Aimee R. Kroll-Desrosiers

Screening Colonoscopy and Risk for Incident Late-Stage Colorectal Cancer Diagnosis in Average-Risk Adults: A Nested Case–Control Study

BACKGROUND The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN Nested case-control study. SETTING Four U.S. health plans. PATIENTS 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. MEASUREMENTS Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. RESULTS In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. LIMITATION The small number of screening colonoscopies affected the precision of the estimates. CONCLUSION Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.

Primary CNS Posttransplant Lymphoproliferative Disease (PTLD): An International Report of 84 Cases in the Modern Era

We performed a multicenter, International analysis of solid organ transplant (SOT)‐related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT‐to‐PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBV+ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first‐line therapy included high‐dose methotrexate (48%), high‐dose cytarabine (33%), brain radiation (24%) and/or rituximab (44%). The overall response rate was 60%, while treatment‐related mortality was 13%. With 42‐month median follow‐up, three‐year progression‐free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high‐dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32–5.17, p = 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29–13.46, p = 0.02). Moreover, lack of response to first‐line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56–29.57, p = 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy

BACKGROUND Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear. PATIENTS AND METHODS We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses. RESULTS PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission. CONCLUSIONS This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.

Expression of CD25 independently predicts early treatment failure of acute myeloid leukaemia (AML)

CD25+ CD34+ CD38 leukaemic cells have been shown to be chemotherapy-resistant and initiate acute myeloid leukaemia (AML) in xenograft models, suggesting a leukaemic stem cells (LSC) biology (Saito et al, 2010). High CD25 (also known as interleukin 2 receptor alpha, IL2RA) expression (>10%) at diagnosis in young (<60 years) AML patients in retrospective analysis correlated with a significantly shorter overall survival (OS, P = 0 0005) and relapse-free survival (RFS, P = 0 005). CD25 expression was also associated with FLT3-internal tandem duplication (ITD) mutation, and double positive patients had the poorest OS and RFS (P = 0 001 and P = 0 003, respectively; Terwijn et al, 2009).

Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression.

Neuroactive steroids (NAS) are allosteric modulators of the γ-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9±0.7ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8±7.5 (p=0.04) and 1.5±0.7ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (β=-0.14±0.05, p=0.01) and positively associated with pregnanolone (β=0.16±0.06, p=0.01). STAI-S was positively associated with pregnanolone (β=0.11±0.04, p=0.004), allopregnanolone (β=0.13±0.05, p=0.006) and pregnenolone (β=0.02±0.01, p=0.04). HAM-A was negatively associated with GABA (β=-0.12±0.04, p=0.004) and positively associated with pregnanolone (β=0.11±0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.

The impact of sleep, stress, and depression on postpartum weight retention: A systematic review

OBJECTIVE To review the impact of sleep, stress, and/or depression on postpartum weight retention. METHODS We searched three electronic databases, PubMed, ISI Web of Science, and PsycInfo. Studies were included if they were published between January 1990 and September 2013 in English, measured sleep, stress, and/or depression in the postpartum period, and assessed the association of these factors with postpartum weight retention. Two reviewers reviewed included articles and rated study quality using a modified version of the Downs and Black scale. RESULTS Thirteen studies met our pre-defined eligibility criteria, reporting on 9 study samples. Two were cross-sectional studies and eleven were longitudinal studies. The study sample size ranged from 74 to 37,127. All four studies examining short sleep duration and postpartum weight retention reported a positive association. The four studies examining postpartum stress and weight retention reported non-significant associations only. Of 7 studies examining postpartum depression and weight retention, 3 reported non-significant associations, and 4 reported positive associations. CONCLUSION Research investigating the impact of postpartum sleep, stress, depression on weight retention is limited. Future longitudinal studies are needed.

Progression of female reproductive stages associated with bipolar illness exacerbation

Marsh WK, Ketter TA, Crawford SL, Johnson JV, Kroll‐Desrosiers AR, Rothschild AJ. Progression of female reproductive stages associated with bipolar illness exacerbation. Bipolar Disord 2012: 14: 515–526.

Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year

Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure.

Improving Pregnancy Outcomes through Maternity Care Coordination: A Systematic Review

BACKGROUND Care during pregnancy is multifaceted and often goes beyond traditional prenatal care from an obstetrical care provider. Coordinating care between multiple providers can be challenging, but is beneficial for providers and patients. Care coordination is associated with decreased costs, greater patient satisfaction, and a reduction in medical errors. To our knowledge, no previous review has examined maternity care coordination (MCC) programs and their association with pregnancy outcomes. METHODS Using a search algorithm comprised of relevant MCC terminology, studies were identified through a systematic search of PubMed, Scopus, ClinicalTrials.gov, and Google Scholar. Studies meeting eligibility criteria (e.g., defining the care coordination components and examining at least one quantitative outcome) were fully abstracted and quality rated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. MAIN FINDINGS Thirty-three observational studies of MCC were included in this review. Quality scores ranged from 27% to 100%. Most studies included strategies with a team approach to decision making and/or individual case management. Social service referrals to outside organizations were also common. Twenty-seven studies reported infant birth weight as a main outcome; 12 found a significant improvement in birth weights among care coordination participants. CONCLUSIONS Roughly one-third of the included studies reported improved birth weights among care coordination participants. However, it remains unknown what effect care coordination strategies have on patient and provider satisfaction in the prenatal care setting, two aspects of maternity care that may advance the quality and utilization of prenatal health services.

Infertility Care Among OEF/OIF/OND Women Veterans in the Department of Veterans Affairs

Background:An increasing number of young women Veterans seek reproductive health care through the VA, yet little is known regarding the provision of infertility care for this population. The VA provides a range of infertility services for Veterans including artificial insemination, but does not provide in vitro fertilization. This study will be the first to characterize infertility care among OEF/OIF/OND women Veterans using VA care. Methods:We analyzed data from the OEF/OIF/OND roster file from the Defense Manpower Data Center (DMDC)—Contingency Tracking System Deployment file of military discharges from October 1, 2001–December 30, 2010, which includes 68,442 women Veterans between the ages of 18 and 45 who utilized VA health care after separating from military service. We examined the receipt of infertility diagnoses and care using ICD-9 and CPT codes. Results:Less than 2% (n=1323) of OEF/OIF/OND women Veterans received an infertility diagnosis during the study period. Compared with women VA users without infertility diagnosis, those with infertility diagnosis were younger, obese, black, or Hispanic, have a service-connected disability rating, a positive screen for military sexual trauma, and a mental health diagnosis. Overall, 22% of women with an infertility diagnosis received an infertility assessment or treatment. Thirty-nine percent of women Veterans receiving infertility assessment or treatment received this care from non-VA providers. Conclusions:Overall, a small proportion of OEF/OIF/OND women Veterans received infertility diagnoses from the VA during the study period, and an even smaller proportion received infertility treatment. Nearly 40% of those who received infertility treatments received these treatments from non-VA providers, indicating that the VA may need to examine the training and resources needed to provide this care within the VA. Understanding women’s use of VA infertility services is an important component of understanding VA’s commitment to comprehensive medical care for women Veterans.