Citations

Objective: To describe interventions that target patient, provider, and system barriers to sedative-hypnotic (SH) deprescribing in the community and suggest strategies for healthcare teams. Data Sources: Ovid MEDLINE ALL and EMBASE Classic + EMBASE (March 10, 2021). Study Selection and Data Extraction: English-language studies in primary care settings. Data Synthesis: 20 studies were themed as patient-related and prescriber inertia, physician skills and awareness, and health system constraints. Patient education strategies reduced SH dose for 10% to 62% of participants, leading to discontinuation in 13% to 80% of participants. Policy interventions reduced targeted medication use by 10% to 50%. Relevance to Patient Care and Clinical Practice: Patient engagement and empowerment successfully convince patients to deprescribe chronic SHs. Quality improvement strategies should also consider interventions directed at prescribers, including education and training, drug utilization reviews, or computer alerts indicating a potentially inappropriate prescription by medication, age, dose, or disease. Educational interventions were effective when they facilitated patient engagement and provided information on the harms and limited evidence supporting chronic use as well as the effectiveness of alternatives. Decision support tools were less effective than prescriber education with patient engagement, although they can be readily incorporated in the workflow through prescribing software. Conclusions: Several strategies with demonstrated efficacy in reducing SH use in community practice were identified. Education regarding SH risks, how to taper, and potential alternatives are essential details to provide to clinicians, patients, and families. The strategies presented can guide community healthcare teams toward reducing the community burden of SH use.

Objective To provide evidence‐based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty‐one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non–hepatitis B–related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long‐term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. Conclusion These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

Objective To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid‐sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

Objective To provide evidence‐based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty‐one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non–hepatitis B–related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long‐term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. Conclusion These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

Objective To provide evidence‐based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low‐quality evidence supporting the recommendations. Conclusion This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

Objective To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid‐sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

Objective To provide evidence‐based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low‐quality evidence supporting the recommendations. Conclusion This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

Background and Purpose: Based on promising results of the Solitaire FR With the Intention for Thrombectomy (SWIFT) trial, Solitaire FR stent retriever device recently received the Food and Drug Administration (FDA) approval for recanalization of cerebral vessels in patients with acute ischemic stroke. Real world experience with this device since its FDA approval in the United States has not been previously described. Methods: We conducted retrospective analysis of consecutive acute ischemic strokes cases from March 2012 to July 2012 in 10 centers within the United States, where Solitaire FR was used as a single device or in conjunction with other intra-arterial endovascular approaches. Results: A total of 107 patients were identified (mean age, 64 years; male gender, 51%; mean admission NIHSS score 17). Mean time from symptom onset to angiogram (groin puncture) was 4 hrs 47 min. Intravenous thrombolysis with tissue plasminogen activator (tPA) was administered in 37% of cases. Other endovascular techniques utilized in conjunction with Solitaire FR included intra-arterial thrombolysis with tPA (12% of patients), aspiration thrombectomy with Penumbra system (29%) and stenting (17%). Complete recanalization (TIMI 2-3) was achieved in 88% of patients. The rate of sICH within the first 24 hours was 15%. In-hospital mortality was 24%. 30-day clinical follow up data was available on 82 (77%) patients. Of those, 28 patients (34%) had favorable functional outcome (defined as modified Ranking Scale,mRS≤2) and 22 patients (27%) had excellent functional outcome (mRS≤1) at 30 days. Three or more passes with the Solitaire device was associated with a higher incidence of mortality compared with patients requiring 1 or 2 passes only (43% and 18% respectively, p = 0.011). No statistically significant correlation between clot location or length and outcome was evident. Use of other devices with the Solitaire FR was correlated with worsened outcome (p=0.037). Conclusions: This is the first study describing real-world experience with Solitaire FR device outside the SWIFT trial in the United States. Out study shows that variety of other endovascular approaches are used in conjunction with Solitaire FR.

