Utilization of Health Services Among Adults With Recurrent Clostridium difficile Infection: A 12-Year Population-Based Study.

BACKGROUND Considerable efforts have been dedicated to developing strategies to prevent and treat recurrent Clostridium difficile infection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited. OBJECTIVE To compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI. METHODS We performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013. We identified CDI through the presence of a positive laboratory test result and divided patients into 3 groups: patients with rCDI, defined as CDI in the 14-57 days after initial CDI; patients with nonrecurrent CDI; and patients who never had CDI. We conducted 3 matched comparisons: (1) rCDI vs no CDI; (2) rCDI vs nonrecurrent CDI; (3) nonrecurrent CDI vs no CDI. We followed patients for 1 year and compared healthcare utilization between groups, after matching patients on age, sex, and comorbidity. RESULTS We found that patients with rCDI consistently have substantially higher levels of healthcare utilization in various settings and greater 1-year mortality risk than both patients who had nonrecurrent CDI and patients who never had CDI. CONCLUSIONS Patients who develop an initial CDI are generally characterized by excess underlying, severe illness and utilization. However, patients with rCDI experience even greater adverse consequences of their disease than patients who do not experience rCDI. Our results further support the need for continued emphasis on identifying and using novel approaches to prevent and treat rCDI. Infect Control Hosp Epidemiol. 2016;1-8.

Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection is implicated in asthma development. RSV immunoprophylaxis during infancy is efficacious in preventing RSV-related hospitalizations and has been associated with decreased wheezing in the first years of life. OBJECTIVE: We investigated whether greater adherence to immunoprophylaxis in infants at high risk for severe RSV would be associated with decreased childhood asthma. METHODS: We conducted a retrospective cohort investigation including children born from 1996-2003 who were enrolled in Kaiser Permanente Northern California or Tennessee Medicaid and eligible to receive RSV immunoprophylaxis. Asthma was defined at 4.5 to 6 years of age by using asthma-specific health care visits and medication fills. We classified children into immunoprophylaxis eligibility groups and calculated adherence (percentage receipt of recommended doses). We used a set of statistical strategies (multivariable logistic regression and propensity score [PS]-adjusted and PS-matched analyses) to overcome confounding by medical complexity because infants with higher adherence (≥70%) have higher prevalence of chronic lung disease, lower birth weight, and longer nursery stays. RESULTS: By using multivariable logistic regression and PS-adjusted models in the combined group, higher adherence to RSV immunoprophylaxis was not associated with decreased asthma. However, in PS-matched analysis, treated children with 70% or greater adherence had decreased odds of asthma compared with those with 20% or less adherence (odds ratio, 0.62; 95% CI, 0.50-0.78). CONCLUSIONS: This investigation of RSV immunoprophylaxis in high-risk children primarily found nonsignificant associations on prevention of asthma in specific preterm groups. Our findings highlight the need for larger studies and prospective cohorts and provide estimates of potential preventive effect sizes in high-risk children.

Correction: Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

[This corrects the article DOI: 10.1371/journal.pone.0151705.].

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

BACKGROUND: Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. METHODS: We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. RESULTS: Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home. CONCLUSION: Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma.

Incidence of Dravet Syndrome in a US Population.

OBJECTIVE: De novo mutations of the gene sodium channel 1α (SCN1A) are the major cause of Dravet syndrome, an infantile epileptic encephalopathy. US incidence of DS has been estimated at 1 in 40 000, but no US epidemiologic studies have been performed since the advent of genetic testing. METHODS: In a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California during 2007-2010, we electronically identified patients who received ≥2 seizure diagnoses before age 12 months and who were also prescribed anticonvulsants at 24 months. A child neurologist reviewed records to identify infants who met 4 of 5 criteria for clinical Dravet syndrome: normal development before seizure onset; ≥2 seizures before age 12 months; myoclonic, hemiclonic, or generalized tonic-clonic seizures; ≥2 seizures lasting >10 minutes; and refractory seizures after age 2 years. SCN1A gene sequencing was performed as part of routine clinical care. RESULTS: Eight infants met the study criteria for clinical Dravet syndrome, yielding an incidence of 1 per 15 700. Six of these infants (incidence of 1 per 20 900) had a de novo SCN1A missense mutation that is likely to be pathogenic. One infant had an inherited SCN1A variant that is unlikely to be pathogenic. All 8 experienced febrile seizures, and 6 had prolonged seizures lasting >10 minutes by age 1 year. CONCLUSIONS: Dravet syndrome due to an SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ≥2 prolonged febrile seizures by 1 year of age.

Adherence to Immunoprophylaxis Regimens for Respiratory Syncytial Virus Infection in Insured and Medicaid Populations.

