Relative Efficacy Of Different Strategies Research Articles

Antiviral Therapy in Lamivudine-Resistant Chronic Hepatitis B Patients: A Systematic Review and Network Meta-Analysis.

The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta-analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36–113.66), ADV (OR, 37.28; 95% CrI: 9.73–142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70–77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R.

The Relative Efficacies of Gastroprotective Strategies in Chronic Users of Nonsteroidal Anti-inflammatory Drugs

There are numerous gastroprotective strategies recommended for reducing the risk of upper gastrointestinal (GI) complications in long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs). The relative efficacy of the different strategies alone or in combination is uncertain. We used the Manitoba Population Health Research Data Repository to perform a population-based matched case-control analysis. All NSAID users (nonselective and cyclooxygenase [COX]-2-specific) users admitted to the hospital with a primary diagnosis for an upper gastrointestinal complication were matched to NSAID-using controls in the community. We used conditional logistic regression analysis to determine the relative efficacy of different gastroprotective strategies (proton pump inhibitors [PPIs], COX-2 inhibitors, and low-dose/high-dose misoprostol) either alone or in combination and to adjust for multiple pertinent covariates. A total of 1382 NSAID/COX-2 users with upper GI complications were matched to 33,957 age- and sex-matched controls. Cotherapy with PPIs or misoprostol or use of a COX-2 inhibitor all significantly reduced the risk of upper GI complications. COX-2 inhibitors were not statistically more likely to prevent upper GI complications than PPIs, although they were superior to low-dose misoprostol. The combination of COX-2 inhibitors with a PPI was associated with the greatest degree of upper GI complication risk reduction. All of the commonly accepted gastroprotective strategies reduce the risk of upper GI complications in NSAID users, although the combination of COX-2 inhibitors with PPIs promotes the greatest risk reduction for NSAID-related upper GI complications. Celecoxib use specifically may be superior to the combination of nonselective NSAIDs with a PPI.

In vitro and in vivo osteoblastic differentiation of BMP‐2‐ and Runx2‐engineered skeletal myoblasts

Genetic engineering with osteogenic factors is a promising approach for cell-based therapeutics and orthopedic regeneration. However, the relative efficacy of different strategies for inducing osteoblastic differentiation remains unclear and is further complicated by varied delivery vehicles, cell types, and evaluation criteria. In order to elucidate the effects of distinct gene-based strategies, we quantitatively evaluated osteoblastic differentiation and mineralization of primary skeletal myoblasts overexpressing either the BMP-2 growth factor or Runx2 transcription factor. Retroviral delivery of BMP-2 or Runx2 stimulated differentiation into an osteoblastic phenotype, as demonstrated by the induction of osteogenic gene expression, alkaline phosphatase activity, and matrix mineralization in monolayer culture and on collagen scaffolds both in vitro and in an intramuscular site in vivo. In general, BMP-2 stimulated osteoblastic markers faster and to a greater extent than Runx2, although we also identified experimental conditions under which these two factors produced similar effects. Additionally, Runx2-engineered cells did not utilize paracrine signaling via secreted osteogenic factors, in contrast to cells overexpressing BMP-2, as demonstrated by conditioned media studies and activation of Smad signaling. These results emphasize the complexity of gene therapy-based orthopedic therapeutics as an integrated relationship of differentiation state, construct maturation, and paracrine signaling of osteogenic cells. This study is significant in evaluating proposed therapeutic systems and defining a successful strategy for integrating gene medicine and orthopedic regeneration.

Assessment of Population Exposure and Carcinogenic Risk Posed by Volatile Organic Compounds in Indoor Air

A number of air pollutants are being found in low concentrations in indoor and outdoor air. Several studies have measured these concentrations for a large number of compounds in hundreds of residences. The concentrations range over several orders of magnitude over time and space. The log-normal distributions that are found make it possible to assess the impact on the health of populations, especially for genotoxic effects for which a threshold concentration is not expected to exist. Spreadsheets can be constructed which incorporate the unit risk of a substance for cancer, the distribution of concentrations of the substance in the population, and the size of the population into an assessment of the expected excess cases of cancer that can be attributed to the population exposure to such a toxicant. This approach allows for the evaluation of population risk for different substances as found in different environments, and for the evaluation of the relative efficacy of different strategies for population risk reduction.