The Effect of Oral Antibiotics on the Development of Community Acquired Clostridium Difficile Colitis in Medicare Beneficiaries

Clostridium difficile infection (CDI) is increasingly prevalent among community dwelling Americans. Older Americans are particularly vulnerable to community-acquired Clostridium difficile (CACD), in part to increasing use of antibiotics. We studied the association between outpatient antibiotics and CACD among Medicare beneficiaries. Case-control study utilizing a 5% sample of Medicare beneficiaries (2009-2011). Patients with CACD severe enough to warrant hospitalization were identified by a primary diagnosis code for CDI and no exposure to a healthcare environment within 90-days of admission. 1,514 CACD cases were matched to ten controls each on birth year and sex. Potential controls with exposure to healthcare environment were excluded. Outpatient oral antibiotic exposure was classified into three groups: ≤30 days, 31-60 days, or 61-90 days prior to case subject’s index admission. Metronidazole and Vancomycin were excluded because they are used to treat CDI. Multivariable models were utilized to determine the independent effect of antibiotics on the development of CACD while controlling for several patient associated characteristics. Cases of CACD had more outpatient antibiotic exposure in each time period examined: ≤30 days = 40.0% vs 8.4%; 31-60 = 10.7% vs 5.0%; and 61-90 = 5.5% vs 4.4% (all p-values \u3c 0.05). Subjects exposed to antibiotics ≤30 days prior to admission had a markedly higher risk of being admitted with CACD compared with those not exposed (OR 8.09, 95% CI 7.13, 9.19). Similarly, subjects taking antibiotics 31-60 days and 61-90 days prior to admission had increased risk of CDI admission (OR 3.65, 95% CI 3.02, 4.41) and (OR 2.06, 95% CI 1.61, 2.63) respectively. Recent exposure to outpatient oral antibiotics increases the risk of CACD among community dwelling elderly with the risk persisting as long as 90 days after exposure. Inappropriate antibiotic usage must be minimized and older Americans who require outpatient antibiotic treatment may warrant close observation for signs of CDI

Identifying the fundamental structures and processes of care contributing to emergency general surgery quality using a mixed-methods Donabedian approach

BACKGROUND: Acute Care Surgery (ACS) was developed as a structured, team-based approach to providing round-the-clock emergency general surgery (EGS) care for adult patients needing treatment for diseases such as cholecystitis, gastrointestinal perforation, and necrotizing fasciitis. Lacking any prior evidence on optimizing outcomes for EGS patients, current implementation of ACS models has been idiosyncratic. We sought to use a Donabedian approach to elucidate potential EGS structures and processes that might be associated with improved outcomes as an initial step in designing the optimal model of ACS care for EGS patients. METHODS: We developed and implemented a national survey of hospital-level EGS structures and processes by surveying surgeons or chief medical officers regarding hospital-level structures and processes that directly or indirectly impacted EGS care delivery in 2015. These responses were then anonymously linked to 2015 data from the American Hospital Association (AHA) annual survey, Medicare Provider Analysis and Review claims (MedPAR), 17 State Inpatient Databases (SIDs) using AHA unique identifiers (AHAID). This allowed us to combine hospital-level data, as reported in our survey or to the AHA, to patient-level data in an effort to further examine the role of EGS structures and processes on EGS outcomes. We describe the multi-step, iterative process utilizing the Donabedian framework for quality measurement that serves as a foundation for later work in this project. RESULTS: Hospitals that responded to the survey were primarily non-governmental and located in urban settings. A plurality of respondent hospitals had fewer than 100 inpatient beds. A minority of the hospitals had medical school affiliations. DISCUSSION: Our results will enable us to develop a measure of preparedness for delivering EGS care in the US, provide guidance for regionalized care models for EGS care, tiering of ACS programs based on the robustness of their EGS structures and processes and the quality of their outcomes, and formulate triage guidelines based on patient risk factors and severity of EGS disease. CONCLUSIONS: Our work provides a template for team science applicable to research efforts combining primary data collection (i.e., that derived from our survey) with existing national data sources (i.e., SIDs and MedPAR)

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

An osteocalcin-deficient mouse strain without endocrine abnormalities

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc– ) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, μCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc− allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/ 2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution

Production of lactic acid esters catalyzed by heteropoly acid supported over ion-exchange resins

