A comparison between the role of enniatins and deoxynivalenol in Fusarium virulence on different tissues of common wheat.

BACKGROUND: Fusarium graminearum and Fusarium avenaceum are two of the most important causal agents of Fusarium head blight (FHB) of wheat. They can produce mycotoxins that accumulate in infected wheat heads, including deoxynivalenol (DON) and enniatins (ENNs), produced by F. graminearum and F. avenaceum, respectively. While the role of DON as a virulence factor in F. graminearum toward wheat is well known, ENNs in F. avenaceum has been poorly explored. Results obtained to-date indicate that ENNs may confer an advantage to F. avenaceum only on particular hosts. RESULTS: In this study, with the use of ENN-producing and ENN non-producing F. avenaceum strains, the role of ENNs on F. avenaceum virulence was investigated on the root, stem base and head of common wheat, and compared with the role of DON, using DON-producing and DON non-producing F. graminearum strains. The DON-producing F. graminearum strain showed a significantly higher ability to cause symptoms and colonise each of the tested tissues than the non-producing strain. On the other hand, the ability to produce ENNs increased initial symptoms of the disease and fungal biomass accumulation, measured by qPCR, only in wheat heads, and not in roots or stem bases. LC-MS/MS analysis was used to confirm the presence of ENNs and DON in the different strains, and results, both in vitro and in wheat heads, were consistent with the genetics of each strain. CONCLUSION: While the key role of DON on F. graminearum virulence towards three different wheat tissues was noticeable, ENNs seemed to have a role only in influencing F. avenaceum virulence on common wheat heads probably due to an initial delay in the appearance of symptoms.

Integrated vascular surgery applicants' perspectives of virtual residency interviews during the coronavirus disease 2019 application cycle.

BACKGROUND: In agreement with Association of American Medical Colleges guidelines, the 2020 to 2021 integrated vascular surgery (I-VS) residency interviews were conducted virtually. In the present study, we collected data about the virtual interview process from the applicant's perspective, including preferences for interview format and the virtual resources they found most helpful. METHODS: An anonymous, online survey study of medical students who had been accepted into I-VS residencies during the 2020 to 2021 application cycle was performed. The survey contained questions about applicant behavior during the virtual application cycle, their perception of the virtual interviews, the utility of the virtual format, their preferences, and the virtual resources they found the most helpful for determining their rank list. RESULTS: Of 72 applicants, 38 (18 women, 19 men, and 1 declined to answer) had completed the survey for a 57.2% response rate. The average number of programs interviewed was 25 to 30 (31%). More than one-half (55%) of the respondents had responded that they had interviewed at more programs than they would have had the interviews been in person. More than one-half of the applicants (55%) reported that they preferred remote interviews with the option to visit in-person at their top choice programs compared with the use of all remote interviews (21%) or all in-person interviews (18%). Most had somewhat or strongly agreed (79%) that virtual interviews allowed them to properly gauge a residency program and provided adequate opportunities to interact with the residents (65%). The online resources the applicants found the most helpful in determining their rank lists were attending educational conferences, prerecorded videos from faculty and residents, and the program's social media platforms. CONCLUSIONS: The results from the present study have illuminated the current trends and attitudes of I-VS applicants for virtual interviews, including the virtual resources they found the most useful. Virtual interviews were a preferred method of interviewing and allowed applicants to assess a residency program and interact with the current residents. These variables should be considered by the program leadership when developing protocols for upcoming application cycles.

Understanding radiation exposure and improving safety for vascular surgery trainees.

OBJECTIVE: Despite having robust radiation safety education procedures and policies in place, we discovered that the trainees at our Accreditation Council for Graduate Medical Education-approved integrated vascular surgery residency and fellowship program were exceeding the annual radiation exposure limits. In the present report, we have described our quality improvement project to identify the root causes and implement policies to improve radiation safety education, oversite, and, ultimately, the exposure levels of our trainees. METHODS: A committee of faculty, fellows, radiology nurses, and radiation safety officers from each of the programs affiliated hospitals convened to identify the potential root causes of the increased radiation exposure and potential modifiable actions. The radiation exposure reports for postgraduate year 4 to 7 trainees were evaluated before and after the interventions. RESULTS: Excessive radiation exposure was found to be more prevalent than anticipated, with multiple trainees surpassing the annual exposure limits. The committee classified the factors at play and interventions into four categories: policies and procedures, curriculum, environment, resources, and equipment. The multisite status of our program was a key factor associated with the increased radiation exposure. In addition, we found that excessive radiation levels were occurring primarily at a single hospital site. After the interventions, the monthly average levels at this site had decreased considerably from 936 mrem to 272 mrem. CONCLUSIONS: We found it alarming that the safety policies in place at vascular residency and fellowship programs were inadequate in securing the safety of their trainees. We found interventions such as inventorying and ensuring the availability of safety equipment, hands-on instruction to complement traditional didactics, lowering the default frame rates, and converting to real-time dosimetry to be effective measures for reducing radiation exposure.

