Chronic Illness in Children and Foregone Care Among Household Adults in the United States: A National Study.

BACKGROUND: Childhood chronic illness imposes financial burdens that may affect the entire family. OBJECTIVE: The aim was to assess whether adults living with children with 2 childhood chronic illnesses-asthma and diabetes-are more likely to forego their own medical care, and experience financial strain, relative to those living with children without these illnesses. RESEARCH DESIGN: 2009-2018 National Health Interview Survey. SUBJECTS: Adult-child dyads, consisting of one randomly sampled child and adult in each family. MEASURES: The main exposure was a diagnosis of asthma or diabetes in the child. The outcomes were delayed/foregone medical care for the adult as well as family financial strain; the authors evaluated their association with the child's illness using multivariable logistic regressions adjusted for potential confounders. RESULTS: The authors identified 93,264 adult-child dyads; 8499 included a child with asthma, and 179 a child with diabetes. Families with children with either illness had more medical bill problems, food insecurity, and medical expenses. Adults living with children with each illness reported more health care access problems. For instance, relative to other adults, those living with a child with asthma were more likely to forego/delay care (14.7% vs. 10.2%, adjusted odds ratio: 1.27; 95% CI: 1.16-1.39) and were more likely to forego medications, specialist, mental health, and dental care. Adults living with a child with diabetes were also more likely to forego/delay care (adjusted odds ratio: 1.76; 95% CI: 1.18-2.64). CONCLUSIONS: Adults living with children with chronic illnesses may sacrifice their own care because of cost concerns. Reducing out-of-pocket health care costs, improving health coverage, and expanding social supports for families with children with chronic conditions might mitigate such impacts.

Magnetic Resonance Angiography After Flow Diversion: The Use of Complementary Magnetic Resonance Angiography Techniques to Monitor Aneurysm Occlusion and Device and Arterial Branch Patency After Flow Diverter Placement.

BACKGROUND: Few studies have evaluated flow diversion with magnetic resonance angiography (MRA). Studies have shown better success of MRA in assessing the aneurysm response, but limited success in assessing stent patency. The patency of arterial branches on MRA remains to be explored. METHODS: Retrospective evaluation of 31 consecutive cases of carotid aneurysms treated with flow diversion was performed with noncontrast time-of-flight (TOF), contrast-enhanced TOF, and cine MRA (time-resolved angiography with interleaved stochastic trajectories) independently by 2 investigators for aneurysm occlusion, stent patency, and arterial branch patency. Digital subtraction angiography served as the gold standard technique. RESULTS: Patients were 6 men and 25 women with a mean ± SD age of 57.8 ± 12.27 years (range, 32-79 years). Stent patency, aneurysm occlusion, and branch patency mostly revealed substantial to perfect interobserver agreement (κ >0.60). Sensitivity, specificity, positive predictive value, and negative predictive value for stent patency on raw data images of TOF were 0.50, 0.86, 0.20, and 0.96 and on contrast-enhanced TOF were 1.0, 0.93, 0.50, and 1.0. Ranges for aneurysm response on the 3 MRA scans were 0.78-0.89 for sensitivity, 0.54-0.92 for specificity, 0.73-0.93 for positive predictive value, and 0.78-0.86 for negative predictive value. Ranges for arterial branch patency among the 3 MRA scans were 0.87-0.96 for sensitivity, 0.50-1.0 for specificity, 0.90-1.0 for positive predictive value, and 0.33-0.80 for negative predictive value. CONCLUSIONS: Aneurysm occlusion, stent patency, and arterial branch patency in flow diversion can be successfully evaluated with the combination of 3 MRA techniques.

Working to Increase Stability through Exercise (WISE): screening, recruitment, and baseline characteristics.

BACKGROUND: The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania. METHODS: The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings. RESULTS: Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%). CONCLUSIONS: The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered.

Primary differentiated respiratory epithelial cells respond to apical measles virus infection by shedding multinucleated giant cells.

Measles virus (MeV) is highly infectious by the respiratory route and remains an important cause of childhood mortality. However, the process by which MeV infection is efficiently established in the respiratory tract is controversial with suggestions that respiratory epithelial cells are not susceptible to infection from the apical mucosal surface. Therefore, it has been hypothesized that infection is initiated in lung macrophages or dendritic cells and that epithelial infection is subsequently established through the basolateral surface by infected lymphocytes. To better understand the process of respiratory tract initiation of MeV infection, primary differentiated respiratory epithelial cell cultures were established from rhesus macaque tracheal and nasal tissues. Infection of these cultures with MeV from the apical surface was more efficient than from the basolateral surface with shedding of viable MeV-producing multinucleated giant cell (MGC) syncytia from the surface. Despite presence of MGCs and infectious virus in supernatant fluids after apical infection, infected cells were not detected in the adherent epithelial sheet and transepithelial electrical resistance was maintained. After infection from the basolateral surface, epithelial damage and large clusters of MeV-positive cells were observed. Treatment with fusion inhibitory peptides showed that MeV production after apical infection was not dependent on infection of the basolateral surface. These results are consistent with the hypothesis that MeV infection is initiated by apical infection of respiratory epithelial cells with subsequent infection of lymphoid tissue and systemic spread.

A Randomized Trial of Complications of Peripherally and Centrally Inserted Central Lines in the Neuro-Intensive Care Unit: Results of the NSPVC Trial.

