2015 - MPH Clinical Effectiveness

Organization / Practice Abstract
Brigham and Women's Hospital, Department of Medicine / 1) evaluated whether medical home transformation was associated with breast cancer screening performance in primary care practices at the Brigham and Women's Hospital /
Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Health Care Institute / My work during fellowship has focused on studying trends in sepsis burden and improving surveillance of this important disease. I was first author on a Perspective article in the New England Journal of Medicine where we suggested that the apparent surge in sepsis rates may actually be an artifact of increasingly aggressive diagnosis and coding practices rather than a true increase in the burden of disease. We used the Nationwide Inpatient Sample to show that the incidence of sepsis as a principal diagnosis almost tripled from 2000-2008 whereas the incidence of pneumonia, intraabdominal infections, urinary tract infections, and bacteremia (the infections that most commonly cause sepsis) were stable or decreasing. We urged caution on implementing mandates for sepsis care and public reporting in light of our current deficiencies in surveillance, and proposed that surveillance should be conducted using objective clinical data instead of claims data. I subsequently published a first-author Major Article in Clinical Infectious Diseases showing that trends in sepsis incidence imputed from administrative data differed markedly from those suggested by objective clinical markers (positive blood cultures) at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH). We also demonstrated steadily rising sensitivity of sepsis codes for capturing patients with unequivocal markers of severe sepsis, positive blood cultures with concurrent vasopressors or lactic acidosis. My next project compared the accuracy of surveillance definitions based on clinical data stored in electronic health records versus claims data to identify true severe sepsis cases. I validated the surveillance definitions with 1000 chart reviews. We found that a surveillance definition based on clinical data (blood culture orders and antibiotics and various organ dysfunction markers) has superior sensitivity to claims and stable sensitivity over time. Importantly, we showed that rising trends in incidence and declining mortality was exaggerated with claims data when compared to clinical data. This manuscript is now under review. /
Boston Children's Hospital, Division of Endocrinology / We examined relationships between autistic traits in children, mothers, and fathers and recalled gender nonconformity (GNC) in children using data from the Nurses' Health Study II (NHSII) and the Growing Up Today Study 1 (GUTS1). Autistic traits of mothers, fathers and children were measured using the Social Responsiveness Scale (SRS). GNC in children was measured using questions from the Recalled Childhood Gender Identity/Gender Role Questionnaire. In multivariable analyses increase in child’s SRS score was associated with increased odds (OR 1.35; p=0.03) of being in a higher GNC category. Increase in maternal SRS score was also associated with increased odds (OR 1.46; p=0.005) of the child being in a higher GNC category. Paternal SRS scores were not related to child's GNC category. These results call for further exploration into the etiology of these associations and suggest the importance of being sensitive to the diversity of gender expression in children with ASD.
Boston Children's Hospital, Department of Surgery / The purpose of this study was to identify which conditions are responsible for the majority of hospital cost and cost variation within the scope of pediatric surgical practice. We described the variation in cost of these procedures in the context of a public health focused prioritization framework. We retrospectively reviewed administrative data from over 60,000 encounters where a proedure was performed at a children's hospital and found that a relatively small number of conditions account for the majority of cost and cost variation burden in general pediatric surgery. The prioritization of these conditions for value-focused comparative effectiveness research may provide a high-yield strategy to improve care from a broad public health perspective. This should segway nicely into more sophisticated analyses of drivers of cost for these high priority conditions. /
Obesity Prevention Program, Department of Population Medicine / Background: Insufficient sleep is a risk factor for obesity, cancer, and other chronic disease. Maternal antenatal stress is associated with child depression and ADHD, perhaps via the hypothalamic-pituitary-adrenal axis, and thus may affect child sleep. / Objective: To determine the relationship between maternal antenatal stress and child sleep duration and efficiency. / Methods: In 2007-2010, we recruited pregnant women at a Mexico City hospital and followed their children to 4 years. In mid-pregnancy (median X weeks gestation) mothers reported stress in the previous month with the Prenatal Stress Scale (PSS) and total lifetime stressful events with the Negative Life Events subscale of the Crisis in Family Systems scale. They also provided 5 salivary