15 results on '"Stevens, S.R."'
Search Results
2. Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes
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Patel, R.A., Mentz, R.J., Schernthaner, G., Hernandez, A.F., Stevens, S.R., Bethel, M.A., Choi, J., Gustavson, S.M., Lecube, A., Öhman, P., Buse, J.B., Holman, R.R., Iqbal, N., and Lokhnygina, Y.
- Abstract
Background: EXSCEL (Exenatide Study of Cardiovascular Event Lowering) assessed the impact of once-weekly exenatide 2 mg versus placebo in patients with type 2 diabetes mellitus, while aiming for glycemic equipoise. Consequently, greater drop-in of open-label glucose-lowering medications occurred in the placebo group. Accordingly, we explored the potential effects of their unbalanced use on major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, and all-cause mortality (ACM), given that some of these agents are cardioprotective. Methods: Cox hazard models were performed by randomized treatment for drug classes where >5% open-label drop-in glucose-lowering medication occurred, and for glucagon-like peptide-1 receptor agonists (GLP-1 RAs; 3.0%) using three methodologies: drop-in visit right censoring, inverse probability for treatment weighting (IPTW), and applying drug class risk reductions. Results: Baseline glucose-lowering medications for the 14 752 EXSCEL participants (73.1% with previous cardiovascular disease) did not differ between treatment groups. During median 3.2 years follow-up, open-label drop-in occurred in 33.4% of participants, more frequently with placebo than exenatide (38.1% versus 28.8%), with metformin (6.1% versus 4.9%), sulfonylurea (8.7% versus 6.9%), dipeptidyl peptidase-4 inhibitors (10.6% versus 7.5%), SGLT-2i (10.3% versus 8.1%), GLP-1 RA (3.4% versus 2.4%), and insulin (13.8% versus 9.4%). The MACE effect size was not altered meaningfully by right censoring, but the favorable HR for exenatide became nominally significant in the sulfonylurea and any glucose-lowering medication groups, while the ACM HR and p-values were essentially unchanged. IPTW decreased the MACE HR from 0.91 (P=0.061) to 0.85 (P=0.008) and the ACM HR from 0.86 (P=0.016) to 0.81 (P=0.012). Application of literature-derived risk reductions showed no meaningful changes in MACE or ACM HRs or P values, although simulations of substantially greater use of drop-in cardioprotective glucose-lowering agents demonstrated blunting of signal detection. Conclusions: EXSCEL-observed HRs for MACE and ACM remained robust after right censoring or application of literature-derived risk reductions, but the exenatide versus placebo MACE effect size and statistical significance were increased by IPTW. Effects of open-label drop-in cardioprotective medications need to be considered carefully when designing, conducting, and analyzing cardiovascular outcome trials of glucose-lowering agents under the premise of glycemic equipoise. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01144338.
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- 2020
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3. Confirming the bidirectional nature of the association between severe hypoglycemic and cardiovascular events in type 2 diabetes: Insights from Exscel
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Angelyn Bethel, M., Gustavson, S.M., Maggioni, A.P., EXSCEL Study Group, Buse, J.B., Stevens, S.R., Mentz, R.J., Holman, R.R., Hernandez, A.F., Lokhnygina, Y., and Standl, E.
