Constantine Daskalakis

Gestational age at cervical length measurement and incidence of preterm birth.

OBJECTIVE: To estimate the risk of spontaneous preterm birth based on transvaginal ultrasound cervical length and gestational age at which cervical length was measured. METHODS: Women at high risk for spontaneous preterm birth and with transvaginal ultrasound cervical length measurements between weeks 12 and 32 were identified at one institution between July 1995 and June 2005. Inclusion criteria for women at high risk for spontaneous preterm birth were prior spontaneous preterm birth at 14 to 35 weeks, cone biopsy, müllerian anomaly, or two or more dilation and evacuations. Women with multiple gestations, cerclage, indicated preterm birth, or fetal anomalies were excluded. Logistic regression was used to estimate the spontaneous preterm birth risk before 35, 32, and 28 weeks. RESULTS: Seven hundred five women received 2,601 transvaginal ultrasound measurements for cervical length. The incidences of spontaneous preterm birth before 35, 32, and 28 weeks were 17.7, 10.6, and 6.7%, respectively. The risk of spontaneous preterm birth before 35 weeks decreased by approximately 6% for each additional millimeter of cervical length (odds ratio 0.94, 95% confidence interval, 0.92–0.95, P=.001) and by approximately 5% for each additional week of pregnancy at which the cervical length was measured (odds ratio 0.95, 95% confidence interval 0.92–0.98, P=.004). Similar results were obtained for spontaneous preterm birth before 32 and 28 weeks. CONCLUSION: Gestational age at which transvaginal ultrasound cervical length is measured significantly affects the calculation of risk of spontaneous preterm birth. The spontaneous preterm birth risk increases as the length of the cervix declines and as the gestational age decreases. These spontaneous preterm birth risks are important for counseling and management for women with various degrees of short cervical length at different gestational ages. LEVEL OF EVIDENCE: II

Efficacy of morning-only compared with split-dose polyethylene glycol electrolyte solution for afternoon colonoscopy: a randomized controlled single-blind study.

OBJECTIVES:Administering a purgative close to the time of colonoscopy is optimal for cleansing. The aim of this study was to compare the efficacy and tolerability of morning-only (AM-only) polyethylene glycol electrolyte solution (PEG-ELS) to split-dose (PM/AM) PEG-ELS for afternoon colonoscopy.METHODS:This was a single-center, prospective, randomized, investigator-blinded, non-inferiority study comparing AM-only to PM/AM PEG-ELS for afternoon outpatient colonoscopy. The primary end point was whole colon prep adequacy. Tolerance and polyp detection were secondary outcomes.RESULTS:Overall, 125 patients were randomized and 9 withdrew without taking any prep. Of 116 analyzed, 62 received AM-only prep and 54 received PM/AM prep. The whole colon prep was adequate in 92% in the AM-only group vs. 94% in the PM/AM group (95% lower confidence limit, LCL, for the difference=−11.3%, non-inferiority P=0.013), whereas the right colon prep was adequate in 93 and 92%, respectively (95% LCL=−7.8%, non-inferiority P=0.003). Polyp detection was greater, and not inferior, in the AM-only group (mean=1.57 vs. 0.94 polyps/patient, non-inferiority P=0.007). The overall incidence of adverse events was not significantly different between the two groups (P=0.273), but the AM-only group had lower incidence of abdominal pain (P=0.024). The AM-only group also had better sleep quality (P=0.007) and less interference with the previous workday (P=0.019).CONCLUSIONS:AM-only and PM/AM PEG-ELS are clinically equivalent with respect to cleansing efficacy and polyp detection. AM-only prep was associated with a lower incidence of abdominal pain, superior sleep quality, and less interference with workday before colonoscopy.

