Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions.

Autosomal recessive diseases, such as cystic fibrosis (CF), require inheritance of 2 mutated genes. However, some studies indicate that CF carriers are at increased risk for some conditions associated with CF. These investigations focused on single conditions and included small numbers of subjects. Our goal was to determine whether CF carriers are at increased risk for a range of CF-related conditions. Using the Truven Health MarketScan Commercial Claims database (2001-2017), we performed a population-based retrospective matched-cohort study. We identified 19,802 CF carriers and matched each carrier with 5 controls. The prevalence of 59 CF-related diagnostic conditions was evaluated in each cohort. Odds ratios for each condition were computed for CF carriers relative to controls. All 59 CF-related conditions were more prevalent among carriers compared with controls, with significantly increased risk (P < 0.05) for 57 conditions. Risk was increased for some conditions previously linked to CF carriers (e.g., pancreatitis, male infertility, bronchiectasis), as well as some conditions not previously reported (e.g., diabetes, constipation, cholelithiasis, short stature, failure to thrive). We compared our results with 23,557 subjects with CF, who were also matched with controls; as the relative odds of a given condition increased among subjects with CF, so did the corresponding relative odds for carriers (P < 0.001). Although individual-level risk remained low for most conditions, because there are more than 10 million carriers in the US, population-level morbidity attributable to the CF carrier state is likely substantial. Genetic testing may inform prevention, diagnosis, and treatment for a broad range of CF carrier-related conditions.

A comprehensive framework to estimate the frequency, duration, and risk factors for diagnostic delays using bootstrapping-based simulation methods.

BACKGROUND: The incidence of diagnostic delays is unknown for many diseases and specific healthcare settings. Many existing methods to identify diagnostic delays are resource intensive or difficult to apply to different diseases or settings. Administrative and other real-world data sources may offer the ability to better identify and study diagnostic delays for a range of diseases. METHODS: We propose a comprehensive framework to estimate the frequency of missed diagnostic opportunities for a given disease using real-world longitudinal data sources. We provide a conceptual model of the disease-diagnostic, data-generating process. We then propose a bootstrapping method to estimate measures of the frequency of missed diagnostic opportunities and duration of delays. This approach identifies diagnostic opportunities based on signs and symptoms occurring prior to an initial diagnosis, while accounting for expected patterns of healthcare that may appear as coincidental symptoms. Three different bootstrapping algorithms are described along with estimation procedures to implement the resampling. Finally, we apply our approach to the diseases of tuberculosis, acute myocardial infarction, and stroke to estimate the frequency and duration of diagnostic delays for these diseases. RESULTS: Using the IBM MarketScan Research databases from 2001 to 2017, we identified 2,073 cases of tuberculosis, 359,625 cases of AMI, and 367,768 cases of stroke. Depending on the simulation approach that was used, we estimated that 6.9-8.3% of patients with stroke, 16.0-21.3% of patients with AMI and 63.9-82.3% of patients with tuberculosis experienced a missed diagnostic opportunity. Similarly, we estimated that, on average, diagnostic delays lasted 6.7-7.6 days for stroke, 6.7-8.2 days for AMI, and 34.3-44.5 days for tuberculosis. Estimates for each of these measures was consistent with prior literature; however, specific estimates varied across the different simulation algorithms considered. CONCLUSIONS: Our approach can be easily applied to study diagnostic delays using longitudinal administrative data sources. Moreover, this general approach can be customized to fit a range of diseases to account for specific clinical characteristics of a given disease. We summarize how the choice of simulation algorithm may impact the resulting estimates and provide guidance on the statistical considerations for applying our approach to future studies.

The Rapid Reduction of Infection-Related Visits and Antibiotic Use Among People With Cystic Fibrosis After Starting Elexacaftor-Tezacaftor-Ivacaftor.

BACKGROUND: People with cystic fibrosis (CF) routinely suffer from recurrent sinopulmonary infections. Such infections require frequent courses of antimicrobials and often involve multidrug-resistant organisms. The goal of this study was to identify real-world evidence for the effectiveness of elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) in decreasing infection-related visits and antimicrobial use in people with CF. METHODS: Using IBM MarketScan data, we identified 389 enrollees with CF who began taking ELX/TEZ/IVA before 1 December 2019 and were enrolled from 1 July 2019 to 14 March 2020. We also identified a comparison population who did not begin ELX/TEZ/IVA during the study period. We compared the following outcomes in the 15 weeks before and after medication initiation: total healthcare visits, inpatient visits, infection-related visits, and antimicrobial prescriptions. We analyzed outcomes using both a case-crossover analysis and a difference-in-differences analysis, to control for underlying trends. RESULTS: For the case-crossover analysis, ELX/TEZ/IVA initiation was associated with the following changes over a 15-week period: change in overall healthcare visit dates, -2.5 (95% confidence interval, -3.31 to -1.7); change in inpatient admissions, -0.16 (-.22 to -.10); change in infection-related visit dates, -0.62 (-.93 to -.31); and change in antibiotic prescriptions, -0.78 (-1.03 to -.54). Results from the difference-in-differences approach were similar. CONCLUSIONS: We show a rapid reduction in infection-related visits and antimicrobial use among people with CF after starting a therapy that was not explicitly designed to treat infections. Currently, there are >30 000 people living with CF in the United States alone. Given that this therapy is effective for approximately 90% of people with CF, the impact on respiratory infections and antimicrobial use may be substantial.

Understanding the Prodromal Period of Necrotizing Soft Tissue Infections of the Genitalia (Fournier's Gangrene) and the Incidence, Duration, and Risk Factors Associated With Potential Missed Opportunities for an Earlier Diagnosis: A Population-based Longitudinal Study.

PURPOSE: The purpose of this paper was to investigate patterns of health care utilization leading up to diagnosis of necrotizing soft tissue infections of the genitalia and to identify risk factors associated with potential diagnostic delay. MATERIALS AND METHODS: IBM MarketScan Research Databases (2001-2020) were used to identify index cases of necrotizing soft tissue infections of the genitalia. We identified health care visits for symptomatically similar diagnoses (eg, penile swelling, cellulitis) that occurred prior to necrotizing soft tissue infections of the genitalia diagnosis. A change-point analysis identified the window before diagnosis where diagnostic opportunities first appeared. A simulation model estimated the likelihood symptomatically similar diagnosis visits represented a missed opportunity for earlier diagnosis. Patient and provider characteristics were evaluated for their associations with delay. RESULTS: We identified 8,098 patients with necrotizing soft tissue infections of the genitalia, in which 4,032 (50%) had a symptomatically similar diagnosis visit in the 21-day diagnostic window, most commonly for "non-infectious urologic abnormalities" (eg, genital swelling; 64%): 46% received antibiotics; 16% saw a urologist. Models estimated that 5,096 of the symptomatically similar diagnosis visits (63%) represented diagnostic delay (mean duration 6.2 days; mean missed opportunities 1.8). Risk factors for delay included urinary tract infection history (OR 2.1) and morbid obesity (OR 1.6). Visits to more than 1 health care provider/location in a 24-hour period significantly decreased delay risk. CONCLUSIONS: Nearly 50% of insured patients who undergo debridement for, or die from, necrotizing soft tissue infections of the genitalia will present to a medical provider with a symptomatically similar diagnosis suggestive of early disease development. Many of these visits likely represent diagnostic delay. Efforts to minimize logistic and cognitive biases in this rare condition may lead to improved outcomes if they lead to earlier interventions.

Associations between body mass index and body composition measures in a birth cohort.