- Abstract
OBJECTIVE We sought to confirm a bidirectional association between severe hypoglycemic events (SHEs) and cardiovascular (CV) event risk and to characterize individuals at dual risk. RESEARCH DESIGN AND METHODS In a post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering (EXSCEL) participants, we examined time-dependent associations between SHEs and subsequent major adverse cardiac events (CV death, nonfatal myocardial infarction [MI] or stroke), fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for acute coronary syndrome (hACS), hospitalization for heart failure (hHF), and all-cause mortality (ACM), as well as time-dependent associations between nonfatal CV events and subsequent SHEs. RESULTS SHEs were uncommon and not associated with once-weekly exenatide therapy (hazard ratio 1.13 [95% CI 0.94–1.36], P 5 0.179). In fully adjusted models, SHEs were associated with an increased risk of subsequent ACM (1.83 [1.38–2.42], P < 0.001), CV death (1.60 [1.11–2.30], P 5 0.012), and hHF (2.09 [1.37–3.17], P 5 0.001), while nonfatal MI (2.02 [1.35–3.01], P 5 0.001), nonfatal stroke (2.30 [1.25–4.23], P 5 0.007), hACS (2.00 [1.39–2.90], P < 0.001), and hHF (3.24 [1.98–5.30], P < 0.001) were all associated with a subsequent increased risk of SHEs. The elevated bidirectional time-dependent hazards linking SHEs and a composite of all CV events were approximately constant over time, with those individuals at dual risk showing higher comorbidity scores compared with those without. CONCLUSIONS These findings, showing greater risk of SHEs after CV events as well as greater risk of CV events after SHEs, validate a bidirectional relationship between CV events and SHEs in patients with high comorbidity scores.
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- 2020
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4. Sunscreens and immune protection
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Baron, E.D. and Stevens, S.R.
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- 2002
5. Increased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOSSuggests an at-risk type 2 diabetes frail patient phenotype
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Standl, E., Stevens, S.R., Van De Werf, F., Green, J.B., Chan, J.C.N., Holman, R.R., Peterson, E.D., Armstrong, P.W., Scheen, A., Travert, F., Lachin, J.M., and Buse, J.B.
- Abstract
OBJECTIVE Severe hypoglycemic events (SHEs) in type 2 diabetes are associated with subsequent cardiovascular (CV) event risk. We examined whether CV events were associated with subsequent SHE risk. RESEARCH DESIGN AND METHODS Time-dependent associations between SHEs and a composite CV end point (fatal/ nonfatal myocardial infarction or stroke, hospitalization for unstable angina, hospitalization for heart failure [hHF]) were examined post hoc in 14,671 TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) participants with type 2 diabetes and CV disease followed for a median of 3.0 years. RESULTS SHEs were uncommon and unassociated with sitagliptin therapy (N = 160 [2.2%], 0.78/100 patient-years vs. N = 143 [1.9%], 0.70/100 patient-years for placebo; hazard ratio [HR] 1.12 [95%CI 0.89, 1.40], P = 0.33). Patients with (versus without) SHEs were older with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate; were more frequently women, nonwhite, and insulin treated; and more often had microalbuminuria or macroalbuminuria. Analyses adjusted for clinical factors showed SHEs were associated with increased risk of the primary composite CV end point (1.55 [1.06, 2.28], P = 0.025), all-cause death (1.83 [1.22, 2.75], P = 0.004), and CV death (1.72 [1.02, 2.87], P = 0.040). Conversely, nonfatal myocardial infarction (3.02 [1.83, 4.96], P < 0.001), nonfatal stroke (2.77 [1.36, 5.63], P = 0.005), and hHF (3.68 [2.13, 6.36], P < 0.001) were associated with increased risk of SHEs. Fully adjusted models showed no association between SHEs and subsequent CV or hHF events, but the association between CV events and subsequent SHEs remained robust. CONCLUSIONS These findings, showing greater risk of SHEs after CV events and greater risk of CV events after SHEs, suggest a common at-risk type 2 diabetes frail patient phenotype.
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- 2018
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6. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial
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Hu, P.T., Lopes, R.D., Stevens, S.R., Wallentin, L., Thomas, L., Alexander, J.H., Hanna, M., Lewis, B.S., Verheugt, F.W.A., Granger, C.B., Jones, W.S., Hu, P.T., Lopes, R.D., Stevens, S.R., Wallentin, L., Thomas, L., Alexander, J.H., Hanna, M., Lewis, B.S., Verheugt, F.W.A., Granger, C.B., and Jones, W.S.
- Abstract
Contains fulltext : 169653.pdf (publisher's version ) (Open Access), BACKGROUND: We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD. METHODS AND RESULTS: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P=0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03). CONCLUSIONS: Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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- 2017
7. Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K.
