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Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.
There is a requirement in some beef markets to slaughter bulls at under 16 months of age. This requires high levels of concentrate feeding. Increasing the slaughter age of bulls to 19 months facilitates the inclusion of a grazing period, thereby decreasing the cost of production. Recent data indicate few quality differences in longissimus thoracis (LT) muscle from conventionally reared 16-month bulls and 19-month-old bulls that had a grazing period prior to finishing on concentrates. The aim of the present study was to expand this observation to additional commercially important muscles/cuts. The production systems selected were concentrates offered ad libitum and slaughter at under 16 months of age (16-C) or at 19 months of age (19-CC) to examine the effect of age per se, and the cheaper alternative for 19-month bulls described above (19-GC). The results indicate that muscles from 19-CC were more red, had more intramuscular fat and higher cook loss than those from 16-C. No differences in muscle objective texture or sensory texture and acceptability were found between treatments. The expected differences in composition and quality between the muscles were generally consistent across the production systems examined. Therefore, for the type of animal and range of ages investigated, the effect of the production system on LT quality was generally representative of the effect on the other muscles analysed. In addition, the data do not support the under 16- month age restriction, based on meat acceptability, in commercial suckler bull production.
The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
To describe urinary tract infection (UTI) treatment among Veterans’ Affairs (VA) Community Living Centers (CLCs) nationally and to assess related trends in antibiotic use.
Setting and participants:
All UTI episodes treated from 2013 through 2017 among residents in 110 VA CLCs. UTI episodes required collection of a urine culture, antibiotic treatment, and a UTI diagnosis code. UTI episodes were stratified into culture-positive and culture-negative episodes.
Frequency and rate of antibiotic use were assessed for all UTI episodes overall and were stratified by culture-positive and culture-negative episodes. Joinpoint software was used for regression analyses of trends over time.
We identified 28,247 UTI episodes in 14,983 Veterans. The average age of Veterans was 75.7 years, and 95.9% were male. Approximately half of UTI episodes (45.7%) were culture positive and 25.7% were culture negative. Escherichia coli was recovered in 34.1% of culture-positive UTI episodes, followed by Proteus mirabilis and Klebsiella spp, which were recovered in 24.5% and 17.4% of culture-positive UTI episodes, respectively. The rate of total antibiotic use in days of therapy (DOT) per 1,000 bed days decreased by 10.1% per year (95% CI, −13.6% to −6.5%) and fluoroquinolone use (ciprofloxacin or levofloxacin) decreased by 14.5% per year (95% CI, −20.6% to −7.8%) among UTI episodes overall. Similar reductions in rates of total antibiotic use and fluoroquinolone use were observed among culture-positive UTI episodes and among culture-negative UTI episodes.
Over a 5-year period, antibiotic use for UTIs significantly decreased among VA CLCs, as did use of fluoroquinolones. Antibiotic stewardship efforts across VA CLCs should be applauded, and these efforts should continue.
We sought to retrospectively report our outcomes using post-operative stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) in place of whole-brain radiation therapy (WBRT) following resection of brain metastases from our hospital-based community practice.
Materials and Methods:
A retrospective review of 23 patients who underwent post-operative SRS at our single institution from 2013 to 2017 was undertaken. Patient records, treatment plans and diagnostic images were reviewed. Local failure, distant intracranial failure and overall survival were studied. Categorical variables were analyzed using Fisher’s exact tests. Continuous variables were analyzed using Mann–Whitney tests. The Kaplan–Meier method was used to estimate survival times.
16 (70%) were single-fraction SRS, whereas the remaining 7 patients received a five-fraction treatment course. The median single-fraction dose was 16 Gy (range, 16–18). The median total dose for fractionated treatments was 25 Gy (range, 25–35). Overall survival at 6 and 12 months was 95 and 67%, respectively. Comparison of SRS versus SRT local control rates at 6 and 12 months revealed control rates of 92 and 78% versus 29 and 14%, respectively. Every patient with dural/pial involvement at the time of surgery had distant intracranial failure at the 12-month follow-up.
Single-fraction frameless SRS proved to be an effective modality with excellent local control rates. However, the five-fraction SRT course was associated with an increased rate of local recurrence. Dural/pial involvement may portend a high risk for distant intracranial disease; therefore, it may be prudent to consider alternative approaches in these cases.
We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.
The ability to understand others’ mental states carries profound consequences for mental and physical health, making efforts at validly and reliably assessing mental state understanding (MSU) of utmost importance. However, the most widely used and current NIMH-recommended task for assessing MSU – the Reading the Mind in the Eyes Task (RMET) – suffers from potential assessment issues, including reliance on a participant's vocabulary/intelligence and the use of culturally biased stimuli. Here, we evaluate the impact of demographic and sociocultural factors (age, gender, education, ethnicity, race) on the RMET and other social and non-social cognitive tasks in an effort to determine the extent to which the RMET may be unduly influenced by participant characteristics.
In total, 40 248 international, native-/primarily English-speaking participants between the ages of 10 and 70 completed one of five measures on TestMyBrain.org: RMET, a shortened version of RMET, a multiracial emotion identification task, an emotion discrimination task, and a non-social/non-verbal processing speed task (digit symbol matching).
Contrary to other tasks, performance on the RMET increased across the lifespan. Education, race, and ethnicity explained more variance in RMET performance than the other tasks, and differences between levels of education, race, and ethnicity were more pronounced for the RMET than the other tasks such that more highly educated, non-Hispanic, and White/Caucasian individuals performed best.