Comparison of outcomes for balloon angioplasty, atherectomy, and stenting in the treatment of infrapopliteal disease for chronic limb-threatening ischemia.

OBJECTIVE: We evaluated limb salvage (LS), amputation-free survival (AFS), and target extremity reintervention (TER) after plain old balloon angioplasty (POBA), stenting, and atherectomy for treatment of infrapopliteal disease (IPD) with chronic limb-threatening ischemia (CLTI). METHODS: All index peripheral vascular interventions for IPD and CLTI were identified from the Vascular Quality Initiative registry. Of the multilevel procedures, the peripheral vascular intervention type was indexed to the infrapopliteal segment. Propensity score matching was used to control for baseline differences between groups. Kaplan-Meier and Cox regression were used to calculate and compare LS and AFS. RESULTS: The 3-year LS for stenting vs POBA was 87.6% vs 81.9% (P = .006) but was not significant on Cox regression analysis (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.56-0.76; P = .08). AFS was superior for stenting vs POBA (78.1% vs 69.5%; P = .001; HR, 0.73; 95% CI, 0.60-0.90; P = .003). LS was similar for POBA and atherectomy (81.9% vs 84.8%; P = .11) and for stenting and atherectomy (87.6% vs 84.8%; P = .23). The LS rate after propensity score matching for POBA vs stenting was 83.4% vs 88.2% (P = .07; HR, 0.71; 95% CI, 0.50-1.017; P = .062). The AFS rate for stenting vs POBA was 78.8% vs 69.4% (P = .005; HR, 0.69; 95% CI, 0.54-0.89; P = .005). No significant differences were found between stenting and atherectomy (P = .21 for atherectomy; and P = .34 for POBA). The need for TER did not differ across the groups but the interval to TER was significantly longer for stenting than for POBA or atherectomy (stenting vs POBA, 12.8 months vs 7.7 months; P = .001; stenting vs atherectomy, 13.5 months vs 6.8 months; P < .001). CONCLUSIONS: Stenting and atherectomy had comparable LS and AFS for patients with IPD and CLTI. However, stenting conferred significant benefits for AFS compared with POBA but atherectomy did not. Furthermore, the interval to TER was nearly double for stenting compared with POBA or atherectomy. These factors should be considered when determining the treatment strategy for this challenging anatomic segment.

Optimal medical management in patients undergoing peripheral vascular interventions for chronic limb-threatening ischemia is associated with improved outcomes.

OBJECTIVE: Optimizing medical management and risk factor modification are underused strategies in patients with chronic limb-threatening ischemia (CLTI), despite evidence of improved outcomes. The Vascular Quality Initiative (VQI) registry is a tool to improve quality of vascular care. In this study, we used the VQI to evaluate trends in medical management in patients with CLTI undergoing peripheral vascular interventions (PVI), and the impact of changes in management on overall survival (OS), amputation-free survival (AFS), and limb salvage (LS). METHODS: Patients undergoing index PVI for CLTI between 2012 and 2016, with ≥24 months of follow-up were identified from the national VQI registry. Patient details including smoking status and medication use, OS, LS, and AFS were analyzed with linear-by-linear association, t test, and logistic regression. RESULTS: There were 12,370 PVI completed in 11,466 patients. There was a significant increase in infrapopliteal interventions (from 29.8% to 39.0%; P < .001) and PVI performed for tissue loss (from 59.1% to 66.5%; P < .001). The percentage of current smokers at time of PVI decreased (from 36.2% to 30.7%; P = .036). At discharge, statins were initiated in 25%, aspirin in 45%, and P2Y12 therapy in 58% of patients not receiving these medications before PVI. Over the course of follow-up, dual antiplatelet therapy (DAPT) (from 41.1% to 48.0%; P < .001), angiotensin-converting enzyme (ACE) inhibitor (from 46.2% to 51.3%; P < .001), and statin (from 70.4% to 77.5%; P < .001) use increased. Combined DAPT, ACE inhibitor and statin use increased from 33.6% to 39.6% (P ≤ .001). Significant improvement in 24-month OS and AFS was noted (OS, from 90.9% to 93.7% [P = .002]: AFS, from 81.2% to 83.1% [P = .046]), but not LS (from 89.6% to 89.0%; P = .83). Combined therapy with P2Y12 inhibitors, statins and ACE inhibitors was an independent predictor of improved OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.96; P = .034). DAPT was independent predictor of improved LS (hazard ratio, 0.83; 95% confidence interval, 0.79-0.87; P < .007). CONCLUSIONS: Antiplatelet, ACE inhibitor, and statin use increased over the study period and was associated with improved OS and AFS. LS trends did not change significantly over time, possibly owing to the inclusion of patients with a greater disease burden or inadequate medical management. Medical management, although improved, remained far from optimal and represents an area for continued development.

