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Biomedical subjects

D J Margolis

Publications and source records attributed to D J Margolis.

At least 19 recordsLinked to original sources
PubMed2005

Healing diabetic neuropathic foot ulcers: are we getting better?

AIM: To benchmark by year the likelihood that an individual with a diabetic neuropathic foot ulcer will heal over more than a 10-year period. PATIENTS AND METHODS: A cohort study within a multicentre wound care network of individuals with a diabetic neuropathic foot ulcer who were treated by a standard wound care algorithm. The main outcome was a healed wound by the 20th week of care stratified by calendar year. RESULTS: We evaluated 27 193 individuals with a neuropathic foot ulcer. Between 1988 and 1990 approximately 66% of patients did not heal. By 1999 this percentage had decreased to 49%. The change in the rate of failure to heal is very closely associated with an increase over time in the proportion of patients seen with wounds identified as prognostically favourable using a previously published prognostic model (i.e. individuals with wounds < or = 2 cm2, wounds < or = 2 months old, and wounds of grade < or = 2). Nevertheless, even among those most likely to heal, the likelihood of failing to heal went from 62% prior to 1991 to 32% in 2000. CONCLUSIONS: We have shown that individuals with a diabetic neuropathic foot ulcer seeking care are more likely to heal today than 10 years ago. The primary reason for this improvement is that individuals are seeking care when their wounds are most easily treated and these are now more likely to heal.

Adult↗
PubMed2005

Colonisation rates of Streptococcus pyogenes and Staphylococcus aureus in the oropharynx of a young adult population.

There are very few reports on the rates of oropharyngeal colonisation by Streptococcus pyogenes and Staphylococcus aureus in young adults. The present study found colonisation rates of 9.6% and 26.2%, respectively. These rates are two-fold higher than historical rates, indicating that these organisms may be more prevalent than thought previously. This finding may have important clinical consequences in certain populations, and requires further investigation.

Adolescent↗
PubMed2004

Medical conditions associated with venous leg ulcers.

BACKGROUND: In patients who have a venous leg ulcer, very little is known about the frequency of their concomitant medical conditions. OBJECTIVES: To evaluate the frequency that other medical conditions are associated with a new venous leg ulcer. METHODS: We studied a 10% random sample of elderly patients registered in the General Practice Research Database between 1988 and 1996. We describe the frequency of medical conditions using simple percentages. In order to assess the associations between medical conditions and the onset of a venous leg ulcer, we used logistic regression models. RESULTS: Several medical conditions occur commonly in patients who develop venous leg ulcers, including anaemia, angina, asthma, cellulitis of the lower extremity, depression, diabetes, limb oedema, hypertension, osteoarthritis, pneumonia and urinary tract infection. After statistical adjustment many medical conditions were significantly associated with those who had recent onset of a venous leg ulcer, including asthma, cellulitis of the lower extremity, congestive heart failure, diabetes, deep venous thrombosis, lower limb oedema, osteoarthritis, peripheral vascular arterial disease of the lower extremity, rheumatoid arthritis, history of hip surgery, and history of venous surgery/ligation. Unexpectedly, some illnesses were inversely associated with those that had recent onset of a venous leg ulcer, including angina, cerebral vascular accident, depression, malignancy, myocardial infarction, pneumonia and urinary tract infection. CONCLUSIONS: Physicians caring for individuals with venous leg ulcers need to be aware that it is likely that these individuals may have one of the comorbid illnesses listed above.

Aged↗
PubMed2002

Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis.

Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.

Adult↗
PubMed2001

Identification of clonal T cells in the blood of patients with systemic sclerosis: positive correlation with response to photopheresis.

OBJECTIVES: To search for circulating clonal T-cell populations in patients with systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood predicts therapeutic response to photopheresis. DESIGN: Analysis of clonal T-cell receptor gamma gene rearrangements before photopheresis treatment and blinded clinical evaluation of cutaneous response to photopheresis in a case series. SETTING: University hospital setting. PATIENTS: Thirteen consecutive patients with SSc. INTERVENTIONS: Photopheresis in 11 patients. MAIN OUTCOME MEASURES: Clonality of T cells in the blood before photopheresis and clinical response to photopheresis. RESULTS: Screening of blood samples from 13 SSc patients for clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in 11 patients was evaluated in a blinded manner using skin severity scores. Clonality of T cells appeared to be associated with a higher chance of response to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs 1 (20%) of 5 in the clone-negative group experienced a clinically significant response to treatment. CONCLUSIONS: A high proportion of patients with SSc have detectable expanded clonal T-cell populations in the peripheral blood, and such patients appear more likely to respond to photopheresis.

