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Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs).
We analyzed 2016–2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders.
The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6–295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24–43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04–1.21; P = .002) after adjusting for confounders.
High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.
We investigated a large multistate outbreak that occurred in the United States in 2015–2016. Epidemiologic, laboratory, and traceback studies were conducted to determine the source of the infections. We identified 907 case-patients from 40 states with illness onset dates ranging from July 3, 2015 to March 2, 2016. Sixty-three percent of case-patients reported consuming cucumbers in the week before illness onset. Ten illness sub-clusters linked to events or purchase locations were identified. All sub-clusters investigated received cucumbers from a single distributor which were sourced from a single grower in Mexico. Seventy-five cucumber samples were collected, 19 of which yielded the outbreak strain. Whole genome sequencing performed on 154 clinical isolates and 19 cucumber samples indicated that the sequenced isolates were closely related genetically to one another. This was the largest US foodborne disease outbreak in the last ten years and the third largest in the past 20 years. This was at least the fifth multistate outbreak caused by contaminated cucumbers since 2010. The outbreak is noteworthy because a recall was issued only 17 days after the outbreak was identified, which allowed for the removal of the contaminated cucumbers still available in commerce, unlike previous cucumber associated outbreaks. The rapid identification and response of multiple public health agencies resulted in preventing this from becoming an even larger outbreak.
Open neural tube defects or myelomeningoceles are a common congenital condition caused by failure of closure of the neural tube early in gestation, leading to a number of neurologic sequelae including paralysis, hindbrain herniation, hydrocephalus and neurogenic bowel and bladder dysfunction. Traditionally, the condition was treated by closure of the defect postnatally but a recently completed randomized controlled trial of prenatal versus postnatal closure demonstrated improved neurologic outcomes in the prenatal closure group. Fetal surgery, or more precisely maternal-fetal surgery, raises a number of ethical issues that we address including who the patient is, informed consent, surgical innovation and equipoise as well maternal assumption of risk. As the procedure becomes more widely adopted into practice, we suggest close monitoring of new fetal surgery centers, in order to ensure that the positive results of the trial are maintained without increased risk to both the mother and fetus.
Replacing a portion of a glucose challenge with whole eggs (EGG) or egg whites (WHITE) was shown to protect against glucose-induced impairments in vascular function. We hypothesised in the present study that previously observed vasoprotection following co-ingestion of EGG or WHITE with glucose was attributed to limiting postprandial hyperglycaemia-induced oxidative stress that improves NO∙ bioavailability. Prediabetic men completed a randomised, cross-over study in which they ingested isoenergetic meals containing 100 g glucose (GLU), or 75 g glucose with 1·5 EGG, seven WHITE or two egg yolks (YOLK). At 30 min intervals for 3 h, we assessed plasma NO∙ metabolites, the lipid peroxidation biomarker malondialdehyde, antioxidants, arginine and its methylated metabolites (asymmetric dimethylarginine and symmetric dimethylarginine), tetrahydrobiopterin redox status, vasoconstrictors and inflammatory markers. Compared with GLU, malondialdehyde was lower and NO∙ metabolites were greater in EGG and WHITE, but YOLK was not different from GLU. Malondialdehyde was inversely correlated with NO∙ metabolites and vascular function, whereas NO∙ metabolites were positively correlated with vascular function. Compared with GLU, arginine was greater, but asymmetric and symmetric dimethylarginine and angiotensin-II were lower in all egg-based meals. Antioxidants, tetrahydrobiopterin redox status and inflammatory markers did not differ among treatments. Thus, while each egg-based meal improved arginine metabolism, only EGG and WHITE limited lipid peroxidation. This suggests that vasoprotection mediated by EGG and WHITE likely occurs in an NO∙-dependent manner by improving arginine metabolism and attenuating oxidative stress that otherwise limit NO∙ biosynthesis and bioavailability to the vascular endothelium.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
This research aims to explore the submerged landscapes of the Pilbara of western Australia, using predictive archaeological modelling, airborne LiDAR, marine acoustics, coring and diver survey. It includes excavation and geophysical investigation of a submerged shell midden in Denmark to establish guidelines for the underwater discovery of such sites elsewhere.
Background: Industry funding of neurosurgery research is on the rise and this creates a conflict of interest (COI) with the potential to bias results. The reporting and handling of COI is impacted by the variation in policies and definitions between journals. In this study we sought to evaluate the prevalence and comprehensiveness of COI policies amongst leading neurosurgical journals. Methods: We conducted a cross-sectional study of publicly available online disclosure policies in the 20 highest-ranking neurosurgical journals, as determined by Google Scholar Metrics, in July of 2016. Results: Eighteen (89.5%) of the top neurosurgical journals included COI policy statements. Ten journals requested declaration of non-financial conflicts, while two journals defined a time period of interest for conflicts. Sixteen journals required declaration from the corresponding author, 13 from all authors, six from reviewers and five from editors. Five journals included COI declaration verification, management or enforcement. Journals with more comprehensive COI policies were significantly more likely to have higher h5-indices (p=0.003) and higher impact factors (p=0.01). Conclusions: In 2016, the majority of high-impact neurosurgical journals had publicly available COI disclosure policies. Policies varied substantially across neurosurgical journals; but COI comprehensiveness was associated with impact factor and h5-index. More comprehensive and consistent COI policies will facilitate increased transparency in neurosurgery research.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.
