Publications by authors named "Michael Yaron"

26 Publications

  • Page 1 of 1

Forecasting fire risk with machine learning and dynamic information derived from satellite vegetation index time-series.

Sci Total Environ 2021 Apr 8;764:142844. Epub 2020 Oct 8.

Department of Geography and Environment, Bar-Ilan University, Israel.

Fire risk mapping - mapping the probability of fire occurrence and spread - is essential for pre-fire management as well as for efficient firefighting efforts. Most fire risk maps are generated using static information on variables such as topography, vegetation density, and fuel instantaneous wetness. Satellites are often used to provide such information. However, long-term vegetation dynamics and the cumulative dryness status of the woody vegetation, which may affect fire occurrence and spread, are rarely considered in fire risk mapping. Here, we investigate the impact of two satellite-derived metrics that represent long-term vegetation status and dynamics on fire risk mapping - the long-term mean normalized difference vegetation index (NDVI) of the woody vegetation (NDVI) and its trend (NDVI). NDVI represents the mean woody density at the grid cell, while NDVI is the 5-year trend of the woody NDVI representing the long-term dryness status of the vegetation. To produce these metrics, we decompose time-series of satellite-derived NDVI following a method adjusted for Mediterranean woodlands and forests. We tested whether these metrics improve fire risk mapping using three machine learning (ML) algorithms (Logistic Regression, Random Forest, and XGBoost). We chose the 2007 wildfires in Greece for the analysis. Our results indicate that XGBoost, which accounts for variable interactions and non-linear effects, was the ML model that produced the best results. NDVI improved the model performance, while NDVI was significant only when NDVI was high. This NDVI-NDVI interaction means that the long-term dryness effect is meaningful only in places of dense woody vegetation. The proposed method can produce more accurate fire risk maps than conventional methods and can supply important dynamic information that may be used in fire behavior models.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142844DOI Listing
April 2021

Mean and variance of greenness and pregnancy outcomes in Tel Aviv during 2000-14: longitudinal and cross-sectional approaches.

Int J Epidemiol 2019 08;48(4):1054-1072

Ministry of Health, Jerusalem, Israel.

Background: Natural environments may have beneficial impacts on pregnancy outcomes. However, longitudinal evidence is limited and the associations with variance in surrounding greenness is unknown. Our objective was to evaluate these associations among 73 221 live births in Tel Aviv, Israel.

Methods: Longitudinal exposure to mean of greenness during pregnancy and trimesters were calculated using satellite-based Moderate Resolution Imaging Spectroradiometer (MODIS) Normalised Difference Vegetation Index (NDVI) data. In addition, exposure to mean and variation of NDVI from high-resolution satellite and percentage of tree cover [Vegetation Continuous Fields (VCF)] at 300-m buffer were evaluated in a cross-sectional approach. Generalized linear models were used to estimate the crude and adjusted associations. We explore the possible mediating role of ambient exposures and distance to 'outdoor gyms' located in parks.

Results: Crude beneficial associations between exposure to higher mean NDVI during pregnancy and pregnancy outcomes were observed [for birthweight, 3rd/1st tertile exposure increased the mean by 25.5 g, 95% confidence intervals (CIs): 15.4, 35.5] and decreased the odds of low birthweight, small for gestational age, preterm deliveries (PTD) and very PTD. Adjustment for individual and neighbourhood-level markers of socio-economic status (SES) attenuated all the associations. Strongest associations were observed during the first and second trimesters. Cross-sectional associations for mean greenness were similar with narrower CIs, and associations with NDVI were stronger than with tree cover and stronger for mean compared with variance of greenness. Associations were consistent for term births, different buffer sizes and for further adjustment to maternal education. Stronger associations were observed for lowest SES. Distance to 'outdoor gyms' and variance of greenness had the largest estimates of mediation.

Conclusion: This study adds to the limited information on when exposure to greenness is most beneficial, on the association with variance of greenness and the possible pathways. These observations require confirmation in other populations.
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http://dx.doi.org/10.1093/ije/dyy249DOI Listing
August 2019

Empirical analysis of vegetation dynamics and the possibility of a catastrophic desertification transition.

PLoS One 2017 20;12(12):e0189058. Epub 2017 Dec 20.

Department of Physics, Bar-Ilan University, Ramat-Gan IL52900, Israel.

The process of desertification in the semi-arid climatic zone is considered by many as a catastrophic regime shift, since the positive feedback of vegetation density on growth rates yields a system that admits alternative steady states. Some support to this idea comes from the analysis of static patterns, where peaks of the vegetation density histogram were associated with these alternative states. Here we present a large-scale empirical study of vegetation dynamics, aimed at identifying and quantifying directly the effects of positive feedback. To do that, we have analyzed vegetation density across 2.5 × 106 km2 of the African Sahel region, with spatial resolution of 30 × 30 meters, using three consecutive snapshots. The results are mixed. The local vegetation density (measured at a single pixel) moves towards the average of the corresponding rainfall line, indicating a purely negative feedback. On the other hand, the chance of spatial clusters (of many "green" pixels) to expand in the next census is growing with their size, suggesting some positive feedback. We show that these apparently contradicting results emerge naturally in a model with positive feedback and strong demographic stochasticity, a model that allows for a catastrophic shift only in a certain range of parameters. Static patterns, like the double peak in the histogram of vegetation density, are shown to vary between censuses, with no apparent correlation with the actual dynamical features. Our work emphasizes the importance of dynamic response patterns as indicators of the state of the system, while the usefulness of static modality features appears to be quite limited.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189058PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737887PMC
January 2018

Wilderness Preparticipation Evaluation and Considerations for Special Populations.