Adult↗
PubMed2001

Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis.

Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.

Contraceptives, Oral↗
PubMed2001

Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness analysis.

BACKGROUND: Diabetic foot ulcers are a common problem and result in more than 85,000 lower extremity amputations each year in the United States. Studies have suggested that between 25% and 50% of costs related to inpatient diabetes care may be directly attributable to the diabetic foot. Novel treatments for these wounds, while expensive, have been reported to improve healing rates, although no formal cost effectiveness analyses have been performed in order to address the cost effectiveness of a given therapy. OBJECTIVE: To estimate the cost effectiveness of common treatment strategies for diabetic neuropathic foot ulcers. METHODS: Four main options are available for the treatment of diabetic foot ulcers: (1) standard care (SC), (2) standard treatment in a specialized wound care center (WCC), (3) treatment with becaplermin, (4) or treatment with platelet releasate (PR). We utilized effectiveness data from published clinical trials, meta-analyses, and a database that includes data on 26,599 patients with these wounds. Effectiveness was assessed as a percentage of ulcers healed at 20 and 32 weeks. RESULTS: Baseline effectiveness (with 95% confidence intervals) for SC, becaplermin, PR, and WCC care were 30.9% (26.6, 35.1), 43.0% (37.3, 48.7), 36.8% (35.4, 38.2), and 35.6% (34.8, 36.4), respectively. Cost:effectiveness ratios for PR versus SC and becaplermin versus SC were 414.40 and 36.59, respectively. Therefore the incremental cost of increasing the odds of healing by 1% over standard therapy was $414.40 for PR and $36.59 for becaplermin. CONCLUSIONS: PR, becaplermin, and WCC care all provided improved healing rates over standard care, and becaplermin was less expensive and more effective than PR after 20 weeks of care.

Ambulatory Care Facilities↗
PubMed2001

Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers.

OBJECTIVE: The goal of this study was to specifically estimate the effectiveness of platelet releasate, a widely available treatment administered by a proprietary group of wound care centers (WCCs) for the treatment of diabetic neuropathic foot ulceration. RESEARCH DESIGN AND METHODS: Treatment effectiveness was estimated in a retrospective cohort study controlling for treatment selection bias using logistic regression-derived propensity scores. RESULTS: Platelet releasate was more effective than standard care. The relative risk for a wound to heal after treatment with platelet releasate compared with standard care at a WCC varied from 1.14 (95% CI 1.03-1.27) to 1.59 (1.49-1.70). The effect was greatest in those with the most severe wounds, i.e., large wounds that affect deeper anatomical structures. CONCLUSIONS: Within the limitations of the ability of propensity score analysis to control for selection bias, platelet releasate is more effective than standard therapy. This effect is more pronounced in more severe wounds. Unfortunately, severe wounds have not been evaluated in randomized clinical trials of new interventions. We encourage the inclusion of these patients in future trials.

Aged↗
PubMed2000

Chlamydia pneumoniae inhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10.

Chlamydia pneumoniae is a common cause of pulmonary infection, with serum positivity in at least 50% of the general population. In this study, we report that human PBMCs exposed to C. pneumoniae are resistant to apoptosis induced by the potent photoactivated chemotherapeutic agents 8-methoxypsoralen and hypericin. In contrast, PBMCs treated with a heat-inactivated inoculum exhibit normal susceptibility to apoptosis. We also observed that human PBMCs are responsive to C. pneumoniae infection by secretion of key immune regulatory cytokines, including IL-12 and IL-10. While IL-12 may play an important role in limiting C. pneumoniae proliferation within cells, IL-10 serves an anti-inflammatory function by down-regulating proinflammatory cytokines such as IL-12 and TNF-alpha. Depletion of endogenous IL-10, but not of IL-12, abolished the apoptosis resistance of C. pneumoniae-infected PBMCs. Furthermore, addition of exogenous IL-10, but not IL-12, significantly increased the resistance of control inoculum-treated PBMCs to photoactivated 8-methoxypsoralen- and hypericin-induced apoptosis. Therefore, we conclude that C. pneumoniae possesses an antiapoptotic mechanism. The resistance to apoptosis observed in PBMCs exposed to C. pneumoniae is due, at least partially, to the IL-10 induced during C. pneumoniae infection.

