Emergency Department Visits for Pedestrians Injured in Motor Vehicle Traffic Crashes - United States, January 2021-December 2023.

Traffic-related pedestrian deaths in the United States reached a 40-year high in 2021. Each year, pedestrians also suffer nonfatal traffic-related injuries requiring medical treatment. Near real-time emergency department visit data from CDC's National Syndromic Surveillance Program during January 2021-December 2023 indicated that among approximately 301 million visits identified, 137,325 involved a pedestrian injury (overall visit proportion = 45.62 per 100,000 visits). The proportions of visits for pedestrian injury were 1.53-2.47 times as high among six racial and ethnic minority groups as that among non-Hispanic White persons. Compared with persons aged ≥65 years, proportions among those aged 15-24 and 25-34 years were 2.83 and 2.61 times as high, respectively. The visit proportion was 1.93 times as high among males as among females, and 1.21 times as high during September-November as during June-August. Timely pedestrian injury data can help collaborating federal, state, and local partners rapidly monitor trends, identify disparities, and implement strategies supporting the Safe System approach, a framework for preventing traffic injuries among all road users.

Alcohol-impaired driving among adults-USA, 2014-2018.

INTRODUCTION: Alcohol-impaired driving (AID) crashes accounted for 10 511 deaths in the USA in 2018, or 29% of all motor vehicle-related crash deaths. This study describes self-reported AID in the USA during 2014, 2016 and 2018 and determines AID-related demographic and behavioural characteristics. METHODS: Data were from the nationally representative Behavioral Risk Factor Surveillance System. Adults were asked 'During the past 30 days, how many times have you driven when you have had perhaps too much to drink?' AID prevalence, episode counts and rates per 1000 population were estimated using annualised individual AID episodes and weighted survey population estimates. Results were stratified by characteristics including gender, binge drinking, seatbelt use and healthcare engagement. RESULTS: Nationally, 1.7% of adults engaged in AID during the preceding 30 days in 2014, 2.1% in 2016 and 1.7% in 2018. Estimated annual number of AID episodes varied across year (2014: 111 million, 2016: 186 million, 2018: 147 million) and represented 3.7 million, 4.9 million and 4.0 million adults, respectively. Corresponding yearly episode rates (95% CIs) were 452 (412-492) in 2014, 741 (676-806) in 2016 and 574 (491-657) in 2018 per 1000 population. Among those reporting AID in 2018, 80% were men, 86% reported binge drinking, 47% did not always use seatbelts and 60% saw physicians for routine check-ups within the past year. CONCLUSIONS: Although AID episodes declined from 2016 to 2018, AID was still prevalent and more common among men and those who binge drink. Most reporting AID received routine healthcare. Proven AID-reducing strategies exist.

An evaluation of PROMIS health domains in adults with haemophilia: A cross-sectional study.

INTRODUCTION: The Patient-Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well-being from the patient perspective. PROMIS measures are used in clinical practice and research across various patient populations but are not yet validated among patients with haemophilia. AIM: Evaluate the sensitivity of PROMIS to indicators of haemophilia clinical severity and compare PROMIS measures to those from other PRO instruments. METHODS: Male adults with haemophilia (n = 115) completed the PROMIS-29 short form which includes 4 questions for each of 7 domains: depression, anxiety, ability to participate in social roles and activities, physical function, pain interference, fatigue and sleep disturbance. Participant responses for each domain were scored on a T-score metric with a mean of 50 and a standard deviation of 10 based on the original PROMIS reference sample of US adults. Participants also completed other generic and haemophilia-specific health-related quality of life questionnaires. RESULTS: Participants who experienced higher pain and depression levels reported significantly worse health in every PROMIS domain compared with their peers. Those who had recently needed to use crutches, visit an emergency department or were currently unemployed or disabled also reported poor PROMIS scores on most domains. Construct validity was supported by correlations between PROMIS domain scores and domain scores reported using the EQ-5D-5L and Haem-A-QoL. CONCLUSION: The PROMIS instrument provides a potentially valuable tool to evaluate the impact of haemophilia and suggests usefulness in research and clinical practice.

