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Following an unexpected pediatric death, survivors undergo unique trauma. Medical examiners (MEs) evaluate most of these deaths. We evaluated the bereavement support available to survivors in the Chicagoland area following a pediatric death. We had two goals: to characterize the available bereavement support options and compare the locations (by zip code) of support groups with the locations (by zip code) in which pediatric ME cases occurred. We identified 48 organizations that provided bereavement support services at 74 locations in the summer and fall of 2020. Locations by zip codes in which the largest number of ME cases occurred did not have support groups. Locations in which more ME cases occurred generally had lower-income populations and a greater proportion of Black or Hispanic residents. Bereavement support following pediatric death is inadequate and unevenly distributed across the Chicagoland area. [ABSTRACT FROM AUTHOR]

Background Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. Methods Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. Results Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2–3.0) in group 2 and 2.9-fold (95% CI = 2.6–3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213–246] after dose 2) did not increase significantly after dose 3. Conclusions A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster. [ABSTRACT FROM AUTHOR]

Perceived discrimination has a significant negative impact on indices of mental health. One potential buffering factor in this is psychological resilience, which encompasses the ability to recover from or adapt successfully to adversity and use coping strategies, such as positive reappraisal of adverse events. This study examines the role of resilience as well as social support in buffering these effects in groups of migrants both with and without local residence permits. We conducted a non-experimental observational study with a cross-sectional design, collecting a variety of health variables in migrant groups in a naturalistic setting, during the COVID-19 period. The total sample consisted of 201 subjects, 88 of whom had a German residence title and 113 did not. These two groups were compared on the following variables of interest: social support, resilience, discrimination, and general mental health. There was no evidence for a difference in mental health between migrants with and without citizenship. However, our results suggested that migrants without citizenship reported less social support, less resilience, and more discrimination, which continued to have a distinct effect on mental health beyond resilience and social support. Psychological resilience mediated the link between social support and mental health, as well as being related to the perception of discrimination in the migrant group without citizenship. In conclusion, our models of migrants with and without citizenship showed that resilience specifically directly affected perceived discrimination in those without citizenship. The high levels of discrimination and lack of social support, particularly in the migrant group without citizenship, are concerning and suggest a focus for future interventions. [ABSTRACT FROM AUTHOR]

Chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) diverged into distinct species approximately 1.7 million years ago when the ancestors of modern‐day bonobo populations were separated by the Congo River. This geographic boundary separates the two species today and the associated ecological factors, including resource distribution and feeding competition, have likely shaped the divergent social behavior of both species. The most striking behavioral differences pertain to between group interactions in which chimpanzees behave aggressively towards unfamiliar conspecifics, while bonobos display remarkable tolerance. Several hypotheses attempt to explain how different patterns of social behavior have come to exist in the two species, some with specific genetic predictions, likening the evolution of bonobos to a process of domestication. Here, we utilize 73 ape genomes and apply linkage haplotype homozygosity and structure informed allele frequency differentiation methods to identify positively selected regions in bonobos since their split from a common pan ancestor to better understand the environment and processes that resulted in the behavioral differences observed today. We find novel evidence of selection in genetic regions that aid in starch digestion (AMY2) along with support for two genetic predictions related to self‐domestication processes hypothesized to have occurred in the bonobo. We also find evidence for selection on neuroendocrine pathways associated with social behavior including the oxytocin, serotonin, and gonadotropin releasing hormone pathways. [ABSTRACT FROM AUTHOR]

Background: Health and medical providers dedicated to serving the poor face daunting challenges, with the most obvious one pertaining to the provision of services with little or no expectation of remuneration. This hardship often is overlooked by broad society as many view the delivery of healthcare services to indigent populations to be covered fully by government health insurance programs or other forms of public assistance. This, however, is only partially true and, even when reimbursements or similar payments are provided, they often fall short of covering the actual costs associated with rendering services.Discussion: With reimbursements from third parties often being unreliable, inadequate, and sometimes nonexistent, healthcare providers dedicated to serving poverty-stricken populations face quite a dilemma. As an institution which is devoted to addressing the disadvantaged, Willis-Knighton Health System has long sought remedies to bolster healthcare access for these vulnerable individuals. While public policy solutions ultimately are desired, historic and recent efforts continue to reveal fractures which in some cases have compelled providers to limit their exposure to indigent populations or withdraw from serving them altogether. Willis-Knighton Health System has addressed these challenges by operating as efficiently as possible, offering and successfully delivering a diverse service mix which permits a healthy margin that can support charitable care initiatives, and remaining steadfastly committed to shoring up indigent services in the community.Conclusions: Given the magnitude, scope, and expenditures associated with comprehensively addressing disadvantaged populations, public policy modifications appear to be the primary hope of remedying associated access gaps fully. Until effective measures are introduced, however, health and medical institutions dedicated to serving the indigent must look within for answers to associated challenges. [ABSTRACT FROM AUTHOR]

Objective: To determine whether central and peripheral vision reaction times (PVRTs) are prolonged in patients with visual dysfunction after sustaining a concussion. Design: Comparison of Dynavision D2 central and PVRTs in patients with postconcussion visual dysfunction were compared with control data from a normative patient database. Concussion patients without visual dysfunction were not included in this study. Setting: National Collegiate Athletic Association Division 1 college training room and university based, academic health center. Participants: Patients were selected for inclusion based on diagnosis of new visual dysfunction as indicated either by physical examination of the team physician or by patient self-report of symptoms. Patients included college athletes, college students, and concussion patient's presenting to a university based, academic health center. Intervention: Measurement of central and PVRTs using a Dynavision D2 reaction time program were used as the dependent variables. Evaluations were conducted from 3 days to 11 months postconcussion, depending on the temporal development of visual symptoms after the concussion. No intervention was used. Main Outcome Measures: Average central and PVRTs for patients with postconcussion visual symptoms were compared with an asymptomatic control group with no history of concussion. Results: Both central and PVRTs were significantly prolonged in patients with postconcussion visual symptoms compared with patients with no history of concussion. Conclusions: Central and PVRTs are both prolonged in patients with postconcussion visual dysfunction with PVRT being disproportionately prolonged. The percent change from central to PVRT was also increased in patients with postconcussion visual dysfunction. [ABSTRACT FROM AUTHOR]

Background: This study uses national survey data to examine the veracity of the longstanding belief that, compared to whites, Native Americans (NA) have elevated alcohol consumption.Methods: The primary data source was the National Survey on Drug Use and Health (NSDUH) from 2009 to 2013: whites (n=171,858) and NA (n=4,201). Analyses using logistic regression with demographic covariate adjustment were conducted to assess differences in the odds of NA and whites being alcohol abstinent, light/moderate drinkers (no binge/heavy consumption), binge drinkers (5+ drinks on an occasion 1-4 days), or heavy drinkers (5+ drinks on an occasion 5+ days) in the past month. Complementary alcohol abstinence, light/moderate drinking and excessive drinking analyses were conducted using Behavioral Risk Factor Surveillance System (BRFSS) data from 2011 to 2013: whites (n=1,130,658) and NA (n=21,589).Results: In the NSDUH analyses, the majority of NA, 59.9% (95% CI: 56.7-63.1), abstained, whereas a minority of whites, 43.1% (CI: 42.6-43.6), abstained-adjusted odds ratio (AOR): 0.64 (CI: 0.56-0.73). Approximately 14.5% (CI: 12.0-17.4) of NA were light/moderate-only drinkers, versus 32.7% (CI: 32.2-33.2) of whites (AOR: 1.90; CI: 1.51-2.39). NA and white binge drinking estimates were similar-17.3% (CI: 15.0-19.8) and 16.7% (CI: 16.4-17.0), respectively (AOR: 1.00; CI: 0.83-1.20). The two populations' heavy drinking estimates were also similar-8.3% (CI: 6.7-10.2) and 7.5% (CI: 7.3-7.7), respectively (AOR: 1.06; CI: 0.85-1.32). Results from the BRFSS analyses generally corroborated those from NSDUH.Conclusions: In contrast to the 'Native American elevated alcohol consumption' belief, Native Americans compared to whites had lower or comparable rates across the range of alcohol measures examined. [ABSTRACT FROM AUTHOR]

We compared the two most commonly used sampling methods, pitfall trapping and quadrat sieving, to study community diversity and talitrid abundance on sandy beaches. They are both widely used methods, however they are related to different behaviors: surface activity (pitfall traps) and burrowing in the substrate (quadrat sieving). To detect bias intrinsically generated by the use of different sampling methods, we applied both methods on a set of five beaches in New South Wales, Australia. The set included non-contiguous beaches, exposed and sheltered, more or less affected by recreational use. The results indicated a high fluctuation in biodiversity features. However, the most human-frequented beaches were grouped together by Multi Dimensional Scaling, and substrate-modifiers talitrid amphipods (sand-hoppers), played a major role in this scaling. The analysis of similarities (ANOSIM) indicated the roles of exposure and human recreational use in shaping the community, while the methods (quadrats vs. traps) resulted in higher fluctuation within samples than between, and informative outliers. Generalized Linear Models developed to estimate the probability of capture of talitrids by sampling method pointed to a higher probability to capture both sand-hoppers and beach-hoppers with the quadrat method. We finally suggest: (1) the comparative use of both sampling methods whenever possible, to capture multiple information and avoid bias in biodiversity estimates; and (2) an ad-hoc strategy when dealing with target populations. In particular, attention should be paid when targeting co-occurring talitrid species characterized by different ecology and behavioral traits: sand-hoppers (substrate modifiers) appeared to be more sensitive than beach-hoppers (non-substrate modifiers) to the impacts considered. In terms of biodiversity assessment the methods were equal, but for talitrid sampling quadrat sieving was more efficient. [ABSTRACT FROM AUTHOR]

Background and Aims Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity-indicators of cocaine availability. Design Autoregressive integrated moving average (ARIMA)-intervention time-series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. Setting Conterminous United States (January 1987-April 2011). Measurements Monthly time-series: purity-adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity-adjusted price (all available seizures), and purity (all available seizures). Data source: System to Retrieve Information from Drug Evidence. Findings The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% ( P < 0.05), a 36% increase in price ( P < 0.05) and a 4% decrease in purity ( P < 0.05). Availability recovered in 1-2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease ( P < 0.05), 100% price increase ( P < 0.05) and 35% purity decrease ( P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. Conclusions In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability. [ABSTRACT FROM AUTHOR]

Lower body negative pressure (LBNP) simulates hemorrhage, and tolerance to LBNP (time to presyncope [TTP]) is indicative of tolerance to blood loss. The purpose of this study was to predict TTP based on demographic characteristics (sex, age, height, and body mass index) and physiological variables (heart rate [HR], systolic arterial pressure, diastolic arterial pressure [DAP], pulse pressure, stroke volume, total peripheral resistance [TPR], and baroreflex sensitivity [BRS]) at baseline, and during 2 levels of LBNP (-15, -30 mm Hg). Multiple linear regression analysis was used to create a model to predict TTP (range: 670 to 2516 seconds, n=187) based on demographic characteristics and physiological variables changes (Δ) from baseline to -30 mm Hg LBNP. The prediction model revealed that TTP (seconds)=1667.5+(5.1×Age)+(61.1×Sex)-(21.5×ΔHR)+(55.3×ΔDAP)-(88.2×ΔTPR)-(4.9×ΔBRS). Most significantly, our analysis demonstrated a lesser survival trajectory for females given the same rate and magnitude of hemorrhage compared to males. Young age and female sex are predictors of low tolerance to blood loss, and should be considered for early triage in the prehospital setting. [ABSTRACT FROM AUTHOR]