Association Between Conduit Type and Outcomes After Open Repair of Popliteal Artery Aneurysms.

INTRODUCTION: Prior studies have demonstrated acceptable midterm outcomes with prosthetic conduits for above-knee bypass for occlusive disease in patients with inadequate segment great saphenous vein (GSV). In this study we aimed to investigate whether this holds true for open repair of popliteal artery aneurysms (PAA). METHODS: We queried the Vascular Quality Initiative data for patients who underwent open PAA repair (OPAR). We divided the cohort into three groups based on the conduit used: GSV, other autologous veins, or prosthetic graft. Study outcomes included primary patency, freedom from major amputation, amputation-free survival, and overall survival at 1 y. Kaplan-Meier survival estimates, log-rank tests and multivariable Cox regression were used to compare outcomes between study groups. RESULTS: A total of 4016 patients underwent bypass for PAA from January 2010 to October 2021. The three cohorts were significantly different in many demographic and clinical characteristics. The adjusted odds of postoperative amputation among symptomatic patients were 3-fold higher for prosthetic conduits compared to the GSV (odds ratio, 3.20; 95% CI, 1.72-5.92; P < 0.001). For the 1-y outcomes, the adjusted risk of major amputation was almost 3-fold higher for patients with symptomatic disease undergoing bypass with prosthetic conduits (hazard ratio [HR], 2.97; 95% CI, 1.35-6.52; P = 0.007). When compared with GSV, prosthetic conduits were associated with 96% increased risk of death when used for repair in symptomatic patients (adjusted hazard ratio (aHR), 1.96; 95% CI, 1.29-2.97; P = 0.002) but no significant association with mortality in asymptomatic patients (aHR, 0.83; 95% CI, 0.37-1.87; P = 0.652). When compared with GSV, prosthetic conduits were associated with a 2-fold increased risk of 1-y major amputation or death when used for repair in symptomatic patients (aHR, 2.03; 95% CI, 1.40-2.94; P < 0.001) but no significant association with mortality in asymptomatic patients (aHR, 0.91; 95% CI, 0.42-1.98; P = 0.816). Comparing bypass with other veins to the GSV among patients with symptomatic disease, there was no statistically significant difference in major amputation risk (HR; 2.44; 95% CI, 0.55-10.82; P = 0.242) and no difference in the adjusted risk of all-cause mortality (aHR, 0.77; 95% CI, 0.26-2.44; P = 0.653). There were no differences in the adjusted risk of loss of primary patency comparing other veins to GSV (HR, 1.53; 95% CI, 0.85-2.76; P = 0.154) and prosthetic conduits to GSV (HR, 0.85; 95% CI, 0.57-1.26; P = 0.422). CONCLUSIONS: This large study shows that among patients undergoing OPAR, 1-y primary patency does not differ between conduit types. However, prosthetic conduits are associated with significantly higher risk of amputation and death compared to GSV among symptomatic patients. Though non-GSV autologous veins are less often used for OPAR, they have comparably acceptable outcomes as GSV.

Impact of Statins on Survival and Limb Salvage in Patients Undergoing Peripheral Endovascular Intervention for Chronic Limb-Threatening Ischemia.