Validation of a new instrument to measure disease-related distress among patients with haemophilia.

INTRODUCTION: In patients with haemophilia, general psychological distress as measured by the National Comprehensive Cancer Network (NCCN) distress thermometer has been associated with pain, disability and increased healthcare utilization. AIMS: To develop and validate a measure of haemophilia-related distress. METHODS: After qualitative interviews, the Hemophilia-Related Distress Questionnaire (HRDq) was developed. To validate the HRDq, adults (≥18 years) with haemophilia were enrolled, reported demographic and clinical information, and completed the HRDq and other questionnaires that measured similar constructs. Analysis included factor analysis and assessment of internal consistency using Cronbach's α, convergent validity using Pearson's correlation coefficient, and discriminant validity by comparing subgroups of patients. Test-retest reliability was assessed using an intraclass correlation coefficient (ICC). RESULTS: Among 130 enrolled participants, 126 (median age=32.7 years) completed the 24 item HRDq in a median time of 5.4 minutes with overall HRDq scores ranging from 2 to 83 (median score=31.5; higher scores indicating higher distress). Assessment of convergent validity demonstrated a strong correlation (ρ>.60) of the HRDq total score with the NCCN Distress Thermometer, Haem-A-QoL total Score, and PROMIS-29 Profile social role domain and a mild to moderate correlation with all other questionnaire domains (.3-.59, p < .05). Distress was higher among those who had less education, were not employed, and were disabled and was not significantly different among those with severe compared with non-severe disease. Assessment of test-retest reliability demonstrated an ICC value of .84 (95% CI .71-.91) for the total score. CONCLUSIONS: The HRDq demonstrates good internal consistency, construct and discriminant validity, and retest reliability with a low responder burden.

Opening of Large Institutions of Higher Education and County-Level COVID-19 Incidence - United States, July 6-September 17, 2020.

During early August 2020, county-level incidence of coronavirus disease 2019 (COVID-19) generally decreased across the United States, compared with incidence earlier in the summer (1); however, among young adults aged 18-22 years, incidence increased (2). Increases in incidence among adults aged ≥60 years, who might be more susceptible to severe COVID-19-related illness, have followed increases in younger adults (aged 20-39 years) by an average of 8.7 days (3). Institutions of higher education (colleges and universities) have been identified as settings where incidence among young adults increased during August (4,5). Understanding the extent to which these settings have affected county-level COVID-19 incidence can inform ongoing college and university operations and future planning. To evaluate the effect of large colleges or universities and school instructional format* (remote or in-person) on COVID-19 incidence, start dates and instructional formats for the fall 2020 semester were identified for all not-for-profit large U.S. colleges and universities (≥20,000 total enrolled students). Among counties with large colleges and universities (university counties) included in the analysis, remote-instruction university counties (22) experienced a 17.9% decline in mean COVID-19 incidence during the 21 days before through 21 days after the start of classes (from 17.9 to 14.7 cases per 100,000), and in-person instruction university counties (79) experienced a 56.2% increase in COVID-19 incidence, from 15.3 to 23.9 cases per 100,000. Counties without large colleges and universities (nonuniversity counties) (3,009) experienced a 5.9% decline in COVID-19 incidence, from 15.3 to 14.4 cases per 100,000. Similar findings were observed for percentage of positive test results and hotspot status (i.e., increasing among in-person-instruction university counties). In-person instruction at colleges and universities was associated with increased county-level COVID-19 incidence and percentage test positivity. Implementation of increased mitigation efforts at colleges and universities could minimize on-campus COVID-19 transmission.

COVID-19 Vaccination Coverage Among Adults - United States, December 14, 2020-May 22, 2021.

