First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

Longer-term Benefits and Risks of Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes: a Systematic Review and Meta-analysis.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks' duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD - 0.55%, 95% CI - 0.62, - 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes.

The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists: a Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.

Technical approach, outcomes, and exposure-related complications in patients undergoing anterior lumbar interbody fusion.

OBJECTIVE: To describe our technique, evaluate access related complications and factors contributing to adverse outcomes in patients undergoing retroperitoneal anterior lumbar interbody fusion (ALIF). METHODS: We conducted a retrospective analysis of prospectively collected data on patients undergoing ALIF at our institution from January 2008 to December 2017. Access was performed by a vascular surgeon who remained present for the duration of the case. Data collected included patients' demographics, comorbidities, exposure related complications and ileus. Study end points included major adverse events and minor complications. Major adverse events included any vascular injuries requiring repair, bowel and ureter injuries, postoperative bleeding requiring reoperation, myocardial infarction, stroke, venous thromboembolism (pulmonary embolism/deep venous thrombosis), wound dehiscence, and death. Minor complications included postoperative paralytic ileus, urinary tract infections, and surgical site infections. The incidence of incisional hernia was also evaluated. RESULTS: During this period, 1178 patients (514 males and 664 females; mean age, 54.1 ± 13.8 years) underwent a total of 2352 levels ALIF at our institution (single level, 422 patients; 2 levels, 450; 3 levels, 205; 4 levels, 98; 5 levels, 6; 6 levels, 1; and 7 levels, 1). The median estimated blood loss was 25 mL (interquartile range, 25-50). There were 57 exposure-related complications (4.8%), including vascular injuries (venous, 13; arterial, 4) in 17 patients (1.4%), bowel injuries in three patients (serosa tear in two and arterial embolization with subsequent bowel ischemia in one). Eleven of the 13 venous injuries (84.6%) occurred while exposing the L4 to L5 lumbar level. Two of the four patients with arterial injuries developed acute limb ischemia requiring embolectomy. One embolized to the superior mesenteric artery and underwent bowel resection. Twenty patients (1.7%) developed venous thromboembolism, two of whom had sustained left iliac vein injury during exposure. Sixteen patients (1.4%) developed a retroperitoneal hematoma/seroma with nine requiring evacuation in the operating room. Thirty-six patients (3.1%) developed postoperative ileus, defined as an inability to tolerate diet on postoperative day 3. Four patients (0.4%) had a postoperative myocardial infarction, and two had a stroke and two (0.17%) died within the first 30 postoperative days. Thirty-one patients developed incisional complications, including surgical site infection in 24 and incisional hernia in 7. CONCLUSIONS: Our findings suggest that ALIF exposure can be performed safely with a relatively low overall complication rate. The majority of vascular injuries associated with this procedure are venous in nature, occurring predominantly while exposing the L4 to L5 level and can be safely addressed by an experienced vascular team.

Lipid-lowering therapies in peripheral artery disease: A review.

Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, patients with PAD are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.

Perioperative Management of Antithrombotic Therapy.

This JAMA Clinical Guidelines Synopsis summarizes the American College of Chest Physicians' 2022 guideline on perioperative management of patients taking oral anticoagulation or antiplatelet therapy who are undergoing an elective surgery or procedure.

Lower Gastrointestinal Hemorrhage.

This JAMA Clinical Guidelines Synopsis summarizes the 2023 American College of Gastroenterology guidelines on management of patients with acute lower gastrointestinal bleeding.

Falls Prevention for Older Adults.

This article summarizes a 2022 clinical practice guideline on falls prevention and management in older adults from the World Falls Guidelines Initiative.

Diagnosis and Management of Celiac Disease.

This JAMA Clinical Guidelines Synopsis summarizes the American College of Gastroenterology's 2023 guideline update on diagnosis and management of celiac disease.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

BACKGROUND: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. METHODS: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. RESULTS: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries. CONCLUSIONS: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

Single-center experience with complex abdominal aortic aneurysms treated by open or endovascular repair using fenestrated/branched endografts.

