KF4 anti-CELA1 Antibody and Purified α1-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine α1-Antitrypsin Deficiency.

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression. Cela1 -deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg/kg reduced the lung elastase activity of AAT -/- mice treated with 0.2 units of PPE. In this injury model, AAT -/- mice treated with KF4 1 mg/kg weekly, human purified AAT 60 mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 & AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.

Anti-CELA1 antibody KF4 prevents emphysema by inhibiting stretch-mediated remodeling.

There are no therapies to prevent emphysema progression. Chymotrypsin-like elastase 1 (CELA1) is a serine protease that binds and cleaves lung elastin in a stretch-dependent manner and is required for emphysema in a murine antisense oligonucleotide model of α-1 antitrypsin (AAT) deficiency. This study tested whether CELA1 is important in strain-mediated lung matrix destruction in non-AAT-deficient emphysema and the efficacy of CELA1 neutralization. Airspace simplification was quantified after administration of tracheal porcine pancreatic elastase (PPE), after 8 months of cigarette smoke (CS) exposure, and in aging. In all 3 models, Cela1-/- mice had less emphysema and preserved lung elastin despite increased lung immune cells. A CELA1-neutralizing antibody was developed (KF4), and it inhibited stretch-inducible lung elastase in ex vivo mouse and human lung and immunoprecipitated CELA1 from human lung. In mice, systemically administered KF4 penetrated lung tissue in a dose-dependent manner and 5 mg/kg weekly prevented emphysema in the PPE model with both pre- and postinjury initiation and in the CS model. KF4 did not increase lung immune cells. CELA1-mediated lung matrix remodeling in response to strain is an important contributor to postnatal airspace simplification, and we believe that KF4 could be developed as a lung matrix-stabilizing therapy in emphysema.

Inpatient Screening of Parental Adversity and Strengths.

BACKGROUND AND OBJECTIVES: Social adversities, including health-harming social risks and adverse childhood experiences, contribute to poor outcomes after hospital discharge. Screening for social adversities is increasingly pursued in outpatient settings. Identifying and addressing such adversities has been linked to improved child outcomes. Screening for social adversities and strengths in the inpatient setting may contribute to better transitions from hospital to home. Our goal was twofold: 1. to use qualitative methods to understand parent perspectives around screening tools for potential use in inpatient settings; and 2. to develop a family-friendly inpatient screening tool for social adversity. METHODS: We used in-depth, cognitive qualitative interviews with parents to elicit their views on existing screening tools covering social adversities and strengths. We partnered with a local nonprofit to recruit parents who recently had a child hospitalized or visited the emergency department. There were 2 phases of the study. In the first phase, we used qualitative methods to develop a screening prototype. In the second phase, we obtained feedback on the prototype. RESULTS: We interviewed 18 parents who identified 3 major themes around screening: 1. factors that promote parents to respond openly and honestly during screening; 2. feedback about screening tools and the prototype; and 3. screening should include resources. CONCLUSIONS: Social adversity routinely affects children; hospitalization is an important time to screen families for adversity and potential coexisting strengths. Using qualitative parent feedback, we developed the family friendly Collaborate to Optimize Parent Experience screening tool.

Outcomes of acute limb ischemia in COVID-19.