The study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.
Introduction: Health advocacy training is an important part of emergency medicine practice and education. There is little agreement, however, about how advocacy should be taught and evaluated in the postgraduate context, and there is no consolidated evidence-base to guide the design and implementation of post-graduate health advocacy curricula. This literature review aims to identify existing models used for teaching and evaluating advocacy training, and to integrate these findings with current best-practices in medical education to develop practical, generalizable recommendations for those involved in the design of postgraduate advocacy training programs. Methods: Ovid MEDLINE and PubMed searches combined both MeSH and non-MeSH variations on advocacy and internship and residency. Forward snowballing that incorporated grey literature searches from accreditation agencies, residency websites and reports were included. Articles were excluded if unrelated to advocacy and postgraduate medical education. Results: 507 articles were identified in the search. A total of 108 peer reviewed articles and 38 grey literature resources were included in the final analysis. Results show that many regulatory bodies and residency programs integrate advocacy training into their mission statements and curricula, but they are not prescriptive about training methods or assessment strategies. Barriers to advocacy training were identified, most notably confusion about the definition of the advocate role and a lower value placed on advocacy by trainees and educators. Common training methods included didactic modules, standardized patient encounters, and clinical exposure to vulnerable populations. Longitudinal exposure was less common but appeared the most promising, often linked to scholarly or policy objectives. Conclusion: This review indicates that postgraduate medical education advocacy curricula are largely designed in an ad-hoc fashion with little consistency across programs even within a given discipline. Longitudinal curriculum design appears to engage residents and allows for achievement of stated outcomes. Residency program directors from emergency medicine and other specialties may benefit from promising models in pediatrics, and a shared portal with access to advocacy curricula and the opportunity to exchange ideas related to curriculum design and implementation.
The Troodos ophiolite Cyprus hosts the type locality for Cyprus-type, mafic volcanogenic massive sulfide (VMS) deposits. Regional soil geochemical data for Troodos are highly variable with the Solea graben, one of three regional graben structures on Cyprus, showing enrichment in Te and Se. Of the three VMS sampled within the Solea graben, Apliki exhibits the most significant enrichment in Se. Samples from the South Apliki Breccia Zone; a zone of hematite-rich breccia containing euhedral pyrite and chalcopyrite, contain up to 4953 and 3956 ppm Se in pyrite and chalcopyrite, respectively. Four paragenetic stages are identified at Apliki and different generations of pyrite are distinguishable using trace-element chemistry analysed via laser ablation inductively coupled plasma mass spectrometry. Results indicate stage I pyrite formed under reduced conditions at high temperatures >280°C and contains 182 ppm (n = 22 σ = 253) Se. Late stage III pyrite which is euhedral and overprints chalcopyrite and hematite is enriched in Se (averaging 1862 ppm; n = 23 σ = 1394). Sulfide dissolution and hematite formation displaced large amounts of Se as hematite cannot accommodate high concentrations of Se in its crystal structure. The mechanisms proposed to explain the pronounced change in redox are twofold. Fault movement leading to localized seawater ingress coupled with a decreasing magmatic flux that generated locally oxidizing conditions and promoted sulfide dissolution. A Se/S ratio of 9280 indicates a probable magmatic component for late stage III pyrite, which is suggested as a mechanism explaining the transition from oxidizing back to reduced conditions. This study highlights the significance of changes in redox which promote sulfide dissolution, mobilization and enrichment of Se.
Vaccination programmes are considered a main contributor to the decline of infectious diseases over the 20th century. In recent years, the national vaccination coverage in the Netherlands has been declining, highlighting the need for continuous monitoring and evaluation of vaccination programmes. Our aim was to quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919–2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 82.4% (95% credible interval (CI): 74.9–87.6) of notified cases of diphtheria averted, 92.9% (95% CI 85.0–97.2) cases of poliomyelitis, and 79.1% (95% CI 67.1–87.4) cases of mumps. Vaccination of 11-year-old girls against rubella averted 49.9% (95% CI 9.3–73.5) of cases, while universal vaccination averted 68.1% (95% CI 19.4–87.3) of cases. These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.
Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs vascular endothelial function (VEF). We hypothesised that co-ingestion of a glucose challenge with egg-based meals would protect against glucose-induced impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross-over study was conducted in prediabetic men (n 20) who ingested isoenegertic meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with 1·5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2-isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were assessed. In GLU, FMD decreased at 30–60 min and returned to baseline levels by 90 min. GLU-mediated decreases in FMD were attenuated at 30–60 min in EGG and WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to baseline, glucose increased at 30–120 min in GLU and YOLK but only at 30–90 min in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK. Postprandial lipids and methylglyoxal did not differ between treatments. Thus, replacing a portion of a glucose challenge with whole eggs or egg whites, but not yolks, limits postprandial impairments in VEF by attenuating increases in glycaemia and lipid peroxidation.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis.
Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3–6 months post-treatment.
Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3–6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition.
CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.