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.

Probabilistic Pairwise Model Comparisons Based on Bootstrap Estimators of the Kullback-Leibler Discrepancy.

When choosing between two candidate models, classical hypothesis testing presents two main limitations: first, the models being tested have to be nested, and second, one of the candidate models must subsume the structure of the true data-generating model. Discrepancy measures have been used as an alternative method to select models without the need to rely upon the aforementioned assumptions. In this paper, we utilize a bootstrap approximation of the Kullback-Leibler discrepancy (BD) to estimate the probability that the fitted null model is closer to the underlying generating model than the fitted alternative model. We propose correcting for the bias of the BD estimator either by adding a bootstrap-based correction or by adding the number of parameters in the candidate model. We exemplify the effect of these corrections on the estimator of the discrepancy probability and explore their behavior in different model comparison settings.

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.

Evaluating the Addition of a Clinical Pharmacist Service to a Midlevel Provider-Driven Culture Follow-up Program in a Community Emergency Department.

Background: The impact that an antimicrobial stewardship program can have on an inpatient setting has been well documented, but there are limited data on the use of an antimicrobial stewardship program in the emergency department (ED). Objective: The objective of this study was to assess the impact of adding a pharmacist service to a midlevel provider-driven culture follow-up program in the ED on achieving optimal therapy. Methods: This was a quasi-experimental study with designations of pre- and post-interventions conducted at a large community hospital with the pre-intervention phase occurring from June 1, 2019, to August 31, 2019, and the post-intervention phase occurring from January 1, 2020, to March 31, 2020. The primary outcome was optimal antimicrobial therapy: a composite of optimal antibiotic, dose, and duration, prescribed after the culture resulted. Secondary outcomes included optimal antibiotic, dose, duration, and return to the ED within 30 days due to infection. Results: Optimal antimicrobial therapy received after the culture resulted occurred in 59 patients (26.81%) in the pre-implementation phase and 40 patients (43.96%) in the implementation phase (P = .003). For the secondary outcomes, optimal antibiotic choice occurred in 115 patients (52.27%) in the pre-implementation phase and 66 patients (72.53%) in the implementation phase (P = .001). Optimal antibiotic dose occurred in 113 patients (51.36%) in the pre-implementation phase and 65 patients (71.43%) in the implementation phase (P = .001). Optimal antibiotic duration occurred in 65 patients (29.55%) in the pre-implementation phase and 40 patients (43.96%) in the implementation phase (P = .014). Conclusions: The addition of a clinical pharmacist service in a midlevel provider-driven ED culture callback program resulted in an increased rate of achieving optimal antimicrobial therapy.

Validation of Bleeding Risk Prediction Scores for Patients With Major Bleeding on Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) offer many benefits over vitamin K antagonists (VKAs) but still carry a significant risk of major bleeding. Bleeding risk prediction scores such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, and Drugs/Alcohol (HAS-BLED), Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk, and Stroke (HEMORR2HAGES), Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), Registro Informatizado Enfermedad TromboEmbólica (RIETE), and CHEST scores were validated or evaluated for use with VKAs and parenteral anticoagulants, but evidence for use with DOACs is lacking. OBJECTIVE: This study aims to evaluate bleeding risk prediction scores for DOAC patients presenting with major bleeding. METHODS: A retrospective analysis of patients presenting from 2015 to 2018 was performed. Patients were separated into bleed and nonbleed groups. The primary objective was to assess the diagnostic accuracy of the bleeding risk prediction scores utilizing the receiver operating characteristic (ROC) curve. RESULTS: A total of 126 patients were included in the analyses. The areas under the curve (AUC) for the ROC curves of the HAS-BLED, HEMORR2HAGES, ATRIA, RIETE, and CHEST scores were 0.645, 0.675, 0.580, 0.638, and 0.667, respectively. CONCLUSION AND RELEVANCE: The HAS-BLED, HEMORR2HAGES, RIETE, and CHEST scores were found to have sufficient diagnostic accuracy for predicting risk of major bleeding in our study population; however, no score was identified as having an AUC greater than 0.7. Caution may be considered when utilizing these scores for patients on DOACs.

