Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Association between polypharmacy and hard braking events in older adult drivers.

BACKGROUND: Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers. METHODS: Data for this study came from a naturalistic driving study of 2990 older adults. Information about medications was collected through the "brown-bag review" method. Primary vehicles of the study participants were instrumented with data recording devices for up to 44 months. Multivariable negative binomial model was used to estimate the adjusted incidence rate ratios (aIRRs) and 95 % confidence intervals (CIs) of hard-braking events (i.e., maneuvers with linear deceleration rates ≥0.4 g) associated with polypharmacy. RESULTS: Of the 2990 participants, 2872 (96.1 %) were eligible for this analysis. At the time of enrollment, 157 (5.5 %) drivers were taking fewer than two medications, 904 (31.5 %) were taking 2-5 medications, 895 (31.2 %) were taking 6-9 medications, 571 (19.9 %) were taking 10-13 medications, and 345 (12.0 %) were taking 14 or more medications. Compared to drivers using fewer than two medications, the risk of hard-braking events increased 8 % (aIRR 1.08, 95 % CI 1.04, 1.13) for users of 2-5 medications, 12 % (aIRR 1.12, 95 % CI 1.08, 1.16) for users of 6-9 medications, 19 % (aIRR 1.19, 95 % CI 1.15, 1.24) for users of 10-13 medications, and 34 % (aIRR 1.34, 95 % CI 1.29, 1.40) for users of 14 or more medications. CONCLUSIONS: Polypharmacy in older adult drivers is associated with significantly increased incidence of hard-braking events in a dose-response fashion. Effective interventions to reduce polypharmacy use may help improve driving safety in older adults.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Interaction between benzodiazepines and prescription opioids on incidence of hard braking events in older drivers.

BACKGROUND: Polypharmacy use among older adults is of increasing concern for driving safety. This study assesses the individual and joint effects of benzodiazepines and prescription opioids on the incidence of hard braking events in older drivers. METHODS: Data for this study came from the Longitudinal Research on Aging Drivers project-a multisite, prospective cohort study of 2990 drivers aged 65-79 years at enrollment (2015-2017). Adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (defined as maneuvers with deceleration rates ≥0.4 g and commonly known as near-crashes) were estimated through multivariable negative binominal modeling. RESULTS: Of the 2929 drivers studied, 167 (5.7%) were taking benzodiazepines,  163 (5.6%) prescription opioids, and 23 (0.8%) both drugs at baseline. The incidence rates of hard braking events per 1000 miles driven were 1.14 (95% CI 1.10-1.18) for drivers using neither benzodiazepines nor prescription opioids, 1.25 (95% CI 1.07-1.43) for those using benzodiazepines only, 1.55 (95% CI 1.35-1.76) for those using prescription opioids only, and 1.63 (95% CI 1.11-2.16) for those using both medications. Multivariable modeling revealed that the use of prescription opioids was associated with a 19% increased risk of hard braking events (aIRR 1.19, 95% CI 1.03-1.36). There existed a positive interaction between the two drugs on the additive scale but not on the multiplicative scale. CONCLUSION: Concurrent use of benzodiazepines and prescription opioids by older drivers appears to affect driving safety through increased incidence of hard braking events.

Sex-Specific Pathways Lead to Statural Growth Impairment in Children with Crohn's Disease.

OBJECTIVES: To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD). STUDY DESIGN: Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined. RESULTS: There were 122 children with CD (63% male) who completed 594 visits. The mean ± SD chronological age was 11.70 ± 1.79 years. The mean ± SD height chronological age-Z-score was -0.03 ± 0.99 in males and -0.49 ± 0.87 in females. The mean ± SD height bone age-Z-score was 0.23 ± 0.93 in males and 0.37 ± 0.96 in females. The magnitude of the mean height Z-score difference was greater in females (-0.87 ± 0.94) than males (-0.27 ± 0.90; P = .005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P < .001) and IL-12p70 (P = .035) with gonadotropin-bone age-Z-scores; IL-8 (P = .010), IL-12p70 (P = .020), and interferon-γ (P = .004) with sex hormone-bone age-Z-scores, and IL-8 (P = .044) and interferon-γ (P < .001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P = .019) and IL-6 (P = .025) with insulin-like growth factor 1-bone age-Z-scores. CONCLUSIONS: Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamic-pituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium.

