To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
We performed a return-on-investment analysis comparing the investment in surgical site infection (SSI) prevention programs in a hospital setting to the savings from averted SSI cases.
A retrospective case costing study using aggregated patient data to determine the incidence and costs of SSI infection in surgical departments over time. We calculated return on investment to the hospital and conducted several sensitivity and scenario analyses.
Data were compiled for the Ottawa Hospital (TOH), a Canadian tertiary-care teaching institution.
We used aggregated records for all hospital patients who underwent surgical procedures between April 2010 and January 2015.
We estimated the potential cost savings of the hospital’s surgical quality improvement program, namely the Surgeons National Surgical Quality Improvement Program (NSQIP) and the Comprehensive Unit-based Safety Program (CUSP).
From 2010 to 2016, TOH invested C$826,882 (US$624,384) in surgical quality improvement programs targeting SSI incidence and accrued C$1,885,110 (US$1,423,460) in cumulative savings from averted SSI cases, generating a return of $2.28 (US$3.02) per dollar invested (95% confidence interval [CI], −0.67 to 7.37). The study findings are sensitive to the estimated cost to the hospital per SSI case and the rate reduction attributable to the prevention program.
The NSQIP and CUSP have produced a positive return on investment at TOH; however, the result rests on several assumptions. This positive return on investment is expected to continue if the hospital can continue to reduce SSI incidence at least 0.25% annually without new investments. Findings from this study highlight the need for continuous program evaluation of the quality improvement initiatives.
Organic mercury, especially methylmercury, poisoning causes chronic neurological disease predominantly affecting the brain. There have been documented exposures from eating fish from contaminated waters in Japan and in northwestern Ontario and in Iraq from eating bread made from seed wheat treated with methylmercuric fungicide. The neurological disease is called Minamata disease in Japan. Visual field constriction due to involvement of the calcarine cortex, sensory disturbance due to involvement of the somatosensory cortex, and cerebellar ataxia due to involvement of granule cell neurons of the cerebellum are common and characteristic features due to methylmercury poisoning. Other neurological features include dysarthria, postural and action tremor, cognitive impairment, and hearing loss and dysequilibrium. In contrast, peripheral nerve disease is more characteristic of inorganic mercury intoxication. Similarly, psychosis is more typical of exposure to inorganic mercury, which has been documented in the felt hat industry (“mad hatter”). Laboratory tests (e.g., on blood and hair and toenail samples) are of limited value in the assessment of chronic neurological disease due to mercury poisoning because they may not reflect remote neuronal injury due to mercury. Methylmercury also causes injury to fetal brains during development. There is no effective treatment.
We aimed to improve the research consenting process by developing and evaluating simplified consent forms.
Four templates written at the eighth-tenth grade reading level were developed and trialed by a group of experts in clinical research, health literacy, national regulatory requirements, and end users. Researchers from protocols which had received expedited review were surveyed at 2 time points regarding their use and assessment of the templates.
At baseline 18/86 (20.9%) responding researchers had heard of the templates and 5 (5.8%) reported that they had used them; 2 years later, 54.2% (32/59) had heard of the templates and 87.5% (28/32) had used them (p<0.001).
Consent form templates may be one mechanism to improve patient comprehension of research protocols as well as efficiency of the review process, but require considerable time for development and implementation, and one key to their success is involvement and support from the IRB and technical staff.
