The SunBEAm birth cohort: Protocol design Keet, Corinne; Sicherer, Scott H.; Bunyavanich, Supinda ...
The journal of allergy and clinical immunology. Global,
08/2023, Letnik:
2, Številka:
3
Journal Article
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Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is ...essential to develop and implement effective prevention and treatment strategies.
We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort.
Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them to 3 years. Questionnaire and biosampling strategies were developed to apply a systems biology approach to identify environmental, immunologic, and multiomic determinants of AD, FA, and other allergic outcomes.
Enrollment is currently underway. On the basis of an estimated FA prevalence of 6%, the enrollment goal is 2500 infants. AD is defined on the basis of questionnaire and assessment, and FA is defined by an algorithm combining history and testing. Although any FA will be recorded, we focus on the diagnosis of egg, milk, and peanut at 5 months, adding wheat, soy, cashew, hazelnut, walnut, codfish, shrimp, and sesame starting at 12 months. Sampling includes blood, hair, stool, dust, water, tape strips, skin swabs, nasal secretions, nasal swabs, saliva, urine, functional aspects of the skin, and maternal breast milk and vaginal swabs.
The SunBEAm birth cohort will provide a rich repository of data and specimens to interrogate mechanisms and determinants of early allergic outcomes, with an emphasis on FA, AD, and systems biology.
Summary Background Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50–60% of patients after traumatic brain ...injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome. Methods We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors. Findings Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0·0009) and spreading depolarisation category (p=0·0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1·56 95% CI 0·72–3·37 and 7·58 2·64–21·8, respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone. Interpretation Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research. Funding US Army CDMRP PH/TBI research programme.
Objective When uterotonics fail to cause sustained uterine contractions and satisfactory control of hemorrhage after delivery, tamponade of the uterus can be effective in decreasing hemorrhage ...secondary to uterine atony. Study Design These data are from a postmarketing surveillance study of a novel dual-balloon catheter tamponade device, the Belfort-Dildy Obstetrical Tamponade System (ebb). Results A total of 57 women were enrolled: 55 women had the diagnosis of postpartum hemorrhage, and 51 women had uterine balloon placement within the uterine cavity. This study reports the outcomes in the 51 women who had uterine balloon placement within the uterine cavity for treatment of postpartum hemorrhage, as defined by the “Instructions for Use.” We further assessed 4 subgroups: uterine atony only (n = 28 women), placentation abnormalities (n = 8 women), both uterine atony and placentation abnormalities (n = 9 women), and neither uterine atony nor placentation abnormalities (n = 6 women). The median (range) time interval between delivery and balloon placement was 2.2 hours (0.3–210 hours) for the entire cohort (n = 51 women) and 1.3 hours (0.5–7.0 hours) for the uterine atony only group (n = 28 women). Bleeding decreased in 22/51 of cases (43%), stopped in 28/51 of cases (55%), thus decreased or stopped in 50/51 of the cases (98%) after balloon placement. Nearly one-half (23/51) of all women required uterine balloon volumes of >500 mL to control bleeding. Conclusion We conclude that uterine/vaginal balloon tamponade is very useful in the management of postpartum hemorrhage because of uterine atony and abnormal placentation.
Background Esophageal anastomotic leaks after cancer surgery remain a major cause of morbidity and mortality. Endoscopic interventions, including covered metal stents (cSEMS), clips, and direct ...percutaneous endoscopic jejunostomy (dPEJ) tubes are increasingly used despite limited published data regarding their utility in this setting. This study aimed to determine the efficacy and safety of a multimodality endoscopic approach to anastomotic leak management after operation for esophageal or gastric cancer. Methods We performed a retrospective review of prospectively maintained databases of gastric and esophageal operations at our hospital between January 2003 and December 2012. Included patients had an operation for esophageal or gastric cancer, demonstrated evidence of an anastomotic leak at the esophageal anastomosis, and underwent attempted endoscopic therapy. Healing was defined as clinical and radiographic leak resolution. Results Forty-nine patients with leaks underwent endoscopic management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a combined approach. Overall, 88% of patients achieved healing in a median of 83 days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic approach healed. Only 1 patient had a major complication associated with stent erosion into the pulmonary artery, which was successfully treated with operative repair. Conclusions Esophageal anastomotic leaks after esophageal and gastric cancer operations can be managed successfully and safely with endoscopic therapy. Combining cSEMS for leak control and dPEJ tube placement for nutritional support was highly effective in achieving healing, without the need for surgical repair.
Abstract The current study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson’s disease (PD), is also associated ...with idiopathic REM sleep behavior disorder (RBD). Two SNPs, rs429358 and rs7412, were genotyped in RBD patients (n=480) and in controls (n=823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR=1.11, 95% CI 0.88-1.40, p =0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to PD (0.12) or multiple system atrophy (0.14, p =1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.
Background We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our institution's operative venous thromboembolism (VTE) prophylaxis policy as part of a ...physician-led quality improvement initiative. Study Design Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and targeted to receive preoperative VTE chemoprophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis. Results The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% received preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-intervention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without significant difference in major bleeding (difference 0.3%, 95% CI −0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post-intervention group. Conclusions In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improvement initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates.
Background Atopic dermatitis (AD) is the most common inflammatory disease. Evolving disease models link changes in epidermal growth and differentiation to TH 2/TH 22 cytokine activation. However, ...these models have not been tested by in vivo suppression of T-cell cytokines. Cyclosporine (CsA) is an immunosuppressant that is highly effective for severe disease, but its mechanism in AD skin lesions has not been studied. Objective We sought to establish the ability of a systemic immunosuppressant to modulate immune and epidermal alterations that form the pathogenic disease phenotype and to correlate changes with clinical improvement. Methods CsA's effects on AD skin pathology were evaluated by using gene expression and immunohistochemistry studies in baseline, week 2, and week 12 lesional and nonlesional biopsy specimens from 19 patients treated with 5 mg/kg/d CsA for 12 weeks. Results After 2 and 12 weeks of treatment, we observed significant reductions of 51% and 72%, respectively, in SCORAD scores. Clinical improvements were associated with significant gene expression changes in lesional but also nonlesional skin, particularly reductions in levels of TH 2-, TH 22-, and some TH 17-related molecules (ie, IL-13, IL-22, CCL17, S100As, and elafin/peptidase inhibitor 3), and modulation of epidermal hyperplasia and differentiation measures. Conclusions This is the first study that establishes a relationship between cytokine activation and molecular epidermal alterations, as well as correlations between disease biomarkers in the skin and clinical improvement. The reversal of the molecular phenotype with CsA and the associated biomarkers can serve as a reference for the successful modulation of tissue inflammation with specific immune antagonists in future studies, contributing to the understanding of the specific cytokines involved in epidermal pathology.
Background Surgical quality improvement requires well-defined benchmarks and accurate reporting of postoperative adverse events, which have not been well defined for total gastrectomy. Study Design ...Detailed postoperative outcomes on 238 patients who underwent total gastrectomy with curative intent, from 2003 to 2012, were reviewed by a dedicated surgeon chart reviewer to establish 90-day patterns of adverse events. Results Of the 238 patients with stage I to III gastric adenocarcinoma who underwent curative-intent total gastrectomy, the median age was 66 years, and 68% were male. Median body mass index was 28 kg/m2 , and 68% of patients had at least 1 medical comorbidity. Forty-three percent of our patients received neoadjuvant chemotherapy, and 34% received postoperative adjuvant chemotherapy. Over the 90-day study period, 30-day mortality was 2.5% (6 of 238), and 90-day mortality was 2.9% (7 of 238). At least 1 postoperative adverse event was documented in 62% of patients, with 28% of patients experiencing a major adverse event requiring invasive intervention. The readmission rate was 20%. Anemia was the most common adverse event (20%), followed by wound complications (18%). The most common major adverse event was esophageal anastomotic leak, which required invasive intervention in 10% of patients. Conclusions This analysis has defined comprehensive 90-day patterns in postoperative adverse events after total gastrectomy with curative intent in a Western population. This benchmark allows surgeons to measure, compare, and improve outcomes and informed consent for this surgical procedure.
Medication Adherence: Truth and Consequences Brown, Marie T; Bussell, Jennifer; Dutta, Suparna ...
The American journal of the medical sciences,
2016-April, Letnik:
351, Številka:
4
Journal Article
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Improving medication adherence may have a greater influence on the health of our population than in the discovery of any new therapy. Patients are nonadherent to their medicine 50% of the time. ...Although most physicians believe nonadherence is primarily due to lack of access or forgetfulness, nonadherence can often be an intentional choice made by the patient. Patient concealment of their medication-taking behavior is often motivated by emotions on the part of both provider and patient, leading to potentially dire consequences. A review of the literature highlights critical predictors of adherence including trust, communication and empathy, which are not easily measured by current administrative databases. Multifactorial solutions to improve medication adherence include efforts to improve patients' understanding of medication benefits, access and trust in their provider and health system. Improving providers' recognition and understanding of patients' beliefs, fears and values, as well as their own biases is also necessary to achieve increased medication adherence and population health.
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