Publications

GOALS

We sought to identify factors associated with gastroenterology clinic attendance in an urban safety net healthcare system.

BACKGROUND

Missed clinic appointments reduce the efficiency and availability of healthcare, but subspecialty clinic attendance among patients with established healthcare access has not been studied.

STUDY

We performed an observational study using secondary data from administrative sources to study patients referred to, and scheduled for an appointment in, the adult gastroenterology clinic serving the safety net healthcare system of San Francisco, CA. Our dependent variable was whether subjects attended or missed a scheduled appointment. Analysis included multivariable logistic regression and classification tree analysis. A total of 1833 patients were referred and scheduled for an appointment between May 2005 and August 2006. Prisoners were excluded. All patients had a primary care provider.

RESULTS

Six hundred eighty-three patients (37.3%) missed their appointment; 1150 patients (62.7%) attended. Language was highly associated with attendance in the logistic regression; non-English speakers were less likely than English speakers to miss an appointment [adjusted odds ratio 0.42 (0.28, 0.63) for Spanish, 0.56 (0.38, 0.82) for Asian language, P<0.001]. Other factors were also associated with attendance, but classification tree analysis identified language to be the most highly associated variable.

CONCLUSIONS

In an urban safety net healthcare population, among patients with established healthcare access and a scheduled gastroenterology clinic appointment, not speaking English was most strongly associated with higher attendance rates. Patient-related factors associated with not speaking English likely influence subspecialty clinic attendance rates, and these factors may differ from those affecting general healthcare access.

BACKGROUND

Social smoking is increasingly prevalent and poses a challenge to traditional cessation practices. Tobacco companies conducted extensive research on social smokers long before health authorities did and marketed products to promote this smoking behavior.

PURPOSE

Research is described and mechanisms identified that are used to promote social smoking to help improve cessation strategies in this growing group.

EVIDENCE ACQUISITION

Searches from 2006 to 2008 of previously secret tobacco industry documents using keywords social smoker, light smoker, casual smoker, youth smoker, and occasional smoker, followed by snowball searching. Data analysis was conducted in 2008.

EVIDENCE SYNTHESIS

Tobacco industry research identified characteristics of social smokers that include: (1) denial of personal nicotine addiction; (2) self-categorization as a nonsmoker; (3) propensity for decreased tobacco use in response to smoke-free laws; (4) variations in age, education, ethnicity, and socioeconomic backgrounds; and (5) a perceived immunity to personal health effects of tobacco but fear of consequences to others. Tobacco companies developed marketing strategies aimed at social smokers, including "non-habit forming" cigarettes.

CONCLUSIONS

Previously considered a transient behavior, social smoking is also a stable consumption pattern. Focused clinical questions to detect social smoking are needed and may include, "Have you smoked any cigarettes or used any tobacco products in the past month?" as opposed to "Are you a smoker?" Clinicians should recognize that social smokers might be motivated to quit after education on the dangers of secondhand smoke rather than on personal health risks or with pharmacotherapy.

BACKGROUND

Claims in the medical literature suggest that neck fullness and witnessed neck pulsations are useful in the diagnosis of typical AV nodal reentrant tachycardia (AVNRT).

HYPOTHESIS

Neck fullness and witnessed neck pulsations have a high positive predictive value in the diagnosis of typical AVNRT.

METHODS

We performed a cross-sectional study of consecutive patients with palpitations presenting to a single electrophysiology (EP) laboratory over a 1 year period. Each patient underwent a standard questionnaire regarding neck fullness and/or witnessed neck pulsations during their palpitations. The reference standard for diagnosis was determined by electrocardiogram and invasive EP studies.

RESULTS

Comparing typical AVNRT to atrial fibrillation (AF) or atrial flutter (AFL) patients, the proportions with neck fullness and witnessed neck pulsations did not significantly differ: in the best case scenario (using the upper end of the 95% confidence interval (CI), none of the positive or negative predictive values exceeded 79%. After restricting the population to those with supraventricular tachycardia (SVT) other than AF or AFL, neck fullness again exhibited poor test characteristics; however, witnessed neck pulsations exhibited a specificity of 97% (95% CI: 90%-100%) and a positive predictive value of 83% (95% CI: 52%-98%). After adjustment for potential confounders, SVT patients with witnessed neck pulsations had a seven-fold greater odds of having typical AVNRT, p = 0.029.