The U.S. COVID-19 vaccination program launched on December 14, 2020. The Advisory Committee on Immunization Practices recommended prioritizing COVID-19 vaccination for specific groups of the U.S. population who were at highest risk for COVID-19 hospitalization and death, including adults aged ≥75 years*; implementation varied by state, and eligibility was gradually expanded to persons aged ≥65 years beginning in January 2021. By April 19, 2021, eligibility was expanded to all adults aged ≥18 years nationwide.† To assess patterns of COVID-19 vaccination coverage among U.S. adults, CDC analyzed data submitted on vaccinations administered during December 14, 2020-May 22, 2021, by age, sex, and community-level characteristics. By May 22, 2021, 57.0% of persons aged ≥18 years had received ≥1 COVID-19 vaccine dose; coverage was highest among persons aged ≥65 years (80.0%) and lowest among persons aged 18-29 years (38.3%). During the week beginning February 7, 2021, vaccination initiation among adults aged ≥65 years peaked at 8.2%, whereas weekly initiation among other age groups peaked later and at lower levels. During April 19-May 22, 2021, the period following expanded eligibility to all adults, weekly initiation remained <4.0% and decreased for all age groups, including persons aged 18-29 years (3.6% to 1.9%) and 30-49 years (3.5% to 1.7%); based on the current rate of weekly initiation (as of May 22), younger persons will not reach the same levels of coverage as older persons by the end of August. Across all age groups, coverage (≥1 dose) was lower among men compared with women, except among adults aged ≥65 years, and lower among persons living in counties that were less urban, had higher social vulnerabilities, or had higher percentages of social determinants of poor health. Continued efforts to improve vaccination confidence and alleviate barriers to vaccination initiation, especially among adults aged 18-49 years, could improve vaccination coverage.

Patterns in COVID-19 Vaccination Coverage, by Social Vulnerability and Urbanicity - United States, December 14, 2020-May 1, 2021.

Disparities in vaccination coverage by social vulnerability, defined as social and structural factors associated with adverse health outcomes, were noted during the first 2.5 months of the U.S. COVID-19 vaccination campaign, which began during mid-December 2020 (1). As vaccine eligibility and availability continue to expand, assuring equitable coverage for disproportionately affected communities remains a priority. CDC examined COVID-19 vaccine administration and 2018 CDC social vulnerability index (SVI) data to ascertain whether inequities in COVID-19 vaccination coverage with respect to county-level SVI have persisted, overall and by urbanicity. Vaccination coverage was defined as the number of persons aged ≥18 years (adults) who had received ≥1 dose of any Food and Drug Administration (FDA)-authorized COVID-19 vaccine divided by the total adult population in a specified SVI category.† SVI was examined overall and by its four themes (socioeconomic status, household composition and disability, racial/ethnic minority status and language, and housing type and transportation). Counties were categorized into SVI quartiles, in which quartile 1 (Q1) represented the lowest level of vulnerability and quartile 4 (Q4), the highest. Trends in vaccination coverage were assessed by SVI quartile and urbanicity, which was categorized as large central metropolitan, large fringe metropolitan (areas surrounding large cities, e.g., suburban), medium and small metropolitan, and nonmetropolitan counties.§ During December 14, 2020-May 1, 2021, disparities in vaccination coverage by SVI increased, especially in large fringe metropolitan (e.g., suburban) and nonmetropolitan counties. By May 1, 2021, vaccination coverage was lower among adults living in counties with the highest overall SVI; differences were most pronounced in large fringe metropolitan (Q4 coverage = 45.0% versus Q1 coverage = 61.7%) and nonmetropolitan (Q4 = 40.6% versus Q1 = 52.9%) counties. Vaccination coverage disparities were largest for two SVI themes: socioeconomic status (Q4 = 44.3% versus Q1 = 61.0%) and household composition and disability (Q4 = 42.0% versus Q1 = 60.1%). Outreach efforts, including expanding public health messaging tailored to local populations and increasing vaccination access, could help increase vaccination coverage in high-SVI counties.

Chronic renal disease among lead-exposed workers.