BACKGROUND: Associations among body composition measures have been limited to cross-sectional analyses of different subjects. We identified cross-sectional relationships between body mass index (BMI) and other body composition measures and predicted body composition measures from BMI throughout childhood and adolescence. METHODS: BMI was calculated and % body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) were measured using dual-energy x-ray absorptiometry at ages 5, 9, 11, 13, 15, and 17 years in a birth cohort (n = 629). Sex-specific body composition measures were calculated for BMI-for-age percentiles; associations between BMI and body composition measures were characterized; and body composition measures were predicted from BMI. RESULTS: %BF, FMI, and FFMI generally increased with BMI-for-age percentiles at each age. Correlations between BMI and %BF or FMI were generally higher at BMI-for-age percentiles ≥95% than for lower BMI-for-age percentiles. Correlations between BMI and FFMI were generally higher for participants at very low and very high BMI-for-age percentiles than at moderate BMI-for-age percentiles. Age- and sex-specific predictions from BMI are provided for %BF, FM, and FFMI. CONCLUSIONS: Sex-specific body composition measures throughout childhood and adolescence are presented. BMI is a better indicator of adiposity at higher than at lower BMI values. IMPACT: Sex-specific body composition measures throughout childhood and adolescence are described. % BF, FMI, and FFMI generally increased with BMI-for-age percentiles for both sexes throughout childhood and adolescence. BMI is a better indicator of adiposity at higher BMI levels than at lower BMI values throughout childhood and adolescence.

Warmer Weather and the Risk of Urinary Tract Infections in Women.

PURPOSE: The incidence of urinary tract infections is seasonal, peaking in summer months. One possible mechanism for the observed seasonality of urinary tract infections is warmer weather. MATERIALS AND METHODS: We identified all urinary tract infection cases located in approximately 400 metropolitan statistical areas in the contiguous United States between 2001 and 2015 using the Truven Health MarketScan® databases. A total of 167,078,882 person-years were included in this data set and a total of 15,876,030 urinary tract infection events were identified by ICD-9 code 599.0. Weather data for each metropolitan statistical area and date were obtained from the National Centers for Environmental Information. We computed the mean temperature during the period 0 to 7 days prior to the urinary tract infection diagnosis. We used a quasi-Poisson generalized linear model. The primary outcome was the number of urinary tract infections each day in a metropolitan statistical area in each age group. Covariates considered included age group, day of week, year and the temperature during the previous 7 days. RESULTS: Warmer weather increases the risk of urinary tract infections among women treated in outpatient settings in a dose-response fashion. On days when the prior week's average temperature was between 25 and 30C, the incidence of urinary tract infections was increased by 20% to 30% relative to when the prior week's temperature was 5 to 7.5C. CONCLUSIONS: The incidence of urinary tract infections increases with the prior week's temperature. Our results indicate that warmer weather is a risk factor for urinary tract infections. Furthermore, as temperatures rise, the morbidity attributable to urinary tract infections may increase.

Approach to analysing correlated contextual factors: an application for studies on violence.

BACKGROUND: Numerous public health studies, especially in the area of violence, examine the effects of contextual or group-level factors on health outcomes. Often, these contextual factors exhibit strong pairwise correlations, which pose a challenge when these factors are included as covariates in a statistical model. Such models may be characterised by inflated standard errors and unstable parameter estimates that may fluctuate drastically from sample to sample, where the excessive estimation variability is reflected by inflated standard errors. METHODS: We propose a three-stage approach for analysing correlated contextual factors that proceeds as follows: (1) a principal components analysis (PCA) is performed on the original set of correlated variables, (2) the primary generated principal components are included in a multilevel multivariable model and (3) the estimated parameters for these components are transformed into estimates for each of the original contextual factors. Using school violence data, we examined the associations between school crime and correlated contextual school factors (ie, English proficiency, academic performance, pupil to teacher ratio, average class size and children on free and reduced meals). RESULTS: From models ignoring correlations, school crime was not reliably associated with any of the contextual school factors. When models were fit with principal components, school crime was found to be positively associated with a school's student to teacher ratio, average classroom size and academic performance but negatively associated with the proportion of children who were on free and reduced meals. CONCLUSION: Our multistep approach is one way to address multicollinearity encountered in social epidemiological studies of violence.

Higher Longitudinal Milk Intakes Are Associated with Increased Height in a Birth Cohort Followed for 17 Years.

