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Serial evaluation of protein C and antithrombin in dogs with sepsis

Wed, 06/18/2014 - 11:01am

BACKGROUND: Protein C (PC) and antithrombin (AT) activities are decreased in humans with severe sepsis, and persistent changes are associated with decreased survival. In dogs with sepsis, PC and AT have been shown to be decreased at the time of diagnosis. HYPOTHESIS: PC and AT activities change significantly over time in dogs with sepsis and may be related to outcome. ANIMALS: Twelve dogs with naturally occurring sepsis. METHODS: Blood was collected from 12 dogs with sepsis, defined as histopathologic or microbiologic confirmation of infection and two of the following: hypo- or hyperthermia, tachycardia, tachypnea, leukopenia, leukocytosis, or >3% bands. The time of 1st sampling was considered day 1 and sampling was repeated every 24 hours for 5 days or until discharge or death. Changes over time were analyzed by ANOVA with repeated measures, and the association between PC and AT and outcome was determined by a 2-equation treatment effects model. RESULTS: Nine dogs and 11 dogs had decreased PC and AT activity on day 1, respectively (mean PC, 66.0 +/- 25.8%; mean AT, 48.1 +/- 16.5%). PC activity significantly decreased from day 1 to day 2 (P= .001), then increased over time. Changes in PC (P < .001) and AT (P < .001) over time were likely associated with outcome with nonsurvivors having lower PC and AT activities than survivors. CONCLUSION: Results of this preliminary study show that PC and AT activities change significantly over time in dogs with sepsis and both are likely related to survival.

Influence of donor cocaine use on outcome after cardiac transplantation: analysis of the United Network for Organ Sharing Thoracic Registry

Wed, 06/18/2014 - 11:01am

Heart transplantation from donors with a history of cocaine abuse remains controversial. Therefore, we examined the consequence of donor cocaine-use history on all-cause mortality and the development of coronary artery disease after heart transplantation. Using the United Network for Organ Sharing Thoracic Registry we identified 9,217 first-time heart-only adult transplant recipients between January 1999 and December 2003, and then divided this cohort into sub-groups based on the reported history of donor cocaine use. Multivariate analysis revealed no difference in mortality or development of coronary artery disease at 1 and 5 years between transplant recipients who received an organ from donors with a history of cocaine use when compared with donors having no history of cocaine use.

Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac)239

Wed, 06/18/2014 - 11:01am

Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIV(mac)239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral antigens and Gag-specific CD4(+) T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIV(mac)239. However, significantly lower viral loads and higher memory CD4(+) T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIV(mac)239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.

Factors associated with hallux valgus in a population-based study of older women and men: the MOBILIZE Boston Study

Wed, 06/18/2014 - 11:01am

OBJECTIVE: To examine potential risk factors for hallux valgus in community-dwelling elders. METHOD: Data from 600 MOBILIZE Boston Study participants (386 women and 214 men) were analyzed. Hallux valgus was defined as >15 degrees angular deviation of the hallux with respect to the first metatarsal bone toward the lesser toes. Associations of hallux valgus with age, body mass index (BMI), race, education, pes planus, foot pain, and in women, history of high heel shoe use, were assessed using sex-specific Poisson regression with robust variance estimation for risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Hallux valgus was present in 58% of women and 25% of men. Higher BMI was inversely associated with presence of hallux valgus in women (P trend=0.001), with the strongest inverse association observed in those with BMI of 30.0 or more compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually wore high-heeled shoes during ages 20-64 years compared to those who did not, had increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men, those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men without pes planus. CONCLUSION: In women, hallux valgus was associated with lower BMI and high heel use during ages 20-64, while in men, associations were observed with higher BMI and pes planus. Our results suggest that the etiologic mechanisms for hallux valgus may differ between men and women. Elsevier Ltd. All rights reserved.

Poor adherence to medications may be associated with falls

Wed, 06/18/2014 - 11:01am

BACKGROUND: Poor medication adherence is associated with negative health outcomes. We investigated whether poor medication adherence increases the rate of falls as part of Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston (MOBILIZE Boston), a prospective, community-based cohort recruited for the purpose of studying novel risk factors for falls. METHODS: A total of 246 men and 408 women (mean age, 78 years) were followed for the occurrence of falls (median follow-up, 1.8 years). Adherence was assessed by the Morisky scale based on the following four questions: whether an individual ever forgets, is careless at times, stops taking medications when feels better, or stops taking medications when feels worse. Low adherence was defined as a "yes" answer to one or more questions. High adherence was defined as a "no" answer to every question. RESULTS: Forty-eight percent of subjects were classified as having low medication adherence. The rate of falls in the low adherence group was 1.1 falls/person-year (95% confidence interval [CI]: 1.0-1.3) compared with 0.7 falls/person-year (95% CI: 0.6-0.8) in the high adherence group. After adjusting for age, sex, race/ethnicity, education, alcohol use, cognitive measures, functional status, depression, and number of medications, low medication adherence was associated with a 50% increased rate of falls compared with high medication adherence (rate ratio = 1.5, 95% CI: 1.2-1.9; p < .001). CONCLUSIONS: Low medication adherence may be associated with an increased rate of falls among older adults. Future studies should confirm this association and explore whether interventions to improve medication adherence might decrease the frequency of falls and other serious health-related outcomes.

Survival after cardiac transplantation in patients with hypertrophic cardiomyopathy

Wed, 06/18/2014 - 11:00am

BACKGROUND: Heart transplant is a treatment option for selected patients with hypertrophic cardiomyopathy (HCM). However, the prevalence, clinical profile, and outcome of this subgroup of HCM patients are uncertain. Therefore, we sought to determine the occurrence, clinical characteristics, and prognosis of HCM patients who underwent cardiac transplantation in the United States during a 15-year period. METHODS AND RESULTS: Demographic, clinical, and survival outcomes of 26 706 adult (age >/=18 years), heart-only transplant recipients between January 1990 and December 2004 were acquired from the United Network of Organ Sharing Registry. Pretransplant diagnoses were classified as follows: HCM (n=303, 1%) and non-HCM (26 403, 99%), comprising 3 patient subgroups: (1) ischemic cardiomyopathy (n=14 308, 54%), (2) dilated cardiomyopathy (n=11 760, 44%), and (3) restrictive cardiomyopathy (n=335, 1%). Study follow-up began at the time of heart transplant and was 76+/-44 months (mean+/-SD) among survivors. The 1-, 5-, and 10-year overall transplant survival for HCM patients was 85%, 75%, and 61%, respectively, with a trend toward greater survival compared with that of non-HCM transplant patients (82%, 70%, and 49%, respectively; log-rank test, P=0.05). However, propensity-matched, covariate-adjusted, Cox regression model analysis showed better survival over time (P<0.01) among the HCM patients. When HCM posttransplant survival was compared with that in each of the non-HCM patient subgroups, HCM patients had more favorable survival than did those transplanted for ischemic cardiomyopathy (P=0.02). In contrast, HCM posttransplant survival did not differ from that of patients transplanted for restrictive (P=0.08) or dilated (P=0.25) cardiomyopathy. CONCLUSIONS: HCM patients compose a small subset (1%) of the overall population of patients who undergo heart transplantation in the United States. Nonetheless, survival after transplant among HCM patients is comparable to that of patients transplanted for non-HCM cardiovascular diseases, with possible enhanced survival over time.

Classification of dengue illness based on readily available laboratory data

Wed, 06/18/2014 - 11:00am

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The sensitivity of the models ranged from 89.2% (dengue versus OFI) to 79.6% (DHF versus DF). The models showed high sensitivity in the validation dataset. These models could be used to calculate a probability and classify patients based on readily available clinical laboratory data, and they will need to be validated in other dengue-endemic regions.

Envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge

Wed, 06/18/2014 - 11:00am

Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on weeks 18 and 24. Although this immunization regimen did not elicit antibodies capable of detectably neutralizing SIV(mac)239 or SIV(mac)251(UCD), neutralizing antibody titers to the envelope-modified strains were selectively enhanced. Virus-specific antibodies and T cells were observed in the vaginal mucosa. After 20 weeks of repeated, low-dose vaginal challenge with SIV(mac)251(UCD), six of eight immunized animals versus six of six naive controls became infected. Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naive control animals.