BACKGROUND: Very high exposure to inorganic lead causes serious kidney damage. We have studied workers with occupational exposure and data on blood lead. METHODS: We extended follow-up for 7 more years, for a previously studied cohort of 58 307 male workers who were part of a surveillance programme in 11 different states. Mortality was assessed using the National Death Index, and end-stage renal disease (ESRD) incidence was assessed using the US Renal Data System. We conducted internal analyses via Cox regression adjusting for age, calendar time and race. RESULTS: The cohort was followed for a median of 18 years and had 524 cases of ESRD and 6527 deaths. Average maximum blood lead was 26 µg/dL; the mean year of first blood lead test was 1997. No trends by lead level were seen overall or when restricting to those with 15+ years follow-up. Among non-Caucasians with >15 years of follow-up, there was a positive but inconsistent trend (Rate ratios (RRs) 1.00, 2.10, 1.33, 2.20 and 2.76 for maximum blood lead categories of <20 µg/dL, 20-29 µg/dL, 30 to <40 µg/dL, 40 to ≤50 µg/dL and >50 µg/dL, respectively (p for linear trend 0.26). Those with >15 years of follow-up and birth year <1941 showed a positive trend with increased blood lead (RRs 1.00, 1.14, 1.18, 1.46, 1.66, p trend=0.26). CONCLUSIONS: We found no association between higher lead exposure and ESRD. There were positive but not statistically significant trends of increased risk for non-Caucasians with >15 years of follow-up and for older men with >15 years of follow-up.

Disease-related distress among adults with haemophilia: A qualitative study.

INTRODUCTION: Distress related to disease burden has been defined and described among people with chronic diseases including diabetes and cancer. In these populations, disease-specific distress is associated with health outcomes. Haemophilia-related distress is less understood. AIM: To identify qualitative features of haemophilia-related distress among affected adults to ultimately inform the creation of a measurement tool. METHODS: Adults with haemophilia A or B associated with a large haemophilia treatment centre in the south-eastern U.S. were recruited to participate in this qualitative study. Fifteen participants completed semi-structured telephone interviews. Interviews lasted 1-2 hours and explored experiences of distress related to various aspects of haemophilia. Interviews were audio taped, transcribed and coded using NVIVO, software for organizing, managing and analysing qualitative data. Coding was deductive and inductive, and the analysis was thematic. RESULTS: Haemophilia-related distress was broadly related to feelings of isolation and vulnerability which incorporated health system factors, physical functioning, caretaker roles and psychological considerations. Specific features associated with haemophilia-related distress included lack of trust in the knowledge of haemophilia and care provided by staff in community healthcare settings, concerns about the future such as health insurance access and ageing/disability, long-standing feelings of being different from others and feeling like an outsider, treatment burdens and fear of acute bleeds. Protective factors included supportive relationships with family, friends and haemophilia care teams through which participants received practical and emotional support. CONCLUSION: Features of haemophilia-related distress were identified. Results will facilitate distress measurement and intervention efforts to reduce distress in adults with haemophilia.

Bone lead associations with blood lead, kidney function and blood pressure among US, lead-exposed workers in a surveillance programme.

OBJECTIVES: Bone lead and past blood lead levels may be more strongly associated with current health effects than current blood lead, representing recent exposure. We examined whether current bone lead was correlated with maximum past blood lead and compared how three lead measures predicted current blood pressure (BP) and kidney function among workers with past occupational lead exposure. METHODS: Adult men in a lead surveillance programme residing near New York City were enrolled. Current bone and blood lead, BP and estimated glomerular filtration rate (eGFR) were measured. Maximum past blood lead was obtained from surveillance data. Regression models were used to determine associations of health with different lead measures. RESULTS: Among 211 participants, median (IQR) bone, maximum past blood and current blood leads were 13.8 (9.4-19.5) µg lead per bone mineral gram, 29.0 (14.0-38.0) µg/dL and 2.5 (1.5-4.4) µg/dL, respectively. Maximum past and current blood lead were significantly associated with current bone lead in adjusted analyses (both p<0.0001), with associations driven by high blood lead. Bone lead was associated with increased continuous systolic BP (coefficient=0.36; 95% CI 0.05 to 0.67; p=0.02); categorical analyses indicated this was driven by the top two bone lead quartiles. Bone lead was non-significantly associated with decreased (worse) eGFR (coefficient=-0.15; 95% CI -0.36 to 0.07; p=0.18). CONCLUSIONS: Bone lead was significantly associated with past maximum and current blood lead. The association between bone and current blood lead was possibly driven by bone lead resorption into blood. Bone lead, but not past or current blood lead, was associated with elevated systolic BP.