Background Abuse against the elderly is recognized as an important challenge to elderly health, but its determinants are not yet well understood. We present findings from a new dataset which covers a representative sample of the population aged 60 years and above from seven Indian states across India - all of which have a higher proportion aged 60 plus compared to the national average. Earlier studies suggest that schooling levels can be relevant in determining the level of abuse against seniors. This study focuses on the role of education on the prevalence of elderly abuse in India. Methods We conduct an analysis of cross sectional primary data that contains information on elderly abuse. The households in the sample were randomly selected from the seven demographically oldest states in India. These states are Himachal Pradesh, Kerala, Maharashtra, Odisha, Punjab, Tamil Nadu and West Bengal. A total of 9852 elderly from 8329 households were interviewed. The statistical analysis is based on logistic regression to understand the independent relation of education with abuse against the elderly. Results Our findings reveal that 11% of 60+ year olds have experienced at least one type of elderly abuse (Physical 5.3%, Verbal 10.2%, Economic 5.4%, Disrespect 6%, Neglect 5.2%). The most common perpetrator is the son, who is reported to be responsible for the abuse among 41% of male victims and 43% of female victims. The formal education among elderly beyond a certain level (8 years) has a strong relation with reduced violence against elderly. Conclusions Our findings suggest that level of schooling among elderly is strongly negatively related to abuse against them. More members in the household reduce the chance of abuse while having a greater number of children increases the chance of abuse (neglect and verbal abuse). We find that education even after controlling for wealth and other relevant variables is the factor that most consistently lowers elderly abuse. However, the relation of education to abuse is limited to those with more than 8 years of schooling. This suggest that the ongoing educational expansion beyond the basic schooling years in India may lead to a decline in the incidence of elderly abuse. [ABSTRACT FROM AUTHOR]

Genetic studies have revealed a large degree of previously unappreciated diversity in morphologically conserved taxa. To understand the implications of this phenomenon, studies investigating the processes responsible for generating and maintaining functional and neutral diversity within such taxa are needed. With this aim, patterns of differentiation across a contact zone between two catchment-specific, and genetically and subtly morphologically distinguishable, races of the onychophoran Euperipatoides rowelli Reid, 1996 at the Tallaganda State Forest study system, Australia, were quantified using diagnostic body-pattern differences, microsatellite markers, and the cytochrome c oxidase subunit I ( COI) mitochondrial gene. These data were used to test whether hybridization occurred, and whether the reduced survival of hybrids compared with non-hybrids and/or assortative mating were potentially important factors in retaining the divergence between these races, which probably arose during isolation in Pleistocene glacial refuges. It was found that hybrids at the focal contact zone do not have reduced embryo-to-adult survival compared with non-hybrids, and that races apparently freely interbreed without substantial assortative mating, consistent with little or no cost to hybridization. Nonetheless, at their respective transect ends the races remain distinct. This phenomenon was attributed to the elevated location of the contact zone, which is likely to make it poor habitat for E. rowelli, and thus may restrict dispersal and gene flow. There was also tentative evidence for a relaxed selection against hybridization in the hybrid zone, and the relative importance of these two explanations will require separate investigation. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111, 589-602. [ABSTRACT FROM AUTHOR]

Highlights: [•] Comparative neuroimaging can identify unique features of the human brain. [•] Comparisons with chimpanzees are crucial for learning about human brain evolution. [•] Human brains are special in terms of size, cortical organization, and connectivity. [•] Human brains are special in terms of development and aging. [ABSTRACT FROM AUTHOR]

Background: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.Objectives: The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.Methods: This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.Results: Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).Conclusions: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522). [ABSTRACT FROM AUTHOR]

Abstract: Background: Understanding the mortality rate of methamphetamine users, especially in relation to other drug users, is a core component of any evaluation of methamphetamine-related harms. Although methamphetamine abuse has had a major impact on United States (US) drug policy and substance-abuse treatment utilization, large-scale cohort studies assessing methamphetamine-related mortality are lacking. Methods: The current study identified cohorts of individuals hospitalized in California from 1990 to 2005 with ICD-9 diagnoses of methamphetamine- (n =74,139), alcohol- (n =582,771), opioid- (n =67,104), cannabis- (n =46,548), or cocaine-related disorders (n =48,927), and these groups were followed for up to 16 years. Age-, sex-, and race-adjusted standardized mortality rates (SMRs) were generated. Results: The methamphetamine cohort had a higher SMR (4.67, 95% CI 4.53, 4.82) than did users of cocaine (2.96, 95% CI 2.87, 3.05), alcohol (3.83, 95% CI 3.81, 3.85), and cannabis (3.85, 95% CI 3.67, 4.03), but lower than opioid users (5.71, 95% CI 5.60, 5.81). Conclusions: Our study demonstrates that individuals with methamphetamine-use disorders have a higher mortality risk than those with diagnoses related to cannabis, cocaine, or alcohol, but lower mortality risk than persons with opioid-related disorders. Given the lack of long-term cohort studies of mortality risk among individuals with methamphetamine-related disorders, as well as among those with cocaine- or cannabis-related conditions, the current study provides important information for the assessment of the comparative drug-related burden associated with methamphetamine use. [Copyright &y& Elsevier]

Abstract: Pulsed OSL is applied to nine fine-grained sediment samples from Sichuan province, China, using stimulating pulses of 10μs on and 240μs off, with an infrared exposure prior to each OSL measurement. Comparison of fading rates between pulsed and non-pulsed signals, the latter also obtained with a preceding IR exposure, shows that fading is significant for mainly the non-pulsed signals. Presence of a pulsed IRSL and the magnitudes of b-value to correct for lower alpha efficiency suggest that pulsing does not fully remove a significant feldspar signal, only a fading component. Comparison with ages of quartz extracts shows that pulsed OSL ages are consistent, while CW-OSL ages are slightly older and CW-IRSL ages are much older. The older ages suggest a less well-bleached feldspar component. [Copyright &y& Elsevier]

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.Methods: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).Results: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar.Conclusions: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522. [ABSTRACT FROM AUTHOR]

