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Objective: Evaluate the efficacy of L-methylfolate in combination with SSRI or SNRI compared to SSRI or SNRI monotherapy in a major depressive episode. Design: A retrospective analysis of L-methylfolate plus SSRI/SNRI at treatment initiation (n=95) and SSRI/SNRI monotherapy (n=147) from patient charts. Setting: Outpatient, private psychiatric clinic/practice. Participants: Adults 18 to 70 with major depressive episode (single or recurrent). Measurements: Clinical Global Impressions-Severity (CGI-S) and safety/tolerability measures. Results: Major improvement (CGI-S reduced by ≥2 points) was experienced by 18.5 percent of L-methylfolate plus SSRI/SNRI patients (CGI-S=4-5) compared to 7.04 percent of SSRI/SNRI monotherapy (p=0.01) patients at 60 days. Forty percent of L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) experienced major improvement compared to 16.3 percent of SSRI/SNRI monotherapy patients (p=0.02). Median times to major improvement were 177 days for L-methylfolate plus SSRI/SNRI patients and 231 days for SSRI/SNRI monotherapy patients (p=0.03). Median time to major improvement for L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) was 85 days and 150 days for SSRI/SNRI monotherapy patients (p=0.018). There were no significant differences between groups in adverse events. Discontinuation due to adverse events was 17.9 percent in L-methylfolate plus SSRI/SNRI patients compared to 34 percent in the SSRI/SNRI monotherapy patients over duration of the study (p=0.0078). Conclusion: L-methylfolate plus antidepressant at treatment onset was more effective in improving depressive symptoms and function measured by CGI-S scores within 60 days than antidepressant monotherapy, led to major symptomatic improvement more rapidly than SSRI/SNRI monotherapy, and was better tolerated. [ABSTRACT FROM AUTHOR]

The levels of sedation required for patients to comfortably undergo colonoscopy with propofol were examined. One hundred patients undergoing colonoscopy with propofol were enrolled. In addition to standard-of-care monitoring, sedation level was monitored with the Patient State Index (PSI) obtained from a brain function monitor, transcutaneous carbon dioxide (tcpCO2) was monitored with the TCM TOSCA monitor, and end-tidal carbon dioxide was monitored via nasal cannula. The Ramsay Sedation Score (RSS) was also assessed and recorded. After baseline data were obtained from the first 40 consecutive patients enrolled in the study, the remaining 60 patients were randomized into two groups. In one group the PSI value was blinded from the anesthesiologist and in the second group the PSI was visible and the impact of this information on the management of the sedation was analyzed. Overall 96% of patients reached levels of deep sedation and 89% reached levels of general anesthesia. When comparing the blinded to PSI versus unblinded groups, the blinded group had a significantly lower PSI and higher RSS and tcpCO2, indicating the blinded group was maintained at a deeper sedation level with more respiratory compromise than the unblinded group. Patients undergoing colonoscopy under propofol sedation delivered by a bolus technique are frequently taken to levels of general anesthesia and are at risk for respiratory depression, airway obstruction, and hemodynamic compromise.

Background: Initial reports of the FUNC score suggest that it may accurately identify those patients suffering from intracerebral hemorrhage (ICH) with an ultra low chance of functional neurologic recovery. This study's aim is to validate the FUNC score and determine if it accurately identifies the cohort of patients with an ultra low chance of survival with good neurologic recovery., Methods: Retrospective review of 501 consecutive primary ICH patients admitted from the Emergency Department to a large healthcare system. Performance of the FUNC, ICH-GS, and oICH scores was determined by calculating areas under the receiver-operator-characteristic curves. Patients with a predicted 100 % chance of poor neurologic outcome (PNO) (FUNC <4 and ICH-GS >10) scores were evaluated to determine if DNR impacted 90 day survival or rate of survival with a Glasgow Outcome Score of <3., Results: In 366 cases of primary ICH who presented during the study period, 222(61 %) survived to discharge. Both the FUNC (AUC: 0.873) and ICH-GS (AUC: 0.888) outperformed the oICH (AUC: 0.743) in predicting 90-day mortality (p = <0.001). Of 68 patients with a FUNC score <4, 67 (98.5 %) had PNO at discharge. The presence of DNR was not associated with a significant difference in the rate of PNO at discharge (40/40 = 100 % vs. 27/28 = 96.4 % p = 0.42) or 90-day mortality (40/40 = 100 % vs. 21/28 = 75 %, p = 0.06)., Conclusion: The FUNC and ICH-GS appear superior to the oICH in predicting outcome in patients with primary ICH. In addition, the FUNC score appears to accurately identify patients with low chance of functional neurologic recovery at discharge.

