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David J Margolis

Publications and source records attributed to David J Margolis.

54 records · Page 3Linked to original sources
PubMed2003

Stroma formation and angiogenesis by overexpression of growth factors, cytokines, and proteolytic enzymes in human skin grafted to SCID mice.

Reorganization of skin during wound healing, inflammatory disorders, or cancer growth is the result of expression changes of multiple genes associated with tissue morphogenesis. We wanted to identify proteins involved in skin remodeling and select those that may be targeted for agonistic or antagonist therapeutic approaches in various disease processes. Full-thickness human skin was grafted to severe combined immunodeficient mice and injected intradermally with 38 different adenoviral vectors inserted with 37 different genes coding for growth factors, cytokines, proteolytic enzymes and their inhibitors, adhesion receptors, oncogenes, and tumor suppressor genes. Responses were characterized for infiltration of inflammatory cells, vascular density, matrix formation, fibroblast-like cell proliferation, and epidermal hyperplasia. Of the 17 growth factor vectors, 16 induced histological changes in human skin. Members of the VEGF and angiopoietin families induced neovascularization. PDGFs and TGF-betas stimulated connective tissue formation, and the chemokines IL-8 and MCP-1 attracted inflammatory neutrophils and monocytes, respectively. The serine protease uPA induced a vascular response similar to that of VEGF. Vectors with adhesion receptors, oncogenes and tumor suppressor genes had, with few exceptions, little effects on skin architecture. The overall results suggest that adenoviral vectors can effectively remodel the architecture of human skin for studies in morphogenesis, inflammatory skin disorders, wound healing, and cancer development.

Adenoviridae↗
PubMed2003

Medical conditions as risk factors for pressure ulcers in an outpatient setting.

OBJECTIVES: the purpose of this study was to evaluate the likelihood that the presence of certain medical conditions in older ambulatory patients are associated with the risk of developing a new pressure ulcer. DESIGN: a cohort study. SETTING AND SUBJECTS: a large outpatient record database from the United Kingdom called the General Practice Research Database. METHODS: the frequency of disease was reported as simple percentages and the associations between the medical conditions and the development of a pressure ulcer as instantaneous rate ratios. RESULTS: we studied 75,168 older individuals. Pressure ulcers occurred in 1,211 individuals. The medical conditions that were significantly associated with the development of a pressure ulcer after adjustment were: Alzheimer's disease, congestive heart failure, chronic obstructive pulmonary disease, cerebral vascular accident, diabetes mellitus, deep venous thrombosis, hip fracture, hip surgery, limb paralysis, lower limb oedema, malignancy, malnutrition, osteoporosis, Parkinson's disease, rheumatoid arthritis, and urinary tract infections. Angina, hypertension, and pneumonia were inversely associated with the development of a pressure ulcer. CONCLUSIONS: it is important that physicians recognise that patients with many medical conditions may be at higher risk for pressure ulcers so that even in the ambulatory care environment appropriate prevention and detection strategies can be directed towards the patients who are most likely to benefit.

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PubMed2003

Surrogate end points for the treatment of diabetic neuropathic foot ulcers.

OBJECTIVE: The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated. RESULTS: Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care. CONCLUSIONS: The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful.

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PubMed2002

Prevalence of erectile dysfunction and active depression: an analytic cross-sectional study of general medical patients.

Erectile dysfunction is a common problem, affecting more than half of all men between the ages of 40 and 70 years. The authors' goal was to quantify the prevalence of concomitant erectile dysfunction and active depression among patients seen in a general medical setting between September 1998 and September 1999. Simple random sampling techniques were used to select a subset of 334 patients from 73 general medical practices affiliated with an academic tertiary referral center in Pennsylvania. Of the 334 patients sampled, the authors received responses from 268 subjects (80.2%) and completed questionnaires from 199 subjects (59.6%) with a mean age of 59 years. The survey instrument consisted of three major sections: demographic and health history information, the Center for Epidemiologic Studies Depression (CES-D) Scale, and the five-item version of the International Index of Erectile Function Scale. The prevalence of moderate or complete erectile dysfunction in this sample was 36.4% (95% confidence interval (CI): 29.6, 43.1). The prevalence of current depression by CES-D Scale criteria was 12.1% (95% CI: 7.5, 16.7), and the prevalence of concomitant erectile dysfunction and depression was 5.1% (95% CI: 2.0, 8.1). Using logistic regression, the authors found that current depressive symptoms were not associated with moderate or complete erectile dysfunction (odds ratio = 1.3, 95% CI: 0.5, 3.1; p = 0.565). Concomitant erectile dysfunction and depression represent a significant public health problem.