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Baron, E.D., primary, Barzilai, D., additional, Johnston, G., additional, Kawashima, M., additional, Takigawa, M., additional, Nakagawa, H., additional, Graham-Brown, R.A.C., additional, and Stevens, S.R., additional
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- 2002
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8. A simple clinical scoring system to improve the sensitivity and standardization of the diagnosis of mycosis fungoides type cutaneous T-cell lymphoma: logistic regression of clinical and laboratory data.
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Stevens, S.R., Ke, M.S., Birol, A., Terhune, M.H., Parry, E.J., Ross, C., Mostow, E.N., Gilliam, A.C., and Cooper, K.D.
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MYCOSIS fungoides , *LYMPHOMAS , *LOGISTIC regression analysis - Abstract
Summary Background The diagnosis of mycosis fungoides (MF) is notoriously difficult to establish because in the early stages, histological features may be nonspecific or merely suggestive. Objectives To standardize the diagnosis of MF. Methods We studied 138 patients with suspected MF referred over a 7-year period to a university department of a dermatology-based cutaneous lymphoma clinic. Six diagnostic criteria were evaluated: clinical morphology, clinical distribution, skin biopsy T-cell receptor gene rearrangement (TCR-GR), skin biopsy pan T-cell marker loss ≥ 2, skin biopsy CD4/CD8 ratio ≥ 6, and skin biopsy diffuse epidermal HLA-DR expression. These six clinical and laboratory criteria were compared by logistic regression analysis in patients with histologically diagnosed MF and those with benign disease. Results Of the 138 patients, 74 had histology of MF, 47 of benign dermatoses and 17 were indeterminate. Close associations were found between a histological diagnosis of MF and TCR-GR (odds ratio 14·4), classical morphology (7·5), classical distribution (2·5) and diffuse epidermal HLA-DR expression (2·8). Logistic regression models were developed depending on the availability of data (either TCR-GR or HLA-DR). Probabilities for correctly diagnosing MF compared with histology as the ‘gold standard’ were derived from these logistic regression models. A scoring system assigning point values based on these probabilities was then created in order to assist the clinician in making the diagnosis. If using TCR-GR data, a positive TCR-GR = 2·5 points, the presence of classical morphology = 2·0 points, and the presence of classical distribution = 1·5 points. A total score of ≥ 3·5 points assigns a high probability (> 85%) of having MF. If using HLA-DR expression, then the presence of classical morphology = 2·5 points, a positive diffuse epidermal HLA-DR expression = 2·0 points, and the presence of classical distribution = 1·5 points. In this case, a total score of ≥ 4·0 points assigns a high probability (> 85%) of MF. Conclusions The logistic regression models and scoring systems integrate clinical and laboratory assessments, allow rapid probability estimation, and provide a threshold for the diagnosis of MF in an objective, standardized manner. [ABSTRACT FROM AUTHOR]
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- 2003
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9. Atopic Dermatitis: The Role of Recombinant Interferon-γ Therapy.
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Chang, T.T. and Stevens, S.R.
