Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States.

BACKGROUND: Recent prevalence estimates for hidradenitis suppurativa (HS), a chronic inflammatory skin condition, are limited by timeliness, population size, and generalizability. OBJECTIVE: We sought to develop prevalence estimates for HS in the United States using large health care claims databases. METHODS: A retrospective analysis used PharMetrics Integrated Database to gather health care claims information for HS among patients with 12 or more months of continuous enrollment in a commercial health care plan throughout 2007. Included patients had: 1 or more diagnoses with International Classification of Diseases, Ninth Revision, Clinical Modification code 705.83 for HS during 2007 without a Current Procedural Terminology code for HS; 1 or more Current Procedural Terminology codes of 11450, 11451, 11462, 11463, 11470, or 11471 during 2007 without International Classification of Diseases, Ninth Revision, Clinical Modification code 705.83; or both. Age- and gender-specific prevalence projections were calculated. RESULTS: Among included patients (n = 7927), mean age (SD) was 38.2 (14.73) years, and 5834 (74%) were women. Most patients (n = 5205; 66%) were aged 30 to 64 years. The overall prevalence estimate was 0.053% (95% confidence interval 0.051-0.054). When adjusted for gender and age, prevalence rates were 0.052% and 0.051%, respectively. The most common procedures for HS were excision of skin and subcutaneous tissue axillary/inguinal simple or intermediate repair. LIMITATIONS: Limitations were a health insured-only population; 12-month enrollment period for 2007; HS-specific procedural codes; and possible HS misclassifications. CONCLUSION: We found a low rate of clinically detected HS (0.053%; approximately 146,000-162,000 patients in the United States in 2007), with affected persons almost 3 times as likely to be female and the highest prevalence in those aged 18 to 44 years.

Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial.

BACKGROUND: Biologic therapies with anti-tumor necrosis factor agents are promising treatments for hidradenitis suppurativa (HS). OBJECTIVE: We assessed the efficacy and safety of infliximab (IFX) for the treatment of moderate to severe HS. METHODS: A prospective double-blind treatment phase of 8 weeks where patients received IFX or placebo was followed by an open-label phase where patients taking placebo were given the opportunity to cross over to IFX, and an observational phase. Primary treatment efficacy was based on HS Severity Index. Secondary end points included Dermatology Life Quality Index, visual analog scale, and Physician Global Assessment scores. Inflammatory markers erythrocyte sedimentation rate and C-reactive protein were also assessed. RESULTS: More patients in the IFX than in the placebo group showed a 50% or greater decrease from baseline HS Severity Index score. In addition, statistically and clinically significant improvement from baseline was observed at week 8 in Dermatology Life Quality Index score, visual analog scale score, erythrocyte sedimentation rate, and C-reactive protein compared with placebo. Patients in the placebo group treated with IFX after week 8 (crossover) responded similarly to the original IFX group. Many patients withdrew during the observational phase to continue anti-tumor necrosis factor-alfa therapy. No unexpected serious adverse events were observed. LIMITATIONS: Results are representative of a single center, patients were treated by a single physician, some patients did not return after their last infusion, and the HS Severity Index requires validation. CONCLUSIONS: This clinical study represents the first formal assessment of IFX for treatment of moderate to severe HS. IFX was well tolerated, no unexpected safety issues were identified, and improvements in pain intensity, disease severity, and quality of life were demonstrated with concomitant reduction in clinical markers of inflammation.

Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: an open-label, dose-ranging, phase I study.

OBJECTIVE: New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes. METHODS: A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3-6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (> or = one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale > or = 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale < or = 2). RESULTS: A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 mug/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients. CONCLUSION: In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Expression and function of periostin-isoforms in bone.

Periostin was originally identified in MC3T3-E1 osteoblast-like cells. We have identified an isoform of periostin referred to as periostin-like-factor (PLF). It is homologous to other proteins such as fasciclin I (fas I), MPB70, betaIG-H3, and Algal-CAMs. All of these proteins are implicated in regulating cell adhesion. PLF and the other isoforms of periostin differ in their C-terminal sequences. PLF and periostin differ in two specific regions, between 673 and 699 amino acids (aa) and 785-812 aa. Periostin isoforms are expressed in vivo and in vitro during the stages of osteoblast differentiation and maturation. Their mRNAs are present in pre-osteoblast cells as detected by in situ hybridization, and the proteins are between 86 and 93 kD in size as determined by Western blot analysis. Antisense oligonucleotides and antibodies directed against the isoforms of periostin were used to block the activity of these proteins. In both cases, the levels of osteoblast-specific-differentiation markers were markedly reduced suggesting a role for these proteins in osteoblast differentiation.

Clot lysis in a primate model of peripheral arterial occlusive disease with use of systemic or intraarterial reteplase: addition of abciximab results in improved vessel reperfusion.

PURPOSE: This study was designed to compare the ability of reteplase (a fibrinolytic agent) alone or in combination with abciximab (a monoclonal antibody antagonist of platelet glycoprotein IIb/IIIa) to achieve and sustain vessel patency in an acute model of peripheral arterial occlusive disease in cynomolgus monkeys. MATERIALS AND METHODS: Total arterial occlusion was induced in the femoral arteries of 32 cynomolgus monkeys (eight groups of four) by endothelial injury and injection of thrombin-treated autologous blood. Reteplase was administered by intravenous bolus dose or by intraarterial infusion at the site of the clot. Abciximab was administered as a single weight-adjusted intravenous bolus dose. Platelet activity was measured by ex vivo platelet aggregation before and after abciximab treatment. Different groups of animals received sequential partial doses of reteplase with or without increasing doses of abciximab until either the weight-adjusted human dose equivalent of reteplase was reached or vessel recanalization was achieved. RESULTS: Animals receiving reteplase-only regimens demonstrated variability in the times required for reperfusion and the permanence of the effect. The coadministration of abciximab at doses of the antibody that achieved near or full inhibition of platelet function generally decreased the time to reperfusion and resulted in more consistent and sustained vessel patency. In the case of systemic intravenous reteplase, the coadministration of abciximab resulted in effective reperfusion of thrombosed vessels at decreased doses of the lytic agent. CONCLUSIONS: Reteplase administered systemically or at the site of thrombotic occlusion restored blood flow for periods of varying duration in monkeys with acute femoral artery thrombosis. The coadministration of systemic intravenous abciximab to intravenous or intraarterial reteplase allowed the use of lower doses of fibrinolytic agent with more accelerated and sustained reperfusion.