Case series of glans injuries during voluntary medical male circumcision for HIV prevention - eastern and southern Africa, 2015-2018.

BACKGROUND: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management. METHODS: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis. RESULTS: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0·7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found. CONCLUSION: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes.

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.

Comparison of Sputum-Culture Conversion for Mycobacterium bovis and M. tuberculosis.

Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.

Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters.

Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

Importance of Pharmacy Involvement in the Treatment of Sepsis.

Purpose: A review of the impact of pharmacists on appropriate medication selection, timing of administration, and as members of a multidisciplinary sepsis response team. Summary: Early goal-directed therapy (EGDT), currently recommended by the 2013 Surviving Sepsis Campaign guidelines for the management of patients with sepsis, includes the administration of appropriate antibiotics in patients with septic shock within the first hour. Multidisciplinary teams containing pharmacists have been shown to decrease time to antibiotic delivery, time to antibiotic administration, and patient mortality. The pharmacist can act as a drug information resource, expedite the medication verification and procurement process, and offer suggestions on how to better manage the patients. Pharmacists are often consulted for dosing and antibiotic selection recommendations for patients with sepsis, but they can also help increase the appropriateness of antibiotics selected. Additional recommendations and interventions made by pharmacists include fluid management and vasopressor facilitation for the more severe patients. A sepsis management team that included a pharmacist increased the number of patients receiving appropriate antibiotics within the first hour by as much as 22-fold. Another study has demonstrated that intensive care units with a pharmacist are associated with a 4% decrease in sepsis patient mortality compared to those without a pharmacist. Conclusion: Multidisciplinary teams containing pharmacists have been shown to decrease time to administration of antibiotics, increase appropriate selection of medications, and decrease mortality; they may also decrease overall health care costs.

Human Tuberculosis Caused by Mycobacterium bovis in the United States, 2006-2013.

BACKGROUND: Using genotyping techniques that have differentiated Mycobacterium bovis from Mycobacterium tuberculosis since 2005, we review the epidemiology of human tuberculosis caused by M. bovis in the United States and validate previous findings nationally. METHODS: All tuberculosis cases with a genotyped M. tuberculosis complex isolate reported during 2006-2013 in the United States were eligible for analysis. We used binomial regression to identify characteristics independently associated with M. bovis disease using adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (CIs). RESULTS: During 2006-2013, the annual percentages of tuberculosis cases attributable to M. bovis remained consistent nationally (range, 1.3%-1.6%) among all tuberculosis cases (N = 59 273). Compared with adults 25-44 years of age, infants aged 0-4 years (aPR, 1.9 [95% CI, 1.4-2.8]) and children aged 5-14 years (aPR, 4.0 [95% CI, 3.1-5.3]) had higher prevalences of M. bovis disease. Patients who were foreign-born (aPR, 1.4 [95% CI, 1.2-1.7]), Hispanic (aPR, 3.9 [95% CI, 3.0-5.0]), female (aPR, 1.4 [95% CI, 1.3-1.6]), and resided in US-Mexico border counties (aPR, 2.0 [95% CI, 1.7-2.4]) also had higher M. bovis prevalences. Exclusively extrapulmonary disease (aPR, 3.7 [95% CI, 3.3-4.2]) or disease that was both pulmonary and extrapulmonary (aPR, 2.4 [95% CI, 2.1-2.9]) were associated with a higher prevalence of M. bovis disease. CONCLUSIONS: Children, foreign-born persons, Hispanics, and females are disproportionately affected by M. bovis, which was independently associated with extrapulmonary disease. Targeted prevention efforts aimed at Hispanic mothers and caregivers are warranted.

Evaluation of community-based treatment for drug-resistant tuberculosis in Bangladesh.

OBJECTIVE: Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013, we sought to evaluate programme performance. METHODS: In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT programme over 6 months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the programme. RESULTS: Chart review was performed on 77 patients. Sputum smears and cultures were performed, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS: The cPMDT programme in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the programme is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritised.

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.