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ATOPIC dermatitis , *THERAPEUTIC use of interferons - Abstract
Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical cellular and humoral immunologic abnormalities that can result in significant physical and psychological morbidity to the patient. Atopic dermatitis typically begins in childhood and can often persist through adolescence into adulthood. Although there are a variety of treatments for atopic dermatitis, many patients' symptoms do not improve or they have adverse reactions to medications, requiring the search for other, effective therapeutic agents. A number of inflammatory and immunological abnormalities have long been noted in patients with atopic dermatitis. Although great strides have been made in understanding the causes, the complex pathophysiology of atopic dermatitis is still not completely understood. Most notably, patients with atopic dermatitis often have an elevation of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated blood eosinophilia, and increased interleukin (IL)-4 production. In addition, peripheral blood mononuclear cells of patients with atopic dermatitis produce reduced levels of interferon-γ spontaneously and in response to stimuli. Due to this constellation of features, atopic dermatitis was initially viewed as a prototypical type 2 helper T lymphocyte (T) disease. These immunological findings led to a number of clinical trials with recombinant interferon-γ in patients who had severe, unremitting atopic dermatitis. Treatment with recombinant interferon-γ was postulated to be able to correct the immunological imbalances in patients with atopic dermatitis by decreasing serum IgE levels, IL-4 levels, restoring immune balance, and thereby leading to clinical improvement. Initial open-label studies, a double-blind placebo trial, and long-term open-label studies have demonstrated the clinical efficacy and tolerability of recombinant interferon-γ in a subset of patients with severe, unremitting atopic dermatitis. Patients receiving treatment often had marked decreases in severity of clinical parameters: erythema, edema/indurations, pruritus, excoriations, dryness, lichenification and associated reduction in total body surface area involvement. Surprisingly, treatment with recombinant interferon-γ did not lower serum IgE levels refuting the hypothesized mechanism by which interferon-γ would bring about clinical improvement in patients with atopic dermatitis. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement. Although the exact mechanism by which recombinant interferon-γ brings about clinical changes in patients with atopic dermatitis is unknown, recombinant interferon-γ should be considered a possible therapy for patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]
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- 2002
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10. Diagnosis and Treatment of Allergic Skin Disorders in the Elderly.
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Nedorost, S.T. and Stevens, S.R.
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SKIN diseases , *ALLERGIES , *DISEASES in older people - Abstract
Allergic skin disorders in the elderly may arise from contact with or ingestion of offending allergens. Itching associated with skin allergy must be distinguished from other causes of itching in the elderly such as xerosis, itching due to systemic disease and bullous disease. Although elderly people have somewhat decreased cell-mediated immunity and may be harder to sensitise under experimental conditions, they have had many years to acquire allergic responses, and therefore develop contact dermatitis frequently. Patch testing is a valuable tool to diagnose contact allergy and should be used often in the elderly, particularly in patients at high risk of contact dermatitis, such as those with chronic lower extremity dermatitis or ulcers due to venous stasis. When prescribing topical medications to high risk patients, a knowledge of the common sensitisers is important. In addition to allergy to medicaments and dressings used to treat stasis ulcers, contact allergy to dental prostheses and medications used to treat ocular disease are common in the elderly as a result of increased usage and exposure. Rash caused by ingested allergens is much more commonly due to medications than to food in the elderly. Allergic noneczematous dermatoses in the elderly are commonly drug-induced. Urticarial skin reactions are often associated with the administration of antibacterials, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants or opioids. Morbilliform rashes are a common sign of systemic reaction to anticonvulsants, gold, allopurinol or diuretics. Phototoxic reactions may be associated with the administration of tetracyclines, diuretics, NSAIDs and antihyperglycaemic agents. Patient-specific variables such as HLA type and concomitant medication may affect the likelihood of an allergic response to medication. Many elderly patients take multiple medications, which can make diagnosis of drug allergy difficult because diagnosis is most commonly accomplished by observing clinical response once the medication is withdrawn. In the case of lichenoid cutaneous reactions, clinical improvement may take several months after withdrawal of the offending drug. Laboratory tests to detect drug-induced allergic skin disorders may be available in the future. [ABSTRACT FROM AUTHOR]
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- 2001
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11. Consensus conference on pediatric atopic dermatitis
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Eichenfield, L.F., Hanifin, J.M., Luger, T.A., Stevens, S.R., and Pride, H.B.
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- 2003
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12. Evaluation methods for helical and spiral VHF/UHF satellite antennas
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Stevens, S.R., primary and Walton, E.K., additional
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13. Evaluation methods for helical and spiral VHF/UHF satellite antennas.
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Stevens, S.R. and Walton, E.K.
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- 2003
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14. Relapsing livedo reticularis in the setting of chronic pancreatitis
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Gould, J.W., Helms, S.E., Schulz, S.M., and Stevens, S.R.
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- 1998
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15. Idiopathic CD4 + T lymphocytopenia in a patient with mycosis fungoides
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Stevens, S.R, Griffiths, T.W, and Cooper, K.D
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- 1995
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