OBJECTIVE: The objective of this study was to evaluate outcomes of patients with complex abdominal aortic aneurysms (cAAAs) treated with open repair (OR) or fenestrated/branched endovascular aneurysm repair (F/B-EVAR) from a single center. METHODS: A retrospective analysis of consecutive patients with cAAAs treated electively by OR or F/B-EVAR between January 2010 and February 2017 was conducted. Demographics of the patients, cardiovascular risk factors, procedure time, number of vessels incorporated, radiation dose, estimated blood loss, intensive care unit (ICU) length of stay (LOS), and hospital LOS were recorded. End points included target vessel patency, aneurysm rupture, freedom from reintervention, and major adverse events (MAEs). RESULTS: During this period, 153 patients (OR, 69; F/B-EVAR, 84) underwent repair of cAAA. The majority were male (OR, 55; F/B-EVAR, 64), with a mean age of 75.8 ± 7.6 years (F/B-EVAR) and 71.2 ± 7.9 years (OR). Patients in the F/B-EVAR group were more likely to be American Society of Anesthesiologists class 3 and 4 (60% vs 0%; P < .001) and had a higher median Society for Vascular Surgery/American Association for Vascular Surgery comorbidity severity score (15 vs 7; P < .001). A total of 235 vessels were targeted in the F/B-EVAR group, with a technical success of 97.6%. Thirty-one patients in the OR group required concomitant renal artery revascularization. Transfusion requirements (100% vs 1.2%), MAEs (40.6% vs 13.1%), procedure length (304 minutes vs 140 minutes), estimated blood loss (2246 mL vs 165 mL), ICU LOS (3 days vs 1 day), and hospital LOS (7 days vs 2 days) were higher (P < .001) in the OR group compared with the F/B-EVAR group. The 30-day mortality was 2.9% and 2.4% (P = .84) in the OR group and F/B-EVAR group, respectively. Supraceliac clamp site was associated with increased incidence of postoperative renal insufficiency. A decrease in procedure time, contrast volume, fluoroscopy time, and fluoroscopy dose was noted in the F/B-EVAR group with increasing experience even as case complexity increased. More patients were discharged home after F/B-EVAR (97.6% vs 59.4%; P < .001). With a mean follow-up of 31 months (F/B-EVAR, 17 months; OR, 48 months), the rate of secondary intervention was 3.7% and 5.8% (P = NS) for F/B-EVAR and OR, respectively. Freedom from branch instability and reintervention was 99% (95% confidence interval, 96.2%-99.8%) and 96% (95% confidence interval, 87.1%-98.6%), respectively. CONCLUSIONS: Results of this "real-world" experience suggest that the use of F/B-EVAR for the treatment of cAAAs in high-risk surgical patients is safe and effective and has comparable short-term results to those of low-risk patients undergoing OR. Patients treated by F/B-EVAR had shorter ICU and hospital LOS, lower MAEs, and faster convalescence. A decrease in procedure time and radiation dose was noted as experience was gained, even as complexity increased.

Topical Therapies for Atopic Dermatitis.

This JAMA Clinical Guidelines Synopsis summarizes the American Academy of Dermatology's 2023 guidelines for topical-therapy management of adults with atopic dermatitis.

Prescribing Opioids for Pain.

This JAMA Clinical Guidelines Synopsis summarizes the Centers for Disease Control and Prevention's 2022 clinical practice guideline for prescribing opioids for pain.

A prospective randomized comparison of contralateral snare versus retrograde gate cannulation in endovascular aneurysm repair.

OBJECTIVE: The objective of this study was to compare snare vs the standard retrograde gate cannulation method during endovascular aneurysm repair to determine the most efficient technique and to evaluate whether time was affected by graft design or the surgeon's experience. METHODS: This was a prospective randomized study involving single-center elective endovascular aneurysm repairs. Patients were randomized to the snare or retrograde group in a 1:1 ratio. The initial method was attempted for 15 minutes; if it was unsuccessful, the team switched to the alternative technique for an additional 15 minutes. The protocol continued until success was achieved. Data collected on demographic, anatomic, and procedural factors were analyzed for statistically significant differences. RESULTS: A total of 101 patients were included. Average age was 75.3 years, and 82% were male; 49 patients were randomized to snare and 52 to retrograde cannulation. The groups were overall similar. Median cannulation times were 3.9 minutes for the snare and 2.7 minutes for the retrograde technique (P = .13). The snare group attempts were successful within the initial 15-minute period in all but one patient (98% success). In the retrograde group, 5 of the 52 (10%) crossed over to snare. This difference did not reach statistical significance (P = .11). A difference was seen in the extremes of cannulation times. The surgeon's experience and graft design were not found to have significant effects on cannulation times. Further analysis of the retrograde group patients with long cannulation time found a relative breakpoint at the 5-minute mark. In those exceeding this time mark, the chance of eventual cannulation within 15 minutes dropped to 67%. In this group, median time to cannulation was 12.2 minutes for retrograde compared with 7.1 minutes for snare after crossover. CONCLUSIONS: Gate cannulation was successful using both methods with no statistical difference between the two in median time. Retrograde cannulation was found to be more likely to have short times. If cannulation by retrograde technique had not been achieved in the first 5 minutes, the chances of eventual success dropped significantly, and crossover to snare was more efficient. This finding suggests that one should consider an alternative method of gate cannulation if it has not been accomplished within this time.

