Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain.

BACKGROUND: Voriconazole is a triazole antifungal medication used for prophylaxis or to treat invasive fungal infections. Inflammation of the periosteum resulting in skeletal pain, known as periostitis, is a reported side effect of long-term voriconazole therapy. The trifluorinated molecular structure of voriconazole suggests a possible link between excess fluoride and periostitis, as elevated blood fluoride has been reported among patients with periostitis who received voriconazole. METHODS: Two hundred sixty-four patients from Michigan were impacted by the multistate outbreak of fungal infections as a result of contaminated methylprednisolone injections. A retrospective study was conducted among 195 patients who received voriconazole therapy at St Joseph Mercy Hospital during this outbreak. Twenty-eight patients who received both bone scan and plasma fluoride measurements for skeletal pain were included in the statistical analyses. Increased tracer uptake on bone scan was considered positive for periostitis. The primary outcome measure was the correlation between plasma fluoride and bone scan results. RESULTS: Blood fluoride (P < .001), alkaline phosphatase (P = .020), daily voriconazole dose (P < .001), and cumulative voriconazole dose (P = .027) were significantly elevated in patients who had periostitis compared with those who did not. Discontinuation or dose reduction of voriconazole resulted in improvement of pain in 89% of patients. CONCLUSIONS: High plasma fluoride levels coupled with skeletal pain among patients who are on long-term voriconazole therapy is highly suggestive of periostitis. Initial measurement of fluoride may be considered when bone scan is not readily available. Early detection should be sought, as discontinuation of voriconazole is effective at reversing the disease.

Heart failure mortality prediction using PRISM score and development of a classification and regression tree model to refer patients for palliative care consultation.

INTRODUCTION: We sought to assess one-year mortality in heart failure (HF) patients by using (Placement Resource Indicator for Systems Management) PRISM, a disease nonspecific risk stratification score, and use it along with modified Seattle Heart Failure Model (SHFM) to guide patient selection for palliative care consultation. METHODS: A retrospective study design was used to examine 1-year mortality in 689 HF patients admitted from 2012 to 2014. One-year mortality was calculated using Pmort30/PRISM and modified SHFM scores, and the predicted scores were validated using the area under the ROC curve. CART was used to develop an algorithm to classify patients based on their mortality risk. RESULTS: The discriminatory ability of PRISM categorical score (AUC = 0.701) was not significantly different than the discriminatory ability of modified SHFM (AUC = 0.686) (DeLong's test p = 0.56) but improved significantly with the combination of PRISM (categorical) score + modified SHFM (AUC = 0.740) (p = 0.002). The predictive capability of the CART tree model after cross-validation was 72.2% (AUC 0.631). CONCLUSION: Our study suggests PRISM score performed as well as modified SHFM for one-year mortality prediction. Moreover, the addition of modified SHFM to PRISM score increases discriminatory ability in predicting 1-year mortality in heart failure patients compared to either of the two models alone. Together, when combined in a CART model, they can be used to identify the population subset with the highest mortality risk and hence guide goals of care discussion.

Analysis to determine cost-effectiveness of procalcitonin-guided antibiotic use in adult patients with suspected bacterial infection and sepsis.

PURPOSE: Results of a study incorporating real-world results into a predictive model to assess the cost-effectiveness of procalcitonin (PCT)-guided antibiotic use in intensive care unit patients with sepsis are reported. METHODS: A single-center, retrospective cross-sectional study was conducted to determine whether reductions in antibiotic therapy duration and other care improvements resulting from PCT testing and use of an associated treatment pathway offset the costs of PCT testing. Selected base-case cost outcomes in adults with sepsis admitted to a medical intensive care unit (MICU) were assessed in preintervention and postintervention cohorts using a decision analytic model. Cost-minimization and cost-utility analyses were performed from the hospital perspective with a 1-year time horizon. Secondary and univariate sensitivity analyses tested a variety of clinically relevant scenarios and the robustness of the model. RESULTS: Base-case modeling predicted that use of a PCT-guided treatment algorithm would results in hospital cost savings of $45 per patient and result in a gain of 0.0001 quality-adjusted life-year. After exclusion of patients in the postintervention cohort for PCT test ordering outside of institutional guidelines, the mean inpatient antibiotic therapy duration was significantly reduced in the postintervention group relative to the preintervention group (6.2 days versus 4.9 days, p = 0.04) after adjustment for patient sex and age, Charlson Comorbidity Index score, study period, vasopressor use, and ventilator use. Total annual hospital cost savings of $4,840 were predicted. CONCLUSION: Real-world implementation of PCT-guided antibiotic use may have improved patients' quality of life while decreasing hospital costs in MICU patients with undifferentiated sepsis.