Wilderness Environ Med 2015 Dec;26(4 Suppl):S76-91

Longs Peak Sports Medicine, Longmont, Colorado (Dr Madden).

Children, older adults, disabled and special needs athletes, and female athletes who participate in outdoor and wilderness sports and activities each face unique risks. For children and adolescents traveling to high altitude, the preparticipation physical evaluation should focus on risk assessment, prevention strategies, early recognition of altitude-related symptoms, management plans, and appropriate follow-up. As the risk and prevalence of chronic disease increases with age, both older patients and providers need to be aware of disease and medication-specific risks relative to wilderness sport and activity participation. Disabled and special needs athletes benefit from careful pre-event planning for the potential medical issues and equipment modifications that may affect their health in wilderness environments. Issues that demand special consideration for female adventurers include pregnancy, contraceptive use, menses, and ferritin levels at altitude. A careful preparticipation evaluation that factors in unique, population- specific risks will help special populations stay healthy and safe on wilderness adventures. The PubMed and SportDiscus databases were searched in 2014 using both MeSH terms and text words and include peer-reviewed English language articles from 1977 to 2014. Additional information was accessed from Web-based sources to produce this narrative review on preparticipation evaluation for special populations undertaking wilderness adventures. Key words include children, adolescent, pediatric, seniors, elderly, disabled, special needs, female, athlete, preparticipiation examination, wilderness medicine, and sports.
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http://dx.doi.org/10.1016/j.wem.2015.09.010DOI Listing
December 2015

Wilderness Preparticipation Evaluation and Considerations for Special Populations.

Clin J Sport Med 2015 Sep;25(5):443-55

*Clinical Outcomes Research, Intermountain Healthcare, Salt Lake City, Utah; †Department of Family Medicine, University of Colorado, Denver, Colorado; ‡CJW Sports Medicine, Richmond, Virginia; §Anne Arundel Medical Center, Orthopedic and Sports Medicine Center, Annapolis, Maryland; ¶Missouri State University, Springfield, Missouri; ‖Department of Emergency Medicine, University of Colorado, Aurora, Colorado; **Big Island Family Medicine Center, Lynchburg, Virginia; and ††Longs Peak Sports Medicine, Longmont, Colorado.

Children, older adults, disabled and special needs athletes, and female athletes who participate in outdoor and wilderness sports and activities each face unique risks. For children and adolescents traveling to high altitude, the preparticipation physical evaluation should focus on risk assessment, prevention strategies, early recognition of altitude-related symptoms, management plans, and appropriate follow-up. As the risk and prevalence of chronic disease increases with age, both older patients and providers need to be aware of disease and medication-specific risks relative to wilderness sport and activity participation. Disabled and special needs athletes benefit from careful pre-event planning for the potential medical issues and equipment modifications that may affect their health in wilderness environments. Issues that demand special consideration for female adventurers include pregnancy, contraceptive use, menses, and ferritin levels at altitude. A careful preparticipation evaluation that factors in unique, population-specific risks will help special populations stay healthy and safe on wilderness adventures. The PubMed and SportDiscus databases were searched in 2014 using both MeSH terms and text words and include peer-reviewed English language articles from 1977 to 2014. Additional information was accessed from Web-based sources to produce this narrative review on preparticipation evaluation for special populations undertaking wilderness adventures. Key words include children, adolescent, pediatric, seniors, elderly, disabled, special needs, female, athlete, preparticipiation examination, wilderness medicine, and sports.
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http://dx.doi.org/10.1097/JSM.0000000000000251DOI Listing
September 2015

Prescription history of emergency department patients prescribed opioids.

West J Emerg Med 2013 May;14(3):247-52

Department of Emergency Medicine, University of Colorado School of Medicine, Denver, Colorado.

Introduction: To use Colorado's prescription drug monitoring program (PDMP) to describe the recent opioid prescription history of patients discharged from our emergency department (ED) with a prescription for opioid pain medications.

Methods: Retrospective cohort study of 300 adult ED patients who received an opioid prescription. We abstracted prescription histories for the six months prior to the ED visit from the PDMP, and abstracted clinical and demographic variables from the chart.

Results: There were 5,379 ED visits during the study month, 3,732 of which were discharged. Providers wrote 1,165 prescriptions for opioid analgesics to 1,124/3,732 (30%) of the patients. Median age was 36 years. Thirty-nine percent were male. Patients were 46% Caucasian, 26% African American, 22% Hispanic, 2% Asian and 4% other. These were similar to our overall ED population. There was substantial variability in the number of prescriptions, prescribers and total number of pills. A majority (205/296) of patients had zero or one prescription. The 90th percentile for number of prescriptions was seven, while the 10th percentile was zero. Patients in the highest decile tended to be older, with a higher proportion of Caucasians and females. Patients in the lowest decile resembled the general ED population. The most common diagnoses associated with opioid prescriptions were abdominal pain (11.5%), cold/flu symptoms (9.5%), back pain (5.4%), flank pain (5.0%) and motor vehicle crash (4.7%).

