Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings.

BACKGROUND: The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life. METHODS: This prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods. RESULTS: Of 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88-9.08), 5.50 (95% CI, 4.21-7.07), and 2.87 (95% CI, 2.18-3.70) cases/100 person-years in children aged 0-5, 6-11, and 12-23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0-5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0-2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs. CONCLUSIONS: A substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most. Clinical Trials Registration. NCT01995175.

Redo-aortic valve replacement in prior stentless prosthetic aortic valves: Transcatheter versus surgical approach.

OBJECTIVES: The objective was to compare outcomes of redo-aortic valve replacement (AVR) via surgical or transcatheter approach in prior surgical AVR with large percentage of prior stentless surgical AVR. BACKGROUND: With the introduction of transcatheter aortic valve replacement (TAVR), patients with increased surgical risks now have an alternative to redo surgical AVR (SAVR), known as valve-in-valve (ViV) TAVR. Stentless prosthetic aortic valves present a more challenging implantation for ViV-TAVR given the lack of structural frame. METHODS: We performed a retrospective study of 173 subjects who have undergone SAVR (N = 100) or ViV-TAVR (N = 73) in patients with prior surgical AVR at Wake Forest Baptist Medical Center from 2009 to 2019. Our study received the proper ethical oversight. RESULTS: The average ages in redo-SAVR and ViV-TAVR groups were 58.03 ± 13.86 and 66.57 ± 13.44 years, respectively (p < 0.0001). The redo-SAVR had significantly lower STS (2.78 ± 2.09 and 4.68 ± 5.51, p < 0.01) and Euroscores (4.32 ± 2.98 and 7.51 ± 8.24, p < 0.05). The redo-SAVR group had higher percentage requiring mechanical support (8% vs. 0%, p < 0.05) and vasopressors (53% vs. 0%, p < 0.0001), longer length of stay (13.65 ± 11.23 vs. 5.68 ± 7.64 days, p < 0.0001), and inpatient mortality (16% vs. 2.78%, p < 0.005). At 30-day follow-up, redo-SAVR group had higher rates of acute kidney injury (10% vs. 0%, p < 0.01), however ViV-TAVR group had more new left bundle branch blocks (6.85% vs. 0%, p < 0.05). No significant differences regarding re-hospitalization rates, stroke, or death up to 1-year. CONCLUSION: Although the ViV-TAVR group had higher risk patients, there were significantly fewer procedural complications, shorter length of stay, and similar mortality outcomes up to 1-year follow-up.

Reduction in the severity and duration of headache following fremanezumab treatment in patients with episodic and chronic migraine.

OBJECTIVE: To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM). BACKGROUND: Fremanezumab is a fully humanized monoclonal antibody (IgGΔa) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency. METHODS: This exploratory post hoc analysis included data from three randomized, double-blind, 12-week, phase 3 studies (HALO CM, HALO EM, and FOCUS). In all three studies, patients with CM or EM were randomized 1:1:1 to receive subcutaneous quarterly fremanezumab (month 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (month 1/2/3: 675 mg [CM], 225 mg [EM]/225 mg/225 mg), or matched monthly placebo. Changes from baseline were evaluated in the proportion of headache days of at least moderate severity, peak severity of headache days, mean monthly headache hours (of any severity and at least moderate severity), and mean headache hours per headache day of any severity. RESULTS: A total of 2843 patients were randomized with 2823 patients included in the efficacy analyses across all studies (HALO CM, N = 1121; HALO EM, N = 865; FOCUS, N = 837). At study baseline, mean (standard deviation [SD]) monthly number of headache days rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 13.2 (5.5), 12.8 (5.8), and 13.3 (5.8) in HALO CM; 7.2 (3.1), 6.8 (2.9), and 6.9 (3.1) in HALO EM; and 12.4 (5.8), 12.7 (5.8), and 12.8 (5.9) in FOCUS. Patients experienced significant least-squares mean (LSM; 95% confidence interval) percent reductions from baseline in monthly number of headache days rated moderate or severe during the 12 weeks: HALO CM, quarterly fremanezumab, 34.5% (-39.8, -29.2) and monthly fremanezumab, 36.2% (-41.4, -31.0) vs. placebo, 19.6% (-20.0, -14.3); HALO EM, quarterly fremanezumab, 40.7% (-47.8, -33.5) and monthly fremanezumab, 43.4% (-50.4, -36.3) vs. placebo, 17.9% (-24.9, -11.0); and FOCUS, quarterly fremanezumab, 36.5% (-41.9, -31.1) and monthly fremanezumab, 38.6% (-44.0, -33.3) vs. placebo, 3.5% (-8.9, 1.8); all p < 0.0001. At study baseline, mean (SD) number of monthly headache hours rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 66.4 (58.8), 68.0 (53.9), and 68.5 (57.0) in HALO CM; 33.3 (25.4), 31.7 (23.7), and 31.6 (23.2) in HALO EM; and 59.2 (54.7), 64.3 (65.2), and 65.9 (70.2) in FOCUS. Significant reductions were observed in LSM (standard error) number of monthly headache hours of at least moderate severity: HALO CM, quarterly fremanezumab, 24.4 (2.5) and monthly fremanezumab, 26.4 (2.3) vs. placebo, 14.1 (2.5); HALO EM, quarterly fremanezumab, 14.5 (1.4) and monthly fremanezumab, 15.5 (1.3) vs. placebo, 8.1 (1.3); and FOCUS, quarterly fremanezumab, 16.8 (3.0) and monthly fremanezumab, 18.3 (3.0) vs. placebo, 2.3 (3.0); all p < 0.001. CONCLUSION: These analyses demonstrated that quarterly or monthly treatment with fremanezumab significantly reduced headache severity and duration in patients with CM or EM, including in patients with documented inadequate response to two to four prior migraine preventive medication classes.

Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials.

BACKGROUND: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials? METHODS: We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL). RESULTS: Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations. CONCLUSIONS: Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

Assessment of the prognostic significance of low gradient severe aortic stenosis and preserved left ventricular function requires the integration of the consistency of stroke volume calculation and clinical data.

BACKGROUND: This study was to evaluate the prognostic significance of low gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF) with the integration of echocardiographic and clinical data. METHODS: The study included 172 patients with LG SAS (AVAi ≤ 0.6 cm2 /m2 , mean aortic pressure gradient < 40 mm Hg) and LVEF (≥ 50%). LV outflow tract diameters were measured at both the aortic valve annulus and 5 mm below the annulus for the measurement consistency. Patients were divided into the low flow LG SAS (LF/LG SAS: SVi < 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ) and normal-flow LG SAS groups (NF/LG SAS: SVi ≥ 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ). Echocardiographic findings and clinical data were systematically analyzed with mean follow-up of 3.0 ± 1.6 years. RESULTS: LF/LG SAS had significantly smaller AVAi, lower SVi, a higher prevalence of atrial fibrillation (28% vs 12% P = .01) and diabetes (47% vs 27% P = .007) and lower 3-year cumulative survival than NF/LG SAS. Multivariable analysis showed that dyspnea, renal dysfunction (CI 1.42-3.99, P < .01), left atrial diameter, and SVi were independently associated with an increased risk for all-cause mortality. Aortic valve intervention (AVI) improved survival in LF/LG SAS (68% vs 48%, P < .05) in comparison with medical management (HR: 4.20, CI: 1.12-15.76, P = .03), but only modestly in NF/LG SAS (75% vs 65% P > .05). CONCLUSION: Outcome of LG SAS was independently associated with clinical characteristics. AVI likely improved outcome of LF/LG SAS who had high-risk clinical characteristics and unfavorable echocardiographic findings.

Improvements across a range of patient-reported domains with fremanezumab treatment: results from a patient survey study.

BACKGROUND: The long-term safety and efficacy of fremanezumab were evaluated in a 52-week extension study (NCT02638103). Patient satisfaction with fremanezumab, dosing preferences, and patient-reported outcomes were assessed in a subpopulation who completed the extension study and consented to a follow-up questionnaire. METHODS: In the extension study (N = 1842), adults with migraine were randomized to quarterly or monthly fremanezumab. After completing active treatment, patients answered a survey evaluating patient satisfaction, treatment and dosing preferences, and changes in patient-reported outcomes. RESULTS: Of the 557 patients who could have been contacted upon completing the extension study, 302 consented and 253 completed the survey. The mean (standard deviation) satisfaction rating for fremanezumab was 6.1 (1.4; 1 = "extremely dissatisfied" to 7 = "extremely satisfied"). Most patients (175 [69.2%]) preferred quarterly over monthly fremanezumab dosing. Among patients taking antiepileptics (most common class of prior preventive medication; n = 130), 91.5% preferred fremanezumab. Patients reported improvements in anxiety (74 [67.9%]), sleep quality (143 [56.5%]), and quality of time spent with others (210 [83.0%]) with fremanezumab. CONCLUSION: In this study, treatment satisfaction with fremanezumab was high, most patients preferred quarterly fremanezumab dosing, and fremanezumab was generally preferred to prior preventive medications. TRIAL REGISTRATION: ClinicalTrials.gov NCT02638103 (HALO LTS), registered December 22, 2015.

A comparison of valve-in-valve transcatheter aortic valve replacement in failed stentless versus stented surgical bioprosthetic aortic valves.

OBJECTIVES: The objectives of this study were to compare short- and intermediate-term clinical outcomes, procedural complications, TAVR prosthesis hemodynamics, and paravalvular leak (PVL) in stentless and stented groups. BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is an alternative to surgical redo for bioprosthetic valve failure. There have been limited data on ViV in stentless surgical valves. METHODS: We retrospectively analyzed 40 patients who underwent ViV TAVR in prior surgical bioprosthetic valves at Wake Forest Baptist Medical Center from October 2014 to September 2017. Eighty percent (32/40) ViV TAVRs were in stentless, while 20% (8/40) were in stented bioprosthetic valves. RESULTS: The primary mode of bioprosthetic valve failure for ViV implantation in the stentless group was aortic insufficiency (78%, 25/32), while in the stented group was aortic stenosis (75%, 6/8). The ViV procedure success was 96.9% (31/32) in stentless group and 100% in stented group (8/8). There were no significant differences in all-cause mortality at 30 days between stentless and stented groups (6.9%, 2/31 versus 0%, 0/8, P = 0.33) and at 1 year (0%, 0/25 versus 0%, 0/5). In the stentless group, 34.4% (11/32) required a second valve compared to the stented group of 0% (0/8). There was a significant difference in the mean aortic gradient at 30-day follow-up (12.33 ± 6.33 mmHg and 22.63 ± 8.45 mmHg in stentless and stented groups, P < 0.05) and at 6-month follow-up (9.75 ± 5.07 mmHg and 24.00 ± 11.28 mmHg, P < 0.05), respectively. CONCLUSIONS: ViV in the stentless bioprosthetic aortic valve has excellent procedural success and intermediate-term results. Our study shows promising data that may support the application of TAVR in stentless surgical aortic valve. However, further and larger studies need to further validate our single center's experience.

Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia.

PURPOSE: Tardive dyskinesia (TD) is a common but serious hyperkinetic movement disorder and side effect of antipsychotic medications used to treat bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). The purpose of this study was to evaluate health-related quality of life (HRQoL) in a population with diagnoses for BD, MDD, or SZ by comparing patients with TD (n = 197) with those without TD (n = 219). HRQoL in each group was also compared with HRQoL of the general population. METHODS: This study employed a cross-sectional web-based survey. HRQoL was assessed by four instruments: the SF-12 Health Survey, Version 2 (SF-12v2), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), the Social Withdrawal subscale of the Internalized Stigma of Mental Illness Scale (SW-ISMI); and two questions on movement disorders. RESULTS: Patients with TD had significantly worse HRQoL and social withdrawal than those without. The differences were more pronounced for physical HRQoL domains than for mental health domains. Patients with more-severe TD, assessed through either self-rating or clinician rating, experienced significantly worse HRQoL than did those with less-severe TD. The impact of TD was substantially greater in patients with SZ than in those with BD or MDD. Compared with the general population, patients with BD, MDD, or SZ experienced significantly worse HRQoL regardless of TD status, although this deficit in HRQoL was greater among those with TD. CONCLUSIONS: The presence of TD is associated with worse HRQoL and social withdrawal. The most severe impact of TD is on physical aspects of patients' HRQoL.

Comparison of outcomes with surgical cut-down versus percutaneous transfemoral transcatheter aortic valve replacement: TAVR transfemoral access comparisons between surgical cut-down and percutaneous approach.

OBJECTIVES: The objective is to compare the short-term (30 days) and late (12 months) vascular adverse events in patients undergoing transfemoral (TF)-transcatheter aortic valve replacement (TAVR) by surgical cut-down (SC) vs. percutaneous (PC) approaches. BACKGROUND: Programs continue to utilize both approaches in TF-TAVR. There are limited data comparing outcomes by SC vs. PC approaches and long-term effects of endovascular intervention facilitated hemostasis on late vascular adverse events. METHODS: A total of 146 men and women aged 79.7 ± 10.0 years with severe aortic stenosis deemed extreme or high risk for surgery underwent TAVR via TF access. 61 had SC and 85 had PC approaches. Valve Academic Research Consortium (VARC-2) outcomes were assessed at an average of 12.1 months after TAVR. RESULTS: Hospital length of stay (LOS) post-TAVR was shorter for the PC group compared to the SC group (5.1 ± 3.9 vs. 8.2 ± 6.6 days; P < 0.001). More patients were discharged directly to home in the PC than the SC group (85.9% vs. 68.9%, P < 0.05). At 30 days, there were 13/61 (21.3%) and 16/85 (18.8%; P < 0.05) of any vascular events, and 2/61 (3.3%) and 2/85 (2.4%; P = 0.73) major vascular events in the SC and PC groups, respectively. There was no difference in all-cause mortality between the SC (14/61; 23%) and PC groups [17/85 (20%); P = 0.34]. There was no difference in any [4/33 (12%) vs. 3/43 (7%); P = 0.84] or major vascular adverse events [1/33 (3%) vs. 1/43 (2%); P = 0.79] in subjects that underwent adjunctive endovascular intervention compared to those who did not, respectively. There were no statistically significant univariate or multivariate predictors of any vascular event at 12 months when comparing SC to PC groups. CONCLUSION: For TF TAVR, the PC approach, when compared to the SC approach, is associated with a shorter hospital LOS and higher rate of direct discharge to home with similar risk of vascular complications, late vascular adverse events, and all-cause mortality at 12 months.

Comparison of paravalvular aortic leak characteristics in the Medtronic CoreValve versus Edwards Sapien Valve: Paravalvular aortic leak characteristics.

OBJECTIVES: Temporally quantify and localize paravalvular aortic leak (PVL) after transcatheter aortic valve replacement (TAVR) in the Medtronic CoreValve (MCV) versus the Edwards Sapien Valve (ESV). BACKGROUND: In order to increase the precision of THV selection and PVL intervention, an understanding of PVL characteristics is essential. METHODS: The frequency, severity, and location of post-TAVR PVL were evaluated with transthoracic echocardiography pre-discharge, one month, and one-year post-procedure in 202 patients receiving a MCV (N = 120) or ESV (N = 81). This was done through application of a clock face to the short axis of the aortic valve in order to divide the area into three tertiles. RESULTS: Pre-discharge differences between PVL frequency and severity in the MCV and ESV lost significance over time. Localizing these trends, MCV PVL frequency and severity significantly decreased in the first and third tertiles during most time periods while PVL in the second tertile of the MCV or in any of the tertiles of the ESV failed to improve. Presence of pre-discharge PVL was predictive of 30-day HF readmission and/or death (OR = 3.16, 95% CI: 0.99-10.12). Presence of pre-discharge and 30-day PVL was predictive of 1-year HF readmissions and/or death (OR = 2.12, 95% CI: 1.09-4.13 and OR = 1.99, 95% CI: 0.96-4.12). CONCLUSIONS: When comparing the MCV and ESV, not all locations of PVL improve equally over time, which has implications for heart failure readmissions. This could be used to influence valve selection and to identify cases in which earlier intervention on PVL may be appropriate.

Comparative efficacy of different modalities for treatment of right heart thrombi in transit: a pooled analysis.

The objective was to compare the efficacy of treatment options for right heart thrombi (RHT) in transit. All published reports between 1992 and 2013 were identified and pooled. We analyzed 328 patients with RHT and pulmonary embolism (PE). The treatments administered were none in 11 patients (3.4%), anticoagulation (AC) with heparin in 70 patients (21.3%), thrombolytics in 122 patients (37.2%), catheter-related treatments in five patients (1.5%) and surgical embolectomy in 120 patients (36.6%). The overall short-term mortality for the entire cohort was 23.2%. The mortality rate associated with no therapy was highest at 90.9%. The mortality associated with AC alone was significantly higher than surgical embolectomy or thrombolysis (37.1% vs 18.3% vs 13.7%, respectively). In univariate analysis, any therapy was better than no therapy with a favorable odds of 16.92 (95% CI 2.05-139.87) for AC, 61.76 (95% CI 7.42-513.81) for thrombolysis and 44.54 (95% CI 5.42-366.32) for surgical embolectomy. In multivariate analysis with age and hemodynamic status entered as covariates, thrombolytic therapy was better than AC with favorable odds of 4.83 (95% CI 1.52-15.36). Similarly, there was a trend in favor of surgical embolectomy with an odds of 2.61 (95% CI 0.90-7.58). The estimated probability of survival in hemodynamically unstable patients with AC, surgical embolectomy and thrombolysis was 47.7%, 70.45% and 81.5%, respectively. There was no significantly increased risk of complications with thrombolytic therapy. In conclusion, left untreated, patients with RHT and PE have very high mortality. Aggressive management with thrombolysis or surgical thrombectomy may be more effective than AC alone in the management of these patients.

Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study.

RATIONALE: MultiStem is an allogeneic bone marrow-derived adherent adult stem cell product that has shown efficacy in preclinical models of acute myocardial infarction (AMI). In this phase I clinical trial in patients with first ST-elevation-myocardial infarction (STEMI), we combine first-in-man delivery of MultiStem with a first-in-coronary adventitial delivery system to determine the effects of this system on left ventricular function at 4 months after AMI. OBJECTIVE: Test the effects of adventitial delivery of Multistem in the peri-infarct period in patients with first STEMI. METHODS AND RESULTS: This study was a phase I, open-label, dose-escalating registry control group study. Nineteen patients received MultiStem (20 million, n=6; 50 million, n=7; or 100 million, n=6) and 6 subjects were assigned to the registry control group. Two to 5 days after AMI, we delivered MultiStem to the adventitia of the infarct-related vessel in patients with first-time STEMI. All patients underwent primary percutaneous coronary intervention with resulting Thrombolysis In Myocardial Infarction grade 3 flow and with ejection fraction (EF) ≤45% as determined by echocardiogram or left ventriculogram within 12 hours of primary percutaneous coronary intervention. The cell product (20 million, 50 million, or 100 million) was well tolerated, and no serious adverse events were deemed related to MultiStem. There was no increase in creatine kinase-MB or troponin associated with the adventitial delivery of MultiStem. In patients with EF determined to be ≤45% by a core laboratory within 24 hours before the MultiStem injection, we observed a 0.9 (n=4), 3.9 (n=4), 13.5 (n=5), and 10.9 (n=2) percent absolute increases in EF in the registry, 20 million, 50 million, and 100 million dose groups, respectively. The increases in EF in the 50 million and 100 million groups were accompanied by 25.4 and 8.4 mL increases in left ventricular stroke volume. CONCLUSIONS: In this study, the delivery of MultiStem to the myocardium in patients with recent STEMI was well tolerated and safe. In patients who exhibited significant myocardial damage, the delivery of ≥50 million MultiStem resulted in improved EF and stroke volume 4 months later. These findings support further development of MultiStem in patients with AMI and they validate the potential of a system for delivery of adult stem cells at any time after primary percutaneous coronary intervention.

Prevalence of Sinus Mucosal Abnormalities on CT of the Head Performed for Headache When Compared With Those Performed for Other Indications.

Background There is a high prevalence of mucosal abnormalities of paranasal sinuses on CT Head scans performed for all indications. The purpose of this study is to see whether or not such abnormalities are more common in scans performed on patients presenting with headaches when compared with those without headaches. Methods Images of CT scans of the brain of 100 consecutive patients from each of the two study groups (a total of 200 scans) were retrospectively reviewed for the presence of sinus mucosal abnormalities and their Lund-Mackay (LM) scores were calculated. A corrected LM score was also calculated using a correction factor for non-visualized sinuses in some scans and osteomeatal complexes in all scans. Radiological reports for these scans were also reviewed to note whether or not they contained any comments on the sinuses. All the reviewed scans were performed between January 1, 2021 and January 22, 2021. Results In the headache group, 17 patients had an LM score above 4 (which was used as the main cut-off point for this study). In the non-headache group, 16 patients had a score greater than 4. The mean LM score in the headache group was 1.24 and in the non-headache group was 1.4. There has been no significant difference in the comparison when corrected LM scores were used. In the headache group, 22 radiology reports contained comments on the sinuses compared to 11 reports in the non-headache group. Conclusion Results of this study indicate that there is no significant difference in the prevalence of clinically important sinus mucosal abnormalities in patients who had a brain CT for headache when compared with other indications. It was found that radiologists tend to comment on the sinuses more often when the indication was headache. It may be reasonable for radiologists to consider reviewing this practice. This might reduce unnecessary referrals to ENT and, more importantly, avoid missing other reasons for headaches.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Diagnostic time course, treatment, and in-hospital outcomes for patients with ST-segment elevation myocardial infarction presenting with nondiagnostic initial electrocardiogram: a report from the American Heart Association Mission: Lifeline program.

BACKGROUND: Prior studies indicate that a subset of patients diagnosed as having ST-segment elevation myocardial infarction (STEMI) will have an initial non-diagnostic electrocardiogram (ECG) during evaluation. However, the timing of diagnostic ECG changes in this group is unknown. Our primary aim was to describe the timing of ECG diagnosis of STEMI in patients whose initial ECG was non-diagnostic. Secondarily, we sought to compare the delivery of American College of Cardiology/American Heart Association guidelines-based care and in-hospital outcomes in this group compared with patients diagnosed as having STEMI on initial ECG. METHODS: We analyzed data from 41,560 patients diagnosed as having STEMI included in the National Cardiovascular Data Registry ACTION Registry-GWTG from January 2007 to December 2010. We divided this study population into 2 groups: those diagnosed on initial ECG (N = 36,994) and those with an initial non-diagnostic ECG that were diagnosed on a follow-up ECG (N = 4,566). RESULTS: In general, baseline characteristics and clinical presentations were similar between the 2 groups. For patients with an initial non-diagnostic ECG, 72.4% (n = 3,305) had an ECG diagnostic for STEMI within 90 minutes of their initial ECG. There did not appear to be significant differences in the administration of guideline-recommended treatments for STEMI, in-hospital major bleeding (P = .926), or death (P = .475) between these groups. CONCLUSIONS: In a national sample of patients diagnosed as having STEMI, 11.0% had an initial non-diagnostic ECG. Of those patients, 72.4% had a follow-up diagnostic ECG within 90 minutes of their initial ECG. There did not appear to be clinically meaningful differences in guidelines-based treatment or major inhospital outcomes between patients diagnosed as having STEMI on an initial ECG and those diagnosed on a follow-up ECG.