Study Objective: To assess whether healthy members of families of patients with inflammatory bowel disease share an immune reactivity to gut epithelial cell antigens.Design: Assessment of immune reactivity against epithelial-cell-associated components (ECAC).Methods: Detection of specific anti-ECAC serum antibodies by antibody-dependent cellular cytotoxicity (percent specific lysis) and by immunoblotting (Western blots).Patients: Index cases (131) and first-degree relatives in 17 families with 2 or more affected members, and 13 with only 1 member affected.Main Results: Compared with a gastrointestinal disease control group (0.5% +/- 0.8%), specific lysis against ECAC-C (colon-derived) among patients with inflammatory bowel disease was significantly greater in both multiply affected (8.4% +/- 8.2%; P less than 0.01) and singly affected (5.2% +/- 5.4%; P less than 0.05) families. In contrast, specific lysis by patients with other inflammatory processes of the small and large bowel (1.1% +/- 1.4%) or autoimmune disease (0.7% +/- 1.0%) did not differ from that of the gastrointestinal disease control group. Among relatives of patients with inflammatory bowel disease (index cases), specific lysis was also significantly higher than in the control group (4.8% +/- 5.5% for multiply affected, P less than 0.01, and 4.3% +/- 5.5% for singly affected, P less than 0.05). Relatives of patients with chronic inflammatory liver disease had a level of lysis (0.6% +/- 0.9%) similar to that of controls. The prevalence of antibodies to ECAC-C was 69.7% among patients with chronic inflammatory bowel disease, and 55.7% among relatives; both prevalences were significantly higher than that of the control group (8.0%, P less than 0.001). Using small-bowel-derived ECAC, the prevalence of antibodies among patients with inflammatory bowel disease and relatives was also significantly higher than that of controls. Reactivity of sera was directed to a 160- and a 137-kilodalton macromolecule.Conclusions: Immune sensitization to intestinal epithelial antigens is common in families with chronic inflammatory bowel disease; its high frequency among asymptomatic relatives suggests it may represent a primary phenomenon, perhaps predisposing individuals to gut tissue injury. [ABSTRACT FROM AUTHOR]

Peroxisomal beta-oxidation and catalase activity were investigated in liver, kidney and heart from pigs at the following timepoints: within 0.5 h after birth (0 h, unfed) and at 24 h (suckled or unsuckled), 10 d (suckled or 24-h food-deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food-deprived). In liver, peroxisomal beta-oxidation increased about twofold at 24 h for suckled pigs (P < 0.001) but did not change for unsuckled pigs. The rate was further increased in 21-d-old pigs compared with 0- (P < 0. 001) or 24-h-old (P < 0.05) pigs, but was lower at 5 mo than at 10 or 21 d (P < 0.01). The rate was higher for food-deprived pigs than suckled pigs at 10 d (P < 0.001) of age. In kidney, peroxisomal beta-oxidation was unchanged during the first 24 h but was higher (P < 0.05) at 10 d for suckled pigs and at 21 d than at 0 h. Nutritional state did not influence renal peroxisomal beta-oxidation. In heart, peroxisomal beta-oxidation did not change with age or nutritional state. The developmental pattern of fatty acyl-CoA oxidase activity was similar to that of peroxisomal beta-oxidation in each tissue. Developmental increases of peroxisomal beta-oxidation were greater than those for first-cycle peroxisomal beta-oxidation reported earlier, suggesting that peroxisomal beta-oxidation became more complete in older pigs. Catalase activity did not change during the first 24 h after birth but then increased 10.5-, 2.9-fold and 33% at 10 d in liver, kidney and heart, respectively. The concentration of catalase mRNA was only 1.1- and 1. 3-fold higher at 10 d than at 24 h in liver and kidney, respectively. Catalase activity was not affected by food deprivation. We concluded the following: 1) peroxisomal beta-oxidation develops rapidly after birth and may be important for piglets to oxidize milk fatty acids; 2) food is required for the initial induction after birth; and 3) rapidly increased catalase activity during the first 10 d of life resulted from both pretranslational and post-translational regulation. [ABSTRACT FROM AUTHOR]

The Bigfoot Unity Diabetes Management System, a smart pen cap system cleared by the U.S. Food and Drug Administration in May 2021, incorporates continuous glucose monitoring data, real-time glycemic alerts, and clinician-directed dose recommendations. This study analyzed real-world clinical outcomes data for an initial cohort (n = 58, from 13 clinics) managing multiple daily injection insulin therapy using the pen cap system for 6 months. We examined glycemic control, including hypoglycemia events and interaction with and use of the pen cap system. In a cohort mainly consisting of adults with type 2 diabetes and an average age of 62 years, the results demonstrate close adherence to established glycemic targets, including a relatively short amount of time spent in the hypoglycemic range. [ABSTRACT FROM AUTHOR]

Background: Changes in radiation therapy practice and cancer incidence bring into question prior evidence suggesting that radiation therapy predominantly injures the brachial plexus upper trunk, while tumor invasion typically injures the lower trunk.Methods: We reviewed electrodiagnostic brachial plexopathy reports in cancer survivors for predominant trunk involvement, injury mechanism (tumor invasion vs radiation), and primary cancer location.Results: Fifty-six cases of cancer-associated brachial plexopathy were identified. There was no relationship between injury mechanism and brachial plexus injury level. However, primary cancer location superior/inferior to the clavicle increased the odds of predominantly upper/lower trunk involvement by a factor of 60.0 (95% confidence interval: 7.9, 1401, respectively).Conclusions: Cancers superior/inferior to the clavicle increase the likelihood of predominantly upper/lower trunk plexopathy, respectively, regardless plexus injury mechanism. These findings contrast with older work, possibly due to more precise radiation therapy techniques and increased incidence of radiosensitive head and neck cancers. [ABSTRACT FROM AUTHOR]

Objective Umbilical cord blood (UCB) for admission laboratories is an approach to decrease anemia risk in very low birth weight (VLBW) neonates. We hypothesized that UCB use results in higher hemoglobin concentration [HgB] around 24 hours of life. Study Design A randomized control trial among VLBW infants whose admission laboratories were drawn from UCB (n = 39) or the infant (n = 41) in three U.S. military NICUs (clinicaltrials.gov#NCT02103296). Results No demographic differences were observed between groups. UCB infants had higher [HgB] at 12 to 24 hours of life (15.5 vs. 14.0 g/dL, p = 0.02). The median time to first transfusion was 17 days longer in the experimental group (p = 0.04), and at discharge, their number of donor exposures was lower (1.1 vs. 1.8, p = 0.04). Conclusion In the first 24 hours of life that is a period of higher risk for hemodynamic instability, UCB utilization for admission bloodwork in VLBW infants results in higher [HgB]. Key Points Umbilical cord blood laboratory work in preterm infants is feasible. Cord blood use for admission laboratories results in increased hemoglobin in the first 24 hours of life. Cord blood use for admission laboratories delays time to first transfusion in preterm infants. [ABSTRACT FROM AUTHOR]

Objective: We compare population aging in Europe and Asia using a measure that is both consistent over time and appropriate for cross-country comparison. Method: Sanderson and Scherbov proposed to estimate the old-age threshold by the age at which the remaining life expectancy (RLE) equals 15 years. We propose an adjustment of this measure, taking into account cross-national differences in the exceptionality of reaching that age. Results: Our old-age threshold was lower than 65 years in 2012 in Central Asia, Southern Asia, Southeastern Asia, and many Eastern European countries. These populations also experienced a higher share of elderly compared with the RLE15 method. Our method revealed more geographical diversity in the shares of elderly. Both methods exhibited similar time trends for the old-age thresholds and the shares of elderly. Discussion: Our prospective and comparative measure reveals higher population aging estimates in most Asian and Eastern European countries and more diversity in aging. [ABSTRACT FROM AUTHOR]

Introduction: Left bundle branch area pacing (LBBP) has emerged as an alternative method for conduction system pacing. While initial experience with delivery systems for stylet‐driven and lumenless lead implantation for LBBP has been described, data comparing outcomes of stylet‐driven versus lumenless lead implantation for LBBP are limited. In this study, we compare success rates and outcomes of LBBP with stylet‐driven versus lumenless lead delivery systems. Methods: Eighty‐three consecutive patients (mean age 74.1 ± 11.2 years; 56 [68%] male) undergoing attempted LBBP at a single institution were identified. Cases were grouped by lead delivery systems used: stylet‐driven (n = 53) or lumenless (n = 30). Baseline characteristics and procedural findings were recorded and compared between the cohorts. Intermediate term follow‐up data on ventricular lead parameters were also compared. Results: Baseline characteristics were similar between groups. Successful LBBP was achieved in 77% of patients, with similar success rates between groups (76% in stylet‐driven, 80% in lumenless, p = 0.79), and rates of adjudicated LBB capture and other paced QRS parameters were also similar. Compared with the lumenless group, the stylet‐driven group had significantly shorter procedure times (90 ± 4 vs. 112 ± 31 min, p = 0.004) and fluoroscopy times (10 ± 5 vs. 15 ± 6 min, p = 0.003). Ventricular lead parameters at follow‐up were similar, and rates of procedural complications and need for lead revision were low in both groups. Conclusion: Delivery systems for stylet‐driven and for lumenless leads for LBBP have comparable acute success rates. Long‐term follow‐up of lead performance following use of the various delivery systems is warranted. [ABSTRACT FROM AUTHOR]

Objectives: To determine the utility of phosphohistone H3 (PHH3) mitotic count (MC) in grading follicular lymphoma (FL).Methods: FL cases were identified (2005-2017). Three hematopathologists recorded their average Ki-67 proliferation index, MC/high-power field (hpf) using PHH3 and H&E stains, and number of centroblasts/hpf. Results were assessed for correlations and interobserver variability.Results: Forty-three cases of FL were studied. PHH3 MC resulted in the strongest correlation to grade (r = 0.701, P < .0001) compared with Ki-67 proliferation index (PI) (r = 0.681, P < .0001) and H&E MC (r = 0.536, P = .0002) and the strongest linear relationship to centroblast count (R2 = 0.453). Agreement among pathologists was strongest for PHH3 (intraclass correlation coefficient [ICC] = 0.86) followed by Ki-67 PI (ICC = 0.85) and H&E MC (ICC = 0.78).Conclusions: PHH3 correlates best to histologic grade and has less interobserver variability compared with Ki-67 PI and H&E MC. These results support using PHH3 as an adjunct in FL grading. [ABSTRACT FROM AUTHOR]

Background: Although nearly two-third of bankruptcy in the United States is medical in origin, a common assumption is that individuals facing a potentially lethal disease opt for cure at any cost. This assumption has never been tested, and knowledge of how the American population values a trade-off between cure and bankruptcy is unknown.Objectives: To determine the relative importance among the general American population of improved health versus improved financial risk protection, and to determine the impact of demographics on these preferences.Methods: A discrete-choice experiment was performed with 2359 members of the US population. Respondents were asked to value treatments with varying chances of cure and bankruptcy in the presence of a lethal disease. Latent class analysis with concomitant variables was performed, weighted for national representativeness. Sensitivity analyses were undertaken to test the robustness of the results.Results: It was found that 31.3% of the American population values cure at all costs. Nevertheless, for 8.5% of the US population, financial solvency dominates concerns for health in medical decision making. Individuals who value cure at all costs are more likely to have had experience with serious disease and to be women. No demographic characteristics significantly predicted individuals who value solvency over cure.Conclusions: Although the average American values cure more than financial solvency, a cure-at-all-costs rubric describes the preferences of a minority of the population, and 1 in 12 value financial protection over any chances of cure. This study provides empirical evidence for how the US population values a trade-off between avoiding adverse health outcomes and facing bankruptcy. These findings bring to the fore the decision making that individuals face in balancing the acute financial burden of health care access. [ABSTRACT FROM AUTHOR]

Objective/background: To compare sleep and circadian variability in adults with delayed sleep-wake phase disorder (DSWPD) to healthy controls.Patients/methods: Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break.Results and Conclusions: Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD.Clinical Trial: Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252. [ABSTRACT FROM AUTHOR]

Background: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding.Methods: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263.Findings: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group.Interpretation: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding.Funding: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway. [ABSTRACT FROM AUTHOR]

Background: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD).Methods: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase.Results: Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]).Conclusions: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients. [ABSTRACT FROM AUTHOR]