cortisol samples over 24 hours from which we derived area under the curve, daytime slope, and cortisol awakening response, which is the difference between the first two cortisol measurements of the day. At 4 years, we measured total sleep time (minutes) and sleep efficiency (% of in-bed time asleep) in children using 7-day wrist actigraphy for up to 7 days. We examined associations of maternal stress with child sleep outcomes in 408 pairs using linear regression analysis, adjusted for maternal age, prenatal body mass index (BMI), socio-economic status, and child sex, gestational age, and birth weight. / Results: mean (SD) maternal age was 27.7 (5.5) years, with 216 (53%) of mothers in the lowest 2 of 6 SES categories, 239 (59%) mothers ever having smoked, and 106 (29%) mothers reporting a victim of violence in the family. Mean (SD) PSS score was 5.2 (2.8) out of 16 and Negative Life Events score was 3.1 (2) out of 11. Half 51%) of children were male, mean (SD) age was 58 (5) months, BMI z-score was 0.19 (1.1), physical activity was 3.1 (0.4) hours per day, hours of sleep per night was 8.0 (0.7), and sleep efficiency was 79% (6). In unadjusted linear regression models, greater cortisol slope was associated with longer sleep duration (effect estimate 9.6, 95% CI 1.7-17.5), but this relationship fell out of significance after adjustment (5.6, 95% CI -5.9, 17.3) each additional point on the NEGATIVE LIFE EVENTS subscale was associated with -1.2 (95% CI -3.6, 1.2) minutes sleep, and -4.2 (95% CI -7.8, -0.6) minutes sleep after adjustment. No predictors were associated with sleep efficiency, before or after adjustment. / Conclusions: Higher maternal lifetime stress, as measured by second trimester Negative Life Events score, was associated with less child sleep, though other measures of maternal antenatal stress were not associated with child sleep outcomes. /
University of Wisconsin Department of Surgery / Our aim is to evaluate the effectiveness of breast MRI on time to breast cancer recurrence and survival in stage II and III breast cancer patients after curative intent therapy with the objective of optimizing surveillance strategies in women with stage II and III breast cancer. Using the National Cancer Database (NCDB) in addition to primary data abstraction, we will evaluate receipt of routine surveillance breast MRI compared to symptom driven imaging and compare primary outcome of time to a second breast event defined as locoregional recurrence, new cancer in the ipsilateral or contralateral breast and secondary outcome of comparing overall survival between these cohorts. We will also assess patterns of MRI use within this cohort including quantity and frequency. We will also examine frequency of subsequent imaging, biopsy rate and results. In addition, we will assess variation in recurrence patterns based on patient and tumor characteristics.
SaveLife Foundation, New Delhi / Trauma and injuries are rising in incidence in LMICs. Western style EMS systems are expensive and are not always optimized to the challenges of overcrowding and road conditions. We worked with SaveLife Foundation, an Indian NGO training police officers in trauma response.
Brigham and Women's Hospital, Department of OB/GYN / Many studies have evaluated pain control options for intrauterine device (IUD) insertion, though few interventions have shown efficacy. Prior studies of naproxen sodium suggest effective pain relief. However, it is unclear if those results apply to modern IUDs utilized in the United States. We hypothesize that administering 550 mg of naproxen sodium orally, 1 hour prior to IUD insertion, will lead to a clinically significant reduction in pain scores compared to placebo. Our primary outcome is pain score with IUD insertion as measured on a 10cm visual analogue scale (VAS). Secondary outcomes will include VAS pain scores for tenaculum placement, uterine sounding, and 5 and 15 minutes post-procedure. We will also evaluate subjective reports of pain and need for additional pain medication. This will be a double-blind, randomized, placebo-controlled trial. Recruitment will take place at Planned Parenthood League of Massachusetts in Boston, MA (PPLM-Boston). Eligible women will be 18 years or older, premenopausal, at least 4 weeks postabortion or postpartum, and presenting for IUD insertion of any type. Women will be ineligible if they have a chronic pain diagnosis or any contraindications to IUD insertion or non-steroidal anti-inflammatory drugs. Given known differences in IUD insertion pain between nulliparous and parous women, we will stratify by parity. Separate sample size calculations were done with different standard deviations for each strata based on published data. Both sample size calculations are based on a clinically significant difference of 1.5cm on a 10 cm VAS. To achieve 80% power with a 5% alpha error rate and allowing for 10% subject discontinuation and/or missing data, 76 parous and 84 nulliparous participants will be required, for a total recruitment of 160 participants. Given the large volume of interval IUD insertions at PPLM-Boston (approximately 970 in 2014) we anticipate recruitment to take approximately 9 months. We plan to establish whether prophylactic naproxen sodium leads to a clinically significant decrease in pain and warrants routine use prior to IUD insertion. /