Background: Height is an indicator of nutritional status; linear growth faltering has recognized consequences for cognitive, emotional, and chronic disease risk. Although height is routinely studied in developing countries, less attention is given to height in the United States. Objective: The objective of this study was to identify longitudinal associations between childhood and adolescent beverage intakes, nutrient adequacy, or energy intake and height in a birth cohort. Methods: Data for participants through ages 2-17 y (n = 717; 353 males, 364 females) recruited at birth for the longitudinal Iowa Fluoride Study (IFS) were used in the current cohort analyses. Beverage intakes (n = 708) were collected by beverage-frequency questionnaires at 3- to 6-mo intervals, whereas nutrient data (n = 652) were obtained from 3-d food diaries completed at 3- to 6-mo intervals through age 8.5 y and from Block Kids' food-frequency questionnaires at 2-y intervals after age 8.5 y. Nutrient adequacy ratios were calculated with the use of age- and sex-specific Estimated Average Requirements. Height was measured at clinic visits when the participants were approximately ages 5, 9, 11, 13, 15, and 17 y. Linear mixed models were used to identify longitudinal associations between dietary variables and height. A baseline model that adjusted for changing growth patterns during adolescence was established. Dietary and potential confounding variables were added to this baseline model. Results: Milk intake adjusted for mean adequacy ratio, energy intake, and baseline socioeconomic status was associated with height; for each additional 8 ounces (236 mL) of milk consumed per day throughout childhood and adolescence, height increased, on average, by 0.39 cm (95% CI: 0.18, 0.60 cm; P < 0.001). Conclusions: IFS participants' height increased by 0.39 cm for each additional 8 ounces (236 mL) of milk consumed throughout childhood and adolescence. The clinical implications of the mild linear growth faltering observed in healthy youth are unknown. This trial was registered at www.clinicaltrials.gov as 199112665.

Mutans Streptococci and Dental Caries: A New Statistical Modeling Approach.

Survival analyses have been used to overcome some of the limitations encountered with other statistical analyses. Although extended Cox hazard modeling with time-dependent variables has been utilized in several medical studies, it has never been utilized in assessing the complex relationship between mutans streptococci (MS) acquisition (time-dependent covariate) and time to having dental caries (outcome). This study involved secondary analyses of data from a prospective study conducted at the University of Alabama at Birmingham. Low socioeconomic status, African-American preschool children from Perry County, AL, USA (n = 95) had dental examinations at age 1 year and annually thereafter until age 6 years by three calibrated dentists. Salivary MS tests were done at ages 1, 1.5, 2, 2.5, 3, and 4 years. The patterns of and relationship between initial MS detection (time-dependent covariate) and dental caries experience occurrence were assessed, using extended Cox hazard modeling. The median time without MS acquisition (50% of the children not having positive MS test) was 2 years. Approximately 79% of the children had positive salivary MS tests by the age of 4 years. The median caries experience survival (50% of the children not having dental caries) was 4 years. During the follow-up period, 65 of the children (68.4%) had their initial primary caries experience. Results of the extended Cox hazard modeling showed a significant overall/global relationship between initial caries experience event at any given time during the follow-up period and having a positive salivary MS test at any time during the follow-up period (hazard ratio = 2.25, 95% CI 1.06-4.75). In conclusion, the extended Cox modeling was used for the first time and its results showed a significant global/overall relationship between MS acquisition and dental caries. Further research using causal mediation analysis with survival data is necessary, where the mediator "presence of MS" is treated as a time-dependent variable.

Lighting and marking policies are associated with reduced farm equipment-related crash rates: a policy analysis of nine Midwestern US states.

OBJECTIVE: To evaluate the effectiveness of roadway policies for lighting and marking of farm equipment in reducing crashes in Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, South Dakota and Wisconsin. METHODS: In this ecological study, state policies on lighting and marking of farm equipment were scored for compliance with standards of the American Society of Agricultural and Biological Engineers (ASABE). Using generalized estimating equations negative binomial models, we estimated the relationships between lighting and marking scores, and farm equipment crash rates, per 100 000 farm operations. RESULTS: A total of 7083 crashes involving farm equipment was reported from 2005 to 2010 in the Upper Midwest and Great Plains. As the state lighting and marking score increased by 5 units, crash rates reduced by 17% (rate ratio=0.83; 95% CI 0.78 to 0.88). Lighting-only (rate ratio=0.48; 95% CI 0.45 to 0.51) and marking-only policies (rate ratio=0.89; 95% CI 0.83 to 0.96) were each associated with reduced crash rates. CONCLUSIONS: Aligning lighting and marking policies with ASABE standards may effectively reduce crash rates involving farm equipment.

Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery.

IMPORTANCE: Previous studies suggested that a bundled intervention was associated with lower rates of Staphylococcus aureus surgical site infections (SSIs) among patients having cardiac or orthopedic operations. OBJECTIVE: To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of S. aureus SSIs in patients undergoing cardiac operations or hip or knee arthroplasties. DESIGN, SETTING, AND PARTICIPANTS: Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014). INTERVENTIONS: Patients whose preoperative nares screens were positive for methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown. MAIN OUTCOMES AND MEASURES: The primary outcome was complex (deep incisional or organ space) S. aureus SSIs. Monthly SSI counts were analyzed using Poisson regression analysis. RESULTS: After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex S. aureus SSIs occurred after 28,218 operations during the preintervention period and 29 occurred after 14,316 operations during the intervention period (mean rate per 10,000 operations, 36 for preintervention period vs 21 for intervention period, difference, -15 [95% CI, -35 to -2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex S. aureus SSIs decreased for hip or knee arthroplasties (difference per 10,000 operations, -17 [95% CI, -39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10,000 operations, -6 [95% CI, -48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57]). CONCLUSIONS AND RELEVANCE: In this multicenter study, a bundle comprising S. aureus screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex S. aureus SSIs.

Performing T-tests to Compare Autocorrelated Time Series Data Collected from Direct-Reading Instruments.

Industrial hygienists now commonly use direct-reading instruments to evaluate hazards in the workplace. The stored values over time from these instruments constitute a time series of measurements that are often autocorrelated. Given the need to statistically compare two occupational scenarios using values from a direct-reading instrument, a t-test must consider measurement autocorrelation or the resulting test will have a largely inflated type-1 error probability (false rejection of the null hypothesis). A method is described for both the one-sample and two-sample cases which properly adjusts for autocorrelation. This method involves the computation of an "equivalent sample size" that effectively decreases the actual sample size when determining the standard error of the mean for the time series. An example is provided for the one-sample case, and an example is given where a two-sample t-test is conducted for two autocorrelated time series comprised of lognormally distributed measurements.

Association of hospitalizations for asthma with seasonal and pandemic influenza.

BACKGROUND AND OBJECTIVE: Although influenza has been associated with asthma exacerbations, it is not clear the extent to which this association affects health care use in the United States. The first goal of this project was to determine whether, and to what extent, the incidence of asthma hospitalizations is associated with seasonal variation in influenza. Second, we used influenza trends (2000-2008) to help predict asthma admissions during the 2009 H1N1 influenza pandemic. METHODS: We identified all hospitalizations between 1998 and 2008 in the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project during which a primary diagnosis of asthma was recorded. Separately, we identified all hospitalizations during which a diagnosis of influenza was recorded. We performed time series regression analyses to investigate the association of monthly asthma admissions with influenza incidence. Finally, we applied these time series regression models using 1998-2008 data, to forecast monthly asthma admissions during the 2009 influenza pandemic. RESULTS: Based on time series regression models, a strong, significant association exists between concurrent influenza activity and incidence of asthma hospitalizations (P-value < 0.0001). Use of influenza data to predict asthma admissions during the 2009 H1N1 pandemic improved the mean squared prediction error by 60.2%. CONCLUSIONS: Influenza activity in the population is significantly associated with asthma hospitalizations in the United States, and this association can be exploited to more accurately forecast asthma admissions. Our results suggest that improvements in influenza surveillance, prevention and treatment may decrease hospitalizations of asthma patients.

Steering teens safe: a randomized trial of a parent-based intervention to improve safe teen driving.