Objective: Despite efforts to improve maternal and child nutrition, undernutrition remains a major public health challenge in Ghana. The current study explored community perceptions of undernutrition and context-specific interventions that could improve maternal and child nutrition in rural Northern Ghana.Design: This exploratory qualitative study used ten focus group discussions to gather primary data. The discussions were recorded, transcribed and coded into themes using Nvivo 12 software to aid thematic analysis.Setting: The study was conducted in rural Kassena-Nankana Districts of Northern Ghana.Study Participants: Thirty-three men and fifty-one women aged 18-50 years were randomly selected from the community.Results: Most participants reported poverty, lack of irrigated agricultural land and poor harvests as the main barriers to optimal nutrition. To improve maternal and child nutrition, study participants suggested that the construction of dams at the community level would facilitate all year round farming including rearing of animals. Participants perceived that the provision of agricultural materials such as high yield seedlings, pesticides and fertiliser would help boost agricultural productivity. They also recommended community-based nutrition education by trained health volunteers, focused on types of locally produced foods and appropriate ways to prepare them to help improve maternal and child nutrition.Conclusion: Drawing on these findings and existing literature, we argue that supporting community initiated nutrition interventions such as improved irrigation for dry season farming, provision of agricultural inputs and community education could improve maternal and child nutrition. [ABSTRACT FROM AUTHOR]

Background: The objective of this report was to compare the prevalence of acute respiratory distress syndrome (ARDS) and associated mortality between military service members with burns sustained during or in support of combat operations and civilian burn patients treated at a single burn center.Methods: Demographic and physiologic data were collected retrospectively on mechanically ventilated military and civilian patients admitted to our burn intensive care unit between January 2003 and December 2011. Patients with ARDS were identified and categorized as mild, moderate, or severe using the Berlin criteria. Demographics and clinical outcomes were compared. After initial comparison, propensity matching was performed and mortality compared.Results: A total of 891 burn patients required mechanical ventilation during the study period; 291 military and 600 civilian. The prevalence of ARDS was 34% (n=304) for the entire cohort, 33% (n=96) for military, and 35% (n=208) for civilians (p=0.55). For the entire cohort, despite more severe injury burden, military patients had a significantly lower overall mortality (17% vs. 28%; p=0.0002) as well as ARDS mortality (33 vs. 48%, p=0.02) when compared to civilians. This difference was not significant after propensity matching based on age.Conclusion: In a retrospective cohort study, burned military patients on mechanical ventilation had a significantly lower overall and ARDS mortality despite larger burns and more severe injury when compared to civilian burn patients. This difference appears to be largely because of age. [ABSTRACT FROM AUTHOR]

We evaluated the effects of simplified habit reversal (HR) that combined competing response training and differential reinforcement on skin picking by an adolescent female with autism attending a classroom at a specialized school. The competing response training procedure allowed her to manipulate preferred sensory stimuli independently and when instructed by classroom staff. Differential reinforcement included praise and tokens that she received following intervals without skin picking and when she performed competing response training. Compared with a baseline phase, skin picking decreased with simplified HR and during a subsequent phase when treatment was faded by implementing differential reinforcement without competing response training. We discuss the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare long-term microtensile bond strength of zirconia, surface-modified via a novel treatment, to current surface conditioning methods for zirconia, when resin bonded to dental composite. Methods: Two ProCAD (porcelain) and 10 sintered ZirCAD (ZrO2) blocks (18mm×14mm×12mm) were obtained from manufacturers. Twelve Herculite XRV composite blocks were fabricated (18mm×14mm×12mm). Bonding surface of blocks was polished through 1200-grit SiC and air-abraded (50μm alumina, 0.28MPa, 20s). Blocks were then separated into six groups: (1) porcelain (control), HF-etched/silane-treated, (2) ZrO2, tribochemical-coated/silane-treated, (3) ZrO2, primer-treated, (4) ZrO2, modified via novel 3.2nm silica layer/silane-treated, (5) ZrO2, modified via novel 5.8nm silica layer/silane-treated, and (6) ZrO2, modified via novel 30.4nm silica layer/silane-treated. Blocks were bonded to composite using Clearfil Esthetic cement. Blocks were stored in distilled water (37°C, 24h), then cut into microtensile bars (n =8/gp), then bond strengths were measured using a universal testing machine at 0, 1, 3, and 6 months. All groups were statistically analyzed (ANOVA, Tukey''s, p <0.05). Results: At 6 months (aging), all silica seed layer specimens displayed microtensile bond strength similar to CoJet specimens but less than that of silane-modified dental porcelain. Conclusion: The deposition of a silica layer on zirconia resulted in similar or superior long-term resin bond strength when compared to traditional silanation and bonding techniques for zirconia but lower than that for silane-treated dental porcelain. [Copyright &y& Elsevier]

Background: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.Research Question: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD.Study Design and Methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status.Results: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001.Interpretation: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions. [ABSTRACT FROM AUTHOR]

Background: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear.Research Question: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes?Study Design and Methods: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site.Results: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66).Interpretation: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies. [ABSTRACT FROM AUTHOR]

Toxicities of the radiolytically generated oxidizing radicals HO˙, CO3˙−a, and NO2˙ toward suspension cultures of a bacterium (Escherichia coli) and a yeast (Saccharomyces cerevisiae) were examined. As demonstrated by the absence of protection from the membrane-impermeable HO˙ scavenger polyethylene glycol (PEG), externally generated HO˙ was not bactericidal under these conditions; however, partial protection by PEG was observed for S. cerevisiae, indicating the presence of a fungicidal pathway involving external HO˙. For both organisms, conversion of external HO˙ to the secondary radical, CO3˙−, by reaction with HCO3− increases their susceptibility to radiolytic killing. In contrast, externally generated NO2˙ exhibited toxicity comparable to that of CO3˙− toward E. coli, but completely blocked the extracellular toxicity of HO˙ toward S. cerevisiae. Cogeneration of equal fluxes of NO2˙− and either HO˙ or CO3˙− also essentially eliminated the extracellular microbicidal reactions. This behavior is consistent with expectations based upon relative rates of radical–radical self-coupling and cross-coupling reactions. The different patterns of toxicity observed imply fundamentally different microbicidal mechanisms for the two organisms, wherein the bacterium is susceptible to killing by oxidation of highly reactive targets on its cellular envelope but, despite undergoing similar oxidative insult, the fungus is not. [Copyright &y& Elsevier]