Design-based random permutation models with auxiliary information

Wed, 06/18/2014 - 11:00am

We extend the random permutation model to obtain the best linear unbiased estimator of a finite population mean accounting for auxiliary variables under simple random sampling without replacement (SRS) or stratified SRS. The proposed method provides a systematic design-based justification for well-known results involving common estimators derived under minimal assumptions that do not require specification of a functional relationship between the response and the auxiliary variables.

The Women's Health Initiative: The food environment, neighborhood socioeconomic status, BMI, and blood pressure

Wed, 06/18/2014 - 11:00am

Using data (n = 60,775 women) from the Women's Health Initiative Clinical Trial (WHI CT)-a national study of postmenopausal women aged 50-79 years-we analyzed cross-sectional associations between the availability of different types of food outlets in the 1.5 miles surrounding a woman's residence, census tract neighborhood socioeconomic status (NSES), BMI, and blood pressure (BP). We simultaneously modeled NSES and food outlets using linear and logistic regression models, adjusting for multiple sociodemographic factors, population density and random effects at the tract and metropolitan statistical area (MSA) level. We found significant associations between NSES, availability of food outlets and individual-level measurements of BMI and BP. As grocery store/supermarket availability increased from the 10th to the 90th percentile of its distribution, controlling for confounders, BMI was lower by 0.30 kg/m(2). Conversely, as fast-food outlet availability increased from the 10th to the 90th percentile, BMI was higher by 0.28 kg/m(2). When NSES increased from the 10th to the 90th percentile of its distribution, BMI was lower by 1.26 kg/m(2). As NSES increased from the 10th to the 90th percentile, systolic and diastolic BP were lower by 1.11 mm Hg and 0.40 mm Hg, respectively. As grocery store/supermarket outlet availability increased from the 10th and 90th percentiles, diastolic BP was lower by 0.31 mm Hg. In this national sample of postmenopausal women, we found important independent associations between the food and socioeconomic environments and BMI and BP. These findings suggest that changes in the neighborhood environment may contribute to efforts to control obesity and hypertension.

Vaccine protection against simian immunodeficiency virus in monkeys using recombinant gamma-2 herpesvirus

Wed, 06/18/2014 - 11:00am

Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. Three RRV-negative and two RRV-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular immune responses were elicited on the basis of major histocompatibility complex (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT) assays. Responses were much greater in magnitude in the monkeys that were initially RRV negative but were still readily detected in the two monkeys that were naturally infected with RRV at the time of immunization. By 3 weeks postimmunization, responses measured by MHC tetramer staining in the two Mamu-A*01(+) RRV-negative monkeys reached 9.3% and 13.1% of all CD8(+) T cells in peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8(+) T cells in peripheral blood to the Tat SL8 epitope. Virus-specific CD8(+) T cell responses persisted at high levels up to the time of challenge at 18 weeks postimmunization, and responding cells maintained an effector memory phenotype. Despite the ability of the RRVenv recombinant to express high levels of Env in cultured cells, and despite the appearance of strong anti-RRV antibody responses in immunized monkeys, anti-Env antibody responses were below our ability to detect them. Immunized monkeys, together with three unimmunized controls, were challenged intravenously with 10 monkey infectious doses of SIVmac239. All five immunized monkeys and all three controls became infected with SIV, but peak viral loads were 1.2 to 3.0 log(10) units lower and chronic-phase viral loads were 1.0 to 3.0 log(10) units lower in immunized animals than the geometric mean of unimmunized controls. These differences were statistically significant. Anti-Env antibody responses following challenge indicated an anamnestic response in the vaccinated monkeys. These findings further demonstrate the potential of recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that this live, replication-competent, persistent herpesvirus vector could match, or come close to matching, live attenuated strains of SIV in the degree of protection if the difficulty with elicitation of anti-Env antibody responses can be overcome.