BACKGROUND: Crashes are the leading cause of death for teens, and parent-based interventions are a promising approach. We assess the effectiveness of Steering Teens Safe, a parent-focused program to increase safe teen driving. METHODS: Steering Teens Safe aimed to improve parental communication with teens about safe driving using motivational interviewing techniques in conjunction with 19 safe driving lessons. A randomized controlled trial involved 145 parent-teen dyads (70 intervention and 75 control). Intervention parents received a 45-minute session to learn the program with four follow-up phone sessions, a DVD, and a workbook. Control parents received a standard brochure about safe driving. Scores were developed to measure teen-reported quantity and quality of parental communication about safe driving. The main outcome measure was a previously validated Risky Driving Score reported by teens. Because the Score was highly skewed, a generalized linear model based on a gamma distribution was used for analysis. RESULTS: Intervention teens ranked their parent's success in talking about driving safety higher than control teens (p = 0.035) and reported that their parents talked about more topics (non-significant difference). The Risky Driving Score was 21% lower in intervention compared to control teens (85% CI = 0.60, 1.00). Interaction between communication quantity and the intervention was examined. Intervention teens who reported more successful communication had a 42% lower Risky Driving Score (95% CI = 0.37, 0.94) than control parents with less successful communication. CONCLUSIONS: This program had a positive although not strong effect, and it may hold the most promise in partnership with other programs, such as Driver's Education or Graduated Driver's License policies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01014923. Registered Nov. 16, 2009.

Creatine kinase levels during preseason camp in National Collegiate Athletic Association Division I football athletes.

OBJECTIVE: To investigate mean creatine kinase (CK) levels in National Collegiate Athletic Association (NCAA) Division I football athletes and the relationship between mean CK levels and demographic variables. DESIGN: Observational cohort. SETTING: NCAA Division I football program. PARTICIPANTS: NCAA Division I football athletes. INTERVENTIONS: Blood and urine samples were obtained from 32 athletes on the first (time 1), third (time 2), and seventh (time 3) days of football camp. MAIN OUTCOME MEASURES: Mean CK levels. The hypotheses were formulated before the data were collected. RESULTS: All urine samples tested negative for blood. Mean CK levels were 284.7 U/L at time 1, 1299.8 U/L at time 2, and 1562.4 U/L at time 3. The increases in means were statistically significant (P < 0.005 for all pairwise comparisons). Most demographic variables were not related to mean CK levels. The number of days in the precamp conditioning program was negatively associated with mean CK levels (P = 0.0284). CONCLUSIONS: Mean CK levels in NCAA Division I football athletes during camp were higher than the serological criteria for rhabdomyolysis commonly used in clinical practice. More data are needed to assess if the number of days of participation in precamp conditioning is related to lower CK levels in NCAA Division I football athletes during camp.

The Increase in Household Transmission of Pertussis Associated With Diagnostic Delays.

BACKGROUND: Pertussis is a highly contagious respiratory illness that can be especially dangerous to young children. Transmission of pertussis often occurs in household settings and is impacted by the timing of treatment and postexposure chemoprophylaxis. This study analyzes the risk for secondary household transmission and if delays in diagnosing pertussis increased the risk for household transmission. METHODS: We conducted 2 population-based studies using a large nationally representative administrative claims database. The first study utilized a stratified monthly incidence model to compare the incidence of pertussis among enrollees exposed to a family member with pertussis versus those not exposed. The second study was conducted at a household level following the index case of pertussis in each household. We identified diagnostic delays in the initial household case and used a logistic regression model to evaluate if such delays were associated with a greater risk for transmission. RESULTS: The incidence rate ratio of pertussis was 938.99 [95% confidence interval (CI): 880.19-1001.73] among enrollees exposed to a family member with pertussis relative to those not exposed. The odds of secondary household transmission in households where the index case experienced a diagnostic delay was 5.10 (CI: 4.44-5.85) times the odds of transmission when the index case was not delayed. We found that longer delays were associated with a greater risk for secondary household transmission ( P < 0.0001). CONCLUSIONS: There is a high rate of secondary transmission of pertussis in household settings. Diagnostic delays increase the likelihood that pertussis will transmit in the household.

Does Implementation Matter? Associations Between Implementation of Maine's Anti- Bullying Law and Bullying Victimization Among High School Youth.