OBJECTIVE: The inflammatory cascade caused by severe acute respiratory syndrome coronavirus 2 infection may result in arterial thrombosis and acute limb ischemia (ALI) with devastating consequences. The aims of this study were to compare outcomes of ALI in the lower extremities in patients with and without coronavirus disease 2019 (COVID-19), and to determine if ALI development in the context of COVID-19 portends a worse prognosis compared with COVID-19 without ALI. METHODS: Queries were built on TriNetX, a federated network of health care organizations across the United States that provides de-identified patient data. International Classification of Diseases, 10th revision diagnostic codes were used to identify patients with acute limb ischemia of the lower extremities and COVID-19. The study timeframe was defined as January 20, 2020 to May 20, 2021. Statistical analyses, including propensity-score matching, were done through TriNetX's internal software. Outcomes looked at are rates of mortality, stroke, myocardial infarction, major adverse limb events, re-intervention, respiratory failure, sepsis, mental health complications, and acute renal failure. Baseline cohort characteristics were also collected. RESULTS: Patients with ALI with COVID-19 (ALI C19+; n = 526) were significantly less likely than patients with ALI without COVID-19 (ALI; n = 14,131) to have baseline comorbidities, including nicotine dependence (18% vs 33%; P < .0001). In contrast, ALI C19+ patients had significantly more comorbidities than hospitalized patients with COVID-19 without ALI (n = 275,903), including nicotine dependence (18% vs 10%; P < .0001). After propensity matching was performed, ALI C19+ patients had significantly higher rates of mortality (24.9% vs 9.2%; P < .0001), major adverse limb events (5.8% vs 2.9%; P = .0223), and acute renal failure (22.2% vs 14.9%; P = .0025) than patients with ALI. Compared with hospitalized patients with COVID-19 without ALI, ALI C19+ patients had higher propensity-matched rates of respiratory failure and being placed on assisted ventilation (32.9% vs 27%; P = .0369), sepsis (16.9% vs 12.2%; P = .0288), acute renal failure (22.1% vs 14.6%; P = .0019), and mortality (24.7% vs 14.4%; P < .0001). CONCLUSIONS: Patients who developed ALI following COVID-19 present with significantly different demographics and comorbidities from those who develop ALI without COVID-19. After controlling for these variables, higher rates of major adverse limb events, acute renal failure, and mortality in patients with ALI with COVID-19 suggest that not only may COVID-19 precipitate ALI, but it may also exacerbate ALI sequelae. Furthermore, development of ALI in COVID-19 portends worse prognosis compared with patients with COVID-19 without ALI.

Opioid Prescribing Behaviors Among Surgical Intensive Care Unit Attending Physicians.

BACKGROUND: More than 5 million Americans misuse opioids. Six percent of patients who receive opioids for acute pain progress to chronic use; this increases with higher doses and longer prescriptions. Prescribing variation exists within trauma centers and after emergency surgery but has not been demonstrated among intensivists. METHODS: Milligram morphine equivalents (MME) per patient-ICU-day provided by eleven surgical intensivists were analyzed. The patients were separated into 2 groups based on their percentage of time intubated in the surgical ICU. Both study groups were compared using demographics and comorbidity scores. The attendings were divided into high- and low-prescribing groups based on their MME/pt-ICU-day for intubated patients, and bivariate statistical analyses were performed. A similar analysis compared surgery vs anesthesia intensivists. RESULTS: The analysis included 257 patients in the "long-vent group" (LVG) and 668 patients in the "short-vent group" (SVG). The average MME/pt-ICU-day for the LVG was 222. Despite no significant differences in age, sex, or Elixhauser Comorbidity Index, there was a 45% difference between the high- and low-prescribing physicians in the LVG (253.7 vs 175.4 MME/pt-ICU-day; P = .008). This difference was not observed for patients in the SVG (74.3 vs 93.1 MME/pt-ICU-day; P = .141) nor based on intensivist specialty (LVG: 217.9 vs 209.5 MME/pt-ICU-day; P = .8) (SVG: 79.0 vs 93.3 MME/pt-ICU-day; P = .288).

Warfarin versus direct oral anticoagulants for patients needing distal deep vein thrombosis treatment.

OBJECTIVE: Great interest exists in standardizing the anticoagulant choice for patients requiring treatment of distal deep vein thrombosis (DDVT). In the present multicenter, retrospective cohort study, we evaluated the outcomes of patients with DDVT who had been treated with warfarin vs direct oral anticoagulants (DOACs; ie, rivaroxaban, apixaban, edoxaban, dabigatran). METHODS: Queries were built for the TriNetX database (TriNetX LLC, Cambridge, Mass), a federated network of healthcare organizations across the United States that provides de-identified patient data through aggregated counts and statistical summaries. International Classification of Diseases, 10th revision, diagnostic codes were used to identify eligible patients. Data from January 1, 2013 to January 1, 2020 were reviewed. Statistical analyses, including propensity matching, were performed using TriNetX's internal software. The inclusion criterion was treatment with either warfarin or a DOAC started within the first 24 hours of diagnosis of an isolated thrombosis of the following veins: anterior tibial, posterior tibial, peroneal, or calf muscular veins. The exclusion criteria were a history of an adverse reaction to anticoagulant agents, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, thrombophilia, mechanical heart valve, chronic proximal DVT (PDVT) and/or DDVT, and 6-month history of the following: acute PDVT, pulmonary embolism (PE), or anticoagulant usage. The outcomes measured included the incidence of mortality, PE, PDVT, stroke, myocardial infarction, and major bleeding within 6 months after initiating anticoagulation therapy. RESULTS: In a cohort of 6509 patients, 1570 were treated with warfarin and 4939 were treated with a DOAC drug. After propensity matching for age, sex, ethnicity, and comorbidities, the DOAC cohort had a significantly lower incidence of PE (1.795% vs 3.590%; P = .0020) and major bleeding (7.949% vs 10.513%; P = .0134). Differences in the incidence of mortality, PDVT, myocardial infarction, and stroke were not statistically significant. CONCLUSIONS: Before the present study, no strong evidence was available to suggest an optimal treatment modality for DDVT requiring anticoagulation therapy. The data from the present study suggest that patients receiving DOACs for the treatment of DDVT will have significantly lower rates of progression to PE and a lower incidence of major bleeding compared with patients receiving warfarin. This suggests that DOACs are superior to warfarin for treatment of DDVT.

