Publications

IMPORTANCE

Many proposals for health care reform incentivize patients to play a more active role in selecting health care providers on the basis of quality and price. While data on quality are increasingly available, availability of pricing data is uncertain.

OBJECTIVE

To examine whether we could obtain pricing data for a common elective surgical procedure, total hip arthroplasty (THA).

DESIGN

We randomly selected 2 hospitals from each state (plus Washington, DC) that perform THA, as well as the 20 top-ranked orthopedic hospitals according to US News and World Report rankings. We contacted each hospital by telephone between May 2011 and July 2012. Using a standardized script, we requested from each hospital the lowest complete "bundled price" (hospital plus physician fees) for an elective THA that was required by one of the author's 62-year-old grandmother. In our scenario, the grandmother did not have insurance but had the means to pay out of pocket. We explained that we were seeking the lowest complete price for the procedure. When we encountered hospitals that could provide the hospital fee only, we contacted a random hospital affiliated orthopedic surgery practice to obtain the physician fee. Each hospital was contacted up to 5 times in efforts to obtain pricing information.

SETTING/PARTICIPANTS

All top-ranked and a sample of non-top-ranked US hospitals performing THA.

MAIN OUTCOME MEASURES

Percentage of hospitals able to provide a complete price estimate for THA (physician and hospital fee) for top-ranked and non-top-ranked hospitals and range of prices quoted by each group.

RESULTS

Nine top-ranked hospitals (45%) and 10 non-top-ranked hospitals (10%) were able to provide a complete bundled price (P < .001). We were able to obtain a complete price estimate from an additional 3 top-ranked hospitals (15%) and 54 non-top-ranked hospitals (53%) (P = .002) by contacting the hospital and physician separately. The range of complete prices was wide for both top-ranked ($12,500-$105,000) and non-top-ranked hospitals ($11,100-$125,798).

CONCLUSIONS AND RELEVANCE

We found it difficult to obtain price information for THA and observed wide variation in the prices that were quoted. Many health care providers cannot provide reasonable price estimates. Patients seeking elective THA may find considerable price savings through comparison shopping.

The increased incidence of drug-resistant tuberculosis has created an urgent necessity for the development of new and effective anti-tuberculosis drugs and for alternative therapeutic regimens. Clofazimine (CFZ) is a fat-soluble riminophenazine dye used in the treatment of leprosy worldwide. CFZ has also been used as a Group 5 drug in the treatment of tuberculosis (TB). A large cohort study from Bangladesh published in 2010 described a treatment regimen for multidrug-resistant tuberculosis (MDR-TB) including CFZ as being highly effective against MDR-TB. We searched multiple databases for studies published through February 2012 that reported use of CFZ in MDR- and extensively drug-resistant TB (XDR-TB) treatment regimens. We identified nine observational studies (6 MDR-TB and 3 XDR-TB) including patients with drug-resistant TB treated with CFZ. Overall, 65% (95% confidence interval [95%CI] 54-76) of the patients experienced favorable outcomes, defined as either cure or treatment completion. Using random effects meta-analysis, 65% (95%CI 52-79) of those with MDR-TB and 66% (95%CI 42-89) of those with XDR-TB experienced favorable treatment outcomes. High-quality prospective cohort studies and clinical trials examining the effect of CFZ as part of drug-resistant TB treatment regimens are needed.

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans.

BACKGROUND

HIV protease inhibitors (PI) are core components of Highly Active Antiretroviral Therapy (HAART), the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER) stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.

METHODOLOGY AND PRINCIPAL FINDINGS

Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP(-/-) mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes.

CONCLUSION AND SIGNIFICANCE

Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients.