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1.
Phys Rev E ; 104(2-1): 024313, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34525638

ABSTRACT

We studied the impact of field heterogeneity on entrainment in a system of uniformly interacting phase oscillators. Field heterogeneity is shown to induce dynamical heterogeneity in the system. In effect, the heterogeneous field partitions the system into interacting groups of oscillators that feel the same local field strength and phase. Based on numerical and analytical analysis of the explicit dynamical equations derived from the periodically forced Kuramoto model, we found that the heterogeneous field can disrupt entrainment at different field frequencies when compared to the homogeneous field. This transition occurs when the phase- and frequency-locked synchronization between groups of oscillators is broken at a critical field frequency, causing each group to enter a new dynamical state (disrupted state). Strikingly, it is shown that disrupted dynamics can differ between groups.

2.
Osteoporos Int ; 28(1): 239-244, 2017 01.
Article in English | MEDLINE | ID: mdl-27421978

ABSTRACT

This study aims to determine what factors are associated with increased risk of fracture among patients with HIV, in particular whether an important medication used to treat HIV, tenofovir, is associated with fracture. Our study found that while co-infection with hepatitis C and markers of HIV severity were associated with fracture, tenofovir was not. INTRODUCTION: Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk. METHODS: We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV. RESULTS: We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43 years, and 72 % were male. The hepatitis C co-infection rate was 28 %, about 40 % had nadir CD4 count <200, and about 40 % had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95 % CI 0.6-1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95 % CI 1.1-2.3), as did nadir CD4 count <200 (aRR 3.1, 95 % CI 1.9-5.0) and history of AIDS-defining illness (aRR 1.6, 95 % CI 1.1-2.2). CONCLUSION: There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.


Subject(s)
HIV Infections/complications , Osteoporotic Fractures/etiology , Adult , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Bone Density/drug effects , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/physiopathology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/epidemiology , Humans , Male , Massachusetts/epidemiology , Middle Aged , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/virology , Retrospective Studies , Risk Factors , Tenofovir/adverse effects , Tenofovir/therapeutic use
3.
Parasitology ; 138(9): 1117-23, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21756421

ABSTRACT

The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%-47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%-67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses from pregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%-6·66%); M. domesticus: 3·08% (95% CI: 0·11%-6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems.


Subject(s)
Coccidiosis , Infectious Disease Transmission, Vertical/veterinary , Neospora/physiology , Toxoplasma/physiology , Toxoplasmosis, Animal , Animals , Antigens, Protozoan/analysis , Brain Chemistry , Cats , Coccidiosis/epidemiology , Coccidiosis/parasitology , Coccidiosis/transmission , Coccidiosis/veterinary , Coinfection , DNA, Protozoan/analysis , Female , Fetus , Membrane Glycoproteins/analysis , Mice , Murinae , Polymerase Chain Reaction/veterinary , Pregnancy , Prevalence , Protozoan Proteins/analysis , Toxoplasmosis, Animal/epidemiology , Toxoplasmosis, Animal/parasitology , Toxoplasmosis, Animal/transmission , United Kingdom
4.
Osteoarthritis Cartilage ; 19(1): 44-50, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20955807

ABSTRACT

OBJECTIVE: To forecast the burden of symptomatic knee osteoarthritis (OA) in the elderly US population over a 10-year horizon. DESIGN: Using a computer simulation model of the natural history and management of knee OA combined with population-based data from the 2008 US Census we projected the 10-year burden of knee OA among persons 60-64 years of age. Knee OA incidence and progression rates were derived from national cohorts and calibrated to published literature. RESULTS: Using national data we estimated that 13% of 14,338,292 adults 60-64 years old have prevalent symptomatic, radiographic knee OA. Among persons surviving the next decade, 20% will have symptomatic advanced (Kellgren-Lawrence [K-L] grade 3) or end-stage (K-L 4) knee OA. Prevalence of advanced knee OA will range from 10% among non-obese to 35% among obese persons. Our estimates show that a more sensitive imaging tool, such as magnetic resonance imaging (MRI), may increase the number of OA cases diagnosed by up to 94% assuming that 50% of all 'pre-radiographic knee OA' (K-L 1) has some evidence of cartilage degeneration seen on MRI. CONCLUSIONS: Projecting new and advanced cases of knee OA among persons aged 60-64 years over the next decade creates a benchmark that can be used to evaluate population-based benefits of future disease-modifying OA drugs that are currently undergoing testing at various stages.


Subject(s)
Osteoarthritis, Knee/epidemiology , Cohort Studies , Disease Progression , Female , Forecasting , Humans , Incidence , Male , Middle Aged , Models, Theoretical , Prevalence , United States/epidemiology
5.
Parasitology ; 136(14): 1877-85, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19765335

ABSTRACT

Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat being the only definitive host, it is found in almost all geographical areas and warm blooded animals. Three routes of transmission are recognised: ingestion of oocysts shed by the cat, carnivory and congenital transmission. In natural populations, it is difficult to establish the relative importance of these routes. This paper reviews recent work in our laboratory which suggests that congenital transmission may be much more important than previously thought. Using PCR detection of the parasite, studies in sheep show that congenital transmission may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on the same farm, exposed to the same sources of oocysts, significant divergent prevalences of Toxoplasma infection and abortion are found between different families. The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs. Congenital transmission rates in a natural population of mice were found to be 75%. Interestingly, congenital transmission rates in humans were measured at 19.8%. The results presented in these studies differ from those of other published studies and suggest that vertical transmission may be much more important than previously thought.


Subject(s)
Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious , Toxoplasma , Toxoplasmosis, Animal/transmission , Toxoplasmosis/transmission , Animals , Cats , Female , Humans , Mice , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/parasitology , Pregnancy Complications, Infectious/veterinary , Prevalence , Sheep , Sheep Diseases/epidemiology , Sheep Diseases/parasitology , Sheep Diseases/transmission , Species Specificity , Toxoplasma/genetics , Toxoplasma/growth & development , Toxoplasma/isolation & purification , Toxoplasma/physiology , Toxoplasmosis/epidemiology , Toxoplasmosis/parasitology , Toxoplasmosis, Animal/epidemiology , Toxoplasmosis, Animal/parasitology , Toxoplasmosis, Congenital/epidemiology , Toxoplasmosis, Congenital/parasitology , Toxoplasmosis, Congenital/transmission
6.
Osteoarthritis Cartilage ; 16(8): 873-82, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18280757

ABSTRACT

OBJECTIVE: While the interpretation of cartilage findings on magnetic resonance imaging (MRI) evolves, plain radiography remains the standard method for assessing progression of knee osteoarthritis (OA). We sought to describe factors that explain variability in published estimates of radiographic progression in knee OA. DESIGN: We searched PubMed between January 1985 and October 2006 to identify studies that assessed radiographic progression using either joint space narrowing (JSN) or the Kellgren-Lawrence (K-L) scale. We extracted cohort characteristics [age, gender, and body mass index (BMI)] and technical and other study factors (radiographic approach, study design, OA-related cohort composition). We performed meta-regression analyses of the effects of these variables on both JSN and K-L progression. RESULTS: Of 239 manuscripts identified, 34 met inclusion criteria. The mean estimated annual JSN rate was 0.13 +/- 0.15 mm/year. While we found no significant association between JSN and radiographic approach among observational studies, full extension was associated with greater estimated JSN among randomized control trials (RCTs). Overall, observational studies that used the semi-flexed approach reported greater JSN than RCTs that used the same approach. The overall mean risk of K-L progression by at least one grade was 5.6 +/- 4.9%, with higher risk associated with shorter study duration, OA definition (K-L > or = 2 vs K-L > or = 1) and cohorts composed of subjects with both incident and prevalent OA. CONCLUSION: While radiographic approach and study design were associated with JSN, OA definition, cohort composition and study duration were associated with risk of K-L progression. These findings may inform the design of disease modifying osteoarthritis drug (DMOAD) trials and assist clinicians in optimal timing of OA treatments.


Subject(s)
Knee Joint/pathology , Osteoarthritis, Knee/pathology , Disease Progression , Humans , Knee Joint/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/epidemiology , Predictive Value of Tests , Radiography , Severity of Illness Index , Statistics as Topic
7.
Lupus ; 14(10): 832-6, 2005.
Article in English | MEDLINE | ID: mdl-16304727

ABSTRACT

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African-American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African-American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African-American women for SLE.


Subject(s)
Black or African American , Lupus Erythematosus, Systemic/diagnosis , Population Surveillance/methods , Surveys and Questionnaires , Urban Population , Adult , False Negative Reactions , Female , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/ethnology , Massachusetts/epidemiology , Middle Aged , Predictive Value of Tests , Risk Factors , Sensitivity and Specificity , White People
8.
Lupus ; 12(4): 280-6, 2003.
Article in English | MEDLINE | ID: mdl-12729051

ABSTRACT

The goal of this work was to develop an economical way of tracking disease activity for large groups of systemic lupus erythematosus (SLE) patients in clinical studies. A Systemic Lupus Activity Questionnaire (SLAQ) was developed to screen for possible disease activity using items from the Systemic Lupus Activity Measure (SLAM) and tested for its measurement properties. The SLAQ was completed by 93 SLE patients just prior to a scheduled visit. At the visit, a rheumatologist, blinded to SLAQ results, examined the subject and completed a SLAM. Associations among SLAQ, and SLAM (omitting laboratory items) and between individual items from each instrument were assessed with Pearson correlations. Correlations between pairs of instruments were compared using Student's t-tests. The mean score across all 24 SLAQ items was 11.5 (range 0-33); mean SLAM without labs was 3.0 (range 0-13). The SLAQ had a moderately high correlation with SLAM-nolab (r = 0.62, P < 0.0001). Correlations between patient-clinician matched pairs of items ranged from r = 0.06 to 0.71. Positive predictive values for the SLAQ ranged from 56 to 89% for detecting clinically significant disease activity. In studies of SLE, symptoms suggesting disease can be screened by self-report using the SLAQ and then verified by further evaluation.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Severity of Illness Index , Surveys and Questionnaires/standards , Adult , Clinical Trials as Topic , Female , Humans , Male , Multivariate Analysis , Physicians , Predictive Value of Tests , Rheumatology/methods
9.
J Bone Joint Surg Am ; 83(12): 1856-64, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11741066

ABSTRACT

BACKGROUND: The aim of this study was to validate the Knee Society Clinical Rating System (knee and function scores) and to compare its responsiveness with that of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form-36 (SF-36). METHODS: Patients were recruited as part of a prospective observational study of the outcomes of primary total knee arthroplasty for the treatment of osteoarthritis in four centers in the United States, six centers in the United Kingdom, and two centers in Australia. Independent research assistants at each site collected the Knee Society clinical data. The WOMAC, SF-36, patient satisfaction, and demographic data were obtained with self-administered questionnaires. RESULTS: A total of 862 eligible patients were recruited, and complete preoperative and twelve-month data were available for 697 (80.9%) of them. The mean age was seventy years (range, thirty-eight to ninety years), and the majority of the patients (58.9%) were women. Low correlations were found among the items of both the knee and the function score at both assessment times. The Knee Society pain and function scores had moderate-to-strong correlations with the corresponding pain and function domains of the WOMAC and SF-36 (r = 0.31 to 0.72). Measurement of the standardized response mean showed the Knee Society knee score to be more responsive (standardized response mean, 2.2) than the WOMAC (standardized response means, 2.0 for pain and 1.4 for function) and the SF-36 (standardized response means, 1.0 for bodily pain and 1.1 for physical functioning). The Knee Society function score was the least responsive measure (standardized response mean, 0.8). Correlation of changes in scores at twelve months with patient reports of satisfaction and improvement in health status showed the WOMAC and SF-36 to be more responsive than the Knee Society scores. CONCLUSIONS: There is a poor correlation among the items of the Knee Society Clinical Rating System, but the rating system has adequate convergent construct validity. The WOMAC and SF-36 are more responsive measures of outcome of total knee arthroplasty. As they are less labor-intensive for researchers to use and as use of these instruments removes observer bias from the study design, they are preferable for knee arthroplasty outcome studies.


Subject(s)
Activities of Daily Living , Arthroplasty, Replacement, Knee/rehabilitation , Pain Measurement/methods , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Osteoarthritis/surgery , Patient Satisfaction , Prospective Studies , Reproducibility of Results
10.
J Bone Joint Surg Am ; 83(8): 1149-56, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11507122

ABSTRACT

BACKGROUND: It is essential to adjust for the level of preoperative pain and functional status when measuring the outcome of total knee arthroplasty. Some study designs rely on postoperative patient recall to derive preoperative status. In this study, we compared prospectively collected preoperative data with data derived from patient recall of preoperative status three months after total knee arthroplasty. METHODS: Patients were recruited as part of a prospective observational study of the outcome of primary total knee arthroplasty for osteoarthritis at four centers in the United States, six centers in the United Kingdom, and two centers in Australia. Independent research assistants recruited patients and collected data with use of a uniform documentation system preoperatively and three months postoperatively. Preoperative data included the findings of a clinical history and physical examination, demographic information, socioeconomic status, and scores from two health-status instruments: the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form-36 Health Survey (SF-36). Postoperative data included the WOMAC and SF-36 scores and patient recall of preoperative status on selected items from these health-status measures. RESULTS: A total of 862 patients were recruited, and recall data were available for 770 patients (89%). The mean age was seventy years (range, thirty-eight to ninety years), and 59% of the patients were women. Comparisons of prospective and recall data on individual pain and function items showed poor-to-fair agreement (weighted kappa, 0.20 to 0.41). Patients recalled significantly more pain than they had reported preoperatively (p < 0.001), but there were random recollection errors for the function items. There was only moderate correlation between the prospective and recalled summary scores for pain (Spearman r = 0.53) and function (Spearman r = 0.48). In addition, 61% of the recalled pain scores and 50% of the recalled function scores differed from the prospective scores by more than 10 points (10% of the total range). CONCLUSIONS: Patients' recall of preoperative pain and functional status three months after total knee arthroplasty demonstrated only moderate agreement with what the patients had reported prospectively. Researchers who use recall data to derive preoperative status must recognize these limitations when drawing conclusions about the effectiveness of total knee arthroplasty.


Subject(s)
Arthroplasty, Replacement, Knee/psychology , Mental Recall , Outcome Assessment, Health Care , Pain Measurement , Activities of Daily Living/classification , Adult , Aged , Aged, 80 and over , Female , Health Status Indicators , Humans , Male , Middle Aged , Preoperative Care , Prospective Studies , Self Efficacy
11.
Am J Prev Med ; 20(3): 219-24, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11275450

ABSTRACT

BACKGROUND: To determine the age-specific prevalence of Lyme disease and whether preventive behaviors on Nantucket Island correlate with Lyme disease, we surveyed island residents. METHODS: A survey with questions on Lyme disease symptoms, history, and preventive behaviors was mailed to all residents. Respondents were stratified by likelihood of having had Lyme disease. A subsample was selected for examination, and then classified according to the Lyme disease national surveillance case definition. RESULTS: The overall lifetime prevalence of Lyme disease for Nantucket residents was 15% (CI, 10%-19.8%): 19% among females, and 11% among males. The prevalence was highest among age groups 0-16 and 30-49 years. Overall, 86% of the population practiced at least one behavior. The most frequently reported preventive behavior was checking oneself for ticks (80%), followed by wearing protective clothing (53%), avoiding tick areas (34%), and using tick repellent (11%). Younger individuals practiced fewer preventive behaviors than older individuals (p=0.001). Although males reported greater tick exposure than females, females uniformly practiced preventive behaviors more frequently (p=0.001). The practice of preventive behaviors was not associated with a history of Lyme disease, but finding more than 5 ticks per year on oneself was (p=0.001). CONCLUSION: Lyme disease is highly prevalent on Nantucket Island. Young people are particularly at risk and health education should emphasize preventive behaviors less frequently practiced: using tick repellent, avoiding tick areas, and wearing protective clothing.