Toxic effect of zinc on NF-kappaB, IL-2, IL-2 receptor alpha, and TNF-alpha in HUT-78 (Th(0)) cells.

Zinc deficiency decreased cellular immune response. Zinc supplementation reverses this response. High concentration of zinc intake is reported to alter immune response. We hypothesize that higher concentration of zinc adversely affects T-cell immune response. In this study, we examined whether higher concentration of zinc affects expression of IL-2, IL-2Ralpha, and TNF-alpha, and NF-kappaB activation in HUT-78 (Th(0)) cells. The results show that HUT-78 cells incubated in 15, 50, and 100 microM zinc medium had significantly higher intracellular zinc contents and faster growth after 4 days of incubation, compared to the cells incubated in 1 microM zinc medium. After PMA/PHA stimulation, 1 microM zinc showed significant decreases in NF-kappaB activation, and in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs compared to 15 microM zinc. The cells incubated in higher concentrations of zinc (50 and 100 microM zinc) showed mild to moderate decreases in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs, and in NF-kappaB activation compared to those incubated in 15 microM zinc medium. These data indicate that not only low level of zinc, but also high levels of zinc decrease Th1 function.

A multifactorial intervention for hospital opioid management.

OBJECTIVE: To determine whether an educational intervention combined with a voluntary decision support system improves inpatient pain control. DESIGN: Retrospective serial cross-sectional study. SETTING: Community teaching hospital. PATIENTS: Patients admitted to internal medicine teaching service from October to December 2011 and 2012. The study cohorts consisted of a random sample of 75 patients each from both time periods. INTERVENTIONS: Beginning in August 2012, internal medicine residents participated in an interactive training session on the use of opioids for hospitalized patients and concurrently, a user initiated voluntary computerized decision support system (CDSS), in the form of computer order entry (COE) and pocket cards were introduced. The COE options correspond to the standardized opioid dosing regimen on the pocket card. Pain scores and opioid doses and demographic information were obtained from administrative databases. Additional covariates were abstracted via programmed electronic medical record (EMR) review. MAIN OUTCOME MEASURES: Pre- and postintervention, maximum reported pain score in every 8-hour period from first analgesic dose, to 72 hours after the first analgesic dose, were compared by fitting a multivariable linear mixed model. Naloxone use was a surrogate measure for secondary outcome of opioid overdose. RESULTS: The intervention had no effect on maximum pain score (MPS) over time, p = 0.0930. The estimated mean MPS (95% confidence interval) was 4.7 (3.9, 5.5) preintervention and 5.2 (4.4, 6.0) postintervention. CONCLUSIONS: A combination of a resident educational intervention, CDSS, and pocket cards did not improve MPSs over time for patients on an internal medicine teaching service.

Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients.

Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.

Flexible sigmoidoscopy for colorectal cancer screening in the elderly.

Data on performance characteristics of flexible sigmoidoscopy (FS) between age groups are limited. This study evaluates screening FS in subjects > or = 75 years of age (elderly) compared with ages 50-74 years (general screening population). Data were collected on patient characteristics, insertion depth, procedural difficulties, complications, and endoscopic findings. There was an increased rate of endoscopist-reported limitations (50.4% vs. 34.9%; P = 0.0001) and incomplete examinations (15.6% vs. 5.4%; P = 0.0001) in the elderly cohort relative to subjects aged 50-74. The complication rate (1.0% vs. 1.5%; P = 0.53), adenoma detection rate (7.2% vs. 5.6%; P = 0.213), and advanced adenoma detection rate (0.71% vs 0.65%; P = 0.86) were similar. More carcinomas were detected in the elderly (0.53% vs. 0.06%; P = 0.042). Factors associated with incomplete examinations in the elderly included age, female gender, and poor bowel preparation. Despite technical difficulties, FS in the elderly is safe and detects significant pathology.