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Clinical Variables Associated With Statural Growth in Pediatric Crohn's Disease Differ by Sex (The Growth Study).

BACKGROUND: Statural growth impairment is more common in male patients with Crohn's disease (CD). We identified clinical variables associated with height z score differences by sex in children participating in the Growth Study, a prospective multicenter longitudinal study examining sex differences in growth impairment in pediatric CD. METHODS: Patients with CD (female patients with bone age [BA] ≥4 years 2 months and ≤12 years; male patients with BA ≥5 years and ≤14 years at screening) who had completed study visit 1 qualified. The height z score difference was computed as height z score based on chronological age minus height z score based on BA. RESULTS: One hundred thirteen patients with CD (36% female) qualified. The mean chronological age was 12.0 ± 1.8 (SD) years. The magnitude of the mean height z score difference was significantly greater in female patients (-0.9 ± 0.8) than in male patients (-0.5 ± 0.9; P = 0.021). An initial classification of inflammatory bowel disease as CD (P = 0.038) and perianal disease behavior at diagnosis (P = 0.009) were associated with higher standardized height gain with BA progression, and arthralgia at symptom onset (P = 0.016), azathioprine/6-merpcaptopurine (P = 0.041), and probiotics (P ≤ 0.021) were associated with lower standardized height gain with BA progression in female patients. Patient-reported poor growth at symptom onset (P = 0.001), infliximab (P ≤ 0.025), biologics (P ≤ 0.015), methotrexate (P = 0.042), and vitamin D (P ≤ 0.010) were associated with higher standardized height gain with BA progression, and initial classification as CD (P = 0.025) and anorexia (P = 0.005) or mouth sores (P = 0.004) at symptom onset were associated with lower standardized height gain with BA progression in male patients. CONCLUSIONS: Different clinical variables were associated with statural growth in male patients vs female patients, suggesting that sex-specific molecular pathways lead to statural growth impairment in CD.

Introduction to and Screening Visit Results of the Multicenter Pediatric Crohn's Disease Growth Study.

BACKGROUND: Statural growth impairment is more common in males with Crohn's disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study. METHODS: Crohn's disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score. RESULTS: One hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was -0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was -0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (-1.0) was significantly lower than in males (-0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6-14.6) years. CONCLUSIONS: Our screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

Implementing the protocol of a pilot randomized controlled trial for the recovery-oriented intervention to people with psychoses in two Latin American cities / Implementação de um protocolo para um estudo piloto randomizado e controlado sobre uma intervenção voltada para a recuperação em pessoas com psicoses em duas cidades latino-americanas / Implementando un protocolo para una prueba piloto controlada aleatorizada en una intervención orientada a la recuperación de personas con psicosis en dos ciudades latinoamericanas

Several Latin American countries have made remarkable strides towards offering community mental health care for people with psychoses. Nonetheless, mental health clinics generally have a very limited outreach in the community, tending to have weaker links to primary health care; rarely engaging patients in providing care; and usually not providing recovery-oriented services. This paper describes a pilot randomized controlled trial (RCT) of Critical Time Intervention-Task Shifting (CTI-TS) aimed at addressing such limitations. The pilot RCT was conducted in Santiago (Chile) and Rio de Janeiro (Brazil). We included 110 people with psychosis in the study, who were recruited at the time of entry into community mental health clinics. Trial participants were randomly divided into CTI-TS intervention and usual care. Those allocated to the intervention group received usual care and, in addition, CTI-TS services over a 9-month period. Primary outcomes include quality of life (WHO Quality of Life Scale - Brief Version) and unmet needs (Camberwell Assessment of Needs) at the 18-month follow-up. Primary outcomes at 18 months will be analyzed by Generalized Estimating Equations (GEE), with observations clustered within sites. We will use three-level multilevel models to examine time trends on the primary outcomes. Similar procedures will be used for analyzing secondary outcomes. Our hope is that this trial provides a foundation for planning a large-scale multi-site RCT to establish the efficacy of recovery-oriented interventions such as CTI-TS in Latin America.

Diversos países latino-americanos já alcançaram avanços notáveis na oferta de assistência em saúde mental para pessoas com psicoses. No entanto, as clínicas de saúde mental geralmente realizam atividades de extensão muito limitadas dentro das comunidades, tendem a ter vínculos fracos com a assistência primária, raramente envolvem os próprios pacientes nos cuidados e poucas vezes prestam serviços orientados para a recuperação. O artigo descreve um estudo piloto randomizado e controlado sobre a Critical Time Intervention-Task Shifting (CTI-TS), que teve como objetivo analisar essas limitações. O estudo piloto foi realizado em Santiago (Chile) e no Rio de Janeiro (Brasil). Teve como meta a inclusão de 110 pessoas com psicose, recrutadas no momento da entrada em clínicas comunitárias de saúde mental. Os participantes foram randomizados para o CTI-TS ou para os cuidados usuais. Aqueles alocados ao grupo da intervenção receberam os cuidados usuais e os serviços de CTI-TS ao longo de 9 meses. Os desfechos primários incluíram a qualidade de vida (WHO Quality of Life Scale - Brief Version) e as necessidades não atendidas (Camberwell Assessment of Needs) no acompanhamento aos 18 meses. Os desfechos primários aos 18 meses serão analisados com a técnica de Equações de Estimação Generalizadas (GEE), com as observações agrupadas dentro dos locais do estudo. Serão utilizados modelos em três níveis para examinar as tendências temporais nos desfechos primários. Procedimentos semelhantes serão utilizados para analisar os resultados secundários. Espera-se que o estudo forneça uma base para planejar um estudo randomizado e controlado em grande escala e em múltiplos locais para estabelecer a eficácia da intervenção orientada para a recuperação, a exemplo da CTI-TS, na América Latina.

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Thiopurines are negatively associated with anthropometric parameters in pediatric Crohn's disease.

AIM: To determine the distribution of anthropometric parameter (AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric Crohn's disease (CD). METHODS: CD patients [< chronological age (CA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants' demographic characteristics and key variables of interest. Paired t-tests were used to compare AP-z-scores calculated based on CA (CA z-scores) and bone age (BA) (BA z-scores) for interpretation of AP's. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-z-scores calculated based on CA (n = 82) and BA (n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals. RESULTS: Mean CA at the time of the study visit was 15.3 ± 3.5 (SD; range = 4.8-20.7) years. Mean triceps skinfold (P = 0.039), subscapular skinfold (P = 0.002) and mid-arm circumference (MAC) (P = 0.001) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold [adalimumab (P = 0.018) and methotrexate (P = 0.027)] and BMI CA z-scores [adalimumab (P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAC (P = 0.045), subscapular skinfold (P = 0.014), weight (P = 0.002) and BMI (P = 0.013) CA z-scores. ESR, CRP, and WBC count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated, with specific AP z-scores (P < 0.05). Mean height CA z-scores were higher in females, not males, treated with infliximab (P = 0.038). Hemoglobin (P = 0.018) was positively associated, while platelets (P = 0.005), ESR (P = 0.003) and CRP (P = 0.039) were negatively associated with height CA z-scores in males, not females. CONCLUSION: Our results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric CD. Prospective longitudinal studies are required.

The effect of albendazole treatment on non-seizure outcomes in patients with symptomatic neurocysticercosis.