Conclusion: Substantial variability exists in the opioid prescription histories of ED patients, but a majority received zero or one prescription in the preceding six months. The top decile of patients averaged more than two prescriptions per month over the six months prior to ED visit, written by more than 6 different prescribers. There was a trend toward these patients being older, Caucasian and female.
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http://dx.doi.org/10.5811/westjem.2012.2.6915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656706PMC
May 2013

Impact on length of stay after introduction of emergency department information system.

West J Emerg Med 2010 Sep;11(4):329-32

University of Colorado Denver, Division of Emergency Medicine, Aurora, CO.

Objective: An electronic emergency department information system (EDIS) can monitor the progress of a patient visit, facilitate computerized physician order entry, display test results and generate an electronic medical record. Ideally, use of an EDIS will increase overall emergency department (ED) efficiency. However, in academic settings where new interns rotate through the ED monthly, the "learning curve" experienced by the new EDIS user may slow down patient care. In this study, we measured the impact of the "intern learning curve" on patient length of stay (LOS).

Methods: We retrospectively analyzed one year of patient care data, generated by a comprehensive EDIS in a single, urban, university-affiliated ED. Intern rotations began on the 23rd of each month and ended on the 22nd of the next month. Interns received a 1.5-hour orientation to the EDIS prior to starting their rotation; none had prior experience using the electronic system. Mean LOS (± standard error of the mean) for all patients treated by an intern were calculated for each day of the month. Values for similar numerical days from each month were combined and averaged over the year resulting in 31 discrete mean LOS values. The mean LOS on the first day of the intern rotation was compared with the mean LOS on the last day, using Student's t-test.

Results: During the study period 9,780 patients were cared for by interns; of these, 7,616 (78%) were discharged from the ED and 2,164 (22%) were admitted to the hospital. The mean LOS for all patients on all days was 267 ± 1.8 minutes. There was no difference between the LOS on the first day of the rotation (263±9 minutes) and the last day of the rotation (276 ± 11 minutes, p > 0.9). In a multiple linear regression model, the day of the intern rotation was not associated with patient LOS, even after adjusting for the number of patients treated by interns and total ED census (β = -0.34, p = 0.11).

Conclusion: In this academic ED, where there is complete intern "turnover" every month, there was no discernible impact of the EDIS "learning curve" on patient LOS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967683PMC
September 2010

Impact of computerized physician order entry on ED patient length of stay.

Am J Emerg Med 2011 Feb 26;29(2):207-11. Epub 2010 Mar 26.

Denver Health and Hospitals, Residency in Emergency Medicine, Denver, CO 80204, USA.

Objectives: We evaluated whether implementation of computerized physician order entry (CPOE) reduces length of stay (LOS) for discharged emergency department (ED) patients.

Methods: Emergency department LOS for discharged and admitted patients were analyzed in a university-affiliated ED before and after introduction of CPOE. Patient demographics and covariates that may affect LOS (mode of arrival, provider staffing, daily census, and admission rate) were measured.

Results: The study included 71,188 patients; 49,175 (69%) were discharged from the ED (28, 687 before and 20,488 after CPOE). Length of stay for discharged patients decreased from 198 to 168 minutes (difference of -30; 95% confidence interval [CI], -28 to -33), whereas LOS for admitted patients increased from 405 to 441 minutes (difference of +36; 95% CI, 26-46). After controlling for covariates, CPOE implementation was associated with a 23-minute decrease in LOS for discharged patients (β = -23 [95% CI, -26 to -19]).

Conclusion: Implementation of CPOE was associated with a clinically significant (23-minute) decrease in LOS among patients who were discharged from the ED.
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http://dx.doi.org/10.1016/j.ajem.2009.10.007DOI Listing
February 2011

Estimation of the prevalence of rheumatic diseases in Israel.

Semin Arthritis Rheum 2011 Apr 11;40(5):473-8. Epub 2010 Aug 11.

Department of Rheumatology, Tel Aviv Sourasky Medical Center Tel Aviv, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objectives: To study the prevalence of rheumatic diseases in Israel by applying the Community Oriented Program for the Control of Rheumatic Diseases core questionnaire (CCQ).

Methods: Representative samples (total of 2520 people) of the Israeli Jewish population aged ≥20 were surveyed for rheumatic complaints on 4 separate occasions by the CCQ telephone interview. The findings of the telephone interview were compared with a face-to-face interview and to rheumatologist examination, in 2 separate stages.

Results: The telephone applied CCQ had a sensitivity level of 88.6% and specificity of 70.0% when compared with the rheumatologist evaluation (κ = 0.576) (P < 0.001). A lower prevalence of rheumatic complaints was found in the summer months (17.7%) than in winter months (26.2%, P < 0.01). Prevalence was related to country of origin (0.008 < P < 0.03) (P range in separate surveys) and increasing age (P < 0.001) and was higher in women than in men (0.003 < P < 0.043). Body sites most affected were the lower back (63%) and the knees (47%). Medically related unemployment was more common in those with rheumatic complaints (7.9%) than in those without such complaints (2.9%, P < 0.01). Among those with rheumatic ailments, 12.7% had a related discapacity recognized by the Israeli National Insurance Institute.