Subject(s)
Health Knowledge, Attitudes, Practice , Lyme Disease/prevention & control , Adolescent , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Female , Health Surveys , Humans , Incidence , Infant , Lyme Disease/epidemiology , Male , Massachusetts/epidemiology , Middle Aged , Sex Factors
12.
Clin Infect Dis ; 31(5): 1149-54, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11073744

ABSTRACT

Previous studies suggest that concurrent Lyme disease and babesiosis produce a more sever illness than either disease alone. The majority of babesiosis infections, however, are subclinical. Our objective was to characterize on the basis of a total-population survey of Nantucket Island, Massachusetts, whether coexposure to Lyme disease and babesiosis causes more severe illness or poorer long-term outcomes than Lyme disease alone. In this retrospective cohort study, residents indicating a history of Lyme disease were compared with randomly selected population controls on a standardized medical history, blinded physical examination, and serological studies for Borrelia burgdorferi and Babesia microti. Serological evidence of exposure to babesiosis was not associated with increased severity of acute Lyme disease. The groups did not differ with regard to the prevalence of constitutional, musculoskeletal, or neurological symptoms a mean of 6 years after acute Lyme disease. Prior Lyme disease and serological exposure to B. microti are not associated with poorer long-term outcomes or more persistent symptoms Lyme disease alone.


Subject(s)
Babesia , Babesiosis/complications , Borrelia burgdorferi Group , Lyme Disease/pathology , Adult , Aged , Aged, 80 and over , Animals , Babesiosis/parasitology , Disease Progression , Female , Humans , Lyme Disease/complications , Lyme Disease/microbiology , Male , Middle Aged , Population Surveillance , Surveys and Questionnaires , Time Factors
13.
J Rheumatol ; 27(3): 680-4, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10743808

ABSTRACT

OBJECTIVE: To determine the prevalence and socioeconomic and clinical predictors of early organ damage in a cohort of patients with systemic lupus erythematosus (SLE) of 2-7 years' duration randomly sampled at 5 centers and balanced by socioeconomic status and race. METHODS: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index was measured in 200 patients who met the ACR criteria for SLE with a mean disease duration of 3.8 years. The SLICC/ACR scores for each organ system and the prevalence of damage within organ systems were assessed. Logistic regression analyses evaluated the simultaneous effects of age at diagnosis, disease duration, disease activity, and sociodemographic factors. RESULTS: Sixty-one percent of the patients had damage within 7 years of onset (mean 3.8 yrs). Neuropsychiatric (20.5%) and musculoskeletal (18.5%) systems were the most frequently involved, followed by renal (15.5%) and skin (12.5%) systems, all with median SLICC/ACR organ system scores of 1. In multivariate models, African-American race was associated with skin damage but not with damage in other specific organ systems. Socioeconomic status was not associated with organ system damage. Older age at diagnosis correlated with cardiovascular, musculoskeletal, gastrointestinal, ocular, and pulmonary damage. Clinical factors such as longer disease duration correlated with higher renal and cardiovascular damage, and greater disease activity at diagnosis of SLE correlated with greater renal, musculoskeletal, and pulmonary damage. CONCLUSION: There is evidence of organ system damage in SLE within a mean of 3.8 years after onset. We found little evidence for differences in early organ damage according to race or socioeconomic status. Damage to most organ systems was related to age at diagnosis of SLE and clinical factors such as disease duration.


Subject(s)
Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/physiopathology , Severity of Illness Index , Social Class , Adult , Black or African American/statistics & numerical data , Cohort Studies , Comorbidity , Female , Humans , Kidney Diseases/etiology , Lupus Erythematosus, Systemic/ethnology , Male , Mental Disorders/etiology , Middle Aged , Multivariate Analysis , Musculoskeletal Diseases/etiology , Nervous System Diseases/etiology , Skin Diseases/etiology , White People/statistics & numerical data
14.
Ann Intern Med ; 131(12): 919-26, 1999 Dec 21.
Article in English | MEDLINE | ID: mdl-10610642

ABSTRACT

BACKGROUND: Previous follow-up studies of patients with Lyme disease suggest that disseminated infection may be associated with long-term neurologic and musculoskeletal morbidity. OBJECTIVE: To determine clinical and functional outcomes in persons who were treated for Lyme disease in the late 1980s. DESIGN: Population-based, retrospective cohort study. SETTING: Nantucket Island, Massachusetts. PARTICIPANTS: 186 persons who had a history of Lyme disease (case-patients) and 167 persons who did not (controls). MEASUREMENTS: Standardized medical history, physical examination, functional status measure (Medical Outcomes Study 36-item Short Form Health Survey [SF-36]), mood state assessment (Profile of Mood States), neurocognitive tests, and serologic examination. RESULTS: The prevalence of Lyme disease among adults on Nantucket Island was estimated to be 14.3% (95% CI, 9.3% to 19.1%). In multivariate analyses, persons with previous Lyme disease (mean time from infection to study evaluation, 6.0 years) had more joint pain (odds ratio for having joint pain in any joint, 2.1 [CI, 1.2 to 3.5]; P = 0.007), more symptoms of memory impairment (odds ratio for having any memory problem, 1.9 [CI, 1.1 to 3.5]; P = 0.003), and poorer functional status due to pain (odds ratio for 1 point on the SF-36 scale, 1.02 [CI, 1.01 to 1.03]; P < 0.001) than persons without previous Lyme disease. However, on physical examination, case-patients and controls did not differ in musculoskeletal abnormalities, neurologic abnormalities, or neurocognitive performance. Persons with previous Lyme disease who had persistent symptoms after receiving treatment (n = 67) were more likely than those who had completely recovered to have had fever, headache, photosensitivity, or neck stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P = 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ. CONCLUSIONS: Because persons with previous Lyme disease exhibited no sequelae on physical examination and neurocognitive tests a mean of 6.0 years after infection, musculoskeletal and neurocognitive outcomes seem to be favorable. However, long-term impairment of functional status can occur.


Subject(s)
Lyme Disease/complications , Musculoskeletal Diseases/etiology , Nervous System Diseases/etiology , Outcome Assessment, Health Care , Adult , Arthralgia/etiology , Fatigue/etiology , Female , Follow-Up Studies , Humans , Lyme Disease/classification , Lyme Disease/epidemiology , Male , Massachusetts/epidemiology , Memory Disorders/etiology , Middle Aged , Multivariate Analysis , Prevalence , Retrospective Studies
15.
Br J Biomed Sci ; 56(1): 78-9, 1999.
Article in English | MEDLINE | ID: mdl-10492919
16.
J Rheumatol ; 25(11): 2249-53, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9818672

ABSTRACT

OBJECTIVE: To study the outcome of Lyme disease (LD) in children identified in a total population survey of an endemic island. METHODS: We conducted a population-based retrospective cohort study off the coast of Massachusetts. Twenty-five children who met the Centers for Disease Control case definition for prior LD were compared with 26 children without LD from the same community. All children with LD received antibiotics during the acute phase of their disease. All 51 children were invited for a clinical evaluation, including 12-lead electrocardiogram (EKG), and measurement of antibodies to Borrelia burgdorferi by antibody-capture ELISA and Western blot. RESULTS: At a mean of 3.2 years from the initial manifestation of LD, children with prior LD did not have a higher prevalence of musculoskeletal or neurological symptoms, examination abnormalities, abnormal EKG, or behavioral difficulties, compared to children with no history of LD. CONCLUSION: Children who receive appropriate antimicrobial therapy for LD appear to have no demonstrable longterm morbidity.