Cancer incidence among workers with blood lead measurements in two countries.

OBJECTIVE: Study carcinogenicity of inorganic lead, classified as 'probably carcinogenic' to humans by the International Agency for Research on Cancer (brain, lung, kidney and stomach). METHODS: We conducted internal and external analyses for cancer incidence in two cohorts of 29 874 lead-exposed workers with past blood lead data (Finland, n=20 752, Great Britain=9122), with 6790 incident cancers. Exposure was maximum measured blood lead. RESULTS: The combined cohort had a median maximum blood lead of 29 µg/dL, a mean first blood lead test of 1977, and was 87% male. Significant (p<0.05) positive trends, using the log of maximum blood lead, were found for brain cancer (malignant), Hodgkin's lymphoma, lung cancer and rectal cancer, while a significant negative trend was found for melanoma. Borderline significant positive trends (0.05≤p≤0.10) were found for oesophageal cancer, meningioma and combined malignant/benign brain cancer. Categorical analyses reflected these trends. Significant interactions by country were found for lung, brain and oesophageal cancer, with Finland showing strong positive trends, and Great Britain showing modest or no trends. Larynx cancer in Finland also showed a positive trend (p=0.05). External analyses for high exposure workers (maximum blood lead >40 µg/dL) showed a significant excess for lung cancer in both countries combined, and significant excesses in Finland for brain and lung cancer. The Great Britain data were limited by small numbers for some cancers, and limited variation in exposure. CONCLUSIONS: We found strong positive incidence trends with increasing blood lead level, for several outcomes in internal analysis. Two of these, lung and brain cancer, were sites of a priori interest.

Lead exposure and mortality among U.S. workers in a surveillance program: Results from 10 additional years of follow-up.

BACKGROUND: A cohort of male lead-exposed workers with past blood lead levels, previously followed for mortality over 12 years, has now been followed for an additional 10 years. This has doubled the number of deaths and allowed for examination of mortality outcomes across a wide range of blood lead levels. OBJECTIVE: Evaluate association between lead exposure and 16 causes of death. METHODS: The cohort included male workers from 11 U.S. states enrolled in a U.S. lead surveillance program. Maximum blood lead level for each worker was abstracted from surveillance records. Mortality was assessed using the National Death Index. We conducted internal analyses via Cox regression adjusting for age, calendar time, and race. External analyses compared cohort mortality rates with those of the U.S. POPULATION: Blood lead categories were defined as 0-<5, 5-<25, 25-<40, and ≥40 µg/dL with the two lower categories combined for outcomes with <5 deaths in the 0-<5 group. RESULTS: The cohort (n = 58,368) was followed for a median of 19 years and experienced 6,527 deaths. Average maximum blood lead was 25.9 µg/dL and mean year of first blood lead test was 1997. Strong associations were found between blood lead level with larynx and lung cancer mortality. For these outcomes, hazard ratios and 95% confidence intervals across blood lead categories were 1.0 (ref), 1.1 (0.4-3.2), 3.4 (1.3-9.1) for larynx and 1.0 (ref), 1.6 (1.0-2.5), 2.0 (1.3-3.1), 2.9 (1.9-4.5) for lung (trend p-values = 0.08 and < 0.01, respectively). Positive significant trends were also seen for mortality from brain cancer, chronic obstructive pulmonary disease, ischemic heart disease, and non-hodgkin's lymphoma. Findings suggested associations with chronic renal disease and rectal cancer mortality, although trends were not statistically significant. CONCLUSIONS: The additional follow up confirmed previous relationships between lead and mortality and also detected new associations.

Serum Perfluorooctanoic Acid and Birthweight: An Updated Meta-analysis With Bias Analysis.

BACKGROUND: A recent meta-analysis of 15 studies found a change in birthweight of -12.8 g (95% CI = -23.1, -2.38) per ng/ml PFOA in maternal or cord blood and -27.1 g (-50.6, -3.6) per log ng/ml PFOA. Almost all studies were done in low-exposed populations. There are nine new studies, adding 6,019 births to the previous 6,937 births. METHODS: We conducted a meta-analysis of 24 studies. To combine all results, we approximated results for untransformed PFOA from nine studies using log-transformed PFOA. We also included another large study, excluded from previous analyses, in a sensitivity analysis. RESULTS: We found a change of birthweight of -10.5 g (-16.7, -4.4) for every ng/ml PFOA in maternal or cord blood. After adding one previously excluded large study, we found little evidence of an association (-1.0 g; 95% CI = -2.4, 0.4). Restricting to studies where blood was sampled from mothers early in the pregnancy or shortly before conception (5,393 births), we found little association of PFOA with birthweight (-3.3 g [-9.6, 3.0]). In studies where blood was sampled late in the pregnancy (7563 pregnancies), lower birthweight was associated with higher PFOA (-17.8 [-25.0, -10.6]). CONCLUSION: Present human evidence provides only modest support for decreased birthweight with increasing PFOA. Studies with a wide range of exposure, and studies with blood sampled early in pregnancy, showed little or no association of PFOA with birthweight. These are studies in which confounding and reverse causality would be of less concern.

Assessing responsiveness over time of the PROMIS® pediatric symptom and function measures in cancer, nephrotic syndrome, and sickle cell disease.

PURPOSE: Previous studies provided evidence for the validity of the PROMIS Pediatric measures in cross-sectional studies. This study evaluated the ability of the PROMIS Pediatric measures to detect change over time in children and adolescents with cancer, nephrotic syndrome (NS), or sickle cell disease (SCD). METHODS: Participants (8-17 years) completed measures of fatigue, pain interference, anger, anxiety, depressive symptoms, mobility, upper extremity, and peer relationships at three or four time points (T1-T4). Between T1 and T2, children with cancer received chemotherapy and children with SCD experienced a pain exacerbation. Children with NS were first assessed during active disease (T2), with T3 and T4 conducted at disease remission. For the primary analysis of responsiveness, we expected better scores at T3 (recovery) compared to T2 (event) for all diseases. T1 and T4 are also expected to have better scores than T2. Linear mixed models were used and adjusted for time, gender, age, race/ethnicity, education, comorbid conditions, and disease. RESULTS: Enrolled were 96 children with cancer, 121 children with SCD, and 127 children with NS. Fatigue, pain interference, mobility, and upper extremity scores worsened from T1 (baseline) to T2 (event) (p < 0.01), and significantly improved from T2 to T3 and T4 (p < 0.01). Similarly, anxiety and depressive symptoms significantly improved from T2 to T3 and T4 (p < 0.01). CONCLUSIONS: This study provides evidence for the responsiveness of seven PROMIS Pediatric measures to clinical disease state in three chronic illnesses. The findings support use of PROMIS Pediatric measures in clinical research.

An Evaluation of Time-Trial-Based Predictions of V[Combining Dot Above]O2max and Recommended Training Paces for Collegiate and Recreational Runners.