Caribbean cheilostomes are a highly diverse component of the tropical American marine benthos with an excellent fossil record. Many workers have tended to lump taxa into morphologically variable, geographically widespread species originating in the Miocene, but recent morphometric and genetic analyses have revealed large suites of cryptic species, barely distinguishable morphologically, within several important genera. Most species in such suites have narrow geographic and stratigraphic ranges. In Stylopoma, for example, canonical discriminant and cluster analyses based on skeletal morphology yielded 19 late Neogene to Holocene species, most of which had been previously classified as S. spongites. Seven species were available for genetic analysis, of which six have been confirmed to differ by protein electrophoresis, either by fixed allele differences or significant genetic distances in sympatry. A combination of cladistic and stratophenetic analysis suggests that the most widely distributed and long-lasting species, which originated early in the Miocene, was ancestor to most or all of the other tropical American Stylopoma species. Despite extensive sampling, five species are narrowly distributed, with all known fossil and viving specimens separated by less than 1000 km, and all but three of the 18 descendant species have been restricted throughout their history to relatively limited parts of the tropical western Atlantic. These patterns are consistent with allopatric speciation of peripheral isolates, only a few of which have achieved wide distributions. Cladogenesis was highly episodic, reaching a peak in Late Miocene time, well before final closure of the Panamanian portal, but after formation of the sill that disrupted oceanic circulation patterns throughout the region.
Objectives: To assess the etiology of cerebrospinal fluid (CSF) pleocytosis in critical care patients with seizure(s) or status epilepticus (SE). Many previous studies, some performed decades ago, concluded that CSF pleocytosis may be entirely attributable to seizure activity. Methods: We undertook a retrospective chart review of adult patients with an admitting or acquired diagnosis of seizure(s) or SE in critical care units at the Winnipeg Health Sciences Centre between 2009 and 2012. Patients were identified through a critical care information database at a tertiary care center. We limited our study to patients who had lumbar punctures at our center within 5 days of seizure(s) or SE. Results: Of 426 patients with seizures in critical care units, 51 met the inclusion criteria. Seizure subtypes included focal seizures (5 or 10%), generalized seizures (14 or 27%), and SE (32 or 63%). Twelve (seven with SE) of the 51 (24%) were found to have CSF pleocytosis. A probable etiological cause for the CSF pleocytosis was identified in all 12 cases. Conclusions: We conclude that seizures do not directly induce a CSF pleocytosis. Instead, the CSF pleocytosis more likely reflects the underlying acute or chronic brain process responsible for the seizure(s). This was not readily apparent in early studies without magnetic resonance imaging (MRI) of the brain and currently available laboratory investigations. An etiological cause of CSF pleocytosis must always be sought when patients present with seizures and it should never be assumed that seizures are the cause.
Background: An increased incidence of hospital admissions coded as acute disseminated encephalomyelitis (ADEM) was noted in Winnipeg, Manitoba, Canada, during the second wave of the influenza pandemic from October 2009 to March 2010. However, it was not clear whether this was due to heightened awareness of potential neurological complications of influenza or influenza vaccination or an actual increase in the number of cases. Methods: We extracted data from the charts of 139 patients hospitalized with an International Classification of Diseases-10 discharge code indicating ADEM (G04.0) or unspecified noninfectious encephalitis or myelitis (G04.8, G04.9) between January 2006 and December 2012. Clinical and laboratory data were reviewed by a neurologist, and diagnoses were determined using the Brighton criteria. Results: Over the entire study period, there were 22 cases of ADEM. During the peak pandemic period (April-December 2009), seven patients were hospitalized with ADEM, corresponding to a rate of 7.8/million/year; 4.7 (95% confidence interval: 1.9-11.4) times higher than the rate before or after the pandemic period. Only one patient with ADEM had received the monovalent A(H1N1)pdm09 vaccine within 12 weeks of hospitalization. Conclusions: We have found an increased incidence of ADEM during the pandemic period that may be related, at least in part, to the increased incidence of influenza during that period. However, there was no temporal relationship with the administration of A(H1N1)pdm09 or seasonal influenza vaccines. Our study provides reassurance that use of these vaccines was not associated with increased risk of ADEM.
Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.