Subject(s)
Amoxicillin/therapeutic use , Lyme Disease/drug therapy , Penicillins/therapeutic use , Administration, Oral , Antibodies, Bacterial/analysis , Borrelia burgdorferi Group/immunology , Child , Child Behavior/physiology , Child, Preschool , Cohort Studies , Electrocardiography , Follow-Up Studies , Humans , Injections, Intravenous , Lyme Disease/immunology , Lyme Disease/physiopathology , Lyme Disease/psychology , Recurrence , Reference Values , Surveys and Questionnaires , Treatment Outcome
17.
J Immunol ; 161(6): 3114-9, 1998 Sep 15.
Article in English | MEDLINE | ID: mdl-9743378

ABSTRACT

IL-16 is a novel cytokine, which is chemoattractant for CD4+ T cells, macrophages, and eosinophils. Recently, it was reported that IL-16 is synthesized as an approximately 80-kDa precursor molecule, pro-IL-16. Since little is known about the processing and tissue distribution of IL-16 and pro-IL-16, we investigated the distribution of IL-16 mRNA and protein in human lymphoid tissue. Northern blotting identified IL-16 mRNA predominantly in normal lymphoid organs, including PBMC, spleen, and thymus. Immunohistochemistry of human lymph node localized IL-16 protein to lymphocyte cytoplasm within T cell zones and occasionally in lymphocytes in B cell zones. Flow cytometric detection of intracellular IL-16 showed that >70% of CD4+ and CD8+ T cells constitutively expressed IL-16 protein. Western blot analysis of PBMC revealed nearly all of this protein to be approximately 80-kDa pro-IL-16 in unstimulated PBMC, and upon cell activation, the amino terminus of pro-IL-16 is processed into multiple fragments. These results show that pro-IL-16 is widely and constitutively expressed and suggest that the amino terminus of the protein can be processed upon cell activation.


Subject(s)
Interleukin-16/metabolism , Protein Precursors/metabolism , T-Lymphocyte Subsets/metabolism , Adolescent , Adult , Amino Acid Sequence , Antibodies, Monoclonal/pharmacology , CD3 Complex/immunology , CD4-Positive T-Lymphocytes/chemistry , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Humans , Interleukin-16/biosynthesis , Interleukin-16/isolation & purification , Leukocytes, Mononuclear/chemistry , Lymphocyte Activation , Molecular Sequence Data , Organ Specificity/immunology , Protein Precursors/biosynthesis , Protein Precursors/isolation & purification , Protein Processing, Post-Translational/immunology , T-Lymphocyte Subsets/chemistry , T-Lymphocyte Subsets/immunology
18.
AIDS ; 11(13): 1595-601, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9365764

ABSTRACT

OBJECTIVE: We hypothesized that differential extravasation of circulating CD4+ or CD8+ T lymphocytes contributes to HIV-associated CD8+ lymphocytic alveolitis. Differences in T-cell transendothelial migration may be intrinsic or emerge at sites where vascular endothelium is activated by overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. DESIGN: We used an in vitro model of lymphocyte extravasation to assess transendothelial migration of peripheral blood mononuclear cells (PBMC) from HIV-positive individuals. We assayed bronchoalveolar lavage (BAL) fluid from HIV-positive and normal individuals to determine if increased levels of TNF-alpha and IFN-gamma were present in the lungs of HIV-infected individuals. METHODS: Transendothelial migration was assessed by determining the number and flow cytometric phenotype of PBMC adherent to or migrating across unstimulated or TNF-alpha and IFN-gamma-activated endothelial cell monolayers. We measured BAL fluid cytokine concentrations using standard antigen-capture enzyme-linked immunosorbent assays for TNF-alpha and IFN-gamma. RESULTS: T cells migrating across unactivated endothelial cells were significantly enriched for CD4+ T cells. Cytokine activation of endothelial cells allowed significantly greater transendothelial migration of CD8+ T cells compared to unactivated endothelial cells. TNF-alpha was increased in BAL fluid from HIV-positive individuals relative to controls. CONCLUSIONS: These data suggest that, in HIV-positive individuals, CD4+ T cells are migration competent and blood CD8+ T cells do not have enhanced migration competence relative to CD4+ T cells. CD8+ T cell extravasation is aided by TNF-alpha and IFN-gamma-induced endothelial cells activation.


Subject(s)
CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/physiology , HIV Infections/immunology , Bronchoalveolar Lavage , Cell Adhesion , Cell Count , Cell Differentiation , Cell Movement , Endothelium, Vascular/immunology , HIV Infections/blood , Humans , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , Leukocytes, Mononuclear/immunology , T-Lymphocyte Subsets/cytology , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology
19.
Arthritis Rheum ; 40(1): 47-56, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9008599

ABSTRACT

OBJECTIVE: To study the relationship of race, socioeconomic status (SES), clinical factors, and psychosocial factors to outcomes in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort was assembled, comprising 200 patients with SLE from 5 centers. This cohort was balanced in terms of race and SES. Patients provided information on socioeconomic factors, access to health care, nutrition, self-efficacy for disease management, health locus of control, social support, compliance, knowledge about SLE, and satisfaction with medical care. Outcome measures included disease activity (measured by the Systemic Lupus Activity Measure), damage (measured by the SLICC/ACR damage index), and health status (measured by the SF-36). RESULTS: In multivariate models that were controlled for race, SES, center, psychosocial factors, and clinical factors, lower self-efficacy for disease management (P < or = 0.0001), less social support (P < 0.005), and younger age at diagnosis (P < 0.007) were associated with greater disease activity. Older age at diagnosis (P < or = 0.0001), longer duration of SLE (P < or = 0.0001), poor nutrition (P < 0.002), and higher disease activity at diagnosis (P < 0.007) were associated with more damage. Lower self-efficacy for disease management was associated with worse physical function (P < or = 0.0001) and worse mental health status (P < or = 0.0001). CONCLUSION: Disease activity and health status were most strongly associated with potentially modifiable psychosocial factors such as self-efficacy for disease management. Cumulative organ damage was most highly associated with clinical factors such as age and duration of disease. None of the outcomes measured were associated with race. These results suggest that education and counseling, coordinated with medical care, might improve outcomes in patients with SLE.


Subject(s)
Confounding Factors, Epidemiologic , Lupus Erythematosus, Systemic/epidemiology , Racial Groups , Social Class , Adult , Black or African American , Cohort Studies , Female , Humans , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/psychology , Male , Middle Aged , Multivariate Analysis , Risk Factors , Severity of Illness Index , Treatment Outcome , White People
20.
Arthritis Rheum ; 40(1): 57-61, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9008600

ABSTRACT

OBJECTIVE: Clinical studies of systemic lupus erythematosus (SLE) often necessitate assessment of previous disease activity, which is sometimes only possible by retrospective evaluation of information from the medical record. Using the Systemic Lupus Activity Measure (SLAM), the present study compared an assessment of disease activity obtained by chart abstraction with a direct clinical assessment. METHODS: A chart SLAM was obtained using information abstracted from the clinic notes of 46 patients with SLE who were being followed up at a referral center. Chart SLAM scores were compared with SLAM scores derived from an independent assessor's direct clinical evaluation. RESULTS: Direct SLAM and chart SLAM scores were correlated (r = 0.67 by Spearman's rank correlation, P = 0.0001). Chart review scores for disease activity tended to be lower, but to an inconsistent degree, reflecting both under- and overestimation of disease activity. The overall misclassification rate on a 3-category scale (mild, moderate, or severe activity) was 59%. CONCLUSION: Although chart SLAM scores were highly correlated with direct SLAM scores, misclassification of disease activity by chart review cannot be rectified. Thus, in research, medical record review should not be used as a proxy for the direct SLAM, nor should it be considered comparable with clinical assessments in the analysis of disease activity.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Medical Records , Outcome Assessment, Health Care , Adult , Female , Humans , Lupus Erythematosus, Systemic/classification , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Severity of Illness Index
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