Background: There is little information about the impact of anthelminthic treatment on clinical symptoms other than seizures in neurocysticercosis (NC). We investigated the effect of albendazole on non-seizure symptoms experienced by patients with NC. Methods: Data are from a randomized controlled trial comparing albendazole plus prednisone with placebo plus prednisone for treatment of NC among 173 patients with active or transitional NC cysts and new-onset symptoms. We performed negative binomial regression to examine the number of follow-up visits when a symptom was reported, logistic regression to examine the probability of experiencing the symptom and Cox proportional hazards models to examine the time to first reporting the symptom. Results: Eighty-five percent of patients reported at least one non-seizure symptom at baseline. Those treated with albendazole had significantly lower odds of memory loss and/or confusion during months 1-24 (odds ratio [OR] 0.42, p=0.037) and significantly increased odds of anxiety and/or depression during months 1-12 (OR 1.87, p=0.049). No treatment difference existed in experiencing symptoms in general or in experiencing headaches, limb weakness or gait disturbances, vomiting, nausea and/or stomach pain or visual disturbances over the follow-up period. Conclusions: While the prevalence of non-seizure symptoms was high, albendazole treatment was associated with only two significant differences in the non-seizure symptoms over follow-up. Further research is needed to identify strategies to reduce the long-term symptom burden in patients with NC.

Adverse Events and Resource Utilization After Spinal and General Anesthesia in Infants Undergoing Pyloromyotomy.

BACKGROUND AND OBJECTIVES: Interest in spinal anesthesia (SA) is increasing because of concern about the long-term effects of intravenous (IV) and inhaled anesthetics in young children. This study compared SA versus general anesthesia (GA) in infants undergoing pyloromyotomy. METHODS: Between 2000 to 2013, the University of Vermont Medical Center almost exclusively used SA for infant pyloromyotomy surgery, whereas Columbia University Medical Center relied on GA. Outcomes included adverse events (AEs) within 48 hours of surgery, operating room (OR) time, and postoperative length of stay (LOS). Regression was used to evaluate the association between anesthesia technique and outcomes, accounting for demographic and clinical covariates. RESULTS: We studied 218 infants with SA at the University of Vermont Medical Center and 206 infants with GA at Columbia University Medical Center. In the SA group, 96.3% of infants had adequate initial analgesic levels, but 35.8% required supplemental IV or inhaled anesthetic agents. Compared with GA, the risk of AEs in SA (adjusted odds ratio, 0.60; 95% confidence interval [CI], 0.27-1.36) did not significantly differ, but SA was associated with shorter OR times (17.5 minutes faster; 95% CI, 13.5-21.4 minutes) and shorter postoperative LOS (GA is 1.19 times longer; 95% CI, 1.01-1.40). CONCLUSIONS: Infants undergoing pyloromyotomy with SA had shorter OR times and postoperative LOS, no significant differences in AE rates, and decreased exposure to IV and inhaled anesthetics, although SA infants often still required supplemental anesthetics. Whether these differences result in any long-term benefit is unclear; further studies are needed to determine the risk of rare AEs, such as aspiration.

Individualized Household Allergen Intervention Lowers Allergen Level But Not Asthma Medication Use: A Randomized Controlled Trial.

BACKGROUND: Environmental exposures to indoor allergens are major contributors to asthma symptoms, particularly in inner cities. The effectiveness of household allergen reduction as an adjunct to National Asthma Education Prevention Program guideline-based pharmacologic therapy in asthma has not been prospectively studied. OBJECTIVE: To study the effect of individualized allergen reduction on ability to reduce asthma pharmacologic therapy over 40 weeks. METHODS: We performed a randomized controlled trial to determine the effect of multifaceted indoor allergen avoidance measures on the ability to reduce asthma controller therapy in adults and children residing in New York City who were both sensitized and exposed to at least 1 indoor allergen. Asthma treatment and control were optimized in all subjects before randomization. RESULTS: A total of 125 subjects were randomized to receive individualized household allergen reduction and 122 received a sham intervention. Subjects in the intervention group significantly reduced all measured allergen levels (cat, dog, dust mite allergens in the bedroom, cockroach and mouse allergens in the kitchen and bedroom); those in the control group reduced only dust mite and mouse allergens in the bedroom and cockroach allergen in the kitchen. Participants in the intervention arm reduced National Asthma Education Prevention Program-based therapy from step 4.4 at randomization to 3.50 postintervention (range, 0-6); participants in the control arm reduced medication from step 4.4 to 3.4 (P = .76). There were no differences in other measured asthma outcomes. CONCLUSIONS: Targeted allergen avoidance measures do not allow for reduction in asthma pharmacologic therapy compared with usual care in patients already receiving optimal controller therapy.