: ObjectivesWe sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD).: BackgroundPrevious studies have suggested associations between cholesterol lowering and psychological well-being.: MethodsStudy subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores.: ResultsStudy subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs'' cholesterol-lowering effects.: ConclusionsLong-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility. [Copyright &y& Elsevier]

The social value of risk reduction (SVRR) is the marginal social value of reducing an individual's fatality risk, as measured by some social welfare function (SWF). This Article investigates SVRR, using a lifetime utility model in which individuals are differentiated by age, lifetime income profile, and lifetime risk profile. We consider both the utilitarian SWF and a "prioritarian" SWF, which applies a strictly increasing and strictly concave transformation to individual utility. We show that the prioritarian SVRR provides a rigorous basis in economic theory for the "fair innings" concept, proposed in the public health literature: as between an older individual and a similarly situated younger individual (one with the same income and risk profile), a risk reduction for the younger individual is accorded greater social weight even if the gains to expected lifetime utility are equal. The comparative statics of prioritarian and utilitarian SVRRs with respect to age, and to (past, present, and future) income and baseline survival probability, are significantly different from the conventional value per statistical life (VSL). Our empirical simulation based upon the U.S. population survival curve and income distribution shows that prioritarian SVRRs with a moderate degree of concavity in the transformation function conform to widely held views regarding lifesaving policies: the young should take priority but income should make no difference. [ABSTRACT FROM AUTHOR]

Introduction: Radiculopathy is diagnosed by needle electromyography, with nerve conduction studies excluding alternative diagnoses.Methods: In patients referred for electrodiagnostic evaluation of radiating limb pain, we compared ulnar motor amplitudes between those with and without electromyographically confirmed C8 radiculopathy, as well as fibular motor amplitudes between those with and without electromyographically confirmed L5 radiculopathy.Results: Patients with electromyographically confirmed C8 or L5 radiculopathy demonstrated decreased ulnar or fibular motor amplitudes, respectively, as compared to patients without radiculopathy. Receiver operating characteristic curves demonstrated good diagnostic accuracy, with areas under the curve of 0.85 and 0.82, respectively. Optimal cut-offs for electromyographically confirmed C8 and L5 radiculopathies were 10.2 mV and 3.6 mV, respectively, with associated sensitivities/specificities of 0.86/0.74 and 0.92/0.60.Discussion: Ulnar and fibular motor amplitudes may have clinical utility in assessing the likelihood of patients demonstrating electromyographically confirmed C8 and L5 radiculopathies with active denervation. The findings may be particularly useful in patients intolerant of needle electromyography. Muscle Nerve 59:561-561, 2019. [ABSTRACT FROM AUTHOR]

Background: Current resuscitation guidelines emphasize the use of waveform capnography to help guide rescuers during cardiopulmonary resuscitation (CPR). However, chest compressions often cause oscillations in the capnogram, impeding its reliable interpretation, either visual or automated. The aim of the study was to design an algorithm to enhance waveform capnography by suppressing the chest compression artefact.Methods: Monitor-defibrillator recordings from 202 patients in out-of-hospital cardiac arrest were analysed. Capnograms were classified according to the morphology of the artefact. Ventilations were annotated using the transthoracic impedance signal acquired through defibrillation pads. The suppression algorithm is designed to operate in real-time, locating distorted intervals and restoring the envelope of the capnogram. We evaluated the improvement in automated ventilation detection, estimation of ventilation rate, and detection of excessive ventilation rates (over-ventilation) using the capnograms before and after artefact suppression.Results: A total of 44 267 ventilations were annotated. After artefact suppression, sensitivity (Se) and positive predictive value (PPV) of the ventilation detector increased from 91.9/89.5% to 98.0/97.3% in the distorted episodes (83/202). Improvement was most noticeable for high-amplitude artefact, for which Se/PPV raised from 77.6/73.5% to 97.1/96.1%. Estimation of ventilation rate and detection of over-ventilation also upgraded. The suppression algorithm had minimal impact in non-distorted data.Conclusion: Ventilation detection based on waveform capnography improved after chest compression artefact suppression. Moreover, the algorithm enhances the capnogram tracing, potentially improving its clinical interpretation during CPR. Prospective research in clinical settings is needed to understand the feasibility and utility of the method. [ABSTRACT FROM AUTHOR]

Objectives: Our goal was to evaluate the efficacy of a fully automated method for assessing the image quality (IQ) of coronary computed tomography angiography (CCTA).Methods: The machine learning method was trained using 75 CCTA studies by mapping features (noise, contrast, misregistration scores, and un-interpretability index) to an IQ score based on manual ground truth data. The automated method was validated on a set of 50 CCTA studies and subsequently tested on a new set of 172 CCTA studies against visual IQ scores on a 5-point Likert scale.Results: The area under the curve in the validation set was 0.96. In the 172 CCTA studies, our method yielded a Cohen's kappa statistic for the agreement between automated and visual IQ assessment of 0.67 (p < 0.01). In the group where good to excellent (n = 163), fair (n = 6), and poor visual IQ scores (n = 3) were graded, 155, 5, and 2 of the patients received an automated IQ score > 50 %, respectively.Conclusion: Fully automated assessment of the IQ of CCTA data sets by machine learning was reproducible and provided similar results compared with visual analysis within the limits of inter-operator variability.Key Points: • The proposed method enables automated and reproducible image quality assessment. • Machine learning and visual assessments yielded comparable estimates of image quality. • Automated assessment potentially allows for more standardised image quality. • Image quality assessment enables standardization of clinical trial results across different datasets. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that the immune system can recognize polyethylene glycol (PEG), leading to the accelerated blood clearance (ABC) of PEGylated particles. Our aim here was to study the generation of anti-PEG immunity and changes in PEGylated microbubble pharmacokinetics during repeated contrast-enhanced ultrasound imaging in rats. We administered homemade PEGylated microbubbles multiple times over a 28-d period and observed dramatically accelerated clearance (4.2 × reduction in half-life), which was associated with robust anti-PEG IgM and anti-PEG IgG antibody production. Dosing animals with free PEG as a competition agent before homemade PEGylated microbubble administration significantly prolonged microbubble circulation, suggesting that ABC was largely driven by circulating anti-PEG antibodies. Experiments with U.S. Food and Drug Administration-approved Definity microbubbles similarly resulted in ABC and the generation of anti-PEG antibodies. Experiments repeated with non-PEGylated Optison microbubbles revealed a slight shift in clearance, indicating that immunologic factors beyond anti-PEG immunity may play a role in ABC, especially of non-PEGylated agents. [ABSTRACT FROM AUTHOR]