CONCLUSIONS

Although neither neck fullness nor witnessed neck pulsations are useful in distinguishing typical AVNRT from AF or AFL, witnessed neck pulsations are specific for the presence of typical AVNRT among those with SVT.

OBJECTIVES

Antimalarial combination therapy is used in persons with HIV infection in the absence of data on drug interactions. The objective of this study was to investigate the pharmacokinetics (PK) of antimalarial combination artemether/lumefantrine (AL) when administered with the protease inhibitor combination lopinavir/ritonavir (LPV/r) in HIV-uninfected healthy volunteers to determine if important drug interactions exist between these agents.

DESIGN

Open-label study in healthy HIV-seronegative adults.

METHODS

Participants received standard 6-dose treatment courses of AL 80/480 mg twice daily on days 1-4 and 28-31. LPV/r 400/100 mg twice daily was administered on days 16-41 after a 2-week washout period. Plasma concentrations of AL, dihydroartemisinin (DHA, artemether metabolite), lopinavir, and ritonavir were measured.

RESULTS

PK of lumefantrine was influenced by LPV/r resulting in 2- to 3-fold increases in area under the curve (AUC) (AUC0-264: 413 versus 931 h.microg.mL; AUC0-inf: 456 versus 1073 h.microg.mL). For artemether, trends toward Cmax and AUC decreases (Cmax 14.3 versus 11.2 ng/mL and 42.7-62.0 versus 25.9-40.5 h.ng.mL for AUC) were noted during coadministration. For DHA, decreases in Cmax (58.8 versus 37.3 ng/mL) and AUC (190-198 versus 104-109 h.ng.mL) were observed during coadministration without changes in DHA:artemether AUC ratios. AL did not affect LPV/r PK.

CONCLUSIONS

Coadministration of artmether/lumefantrine and LPV/r can be carried out for patients coinfected with malaria and HIV. Formal safety analysis of concomitant therapy should be addressed by future studies among individuals living in malaria-endemic regions.

BACKGROUND

Kaposi sarcoma-associated herpesvirus (KSHV) infection is endemic among adult populations in Africa. A prevailing view is that childhood transmission is primarily responsible for the high seroprevalence of KSHV among adults that is observed throughout the continent. However, few studies have directly examined children, particularly in locations where KS is not commonly endemic.

METHODS

Participants were children aged 1.5-8.9 years, including 427 children from a population-based sample in South Africa, 422 from a population-based sample in Uganda, and 567 from a clinic-based sample in Uganda. All serum specimens were tested by the same laboratory for KSHV antibodies with use of 2 enzyme immunoassays (against K8.1 and ORF65) and 1 immunofluorescence assay.

RESULTS

KSHV seroprevalence was 7.5%-9.0% among South African children and was not associated with age. In contrast, in the Ugandan population-based sample, KSHV seroprevalence increased from 10% among 2-year-old children to 30.6% among 8-year-old children (P(trend) < .001). In the Ugandan clinic-based sample, seroprevalence increased from 9.3% among 2-year-old children to 36.4% among 8-year-old children (P(trend) < .001).

CONCLUSION

Two distinct relationships between age and KSHV infection among children imply that KSHV transmission among children is not uniform throughout Africa and is therefore not always responsible for the high seroprevalence observed in adults. There are at least 2 patterns of KSHV transmission in Africa.

Dysfunction of lymphatic valves underlies human lymphedema, yet the process of valve morphogenesis is poorly understood. Here, we show that during embryogenesis, lymphatic valve leaflet formation is initiated by upregulation of integrin-alpha9 expression and deposition of its ligand fibronectin-EIIIA (FN-EIIIA) in the extracellular matrix. Endothelial cell-specific deletion of Itga9 (encoding integrin-alpha9) in mouse embryos results in the development of rudimentary valve leaflets characterized by disorganized FN matrix, short cusps, and retrograde lymphatic flow. Similar morphological and functional defects are observed in mice lacking the EIIIA domain of FN. Mechanistically, we demonstrate that in primary human lymphatic endothelial cells, the integrin-alpha9-EIIIA interaction directly regulates FN fibril assembly, which is essential for the formation of the extracellular matrix core of valve leaflets. Our findings reveal an important role for integrin-alpha9 signaling during lymphatic valve morphogenesis and implicate it as a candidate gene for primary lymphedema caused by valve defects.

BACKGROUND

Prior research on the risk of depression in chronic obstructive pulmonary disease (COPD) has yielded conflicting results. Furthermore, we have an incomplete understanding of how much depression versus respiratory factors contributes to poor health-related quality of life.

METHODS

Among 1202 adults with COPD and 302 demographically matched referents without COPD, depressive symptoms were assessed using the 15-item Geriatric Depression Score. We measured COPD severity using a multifaceted approach, including spirometry, dyspnea, and exercise capacity. We used the Airway Questionnaire 20 and the Physical Component Summary Score to assess respiratory-specific and overall physical quality of life, respectively.

RESULTS

In multivariate analysis adjusting for potential confounders including sociodemographics and all examined comorbidities, COPD subjects were at higher risk for depressive symptoms (Geriatric Depression Score >or=6) than referents (odds ratio [OR] 3.6; 95% confidence interval [CI], 2.1-6.1; P <.001). Stratifying COPD subjects by degree of obstruction on spirometry, all subgroups were at increased risk of depressive symptoms relative to referents (P <.001 for all). In multivariate analysis controlling for COPD severity as well as sociodemographics and comorbidities, depressive symptoms were strongly associated with worse respiratory-specific quality of life (OR 3.6; 95% CI, 2.7-4.8; P <.001) and worse overall physical quality of life (OR 2.4; 95% CI, 1.8-3.2; P <.001).

CONCLUSIONS

Patients with COPD are at significantly higher risk of having depressive symptoms than referents. Such symptoms are strongly associated with worse respiratory-specific and overall physical health-related quality of life, even after taking COPD severity into account.

Predicting drug kinetics and dynamics in an individual patient is a worthy goal and has some chance of success for drugs subject to marked pharmacogenetic differences. However, one should not expect any prediction success for drugs primarily metabolized by the major cytochrome P450 enzyme, CYP3A4, whether one uses an exogenous drug or an endogenous metabolic process, such as the oxidation of cortisol.

BACKGROUND

The selective MAO-B inhibitor selegiline has been evaluated in clinical trials as a potential medication for the treatment of cocaine dependence. This study evaluated the safety of and pharmacologic interactions between 7 days of transdermal selegiline dosed with patches (Selegiline Transdermal System, STS) that deliver 6 mg/24 hours and 2.5 mg/kg of cocaine administered over 4 hours.

METHODS

Twelve nondependent cocaine-experienced subjects received deuterium-labeled cocaine-d5 intravenously (IV) 0.5 mg/kg over 10 minutes followed by 2 mg/kg over 4 hours before and after one week of transdermal selegiline 6 mg/24 hours. Plasma and urine were collected for analysis of selegiline, cocaine, catecholamine and metabolite concentrations. Pharmacodynamic measures were obtained.

RESULTS

Selegiline did not change cocaine pharmacokinetic parameters. Selegiline administration increased phenylethylamine (PEA) urinary excretion and decreased urinary MHPG-sulfate concentration after cocaine when compared to cocaine alone. No serious adverse effects occurred with the combination of selegiline and cocaine, and cocaine-induced physiological effects were unchanged after selegiline. Only 1 peak subjective cocaine effects rating changed, and only a few subjective ratings decreased across time after selegiline.

CONCLUSION

No pharmacological interaction occurred between selegiline and a substantial dose of intravenous cocaine, suggesting the combination will be safe in pharmacotherapy trials. Selegiline produced few changes in subjective response to the cocaine challenge perhaps because of some psychoactive neurotransmitters changing in opposite directions.