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline.

Atrial Cardiopathy and Cryptogenic Stroke: A Cross-sectional Pilot Study.

BACKGROUND: There is increasing evidence that left atrial dysfunction or cardiopathy is associated with ischemic stroke risk independently of atrial fibrillation. We aimed to determine the prevalence of atrial cardiopathy biomarkers in patients with cryptogenic stroke. METHODS: We included consecutive patients with ischemic stroke enrolled in the New York Columbia Collaborative Specialized Program of Translational Research in Acute Stroke registry between December 1, 2008, and April 30, 2012. Medical records were reviewed and patients with a diagnosis of cryptogenic stroke were identified. Atrial cardiopathy was defined as at least one of the following: serum N-terminal probrain natriuretic peptide (NT-proBNP) level greater than 250 pg/mL, P-wave terminal force velocity in lead V1 (PTFV1) on electrocardiogram (ECG) greater than 5000 µV⋅ms, or severe left atrial enlargement (LAE) on echocardiogram. We compared clinical, echocardiographic, and radiological characteristics between patients with and without atrial cardiopathy. RESULTS: Among 40 patients with cryptogenic stroke, 63% had at least one of the biomarkers of atrial cardiopathy; 49% had elevated NT-proBNP levels, 20% had evidence of increased PTFV1 on ECG, and 5% had severe LAE. Patients with atrial cardiopathy were more likely to be older (76 versus 62 years, P = .012); have hypertension (96% versus 33%, P < .001), hyperlipidemia (60% versus 27%, P = .05), or coronary heart disease (28% versus 0%, P = .033); and less likely to have a patent foramen ovale (4% versus 40%, P = .007). CONCLUSION: There is a high prevalence of biomarkers indicative of atrial cardiopathy in patients with cryptogenic stroke. Clinical trials are needed to determine whether these patients may benefit from anticoagulation to prevent stroke.

The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis.

BACKGROUND: Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. METHODS: In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. RESULTS: Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. CONCLUSIONS: Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis.

Olfactory identification deficits and increased mortality in the community.

OBJECTIVE: To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. METHODS: Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index. RESULTS: During follow-up (mean = 4.1 years, standard deviation = 2.6), 349 of 1,169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), be male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (hazard ratio [HR] = 1.07 per point interval, 95% confidence interval [CI] = 1.05-1.08, p < 0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, body mass index, and vision and hearing impairment (HR = 1.05, 95% CI = 1.03-1.07, p < 0.001). Compared to the fourth quartile with the highest UPSIT scores, HRs for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95% CI = 2.71-5.34), 1.75 (95% CI = 1.23-2.50), and 1.58 (95% CI = 1.09-2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores. INTERPRETATION: Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity.

Fetal echocardiographic measurements and the need for neonatal surgical intervention in Tetralogy of Fallot.