A Dedicated Surveillance Program Improves Compliance with Endovascular Aortic Aneurysm Repair Follow-up.

BACKGROUND: Current recommendations suggest lifetime follow-up for endovascular aortic aneurysm repair (EVAR) patients to avoid consequences associated with endoleak and aneurysm enlargement. Follow-up compliance has been reported between 43% and 92%, with most single-center studies citing successful follow-up surveillance at less than 60%. We investigated follow-up completeness with a defined surveillance program and subsequent secondary intervention prevalence from a single center. METHODS: Our surveillance program notified patients of the need for follow-up imaging and surgeon review. Data were obtained from retrospective review of a prospective database, including operative and follow-up details, follow-up imaging completeness, endoleak incidence, and secondary intervention prevalence. RESULTS: Five hundred seventeen patients received elective EVAR from 2005 to 2015. Surveillance was achieved in 425 (82.3%). Mean number of follow-up studies was 4.2 ± 2.9 and median time to first follow-up was 36 days. Four hundred forty-eight patients (86.7%) had freedom from intervention. Sixty-nine unique patients (13.3%) had 107 secondary interventions. Median time to first secondary intervention in 69 patients was 476 days. Mean number of imaging studies for secondary intervention patients was 6.1 ± 3.9, compared with mean 3.4 ± 2.3 for patients without (P < 0.001). Overall mortality was 24.6% (n = 127), including 32 deaths of unknown cause (6.2% overall) and 95 of non-EVAR-related causes (18.3%). No aneurysm-related deaths were reported. CONCLUSIONS: Regular post-EVAR surveillance through a dedicated program resulted in a high rate of follow-up compliance, 13.3% rate of secondary intervention, and low aneurysm-related mortality. Careful lifetime surveillance remains important in long-term care following elective EVAR.

Preoperative Inferior Mesenteric Artery Embolization: A Valid Method to Reduce the Rate of Type II Endoleak after EVAR?

BACKGROUND: Type II endoleak is the most commonly encountered endoleak after endovascular abdominal aortic aneurysm repair (EVAR). Some have advocated preoperative inferior mesenteric artery (IMA) embolization as a valid method for reducing the incidence of this endoleak, but controversies exist. We sought to demonstrate the impact of IMA embolization using a meta-analysis of currently available studies combined with our own experience. METHODS: We conducted an institutional review board-approved, retrospective analysis of all patients undergoing IMA embolization before EVAR between the years 2010 and 2015 and used as a control a similar group of patients with patent IMA. We divided patients from our own experience and 5 other studies into 2 groups: those who did not undergo IMA embolization (control) before EVAR and those who did. Rates of type II endoleaks, aneurysm sac regression, and secondary interventions were analyzed. RESULTS: A total of 620 patients from 6 studies were analyzed, including 258 patients who underwent an attempted IMA embolization before EVAR with a cumulative success rate of 99.2% (range, 93.8% to 100%). There was 1 fatality associated with IMA embolization. A meta-analysis showed that preoperative IMA embolization protected against type II endoleaks compared to the control group (odds ratio [OR], 0.31 [0.17-0.57]; P < 0.001, I2 = 43%). Furthermore, the rate of secondary intervention was significantly lower in the treatment group (OR, 0.12 [0.004-0.36]; P < 0.001, I2 = 0%). After IMA embolization, type II endoleak resulted from patent lumbar arteries in all 62 patients with persistent endoleak. CONCLUSIONS: Preoperative embolization of the IMA protects against the development of type II endoleaks and secondary interventions and may potentially lead to a rapid aneurysm sac regression. The procedure can be performed with a high technical success rate and minimal complications and should be considered in patients with IMA >3 mm before EVAR. A randomized trial, however, is required to clearly delineate the clinical significance of this technique.

Unique Case of Takayasu Arteritis with Severe Distal Aortic Stenosis and Iliac Thrombosis.

Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which predominantly affects women younger than 40 years of age. Symptoms are highly variable based on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis. Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants, and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery and leading to left iliac artery thrombosis. Based on our literature review, our article represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis.