Background Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1 -antihistamines ...along with 1 or more add-on therapies. Objectives We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1 -antihistamines at up to 4 times the approved dose plus H2 -antihistamines, leukotriene receptor antagonists, or both. Methods In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group ( P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1 -antihistamines (up to 4 times the approved dose) plus H2 -antihistamines, leukotriene receptor antagonists, or both.
Summary Background There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant ...monitoring on maternal and neonatal outcomes in such women. Methods We did an open-label, randomised controlled trial , in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). Findings Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk RR 0·36, 95% CI 0·12–1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4–8·2; p=0·005). No maternal or perinatal deaths occurred. Interpretation For women with non-severe hypertensive disorders at 34–37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered. Funding ZonMw.
Background Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains ...unclear. Methods This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. Results Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. Conclusion Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.
Purpose The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multicenter community based cohort study of Hispanics/Latinos in the United States. Methods The Study ...rationale, objectives, design, and implementation are described in this report. Results The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, 18 to 74 years of age, from a random sample of households in defined communities in the Bronx, Chicago, Miami, and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders. Conclusions The HCHS/SOL will (1) characterize the health status and disease burden in the largest minority population in the United States; (2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream United States life-styles, environment and health care opportunities; and (3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds, and early life experiences.
In the United States, TDM assays for most antihypertensive drugs are available in clinical practice, including thiazide diuretics, beta-blockers, calcium channel blockers, and spironolactone (Fig. ...1A) but not angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or direct renin inhibitors.
Humanitarian crises create opportunities for both in-person and remote aid. Durable, complex, and team-based care may leverage a telemedicine approach for comprehensive support within a conflict ...zone. Barriers and enablers are detailed, as is the need for mission expansion due to initial program success. Adapting a telemedicine program initially designed for critical care during the severe acute respiratory syndrome coronavirus 2 pandemic offers a solution to data transfer and data analysis issues. Staffing efforts and grouped elements of patient care detail the kinds of remote aid that are achievable. A multiprofessional team-based approach (clinical, administrative, nongovernmental organization, government) can provide comprehensive consultation addressing surgical planning, critical care management, infection and infection control management, and patient transfer for complex care. Operational and network security create parallel concerns relevant to avoid geolocation and network intrusion during consultation. Deliberate approaches to address cultural differences that influence relational dynamics are also essential for mission success.
OBJECTIVES:
Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) ...provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients.
DATA SOURCES:
MEDLINE, PubMed Central, Embase, and CENTRAL.
STUDY SELECTION:
Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021.
DATA EXTRACTION:
Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison.
DATA SYNTHESIS:
Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17–0.91;
p
= 0.030).
CONCLUSIONS:
Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.
Purpose The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a multicenter, community-based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample ...is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this study. Methods The study design calls for recruitment and follow-up of a cohort of 16,000 Hispanics/Latinos 18–74 years of age, with 62.5% (10,000) over 44 years of age and adequate subgroup sample sizes to support inference by Hispanic/Latino background. Participants are recruited in community areas surrounding four field centers in the Bronx, Chicago, Miami, and San Diego. A two-stage area probability sample of households is selected with stratification and oversampling incorporated at each stage to provide a broadly diverse sample, offer efficiencies in field operations, and ensure that the target age distribution is obtained. Conclusions Embedding probability sampling within this traditional, multisite cohort study design enables competing research objectives to be met. However, the use of probability sampling requires developing solutions to some unique challenges in both sample selection and recruitment, as described here.
We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
Summary Background Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association ...between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. Methods We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Findings Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Interpretation Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. Funding National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.
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