Faculty Bibliography

The purpose of this review is to summarize the available information regarding salt sensitivity particularly as it relates to non-Hispanic blacks and Hispanics and to clarify possible etiologies, especially those that might shed light on potential treatment options. In non-Hispanic blacks, there is evidence that endothelial dysfunction, reduced potassium intake, decreased urinary kallikrein excretion, upregulation of sodium channel activity, dysfunction in atrial natriuretic peptide (ANP) production, and APOL1 gene nephropathy risk variants may cause or contribute to salt sensitivity. Supported treatment avenues include diets high in potassium and soybean protein, the components of which stimulate nitric oxide production. Racial heterogeneity complicates the study of salt sensitivity in Hispanic populations. Caribbean Hispanics, who have a higher proportion of African ancestry, may respond to commonly prescribed anti-hypertensive agents in a way that is characteristic of non-Hispanic black hypertensives. The low-renin hypertensive phenotype commonly seen in non-Hispanic blacks has been linked to salt sensitivity and may indicate an increased risk for salt sensitivity in a portion of the Hispanic population. In conclusion, increased morbidity and mortality associated with salt sensitivity mandates further studies evaluating the efficacy of tailored dietary and pharmacologic treatment in non-Hispanic blacks and determining the prevalence of low renin hypertension and salt sensitivity within the various subgroups of Hispanic Americans.

BACKGROUND: : Patients with ulcerative colitis and Crohn's colitis have an increased risk of colon cancer influenced by the duration, extent, and severity of disease. Surveillance colonoscopy serves to detect cancer and precancerous dysplasia at the earliest possible time. Reduction of inflammation should theoretically reduce the development of cancer. Immunosuppressives should do so, but there is a fear that indeed the risk of cancer might be increased with their use. Our study was conducted to determine whether a relationship exists between receiving treatment with 6-MP for ulcerative and Crohn's colitis and increasing or decreasing the incidence of colorectal cancer (CRC). METHODS: : We conducted a single-center, retrospective cohort study of patients with long standing colitis (ulcerative and Crohn's) using the database of the senior investigator (B.I.K.). Two groups were matched based on their propensity to receive treatment with 6-MP; one group received 6-MP treatment, the other did not. Both groups were compared on the incidence of colon cancer. RESULTS: : No significant differences existed between the two cohorts with regard to type of disease, duration, extent, age, and sex. Six out of 27 patients not on 6-MP and seven out of 27 patients on 6-MP developed CRC (P= 1). CONCLUSIONS: : We conclude that there is neither sufficient evidence currently to state that 6-MP is associated with an increased development of CRC, nor that it has a chemopreventive effect.

OBJECTIVE:A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. METHODS:A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. RESULTS:Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. INTERPRETATION/CONCLUSIONS:Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences.

Multiple myeloma (MM) is an ancient disease, but until the alkylating agent melphalan was found to have anti-myeloma properties in the 1950s there was virtually no effective therapy. By the late 1960s, extended dosing with melphalan and prednisone tripled survival from diagnosis and became the standard of care for newly diagnosed MM. "Maintenance therapy" to prolong survival through sustained disease control following induction chemotherapy was sought by 1970, but early strategies were ineffective and toxic. Subsequent applications of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment paradigm for MM from extended dosing to an intensive strategy designed to eradicate the malignant cells in a single course of treatment. Although HDT-ASCT resulted in prolonged duration of remission and improved survival, the vast majority of patients still relapsed. Interferon (IFN) and glucocorticoid maintenance therapies demonstrated marginal improvements in outcomes but significant adverse effects. Novel agents introduced over the last decade have prolonged survival when given for maintenance following HDT-ASCT, but have also challenged the HDT-ASCT paradigm by achieving comparable remission rates when used alone as extended frontline therapy. This article reviews the evolution of therapeutic strategies for MM and discusses future questions facing MM investigators.

We used data from the STD Surveillance Network to estimate HIV testing among patients being tested or treated for gonorrhea. Of 1,845 gonorrhea-infected patients identified through nationally notifiable disease data, only 51% were tested for HIV when they were tested or treated for gonorrhea. Among the 10 geographic sites in this analysis, the percentage of patients tested for HIV ranged from 22-63% for men and 20-79% for women. Nearly 33% of the un-tested patients had never been previously HIV-tested. STD clinic patients were more likely to be HIV-tested than those in other practice settings.

