Publications

The Model for End-Stage Liver Disease (MELD) score incorporates serum creatinine and was introduced to facilitate allocation of orthotopic liver transplantation (LT). The objective is to determine the impact of MELD and kidney function on all-cause mortality. Among LTs performed in a tertiary referral hospital between 1995 and 2009, 419 cases were studied. Cox proportional hazards models were constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD era, 57 and 63 deaths were observed, respectively. Those transplanted during the MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01), lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs 92.6 mL/ min/1.73 m(2), P < 0.01), and more pretransplantation renal replacement therapy (RRT) (5% vs 1%; P < 0.01). All-cause mortality risk was similar in the MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58-1.65). The risk of death, however, was nearly 3-fold greater (95% CI: 1.14-6.60) among those requiring pre- transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m(2) post-transplant was associated with a 2.5-fold higher mortality (95% CI: 1.48-4.11). The study suggests that MELD implementation had no impact on all-cause mortality post-LT. However, the need for pre-transplant RRT and post-transplant kidney dysfunction was associated with a more than 2-fold greater risk of subsequent death.

BACKGROUND & AIMS

Diverticular bleeding is the most common cause of acute severe lower gastrointestinal bleeding (LGIB) in Western countries. Diagnostic and therapeutic approaches, including endoscopy, radiology, or surgery, have not been standardized. We investigated colonoscopy as a first-line modality to diagnose and manage patients with LGIB.

METHODS

We performed a retrospective study of data collected from 2 tertiary Veterans hospitals of 64 patients (61 men, 76 ± 11 years) with acute severe diverticular bleeding, based on colonoscopy examination. We assessed primary hemostasis using endoscopic clipping for diverticular bleeding and described the bleeding stigmata. We measured early (<30 days) and late rebleeding, blood transfusion requirements, hospital stay and complications.

RESULTS

Patients received 3.1 ± 3.0 and 0.9 ± 2.2 U of blood before and after colonoscopy, respectively. Twenty-four of the 64 patients (38%) had diverticular stigmata of recent hemorrhage; and 21 of these patients (88%) were treated successfully using endoscopic clips, without complication or early rebleeding. Hospital stays averaged 6.4 ± 5.6 days. Endoscopic clipping provided primary hemostasis in 9/12 patients (75%) with active diverticular bleeding. During 35 ± 18 months of follow-up, late recurrent diverticular bleeding occurred in 22% of the patients (14/64) after a mean time period of 22 months; 5 of the patients (21%) with stigmata of recent hemorrhage who received clip treatment had rebleeding at 43 months. Rebleeding was self-limited in 8 patients (57%), was clipped in 4 (29%), or was embolized in 2 (14%).

CONCLUSIONS

Colonoscopy can be a safe first-line diagnostic and therapeutic approach for patients with severe LGIB. Endoscopic clipping provides hemostasis of active diverticular bleeding. Recurrent bleeding occurs in about 21% of patients who were treated with clips, at approximately 4 years; most bleeding is self-limited or can be retreated by endoscopic clipping.

BACKGROUND

Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.

METHODS

The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.

RESULTS

HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.

CONCLUSION

HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.

Anemia is a significant health concern worldwide and can be the result of nutritional, environmental, social, and infectious etiologies. We estimated the prevalence of anemia in 336 pre-school children and 132 adults in the rural Central Plateau of Haiti and assessed associations with age, sex, household size, water source, sanitation, and Helicobacter pylori seroreactivity using logistic regression analysis; 80.1% (269/336) of children and 63.6% (84/132) of adults were anemic. Among children, younger age was associated with increased prevalence of anemia (adjusted odds ratio [aOR] = 4.1, 95% confidence interval [CI] = 1.5-11.1 for children 6-11 months compared with children 48-59 months). Among adults, 50.8% were H. pylori-seropositive, and seropositivity was inversely associated with anemia (aOR = 0.4, 95% CI = 0.2-0.9). Anemia prevalence in this region of Haiti is very high and not attributable to sanitary conditions or a high prevalence of H. pylori infection.

In this issue of Academic Medicine, Kitterman and colleagues report the results of an evaluation of the prevalence and cost of low-enrolling studies (zero or one participant enrolled) conducted at Oregon Health & Science University (OHSU). They found that one-third of all studies terminated between 2005 and 2009 at OHSU had low enrollment and that these low-enrolling studies cost the institution almost $1 million annually. The recruitment of research participants is critical to conducting clinical and translational research. Failure to recruit research participants has a negative financial impact, but, more importantly, underenrolled studies do not contribute to scientific or clinical knowledge. In this commentary, the authors describe four areas in which academic health centers (AHCs) could invest more effort and resources to improve the recruitment of research participants. First, more planning and resources should be put into determining the feasibility of participant recruitment. Second, studies that are underenrolling should be terminated early to prevent unethical research, to save financial and other resources, and to allow these resources to be applied to successful research. Third, AHCs should professionalize, centralize, and automate participant recruitment. Fourth, AHCs should take a leadership role in partnering with the public to improve participation in clinical research. Participant recruitment must be improved if clinical and translational research is to meet its promise of improving health.