Prediction with measurement errors in finite populations

Wed, 06/18/2014 - 11:00am

We address the problem of selecting the best linear unbiased predictor (BLUP) of the latent value (e.g., serum glucose fasting level) of sample subjects with heteroskedastic measurement errors. Using a simple example, we compare the usual mixed model BLUP to a similar predictor based on a mixed model framed in a finite population (FPMM) setup with two sources of variability, the first of which corresponds to simple random sampling and the second, to heteroskedastic measurement errors. Under this last approach, we show that when measurement errors are subject-specific, the BLUP shrinkage constants are based on a pooled measurement error variance as opposed to the individual ones generally considered for the usual mixed model BLUP. In contrast, when the heteroskedastic measurement errors are measurement condition-specific, the FPMM BLUP involves different shrinkage constants. We also show that in this setup, when measurement errors are subject-specific, the usual mixed model predictor is biased but has a smaller mean squared error than the FPMM BLUP which point to some difficulties in the interpretation of such predictors.

The effect of systematic clinical interventions with cigarette smokers on quit status and the rates of smoking-related primary care office visits

Wed, 06/18/2014 - 11:00am

BACKGROUND: The United States Public Health Service (USPHS) Guideline for Treating Tobacco Use and Dependence includes ten key recommendations regarding the identification and the treatment of tobacco users seen in all health care settings. To our knowledge, the impact of system-wide brief interventions with cigarette smokers on smoking prevalence and health care utilization has not been examined using patient population-based data. METHODS AND FINDINGS: Data on clinical interventions with cigarette smokers were examined for primary care office visits of 104,639 patients at 17 Harvard Vanguard Medical Associates (HVMA) sites. An operational definition of "systems change" was developed. It included thresholds for intervention frequency and sustainability. Twelve sites met the criteria. Five did not. Decreases in self-reported smoking prevalence were 40% greater at sites that achieved systems change (13.6% vs. 9.7%, p<.01). On average, the likelihood of quitting increased by 2.6% (p<0.05, 95% CI: 0.1%-4.6%) per occurrence of brief intervention. For patients with a recent history of current smoking whose home site experienced systems change, the likelihood of an office visit for smoking-related diagnoses decreased by 4.3% on an annualized basis after systems change occurred (p<0.05, 95% CI: 0.5%-8.1%). There was no change in the likelihood of an office visit for smoking-related diagnoses following systems change among non-smokers. CONCLUSIONS: The clinical practice data from HVMA suggest that a systems approach can lead to significant reductions in smoking prevalence and the rate of office visits for smoking-related diseases. Most comprehensive tobacco intervention strategies focus on the provider or the tobacco user, but these results argue that health systems should be included as an integral component of a comprehensive tobacco intervention strategy. The HVMA results also give us an indication of the potential health impacts when meaningful use core tobacco measures are widely adopted.

Use of practice-based research network data to measure neighborhood smoking prevalence

Wed, 06/18/2014 - 11:00am

INTRODUCTION: Practice-Based Research Networks (PBRNs) and health systems may provide timely, reliable data to guide the development and distribution of public health resources to promote healthy behaviors, such as quitting smoking. The objective of this study was to determine if PBRN data could be used to make neighborhood-level estimates of smoking prevalence. METHODS: We estimated the smoking prevalence in 32 greater Boston neighborhoods (population = 877,943 adults) by using the electronic health record data of adults who in 2009 visited one of 26 Partners Primary Care PBRN practices (n = 77,529). We compared PBRN-derived estimates to population-based estimates derived from 1999-2009 Behavioral Risk Factor Surveillance System (BRFSS) data (n = 20,475). RESULTS: The PBRN estimates of neighborhood smoking status ranged from 5% to 22% and averaged 11%. The 2009 neighborhood-level smoking prevalence estimates derived from the BRFSS ranged from 5% to 26% and averaged 13%. The difference in smoking prevalence between the PBRN and the BRFSS averaged -2 percentage points (standard deviation, 3 percentage points). CONCLUSION: Health behavior data collected during routine clinical care by PBRNs and health systems could supplement or be an alternative to using traditional sources of public health data.