BACKGROUND: Statin therapy is recommended in all patients with peripheral arterial disease (PAD). Its impact on reduction in mortality has been well-documented, yet effect on limb-specific outcomes has been less conclusive. Differences among PAD subgroups or variability of statin use may contribute to the inconsistent findings. We evaluated statin use in patients who underwent peripheral endovascular intervention (PVI) for chronic limb-threatening ischemia (CLTI) and its impact on overall survival (OS), amputation-free survival (AFS) and limb salvage (LS). METHODS: The national Vascular Quality Initiative was queried for the index PVI for CLTI during the period 2010-2016; follow-up (FU) through 2020. Demographics, comorbidities, operative details, and FU status were recorded. Patients were categorized as E-Statin: statin use pre-PVI through discharge (D/C) and FU or N-Statin: No statins pre-PVI, at D/C or any time during FU. The propensity score matched model (PSM) was constructed. Groups were compared using chi-square, Kaplan-Meier survival and Cox regression analysis. RESULTS: There were 9,089 index PVI in 8,402 patients; E-Statin: 7149 index PVI in 6,591 patients; and N-Statin: 1940 index PVI in 1811 patients. The mean age was 69 ± 12 years and 58% were male. Statin use was associated with improved 3-year OS-E Statin: 92.9% ± 0.9 versus N Statin: 91.1% ± 2.2%; P = 0.003; hazard ratio (HR): Exp (B) (95% confidence interval): 0.66 (0.44-0.99); P = 0.047 and remained significant following PSM: E Statin: 95.1% ± 0.2% versus 90.8% ± 0.3%; P = 0.02; HR: 0.50 (0.27-0.92); P = 0.025. No significant differences in 3-year LS or AFS were noted between the prematched groups; LS: E Statin: 83.7% ± 0.8 versus N Statin: 84.0% ± 1.7%; P = 0.89; HR: 1.09 (0.88-1.35); P = 0.44; AFS-E Statin: 77.2% ± 1.1% versus 76.1% ± 2.5%; P = 0.17; HR: 0.97 (0.79-1.18); P = 0.74. or following PSM: AFS: 80.2% ± 2.8% vs. 74.7% ± 3.9%; P = 0.53, HR: 0.92 (0.72-1.19); P = 0.54; LS 85.3% ± 1.9% vs. 83.5% ± 2.6%; P = 0.51, HR: 1.08 (0.83-1.4); P = 0.57. Statins significantly improved LS among those with renal failure: 67.8% ± 2.6% vs. 59.7% ± 4.4%; P = 0.003; HR: 56 (0.40-0.79); P = 0.001. CONCLUSIONS: Statins are independently associated with improved OS in patients who undergo PVI for CLTI and should be considered for all barring intolerance. Statin use was associated with improved LS in patients with end-stage renal disease. Additional research is needed in this area, particularly, the impact of statin therapy in high-risk CLTI subgroups.

Transfer of Enterococcus faecium and Salmonella enterica during simulated postharvest handling of yellow onions (Allium cepa).

Bacterial transfer during postharvest handling of fresh produce provides a mechanism for spreading pathogens, but risk factors in dry environments are poorly understood. The aim of the study was to investigate factors influencing bacterial transfer between yellow onions (Allium cepa) and polyurethane (PU) or stainless steel (SS) under dry conditions. Rifampin-resistant Enterococcus faecium NRRL B-2354 or a five-strain cocktail of Salmonella was inoculated onto onion skin or PU surfaces at high or moderate levels using peptone, onion extract, or soil water as inoculum carriers. Transfer from inoculated to uninoculated surfaces was conducted using a texture analyzer to control force, time, and number of contacts. Transfer rates (ratio of recipient surface to donor surface populations) of E. faecium (4-5%) were significantly higher than those of Salmonella (0.5-0.6%) at the high (7 log CFU/cm2) but not moderate (5 log CFU/cm2) inoculum levels. Significantly higher populations of E. faecium transferred from onion to PU than from PU to onion. The transfer rates of E. faecium were impacted by inoculum carrier (61% [onion extract], 1.6% [peptone], and 0.31% [soil]) but not by inoculation level or recipient surface (PU versus SS). Bacterial transfer during dry onion handling is significantly dependent on bacterial species, inoculation levels, inoculum carrier, and transfer direction.

Survival of Listeria monocytogenes and Salmonella in citrus storage waxes or on lemons held under common commercial storage conditions.

To prolong cold storage, diluted storage waxes are applied to washed lemons after harvest and before packing, without drying steps, to reduce premature rotting and water loss. The survival of Listeria monocytogenes and Salmonella in undiluted and diluted storage waxes (S1-S4), and on lemon surfaces under common commercial storage were investigated. Populations of L. monocytogenes declined more slowly than Salmonella in undiluted storage waxes over 24 h of storage at 4 or 22 °C. L. monocytogenes (inoculated at ∼6 log CFU/mL) was detected by enrichment in undiluted waxes S2, S3, and S4 after 75-135 days at 4 °C but not after 30, 10, or 105 days, respectively at 22 °C. L. monocytogenes survived better in diluted than in undiluted storage waxes at 22 °C. Populations of L. monocytogenes (∼6 log CFU/lemon) declined by 0.64-1.62 log on lemon surfaces right after waxing. Populations of L. monocytogenes decreased to <1.30 log CFU/lemon after 28 days (1:9 S1) or 75 days (other treatments) at 12 °C and ≥93% RH. Except for 1:9 S1, L. monocytogenes was detected by enrichment in all lemon samples over 87 days of storage. Packinghouses should consider the survival of L. monocytogenes and Salmonella in citrus storage waxes in their food safety programs.