Adult↗
PubMed2002

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.

OBJECTIVE: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. DESIGN: Cohort study of outpatients using administrative data. SETTING: 3 US Medicaid programmes. PARTICIPANTS: Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. MAIN OUTCOME MEASURE: Diagnosis of cardiac arrest or ventricular arrhythmia. RESULTS: Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). CONCLUSIONS: The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.

Adult↗
PubMed2002

Hormone replacement therapy and prevention of pressure ulcers and venous leg ulcers.

Pressure ulcers and venous leg ulcers are common chronic wounds. Oestrogens in the form of hormone replacement therapy (HRT) might have an effect on wound healing, but this possibility has not been studied in detail. Using a case-cohort study including elderly patients in the UK General Practice Research Database, we showed that patients who received HRT were less likely to develop a venous leg ulcer (age-adjusted relative risk 0.65 [95% CI 0.61-0.69]) or a pressure ulcer (0.68 [0.62-0.76]) than those who did not use HRT. Therefore, we believe that HRT could be beneficial for the prevention of these wounds.

Adult↗
PubMed2002

Statistical characteristics of area under the receiver operating characteristic curve for a simple prognostic model using traditional and bootstrapped approaches.

Prognostic models are increasingly common in the biomedical literature. These models are frequently evaluated with respect to their ability to discriminate between those with and without an outcome. The area under the receiver-operating curve (AROC) is often used to assess discrimination. In this study, we introduce a bootstrap method, and, using Monte Carlo simulation, we compare three different bootstrap approaches with four commonly used methods in their ability to accurately estimate 95% confidence intervals (CIs) around the AROC for a simple prognostic model. We also evaluated the power of a bootstrap method and the commonly used trapezoid rule to compare different prognostic models. We show that several good methods exist for calculating 95% CIs of AROC, but the maximum likelihood estimation method should not be used with small sample sizes. We further show that for our simple prognostic model a bootstrap z-statistic approach is preferred over the trapezoidal method when comparing the AROCs of two related models.

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PubMed2002

The incidence and prevalence of pressure ulcers among elderly patients in general medical practice.

PURPOSE: The objective of this study was to estimate the period prevalence and incidence of pressure ulcer among those 65 years of age and older. METHODS: We used a patient-record database called the General Practice Research Database (GPRD). Subjects were 65 years of age and older and cases were ascertained based on strict inclusion and exclusion criteria. The accuracy of the ascertainment strategy was estimated using mailed physician-answered questionnaires. Annual period prevalence and age-specific incidence were estimated per 100 person-years with exact 95% confidence intervals (CI). RESULTS: The accuracy of our ascertainment strategy was excellent, with a positive predictive value of 100% (95% CI: 92%,100%) and negative predictive value of 95% (85%, 95%). Over 200,000 person-years of data were analyzed. The annual period prevalence of pressure ulcer among those 65 years of age and older varied from 0.31% to 0.70%. The incidence varied significantly with advancing patient age from 0.18 to 3.36 per 100-person years (p < 0.001) but was not associated with gender (p = 0.95). CONCLUSIONS: Pressure ulcers are seen in the general practice setting. They are most likely to occur in those over 85 years of age. Preventative strategies within the general practice setting should concentrate on the oldest of the elderly.

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PubMed2002

Surrogate endpoints for the treatment of venous leg ulcers.

Surrogate markers are endpoints that occur early in the course of treatment and are intended to predict the true, meaningful clinical endpoint. Surrogate markers have been used to study treatments for a wide range of diseases in which the true outcome is delayed. The evaluation of therapies for venous leg ulcers is challenged by the prolonged observation period necessary to reach the endpoint of healing. We have performed a large cohort study to examine wound healing characteristics as candidate surrogate markers of venous leg ulcer healing using the Curative Health Services population. A total of 58,038 wounds met our definition of venous leg ulcer; however, 1550 wounds were excluded based on size, depth, site, and/or involvement of tendon or bone, leaving 56,488 wounds in 29,189 patients for analysis. The median wound size was 189 mm2, with a median wound duration of 3 mo. Using a large cohort of diverse venous leg ulcer patients, we demonstrate that after only 4 wk of treatment the wound parameters log healing rate, log wound area ratio, and percentage change in wound area can be valid surrogate markers of healing at 12 or 24 wk of care. Based on the area under the receiver operator characteristic curve log rate, log area ratio, and percentage change in area can discriminate which patients will heal at 12 or 24 wk of care (receiver operator characteristic 0.72-0.80). These surrogates were further validated by demonstrating that established risk factors for not healing such as wound size and wound duration are also important risk factors for not achieving the surrogate endpoint. These surrogate markers for venous leg ulcer healing may allow for early clinical trials to be more efficient, and can allow clinicians to identify patients unlikely to heal early in the course of treatment in order to expedite referral to specialty centers or for the selection of stepped treatment algorithms.