Anthracenes↗
PubMed2000

Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis.

OBJECTIVE: To estimate the effect of various risk factors on the probability that neuropathic diabetic foot ulcers will heal within 20 weeks of care. DESIGN AND SETTING: A pooled or meta-analysis of individual patient data from the standard care arms of 5 randomized clinical trials was conducted. We analyzed 586 subjects with diabetes mellitus who had a neuropathic diabetic foot ulcer. All patients received good wound care, debridement, and "off-loading" of the wound. MAIN OUTCOME MEASURE: Multivariable logistic regression was used to calculate the magnitude of the association of each risk factor with patients having healed wounds. RESULTS: Logistic regression odds ratios (ORs; 95% confidence intervals [95% CIs]) revealed that those patients with a diabetic neuropathic foot ulcer that healed within 20 weeks using standard care were more likely to have a smaller wound (OR = 0.67; 95% CI, 0.55-0.81), a wound that existed for a shorter period (OR = 0.73; 95% CI, 0.61-0.87), and be nonwhite (OR = 0.64; 95% CI, 0.43-0.96) compared with patients whose wounds did not heal within 20 weeks. The patient's age (OR = 0.99; 95% CI, 0.89-1.01), serum level of glycosylated hemoglobin at the start of the study (OR = 1.03; 95% CI, 0.97-1.10), and sex (OR = 1. 02; 95% CI, 0.69-1.50) were unassociated with the probability of wound healing. Substantial heterogeneity was not found among the studies. CONCLUSIONS: A standard care regimen for diabetic neuropathic foot ulcers is most likely to be effective for patients who have wounds that are small and of brief duration. This information should help dermatologists decide initially whether to use standard care, to try a new treatment, or to refer the patient to a specialty center.

Adult↗
PubMed2000

Which venous leg ulcers will heal with limb compression bandages?

PURPOSE: To develop a simple prediction rule to identify patients in whom a venous leg ulcer will heal using a limb compression bandage (eg, Unna's boot). SUBJECTS AND METHODS: We performed a retrospective cohort study of patients with venous leg ulcers who received a limb compression bandage applied weekly. Prognostic factors were assessed from the patient's history before the start of treatment. The outcome of interest was a healed wound within 24 weeks of treatment. The final model was validated in another data set. RESULTS: Several accurate prognostic models were developed. The simplest model summed the size and duration of the wound before treatment, with 1 point given for a wound with an area >5 cm(2) and another if the wound was >6 months old. In the development data set, ulcers healed in 93% (110 of 118) of patients with a score of 0, but in only 13% (9 of 67) of those with a score of 2. In the validation data set, ulcers healed in 95% (19 of 20) of patients with a score of 0, and 37% (44 of 120) of those with a score of 2. CONCLUSIONS: This simple prognostic model can be used to discriminate between patients with a venous leg ulcer that will or will not heal within 24 weeks of care with a limb compression bandage. The model may be useful in determining which patients to treat with a limb compression, and which patients should be referred or considered for alternative treatments.

Aged↗
PubMed2000

A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks.

Venous leg ulcers, which may take months to heal, account for 40-70% of all lower extremity chronic wounds. New treatment options for venous leg ulcers have recently been proposed, and therefore deciding which patients are candidates for these novel-and often expensive-treatments is an important task. Moreover, researchers conducting clinical trials often wish to enroll patients who are unlikely to heal in order to minimize sample sizes needed and research costs. Our purpose was to assess the use of percentage change in venous leg ulcer area over the first few weeks of treatment as a prognostic indicator of healing or non-healing at 24 weeks. We conducted a cohort study based on an existing data set from a multicentre randomized clinical trial that enrolled 104 patients. Wounds were measured using digital planimetry for 4 consecutive weeks following the inception of good wound care. Utilizing the Wilcoxon rank sum (Mann-Whitney) test, we found that percentage change in area over time distinguished between those who healed and those who failed to heal after 24 weeks of good wound care (P < 0.05). The rate of healing, or area healed per week, did not differentiate between those who healed at 24 weeks and those who did not, as all patients had similar rates of healing over the first 4 weeks of treatment. Percentage change in area from baseline to week 4 provided the best combination of positive and negative predictive values (68.2%, 74.7%) and the largest area under the receiver operating characteristic curve (0.75). Thus, percentage change in area over the first 4 weeks of treatment represents a practical and predictive measure of complete wound healing by 24 weeks.