Female sex portends increased risk of major amputation following surgical repair of symptomatic popliteal artery aneurysms.

OBJECTIVE: Popliteal artery aneurysms (PAAs) are rare in women, with only ∼5% of all PAAs occurring in women. The aim of the present study was to investigate whether sex disparities exist for patients treated with open PAA repair. METHODS: We reviewed all patients with PAAs who had undergone open PAA repair in the Vascular Quality Initiative from January 2010 to July 2021. Univariate analyses and multivariable logistic or Cox regression analyses controlling for potential confounders were performed. The study outcomes included primary patency, major amputation, overall survival, and amputation-free survival at 1 year. RESULTS: The study included 3807 adult patients, of whom 160 were women (4.2%). The female patients were younger (age, 66.1 years vs 68.3 years; P = .012) and less likely to have coronary artery disease (14.5% vs 23.4%; P = .009). However, the women were more likely to be taking aspirin (69.2% vs 60.4%; P = .019) and statins (67.8% vs 60.4%; P < .001) and to undergo repair for symptomatic disease (77.5% vs 64.1%; P = .001). No difference was found between the women and men in primary patency (95.2% vs 90.8%; P = .230) and overall survival (94.3% vs 96.1%; P = .270). Amputation-free survival was lower for women than for men (91.4% vs 95.3%; P = .033). This finding resulted from by lower freedom from major amputation for women (96.1% vs 98.9%; P = .010). After adjustment for confounders, no differences were found between the women and men regarding the loss of primary patency and all-cause mortality. For symptomatic PAAs, the risk of major amputation was threefold greater for women (adjusted hazard ratio, 3.09; 95% confidence interval, 1.05-9.06; P = .040), and the risk of the composite end point of major amputation or death was twofold higher for women than for men (adjusted hazard ratio, 1.97; 95% confidence interval, 1.02-3.79; P = .043). CONCLUSIONS: In our large national study of patients with PAAs, women were more likely to be treated for symptomatic PAAs. The risk of 1-year major amputation was threefold greater for women with symptomatic PAAs than for men with a similar presentation. Early recognition and treatment of PAAs in women before the PAAs have become symptomatic could optimize limb salvage outcomes in women.

P2Y12 inhibitor monotherapy is associated with superior outcomes as compared with aspirin monotherapy in chronic limb-threatening ischemia.

OBJECTIVE: Antiplatelet therapy is recommended in patients with peripheral arterial disease to reduce cardiovascular risk and improve outcomes. However, issues including the drug of choice and use of dual antiplatelet therapy (DAPT) vs monotherapy remain unclear. This study aims to compare the impact of aspirin (ASA) monotherapy, P2Y12 monotherapy, and DAPT on limb salvage (LS), amputation-free survival (AFS), and overall survival (OS) in patients undergoing lower extremity peripheral endovascular intervention (PVI) for chronic limb-threatening ischemia (CLTI). METHODS: The Vascular Quality Initiative PVI registry was used to identify index procedures completed for CLTI between March 1, 2010 and September 30, 2017. Patients were categorized by antiplatelet use at the time of last follow-up. Patients not on antiplatelet therapy were compared with ASA, P2Y12 monotherapy, and DAPT. Propensity score-matched samples were created for direct ASA vs P2Y12 and P2Y12 vs DAPT comparisons; veracity was confirmed by χ2 and Hosmer-Lemeshow tests. Kaplan-Meier and Cox regression were performed for OS, AFS, and LS. RESULTS: A total of 12,433 index PVI were completed for CLTI in 11,503 subjects in the pre-matched sample. Antiplatelet use at follow-up was: 12% none, 31% ASA, 14% P2Y12, and 43% DAPT. Median follow-up was 1389 days. P2Y12 monotherapy was associated with improved outcomes as compared with ASA monotherapy, OS (87.8% vs 85.5%l P = .026; Cox hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.98; P = .03), AFS (79.6% vs 74.8%; P < .001; Cox HR, 0.75; 95% CI, 0.65-0.86; P < .001) and LS (89.5% vs 86.8%; P = .013; Cox HR, 0.74; 95% CI, 0.60-0.91; P = .004). P2Y12 monotherapy and DAPT had comparable OS (87.8% vs 88.9%; P = .62; Cox HR, 0.94; 95% CI, 0.77-1.14; P = .50), AFS (79.6% vs 81.5%; P = .33; Cox HR, 0.92; 95% CI, 0.78-1.07; P = .28), and LS (91.7% vs 89.4; P = .03; Cox HR, 0.80; 95% CI, 0.64-1.00; P = .06). CONCLUSIONS: P2Y12 monotherapy was associated with superior OS, AFS, and LS as compared with ASA monotherapy, and comparable OS, LS, and AFS with DAPT in patients undergoing PVI for CLTI. P2Y12 monotherapy may be considered over ASA monotherapy and DAPT in patients with CLTI, especially in patients with high bleeding risk.