Cost effectiveness of radial access for diagnostic cardiac catheterization and coronary intervention.

OBJECTIVES: To evaluate the cost effectiveness of diagnostic cardiac catheterizations (CATH) and coronary interventions (PCI) performed using radial artery (RA) access compared to femoral artery (FA) access. BACKGROUND: CATH and PCI performed from the RA reduce access site complications compared to FA, but can increase procedure duration, and equipment and contrast use. Whether resulting increases in utilization costs are offset by reduced costs of complications is uncertain. METHODS: In all, 6,726 CATH and PCI (RA, 3,368; FA, 3,358) were performed from January 2009 to December 2011. Procedural costs and cost of access site complications were compared for propensity-matched CATH (RA and FA, 1,222) and PCI (RA and FA, 570) throughout a complete transition of the lab from a preferred FA to preferred RA strategy. RESULTS: Adjusted mean total costs were $10 more (95% confidence interval $613 less to $610 more) for RA-CATH versus FA-CATH and $732 less ($1,345 less to $156 less) for RA-PCI versus FA-PCI. The incremental cost per vascular or bleeding complication avoided with RA-CATH was $1,265, whereas RA was economically dominant with lower costs and fewer complications compared to FA for PCI and all procedures. CONCLUSIONS: Radial access for CATH and PCI reduced access site complications and overall costs compared to FA procedures with similar baseline clinical and procedural characteristics, making it an economically advantageous strategy.

Workforce Crisis in Radiology in the UK and the Strategies to Deal With It: Is Artificial Intelligence the Saviour?

Radiology has seen rapid growth over the last few decades. Technological advances in equipment and computing have resulted in an explosion of new modalities and applications. However, this rapid expansion of capability and capacity has not been matched by a parallel growth in the number of radiologists. This has resulted in global shortages in the workforce, with the UK being one of the most affected countries. The UK National Health Service has been employing several conventional strategies to deal with the workforce situation with mixed success. The emergence of artificial intelligence (AI) tools that have the potential to increase efficiency and efficacy at various stages in radiology has made it possible for radiology departments to use new strategies and workflows that can offset workforce shortages to some extent. This review article discusses the current and projected radiology workforce situation in the UK and the various strategies to deal with it, including applications of AI in radiology. We highlight the benefits of AI tools in improving efficiency and patient safety. AI has a role along the patient's entire journey from the clinician requesting the appropriate radiological investigation, safe image acquisition, alerting the radiologists and clinicians about critical and life-threatening situations, cancer screening follow up, to generating meaningful radiology reports more efficiently. It has great potential in easing the workforce crisis and needs rapid adoption by radiology departments.

Adverse Events Reported with Therapies Targeting the CGRP Pathway During the First 6 Months Post-launch: A Retrospective Analysis Using the FDA Adverse Events Reporting System.

INTRODUCTION: Through 2018, three calcitonin gene-related peptide pathway-targeted monoclonal antibodies (CGRP mAbs) had received US Food and Drug Administration (FDA) approval for migraine prevention: erenumab, fremanezumab, and galcanezumab. METHODS: This retrospective analysis evaluated adverse events (AEs) spontaneously reported to the FDA Adverse Event Reporting System (FAERS) safety surveillance database during the first 6 months post-approval of erenumab (May 2018 to November 2018), fremanezumab (September 2018 to March 2019), and galcanezumab (September 2018 to March 2019). Reporting rates (RR) per 1000 exposed patients were calculated from number of reported events (when product classified as "primary suspect") in each AE category and estimated number of treated patients based on de-identified prescription data (IQVIA database) and were ranked on the basis of frequency for each product. RESULTS: RR per 1000 exposed patients for "migraine" (erenumab, 4.89; fremanezumab, 1.01; galcanezumab, 2.99), "headache" (3.32, 1.27, 3.07), and "drug ineffective" (3.68, 1.14, 1.69) were commonly reported for all three products, as were migraine-associated symptoms ("nausea": 2.94, 0.91, 1.09) and "injection-site" reactions ("pain": 2.94, 0.8, 4.9; "swelling": 0.56, 0.53, 1.25; "pruritus": 0.26, 0.63, 1.14; "erythema": 0.58, 0.71, 1.58). "Constipation" ranked second for erenumab (4.90) but did not make the top ten events for fremanezumab (0.46) or galcanezumab (0.76); cardiovascular events did not rank in the top ten AEs for any product. The frequency of serious outcomes was low, with ≤ 2% of AEs categorized as serious across the CGRP mAbs. CONCLUSION: These results aid in supporting the safety profile of CGRP mAbs in the real-world setting and may provide clinicians and patients with additional insight when considering migraine preventive treatments.