We compared phylogenies derived from morphological data for two cheilostome bryozoan genera, Stylopoma and Metrarabdotos, with genetic differences between species (Stylopoma) and the stratigraphic occurrence of fossils (both genera). Correspondence between species of Stylopoma defined by protein electrophoresis and on preservable skeletal morphology is excellent, despite great morphological variability within colonies and the predominance of quantitative over discrete characters. Moreover, agreement between genetic and morphological classifications increased greatly when morphological discrimination was pushed to the limit, despite inability to consistently assign all specimens to species with high confidence. This “splitting” strategy also maximized the correlation between genetic distances and the distances between species in cladistically derived phylogenies.
Fossil and living species of both genera are sufficiently abundant and widespread to provide credible limits for inferred ancestral relationships. Inclusion of fossils in cladistic analyses of Stylopoma increased the consistency of cladistic hypotheses by up to 30% and provided a more effective means of rooting trees than comparison with living species of the most closely related genus (“outgroup”). Moreover, in the case of Metrarabdotos, failure to incorporate stratigraphic information turned the cladogram virtually upside down, so that postulated ancestors first appear in the fossil record 6–16 m.y. after their putative descendants became extinct.
Stratigraphically rooted trees suggest that most well-sampled Metrarabdotos and Stylopoma species originated fully differentiated morphologically and persisted unchanged for > 1 to > 16 m.y., typically alongside their putative ancestors. Moreover, the tight correlation between phenetic, cladistic, and genetic distances among living Stylopoma species suggests that changes in all three variables occurred together during speciation. All of these observations support the punctuated equilibrium model of speciation.
During pregnancy, glycine and serine become more important because they are the primary suppliers of methyl groups for the synthesis of fetal DNA, and more glycine is required for fetal collagen synthesis as pregnancy progresses. In an earlier study, we reported that glycine flux decreased by 39 % from the first to the third trimester in pregnant adolescent girls. As serine is a primary precursor for glycine synthesis, the objective of this study was to measure and compare glycine and serine fluxes and inter-conversions in pregnant adolescent girls and adult women in the first and third trimesters. Measurements were made after an overnight fast by continuous intravenous infusions of 2H2-glycine and 15N-serine in eleven adolescent girls (17·4 (se 0·1) years of age) and in ten adult women (25·8 (se 0·5) years of age) for 4 h. Adolescent girls had significantly slower glycine flux and they made less glycine from serine in the third (P<0·05) than in the first trimester. Baby birth length was significantly shorter of adolescent girls (P=0·04) and was significantly associated with third trimester glycine flux. These findings suggest that the pregnant adolescent cannot maintain glycine flux in late pregnancy compared with early pregnancy because of decreased synthesis from serine. It is possible that the inability to maintain glycine synthesis makes her fetus vulnerable to impaired cartilage synthesis, and thus linear growth.
The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.
The fundamental role played by good nutrition in enabling personal, social and economic development is now widely recognised as presenting a fundamental global challenge that has to be addressed if major national and international problems are to be resolved in the coming decades. The recent focus provided by the Millennium Development Goals and the Scaling-Up-Nutrition (SUN) movement has been towards reducing the extent of nutrition-related malnutrition in high-burden countries. This has served to emphasise that there is a problem of inadequate professional capacity in nutrition that is sufficiently widespread to severely limit all attempts at the effective delivery and sustainability of nutrition-related and nutrition-enabling interventions that have impact at scale. Many high-burden countries are in sub-Saharan Africa where there is a high dependency on external technical support to address nutrition-related problems. We have sought to explore the nature and magnitude of the capacity needs with a particular focus on achieving levels of competency within standardised professional pre-service training which is fit-for-purpose to meet the objectives within the SUN movement in Africa. We review our experience of engaging with stakeholders through workshops, a gap analysis of the extent of the problem to be addressed, and a review of current efforts in Africa to move the agenda forward. We conclude that there are high aspirations but severely limited human resource and capacity for training that is fit-for-purpose at all skill levels in nutrition-related subjects in Africa. There are no structured or collaborative plans within professional groups to address the wide gap between what is currently available, the ongoing needs and the future expectations for meeting local technical and professional capability. Programmatic initiatives encouraged by agencies and other external players, will need to be matched by improved local capabilities to address the serious efforts required to meet the needs for sustained improvements related to SUN in high-burden countries. Importantly, there are pockets of effort which need to be encouraged within a context in which experience can be shared and mutual support provided.