National survey of vascular surgery residents and fellows on radiation exposure and safety practices.

OBJECTIVE: The objective of the present study was to evaluate radiation safety practices, radiation training, and radiation exposure among senior vascular residents and fellows in Accreditation Council for Graduate Medical Education-accredited programs across the United States. METHODS: Anonymous surveys were sent to all Accreditation Council for Graduate Medical Education program directors to be distributed to postgraduate year 4 to 7 vascular trainees for completion. The survey questions focused on program type (single vs multiple hospital site), familiarity with their radiation officer, formal radiation training, frequency of radiation feedback, use of safety equipment, and adherence to as low as reasonably achievable principles. RESULTS: A total of 95 trainees responded (27% response rate). Of the 95 trainees, 49 (51.6%) had reported they had never met their radiation safety officer, 74 (77.9%) reported they had received formal radiation safety education, 50 (53%) reported receiving feedback regarding their monthly radiation exposure, and 24 (25%) reported never having received such feedback. All the findings were more common among the multiple hospital site program respondents. CONCLUSIONS: It should be of significant concern that such a high number of trainees have been exceeding radiation exposure limits. Programs should strive to reduce radiation exposure through formal training, provision of safety equipment, modeling by attendings of adherence to as low as reasonably achievable principles, and timely feedback on radiation exposure.

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis.

BACKGROUND: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment. METHODS: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression. RESULTS: A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2-3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG. CONCLUSIONS: These results show that conventional treatments for MG are not adequately managing patients' symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Real-world assessment of the relationship between migraine-related disability and healthcare costs in the United States.

OBJECTIVE: The objective of this study was to determine the associations among migraine disability assessment scores, healthcare resource utilization (HCRU; medical visits and pharmacy use) and direct medical costs among people with episodic migraine in a real-world setting. BACKGROUND: Migraine is a public health concern associated with a substantial economic burden in the United States. However, the association between migraine disability and direct medical costs among people with migraine is unknown. METHOD: This retrospective, cohort study used claims and electronic health record data from the Decision Resources Group database. Adults with migraine with or without aura, defined by International Classification of Disease Revision 9 (ICD-9) or ICD Revision 10 (ICD-10) codes, and a completed Migraine Disability Assessment Scale (MIDAS) questionnaire from January 2016 to December 2018 were included (chronic migraine codes not included). The associations of MIDAS score with the cost of HCRU for the 6 months after MIDAS assessment were explored. Results were stratified by treatment setting. RESULTS: Among 7662 included patients, MIDAS scores were distributed as: 3348 (43.7%; I, little/none), 1107 (14.4%; II, mild), 1225 (16.0%; III, moderate), 893 (11.7%; IVa, severe), and 1089 (14.2%; IVb, very severe). Worsening disability was associated with higher medical costs (adjusted from a multivariable model). In the primary care setting, healthcare visit costs were $206 (95% confidence interval: $144-294) for grade I and $631 ($384-1036) for grade IVb patients; corresponding pharmacy costs were $203 (grade I; $136-301) and $719 (grade IVb; $410-1259). For specialty care (e.g., neurologist), healthcare visits cost $509 ($411-629) for grade I and $885 ($634-1236) for grade IVb patients; corresponding pharmacy costs were $494 (grade I; $378-645) and $1020 (grade IVb; $643-1620). CONCLUSION: Higher levels of migraine-related disability (MIDAS assessed) are associated with increased HCRU costs among Americans with episodic migraine. Migraine disability assessment could be useful in the development, testing, and prescription of cost-effective treatments for people with high migraine-related disability.

A stated preference survey to explore patient preferences for novel preventive migraine treatments.

