System (CCLADS) known as the "wand," was evaluated. Patient anxiety and pain associated with the injection of anesthesia both decreased using this method.     

In vitro evaluation of the quality of essential drugs on the Tanzanian market

We evaluated the in vitro availability and its stability under simulated tropical conditions of various formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro availability (dissolution) and its stability under simulated tropical conditions were determined using methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All formulations passed the pharmacopoeia requirements for the drug content. However, seven formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated stability test under simulated tropical conditions (75% RH/40 degrees C) for 6 months. The study has demonstrated the presence on the Tanzanian market of essential drug formulations that met potency requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand storage under simulated tropical conditions.     

Glycaemic responses after ingestion of 3 local carbohydrate-based foods in West Indian patients with type-2 diabetes mellitus

BACKGROUND & AIM: Previous studies suggest that inadequate glycaemic control in diabetic patients might be related to the type of carbohydrates the patients consume regularly. Thus, we aimed to assess glucose and insulin responses after diabetic and non-diabetic subjects ingested 3 commonly consumed carbohydrate-based foods. METHODS: Thirty-eight type-2 diabetic and 27 non-diabetic subjects were studied in 3 different occasions of 7 days apart. On each day of the study, anthropometric indices were measured and after collecting fasting blood samples, subjects randomly consumed bread, roti or rice within 10 min. Subsequently 7 ml of venous blood samples were collected at 60, 90, 120 and 150 min for determination of glucose and insulin responses. RESULTS: Although the diabetic patients were older than the healthy subjects (P < 0.05), both subjects had similar weight, body mass index and waist and hip circumferences (P > 0.05). The mean fasting and post meal plasma glucose concentrations for the 3 test foods were higher in diabetic patients than the corresponding values for the healthy subjects (all; P < 0.001). Generally, roti elicited the highest total incremental glucose responses in the diabetic patients irrespective of ethnic group (P < 0.05). CONCLUSION: There were variations in glucose and insulin responses to the 3 test foods. However, roti elicited the highest postprandial hyperglycaemia and should therefore be discouraged in regular dietary plan of diabetic patients.     

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.     

Primary vascular neoplasms unique to the spleen: littoral cell angioma and splenic hamartoma diagnosis by fine-needle aspiration biopsy

We report the fine-needle aspiration (FNA) biopsy diagnosis of two rare cases of primary vascular neoplasms unique to the spleen: a littoral cell angioma from a 31-yr-old Caucasian woman and a splenic hamartoma from a 46-yr-old black man. The cytologic features of splenic hamartoma and of littoral cell angioma of the spleen were described three times in cytologic literature: two were bench-top aspirates and one was FNA biopsy thought to be metastatic carcinoma. To the best of our knowledge, the current two cases were the first diagnosed by FNA biopsy. Our approach to the FNA biopsy diagnosis of these rare vascular neoplasms via compact cell block and immunohistochemistry is described. The differential diagnosis with other primary vascular splenic neoplasms is also discussed.     

CMS Reimbursement Reform and the Incidence of Hospital-Acquired Pulmonary Embolism or Deep Vein Thrombosis

BACKGROUND

In October 2008, the Centers for Medicare & Medicaid Services (CMS) stopped reimbursing hospitals for the marginal cost of treating certain preventable hospital-acquired conditions.

OBJECTIVE

This study evaluates whether CMS’s refusal to pay for hospital-acquired pulmonary embolism (PE) or deep vein thrombosis (DVT) resulted in a lower incidence of these conditions.

DESIGN

We employ difference-in-differences modeling using 2007–2009 data from the Nationwide Inpatient Sample, an all-payer database of inpatient discharges in the U.S. Discharges between 1 January 2007 and 30 September 2008 were considered “before payment reform;” discharges between 1 October 2008 and 31 December 2009 were considered “after payment reform.” Hierarchical regression models were fit to account for clustering of observations within hospitals.

PARTICIPANTS

The “before payment reform” and “after payment reform” incidences of PE or DVT among 65–69-year-old Medicare recipients were compared with three different control groups of: a) 60–64-year-old non-Medicare patients; b) 65–69-year-old non-Medicare patients; and c) 65–69-year-old privately insured patients. Hospital reimbursements for the control groups were not affected by payment reform.

INTERVENTION

CMS payment reform for hospital-based reimbursement of patients with hip and knee replacement surgeries.

MAIN MEASURES

The outcome was the incidence proportion of hip and knee replacement surgery admissions that developed pulmonary embolism or deep vein thrombosis.

KEY RESULTS

At baseline, pulmonary embolism or deep vein thrombosis were present in 0.81 % of all hip or knee replacement surgeries for Medicare patients aged 65–69 years old. CMS payment reform resulted in a 35 % lower incidence of hospital-acquired pulmonary embolism or deep vein thrombosis in these patients (p = 0.015). Results were robust to sensitivity analyses.

CONCLUSION

CMS’s refusal to pay for hospital-acquired conditions resulted in a lower incidence of hospital-acquired pulmonary embolism or deep vein thrombosis after hip or knee replacement surgery. Payment reform had the desired direction of effect.KEY WORDS: payment reform, pay-for-performance, hospital-acquired conditions, pulmonary embolism, deep vein thrombosis