作者: Kazemi, Ali ; Arney, Lucas A. ; Yu-Shan, Andrea A. ; Peterman, Nicholas J. ; Joseph, Julie A. ; Smith, George L. ; Tuttle, John R. ; Cablay, Kory J.

Background::

Shoulder arthroscopy is commonly performed at ambulatory surgical centers (ASCs) with use of an interscalene block and inhaled general anesthesia (IGA). However, an alternative option known as total intravenous anesthesia with propofol (TIVA-P) has shown promising results in reducing recovery time for other surgeries. The objective of this study was to assess whether there is a clinically meaningful difference in post-anesthesia care unit phase-I (PACU-I) time following shoulder arthroscopy between patients receiving an interscalene block with IGA and those receiving an interscalene block with TIVA-P.

Methods::

Patients who underwent shoulder arthroscopy performed by a single surgeon at the ASC of our institution between 2020 and 2023 were enrolled. Enrollment was conducted in blocks, with up to 3 planned interim analyses. After 2 blocks, enrollment was halted because the study arms demonstrated a significant difference in the primary outcome measure, PACU-I time. A total of 96 patients were randomized into the TIVA-P and IGA groups; after patient withdrawals, the groups comprised 42 and 40 patients, respectively. Patients underwent shoulder arthroscopy with use of the anesthesia method corresponding to their assigned group. Pain, satisfaction, antiemetic use, perioperative interventions, surgical time, PACU-II time, postoperative care time, and total time until discharge were recorded and were analyzed with use of chi-square and Mann-Whitney U tests with a significance cutoff of 0.0167 to account for the interim analyses.

Results::

Across groups, 81.7% of patients were non-Hispanic White and 58.5% were male. Significant differences were observed between the TIVA-P and IGA groups with respect to median PACU-I time (0.0 minutes [interquartile range (IQR), 0.0 to 6.0 minutes] versus 25.5 minutes [IQR, 20.5 to 32.5 minutes]; p < 0.001) and median total time until discharge (135.5 minutes [IQR, 118.5 to 156.8 minutes] versus 148.5 minutes [IQR, 133.8 to 168.8 minutes]; p = 0.0104). The TIVA-P group had a 9.1% quicker discharge time, primarily as a result of bypassing PACU-I (66.7% of patients) and spending 25.5 fewer minutes there overall. The TIVA-P group also had a lower rate of antiemetic use than the IGA group (59.5% versus 92.5% of patients; p = 0.0013). No significant differences were detected between the TIVA-P and IGA groups in terms of median pain improvement (1.0 [IQR, 0.0 to 2.0] versus 1.0 [IQR, 0.0 to 2.0]; p = 0.6734), perioperative interventions (78.6% versus 77.5% of patients, p = 1.0000), or median patient satisfaction (4.0 [IQR, 4.0 to 4.0] versus 4.0 [IQR, 3.8 to 4.0]; p = 0.4148).

Conclusions::

TIVA-P showed potential to improve both PACU-I time and the total time until discharge while reducing antiemetic use without impacting pain or satisfaction. TIVA-P thus warrants consideration by orthopaedic surgeons for use in shoulder arthroscopy performed at ASCs.

Level of Evidence::

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

2024-07-01·AMERICAN JOURNAL OF CLINICAL DERMATOLOGY

Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies

Article

作者: Kircik, Leon ; Siegfried, Elaine C ; Silverberg, Jonathan I ; Blauvelt, Andrew ; Paller, Amy S ; Venturanza, May E ; Papp, Kim ; Simpson, Eric L ; Kallender, Howard ; Kuligowski, Michael E ; Eichenfield, Lawrence F ; Szepietowski, Jacek C ; Ren, Haobo

BACKGROUND:

Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2).

OBJECTIVE:

To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data.

METHODS:

Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study.

RESULTS:

Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events.

CONCLUSIONS:

Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018).

2024-01-01·Advances in experimental medicine and biology

Development of Orally Ingestible IgA Antibody Drugs to Maintain Symbiosis Between Humans and Microorganisms

Article

作者: Shinkura, Reiko

In recent years, dysbiosis, abnormalities in the gut microbiota, has been reported to be associated with the development of many diseases, and improving the gut microbiota is important for health maintenance. It has been shown that the host recognizes and regulates intestinal bacteria by means of IgA antibodies secreted into the gut, but the precise nature of the commensal gut bacteria recognized by each IgA antibody is unclear. We have cloned monoclonal IgA antibodies from mouse intestinal IgA-producing cells and are searching for bacterial molecules recognized by each IgA clone. Although the interaction of IgA antibodies with intestinal bacteria is still largely unknown and requires further basic research, we discuss the potential use of orally ingestible IgA antibodies as agents to improve intestinal microbiota.

100 项与 IgA蛋白酶(IGAN) 相关的药物交易

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