Dampness and Mold in the Home and Depression: An Examination of Mold-Related Illness and Perceived Control of One’s Home as Possible Depression Pathways

OBJECTIVES We evaluated a previously reported association between residence in a damp and moldy dwelling and the risk of depression and investigated whether depression was mediated by perception of control over ones home or mold-related physical illness. METHODS We used survey data from 8 European cities. A dampness and mold score was created from resident- and inspector-reported data. Depression was assessed using a validated index of depressive symptoms. RESULTS Dampness or mold in the home was associated with depression (odds ratio [OR]=1.39, 1.44, and 1.34, for minimal, moderate, and extensive exposure, respectively, compared with no exposure). This association became attenuated when perception of control (OR=1.34, 1.40, and 1.24; global P=.069) or a physical health index (OR = 1.32, 1.37, and 1.15; global P= .104) was included in the model. The mediation effects of perception of control over ones home and by physical health appeared to be additive. CONCLUSIONS Dampness and mold were associated with depression, independent of individual and housing characteristics. This association was independently mediated by perception of control over ones home and by physical health.

Safety of Selective Serotonin Reuptake Inhibitor in Adults Undergoing Coronary Artery Bypass Grafting

Selective serotonin reuptake inhibitors (SSRIs) are commonly used in patients with coronary artery disease and depression, but they have been reported to increase the risk for bleeding. However, data on the short-term outcomes comparing SSRI and non-SSRI antidepressant use after coronary artery bypass grafting (CABG) are limited. A retrospective analysis was conducted of 1,380 adults who received any antidepressants before CABG from 2003 to 2006 at academic medical centers participating in the University HealthSystem Consortium. The primary end point was defined as a composite of in-hospital mortality or any bleeding events, including postprocedural hemorrhage or hematoma, gastrointestinal hemorrhage, and reopening of surgical site. A total of 1,076 adults (78%) received SSRIs. After controlling for propensity of receiving SSRIs compared with non-SSRIs, no significant differences were found in the primary end point (9.4% vs 8.2%, adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 0.60 to 1.78), any bleeding events (6.5% vs 7.2%, OR 0.93, 95% CI 0.50 to 1.76), or in-hospital mortality (3.1% vs 2.3%, OR 0.88, 95% CI 0.47 to 1.65). There was no increased risk associated with SSRI use when the analysis was restricted to patients who received antiplatelet and anticoagulant therapy for acute coronary syndromes (OR 1.03, 95% CI 0.40 to 2.61) and when examined by age, gender, nonsteroidal anti-inflammatory drug use, and type of CABG (on pump or off pump). In conclusion, compared with non-SSRIs, the preoperative use of SSRIs does not seem to increase the risk for bleeding or in-hospital mortality after CABG.

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

GATA3 is a transcription factor closely associated with estrogen receptor alpha in breast carcinoma, with a potential prognostic utility. This study investigated the immunohistochemical expression of GATA3 in estrogen receptor alpha-positive and estrogen receptor alpha-negative breast carcinomas. One hundred sixty-six cases of invasive breast carcinomas with 10-year follow-up information were analyzed. Positive GATA3 and estrogen receptor alpha cases were defined as greater than 20% of cells staining. Time to cancer recurrence and time to death were analyzed with survival methods. Of 166 patients, 40 were estrogen receptor alpha negative and 121 estrogen receptor alpha positive. Thirty-eight (23%) recurrences and 51 (31%) deaths were observed. In final multivariable analyses, GATA3-positive tumors had about two thirds the recurrence risk of GATA3-negative tumors (hazard ratio = 0.65, P = .395) and comparable mortality risk (hazard ratio = 0.86, P = .730). In prespecified subgroup analyses, the protective effect of GATA3 expression was most pronounced among estrogen receptor alpha-positive patients who received tamoxifen (hazard ratio = 0.57 for recurrence and 0.68 for death). We found no statistically significant differences in recurrence or survival rates between GATA3-positive and GATA3-negative tumors. However, there was a suggestion of a modest-to-strong protective effect of GATA3 expression among estrogen receptor alpha-positive patients receiving hormone therapy.

Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting

OBJECTIVE Preoperative use of clopidogrel increases the risk of bleeding, but its postoperative use has not been studied. We studied early postoperative clopidogrel use in on-pump and off-pump coronary artery bypass grafting. METHODS Data were obtained from the University HealthSystem Consortium database. We conducted a retrospective analysis of data of 15,067 adults who had coronary artery bypass grafting between 2003 and 2006 and received perioperative aspirin alone or in combination with clopidogrel, with the latter administered within 2 days after coronary artery bypass grafting. Logistic regression was used to analyze in-hospital mortality, 30-day readmission, ischemic or thrombotic events, and bleeding events, with propensity score adjustment for clopidogrel treatment. RESULTS Combined aspirin and clopidogrel were used in 3268 patients (22%). Compared with aspirin alone, aspirin plus clopidogrel was associated with reductions of in-hospital mortality (0.95% vs 1.78%; adjusted odds ratio: 0.50; 95% confidence interval: 0.25, 0.99) and bleeding events (4.19% vs 5.17%; adjusted odds ratio: 0.70; 95% confidence interval: 0.51, 0.97). Ischemic or thrombotic events were not significantly different (1.29% vs 1.53%; adjusted odds ratio, 0.99; 95% confidence interval: 0.59, 1.64). The relative effect of combined treatment did not differ between on-pump and off-pump coronary artery bypass grafting. CONCLUSIONS Early postoperative clopidogrel combined with aspirin may be safe and beneficial compared with perioperative aspirin treatment alone, in both on-pump and off-pump coronary artery bypass grafting. However, a possibility of selection bias calls for randomized controlled trials to confirm our findings.

A Randomized Controlled Trial of a Tailored Navigation and a Standard Intervention in Colorectal Cancer Screening

Background: This randomized, controlled trial assessed the impact of a tailored navigation intervention versus a standard mailed intervention on colorectal cancer screening adherence and screening decision stage (SDS). Methods: Primary care patients (n = 945) were surveyed and randomized to a Tailored Navigation Intervention (TNI) Group (n = 312), Standard Intervention (SI) Group (n = 316), or usual care Control Group (n = 317). TNI Group participants were sent colonoscopy instructions and/or stool blood tests according to reported test preference, and received a navigation call. The SI Group was sent both colonoscopy instructions and stool blood tests. Multivariable analyses assessed intervention impact on adherence and change in SDS at 6 months. Results: The primary outcome, screening adherence (TNI Group: 38%, SI Group: 33%, Control Group: 12%), was higher for intervention recipients than controls (P = 0.001 and P = 0.001, respectively), but the two intervention groups did not differ significantly (P = 0.201). Positive SDS change (TNI Group: +45%, SI Group: +37%, and Control Group: +23%) was significantly greater among intervention recipients than controls (P = 0.001 and P = 0.001, respectively), and the intervention group difference approached significance (P = 0.053). Secondary analyses indicate that tailored navigation boosted preferred test use, and suggest that intervention impact on adherence and SDS was attenuated by limited access to screening options. Conclusions: Both interventions had significant, positive effects on outcomes compared with usual care. TNI versus SI impact had a modest positive impact on adherence and a pronounced effect on SDS. Impact: Mailed screening tests can boost adherence. Research is needed to determine how preference, access, and navigation affect screening outcomes. Cancer Epidemiol Biomarkers Prev; 22(1); 109–17. ©2012 AACR.