Scudamore, EM, Barry, VW, and Coons, JM. An Evaluation of time-trial-based predictions of V[Combining Dot Above]O2max and recommended training paces for collegiate and recreational runners. J Strength Cond Res 32(4): 1137-1143, 2018-The purpose of the current study was to determine the accuracy of Jack Daniels' VDOT Running Calculator for the prediction of V[Combining Dot Above]O2max, and recommendations of interval and training paces (pIN and pTH) in samples of National Collegiate Athletic Association Division 1 track athletes (ATH, n = 11) and recreational runners (REC; n = 9). Predicted variable data were obtained using results from indoor 5-km time-trials. Data from the VDOT Calculator were compared with laboratory-tested V[Combining Dot Above]O2max, pace at V[Combining Dot Above]O2max (V[Combining Dot Above]O2maxpace), and lactate threshold pace (LTpace). Results indicated that VDOT underestimated V[Combining Dot Above]O2max in ATH (t(10) = -6.00, p < 0.001, d = 1.75) and REC (t(8) = -8.96, p < 0.001, d = 3.44). Follow-up between-groups analysis indicated that the difference between VDOT and V[Combining Dot Above]O2max was significantly greater in REC than in ATH (p = 0.0031, d = 1.59). pIN was slower than V[Combining Dot Above]O2maxpace in REC (t(8) = -4.26, p = 0.003, d = 1.76), but not different in ATH (t(10) = 0.52, p = 0.614, d = 0.14). Conversely, pTH was faster than LTpace in ATH (t(8) = -4.17, p = 0.003, d = 1.49), but not different in REC (t(8) = 1.64, p = 0.139, d = 0.57). Practically, pTH can be confidently used for threshold training regardless of the ability level. pIN also seemed to be accurate for ATH, but may be not be optimal for improving V[Combining Dot Above]O2max in REC. Practitioners should interpret VDOT with caution as it may underestimate V[Combining Dot Above]O2max.

Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective, population-based cohort.

The clinical efficacy of hydroxyurea in patients with sickle cell anemia (SCA) has been well established. However, data about its clinical effectiveness in practice is limited. We evaluated the clinical effectiveness of hydroxyurea in a large pediatric population using a retrospective cohort, pre-post treatment study design to control for disease severity selection bias. The cohort included children with SCA (SS, Sß0 thalassemia) who received care at Children's Healthcare of Atlanta (CHOA) and who initiated hydroxyurea in 2009-2011. Children on chronic transfusions, or children with inadequate follow up data and/or children who had taken hydroxyurea in the 3 years prior were excluded. For each patient healthcare utilization, laboratory values, and clinical outcomes for the 2-year period prior to hydroxyurea initiation were compared to those 2 years after initiation. Of 211 children with SCA who initiated hydroxyurea in 2009-2011, 134 met eligibility criteria. After initiation of hydroxyurea, rates of hospitalizations, pain encounters, and emergency department visits were reduced by 47% (<0.0001), 36% (P = 0.0001) and 43% (P < 0.0001), respectively. Average hemoglobin levels increased by 0.7 g/dl (P < 0.0001). Hydroxyurea effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger children. Am. J. Hematol. 92:77-81, 2017. © 2016 Wiley Periodicals, Inc.

A cohort mortality study of lead-exposed workers in the USA, Finland and the UK.

OBJECTIVES: To investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study. METHODS: We conducted internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates. RESULTS: The combined cohort had a median BL of 26 µg/dL, a mean first-year BL test of 1990 and was 96% male. Fifty per cent had more than one BL test (mean 7). Significant (p<0.05) positive trends, using the log of each worker's maximum BL, were found for lung cancer, chronic obstructive pulmonary disease (COPD), stroke and heart disease, while borderline significant trends (0.05≤p≤0.10) were found for bladder cancer, brain cancer and larynx cancer. Most results were consistent across all three cohorts. In external comparisons, we found significantly elevated SMRs for those with BLs>40 µg/dL; for bladder, lung and larynx cancer; and for COPD. In a small subsample of the US cohort (n=115) who were interviewed, we found no association between smoking and BL. CONCLUSIONS: We found strong positive mortality trends, with increasing BL level, for several outcomes in internal analysis. Many of these outcomes are associated with smoking, for which we had no data. A borderline trend was found for brain cancer, not associated with smoking.