OBJECTIVE: The objective of this study was to explore patient preference for attributes of calcitonin gene-related peptide (CGRP) inhibitors for the preventive treatment of migraine and to describe differences in treatment preferences between patients. BACKGROUND: CGRP inhibitors are a novel class of migraine drugs specifically developed for the preventive treatment of migraine. Clinicians should understand patient preferences for CGRP inhibitors to inform and support prescribing choices. METHODS: Patients with migraine in the US and Germany were recruited to participate in an online discrete choice experiment (DCE) survey, which presented hypothetical treatment choices using five attributes: mode of administration, side effects, migraine frequency, migraine severity, and consistency of treatment effectiveness. Attribute selection was informed by a literature review and semi-structured patient interviews (n = 35), and evaluated using patient cognitive debriefing interviews (n = 5). RESULTS: Of 680 who consented to participate, 506 participants completed the survey and were included in the study (US = 257; Germany = 249). Overall, participants placed highest importance (preference weight, beta = 1.65, p < 0.001) on the treatment's ability to reduce the severity of migraine (mild vs. unchanged severity), followed by consistent treatment effectiveness (beta = 1.13, p < 0.001), and higher chance of reduced migraine frequency (beta = 1.00, p < 0.001). Participants preferred an oral tablet every other day (beta = 1.00, p < 0.001) over quarterly infusion, quarterly injections (p = 0.019), or monthly injection (p < 0.001). Preference for all treatment attributes were heterogeneous, and the subgroup analyses found that participants naïve to CGRP monoclonal antibody treatments had a stronger preference for oral therapy compared to those with such experience (p = 0.006). CONCLUSION: In this DCE assessing CGRP inhibitors attributes, the main driver of patient choice was treatment effectiveness, specifically reduced migraine severity, and consistent treatment effectiveness. Further, patients exhibited an overall preference for an oral tablet every other day over injectables. Patients' experience with previous treatments informs the value they place on treatment characteristics.

Need for Routine Preoperative Insertion of Indwelling Urinary Catheter Prior to Endovascular Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Evaluate outcomes following urinary catheter (UC) versus no urinary catheter (NUC) insertion in elective endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: Retrospective record review of all elective EVAR at a university affiliated medical center over a 5-year period. Statistical analysis included Chi Sq, Independent Student t Test. RESULTS: Six surgeons performed 272 elective EVAR. Three surgeons preferred selective insertion of indwelling UC, such that 86 (32%) EVAR were completed without indwelling urinary catheters (NUC). Differences between NUC versus UC included; male: (86% vs. 70%; P = 0.004), CAD: (45% vs. 33%; p = 0.046), conscious sedation: (36% vs. 8%; P < 0.001), bilateral percutaneous EVAR (PEVAR): (100% vs. 90%; P = 0.01), within ProglideTM IFU guidelines (87% vs 75%; P = .05), major adverse operative event (MAOE): (3.5% vs. 10%; P = 0.05) and mean operative time (185 ± 73 vs. 140 ± 37; P < 0.001). Intra-operative catheterization was never required among NUC. Postoperative adverse urinary events (AUE) were more common among UC (11.4% vs. 8.1%; P = 0.41); with longer times to straight catheterization/reinsertion (1575 ± 987 vs, 522 ± 269 min; P = 0.015) and lower likelihood of eligibility for same day discharge (SDD); (41% vs. 59%; P = 0.008). Ineligibility for SDD was due to AUE in 18% of UC patients. CONCLUSION: Selective preoperative UC insertion should be considered for EVAR, with particular consideration to no preoperative catheterization in men meeting Proglide IFU. Adverse urinary events occurred less frequently among NUC and were identified/ treated earlier. Moreover, AUEs were the most common reason for potential SDD ineligibility among UC patients. Selective policies may facilitate SDD.

Salmonella enterica subsp. enterica virulence potential can be linked to higher survival within a dynamic in vitro human gastrointestinal model.

Salmonella enterica subsp. enterica is one of the leading causes of human foodborne infections and several outbreaks are now associated with the consumption of fresh fruit and vegetables. This study aims at evaluating whether Salmonella virulence can be linked to an enhanced ability to survive successive digestive environments. Thirteen S. enterica strains were selected according to high and low virulence phenotypes. Lettuce inoculated separately with each S. enterica strain was used as food matrix in the TNO gastrointestinal model (TIM-1) of the human upper gastrointestinal tract. During the passage in the stomach, counts determined using PMA-qPCR were 2-5 logs higher than the cultivable counts for all strains indicating the presence of viable but non-cultivable cells. Bacterial growth was observed in the duodenum compartment after 180 min for all but one strain and growth continued into the ileal compartment. After passage through the simulated gastrointestinal tract, both virulent and avirulent S. enterica strains survived but high virulence strains had a significantly (p = 0.004) better average survival rate (1003 %-3753 %) than low virulence strains (from 25 % to 3730%). The survival rates of S. enterica strains could be linked to the presence of genes associated with acid and bile resistance and their predicted products. The presence of single nucleotide polymorphisms may also impact the function of virulence associated genes and play a role in the resulting phenotype. These data provide an understanding of the relationship between measured virulence potential and survival of S. enterica during dynamic simulated gastrointestinal transit.