Most studies on Staphylococcus aureus have focused on the molecular epidemiology of methicillin-resistant S. aureus (MRSA) infections. In contrast, little information is available regarding the molecular epidemiology of currently circulating methicillin-susceptible S. aureus (MSSA) isolates in hospital settings, an epoch when the epidemiology of S. aureus has undergone significant changes. We conducted a cross-sectional study to compare the clinical, epidemiological, and genetic characteristics of MSSA and MRSA isolates at 3 tertiary-care hospitals in Medellin, Colombia, from February 2008 to June 2010. The infections were classified according to the Centers for Disease Control and Prevention (CDC) definitions. Genotypic analysis included spa typing, multilocus sequence typing (MLST) and staphylococcal cassette chromosome (mec) (SCCmec) typing. A total of 810 patients was enrolled. One hundred infections (12.3%) were classified as community-associated (31 CA-MSSA, 69 CA-MRSA), 379 (46.8%) as healthcare-associated community-onset (136 HACO-MSSA, 243 HACO-MRSA), and 331 (40.9%) as healthcare-associated hospital-onset (104 HAHO-MSSA, 227 HAHO-MRSA). Genotype analyses showed a higher diversity and a more varied spa type repertoire in MSSA than in MRSA strains. Most of the clinical-epidemiological characteristics and risk factors evaluated did not allow for discriminating MRSA- from MSSA-infected patients. The lack of equivalence among the genetic backgrounds of the major MSSA and MRSA clones would suggest that the MRSA clones are imported instead of arising from successful MSSA clones. This study emphasizes the importance of local surveillance to create public awareness on the changing S. aureus epidemiology.

Past work has suggested a lasting impact of military service on the lives of veterans. By intervening at a critical stage in the lives of young men, service may open up opportunities for disadvantaged youth. In contrast, the negative consequences of exposure to combat may offset these presumed advantages. Induction into the military is also a nonrandom process that makes identifying the effects of service exceedingly difficult. In this study we use an instrumental variable (IV) approach to model the causal impact of Vietnam-era military service on two outcomes, marital stability and co-residence with adult offspring. We find limited evidence to suggest that military service may have a lasting effect on family life. In particular, we find that service reduces the probability of marital dissolution for white men. Service also significantly increases the probability of filial co-residence for men of other races.

STUDY OBJECTIVE: Our objective is to determine whether a point-of-care intervention that navigates willing, low-acuity patients from the emergency department (ED) to a Primary Care Clinic will increase future primary care follow-up. METHODS: We conducted a quasi-experimental trial at an urban safety net hospital. Adults presenting to the ED for select low-acuity problems were eligible. Patients were excluded if arriving by emergency medical services, if febrile, or if the triage nurse believed they required ED care. We enrolled 965 patients. Navigators escorted a subset of willing participants to the Primary Care Clinic (in the same hospital complex), where they were assigned a personal physician, were given an overview of clinic services, and received same-day clinic care. The primary outcome was Primary Care Clinic follow-up within 1 year of the index ED visit among patients having no previous primary care provider. RESULTS: In the bivariate intention-to-treat analysis, 50.3% of intervention group patients versus 36.9% of control group patients with no previous primary care provider had at least 1 Primary Care Clinic follow-up visit in the year after the intervention. In the multivariable analysis, the absolute difference in having at least 1 Primary Care Clinic follow-up for the intervention group compared with the control group was 9.3% (95% confidence interval 2.2% to 16.3%). There was no significant difference in the number of future ED visits. CONCLUSION: A point-of-care intervention offering low-acuity ED patients the opportunity to alternatively be treated at the hospital's Primary Care Clinic resulted in increased future primary care follow-up compared with standard ED referral practices.

INTRODUCTION: Special concerns often arise when medical students are themselves the subjects of education research. A recently completed large, multi-center randomized controlled trial of computer-assisted learning modules for surgical clerks provided the opportunity to explore the perceived level of risk of studies where medical students serve as human subjects by reporting on: 1) the response of Institutional Review Boards (IRBs) at seven institutions to the same study protocol; and 2) the thoughts and feelings of students across study sites about being research subjects. METHODS: From July 2009 to August 2010, all third-year medical students at seven collaborating institutions were eligible to participate. Patterns of IRB review of the same protocol were compared. Participation burden was calculated in terms of the time spent interacting with the modules. Focus groups were conducted with medical students at each site. Transcripts were coded by three independent reviewers and analyzed using Atlas.ti. RESULTS: The IRBs at the seven participating institutions granted full (n=1), expedited (n=4), or exempt (n=2) review of the WISE Trial protocol. 995 (73% of those eligible) consented to participate, and 207 (20%) of these students completed all outcome measures. The average time to complete the computer modules and associated measures was 175 min. Common themes in focus groups with participant students included the desire to contribute to medical education research, the absence of coercion to consent, and the low-risk nature of the research. DISCUSSION: Our findings demonstrate that risk assessment and the extent of review utilized for medical education research vary among IRBs. Despite variability in the perception of risk implied by differing IRB requirements, students themselves felt education research was low risk and did not consider themselves to be vulnerable. The vast majority of eligible medical students were willing to participate as research subjects. Participants acknowledged the time demands of their participation and were readily able to withdraw when those burdens became unsustainable.