A validation study of 3 grading systems to evaluate small-bowel cleansing for wireless capsule endoscopy : a quantitative index, a qualitative evaluation, and an overall adequacy assessment

BACKGROUND Capsule endoscopy (CE) is a powerful tool for evaluating the small bowel. Assessment of small-bowel cleansing for CE is an essential quality measure. OBJECTIVE Our purpose was to validate 3 new scales that grade small-bowel cleansing for CE. DESIGN Prospective, randomized, single-center study. SETTING Tertiary university hospital. INTERVENTION Five experienced capsule endoscopists read 40 CEs twice, separated by 1 month, to grade small-bowel cleansing on 3 scales-quantitative index (QI; 0-10), qualitative evaluation (QE; poor, fair, good, excellent), and overall adequacy assessment (OAA; inadequate, adequate). The QI and QE evaluated both the entire and distal small bowel. Investigators received no prior training in these scales. MAIN OUTCOME MEASUREMENTS Intraclass correlation coefficients to assess intraobserver (test-retest) and interobserver reliability. PATIENTS Forty patients who underwent 1 CE between June 2005 and May 2006 and who satisfied entry criteria. RESULTS Intraobserver reliability was moderate to substantial for the QI (0.60-0.66), moderate for the OAA (0.56), and fair to moderate for the QE (0.37-0.47). Interobserver scores were lower: QI and OAA moderate (0.47-0.52, 0.41, respectively) and slight to fair for the QE (0.20-0.24). QI scores for the entire and distal small bowel were highly correlated for each reader (0.57-0.87), and distal small-bowel scores were lower by 1.3 points, indicating poorer cleansing (P = .001). A dichotomized QE of excellent/good versus fair/poor had moderate to substantial intraobserver and interobserver reliability (0.58-0.66, 0.41-0.49, respectively). There was a strong and highly significant association among all 3 scales (P < .001 between QI and both QE and OAA). CONCLUSION We have described and validated 3 scales for grading small-bowel cleansing for CE. An evaluation of small-bowel cleansing should be routinely incorporated into the CE report.

Ablation of Tumor Progression Locus 2 Promotes a Type 2 Th Cell Response in Ovalbumin-Immunized Mice

The protein kinase encoded by the Tpl2 proto-oncogene regulates ERK activation and cytokine gene expression in macrophages in response to LPS and TNF-α. In this study we show that OVA-immunized Tpl2−/− mice express high levels of IgE and develop more severe bronchoalveolar eosinophilic inflammation than Tpl2+/+ controls, when challenged with OVA intranasally. Bronchoalveolar exudates and supernatants of OVA-stimulated splenocytes from immunized Tpl2−/− mice express elevated levels of IL-4 and IL-5, suggesting that Tpl2 ablation promotes the Th2 polarization of the T cell response. Anti-CD3 stimulation of CD4+ T cells of wild-type and Tpl2 knockout mice revealed that Tpl2 ablation gives rise to a cell autonomous T cell defect that is primarily responsible for the Th2 polarization of the T cell response to Ag. This observation was further supported by experiments addressing the expression of Th1 and Th2 cytokines in OVA-stimulated mixed cultures of CD4+ T cells from Tpl2+/+/OT2 or Tpl2−/−/OT2 mice and dendritic cells from Tpl2+/+ or Tpl2−/− mice. Further studies revealed that Th1 cells express significantly higher levels of Tpl2 than Th2 cells. As a result, Tpl2−/− Th1 cells exhibit a stronger defect in ERK activation by anti-CD3 than Th2 cells and express low levels of T-bet. Given that the development of Th1 and Th2 cells depends on positive feedback signals from the T cells, themselves, the functional defect of the Tpl2−/− Th1 cells provides a mechanistic explanation for the T cell autonomous Th2 polarization in Tpl2−/− mice.

Modifiable cardiovascular risk factors among individuals in low socioeconomic communities and homeless shelters.

To understand cardiovascular health in low socioeconomic populations, we analyzed the data from 426 low socioeconomic community-dwelling males and females and 287 homeless males in Philadelphia. Despite higher prevalence of smoking and hypertension, the proportion of homeless participants at increased risk for coronary heart disease was comparable with that of low socioeconomic community-dwelling participants. Among various characteristics, emotional stress was significantly associated with coronary heart disease risk in low socioeconomic community-dwelling participants only, suggestive of a differential psychosocial effect of stress. Our findings suggest that low socioeconomic populations are heterogeneous with respect to their risk factors and needs for interventions.