Purpose: Little is known about the comparative effects of common oral antidiabetic drugs ([OADs] metformin, sulfonylureas, or thiazolidinediones [THZs]) on chronic kidney disease (CKD) outcomes in patients newly diagnosed with type 2 diabetes (T2DM) and followed in community primary care practices. Electronic health records (EHRs) were used to evaluate the relationships between OAD class use and incident proteinuria and prevention of glomerular filtration rate decline., Methods: A retrospective cohort study on newly diagnosed T2D cases requiring OADs documented in the EHRs of two primary care networks between 1998 and 2009 was conducted. CKD outcomes were new-onset proteinuria and estimated GFR (eGFR) falling below 60 ml/min/1.73 m(2). OAD exposures defined cohorts. Hazard ratios represent differential CKD outcome risk per year of OAD class use., Results: A total of 798 and 977 patients qualified for proteinuria and eGFR outcome analyses, respectively. With metformin as the reference group, sulfonylurea exposure trended toward association with an increased risk of developing proteinuria ([adjusted hazard ratio; 95% CI] 1.27; 0.93, 1.74); proteinuria risk associated with THZ exposure (1.00; 0.70, 1.42) was similar to metformin. Compared with metformin, sulfonylurea exposure was associated with an increased risk of eGFR reduction to <60 ml/min/1.73 m(2) (1.41; 1.05, 1.91). THZ exposure (1.04; 0.71, 1.50) was not associated with change in the risk of eGFR decline., Conclusions: In a primary care population, metformin appeared to decrease the risk of CKD development compared with sulfonlyureas; risks of CKD development between metformin and THZs were similar. EHR use in pharmacotherapy comparative effectiveness research creates specific challenges and study limitations., (Copyright © 2013 John Wiley & Sons, Ltd.)

Purpose: This retrospective study tests if runners who habitually forefoot strike have different rates of injury than runners who habitually rearfoot strike., Methods: We measured the strike characteristics of middle- and long-distance runners from a collegiate cross-country team and quantified their history of injury, including the incidence and rate of specific injuries, the severity of each injury, and the rate of mild, moderate, and severe injuries per mile run., Results: Of the 52 runners studied, 36 (69%) primarily used a rearfoot strike and 16 (31%) primarily used a forefoot strike. Approximately 74% of runners experienced a moderate or severe injury each year, but those who habitually rearfoot strike had approximately twice the rate of repetitive stress injuries than individuals who habitually forefoot strike. Traumatic injury rates were not significantly different between the two groups. A generalized linear model showed that strike type, sex, race distance, and average miles per week each correlate significantly (P < 0.01) with repetitive injury rates., Conclusions: Competitive cross-country runners on a college team incur high injury rates, but runners who habitually rearfoot strike have significantly higher rates of repetitive stress injury than those who mostly forefoot strike. This study does not test the causal bases for this general difference. One hypothesis, which requires further research, is that the absence of a marked impact peak in the ground reaction force during a forefoot strike compared with a rearfoot strike may contribute to lower rates of injuries in habitual forefoot strikers.

Background: The role of folate in pregnancy is well established, with most prenatal vitamins (PNVs) on the market containing at least 800 μg of folic acid. Folic acid must be converted in the body to L-methylfolate, the natural and biologically active form of folate. The role of vitamin B(12) in pregnancy is less characterized, and most PNV formulations contain only 0 to 12 μg. The present study was undertaken to evaluate whether taking a prenatal medical food containing L-methylfolate and much higher doses of vitamin B(12) results in higher hemoglobin levels and thus, a lower incidence of anemia during pregnancy., Objective: The objective of this exploratory study was to evaluate the effects of the prenatal medical food versus standard PNVs on hemoglobin levels and adverse outcomes throughout pregnancy., Methods: For this retrospective analysis, we reviewed the charts of female patients taking either a prenatal medical food or standard PNV during pregnancy. Hemoglobin levels measured at initiation of prenatal care, end of second trimester, and delivery were recorded. Patients who had received additional iron supplementation, beyond that contained in the prenatal medical food or PNV they were taking and before anemia screening at the end of the second trimester, were excluded from the study. Fisher exact test, χ(2) test, student t test, and ANOVA were used to evaluate differences between the treatment groups., Results: Data were analyzed from 112 charts: 58 patients (51.8%) were taking the prenatal medical food; 54 patients (48.2%) were taking standard PNVs. Mean (SD) age at first prenatal visit was 27 (4.6) years in the medical food group and 28.8 (3.5) years in the PNV group (P = 0.024). Mean (SD) body mass indices were 29.1 (6.5) and 31.7 (8.9) in the medical food and PNV groups, respectively (P = NS). In the medical food group, 35 women (60.3%) were white/Caucasian, 17 (29.3%) were African American, and 6 (10.4%) were of other races. In the PNV group, 24 women (44.4%) were white/Caucasian, 25 (46.3%) were African American, and 5 (9.3%) were of other races. However, race was not significantly different between the two groups. At end of second trimester and at delivery, mean (SD) hemoglobin levels were higher in the prenatal medical food group (11.8 [1.1] g/dL and 11.8 [1.3] g/dL, respectively) than in the PNV group (11.3 [1.2] g/dL and 10.7 [1.2] g/dL, respectively) (P = 0.011 and P = 0.001, respectively). Significantly fewer cases of anemia were reported at end of second trimester in the prenatal medical food group than in the PNV group (39.7% vs 74.1%; P = 0.001)., Conclusions: In the present study, supplementation with a prenatal medical food containing L-methylfolate and high-dose vitamin B(12) may maintain hemoglobin levels and decrease rates of anemia in pregnancy more effectively than standard prenatal vitamins; however, prospective, controlled studies are warranted. ClinicalTrials.gov identifier: NCT01193192., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

