Publications (35) View all
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Article: Randomized Multicenter Investigation of Folate Plus Vitamin B12 Supplementation in Schizophrenia.
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ABSTRACT: IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation. OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response. DESIGN Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12. SETTING Three community mental health centers affiliated with academic medical centers in the United States. PARTICIPANTS Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale. INTERVENTION One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B12 or placebo. MAIN OUTCOME MEASURES Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale). RESULTS Folate plus vitamin B12 improved negative symptoms significantly compared with placebo (group difference, -0.33 change in SANS score per week; 95% CI, -0.62 to -0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P = .02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS score per week; 95% CI, -0.99 to -0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P = .03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups. CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00611806.JAMA psychiatry (Chicago, Ill.). 03/2013; -
Article: Low back pain does not improve with surgical treatment of pelvic organ prolapse.
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ABSTRACT: INTRODUCTION AND HYPOTHESIS: Our goal was to determine if there is a correlation between low back pain (LBP) and pelvic organ prolapse (POP) by assessing for change in LBP after surgical correction of prolapse. METHODS: Patients undergoing POP surgery were recruited to participate. They completed the Oswestry Disability Index (ODI), a validated back pain questionnaire, at their preoperative and postoperative visits at 1, 3, and 6 months. A higher ODI score (0-100) represents more severe disability. A 9-point change represents a minimal clinically important difference (MCID). The primary outcome was the change in ODI scores from preoperative to 3 months postoperative. We analyzed ODI scores with repeated measures analysis of variance (ANOVA). Power analysis showed that a sample size of 50 was needed for 88 % power to resolve a MCID on ODI. RESULTS: A total of 51 patients were recruited and 43 (84 %), 34 (67 %), and 36 (71 %) completed the 1-, 3-, and 6-month follow-up, respectively. The mean ODI scores at the preoperative and the 1-, 3-, and 6-month postoperative visits were 15, 19, 9, and 9. The mean ODI score from preoperative to 3 months postoperative improved by 5 points [confidence interval (CI) -9.2 to -0.5, p = 0.03]. Of the participants 7 (20.6 %, CI 11-35 %) experienced a MCID improvement, 24 (70.6 %, CI 56-83 %) reported no substantial change, and 3 (8.8 %, CI 3-20 %) experienced a MCID worsening. CONCLUSIONS: Our study found a statistically significant but not clinically significant improvement of LBP after surgical repair of prolapse.International Urogynecology Journal 05/2012; · 1.83 Impact Factor -
Article: Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia.
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ABSTRACT: Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients.Schizophrenia Bulletin 10/2011; · 8.80 Impact Factor -
Article: The importance of chemotherapy and radiation in uterine papillary serous carcinoma.
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ABSTRACT: To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC). Patient, tumor, treatment and relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980 and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity. Mean follow-up was 5.5 years (range, 0.01-25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR]=0.34, 95% confidence interval [CI] 0.15-0.74, p=0.007) and RFS (HR=0.45, 95% CI 0.22-0.92, p=0.03). RFS was improved for patients treated with RT (HR=0.44, 95% CI 0.25-0.77, p=0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p=NS). Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis.Gynecologic Oncology 09/2011; 123(3):542-7. · 3.89 Impact Factor -
Article: Trabecular structure analysis using C-arm CT: comparison with MDCT and flat-panel volume CT.
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ABSTRACT: This paper assesses interscan, interreader, and intrareader variability of C-arm CT and compares it to that of flat-panel volume-CT (fpVCT) and high-definition multi-detector-CT (HD-MDCT). Five cadaver knee specimens were imaged using C-arm-CT, fpVCT, and HD-MDCT. Apparent (app.) trabecular bone volume fraction (BV/TV), app. trabecular number (TbN), app. trabecular spacing (TbSp), and app. trabecular thickness (TbTh) of the proximal tibia were measured by three readers. Interreader, intrareader, and interscan variability for C-arm CT was expressed as coefficient of variation (CV), standard deviation (SD), and intraclass correlation coefficient (ICC). With the exception of app.TbSp (CV: 7.05-9.35%, SD: 0.06-0.09, ICC: 0.89-0.94), the variability of C-arm CT was low (CV: 2.41-6.43%, SD: 0.01-0.048, ICC: 0.65-0.98). Its interreader reliability (CV: 2.66-4.55%, SD: 0.01-0.03, ICC: 0.81-0.95) was comparable to that of HD-MDCT (CV: 2.41-4.08%, SD: 0.014-0.016, ICC: 0.95-0.96), and fpVCT (CV: 3.13-5.63%, SD: 0.009-0.036, ICC: 0.64-0.98) for all parameters except app.TbSp. C-arm CT is a reliable method for assessing trabecular bone architectural parameters with the exception of app.TbSp due to spatial resolution limitation.Skeletal Radiology 08/2011; 40(8):1065-72. · 1.54 Impact Factor