Cohort Studies↗
PubMed2000

Cutaneous microenvironment of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative individuals, with special reference to Staphylococcus aureus colonization.

A cross-sectional quantitative study of cutaneous bacterial and yeast flora at seven body sites in 99 human immunodeficiency virus-seropositive and 50 seronegative military personnel was performed. Statistically significant differences in carriage rates were only observed for Staphylococcus aureus on the foreheads of seropositive individuals. Seronegative individuals demonstrated staphylococcal carriage rates 1.3 to 2 times as great as those of historical controls (defined as healthy individuals not receiving any medications) at five of six body sites. We conclude that seropositive military personnel do not exhibit statistically significant elevations in densities and carriage rates of the microorganisms examined (except Staphylococcus aureus), relative to seronegative individuals. Seropositive individuals may be predisposed to staphylococcal carriage. The elevated staphylococcal carriage rates of military personnel undergoing basic training warrants a formal evaluation of the impact of training exercises on cutaneous flora. The information gained may serve to limit the spread of infection during training exercises and battlefield conditions.

Adolescent↗
PubMed1999

Risk factors associated with the failure of a venous leg ulcer to heal.

BACKGROUND: Venous leg ulcers afflict a significant portion of the population. The most popular form of therapy for venous leg ulcers is a compression bandage (eg, Unna boot), a therapy that is frequently unsuccessful. OBJECTIVE: To describe risk factors associated with the failure of a wound to heal when treated with a limb-compression bandage for 24 weeks. DESIGN: A retrospective cohort study. SETTING: Single-center outpatient specialty clinic at an academic medical center. PARTICIPANTS: Two hundred sixty consecutive patients with chronic venous leg ulcers. MAIN OUTCOME MEASURE: The magnitude of the effect of a given risk factor on the probability that a wound will heal within 24 weeks of care. RESULTS: Based on an assessment of leg wounds during initial office visits, we observed that the failure of a wound to heal within 24 weeks was significantly associated with larger wound area, measured in square centimeters (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11-1.27), duration of the wound in months (OR, 1.09; 95% CI, 1.04-1.16), history of venous ligation or venous stripping (OR, 4.58; 95% CI, 1.84-11.36), history of hip or knee replacement surgery (OR, 3.52; 95% CI, 1.12-11.08), ankle brachial index of less than 0.80 (OR, 3.52; 95% CI, 1.12-11.08), and the presence of fibrin on more than 50% of the wound surface (OR, 3.42; 95% CI, 1.38-8.45). CONCLUSIONS: Several risk factors are associated with the failure of a patient's venous leg ulcer to heal while using limb-compression therapy. It is prudent to consider these factors when referring a patient to a wound care subspecialists or for alternative therapies.

Aged↗
PubMed1999

A comparison of sensitivity analyses of the effect of wound duration on wound healing.

The effect of an unmeasured exposure on the association between an exposure and outcome can never be fully known in an observational study. The purpose of the current study was to evaluate the sensitivity to unmeasured confounding of the previously published association between wound duration and wound healing in a chronic venous leg ulcer. This was estimated using two methods of sensitivity analysis, called Rosenbaum's method and Greenland's external adjustment. The association between wound duration and wound healing was insensitive to confounding unless the odds ratio for the association between the confounder and a younger wound was almost nine (Rosenbaum). In fact, the association between this hypothetical confounder and healing must have an odds ratio of 100 to remove the effect of duration fully (Greenland). Both of these techniques provide useful and complementary information when assessing the effects of a potential unmeasured confounder.

Bandages↗
PubMed1999

Prognostic models: evidence-based approach to predicting disease outcome.

BACKGROUND: A thorough understanding of the techniques underlying prognostic modelling, the potential shortcomings of prognostic models, and their applicability to dermatology are important for both clinicians and researchers. OBJECTIVE: This article distinguishes between prognostic and explanatory (causal) models, discusses some of the techniques used in developing a prognostic model, and addresses the importance of model generalizability. CONCLUSION: Prognostic models may be useful to the clinician, but must be used with care. It is important to critically appraise prognostic models and to assure that they are relevant to the population of interest. The ability to critically appraise prognostic models is predicated on a thorough understanding of the techniques used in their development and evaluation.

Decision Support Techniques↗