BACKGROUND: This study aimed to evaluate fetal echocardiographic measurements at the time of the first fetal echocardiogram as predictors of neonatal outcome for tetralogy of Fallot (TOF). METHODS: The study reviewed all infants with a prenatal diagnosis of TOF from January 2004 to June 2011. Aortic valve (AoV), pulmonary valve (PV), main pulmonary artery (MPA), left and right pulmonary artery diameters, and ductus arteriosus flow were evaluated on fetal echocardiograms, and associations between the fetal echocardiogram and the neonatal echocardiogram measurements and outcomes were assessed. RESULTS: The study identified 67 TOF patients who had an initial fetal echocardiogram at a mean gestational age of 25.0 ± 5.2 weeks. Patients with absent PV syndrome or major aortopulmonary collaterals were excluded from the study, as were those without anterograde pulmonary blood flow at the first fetal echocardiogram. Of the remaining 44 patients, 10 were ductal dependent and required neonatal surgery. Infants who were ductal dependent had lower fetal PV (-5.38 ± 2.95 vs. -3.51 ± 1.66; p < 0.05) and MPA (-3.94 ± 1.66 vs. -2.87 ± 1.04; p < 0.05) z-scores. A fetal PV z-score of -5 predicted ductal dependence with 78 % sensitivity and 87 % specificity, and a PV z-score of -3 showed 100 % sensitivity and 34 % specificity (p < 0.001). Fetuses with a reversed left-to-right flow across the ductus arteriosus (DA) were more likely to be ductal dependent (odds ratio, 25; p < 0.001) than those who had normal ductal flow. CONCLUSIONS: In TOF, fetal PV and MPA z-scores and direction of the DA blood flow predict neonatal ductal dependence. Patients with fetal PV z-scores lower than -3 or any left-to-right flow at the level of the DA should be admitted to a center where prostaglandin is available.

Primary arterial switch operation as a strategy for total correction of Taussig-Bing anomaly: a 21-year experience.

BACKGROUND: Studies of the arterial switch operation for Taussig-Bing anomaly demonstrate significant rates of reintervention and mortality, particularly after initial palliation to delay complete repair. We aimed to describe the long-term outcomes of our 21-year practice of single-stage arterial switch operation for all patients with Taussig-Bing anomaly. METHODS AND RESULTS: A retrospective study was performed, and 43 patients with Taussig-Bing anomaly were identified between 1990 and 2011. Median age at arterial switch operation was 7 (range, 2-192) days, and median operative weight was 3.2 (1.4-6.2) kg. Aortic arch obstruction was present in 30 patients (70%). Hospital mortality was 7% (n=3). Follow-up was available for 37 hospital survivors at a mean of 8.1 (± 6.3) years. Late mortality was 2% (n=1). At follow-up, all patients were in New York Heart Association functional class I. Freedom from transcatheter or surgical reintervention was 73% at 1 year, 64% at 5 years, and 60% at 10 years. Eleven patients underwent 13 catheter reinterventions on the pulmonary arteries (n=8) or aortic arch (n=5). Seven patients underwent 11 reoperations, including relief of right ventricular outflow tract obstruction (n=5), pulmonary arterioplasty (n=3), recoarctation repair (n=2), and tricuspid valve repair (n=1). By multivariate analysis, a preoperative aortic valve annulus z score of ≤-2.5 was associated with reintervention (hazard ratio, 7.66 [95% confidence interval, 1.29-45.6], P=0.03). CONCLUSIONS: Although reintervention is common, primary correction of Taussig-Bing anomaly with arterial switch operation can be achieved in all patients with low mortality and good long-term outcomes.

The association of living conditions and lifestyle factors with burden of cysts among neurocysticercosis patients in Ecuador.

We used baseline data on 154 symptomatic neurocysticercosis (NCC) patients in Ecuador to identify predictors of the burden of cysts. We ran logistic regression models with the burden of cysts as the outcome, defined as the number of cysts in the brain (1 vs >1), and having cysts in all 3 phases of evolution (active, transitional and calcifications) vs <3. These two outcomes are thought to be indicators of exposure dose and/or repeated exposure over time. The predictors examined were: living in a rural area, living on a dirt road, living in an adobe or wood house (vs brick/cement), no running water in the house, no bathroom in the house, having a domestic employee cook in the home, eating most meals at restaurants or street vendors, working in a manual labour job. We found that the odds of having multiple NCC cysts was higher among those working in manual labour (OR=3.5, p=0.004), and those who ate most meals outside the home had higher odds of having cysts in all 3 phases (OR=5.0, p=0.007). Burden of cysts may be a useful outcome when looking to identify exposure risk factors in the absence of an uninfected control group.