Echocardiographic Evaluation of Pulmonary Embolism: A Review.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death in the United States. Appropriate risk stratification is an important component of the initial evaluation for acute management of these patients. Echocardiography plays a crucial role in the risk stratification of patients with PE. In this literature review, we describe the current strategies in risk stratification of patients with PE using echocardiography and the role of echocardiography in the diagnosis of PE.

Patient and Healthcare Professional Preferences for Characteristics of Long-Acting Injectable Antipsychotic Agents for the Treatment of Schizophrenia.

INTRODUCTION: Studies evaluating patient and healthcare professional (HCP) preferences regarding long-acting injectable (LAI) antipsychotic agent attributes are lacking. METHODS: Surveys were administered to physicians, nurses, and patients who had at least two experiences with TV-46000, an investigational subcutaneous LAI antipsychotic agent for the treatment of schizophrenia, as part of the SHINE study (NCT03893825). Survey topics included preferences for route of administration, potential LAI dosing intervals (once-weekly, twice a month, once a month [q1m], every 2 months [q2m]), injection location, ease of use, syringe type, needle length, and need for reconstitution. RESULTS: Patients (n = 63) had a mean (SD) age of 35.6 (9.6) years, age at diagnosis of 18 (10) years, and were mostly male (75%). There were 49 HCPs: 24 physicians and 25 nurses. Patients rated "a short needle" (68%), a "choice of [q1m or q2m] dosing interval" (59%), and "injection instead of oral tablet" (59%) as the most important features. HCPs rated "single injection to initiate treatment" (61%), "flexible dosing interval" (84%), and "injection instead of oral tablet" (59%) as the most important features. Subcutaneous injections were rated "easy to [receive/administer]" by 62% of patients and 84% of HCPs. When choosing between subcutaneous injections and intramuscular injections, 65% of HCPs preferred subcutaneous injections and 57% of patients preferred intramuscular injections. It was important to most HCPs to have four dose strength options (78%), a prefilled syringe (96%), and no need for reconstitution (90%). CONCLUSIONS: Patients had a range of responses, and on some issues patient and HCP preferences differed. Altogether, this suggests the importance of providing patients with a range of options and the importance of patient-HCP discussions on treatment preference for LAIs.

Several medications for treating schizophrenia are available as long-acting injections. One advantage of these medications is that patients do not need to take pills daily. In this study, patients, doctors, and nurses were asked what medication characteristics they preferred. Question topics were similar to the following: "how often should it be taken?"; "what method of delivery do you prefer?"; "where on the body should it be injected?"; "how easy was it to use?"; "what physical properties do you like?"; and "do preparation steps matter?" Patients thought that being able to be given monthly or every other month was one of the most important features of an injection (59%). Patients also liked a short needle (68%) and an injection instead of an oral pill (59%). Doctors and nurses responded that it was important to have a single injection to start treatment (61%). They also liked having options for how often the medication was given (84%), and an injection instead of an oral pill (59%). An injection was "easy to [get/give]" for most patients (62%) and doctors and nurses (84%). Most doctors and nurses (65%) liked giving injections under the skin. Most patients (57%) liked injections into the muscle. Overall, patients and doctors/nurses agreed on most topics. There were, however, a range of patient responses; therefore, it is important for patients and doctors and nurses to talk about the available treatment options. Each individual patient may have their own preferences.