Epidemic Clostridium difficile (027/BI/NAP1) rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key moments in the evolutionary history leading to its emergence and subsequent patterns of global spread remain unknown. Here we define the global population structure of C. difficile 027/BI/NAP1 based on whole-genome sequencing and phylogenetic analysis. We demonstrate that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance mutation and a highly-related conjugative transposon. The two epidemic lineages displayed distinct patterns of global spread, and the FQR2 lineage spread more widely leading to healthcare outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid trans-continental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.

Poor coordination of care across providers and birth settings has been associated with adverse maternal-newborn outcomes. Research suggests that integration of midwives into regional health systems is a key determinant of optimal maternal-newborn outcomes, yet, to date, the characteristics of an integrated system have not been described, nor linked to health disparities.MethodsOur multidisciplinary team examined published regulatory data to inform a 50-state database describing the environment for midwifery practice and interprofessional collaboration. Items (110) detailed differences across jurisdictions in scope of practice, autonomy, governance, and prescriptive authority; as well as restrictions that can affect patient safety, quality, and access to maternity providers across birth settings. A nationwide survey of state regulatory experts (n = 92) verified the ‘on the ground’ relevance, importance, and realities of local interpretation of these state laws. Using a modified Delphi process, we selected 50/110 key items to include in a weighted, composite Midwifery Integration Scoring (MISS) system. Higher scores indicate greater integration of midwives across all settings. We ranked states by MISS scores; and, using reliable indicators in the CDC-Vital Statistics Database, we calculated correlation coefficients between MISS scores and maternal-newborn outcomes by state, as well as state density of midwives and place of birth. We conducted hierarchical linear regression analysis to control for confounding effects of race.ResultsMISS scores ranged from lowest at 17 (North Carolina) to highest at 61 (Washington), out of 100 points. Higher MISS scores were associated with significantly higher rates of spontaneous vaginal delivery, vaginal birth after cesarean, and breastfeeding, and significantly lower rates of cesarean, preterm birth, low birth weight infants, and neonatal death. MISS scores also correlated with density of midwives and access to care across birth settings. Significant differences in newborn outcomes accounted for by MISS scores persisted after controlling for proportion of African American births in each state.ConclusionThe MISS scoring system assesses the level of integration of midwives and evaluates regional access to high quality maternity care. In the United States, higher MISS Scores were associated with significantly higher rates of physiologic birth, less obstetric interventions, and fewer adverse neonatal outcomes.

BackgroundClostridium difficile infection poses a significant healthcare burden. However, the derivation of a simple, evidence based prediction rule to assist patient management has not yet been described.This study aimed to identify such a prediction rule to stratify hospital inpatients according to risk of all-cause mortality, at initial diagnosis of infection.MethodUnivariate, multivariate and decision tree procedures were used to deduce a prediction rule from over 186 variables; retrospectively collated from clinical data for 213 patients. The resulting prediction rule was validated on independent data from a cohort of 158 patients described by Bhangu et al. (Colorectal Disease, 12(3):241-246, 2010).ResultsSerum albumin levels (g/L) (P = 0.001), respiratory rate (resps /min) (P = 0.002), C-reactive protein (mg/L) (P = 0.034) and white cell count (mcL) (P = 0.049) were predictors of all-cause mortality. Threshold levels of serum albumin ≤ 24.5 g/L, C- reactive protein >228 mg/L, respiratory rate >17 resps/min and white cell count >12 × 103 mcL were associated with an increased risk of all-cause mortality. A simple four variable prediction rule was devised based on these threshold levels and when tested on the initial data, yield an area under the curve score of 0.754 (P < 0.001) using receiver operating characteristics. The prediction rule was then evaluated using independent data, and yield an area under the curve score of 0.653 (P = 0.001).ConclusionsFour easily measurable clinical variables can be used to assess the risk of mortality of patients with Clostridium difficile infection and remains robust with respect to independent data.

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