BACKGROUND: Immunoprophylaxis is the only pharmaceutical intervention for mitigating respiratory syncytial virus (RSV) infection. Patient level data on adherence to American Academy of Pediatrics (AAP) immunoprophylaxis recommendations are limited. This study characterizes adherence to AAP guidelines in privately insured and Medicaid populations. METHODS: We performed a retrospective birth cohort study of 211 174 privately insured children in Northern California; and 458 837 publicly insured children in Tennessee born between January 1, 1996 and December 31, 2008. Adherence to the AAP guideline was defined for eligible infants as the number of doses of RSV immunoprophylaxis administered over the number recommended for 4 mutually exclusive eligibility groups: chronic lung disease, prematurity <29 weeks, prematurity <32 weeks, and other eligibility. RESULTS: We identified 3456 California (Kaiser Permanente Northern California [KPNC]) and 12 251 Tennessee (Tennessee Medicaid [TennCare]) infants meeting AAP eligibility criteria. Immunoprophylaxis administration increased over the study period, from 15% for all eligible groups in 1998 to 54% in 2007. Adherence was highest among babies with chronic lung disease (KPNC 67% and TennCare 55%). Nonadherence (0% adherence) was greatest among infants of African American mothers (adjusted odds ratio [AOR] = 1.32; 95% confidence interval [CI] = .98-1.78); those with mothers with less than a high school education (AOR = 1.58; CI = 1.09-2.30) in KPNC; and in infants of Hispanic mothers in TennCare (AOR = 1.65; CI = 1.24-2.20). In KPNC, 0.11% of ineligible term infants and 5% of ineligible premature infants received immunoprophylaxis; the corresponding proportions in TennCare were 1% and 11%. CONCLUSIONS: Overall adherence with AAP guidelines has increased over time. Considerable overuse and underuse of immunoprophylaxis are evident with identifiable risk groups to target for improvement.

Frequency, duration and predictors of bronchiolitis episodes of care among infants ≥32 weeks gestation in a large integrated healthcare system: a retrospective cohort study.

BACKGROUND: Bronchiolitis is common in the first two years of life and is the most frequent cause of hospitalization in this age group. No previous studies have used an episode-of-care analysis to describe the frequency, duration, and predictors of bronchiolitis episodes of care during the first two years. METHODS: We conducted a retrospective cohort study of 123,264 infants ≥32 weeks gestation born at 6 Northern California Kaiser Permanente hospitals between 1996 and 2002. We used electronic medical records to concatenate hospital, emergency department and outpatient health care encounters for bronchiolitis into discrete episodes of care. We used descriptive statistics to report frequency and duration of bronchiolitis episodes and used logistic regression to assess the effect of gestational age and other clinical and demographic predictors on the outcome of bronchiolitis episodes. RESULTS: Among all infants, the rate of bronchiolitis episodes was 162 per 1000 children during the first 2 years of life; approximately 40% required >1 day of medical attention with a mean duration of 7.0 ± 5.9 days. Prematurity was associated with increased risk of bronchiolitis episodes and longer duration. Bronchiolitis episodes rates per 1000 infants were 246 for 32-33 weeks gestational age, 204 for 34-36 weeks, and 148-178 for >36 weeks. Male gender, African-American and Hispanic race/ethnicity, and parental history of asthma were associated with an increased risk of having a bronchiolitis episode and/or longer duration. CONCLUSIONS: Bronchiolitis episodes of care are frequent during the first two years of life and the duration ranges from 1 to 27 days. Prematurity was associated with more frequent and longer duration of bronchiolitis episodes of care, which may reflect illness severity and/or perceived vulnerability.

Recurrent wheezing in the third year of life among children born at 32 weeks' gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life.

OBJECTIVE: To quantify the relationship between recurrent wheezing (RW) in the third year of life and respiratory syncytial virus (RSV) infection, prematurity, and neonatal oxygen exposure. DESIGN: Retrospective cohort study linking inpatient, outpatient, and laboratory databases for cohort assembly and logistic regression analysis. SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: A total of 71,102 children born from 1996 to 2002 at 32 weeks' gestational age or later who were health plan members for 9 or more months in their first and third years. MAIN EXPOSURES: Laboratory-confirmed, medically attended RSV infection during first year and supplemental oxygen during birth hospitalization. OUTCOME MEASURES: Recurrent wheezing, quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The rate of RW in the third year of life was 16.23% among premature infants with RSV and 6.22% among those without RSV. The risk of RW increased among infants who had an RSV outpatient encounter (adjusted odds ratio [AOR], 2.07; 95% CI, 1.61-2.67), uncomplicated RSV hospitalization (AOR, 4.66; 95% CI, 3.55-6.12), or prolonged RSV hospitalization (AOR, 3.42; 95% CI, 2.01-5.82) compared with infants without RSV encounters. Gestational age of 34 to 36 weeks was associated with increased risk of RW (AOR, 1.23; 95% CI 1.07-1.41) compared with 38 to 40 weeks, while a gestational age of 41 weeks or more was protective (AOR, 0.90; 95% CI, 0.81-0.99). Supplemental oxygen exposure was associated with increased risk at all levels. CONCLUSION: Laboratory-confirmed, medically attended RSV infection, prematurity, and exposure to supplemental oxygen during the neonatal period have independent associations with the development of RW in the third year of life.

Antenatal ultrasound and risk of autism spectrum disorders.

We evaluated antenatal ultrasound (U/S) exposure as a risk factor for autism spectrum disorders (ASD), comparing affected singleton children and control children born 1995-1999 and enrolled in the Kaiser Permanente health care system. Among children with ASD (n = 362) and controls (n = 393), 13% had no antenatal exposure to U/S examinations; case-control differences in number of exposures during the entire gestation or by trimester were small and not statistically significant. In analyses adjusted for covariates, cases were generally similar to controls with regard to the number of U/S scans throughout gestation and during each trimester. This study indicates that antenatal U/S is unlikely to increase the risk of ASD, although studies examining ASD subgroups remain to be conducted.