OBJECTIVE: The objective of this study was to compare the relative number of complications from peripherally inserted central venous catheters (PICC) and centrally inserted central venous catheters (CVC) in the neuroscience intensive care unit (NSICU). METHODS: This study was carried out in a 32-bed NSICU in a large academic hospital in the USA from July 2015 until January 2017. Patients admitted requiring central venous access were randomly assigned to have a PICC or CVC inserted. Complications were recorded and compared. The primary outcome was all complications as well as combined numbers of large vein thrombosis, central-line-associated blood stream infections, and insertional trauma. Outcomes were compared using the Fisher's exact test, logistic regression, or unpaired T tests, as appropriate. RESULTS: One hundred and fifty-two patients were enrolled; 72 were randomized to the PICC arm and 80 to the CVC arm. There were no crossovers, withdrawals, nor losses to follow-up. The study was stopped at the second pre-planned interim analysis for futility. The combined number of large vein thrombosis, central-line-associated blood stream infection, and insertional trauma was 4/72 in the PICC arm and 1/80 in the CVC group (OR 4.6 (95% CI 0.5-42.6) p = 0.14). The number of all complications in the PICC arm was 14/72 compared to 10/80 in the CVC arm (OR 1.7 (95% CI 0.7-4.1) p = 0.24). CONCLUSIONS: PICCs and CVCs have similar numbers of complications when placed in patients admitted to the NSICU.

Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.

Hit or a miss: Concordance between histopathologic-endoscopic findings in gastric mucosal biopsies.

BACKGROUND: Current literature shows a variable degree of concordance between endoscopic and histopathologic findings in gastric mucosal biopsies. Most prior studies have focused on specific gastric entities such as gastritis in patients with high prevalence of Helicobacter pylori (H. pylori). In this study, we assess concordance between histologic and endoscopic findings in a wide spectrum of targeted as well as non-targeted gastric endoscopic biopsies. METHODS: We retrospectively reviewed pathology database and slides at Hershey Medical Center to identify 630 gastric mucosal biopsies obtained from 525 consecutive patients. The corresponding clinical and endoscopic findings were retrieved from the electronic medical record. RESULTS: The rate of abnormal endoscopic and histologic findings was 72.9% and 74.4%, respectively, with Cohen's ĸ coefficient of 0.24. There were 444 (70.5%) concordant cases and 186 (29.5%) discordant cases (88 cases with abnormal endoscopy but normal histology, and 98 cases with normal endoscopy but abnormal histology). Some endoscopic findings, in particular, mass, polyp, ulcer, and nodule/papule were highly concordant with abnormal histopathologic findings; while other endoscopic findings such as inflammatory changes, normal and prominent folds were associated with normal and a variety of abnormal histopathology. Multivariate analysis showed no significant association between intestinal metaplasia and H. pylori in this study. CONCLUSIONS: Histopathologic-endoscopic correlation in gastric biopsies varies depending on endoscopic mucosal patterns. Intestinal metaplasia may not have a significant association with H. pylori infection in populations with low prevalence of H. pylori.

Mitohormesis in Mice via Sustained Basal Activation of Mitochondrial and Antioxidant Signaling.

Transient mitochondrial stress can promote beneficial physiological responses and longevity, termed "mitohormesis." To interrogate mitohormetic pathways in mammals, we generated mice in which mitochondrial superoxide dismutase 2 (SOD2) can be knocked down in an inducible and reversible manner (iSOD2-KD mice). Depleting SOD2 only during embryonic development did not cause post-natal lethality, allowing us to probe adaptive responses to mitochondrial oxidant stress in adult mice. Liver from adapted mice had increased mitochondrial biogenesis and antioxidant gene expression and fewer reactive oxygen species. Gene expression analysis implicated non-canonical activation of the Nrf2 antioxidant and PPARγ/PGC-1α mitochondrial signaling pathways in this response. Transient SOD2 knockdown in embryonic fibroblasts from iSOD2-KD mice also resulted in adaptive mitochondrial changes, enhanced antioxidant capacity, and resistance to a subsequent oxidant challenge. We propose that mitohormesis in response to mitochondrial oxidative stress in mice involves sustained activation of mitochondrial and antioxidant signaling pathways to establish a heightened basal antioxidant state.

Contrast Enhancement of Aneurysm Sac Post-Pipeline Treatment Interpreted as Recanalization.

Multiple imaging modalities are available to evaluate aneurysms post-flow diverter (FD) placement. Though digital subtraction angiography (DSA) is the gold standard imaging modality post-FD placement, it is not perfect, and neither are other techniques, including contrast-enhanced magnetic resonance angiography (CE-MRA) and magnetic resonance imaging (MRI). We present a case of a 73-year-old woman with a right internal carotid artery (ICA) aneurysm treated with a pipeline embolization device (PED). Initial follow-up post-PED placement by three-dimensional time-of-flight (3D-TOF) MRA demonstrated aneurysm occlusion, which was confirmed by computed tomography angiography (CTA) and CE-MRA in subsequent follow-up appointments. However, repeat CE-MRA two years later suggested recanalization of the aneurysm. After discussion with neuroradiologists and follow-up with a dynamic MRA, this finding was determined to be false. These findings shed light on the potential pitfall of using CE-MRA alone or any single imaging modality in the assessment of aneurysms post-PED placement. Our case report explores various imaging modalities used in the assessment of aneurysms post-PED placement and highlights the need to use multiple techniques for an accurate assessment.