Stiffness control of balance during dual task and prospective falls in older adults: the MOBILIZE Boston Study

Wed, 06/18/2014 - 11:00am

Outdoor fallers differ from indoor fallers substantially in demographics, lifestyle, health condition and physical function. Biomechanical predictors of outdoor falls have not been well characterized. Current validated measures of postural deficits, which describe only the overall postural behavior, are predictive of indoor falls but not outdoor falls. We hypothesized that a model-based description of postural muscle tone and reflexes, particularly during dual tasking, would predict outdoor falls. We tested whether postural stiffness and damping from an inverted pendulum model were predictive of future indoor and outdoor falls among older adults from the MOBILIZE Boston Study. The center of pressure data during standing were obtained from 717 participants aged 77.9+/-5.3 years. Participants stood barefoot with eyes open for 30s per trial, in two sets of five standing trials. One set included a serial subtractions task. Postural stiffness and damping values were determined from the postural sway data. After the postural measurements, falls were monitored prospectively using a monthly mail-in calendar over 6-36 months. Associations of postural measures with fall rates were determined using negative binomial regressions. After covariate adjustments, postural stiffness (p=0.02-0.05) and damping (p=0.007-0.1) were associated with lower outdoor falls risk, but not with indoor falls. Results were invariant by direction (anteroposterior versus mediolateral) or by condition (quiet standing versus dual task). Outdoor fall risk may be tied to postural control more so than indoor falls. Dual tasking is likely related to fall risk among older and sicker older adults, but not those relatively healthy.

Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years

Wed, 06/18/2014 - 11:00am

IMPORTANCE: Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women's cognitive function. It is not known whether this extends to younger women. OBJECTIVE: To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function. DESIGN: Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999. SETTING: Forty academic research centers. PARTICIPANTS: The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years. INTERVENTION: The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory. RESULTS: Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (-0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of -0.17 (-0.33 to -0.02) and -0.25 (-0.42 to -0.08), respectively; however, this may be a chance finding. CONCLUSIONS AND RELEVANCE: CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01124773.

Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys

Wed, 06/18/2014 - 11:00am

The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:

Tailoring community-based wellness initiatives with latent class analysis--Massachusetts Community Transformation Grant projects

Wed, 06/18/2014 - 11:00am

INTRODUCTION: Community-based approaches to preventing chronic diseases are attractive because of their broad reach and low costs, and as such, are integral components of health care reform efforts. Implementing community-based initiatives across Massachusetts' municipalities presents both programmatic and evaluation challenges. For effective delivery and evaluation of the interventions, establishing a community typology that groups similar municipalities provides a balanced and cost-effective approach. METHODS: Through a series of key informant interviews and exploratory data analysis, we identified 55 municipal-level indicators of 6 domains for the typology analysis. The domains were health behaviors and health outcomes, housing and land use, transportation, retail environment, socioeconomics, and demographic composition. A latent class analysis was used to identify 10 groups of municipalities based on similar patterns of municipal-level indicators across the domains. RESULTS: Our model with 10 latent classes yielded excellent classification certainty (relative entropy = .995, minimum class probability for any class = .871), and differentiated distinct groups of municipalities based on health-relevant needs and resources. The classes differentiated healthy and racially and ethnically diverse urban areas from cities with similar population densities and diversity but worse health outcomes, affluent communities from lower-income rural communities, and mature suburban areas from rapidly suburbanizing communities with different healthy-living challenges. CONCLUSION: Latent class analysis is a tool that may aid in the planning, communication, and evaluation of community-based wellness initiatives such as Community Transformation Grants projects administrated by the Centers for Disease Control and Prevention.

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women's health initiative

Wed, 06/18/2014 - 11:00am

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50-79 at enrollment in the women's health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 +/- 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60-0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.

Overcoming inertia: increasing public health departments' access to evidence-based information and promoting usage to inform practice

Wed, 06/18/2014 - 10:52am

In 2010, the New England Region-National Network of Libraries of Medicine at University of Massachusetts Medical School received funding to improve information access for public health departments in 6 New England states and Colorado. Public health departments were provided with desktop digital access to licensed e-resources available through special pricing. In January through mid-April 2012, we evaluated the effectiveness of providing access to and training for using e-resources to public health department staff to motivate usage in practice. We found that additional strategies are needed to accomplish this.