These data suggest that the RMET may be unduly influenced by social class and culture, posing a serious challenge to assessing MSU in clinical populations given shared variance between social status and psychiatric illness.
This article describes a clinical protocol for supporting those presenting with post-traumatic stress disorder (PTSD) and dissociative symptoms, particularly dissociative flashbacks, based on a cross-culturally applicable model. The protocol is discussed from the perspective of working with a refugee and asylum seeker population, although many of the principles will be applicable to clients from any background presenting with these dissociative symptoms. The protocol addresses the assessment and formulation of a client’s dissociative symptoms. It includes guidance on sharing psycho-education with clients regarding the evolutionary function of dissociation and developing practical strategies to monitor and manage dissociative symptoms. The strengths and limitations of this protocol are also discussed.
Key learning aims
After reading this article people will:
(1) Be able to understand a cross-culturally applicable model of dissociation and how it applies to clinical practice when working with clients presenting with dissociative symptoms, particularly dissociative flashbacks, in the context of a diagnosis of PTSD.
(2) Be able to assess and formulate dissociative symptoms as part of an overall PTSD formulation.
(3) Be able to develop practical strategies for assisting clients in monitoring and managing their dissociative symptoms.
(4) Be familiar with adaptations for using this approach with refugee and asylum seeker populations.
Despite aspirations to be a world-class national curriculum, the Australian Curriculum (AC) has been criticised as ‘manifestly deficient’ (Australian Government Department of Education and Training, 2014 p. 5) as an inclusive curriculum, failing to meet the needs of all students with disabilities (SWD) and their teachers. There is a need for research into the daily attempts of educators to navigate the tension between a ‘top-down’ system-wide curriculum and a ‘bottom-up’ regard for individual student needs, with a view to informing both policy and practice. This article is the first of two research papers in which we report the findings from a national online Research in Special Education (RISE) Australian Curriculum Survey of special educators in special schools, classes, and units regarding their experience using the AC to plan for and teach SWD. Survey results indicated (a) inconsistent use of the AC as the primary basis for developing learning objectives and designing learning experiences, (b) infrequent use of the achievement standards to support assessment and reporting, and (c) considerable supplementation of the AC from other resources when educating SWD. Overall, participants expressed a lack of confidence in translating the AC framework into a meaningful curriculum for SWD. Implications for policy, practice, and future research are discussed.
To determine which healthcare worker (HCW) roles and patient care activities are associated with acquisition of vancomycin-resistant Enterococcus (VRE) on HCW gloves or gowns after patient care, as a surrogate for transmission to other patients.
Prospective cohort study.
Medical and surgical intensive care units at a tertiary-care academic institution.
VRE-colonized patients on Contact Precautions and their HCWs.
Overall, 94 VRE-colonized patients and 469 HCW–patient interactions were observed. Research staff recorded patient care activities and cultured HCW gloves and gowns for VRE before doffing and exiting patient room.
VRE were isolated from 71 of 469 HCWs’ gloves or gowns (15%) following patient care. Occupational/physical therapists, patient care technicians, nurses, and physicians were more likely than environmental services workers and other HCWs to have contaminated gloves or gowns. Compared to touching the environment alone, the odds ratio (OR) for VRE contamination associated with touching both the patient (or objects in the immediate vicinity of the patient) and environment was 2.78 (95% confidence interval [CI], 0.99–0.77) and the OR associated with touching only the patient (or objects in the immediate vicinity) was 3.65 (95% CI, 1.17–11.41). Independent risk factors for transmission of VRE to HCWs were touching the patient’s skin (OR, 2.18; 95% CI, 1.15–4.13) and transferring the patient into or out of bed (OR, 2.66; 95% CI, 1.15–6.43).
Patient contact is a major risk factor for HCW contamination and subsequent transmission. Interventions should prioritize contact precautions and hand hygiene for HCWs whose activities involve touching the patient.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15–24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18–24-month WLZ change (β −0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15–18-month WLZ change (β −0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β −0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15–18 and 18–24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.
To analyze whether electronically available comorbid conditions are risk factors for Centers for Disease Control and Prevention (CDC)-defined, hospital-onset Clostridium difficile infection (CDI) after controlling for antibiotic and gastric acid suppression therapy use.
Patients aged ≥18 years admitted to the University of Maryland Medical Center between November 7, 2015, and May 31, 2017.
Comorbid conditions were assessed using the Elixhauser comorbidity index. The Elixhauser comorbidity index and the comorbid condition components were calculated using the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes extracted from electronic medical records. Bivariate associations between CDI and potential covariates for multivariable regression, including antibiotic use, gastric acid suppression therapy use, as well as comorbid conditions, were estimated using log binomial multivariable regression.
After controlling for antibiotic use, age, proton-pump inhibitor use, and histamine-blocker use, the Elixhauser comorbidity index was a significant risk factor for predicting CDI. There was an increased risk of 1.26 (95% CI, 1.19–1.32) of having CDI for each additional Elixhauser point added to the total Elixhauser score.
An increase in Elixhauser score is associated with CDI. Our study and other studies have shown that comorbid conditions are important risk factors for CDI. Electronically available comorbid conditions and scores like the Elixhauser index should be considered for risk-adjustment of CDC CDI rates.
We assessed various locations and frequency of environmental sampling to maximize information and maintain efficiency when sampling for Acinetobacter baumannii. Although sampling sites in closer proximity to the patient were more likely positive, to fully capture environmental contamination, we found value in sampling all sites and across multiple days.