Conclusions: The telephone applied CCQ was reliable in screening for rheumatic complaints. Rates for rheumatic complaints in Israel were similar to those in some other countries. Rheumatic complaints were common, age- and gender-related, associated with work discapacity, and with country of origin. This is the first longitudinal prevalence survey of rheumatic complaints in Israel.
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http://dx.doi.org/10.1016/j.semarthrit.2010.05.010DOI Listing
April 2011

The effect of removal of point-of-care fecal occult blood testing on performance of digital rectal examinations in the emergency department.

Ann Emerg Med 2010 Aug 8;56(2):135-41. Epub 2010 Jan 8.

Denver Health Medical Center, CO, USA.

Study Objective: We determine whether removing point-of-care fecal occult blood testing from the emergency department (ED) is associated with a decrease in documented digital rectal examinations.

Methods: We performed a retrospective observational chart review study examining documented digital rectal examinations, before and after removal of a point-of-care fecal occult blood test, on all adult patients who presented to our ED with chief complaints that were likely to warrant a fecal occult blood test (intervention-sensitive). We studied the 6 months immediately before and after switching from bedside fecal occult blood testing to immunohistochemical laboratory fecal occult blood testing. We compared the results with those from a similar cohort of patients who presented during the same period, with chief complaints that would warrant a digital rectal examination for reasons other than fecal occult blood test (intervention-insensitive).

Results: A total of 4,981 and 5,557 patients met our inclusion criteria during the before and after intervention periods, respectively. We observed an overall reduction of 10% (95% confidence interval [CI] 8% to 12%) in digital rectal examinations in patients with intervention-sensitive chief complaints. The largest relative decreases in digital rectal examinations were observed in patients with chief complaints of abdominal pain, nausea/vomiting, and diarrhea. Smaller decreases were observed in gastrointestinal bleeding, constipation, and rectal problem. There was an overall reduction of 3% (95% CI 0% to 5%) in documented digital rectal examinations in intervention-insensitive chief complaints. After controlling for all covariates, digital rectal examinations decreased in the postintervention period for intervention-sensitive (odds ratio 0.44 [95% CI 0.39 to 0.50]) and, to a lesser extent, for intervention-insensitive (odds ratio 0.67 [95% CI 0.52 to 0.86]) conditions.

Conclusion: Removal of point-of-care fecal occult blood test from our ED was associated with a reduction in digital rectal examinations, particularly among chief complaints that may require fecal occult blood testing.
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http://dx.doi.org/10.1016/j.annemergmed.2009.12.021DOI Listing
August 2010

Simvastatin induces apoptosis of fibroblast-like synoviocytes.

Open Rheumatol J 2009 Sep 7;3:35-40. Epub 2009 Sep 7.

Department of Rheumatology, Sourasky Medical Center and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.

Background: Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert favorable effects on lipoprotein metabolism, but appeared to possess anti-inflammatory properties among others, as suggested by their ability to inhibit collagen-induced arthritis in mice. Their activity in fibroblast-like synovial cells (FLS) has not yet been studied.

Objectives: To evaluate the effect of varying doses of simvastatin on apoptosis of FLS.

Methods: Synovial tissue, obtained during total knee replacement due to osteoarthritis, was cut into small pieces and cultured in Petri dishes with test materials, as previously described. FLS were incubated for 48 hours with 1 mumol/ml, 5 mumol/ ml, 15 mumol/ml and 50 mumol/ml of simvastatin. Following incubation, apoptosis was analyzed by two-dimensional flow cytometry (FACS) using annexin V/PI staining according to the manufacturer's instructions.

Results: Different concentrations of simvastatin induced apoptosis of FLS. The level proportion of apoptotic cells of resting or activated with lipopolysaccharide (LPS; 3 mug/ml) FLS, not treated with simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated fibroblasts, incubated with 1 mumol/ml, 5 mumol/ml, 15 and 50 mumol/ml was 22%, 32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium salt XXT was unaffected by the simvastatin concentration used.

Conclusion: Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.
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http://dx.doi.org/10.2174/1874312900903010035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746119PMC
September 2009

Travel to high altitude with young children: an approach for clinicians.

High Alt Med Biol 2008 ;9(4):265-9

University of Colorado Denver School of Medicine, Department of Surgery, Division of Emergency Medicine, Aurora, CO 80045, USA.

As more families travel to mountainous destinations, clinicians are frequently asked for advice regarding children at altitude. We briefly review the principles of altitude illness in children, offer a management plan for the clinician, and highlight the gaps in current evidence. Planning for ascent, altitude illness management, and diagnostic follow-up are discussed.
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http://dx.doi.org/10.1089/ham.2008.1066DOI Listing
April 2009

Language used in Lake Louise Scoring System underestimates symptoms of acute mountain sickness in 4- to 11-year-old children.

High Alt Med Biol 2007 ;8(2):124-30

University of Colorado Health Sciences Center, School of Medicine, Denver, Colorado 80262, USA.