Cultivating social relationships and disrupting social isolation in low-income, high-disparity neighbourhoods in Ohio, USA.

Social isolation undermines health. Inequities in social networks exist due to historical and contemporary practices of socioeconomic and racial segregation. Thus, lower income and minority families are less likely to have the number, strength, and variety of social connections as higher income and white families. Therefore, social isolation may contribute to inequities in health and well-being across socioeconomic and racial groups. Disrupting social isolation by strengthening social networks may be a meaningful way to equitably improve population health. In this study we aimed to better understand the factors that influence the formation and sustainment of social connections in neighbourhoods experiencing a disproportionate burden of social needs and poor health outcomes. Participants were recruited through our community-academic partnership, Healthy Homes (HH). Healthy Homes serves families with pregnant women and/or children <6 years in two low-income, high-morbidity neighbourhoods, focusing on supporting families' needs and hopes. Between October 2016 and April 2017, we conducted in-depth qualitative interviews (n = 20) with English-speaking mothers and grandmothers of children under <6 years. Interviews were audio-recorded, transcribed verbatim and independently coded. After applying an a priori code list, we conducted emergent coding to identify additional themes. Themes focused on the social environment, including social connections and social isolation, among vulnerable populations in included neighbourhoods. Families want connection to one another and to resources but look to others to facilitate those connections. Families may want or need social connections but do not engage if it means sacrificing their values or sense of self-worth. These findings provide a deeper understanding of the factors that might allow us to disrupt social isolation by building relationships in communities that face social and health inequities.

Racial Disparities in Resection of Early Stage Non-Small Cell Lung Cancer: Variability Among Surgeons.

BACKGROUND: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited. OBJECTIVE: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care. METHODS: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients. RESULTS: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased. CONCLUSIONS: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels.

Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 16 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short-term or long-term DR, with the majority of effects noted in brain following long-term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short-term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues.

Global burden of late-stage chronic kidney disease resulting from dietary exposure to cadmium, 2015.

Chronic exposures to cadmium (Cd) are associated with reduced glomerular filtration rate (GFR), increasing the risk of chronic kidney disease (CKD). In support of the World Health Organization (WHO)'s initiative to estimate the global burden of foodborne diseases, a risk assessment was performed to estimate the Disability-Adjusted Life Years (DALYs) due to late-stage CKD associated with dietary exposures to cadmium. Using the distribution of population GFRs, the prevalence of CKD was calculated as the proportion of humans whose GFR fall in the ranges corresponding to Stage 4 or Stage 5 CKD. The increase in the CKD prevalence due to cadmium exposure was simulated based on a previously reported pharmacokinetic model describing the relationship between dietary cadmium intake and urinary cadmium (UCd), as well as a previously published dose-response relationship between UCd and GFR. Cadmium-related incidence rate, calculated as the change in the prevalence during a one-year period, were used to compute the mortality and DALY in all WHO regions. It is estimated that dietary cadmium would result in a median of 12,224 stage 4 and stage 5 new CKD cases per year worldwide, resulting in 2064 global deaths and 70,513 DALYs. These data translate into a median global burden of 1.0 DALY per 100,000 population, which account for 0.2% of the global DALYs of CKD. While these results suggest that the overall impact of dietary cadmium exposure on global CKD is low, they do indicate that reasonable efforts to reduce dietary exposure will result a positive public health impact. This would be particularly the case in areas with elevated levels of dietary cadmium.

Self-management behaviors in World Trade Center rescue and recovery workers with asthma.

BACKGROUND: Asthma is a major source of morbidity among World Trade Center (WTC) rescue and recovery workers. While physical and mental health comorbidities have been associated with poor asthma control, the potential role and determinants of adherence to self-management behaviors (SMB) among WTC rescue and recovery workers is unknown. OBJECTIVES: To identify modifiable determinants of adherence to asthma self-management behaviors in WTC rescue and recovery worker that could be potential targets for future interventions. METHODS: We enrolled a cohort of 381 WTC rescue and recovery workers with asthma. Sociodemographic data and asthma history were collected during in-person interviews. Based on the framework of the Model of Self-regulation, we measured beliefs about asthma and controller medications. Outcomes included medication adherence, inhaler technique, use of action plans, and trigger avoidance. RESULTS: Medication adherence, adequate inhaler technique, use of action plans, and trigger avoidance were reported by 44%, 78%, 83%, and 47% of participants, respectively. Adjusted analyses showed that WTC rescue and recovery workers who believe that they had asthma all the time (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.38-4.08), that WTC-related asthma is more severe (OR: 1.73; 95% CI: 1.02-2.93), that medications are important (OR: 12.76; 95% CI: 5.51-29.53), and that present health depends on medications (OR: 2.39; 95% CI: 1.39-4.13) were more likely to be adherent to their asthma medications. Illness beliefs were also associated with higher adherence to other SMB. CONCLUSIONS: Low adherence to SMB likely contributes to uncontrolled asthma in WTC rescue and recovery workers. Specific modifiable beliefs about asthma chronicity, the importance of controller medications, and the severity of WTC-related asthma are independent predictors of SMB in this population. Cognitive behavioral interventions targeting these beliefs may improve asthma self-management and outcomes in WTC rescue and recovery workers. Key message: This study identified modifiable beliefs associated with low adherence to self-management behaviors among World Trade Center rescue and recovery rescue and recovery workers with asthma which could be the target for future interventions. CAPSULE SUMMARY: Improving World Trade Center-related asthma outcomes will require multifactorial approaches such as supporting adherence to controller medications and other self-management behaviors. This study identified several modifiable beliefs that may be the target of future efforts to support self-management in this patient population.

Outcomes after Video-assisted Thoracoscopic Lobectomy versus Open Lobectomy for Early-Stage Lung Cancer in Older Adults.

RATIONALE: Video-assisted thoracoscopic surgery (VATS) and open lobectomy are both standard of care for the treatment of early-stage non-small cell lung cancer (NSCLC) because of equivalent long-term survival. OBJECTIVES: To evaluate whether the improved perioperative outcomes associated with VATS lobectomy are explained by surgeon characteristics, including case volume and specialty training. METHODS: We analyzed the Surveillance, Epidemiology, and End Results-Medicare-linked registry to identify stage I-II NSCLC in patients above 65 years of age. We used a propensity score model to adjust for differences in patient characteristics undergoing VATS versus open lobectomy. Perioperative complications, extended length of stay, and perioperative mortality among patients were compared after adjustment for surgeon's volume and specialty using linear mixed models. We compared survival using a Cox model with robust standard errors. RESULTS: We identified 9,508 patients in the registry who underwent lobectomy for early-stage NSCLC. VATS lobectomies were more commonly performed by high-volume surgeons (P < 0.001) and thoracic surgeons (P = 0.01). VATS lobectomy was associated with decreased adjusted odds of cardiovascular complications (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.47-0.90), thromboembolic complications (OR = 0.47; 95% CI = 0.38-0.58), extrapulmonary infections (OR = 0.75; 95% CI = 0.61-0.94), extended length of stay (OR = 0.47; 95% CI = 0.40-0.56), and perioperative mortality (OR = 0.33; 95% CI = 0.23-0.48) even after controlling for differences in surgeon volume and specialty. Long-term survival was equivalent for VATS and open lobectomy (hazard ratio = 0.95; 95% CI = 0.85-1.08) after controlling for patient and tumor characteristics, surgeon volume, and specialization. CONCLUSIONS: VATS lobectomy for NSCLC is associated with better postoperative outcomes, but similar long-term survival, compared with open lobectomy among older adults, even after controlling for surgeon experience.

Limited Resection Versus Lobectomy for Older Patients With Early-Stage Lung Cancer: Impact of Histology.