The heterogeneous liquid-phase esterification reaction of lactic acid with ethyl alcohol accompanied with lactoyllactic acid hydrolysis over heteropoly acid supported on ion exchange resin catalysts was investigated at 343 K with ethanol to lactic acid molar ratio of 1:1. The catalysts with 5-20% of tungstophosphoric (H(3)PW(12)O(40).xH(2)O) and molybdophosphoric (H(3)PMo(12)O(40).xH(2)O) acid type of heteropoly acids over Lewatit(R) S100 showed higher activities than the resin itself. DRIFTS and XRD analysis indicated the formation of amorphous heteropoly acid layer, which is strongly bonded to the resin surface with hydrate structure. Reaction experiments showed molybdophosphoric acid has slightly higher activity than the tungstophosphoric acid, which yields slower deactivation. The reaction model was established by considering the hydrolysis reaction of lactoyllactic acid under the reaction conditions and the esterification step. Reaction rate constants for homogeneous self catalyzed, ion exchange resin catalyzed, and kinetic contribution of heteropoly acid loading were calculated. Kinetic analysis of the reaction data revealed that the active proton sites do not increase proportionally with the amount of heteropoly acids over the resin surface and proton efficiency of the catalysts decreases with increasing loading. It was observed that molybdophosphoric acid loaded S100 catalysts have higher proton efficiency than the tungstophosphoric acid loaded counterpart

What explains corporate sukuk primary market spreads?

This study investigates the determining factors of international corporate sukuk pricing in the primary market for the period of 2004–2015. We present novel evidence for a unique data set covering all 63 international corporate sukuk issuances consisting of both a fixed margin rating as well a credit rating score. Our cross-sectional analysis indicates that both credit rating and maturity are significant factors which reduce issue spreads, whereas sukuk margin rating increases issue spreads. More prominently, Shari’ah scholar reputation and the type of sukuk are not statistically significant factors in the explanation of the issue spread. Our results are comparable with determinants of conventional bond pricing, and our findings further confirm existing sukuk market practices

The Effects of Regulation and Supervision on the Risk-Taking Behaviour of Islamic Banks

Purpose: This study examines the impact of the regulatory and supervisory environment on the risk-taking behaviour of Islamic banks. The impact of the heterogeneous nature of the banking environment in the sampled countries is also considered. Design/methodology/approach: A dynamic panel data analysis with system GMM estimators was used with a sample consisting of 120 Islamic banks from 21 countries for the period 2000-2013. Findings: The results demonstrate that main regulation and supervision proxies have significant negative effects on risk levels of Islamic banks, which implies that further restricted regulatory and supervisory environment can lower risk levels of Islamic banks. In addition, the Islamic banks operating under the dual banking system seem to prefer to take a lower risk. Furthermore, the results identify that a stable political environment encourages Islamic banks to take higher risks in their operations. Originality/value: In addition to examining the common factors, the empirical analysis in this study is extended to the investigation of the effects of several political indicators on risk-taking behaviour of Islamic banks, which should be considered as an important contribution

The impact of acute care surgery on appendicitis outcomes: Results from a national sample of university-affiliated hospitals

BACKGROUND: Acute appendicitis is the most common indication for emergency general surgery (EGS) in the United States. We examined the role of acute care surgery (ACS) on interventions and outcomes for acute appendicitis at a national sample of university-affiliated hospitals. METHODS: We surveyed senior surgeons responsible for EGS coverage at University HealthSystems Consortium hospitals, representing more than 90% of university-affiliated hospitals in the United States. The survey elicited data on resources allocated for EGS during 2013. Responses were linked to University HealthSystems Consortium outcomes data by unique hospital identifiers. Patients treated at hospitals reporting hybrid models for EGS coverage were excluded. Differences in interventions and outcomes between patients with acute appendicitis treated at ACS hospitals versus hospitals with a general surgeon on-call model (GSOC) were analyzed using univariate comparisons and multivariable logistic regression models adjusted for patient demographics, clinical acuity, and hospital characteristics. RESULTS: We found 122 hospitals meeting criteria for analysis where 2,565 patients were treated for acute appendicitis. Forty-eight percent of hospitals had an ACS model (n = 1,414), and 52% had a GSOC model (n = 1,151). Hospitals with ACS models were more likely to treat minority patients than those with GSOC models. Patients treated at ACS hospitals were more likely to undergo laparoscopic appendectomy. In multivariable modeling of patients who had surgery (n = 2,258), patients treated at ACS hospitals had 1.86 (95% confidence interval, 1.23-2.80) greater odds of undergoing laparoscopic appendectomy. CONCLUSION: In an era when laparoscopic appendectomy is increasingly accepted for treating uncomplicated acute appendicitis, particularly in low-risk patients, it is concerning that patients treated at GSOC model hospitals are more likely to undergo traditional open surgery at the time of presentation. Furthermore, hospitals with ACS are functioning as safety-net hospitals for vulnerable patients with acute appendicitis. LEVEL OF EVIDENCE: Therapeutic study, level IV