Division of Preventive Medicine - Brigham and Women's Hospital / It is uncertain whether subclinical hypothyroidism (SCH) is associated with lipid abnormalities. Therefore, we examined a range of lipid and lipoprotein subclasses across the spectrum of euthyroid, SCH, and overt hypothyroidism (HT) in apparently healthy women free of CVD. A random sample of 3914 individuals from the Women’s Health Study was selected for thyroid function analysis. From this sample, 3321 individuals were not on lipid lowering therapy and had thyroid profiles compatible with euthyroid, 2571 (77.4%); SCH, 573 (17.3%); and HT, 177 (5.3%). Lipids were measured directly, and lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Statistical comparison was performed by ANOVA, after adjusting for age, BMI, menopausal status, HRT, blood pressure, anti-hypertensive medication, diabetes, and current smoking. Compared with euthyroid individuals, those with SCH and HT were older, had higher BMI, greater prevalence of post-menopausal status and metabolic syndrome, and lower prevalence of smoking. They also had higher triglycerides and lower HDL-C, but similar LDL-C (Table ). More detailed lipoprotein phenotyping showed that SCH and HT were associated with an insulin resistant lipoprotein subclass profile. Going from euthyroid to SCH to HT, there was a graded increase in concentrations of VLDL particles (mainly due to large and medium VLDL), reflected by larger VLDL size; higher concentration of LDL particles as well as apolipoprotein B concentration despite no difference in LDL-C; and higher concentration of small HDL particles. Similarly, the lipoprotein insulin resistance score of SCH and HT was worse than euthyroid. In this large population of apparently healthy women, individuals with SCH had differences in the lipid and lipoprotein subclass profile that indicated worsening insulin resistance compared with euthyroid individuals, despite having similar LDL-C and total cholesterol. /
Institue for Aging Research, Hebrew SeniorLife / OBJECTIVES: To examine baseline (preoperative) neuro- / psychological test performance in a cohort of elderly indi- / viduals undergoing elective surgery and the association / between specific neuropsychological domains and postop- / erative delirium. / SETTING: Successful Aging after Elective Surgery Study. / PARTICIPANTS: Elderly adults (N = 300) scheduled for / elective (noncardiac) surgery. / MEASUREMENTS: Neuropsychological testing, including / standardized assessments of memory, divided and sus- / tained attention, speed of mental processing, verbal flu- / ency, working memory, language, and an overall measure / of premorbid cognitive functioning, was performed 2 to / 4 weeks before surgery. The relationship between the indi- / vidual neuropsychological tests and delirium status was / examined using linear regression, adjusting for age, sex, / and education. / RESULTS: Study participants were generally highly edu- / cated (mean years of education 15.0 2.9), with minimal / or no cognitive impairment (mean Modified Mini-Mental / State Examination score 93.2 out of 100). After adjust- / ment, participants who developed postoperative delirium / had performed significantly lower preoperatively on mea- / sures of speed of mental processing and divided attention / (Trail-Making Test Part B, mean difference 17.55, / P = .02), category fluency (animal naming, mean differ- / ence 1.94, P = .01), sustained visual attention (Visual / Search and Attention, mean difference 3.19, P < .001), / and working memory with new learning and recall (Hop- / kins Verbal Learning Test—Revised Total mean difference / 0.53 to 0.79, P < .01). / CONCLUSION: Individuals who later develop delirium / have lower scores on tests evaluating the areas of complex / attention, executive functioning, and rapid access to verbal / knowledge or semantic networks at baseline. Future stud- / ies to better understand how the cognitive profiles identi- / fied may predispose individuals to developing delirium / may help pave the way to greater understanding of the / mechanisms of delirium. J Am GeriatrSoc 2015.
Dana-Farber Cancer Institute, Division of Population Sciences / We performed a case control study to identify predictors of chemotherapy-related hospitalization. The study population included patients treated for advanced solid tumor cancers at the North Shore Cancer Center between 2003 and 2011. 292 case patients who experienced chemotherapy-related hospitalization were identified from a parent cohort of 1579 patients receiving chemotherapy. Case patients were matched to controls in a 2:1 ratio. Age, Charlson comorbidity score, creatinine clearance, calcium, below-normal white blood cell or platelet count, polychemotherapy, and camptothecin chemotherapy were identified as independent predictors of chemotherapy-related hospitalization. The final model exhibited a bootstrap adjusted c-statistic of 0.71 with acceptable calibration. Among patients with a hospitalization risk of 15% or more, the model exhibited a sensitivity of 49% and a specificity of 85% for predicting chemotherapy-related hospitalization.