PURPOSE: To characterize the relationship between implementation of an antibullying law and bullying rates among high school youth. METHODS: School staff (administrators, counselors, and teachers) from public high schools in Maine completed a survey assessing: (1) the frequency with which they implemented 17 components of their district's antibullying policy as mandated by state law; and (2) confidence in implementing the law. Their responses were linked to data on bullying victimization among high school respondents to the Maine Integrated Youth Health Survey, which created a population-based dataset of 84 high schools with 29,818 student responses. RESULTS: Students in schools where administrators (adjusted odds ratio = 0.93; 95% CI: 0.89, 0.97) and counselors (adjusted odds ratio = 0.86; 95% CI: 0.81, 0.92) reported implementing more mandated components of the law experienced notable reductions in the odds of bullying, controlling for student-level characteristics (sex, race, grade) and for school-level bullying rates assessed prior to the passage of the law. With respect to specific implementation components, bullying was most consistently reduced in schools where staff reported increased referrals for counseling and other supports for targets of bullying and in schools where counselors and teachers were interviewed as part of bullying investigations. Students in schools where teachers reported increased confidence in implementing the antibullying law also had reduced odds of bullying. DISCUSSION: These data provide some of the first evidence that the efficacy of a state's antibullying law depends in part on the extent to which school personnel implement the law.

Diurnal temperature variation and the implications for diagnosis and infectious disease screening: a population-based study.

OBJECTIVES: Fevers have been used as a marker of disease for hundreds of years and are frequently used for disease screening. However, body temperature varies over the course of a day and across individual characteristics; such variation may limit the detection of febrile episodes complicating the diagnostic process. Our objective was to describe individual variation in diurnal temperature patterns during episodes of febrile activity using millions of recorded temperatures and evaluate the probability of recording a fever by sex and for different age groups. METHODS: We use timestamped deidentified temperature readings from thermometers across the US to construct illness episodes where continuous periods of activity in a single user included a febrile reading. We model the mean temperature recorded and probability of registering a fever across the course of a day using sinusoidal regression models while accounting for user age and sex. We then estimate the probability of recording a fever by time of day for children, working-age adults, and older adults. RESULTS: We find wide variation in body temperatures over the course of a day and across individual characteristics. The diurnal temperature pattern differed between men and women, and average temperatures declined for older age groups. The likelihood of detecting a fever varied widely by the time of day and by an individual's age or sex. CONCLUSIONS: Time of day and demographics should be considered when using body temperatures for diagnostic or screening purposes. Our results demonstrate the importance of follow-up thermometry readings if infectious diseases are suspected.

Association between household opioid prescriptions and risk for overdose among family members not prescribed opioids.

BACKGROUND: Prescription opioids have contributed to the rise in opioid-related overdoses and deaths. The presence of opioids within households may increase the risk of overdose among family members who were not prescribed an opioid themselves. Larger quantities of opioids may further increase risk. OBJECTIVES: To determine the risk of opioid overdose among individuals who were not prescribed an opioid but were exposed to opioids prescribed to other family members in the household, and evaluate the risk in relation to the total morphine milligram equivalents (MMEs) present in the household. METHODS: We conducted a cohort study using a large database of commercial insurance claims from 2001 to 2021. For inclusion in the cohort, we identified individuals not prescribed an opioid in the prior 90 days from households with two or more family members, and determined the total MMEs prescribed to other family members. Individuals were stratified into monthly enrollment strata defined by household opioid exposure and other confounders. A generalized linear model was used to estimate incidence rate ratios (IRRs) for overdose. RESULTS: Overall, the incidence of overdose among enrollees in households where a family member was prescribed an opioid was 1.73 (95% confidence interval [CI]: 1.67-1.78) times greater than households without opioid prescriptions. The risk of overdose increased continuously with the level of potential MMEs in the household from an IRR of 1.23 (95% CI: 1.16-1.32) for 1-100 MMEs to 4.67 (95% CI: 4.18-5.22) for >12,000 MMEs. The risk of overdose associated with household opioid exposure was greatest for ages 1-2 years (IRR: 3.46 [95% CI: 2.98-4.01]) and 3-5 years (IRR: 3.31 [95% CI: 2.75-3.99]). CONCLUSIONS: The presence of opioids in a household significantly increases the risk of overdose among other family members who were not prescribed an opioid. Higher levels of MMEs, either in terms of opioid strength or quantity, were associated with increased levels of risk. Risk estimates may reflect accidental poisonings among younger family members.