PURPOSE: Limited resection has been increasingly used in older patients with stage IA lung cancer. However, the equivalency of limited resection versus lobectomy according to histology is unknown. METHODS: We identified patients older than 65 years with stage IA invasive adenocarcinoma or squamous cell carcinoma ≤ 2 cm who were treated with limited resection (wedge or segmentectomy) or lobectomy in the Surveillance, Epidemiology, and End Results-Medicare database. We estimated propensity scores that predicted the use of limited resection and compared survival of patients treated with limited resection versus lobectomy. Treatments were considered equivalent if the upper 95th percentile of the hazard ratio (HR) for limited resection was ≤ 1.25. RESULTS: Overall, 27% of 2,008 patients with adenocarcinoma and 32% of 1,139 patients with squamous cell carcinoma underwent limited resection. Survival analyses, adjusted for propensity score by using inverse probability weighting, showed that limited resection was not equivalent to lobectomy in patients with adenocarcinoma (HR, 1.21; upper 95% CI,1.34) or squamous cell carcinoma (HR, 1.21; upper 95% CI, 1.39). Although patients with adenocarcinomas treated with segmentectomy had equivalent survival rates to those treated with lobectomy (HR, 0.97; upper 95% CI, 1.07), outcomes of those treated with wedge resection (HR, 1.29; upper 95% CI, 1.42) did not. Among patients with squamous cell carcinoma, neither wedge resection (HR, 1.34; upper 95% CI, 1.53) nor segmentectomy (HR, 1.19; upper 95% CI, 1.36) were equivalent to lobectomy. CONCLUSION: We found generally that limited resection is not equivalent to lobectomy in older patients with invasive non-small-cell lung cancer ≤ 2 cm in size, although segmentectomy may be equivalent in patients with adenocarcinoma.

Consequences of Delayed Dental Extraction in Lesch-Nyhan Disease.

Patients with Lesch-Nyhan disease (LND) often engage in self-injurious biting. This problem requires difficult management choices, sometimes including removal of the teeth. Although many health care professionals are reluctant to remove teeth in a child because of the permanent negative cosmetic consequences of the edentulous state, disfigurement of the face and tongue from self-biting can be worse. We analyzed the records of 5 LND patients who used mouth guards to spare the teeth. Success was variable, and dental extraction ultimately was required in 4 cases. We also reviewed previously published cases on the use of dental devices to spare teeth in LND. Various devices have been recommended, but failure rates are high, and tooth extraction often is still needed. Although dental extraction is not required in all cases, it should not be delayed when biting is severe.

How long does it take to diagnose cervical dystonia?

BACKGROUND: Dystonia is a neurological disorder characterized by involuntary twisting movements and postures. The neck is among the most commonly affected regions, and diagnosis can be made readily through a simple clinical evaluation. The goal of this study was to explore how long it took patients to receive a diagnosis of cervical dystonia after symptom onset. METHODS: A structured questionnaire was administered at outpatient clinics of a tertiary care academic medical center to 146 consecutively evaluated patients. The questionnaire addressed the length of time from symptom onset to diagnosis, the numbers and types of providers seen before reaching a diagnosis, and treatments attempted prior to receiving botulinum toxin. RESULTS: A total of 108 patients saw a mean of 3.5 providers over a mean period of 44 months from symptom onset to diagnosis. For patients with symptom onset in the last decade only, patients saw a mean of 3.0 providers over a mean of 14 months. CONCLUSIONS: Although cervical dystonia is the most common form of dystonia with clinical features readily identifiable by a simple history and examination, patients typically see multiple providers over more than a year before reaching a diagnosis and receiving optimal therapy. Improved awareness of the clinical features will enable patients to obtain appropriate therapy more rapidly.

Preliminary evidence for school-based physical activity policy needs in Washington, DC.

BACKGROUND: The school setting could be a primary venue for promoting physical activity among inner-city children due to the structured natured of the school day. We examined differences in step counts between structured school days (SSD) and weekend days (WED) among a sample of public school children in Washington, DC. METHODS: Subjects (N = 29) were third- to sixth-grade students enrolled in government-funded, extended-day enrichment programs. Step counts were measured using a pedometer (Bodytronics) over 2 SSD and 2 WED. Differences in mean step counts between SSD and WED were determined using multivariable linear regression, with adjustments for age, sex, and reported distance between house and school (miles). RESULTS: Recorded step counts were low on both SSD and WED (7735 ± 3540 and 8339 ± 5314 steps/day). Boys tended to record more steps on SSD compared with girls (8080 ± 3141 vs. 7491 ± 3872 steps/day, respectively), whereas girls recorded more steps on the WED compared with boys (9292 ± 6381 vs. 7194 ± 3669 steps/day). Parameter estimates from the regression modeling suggest distance from school (P < .01) to be the strongest predictor of daily step counts, independent of day (SSD/WED), sex, and age. CONCLUSION: Among inner-city school children, a safe walking route to and from school may provide an important opportunity for daily physical activity.