Demographic, geographic, and temporal patterns of ambulance runs for suspected opiate overdose in Rhode Island, 1997-20021
We examine ambulance runs for suspected opiate overdose from 1997 to 2002 using a Rhode Island Department of Health database. Of the 8,763 ambulance runs for overdoses, 18.6% were for suspected opiate overdoses. Most cases were males under age 54. Suspected opiate overdoses were more likely to occur in a private residence, were more frequent on Fridays and Saturdays, and peaked in incidence around 9:00 p.m. The incidence rate of suspected opiate overdose by year was similar. The study results may help identify areas for preventive intervention and demonstrate the limitation of using naloxone as a marker of opiate overdose events.
Factors contributing to spontaneous Enterocytozoon bieneusi infection in simian immunodeficiency virus-infected macaques
BACKGROUND: A cohort of SIV-infected macaques had been used to investigate the effect of dietary supplement, immune status, SIV/AIDS disease progression and serum micronutrients levels on spontaneous acquisition of Enterocytozoon bieneusi infection in SIV-infected macaques. METHODS: Twenty-four SIV-infected macaques were randomized into 2 groups. One group received a vitamin/mineral supplementation and a second group received a placebo. Both groups were examined for E. bieneusi infection. RESULTS: SIV-infected macaques were more prone to acquire E. bieneusi with the progression of SIV/AIDS, and the increased shedding of infectious spores was directly associated with decreased CD4 lymphocyte and increased circulating SIV, in both supplemented and unsupplemented groups of animals. Dietary supplementation, body composition factors and serum micronutrients levels however had no association with the acquisition of E. bieneusi infection in these animals. CONCLUSIONS: Acquisition of E. bieneusi infection is related to SIV disease progression, CD4 counts and viral load but independent of changes in body composition and serum micronutrient levels.
OBJECTIVES: Although risk factors for indoor falls among older individuals have been well studied, little is known about the etiology of outdoor falls. We examined risk factors for outdoor falls among middle-aged and older adults. METHODS: We analyzed data on the most recent fall during the past year among participants aged 45 years and older in the control group (N=2193) of a case-control study of fractures. The study was conducted at 5 Northern California Kaiser Permanente Medical Centers between 1996 and 2001. RESULTS: Falls occurred outdoors more often than indoors among most age groups. Study participants who reported more leisure-time physical activity had a higher risk for outdoor falls, and participants who were in poorer health had a greater risk for indoor falls. Most outdoor falls (73%) were precipitated by environmental factors, such as uneven surfaces and tripping or slipping on objects, and usually occurred on sidewalks, curbs, and streets. Walking (47.3%) was the most common fall-related activity. CONCLUSIONS: Outdoor falls among adults aged 45 years and older were frequently attributable to modifiable environmental factors. With the widespread promotion of active lifestyles among older people, improvements in their outdoor environment are urgently needed.
A diet high in saturated fat and cholesterol accelerates simian immunodeficiency virus disease progression
Several lines of evidence suggest that dietary fat and cholesterol may play a role in the pathogenesis of human immunodeficiency virus (HIV) infection and disease progression. We examined the effect that an atherogenic diet (AD) high in saturated fatty acids and cholesterol has on disease progression and systemic inflammation in the simian immunodeficiency virus (SIV)-infected macaque model of acquired immunodeficiency syndrome. Macaques fed an AD had significantly more rapid disease progression, resulting in an increased risk of SIV-related death compared with that in control macaques (hazard ratio, 5.4 [95% confidence interval, 1.7-17.0]; P<.001). Peak viral load was higher in the AD group compared with control values, but further statistically significant differences were not detected at viral set point. The baseline plasma interleukin-18 level after 6 months of the AD was predictive of disease progression. Our findings may have important implications for HIV-infected individuals, because they suggest that dietary changes and manipulation of lipid metabolism could offer potential benefits by slowing disease progression.
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
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
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
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.
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.
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.
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
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.
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
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
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.
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
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.
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
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.