The CpG island methylator phenotype is characterized by DNA hypermethylation in the promoters of tumor suppressor genes with silencing of transcription. Hypermethylation of the promoter of hMLH1 and subsequent microsatellite instability occurs in approximately 12% of sporadic colorectal cancers (CRC). Annurca apple, a variety of southern Italy, is rich in polyphenols that are associated with anticancer properties. Populations in southern Italy have lower incidences of CRC than elsewhere in the western world. We evaluated the mechanisms of putative anticancer effects of Annurca polyphenol extract (APE) in in vitro models of CRC. We extracted polyphenols from Annurca apples and treated RKO, SW48, and SW480 cells with APE and assessed the cell viability, apoptosis, and cell cycle. DNA methylation of selected tumor suppressor genes was evaluated after treatment with APE and was compared with the synthetic demethylating agent 5-aza-2'deoxycytidine (5-aza-2dC). DNA methyltransferase (DNMT)-1 and -3b levels were evaluated. Decreased cell viability and induction of apoptosis was evident after treatment. We found no significant changes in cell cycle dynamics. We observed significant increases of p53 protein expression in RKO after treatment. APE treatment strongly reduced DNA methylation in the promoters of hMLH1, p14(ARF), and p16(INK4a) with consequent restoration of normal expression. These effects were qualitatively comparable with those obtained with 5-aza-2dC. We observed a significant reduction in expression of DNMT proteins after treatment without changes in messenger RNA. In conclusion, APE have potent demethylating activity through the inhibition of DNMT proteins. The lack of toxicity in Annurca extracts makes them excellent candidates for the chemoprevention of CRC.

An 8-year analysis of nonoperative management (NOM) of spleen and liver trauma was done in a level 1 trauma center. Spleen and liver trauma was diagnosed in 279 patients: 93 children (<18), 137 younger adults (18-54), and 49 older adults (> or = 55). Nineteen patients who failed resuscitations died within 0-60 minutes of arrival and were excluded from treatment analysis. Operative management (OM) was done in 39 (15%) and NOM in 221 (85%) patients with failure (NOMF) in 11 (5%). NOM and NOMF was 82 per cent and 5.6 per cent in spleen, 74 per cent and 14.3 per cent in combined spleen/liver, and 96 per cent and 1.5 per cent in liver trauma (P value <0.001). NOM was done in 99 per cent of children, 81 per cent of younger adults, and 68 per cent of older adults with 0 per cent, 8 per cent, and 10 per cent NOMF. Higher grades of splenic trauma and CT fluid had higher OM rate. NOM success rates were 93.8 per cent in grade 3 and 90.3 per cent in higher grades of spleen trauma. There was no NOMF in higher grades of liver trauma. CT fluid grade had no impact on NOMF. Female patients had higher mean injury severity score, age, and mortality compared to cohorts. NOM should be attempted in hemodynamically stable patients. Age over 55, higher grades of injury, and large hemoperitoneum were not predictors of failure of NOM.

In the past decade, expected in-hospital length of stay (LOS) after carotid endarterectomy (CEA) has decreased from 4 days to 1. Long LOS is associated with known complications and factors affecting severity of the patient's condition. Factors affecting an intermediate stay of 2 to 4 days need further clarification. The vascular registry at Jobst Vascular Center includes data on manifestation of disease; cardiovascular history; operation and discharge dates; surgeon; surgical details such as patching, shunting, and completion arteriography; and complications. Univariate chi-square and ANOVA and multivariate logistic regression were applied to analyze 635 CEAs performed in 1998, 1999, and 2000. Statistical significance was at a p value less than 0.05 (two-sided). Overall morbidity rate was 8.2% with three (0.5%) in-hospital neurologic complications and one death for a 0.16% mortality rate. Fifty-eight percent of the patients were discharged in 1 day. Patients staying 1 day were 3 years younger. Female gender and prior cerebrovascular accident were factors extending LOS to 2 and 3 days. History of angina, heart failure, valve disease, and vein patch or no patch contributed to LOS of 3 or 4 days. Completion arteriography had an association with LOS of 2 days. The relative percentage of patients with complications increased with LOS. No significant relationship was found for symptoms, smoking, myocardial infarction, atrial fibrillation, cardiac revascularization, or surgeon. Insulin-treated diabetes mellitus, cardiac risk factors, cerebrovascular accident, and vein patch or no patch correlated with prolonged hospitalization. Factors were identified that may alter a clinical pathway designed for discharge 1 day after CEA. Focused management of patients with cardiac and cerebrovascular accident history or requiring vein patch and a better understanding of CEA in women may further increase the percentage of patients discharged 1 day after CEA.