The aim of this study was to characterise a recently identified adult smooth muscle stem-like/progenitor cell (SMSPC) and exploit the ability to differentiate contractile smooth muscle cells (SMC) from SMSPCs facilitating tissue engineering of small to medium arteries, an approach which is hampered by inadequate sources of, and scale up methodologies for autologous SMCs. We initially identified a novel SMSPC in the bone marrow (BM) of rats that retained classic stem cell-like characteristics (clonogenicity, unlimited self-renewal, high telomerase activity, expression of stem cell markers) whilst expressing low levels of SMC-like transcripts. Spontaneous differentiation favoured a SMC phenotype where ~20-fold increases in calponin and SM-MHC protein expression were observed 10 days post-embryoid body formation, an effect augmented by TGFβ (P < 0.0001). Differentiation of SMSPCs from an undifferentiated state towards contractile SMCs was Myocd-dependent. Overexpression of Myocd in SMSPCs increased their percentage contraction in response to AngII (P < 0.05) and KCL (P < 0.05) and Ca2+ signalling to levels indistinguishable from rat SMCs. Knockdown of SMC-specific repressors resulted in Myocd-dependent SMC differentiation of SMSPCs. Taking advantage of the fact that SMSPCs possessed unlimited self-renewal capacity ex vivo and could be successfully reprogrammed into functional SMCs, we determined the vascular tissue engineering potential of SMSPCs and showed these cells integrate as viable tissue engineered vascular grafts in vivo. Specifically, after 1 month implantation, a Myocd-GFP+/Isl1+ smooth muscle layer was observed in the grafts along with a vWF+ luminal endothelial layer and multi-layered collagen and elastin fibre formation throughout the graft wall. We have recently isolated cells with similar SMSPC phenotype and differentiation potential from human peripheral blood. This study demonstrates that adult SMSPCs derived from rat BM and human blood can be reprogrammed to efficiently generate large quantities of mature contractile SMCs, displaying great utility as a cellular backbone for tissue engineered vascular grafts, making them an attractive source for vascular cell therapy and surgical applications.

Introduction: β-blockers, including atenolol, are among the most widely prescribed antihypertensive drug classes. However, their use has been associated with hyperglycemia and incident diabetes, which poses concern for prescribers and patients. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a multicenter clinical trial with one of its objectives to identify genetic influences on adverse metabolic events in patients treated with atenolol. Here we report a genomics-metabolomics integrative approach to identify biomarkers associated with atenolol-induced glucose change. Methods: PEAR participants were genotyped using the Illumina Omni 1M-Quad Chip. Metabolite profiles were acquired through GC-TOF-MS. Association between baseline levels of metabolites and glucose change was conducted using a multivariate linear regression model adjusted for age, gender and baseline fasting glucose. Genomics-metabolomics integration included selecting SNPs within genes involved in the synthesis and degradation of top metabolites and testing their effect on glucose change in 234 atenolol-treated Caucasians in PEAR, adjusting for age, gender, baseline glucose and principal components 1 and 2. A false discovery rate (FDR) of .05 was used to adjust for multiple comparisons. Replication of significant SNPs was conducted in an additional 228 participants treated with atenolol in PEAR. Results: Metabolomics analysis revealed 3 metabolites associated with glucose change that passed FDR adjustment. The top metabolite signal was beta-alanine. Increasing levels of baseline beta-alanine was significantly correlated with greater glucose increases after atenolol treatment (p=.0003). A total of 79 SNPs in 12 genes in the beta-alanine pathway were explored. SNP rs2669429 in DPYS was significantly associated with glucose change, after FDR adjustment. We found that G allele carriers had significantly greater glucose change compared with non-carriers (p=.0006; β=+2.76 mg/dL). This finding was successfully replicated in the other 228 patients who received atenolol (p=.04; β=+1.86 mg/dL). Conclusions: These results suggest that beta alanine and DPYS rs2669429 SNP might be an important predictor of atenolol-induced dysglycemia.