The Lake Louise Scoring System (LLSS) was designed to evaluate adults for symptoms of acute mountain sickness (AMS). The language used in the LLSS may be too complex for young children to comprehend. This study evaluates if age-appropriate language alters the results of AMS diagnostic scores in 4- to 11-yr-old children. With parental help, subjects completed the LLSS and an equivalent Lake Louise Age-Adjusted Symptom Score (LLAASS) daily for 3 days. Measurements were made at 1605 m, in the subjects' homes, without any altitude change. Equivalent questions between the two surveys were assessed for agreement on the day when the most symptoms were recorded for each question. Thirty-seven children (19 girls), ages 4 to 11 yr (mean age 7.4 +/- 2.3 yr) completed the study. Kappa values: headache (kappa = 0.22), gastrointestinal (kappa = 0.34), fatigue (kappa = 0.88), dizziness (kappa = 0.65), and sleep (kappa = 0.88) ranged from fair to very good. The LLAASS resulted in higher mean symptom scores (1.14 +/- 0.98) compared to LLSS questions (0.61 +/- 0.82) (p < 0.01). The AMS diagnostic threshold was reached in 9% (95% CI, 4-16) of measurements using the LLAASS and 4.5% (95% CI, 1.5-10) with the LLSS. The LLSS results in reporting of fewer AMS symptoms in this population when compared with a diagnostic tool using age-appropriate language and/or visual representations. Age-appropriate communication must be used to assess AMS, particularly for headache (the key symptom of AMS) and gastrointestinal symptoms. Young children report symptoms of AMS at baseline without altitude gain; therefore, the AMS diagnostic threshold in this population may require modification.
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http://dx.doi.org/10.1089/ham.2006.1014DOI Listing
September 2007

Distribution of HLA-B27 subtypes in ankylosing spondylitis in an Israeli population.

Arch Med Res 2007 May 6;38(4):452-5. Epub 2007 Mar 6.

Department of Immunology and Immunogenetics, Instituto de Diagnóstico y Referencia Epidemiológicos, InDRE, SSA, Mexico.

Background: The aim of this study was to investigate the contribution of the B27 subtypes to ankylosing spondylitis (AS) expression in a group of Jewish patients from Israel and to compare their distribution with that found in Mexican Mestizo patients. Several HLA-B27 alleles have been clearly associated with AS. Among them, B( *)2705 and B( *)2702 are involved in susceptibility in different populations worldwide. The aim of this study was to investigate the associated subtypes in Israel and to compare the results with Mexican Mestizos, who have Semitic genes as part of their ancestry.

Methods: This is a case/control study that included a group of 24 HLA-B27+ Israeli patients with AS and 51 B27+ healthy subjects, most of them Ashkenazi Jews. The B27 subtypes were characterized using a PCR-SSP method.

Results: Only B( *)2702 and B( *)2705 alleles were present in AS patients. However, their allele frequency was not significantly different from that found in the control group, probably because of the small sample size: B( *)2702 (patients 62.5% vs. controls 41.2%, OR = 2.31) and B( *)2705 (patients 37.5% vs. controls 50.9%). Two additional alleles were present only in the controls in low frequency: B( *)2707(5.9%) and B( *)2701(1.9%). It is clear that the major susceptibility allele in Ashkenazi Jews from Israel is B( *)2702.

Conclusions: The only allele conferring risk to AS expression in Israeli Jews was B( *)2702, as was previously described in Mexican Mestizos. Populations of Mediterranean ancestry, such as Latin Americans, should be further explored to understand the contribution of ethnicity to the etiopathogenesis of AS.
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http://dx.doi.org/10.1016/j.arcmed.2006.12.001DOI Listing
May 2007

The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis.

Cytokine 2006 Jan 17;33(2):106-10. Epub 2006 Feb 17.

Department of Rheumatology, Sourasky Medical Center, and Sackler, Faculty of Medicine, University of Tel Aviv, 6 Weizman Street, Tel Aviv 64239, Israel.

Objective: The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters.

Patients And Methods: Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were on stable treatment for at least 3 months before starting the protocol. The patients received a loading dose of 100 mg for 3 days followed by 20 mg/day thereafter and followed up monthly for 6 months. Disease activity was assessed at baseline, 2 weeks, and every month of therapy thereafter using the following variables: tender joint count, swollen joint count, morning stiffness duration, pain, tiredness, physician's and patient's global assessment, using VAS, ESR and CRP. Clinical effects of the treatment regimen were calculated using the American College of Rheumatology (ACR) criteria for clinical response. Adverse events were recorded. Serum levels of MMP-1, MMP-3, IL-10 and IL-6 were measured before and 3 months after starting the protocol.

Results: Except for tiredness, a statistically significant improvement in all clinical and laboratory parameters of disease activity was reached after 3 months. At this time point the ACR-20 response rate was 46.2%. The levels of MMP-1, MMP-3, IL-6 and IL-10 decreased significantly after 3 months. A statistically significant correlation between serum levels of MMP-1, IL-10 and IL-6 and clinical and laboratory parameters was also shown. After 6 months, 16 out of 30 patients withdrew from the study [adverse events (35.4%), lack of efficacy (9.7%), and low compliance (6.4%)].

Conclusions: Leflunomide was clinically efficacious in this group of long standing resistant RA in an open study "real life" design. These results comply with those reported in previous clinical trials. Serum MMP-1, MMP-3, IL-10 and IL-6 levels decreased significantly. Despite high withdrawal rate, no serious adverse effects were recorded.
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http://dx.doi.org/10.1016/j.cyto.2005.12.009DOI Listing
January 2006

Sleep disturbance after rapid ascent to moderate altitude among infants and preverbal young children.