Monthly migraine days, tablet utilization, and quality of life associated with Rimegepant - post hoc results from an open label safety study (BHV3000-201).

BACKGROUND: The objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks. METHODS: Eligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-specific quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free. RESULTS: One thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of 0.08 incremental QALYs were associated with rimegepant use. CONCLUSION: For subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03266588 .

Real-World experience of interictal burden and treatment in migraine: a qualitative interview study.

BACKGROUND: The debilitating nature of migraine attacks is widely established; however, less is known about how the interictal burden (i.e., how patients are affected in-between migraine episodes) of migraine impacts on patients' health-related quality of life (HRQL). Acute and preventive treatments may lift the burden of the disease, but they often have unwanted side effects and limited effectiveness. The objective of this study was to understand the interictal burden of migraines, from the patient perspective, and to explore patient experience with migraine treatments. METHODS: Participants (n=35) with a self-reported diagnosis of migraine were recruited in the US, UK and Canada, including a subgroup of patients who had taken calcitonin gene-related peptide monoclonal antibody (CGRP mAb) treatment for at least three months. Participants completed a background questionnaire, followed by a semi-structured interview via telephone or video call. The interviews explored patients' migraine symptoms, perception of interictal burden and treatment experience. The interview transcripts were analysed using thematic analysis. RESULTS: The most reported migraine symptom was migraine pain, followed by aura, sensory sensitivity and nausea. Most participants reported interictal impact on HRQL, lifestyle changes they made to avoid triggers or in anticipation of an attack, impacts on work, career, daily activities and relationships. Emotional impacts were reported by all participants, including anger, depression, anxiety and hopelessness. Many participants who took preventive treatments reported improvements in HRQL and functioning but still experienced breakthrough attacks. Among patients who took CGRP mAbs, participants noted varying consistency of treatment effectiveness between treatment administrations. CONCLUSION: This study detailed the additional HRQL impact of migraine in-between migraine attacks and described the unmet need for effective treatment options to prevent and mitigate migraine attacks.

Measuring interictal burden among people affected by migraine: a descriptive survey study.

BACKGROUND: Previous research has extensively documented the impact of migraine episodes ('ictal') on patients' health-related quality of life. Few studies have looked at the impact of migraine on migraine-free days ('interictal'). This study was designed to describe interictal burden of migraine in a mixed group of people affected by migraine and to explore patient characteristics associated with interictal burden. METHODS: People with migraine in the United States (US) and Germany were recruited for a cross-sectional online survey, including a subgroup treated with calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). The survey included the Migraine Interictal Burden Scale (MIBS-4), Headache Impact Test (HIT-6), and items measuring patient demographics, clinical and treatment background. Data were analyzed using descriptive statistics and linear regression. RESULTS: Five hundred six people with migraine completed the survey (US: n = 257; Germany: n = 249), of whom 195 had taken a CGRP mAb for three or more months. Participants had a mean of 8.5 (SD = 6.4) Monthly Migraine Days (MMD) and 10.4 (SD = 7.1) Monthly Headache Days (MHD). The mean MIBS-4 score was 6.3 (SD = 3.4), with 67% reporting severe interictal burden (MIBS-4: ≥5). The mean HIT-6 score was 65.3 (SD = 6.0), with 86% reporting severe migraine impact (HIT-6: ≥60). MIBS-4 was correlated with the HIT-6 (r = 0.37), MMD and MHD (both r = 0.27). The HIT-6, MMD, MHD, CGRP mAb treatment, and depression all had an independent positive association with the MIBS-4. CONCLUSION: Two-thirds of the study sample reported substantial interictal burden. Whilst interictal burden was associated with migraine frequency and impact of migraine attacks, study results also show it represented a distinct aspect of the overall disease burden. Study findings further indicate unique associations between interictal burden and depression. A unique positive association between interictal burden and CGRP mAb treatment suggests a remaining unmet need among people affected by migraine treated with CGRP mAb.