Publications

BACKGROUND

Primary care providers (PCPs) must balance treatment of chronic non-cancer pain with opioid analgesics with concerns about opioid misuse.

OBJECTIVE

We co-enrolled community-based indigent adults and their PCPs to determine PCPs’ accuracy of estimating opioid analgesic misuse and illicit substance use.

DESIGN

Patient-provider dyad study.

PARTICIPANTS

HIV-infected, community-based indigent adults (‘patients’) and their PCPs.

MAIN MEASURES

Using structured interviews, we queried patients on use and misuse of opioid analgesics and illicit substances. PCPs completed patient- and provider-specific questionnaires. We calculated the sensitivity, specificity, and measures of agreement between PCPs’ judgments and patients’ reports of opioid misuse and illicit substance use. We examined factors associated with PCPs’ thinking that their patients had misused opioid analgesics and determined factors associated with patients’ misuse.

KEY RESULTS

We had 105 patient-provider dyads. Of the patients, 21 had misused opioids and 45 had used illicit substances in the past year. The sensitivity of PCPs’ judgments of opioid analgesic misuse was 61.9% and specificity, 53.6% (Kappa score 0.09, p = 0.10). The sensitivity of PCPs’ judgments of illicit substance use was 71.1% and specificity, 66.7% (Kappa score 0.37, p <0.001). PCPs were more likely to think that younger patients (Adjusted odds ratio (AOR) 0.89, 95% CI 0.84-0.97), African American patients (AOR 2.53, 95% CI 1.05-6.07) and those who had used illicit substances in the past year (AOR 3.33, 95% CI 1.35-8.20) had misused opioids. Younger (AOR 0.94, 95% CI 0.86-1.02) and African American (AOR 0.71, 95% CI 0.25-1.97) patients were not more likely to report misuse, whereas persons who had used illicit substances were (AOR 3.01, 95% CI 1.04-8.76).

CONCLUSION

PCPs’ impressions of misuse were discordant with patients’ self-reports of opioid analgesic misuse. PCPs incorrectly used age and race as predictors of misuse in this high-risk cohort.

We demonstrate how an industry promoted and defined masculinity as a product of consumption. We analyze previously-secret tobacco industry documents and the content of two tobacco industry-produced magazines, Unlimited (from Philip Morris, makers of Marlboro) and Real Edge (from Brown & Williamson, makers of Lucky Strike), which were distributed to millions of young adult men from the late 1990s and early 2000s to promote their tobacco brands. We find that Unlimited and Real Edge exhibited similar themes previously reported to typify "new lad" magazines, but with risky behaviors in the forefront. We build upon the existing masculinity literature by providing insight into how corporations study and interpret cultural constructions of masculinity, and then use masculinity as both a vehicle and a product of consumption.

Non-alcoholic fatty liver disease is associated with multiple comorbid conditions, including diabetes, obesity, infection, and malnutrition. Mice with hepatocyte-specific disruption of growth hormone (GH) signaling develop fatty liver (FL), although the precise mechanism underlying this finding remains unknown. Because GH signals through JAK2, we developed mice bearing hepatocyte-specific deletion of JAK2 (referred to herein as JAK2L mice). These mice were lean, but displayed markedly elevated levels of GH, liver triglycerides (TGs), and plasma FFAs. Because GH is known to promote lipolysis, we crossed GH-deficient little mice to JAK2L mice, and this rescued the FL phenotype. Expression of the fatty acid transporter CD36 was dramatically increased in livers of JAK2L mice, as was expression of Pparg. Since GH signaling represses PPARγ expression and Cd36 is a known transcriptional target of PPARγ, we treated JAK2L mice with the PPARγ-specific antagonist GW9662. This resulted in reduced expression of liver Cd36 and decreased liver TG content. These results provide a mechanism for the FL observed in mice with liver-specific disruption in GH signaling and suggest that the development of FL depends on both GH-dependent increases in plasma FFA and increased hepatic uptake of FFA, likely mediated by increased expression of CD36.

A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.

Drug tolerance in bacteria is widely believed to be due to metabolic changes that accompany growth arrest. A study in this issue of Cell reveals a drug tolerance mechanism in replicating mycobacteria that is induced by residence in macrophages and depends on drug efflux.

PURPOSE

To determine the reproducibility of proton MR spectroscopy ((1) H-MRS) for assessing vertebral bone marrow adiposity at 3 Tesla (T); to evaluate variation of marrow adiposity at different vertebral levels; and to demonstrate the feasibility of using (1) H-MRS at 3T for evaluating marrow adiposity in subjects with low bone density.

MATERIALS AND METHODS

Single voxel MRS was acquired at vertebral body L1 to L4 at 3T in 51 postmenopausal females including healthy controls (n = 13) and patients with osteoporosis/osteopenia (n = 38). Marrow fat contents were compared between vertebral levels and between groups using analysis of variance (ANOVA). Six subjects were scanned twice to evaluate technique reproducibility.

RESULTS

The average coefficient of variation of vertebral marrow fat content quantification was 1.7%. Marrow fat content significantly increased from L1 to L4. The average fat content was significantly elevated in patients with osteoporosis/osteopenia compared with controls, adjusted for age and body mass index (P < 0.05).

CONCLUSION

In vivo MRS at high field strength provides reliable measurement of marrow adiposity with excellent reproducibility and can be a valuable tool for providing complementary information on bone quality and potentially also fracture risk.

Invasive fungal infections, most commonly candidiasis or aspergillosis, are a major cause of morbidity and mortality among patients with neutropenia. Difficulty in diagnosing invasive fungal infections in these patients complicates decisions regarding pharmacotherapy. Because of the difficult diagnosis and the significant morbidity and mortality of fungal infections in patients with neutropenia, systemic antifungal agents are used as empiric antifungal therapy in patients with febrile neutropenia who are not responding to antibacterial therapy. The pharmacotherapy of invasive fungal infections has evolved rapidly within the past several years as numerous antifungal agents--different formulations of amphotericin B, azoles, and echinocandins--have become available for use as empiric antifungal therapy in patients with febrile neutropenia. Various levels of evidence support the use of these agents for this indication. Their use is limited, however, by drug intolerance, drug interactions, adverse-event profiles, and limited activity with some mold species. Thus, considerations for selecting an antifungal drug for empiric use in patients with febrile neutropenia should include the epidemiology of fungal infections in the individual patient's institution and the specific clinical circumstances of the patient.

The formation of a permeability barrier between the external environment and the host is essential for survival. To provide this barrier keratinocytes undergo a complex pathway of differentiation, which culminates in keratinocyte cornification and the formation of extracellular lipid enriched lamellar membranes in the stratum corneum. The mechanisms that coordinately regulate the parallel formation of the corneocytes and lamellar membranes are unknown. The extracellular lamellar membranes are derived from the exocytosis of lamellar bodies and to synthesize lamellar bodies the keratinocyte must have abundant quantities of cholesterol, fatty acids and ceramides. These lipids could serve as signaling molecules and thereby coordinately regulate the formation of the stratum corneum. Fatty acids activate PPARs and studies have shown that PPAR activation stimulates keratinocyte differentiation. Cholesterol is converted to oxysterols that activate LXR and studies have shown that LXR activation also stimulates keratinocyte differentation. Additionally, PPAR and LXR activation also facilitates the formation of the lipid enriched lamellar membranes. Ceramides, via a number of mechanisms also stimulate keratinocyte differentiation. Recently, studies have shown that ceramides by increasing PPAR delta also increase the expression of ABCA12, which would facilitate the formation of lamellar bodies. Finally, keratinocytes accumulate a large quantity of cholesterol sulfate, which plays a key role in regulating desquamation. Cholesterol sulfate has also been shown to stimulate keratinocyte differentiation. Thus, cholesterol, cholesterol sulfate, fatty acids and ceramides all stimulate keratinocyte differentiation and thereby could coordinately regulate the formation of the stratum corneum.