High Alt Med Biol 2004 ;5(3):314-20

University of Colorado Health Sciences Center, Department of Surgery, Division of Emergency Medicine, Colorado Emergency Medicine Research Center, Denver, CO, USA.

Rapid ascent to high altitude is known to result in sleep disturbances among adults. No data exist regarding the effects of altitude exposure on sleep in children. The objective of this study was to determine the effect of rapid ascent to moderate altitude on sleep in infants and young children. In this prospective study, each child served as his or her own control. Each subject was studied over 7 days and nights. On days 1 and 2, children were studied at home (1601 m), day 3 at a hotel without ascent (travel control), day 4 at home, days 5 and 6 at a hotel after ascent (3109 m), and day 7 at home. Since increased motion is a characteristic of sleep disturbance among infants and young children, continuous measurements of motion were made using an ankle-mounted Actigraph. Thirty children, 17 girls and 13 boys, with a median age of 16.5 months (range = 4 to 33 months) participated in the study. Significant changes in the activity counts, reflecting a sleep disturbance during nocturnal sleep, were noted between the travel control night (20.9 +/- 1.9) and the first night at altitude (29.4 +/- 2.5): p < 0.01. This sleep disturbance is most significant during the first night at altitude and may be similar to sleep disturbance with altitude exposure seen in adults.
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http://dx.doi.org/10.1089/ham.2004.5.314DOI Listing
January 2005

The effect of infliximab on extraintestinal manifestations of Crohn's disease.

Rheumatol Int 2005 Aug 12;25(6):406-10. Epub 2004 Aug 12.

Department of Rheumatology, Sourasky Medical Center and the Sackler Faculty of Medicine, University of Tel Aviv, Israel.

Objective: The purpose of this open pilot study was to assess prospectively the effect of infliximab on extraintestinal manifestations in patients with active Crohn's disease refractory to conventional treatment.

Patients And Methods: Twenty-two consecutive patients with Crohn's disease and one with ulcerative colitis presenting at least one of the known extraintestinal manifestations of Crohn's disease participated in the study. All the patients had Crohn's disease activity index (CAI) scores above 2. Each patient received an intravenous infusion of infliximab at a dosage of 5 mg/kg. A thorough questionnaire was used reviewing the extraintestinal manifestations of Crohn's disease such as erythema nodosum, pyoderma gangrenosum, eye lesions, arthritis or arthralgia, sacroiliitis or inflammatory back pain, hepatic disease, hematologic manifestations (megaloblastic, iron deficiency or hemolytic anemia, thrombocytosis), thrombosis, and nephrolithiasis. Musculoskeletal complaints were evaluated using the parameters intensity of pain, duration of morning stiffness (in minutes), presence of inflammatory back pain, Schober's test of the lumbar region, chest expansion, and distance from occiput to wall. The clinical assessment was performed on the day of the infusion and 2 weeks later.

Results: Eleven out of 23 patients had arthralgia of inflammatory nature, three others had evidence of active synovitis on physical examination, and 11 reported inflammatory back pain. Four patients suffered from protracted pyoderma gangrenosum; three had resistant aphthous stomatitis. Eleven patients had more than one extraintestinal manifestation. All four with pyoderma gangrenosum demonstrated significant improvement of their ulcers after one course of infliximab, with complete resolution of the skin lesions in three of them after repeated infusions of infliximab. Aphthous stomatitis completely responded in all patients after a single infusion. Seven out of 11 patients with arthralgia and seven out of 11 with inflammatory back pain/sacroiliitis experienced benefit after treatment with infliximab and reported at least partial clinical improvement in duration of morning stiffness, tender joint count, and visual analogue scale for pain. Only one of three patients with frank arthritis demonstrated clear improvement, and two others failed to respond to infliximab treatment.

Conclusion: These preliminary results are encouraging and suggest a promising role of infliximab in the treatment of extraintestinal symptoms of Crohn's disease.
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http://dx.doi.org/10.1007/s00296-004-0467-8DOI Listing
August 2005

Somatostatin analogue treatment attenuates histological findings of inflammation and increases mRNA expression of interleukin-1 beta in the articular tissues of rats with ongoing adjuvant-induced arthritis.

Rheumatol Int 2005 Jun 26;25(5):350-6. Epub 2004 Mar 26.

Department of Rheumatology, Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weizmann Street, Tel-Aviv 64239, Israel.

Objective: Somatostatin is a neuropeptide with modulatory effects on the immune system and the function of synovial cells; it has antiangiogenic and antiproliferative properties. This study aimed to evaluate the clinical, histological, and articular tissue cytokine mRNA response to somostatin treatment in rat adjuvant-induced arthritis (AIA).

Methods: Adjuvant-induced arthritis was induced in a total of 68 Lewis rats by immunization with complete Freund's adjuvant. Twenty-four rats were treated with a long-acting somostatin analogue 14 days after disease induction. Twenty-four untreated rats served as controls. The severity of arthritis was scored weekly for 42 days. In a second experiment, 20 rats (ten treated, ten controls) were killed 21 days after treatment for assessment of joint histopathology and articular tissue cytokine mRNA expression.