During pregnancy, adult women with a normal BMI synthesise extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and compare the protein, glutamine and alanine kinetics of adult women and adolescent girls at early-, mid- and late-pregnancy. Kinetics were measured in the overnight fasted state using intravenous infusions of 13C-leucine, 15N-glutamine and 15N-alanine in ten adults and twenty adolescents aged 14–17 years in the first and second trimesters (phase 1 study) and infusions of 13C-leucine and 15N2-urea in ten adults and eleven adolescents aged 16–17 years in the first and third trimesters (phase 2 study). In phase 1 study, there were no significant differences between the groups with regard to any of the kinetic parameters measured. In both groups, leucine flux increased (P< 0·05), the percentage of leucine flux oxidised decreased (P< 0·05) and non-oxidative leucine disposal to protein synthesis increased (P< 0·05) from the first to the second trimester. In phase2 study, leucine flux was significantly slower (P< 0·05) in the adult group than in the adolescent group during both trimesters, and whole-body leucine flux and non-oxidative leucine disposal increased significantly in the adolescent group (P< 0·05, respectively) and were higher in the adult group from the first to the third trimester. These results suggest that similar to their adult counterparts after an overnight fast, adolescent girls with a normal BMI provide extra amino acids required for net protein deposition during pregnancy by increasing protein breakdown and decreasing amino acid oxidation.
Large impacts in the outer parts of a planetary system will produce debris discs that display a strong, distinctive, asymmetry, which will last for 105 year timescales. Debris resulting from a large impact may be able to explain the asymmetries in some known debris discs that have hitherto been difficult to understand.
The benefits of intravenous recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke is time dependent. Guidelines recommend a door-to-needle (DTN) time of less than 60 minutes.
A retrospective audit of 730 stroke charts from 2008 - 2011 was conducted at Health Sciences Centre. 158 patients treated with IV rt-PA were identified. The time intervals between Emergency Department (ED) arrival, administration of rt-PA and uninfused brain computed axial tomographic scan (CT) were recorded. From this, CT to needle times were calculated. During November 2010 to January 2011 feedback was given to neurologists, ED physicians, ED nurses, and CT technologists. This raised awareness and emphasized the importance of this time driven protocol.
The median DTN times for 2008, 2009, and 2010 were 69, 71 and 76 minutes respectively. The median CT-to-needle time for this time period was 47 minutes. In 2011 (n =58) the median DTN time was 49 minutes and the median CT-to-needle was 18 minutes, which were marked improvements (p<0.00005 and p<0.005, respectively). In 2008-2010 only 31% of treated patients (n=100) received rt-PA within 60 minutes, whereas in 2011 this increased to 64%.
Dramatic improvements in DTN times and in the percentage of patients receiving rt-PA treatment within 60 minutes were observed in 2011 after feedback was provided regarding the suboptimal performance. Prior to receiving feedback, DTN times were similar to national median DTN times. All centres administering rt-PA for acute ischemic stroke should monitor their clinical performance and give feedback on a regular basis.
Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE.
Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined.
Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%).
Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.
Worldwide, human rabies is prevalent where there is endemic dog rabies, but the disease may present unexpectedly in critical care units when suggestive clinical features have passed. In North America transmission from bats is most common and there is often no history of a bat bite or even contact with bats. Laboratory diagnostic evaluation for rabies includes serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Rare patients have survived rabies, and most received rabies vaccine prior to the onset of illness. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (dubbed the "Milwaukee Protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. There have been many subsequent failures of similar therapeutic approaches. There is no scientific rationale for the use of therapeutic coma in human rabies. New approaches to treating human rabies need to be developed.