Brigham and Women's Hospital, Department of medicine and Division of Pharmacoepidemiology and Pharmacoeconomics / Abstract / Background / Physicians’ financial relationships with pharmaceutical companies have long been controversial. These relationships can consist of receipt of industry-sponsored meals, money for continuing medical education (CME) activities, reimbursements for consulting and participation on speaking bureaus, grants, and payments for education and training. Numerous small studies and surveys suggest that these financial relationships affect prescribing practices, but many physicians and policymakers remain unconvinced. Using a comprehensive Massachusetts medical conflicts of interest database and a prescription claims database, we sought to evaluate the association between physicians’ financial relationships and their prescribing of brand-name versus generic cholesterol-lowering medications. / Methodology / We manually linked Medicare prescription claims data prepared by the Centers for Medicare and Medicaid Services relating to Massachusetts physicians with the Massachusetts physician open-payment database from 2011. The exposure variable was the listing of physicians’ financial relationship and outcome measurement was physicians’ prescribing of any brand-name-only cholesterol-lowering medication. The analysis was limited to physicians who had at least 50 claims of a particular drug. We used chi-square and ANOVA tests to analyze the association between the intensity of physician-industry relationships (determined by monetary value of payments) and physicians’ prescribing practices. We used logistic regression model to determine the relationship between the types of physician-industry relationships and their brand-name prescribing behavior. / Results / Our analysis included 2444 physicians. Approximately one-third (899, 37%) had some sort of financial relationship with a pharmaceutical company, while 63% (1546) had no industry payments in 2011. The most common payment type was for company-sponsored meals (639, 71%), followed by grants (458, 51%), consulting and speaking bureau (236, 26%), and educational training grants (95, 11%). Compared to physicians without pharmaceutical company payments, physicians in the top quartile of total value of payments (>$1188) had higher rates of brand-name cholesterol-lowering medication prescriptions (21% versus 18%, p<0.01). When physicians were categorized by quartiles based on their rates of brand-name prescribing, there was a significant positive relationship between the average total monetary value of drug company payments ($3696, $1419, $701, and $542, p<0.01) and brand-name prescribing percentage (39%, 19%, 10%, and 4%, p<0.01), respectively. Among physicians who received pharmaceutical company payments, educational training payments were significantly associated with increased brand-name prescribing (18% versus 22%, p<0.01), but the other payment types were not. / Conclusion / Physicians who have financial relationships with pharmaceutical companies have higher brand-name cholesterol-lowering medication prescribing than physicians who do not have such relationships. The rate of brand-name prescribing was associated with the intensity of physician-industry relationships measured by the total value of monetary payments. The receipt of educational training payments may be a significant predictor of brand-name prescribing. The study findings only apply to physicians prescribing substantial numbers of cholesterol-lowering medication each year and may be limited by the integrity of pharmaceutical companies’ self-reporting of physician payments. /
Harvard Wide Pediatric Health Services Fellowship / Objective: To examine if proximity to a supermarket modified the effects of an obesity intervention. We hypothesized that children living closer to a supermarket would have larger improvements in diet quality and weight status than those living further away. / Methods: We examined 498 children ages 6-12 with a BMI ≥ 95th percentile, participating in an obesity trial from 2011-2013. The main exposure was the intervention. Outcomes were 1-year change in BMI z-score, sugar-sweetened beverage intake and fruit/vegetable intake. Distance to the closest supermarket was examined as an effect modifier. / Results: Distance to supermarkets was an effect modifier of 1-year change in BMI z-score and fruit/vegetable intake but not sugar-sweetened beverage intake. With each 1-mile shorter distance to a supermarket intervention participants increased their fruit/vegetable intake by 0.31 servings/day and decreased their BMI z-score by -0.04 units relative to controls. / Conclusions: Living closer to a supermarket was associated with greater improvements in fruit/vegetable intake and weight status in an obesity intervention. Future public health efforts should examine children’s environments and seek ways to help families who do not have readily-available supermarkets. /