Initial Evaluation of the Pediatric PROMIS® Health Domains in Children and Adolescents With Sickle Cell Disease.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS®) has developed pediatric self-report scales measuring several unidimensional health attributes (domains) suitable for use in clinical research, but these measures have not yet been validated in sickle cell disease (SCD). PROCEDURE: A convenience sample of SCD children, aged 8-17 years, from two sickle cell programs was recruited at routine clinic visits, including some for hydroxyurea monitoring or monthly transfusions. Children completed PROMIS pediatric items using an online data collection platform, the PROMIS Assessment Center Web site. RESULTS: A total of 235 participants (mean age 12.5 ± 2.8 years, 49.8% female) participated in the study. Adolescents (ages 12-17 years) reported significantly higher pain interference and depressive symptoms, and worse lower extremity physical functioning domain scores compared to younger children (ages 8-11 years). Female participants reported significantly higher pain interference, fatigue, and depressive symptoms, and worse lower extremity physical functioning domain scores compared with their male counterparts. Participants with hip or joint problems that limited usual activities reported significantly higher pain, fatigue, and depressive symptoms scores, and worse upper/lower extremity physical functioning scores as did participants who had experienced sickle pain in the previous 7 days. CONCLUSIONS: PROMIS pediatric measures are feasible in a research setting and identify expected differences in known group comparisons in a sample of SCD children. The large domain score differences between those with or without SCD-related complications suggest the potential usefulness of these measures in clinical research, but further validation studies are needed, particularly in clinical practice settings.

Responsiveness of PROMIS® Pediatric Measures to Hospitalizations for Sickle Pain and Subsequent Recovery.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System(®) (PROMIS(®) ) created pediatric self-report scales measuring a variety of health attributes (domains), but their responsiveness to changes in health status has not yet been determined in children with sickle cell disease (SCD). PROCEDURE: A convenience cohort of symptomatic SCD children, aged 8-17 years, was asked to complete PROMIS pediatric scales at an initial clinic visit, at the end of a subsequent hospitalization for sickle pain, at a subsequent clinic visit or at home 2-3 weeks after hospitalization, and at a clinic visit 1-2 years after their initial assessment. RESULTS: A total of 121 participants (mean age 12.5 ± 3.1 years, 56.2% female) participated in the study. Pain interference and fatigue domain scores were elevated at baseline, increased substantially during hospitalization, and largely returned to baseline by the recovery period, whereas the depressive symptoms, anger, and anxiety domain scores displayed a less pronounced elevation during hospitalizations and a slower return to baseline levels. The two physical functioning scales showed a substantial decline in response to hospitalization, but only modest improvements at the recovery assessment, likely representing incomplete recovery. CONCLUSIONS: Several PROMIS pediatric measures were responsive to changes in health status associated with occurrence and resolution of acute vaso-occlusive pain requiring hospitalization. The substantial differences in these domains during SCD-related pain exacerbations support their potential usefulness in clinical research or in clinical practice. Further studies to characterize variations in symptom patterns over time may provide insights into strategies for more effective management of sickle pain.

Attenuation of exposure-response rate ratios at higher exposures: a simulation study focusing on frailty and measurement error.

BACKGROUND: Positive exposure-response trends for rate ratios (RRs) often diminish at higher exposures. Depletion of susceptibles with higher exposure and increased measurement error at higher exposures are possible reasons. METHODS: We conducted simulations to investigate attenuation under various assumptions about susceptibility to exposure effects and measurement error, considering a hypothetical occupational cohort, using an excess relative risk model. We simulated an occupational cohort in which entry occurred over time. The metric of interest was cumulative exposure, which had a strong linear effect (RR = 4 for mean exposure), maximizing potential depletion. Measurement error of both classical and Berkson types was also simulated, increasing with increasing exposure. We conducted 100 simulations per scenario, each with 25,000 subjects enrolled from years 1940 to 2010, followed through 2010. RESULTS: With less than 100% susceptibility to exposure (a requirement for depletion), there was only modest evidence of depletion of susceptibles with increasing cumulative exposure distributed normally. There was correspondingly little attenuation of RRs, and linear exposure-response models fit well. Adding classical measurement error to cumulative exposure, increasing with increasing exposure, resulted in some modest attenuation. Using log normal instead of normally distributed cumulative exposure also resulted in some attenuation. CONCLUSIONS: Strong attenuation of relatively strong linear exposure-response trends using cumulative exposure, with relatively common disease and heterogeneous susceptibility, does not appear likely due to depletion of susceptibles. Strong attenuation seems more likely to be due to other mechanisms.