Results: Somatostatin analogue treatment significantly reduced histological scores of early inflammatory changes and increased articular tissue mRNA expression of interleukin-1 beta (IL-1beta). A trend toward improvement in physical scores of joint inflammation was seen in the treated group. Late destructive changes were not significantly different.

Conclusion: Treatment with a somostatin analogue attenuated early inflammatory changes in AIA joints and increased mRNA expression of IL-1beta in the articular tissues of rats with ongoing arthritis. Improvement in the physical findings of joint inflammation was mild.
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http://dx.doi.org/10.1007/s00296-004-0455-zDOI Listing
June 2005

Early and late effects of low-dose aspirin on renal function in elderly patients.

Am J Med 2003 Oct;115(6):462-6

Department of Geriatrics, Shmuel Harofeh Geriatric Medical Center, Beer Yaacov, Israel.

Background: Although low-dose aspirin is used by many elderly patients, monitoring of renal function is currently not recommended. We recently reported transient retention of uric acid and creatinine caused by aspirin in doses of 75 to 325 mg/d. We therefore evaluated the renal effects of aspirin (100 mg/d), including post-treatment effects.

Methods: We studied 83 stable geriatric patients in long-term care (aged 56 to 98 years) who were treated with low-dose aspirin (100 mg/d) for 2 weeks and 40 control patients. Other medications and diet were kept constant. Biochemical monitoring including blood samples and 24-hour urinary collections for creatinine and uric acid at baseline and weekly for a total of 5 weeks.

Results: After 2 weeks on aspirin, urinary excretion of creatinine decreased in 60 (72%) and excretion of uric acid decreased in 54 (65%) of the 83 patients, and their mean clearances decreased; during the same period, serum blood urea nitrogen, creatinine, and uric acid levels increased (P <0.05 for all). Deterioration from baseline levels was significantly greater (and more prevalent) in the aspirin-treated group than in the 40 control patients (P = 0.001 to 0.09). After withdrawal of aspirin these parameters improved. However, 3 weeks after stopping aspirin, 48% (35 of the 73 in whom this measurement was available) had a persistent decline in creatinine clearance from baseline, as compared with only 8% (3/36) controls (P <0.001).

Conclusion: Short-term low-dose aspirin treatment may affect renal function in elderly patients. These effects persist 3 weeks after cessation of the drug in some of these patients.
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http://dx.doi.org/10.1016/s0002-9343(03)00436-4DOI Listing
October 2003

Protracted Mycobacterium kansasii carpal tunnel syndrome and tenosynovitis.

Isr Med Assoc J 2003 Jun;5(6):453-4

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

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June 2003

Physiologic response to moderate altitude exposure among infants and young children.

High Alt Med Biol 2003 ;4(1):53-9

University of Colorado Health Sciences Center, Department of Surgery, Division of Emergency Medicine, Denver, CO 80262, USA.

Substantial numbers of children are exposed to moderate altitude while traveling to mountain resorts with their families. Although there has been extensive study of the adult physiologic response to altitude exposure, few studies of infants and young children exist. This investigation examines the acute physiologic responses to moderate altitude exposure among young children and the relationship of these responses to the development of acute mountain sickness (AMS). Children 3 to 36 months old participated in the prospective observational study, which included baseline measurements at 1610 m and measurements after a 24-h exposure to 3109 m. Measurements included pulse and respiratory rate, end-tidal CO(2), arterial oxygen saturation (pulse oximetry), cerebral tissue oxygenation (St(O2)) by near-infrared spectroscopy, middle cerebral artery resistive index by transcranial Doppler, lateral ventricle volumes (ultrasound), and clinical evaluation for the presence of acute mountain sickness (Children's Lake Louise Score). Twenty-four children (13 girls and 11 boys, age 14.5 +/- 10.2 months) participated. After acute exposure to 3109 m, these children showed an increase in respiratory rate from 45 +/- 13 to 51.9 +/- 15 breaths/min (p < 0.008), accompanied by a decrease of end-tidal CO(2) from 31 +/- 3 to 28 +/- 2 mm Hg (p < 0.001) and a reduction of arterial oxygen saturation from 95 +/- 2 to 91 +/- 2% (p < 0.001). St(O2) also decreased from 78 +/- 8 to 67 +/- 13% (p < 0.001), and this reduction appeared to be related to age (r = 0.58, p < 0.05), with lower saturations found in younger children. No evidence of increased intracranial pressure, as assessed by middle cerebral artery resistive index, was seen during ascent. Seven subjects developed symptoms of AMS; however, no relationship was found between the physiologic changes observed and the presence of symptoms. Ascent from 1610 to 3109 m resulted in tachypnea, relative hypoxia, hypocapnia, and a reduction in cerebral tissue oxygenation (St(O2)). The reduction in St(O2) appeared to be related to age, with infants appearing to be the most susceptible to cerebral tissue oxygen desaturation at high altitude. No relationship appears to exist between the presence of AMS and the physiologic measurements.
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http://dx.doi.org/10.1089/152702903321488988DOI Listing
August 2003

Rapid and complete resolution of proteinuria due to renal amyloidosis in a patient with rheumatoid arthritis treated with infliximab.

Arthritis Rheum 2002 Oct;46(10):2571-3

Department of Rheumatology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel.

We describe herein a patient with rheumatoid arthritis who developed proteinuria due to AA amyloidosis, in whom the inflammatory disease was rapidly and completely suppressed by treatment with infliximab. This response was accompanied by resolution of the proteinuria and stabilization of the amyloid deposits as seen on serial (123)I-labeled serum amyloid P scintigraphy.
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http://dx.doi.org/10.1002/art.10581DOI Listing
October 2002

Abdominal scintigraphy using technetium Tc 99m hexylmethylpropylene amine oxime-labeled leukocytes in patients with seronegative spondyloarthropathies.

Semin Arthritis Rheum 2002 Jun;31(6):406-12

Department of Rheumatology, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.

Objective: To assess the potential benefits of technetium Tc 99m hexylmethylpropylene amine oxime (Tc 99m HMPAO)-labeled leukocyte scintigraphy in a group of patients with spondyloarthropathies (SpAs), overt gastrointestinal symptoms, and negative extensive endoscopic/radiologic test results.

Patients And Methods: Ten patients with SpAs and overt gastrointestinal symptoms were included in this study. All patients underwent colonoscopy and small bowel barium studies, and results were negative. Abdominal scintigraphy with Tc 99m HMPAO-labeled leukocytes was performed in all the patients. Clinical and laboratory data and response to treatment was recorded.

Results: The Tc 99m HMPAO-labeled leukocyte scintigraphy was positive in 5 of 10 patients, demonstrating uptake at the terminal ileum which is very suggestive of Crohn disease. The 5 scintigraphically positive patients were treated with sulfasalazine (SSZ). Four patients responded to SSZ with significant improvement of both gastrointestinal and joint symptoms.

Conclusions: In 5 of 10 patients with SpA and suspected inflammatory bowel disease on clinical grounds, evidence of inflammatory bowel disease was shown by scintigraphic studies in which conventional invasive procedures failed. Tc 99m HMPAO-labeled leukocyte scintigraphy should be considered in the evaluation of patients with SpA.
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http://dx.doi.org/10.1053/sarh.2002.32550DOI Listing
June 2002

Evaluation of diagnostic criteria and incidence of acute mountain sickness in preverbal children.

Wilderness Environ Med 2002 ;13(1):21-6

University of Colorado Health Sciences Center, Department of Surgery, Denver 80262, USA.

Objective: The Children's Lake Louise Score (CLLS) established the diagnostic criteria for acute mountain sickness (AMS) in preverbal children. Prospective application of the CLLS and interobserver agreement for the score had not been evaluated in a controlled trial. A study of children and their parents was used to evaluate the CLLS and determine the incidence of AMS in preverbal children.

Methods: A prospective, controlled trial. Children > or =3 months and < or =36 months old and their parents living below 1645 m were studied over 7 separate days. The CLLS, measured daily by the mother as well as by the father on days 5 and 6, is the sum of scores for fussiness (FS), eating (E), playfulness (P), and sleep (S). Children were studied on days 1 and 2 at home, on day 3 after travel without altitude gain to a hotel, on day 4 at home, on days 5 and 6 at a hotel at 3109 m, and on day 7 at home. Using our previous criteria, AMS was diagnosed if the CLLS was > or =7 with both the FS > or =4 and the E + P + S > or =3. Agreement between mothers' and fathers' CLLS values was measured with the kappa statistic (K). Adults were also evaluated for AMS by the CLLS on days 5 and 6.

Results: Thirty-seven children (mean age +/- SD = 16.5+/-10.5 months; 21 girls) participated, and AMS occurred in 7 of them (19%; 95% CI, 8.35%). Among 33 adults, 8 (24%; 95% CI, 9.39%) had AMS. Although the agreement of the parents on the CLLS components was poor, the agreement on the classification of AMS between mother and father was excellent (K = .67; P < .001), with both parents' scores exceeding the CLLS threshold for AMS.

Conclusions: In this prospective trial, parents demonstrated excellent interobserver agreement for independent use of the CLLS to detect AMS. Consistent with our previous retrospective study, the incidence of AMS at moderate altitude in preverbal children (19%) was similar to that in adults (24%).
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http://dx.doi.org/10.1580/1080-6032(2002)013[0021:eodcai]2.0.co;2DOI Listing
May 2002

Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthritis or systemic lupus erythematosus.

Clin Infect Dis 2002 Jan 4;34(2):147-53. Epub 2001 Dec 4.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Prevention of bacterial infection, which is a leading cause of morbidity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a priority. However, the safety and immunogenicity of the pneumococcal vaccine in such patients remain controversial. We evaluated the currently available pneumococcal vaccine in patients with RA or SLE. Pneumococcal vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease activity in either group. One month after vaccination, patients in both groups had significant increases in geometric mean concentrations of pneumococcal polysaccharide-specific IgG to all 7 serotypes tested, as did control subjects. However, 14 (33.3%) of 42 patients with RA and 5 (20.8%) of 24 patients with SLE responded either to none or to only 1 of the 7 polysaccharides. Pneumococcal vaccination is generally safe and immunogenic in patients with RA or SLE, but a subset of patients may remain unprotected by the currently available vaccine.
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http://dx.doi.org/10.1086/338043DOI Listing
January 2002
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