Background: Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness.Methods: The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat.Discussion: This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis.Trial Registration: ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation.Methods: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked.Results: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes.Conclusions: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .). [ABSTRACT FROM AUTHOR]

Background: Absence of subclinical atherosclerosis is considered safe to defer statin therapy in general population. However, impact of statins on atherosclerotic cardiovascular disease in patients with diabetes stratified by coronary artery calcium (CAC) scores and extent of non-obstructive CAD on coronary computed tomography angiography (CCTA) has not been evaluated.Methods: CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multi-center Registry) study enrolled consecutive adults 18 years of age between 2005 and 2009 who underwent 364-detector row CCTA for suspected CAD. The long-term registry includes data on 12,086 subjects who underwent CCTA at 17 centers in 9 countries. In this sub-study of CONFIRM registry, patients with diabetes mellitus (DM) and without diabetes mellitus with normal CCTA or non-obstructive plaque (<50 % diameter stenosis) for whom data on baseline statin use was available were included. CAC score was calculated using Agatston score. The magnitude of non-obstructive coronary artery disease on CCTA was quantified using segment involvement score (SIS). Primary outcome was major cardiovascular events (MACE) which included all-cause mortality, myocardial infarction, and target vessel re-vascularization.Results: A total of 7247 patients (Mean age 56.8 years) with a median follow up of 5 years were included. For DM patients, baseline statin therapy significantly reduced MACE for patients with CAC ≥100 (HR: 0.24; 95 % CI 0.07-0.87; p = 0.03) and SIS≥3 (HR: 0.23; 95 % CI 0.06-0.83; p = 0.024) compared to those not on statin therapy. Among Diabetics with lower CAC (<100) and SIS (≤3) scores, MACE was similar in statin and non-statin groups. In contrast, among non-DM patients, MACE was similar in statin and no statin groups irrespective of baseline CAC (1-99 or ≥100) and SIS.Conclusion: In this large multicenter cohort of patients, the presence and extent of subclinical atherosclerosis as assessed by CAC and SIS identified patients most likely to derive benefit from statin therapy. [ABSTRACT FROM AUTHOR]

Background: Breastfeeding promotion is regarded as one of the most effective interventions to improve child health, and could reduce under-5-mortality by 8 % globally. Few studies have assessed the health outcomes beyond infancy of interventions promoting exclusive breastfeeding.Methods: This study assessed growth in under-five children who participated in a cluster-randomised trial in Eastern Uganda (ClinicalTrials.gov.no.NCT00397150). In the intervention arm, peer counsellors promoted exclusive breastfeeding during the first 6 months of infancy. There were no interventions after 6 months of age. Mother-infant pairs were interviewed at visits scheduled at 3, 6, 12 and 24 weeks after birth and follow-up visits at 2 and 5 years, with 765 included in the analyses.Results: The mean length/height-for-age and weight-for-age-z-score (HAZ, WAZ) decreased with increasing age in both the intervention and control arms. At the three weeks visit, HAZ in the intervention was -0.45 (-0.68;-0.21) and -0.32 (-0.56;-0.07) in the control arm. At the 2 year follow-up, the mean HAZ in the intervention was -1.85 (95 % CI -1.97;-1.73) compared to -1.61 (-1.87;-1.34) in the control. Similarly, at the 5 year follow-up, the mean HAZ in the intervention was -1.78 (-2.08;-1.47) compared to -1.53 (-1.79;-1.28) in the control arm. At the 2 year follow-up visit, 139 (45 %) were stunted (HAZ<-2) in the intervention compared to 109 (37 %) in the control arm, odds ratio (OR) 1.7 (1.1;2.4). Underweight (WAZ<-2) was also more common in the intervention arm than in the control at the five years follow-up (OR 1.7 (1.0;2.8)), with a mean WAZ of -1.28 (-1.47;-1.08) and -1.06 (-1.19;-0.92) in the intervention and control arm, respectively.Conclusion: While stunting was widespread at 2 and 5 years of age in both arms, it was more common in the intervention arm. It is questionable whether community-based support from lay people with short training and focussing only on exclusive breastfeeding, is an appropriate strategy to improve child health and development.Trial Registration: ClinicalTrials.gov.no. NCT00397150 . Registered 7th of November 2006. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management.Objectives: This study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD).Methods: Patients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications.Results: VAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02).Conclusions: Patients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing. [ABSTRACT FROM AUTHOR]

We allocated 76 men scheduled for radical retropubic prostatectomy to peri-operative lidocaine 2% or saline 0.9%: a pre-operative 0.075 ml.kg(-1) intravenous bolus; an intra-operative intravenous infusion at 0.075 ml.kg(-1) .h(-1) ; and 24 hours' postoperative subcutaneous infusion at 0.075 ml.kg(-1) .h(-1) . Lidocaine reduced the postoperative hospital stay by a mean (95% CI) of 1.3 (0.3-2.4) days, p = 0.017, from a mean (SD) of 4.6 (3.2) days with saline. There were no significant differences in pain at rest or on coughing at 24 h. [corrected]. Lidocaine reduced 24-h morphine consumption by a mean (95% CI) of 13.9 (2.2-25.7) mg, p = 0.021, from a mean (SD) of 52.3 (26.9) mg with saline. There were no differences in other outcomes. [ABSTRACT FROM AUTHOR]