Biomarkers↗
PubMed2002

Venous leg ulcer: incidence and prevalence in the elderly.

BACKGROUND: Venous leg ulcer is a disease most common in those aged 65 years and older. However, the incidence and prevalence have not been well established. OBJECTIVE: Our purpose was to estimate the prevalence and incidence of venous leg ulcers in the elderly. METHODS: We studied the General Practice Research Database, validated our case ascertainment strategy, and estimated the annual prevalence and incidence of venous leg ulcer. RESULTS: The positive predictive value of our ascertainment strategy was 98.3% (95% confidence interval [CI], 90.0, 100.0). The annual prevalence of venous leg ulcer among the elderly was 1.69 (95% CI, 1.65, 1.74). The overall incidence rate was 0.76 (95% CI, 0.71, 0.83) for men and 1.42 (1.35, 1.48) per 100 person-years for women. CONCLUSION: Venous leg ulcer is a significant problem in those aged 65 years and older. As compared with previous studies, because we used medical records from a population of known size, our results are precise and less biased.

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PubMed2002

Diabetic neuropathic foot ulcers: the association of wound size, wound duration, and wound grade on healing.

OBJECTIVE: The goal of this study was to evaluate whether simple risk factors can be identified that successfully characterize who will heal and who will not heal among patients who have received standard therapy for diabetic neuropathic foot ulcers. RESEARCH DESIGN AND METHODS: For this cohort study, we evaluated >31,000 individuals with a diabetic neuropathic foot ulcer seen in the Curative Health Services System. Using multivariate logistic regression, we evaluated the association between wound size, wound duration, wound grade, and other variables and their effect on whether a patient would heal by the 20th week of care. RESULTS: We demonstrated that wound size, wound duration, and wound grade are all significantly associated with the likelihood of a wound healing by the 20th week of care. In addition, we noted that these associations were not significantly affected by the treating wound care center, whether the unit of analysis was one wound on a patient or all of their wounds, or current adjuvant therapies. CONCLUSIONS: We have shown that three easy-to-measure risk factors are associated with a wound healing. These results should help clinicians understand the likelihood that a wound will heal and help those conducting clinical investigations to design better trials.

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PubMedDate not supplied

The incidence and risks of failure to heal after lower extremity amputation for the treatment of diabetic neuropathic foot ulcer.

The primary goal of this retrospective cohort study was to determine the incidence of failure to heal after lower extremity amputation for the treatment of diabetic neuropathic foot ulcer, and the secondary goal was to identify risk factors associated with the outcome. We evaluated 1775 patients who underwent amputation for the treatment of 5314 neuropathic foot ulcers, and who were treated in a network of wound care centers. We calculated the incidence of failure to heal after the initial amputation, and used generalized estimation equations and generalized linear latent and mixed model regression to evaluate the association of failure to heal by the 20th week of care. The unadjusted incidence of failure to heal was 34.01%, and male sex, number of wounds, wound grade, and adjunct therapy were all significantly associated with failure to heal. With the exception of wound grade, the associations were not significantly affected by the treating wound care center, and a sensitivity analysis showed the results to be resistant to the theoretical influence of an unmeasured potential confounder. These findings should be useful to clinicians treating diabetic neuropathic foot ulcers, and should aid surgeons in the determination of the most appropriate level for lower extremity amputation.

Age Factors↗
PubMedDate not supplied

The accuracy of venous leg ulcer prognostic models in a wound care system.

Venous leg ulcers are among the most common chronic wounds. Treatment is commonly with a limb compression bandage. Previous small, often single-center, studies have shown that it is possible to predict which wounds are likely to respond to compression therapy. We designed this cohort study using a dataset of over 20,000 individuals with a venous leg ulcer to investigate the accuracy of several prognostic models. Creating complex models using logistic regression, as well as simply counting prognostic factors, we show that initial measures of wound size and duration accurately predict, as measured by area under the receiver operator curve and Brier score, who will heal by the 24th week of care. For example, a wound that is less than 10 cm(2) and less than 12 months old at the first visit has a 29 percent chance of not healing by the 24th week of care, while a wound greater than 10 cm(2) and greater than 12 months old has a 78 percent chance of not healing. Ultimately, these models can be applied by a clinician to help determine whom to continue to treat with standard care and perhaps whom to treat with adjuvant therapies. They may also aid in the design of clinical trials.

Adult↗
PubMedDate not supplied

Diabetic neuropathic foot ulcers and amputation.

A neuropathic foot ulcer is a severe complication of diabetes that can result in a more severe complication, a lower extremity amputation. We conducted a cohort study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within a multicenter wound care network. A total of 1653 (6.7%) individuals had an amputation and 46.3% of these amputations were of a toe or ray (minor amputation). In the more than 10-year follow-up period that we studied, the percentage of those who had an amputation varied between 5.6% and 8.4%. Of those who had an amputation, the percentage that had a minor amputation increased over time from 4.0% in the earliest years to more than 60% in the later years of observation. The single most important determinant of amputation was the observation of fascia, tendon, and bone at the initial assessment. In conclusion, about 7% of those with a diabetic neuropathic foot ulcer will have an amputation and in the past 10 years there has been a remarkable increase in the number of minor as compared to major amputations.

Aged↗
PubMedDate not supplied

Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers.

The goal of this study was to estimate the effectiveness in actual clinical practice of recombinant human platelet-derived growth factor (rhPDGF) for the treatment of diabetic neuropathic foot ulcer (DNFU). Previously published pivotal trials have shown that by the 20th week of care 35 percent more ulcers healed in the group randomized to receive rhPDGF than those who did not receive rhPDGF (i.e., a relative risk [RR] of about 1.35). This represents an estimate of the efficacy of rhPDGF under the tightly controlled conditions of randomized clinical trials. Treatment effectiveness under standard clinical practice was estimated in a retrospective cohort study, controlling for treatment selection bias using propensity scores. We noted 24,898 individuals with a DNFU, of whom 9.6 percent received rhPDGF. We successfully created a propensity score model that evenly balanced many wound characteristics between those who received rhPDGF and those who did not. We created five groups, which varied from those least likely to receive rhPDGF to those most likely to receive rhPDGF. The RR, controlling for the propensity, to receive rhPDGF for a healed wound after treatment with rhPDGF as compared with standard care was 1.32 (1.22, 1.38). With respect to amputation, the RR for undergoing amputation after receiving rhPDGF was 0.65 (0.54, 0.78) as compared with those who did not receive rhPDGF. Within the limitations of our study, rhPDGF is more effective than standard therapy in both helping a wound to heal and preventing amputation, and its effect is similar to the efficacy estimates from previously published randomized controlled trials.

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PubMedDate not supplied

Use of photographs for the identification of pressure ulcers in elderly hospitalized patients: validity and reliability.

To evaluate the ability of research nurses to identify pressure ulcers, the authors assembled digital photographs of the skin of 160 consenting elderly patients (80% African American, 63% women). The series included 39 photos of pressure ulcers, 109 of normal skin, and 12 of other skin conditions, determined by consensus by two experts (D.J.M. and S.H.K.). Photos were packaged electronically into eight blocks of 20, with pressure ulcer prevalence ranging from 20% to 30% per block. The eight blocks were duplicated to create two sets of 160 photos each. Each of six raters (experienced clinical research nurses), working independently, evaluated the 320 photos as if each photo depicted a different patient. For analysis, the ratings were collapsed into binary determinations (any pressure ulcer vs. none). The overall sensitivity and specificity of the ratings were 0.97 (95% confidence interval: 0.94, 0.98) and 0.81 (95% confidence interval: 0.77, 0.86), respectively. Rater-specific prevalence (range: 31.8-47.5%) exceeded the true prevalence (24.4%). Inter- and intrarater reliability coefficients were 0.69 and 0.84, respectively. Trained research nurses can accurately classify pressure ulcers from photographs, even when patients are largely non-White and the photographs depict pressure ulcers spanning all pressure ulcer stages.

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