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Infants asymptomatically excrete Clostridioides difficile during their first year of life, suggesting that they may represent a source of infection for adults who acquire community-associated C. difficile infection (CA-CDI). The genetic relationship of C. difficile strains from asymptomatic infants and adults with CA-CDI is not well defined.
In this study, 50 infants were recruited at birth, and stool samples were collected at routine well-child visits. Adult stool samples collected during the same period and geographical area from patients who were diagnosed with CA-CDI were selected for comparison. C. difficile was cultivated and probed by PCR for toxin genes and were typed by PCR fluorescent ribotyping. Isolates from adults and infants with shared ribotypes were subjected to whole-genome sequencing (WGS).
Of these 50 infants, 36 were positive for C. difficile at least once in their first year of life, with a peak incidence at 6 months. Among 180 infant stool samples, 48 were positive. Of 48 isolates from positive stools, 29 were toxigenic by polymerase chain reaction (PCR) and 8 of 48 stool samples were positive for toxin by enzyme immunoassays (EIAs). Ribotypes F106 and F014-020 were present in both colonized infants and adults with CA-CDI. WGS identified 1 adult–infant pair that differed by 5 single-nucleotide polymorphisms (SNPs). Also, 4 additional adult–infant clusters differed by ≤16 SNPs.
Infants that are colonized with C. difficile share ribotypes with adults from the same geographical region with CA-CDI. Selected isolates in the 2 populations show a genetic relationship by WGS.
Cleaning mutualisms are important interactions on coral reefs. Intraspecific variation in cleaning rate and behaviour occurs geographically and is often attributed to local processes. However, our understanding of fine-scale variation is limited, but would allow us to control for geography and region-specific behavioural patterns. Here, we compare the cleaning activity of Pederson's cleaner shrimp (Ancylomenes pedersoni) on two neighbouring, yet ecologically dissimilar, reef systems in Honduras: Banco Capiro, an offshore bank close to significant land runoff with high coral cover but a depleted fish population, and an oligotrophic fringing reef around the island of Utila, with lower coral cover but high fish abundance and diversity. The proportion of realized to potential fish clientele was <60% at both sites, and the composition of clientele was neither reflective of the demographics of the resident assemblages at each site nor similar between sites. Parrotfishes represented 13–15% of total fish abundance at both sites yet accounted for >50% (Banco Capiro) and 10% (Utila) of all cleans. Conversely, the schoolmaster snapper (Lutjanus apodus) represented ~1% of total fish abundance at both sites yet accounted for 40% (Utila) and 1% (Banco Capiro) of all cleans. After standardizing our cleaning rate data by clientele abundance, we find that clientele at Banco Capiro engage in over four times as many cleaning encounters per hour with A. pedersoni than at Utila. Our study highlights the variable nature of coral reef cleaning interactions and the need to better understand the ecological and environmental drivers of this biogeographic variation.
This article presents the first meta-analysis documenting the extent of publication selection biases in stated preference estimates of the value of a statistical life (VSL). Stated preference studies fail to overcome the publication biases that affect much of the VSL literature. Such biases account for approximately 90% of the mean value of published VSL estimates in this subset of the literature. The bias is greatest for the largest estimates, possibly because the high-income labor market and stated preference estimates from the USA serve as an anchor for the VSL in other higher income countries. Estimates from lower-income countries exhibit less bias but remain unreliable for benefit-cost analysis. Unlike labor market estimates of the VSL, there is no evidence that any subsample of VSL estimates is free of significant publication selection biases. Although stated preference studies often provide the most readily accessible country-specific VSL estimates, a preferable approach to monetizing mortality risk benefits is to draw on income-adjusted estimates from labor market studies in the USA that use Census of Fatal Occupational Injuries risk data. These estimates lack publication selection effects as well as the limitations that are endemic to stated preference methods.
Copper is one of the six transition metals that have important biochemical roles in humans, particularly in catalysis and electron transport [1, 2]. Because it can exist in two redox states (Cu2+/Cu+), it can participate in redox reactions involving transfer of an electron, but if it builds up it can also generate potentially toxic reactive oxygen species by Fenton chemistry. Examples of copper in redox enzymes include: complex IV of the mitochondrial respiratory chain, copper–zinc superoxide dismutase, ceruloplasmin (ferroxidase), lysyl oxidase, dopamine beta-hydroxylase, and tyrosinase.
Lengthy debates over the process of secularization in the West have concluded. In many ways, secularization theorists appear to have “won” the debate: traditional measures of religious vitality reveal a decline in religion. Yet, recent events, especially those involving politics and national identity, have encouraged scholars and members of the public to reconsider the ways in which something like religion might endure and influence public life in secularized Western nations. This paper uses the “exceptional-typical” case of Iceland—a modern, Western, secularized country of comparatively small population size—to observe and conceptualize a variety of processes which are here collectively named “post-secularization.” Its findings suggest that processes which may appear as unrelated or opposing forces—the emergence of new religious movements, the transformation of traditional religious symbols into profane branding, far right nationalist movements—may be part of a single, post-secularization process. Secularization, having fissured the sacred, leaves religion a pliable cultural tool.
Prehospital intramuscular (IM) ketamine is increasingly used for chemical restraint of agitated patients. However, few studies have assessed emergency department (ED) follow-up of patients receiving prehospital ketamine for this indication, with previous reports suggesting a high rate of post-administration intubation. This study examines the rate of and reasons for intubation and other airway interventions in agitated patients who received ketamine by Emergency Medical Services (EMS).
This retrospective cohort study included patients who received prehospital ketamine for agitation and were transported to two community hospital EDs. Charts were reviewed for demographics, ketamine dose, and airway intervention by EMS or in the ED. Characteristics of patients who were intubated versus those who did not receive airway intervention were analyzed.
Over 28 months, 86 patients received ketamine for agitation. Fourteen (16.3%) underwent endotracheal intubation. Patients with a higher temperature and a lower Glasgow Coma Score (GCS) were more likely to require intubation. There was no age or dose-dependent association on intubation rate. Intubated patients averaged 39 years old versus 44 for patients not intubated (negative five-year difference; 95% CI, -16 to 6). The mean ketamine dose was 339.3mg in patients intubated versus 350.7mg in patients not (-11.4mg difference; 95% CI, -72.4 to 49.6). The mean weight-based ketamine dose was 4.44mg/kg in patients intubated versus 4.96mg/kg in patients not (-0.53mg/kg difference; 95% CI, -1.49 to 0.43).
The observed rate of intubation in patients receiving prehospital ketamine for agitation was 16.3%. Study data did not reveal an age or dose-dependent rate of intubation. Further research should be conducted to compare the airway intervention rate of agitated patients receiving ketamine versus other sedatives in a controlled fashion.
Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.
The objective of this study was to evaluate the effectiveness of a 911 trauma re-triage protocol implemented at a new community hospital in a region with a high volume of trauma and frequent transports by private vehicle.
This retrospective cohort study included all trauma patients ≥15 years old transferred via 911 trauma re-triage from a new community hospital over a 10-month period from August 2015 through April 2016. Criteria for 911 trauma re-triage were developed with input from local Emergency Medical Services (EMS) and trauma experts. An educational module, along with the criteria and implementation steps, was distributed to the emergency department (ED) personnel at the community hospital. Data were abstracted from the regional trauma registry, and the EMS patient care records were reviewed. Primary outcomes were: (1) median total transport time; and (2) proportion of patients who met the 911 re-triage criteria.
During the study period, 32 patients with traumatic injuries were transferred via 911 re-triage to the closest trauma center (TC). The median age of patients was 31 years (IQR 24-45 years) with 78% male and 66% suffering from a penetrating mechanism. The median prehospital provider scene time was 10 minutes (IQR 8-12 minutes) and transport time was seven minutes (IQR 6-9 minutes). Median total transport time was 17 minutes (IQR 15-20 minutes). Seventeen patients (53%) met 911 re-triage criteria as determined by study investigators. The most common criteria met was “penetrating injury to the head, neck, or torso” in 14 cases.
This study demonstrated that 911 re-triage was a feasible strategy to expeditiously transfer critical trauma patients to a TC within a mature trauma system in an urban-suburban setting with a median total transport time of 17 minutes.
Trypanosomes strongly rely on post-transcriptional mechanisms to control gene expression. Several Opisthokont Pumilio domain proteins are known to suppress expression when bound to mRNAs. The Trypanosoma brucei Pumilio domain protein PUF3 is a cytosolic mRNA-binding protein that suppresses expression when tethered to a reporter mRNA. RNA-binding studies showed that PUF3 preferentially binds to mRNAs with a classical Pumilio-domain recognition motif, UGUA[U/C]AUU. RNA-interference-mediated reduction of PUF3 in bloodstream forms caused a minor growth defect, but the transcriptome was not affected. Depletion of PUF3 also slightly delayed differentiation to the procyclic form. However, both PUF3 genes could be deleted in cultured bloodstream- and procyclic-form trypanosomes. Procyclic forms without PUF3 also grew somewhat slower than wild-type, but ectopic expression of C-terminally tagged PUF3 impaired their viability. PUF3 was not required for RBP10-induced differentiation of procyclic forms to bloodstream forms. Mass spectrometry revealed no PUF3 binding partners that might explain its suppressive activity. We conclude that PUF3 may have a role in fine-tuning gene expression. Since PUF3 is conserved in all Kinetoplastids, including those that do not infect vertebrates, we suggest that it might confer advantages within the invertebrate host.
Introduction: Atrial Fibrillation (AF) is the most common arrhythmia seen in patients presenting to the emergency department (ED). AF increases the risk of ischemic stroke which can be mitigated by anticoagulant prescription. National guidelines advise that emergency physicians initiate anticoagulation when AF is first diagnosed. We aimed to evaluate the 90-day incidence of stroke and major bleeding among emergency patients discharged home with a new diagnosis of AF. Methods: This was a health records review of patients diagnosed with AF in two EDs. We included patients ≥ age 18, with a new diagnosis of AF who were discharged from the ED, between 1st May 2014 and 1st May 2017. Using a structure review we collected data on CHADS65 and CHADS2 scores, contraindications to direct oral anticoagulant (DOAC) prescription and initiation of anticoagulation in the ED. Patient charts were reviewed for the diagnosis of stroke, transient ischemic attack (TIA), ischemic gut, ischemic limb or other systemic embolism within 90 days of the index ED presentation. We extracted data on major bleeding events within 90 days, defined by the International Society of Thrombosis and Haemostasis criteria. All data were extracted in duplicate for validation. Results: We identified 399 patients fulfilling the inclusion criteria, median age 68 (IQR 57-79), 213 (53%) male. 11 patients were already prescribed an anticoagulant for another indication and 19 had a contraindication to prescription of a DOAC. 48/299 (16%) CHADS65 positive patients were initiated on an anticoagulant, 3 of whom had a contra-indication to initiation of anticoagulation in the ED (1 dual antiplatelet therapy, 2 liver cirrhosis). 1/100 CHADS65 negative patients was initiated on anticoagulation. The median CHADS2 score was 1 (IQR 0-2). Among the 49 patients initiated on anticoagulation, 3 patients had a stroke/TIA within 90 days, 6.1% (95% CI; 2.1-16.5%). There were no bleeding events 0.0% (95% CI; 0.0-7.3%). Among the 350 patients who were not initiated on anticoagulation in the ED, 4 patients had a stroke/TIA 1.1% (95% CI; 1.1-2.9%) within 90 days and 2 patients had a major bleeding event. Conclusion: Prescription of anticoagulation for new diagnoses of AF was under-utilized in these EDs. The 90-day stroke/TIA rate was high, even among those given an anticoagulant prescription in the ED. No patient had an anticoagulant-associated bleeding event.
Introduction: Participant interviews are often considered the ‘gold standard’ for measuring outcomes in diagnostic and prognostic studies. Participant exposure data are frequently collected during study interviews, but the reliability of this information often remains unknown. The objective of this study was to compare patient-reported medication exposures and outcomes to data extracted from electronic medical records (EMRs) to determine reliability. Methods: This was a secondary data analysis from a prospective observational cohort study enrolling older (≥ 65 years) patients who presented to one of three emergency departments after a fall. After patients had consented to participate in the study, they were asked about their use of antiplatelet and anticoagulation medications (exposures of interest). During follow up, participants were asked if a physician had told them they had bleeding in their head (diagnosis of intracranial hemorrhage). Patient-reported responses were compared to data extracted from a structured EMR review. Trained research assistants extracted medication exposure and outcome data from the hospital EMRs in duplicate for all visits to any hospital within 42 days. Inter-rater agreement was estimated using Cohen's kappa (K) statistics with 95% confidence intervals (CIs). Results: 1275 patients completed study interviews. 1163 (91%) responded to questioning about antiplatelet use and 1159 (91%) to anticoagulant use. Exact agreement between patient reported antiplatelet use compared to EMR review was 77%, with K = 0.50 (95% CI: 0.44 to 0.55). For anticoagulation use, exact agreement was 87%, with K = 0.68 (95% CI: 0.63 to 0.72). 986 (78%) patients had a follow up interview after 42 days. Exact agreement between patient reported intracranial bleeding and EMR review was 95%, with K = 0.30 (95% CI: 0.15 to 0.45). Using the EMR review as the reference standard, the sensitivity and specificity of patient reported intracranial bleeding was 34% (95% CI: 20 to 52%) and 97% (95% CI: 96 to 98%), respectively. Conclusion: In this population of older adults who presented to the ED after a fall, patient reported use of antiplatelet and anticoagulant medications was not a reliable method to identify medication use. Patients who were diagnosed with intracranial bleeding were particularly poor at reporting this diagnosis.
Background: Atrial fibrillation (AF) is a risk for stroke. The Canadian Cardiovascular Society advises patients who are CHADS65 positive should be started on oral anticoagulation (OAC). Our local emergency department (ED) review showed that only 16% of CHADS65 positive patients were started on OAC and that 2% of our patients were diagnosed with stroke within 90 days. We implemented a new pathway for initiation of OAC in the ED (the SAFE pathway). Aim Statement: We report the effectiveness and safety of the SAFE pathway for initiation of OAC in patients treated for AF in the ED. Measures & Design: A multidisciplinary group of physicians and pharmacist developed the SAFE pathway for patients who are discharged home from the ED with a diagnosis of AF. Step 1: contraindications to OAC, Step 2: CHADS65 score, Step 3: OAC dosing if indicated. The pathway triggers referral to AF clinic, family physician letter and follow up call from the ED pharmacist. Patients are followed for 90 days by a structured medical record review and a structured telephone interview. We record persistence with OAC, stroke, TIA, systemic arterial embolism and major bleeding (ISTH criteria). Patient outcomes are fed back to the treating ED physician. Evaluation/ Results: The SAFE pathway was introduced in two EDs in June 2018. In total, 177 patients have had the pathway applied. The median age was 70 (interquartile range (IQR) 61-78), 48% male, median CHADS2 score 2 (IQR 0-2). 19/177 patients (11%) had a contraindication to initiating OAC. 122 patients (69%) had no contraindication to OAC and were CHADS65 positive. Of these 122 patients, 109 were given a prescription for OAC (96 the correct dose, 9 too high a dose and 4 too low a dose). 6 patients declined OAC and the physician did not want to start OAC for 7 patients. 73/122 were contacted by phone at 90 days, 15 could not be reached and 34 have not completed 90 days of follow up since their ED visit. Of the 73 who were reached by phone after 90 days, 65 were still taking an anticoagulant. To date, 1 patient who declined OAC (CHADS2 score of 2) had a stroke within 90 days and one patient prescribed OAC had a gastrointestinal bleed. Discussion/Impact: The SAFE pathway appears safe and effective although we continue to evaluate and improve the process.
This presentation addresses impacts of adjunctive aripiprazole (AA) in major depressive disorder (MDD).
Assess impacts of long-term (≤52 weeks) open-label AA to ADT on efficacy, sexual function and weight change in MDD.
Data were analyzed post-hoc from de novo patients enrolled in an open-label safety study of AA after inadequate response to one or more ADT. Three ADT classes were included: SSRIs, SNRIs, and a noradrenaline-dopamine reuptake inhibitor, bupropion.
Global well-being with AA was assessed (mean change in CGI-S score from baseline by ADT). Sexual functioning was assessed by Sexual Function Inventory (SFI) items: interest in sex, sexual arousal, achievement of orgasm, erection maintenance and sexual satisfaction. Item 6 captured change in the overall improvement score. Weight change at Week 52 (last observation carried forward) was assessed.
Overall mean change in CGI-S (n = 285) by Week 52 was -1.5. Mean changes in CGI-S from baseline scores (4.2-4.4) were: escitalopram (n=64) -1.5, venlafaxine XL (n = 48) -1.4, sertraline (n = 39) -1.7, fluoxetine (n = 41) -1.3, paroxetine or CR (n = 37) -1.5 and bupropion XL or SR (n = 46) -1.4. Improvements on SFI items (n = 155) ranged from -0.2 (sexual satisfaction) to -0.6 (interest in sex and orgasm). Mean overall improvement score (3.8) indicated mild-to-moderate sexual dysfunction. All AA groups experienced a mean weight increase (range +1.8 kg [sertraline] to +3.3 kg [fluoxetine]).
AA moderately improved CGI-S scores (to a similar degree) when added to three different classes of ADTs. Sexual functioning in patients on ADT modestly improved after adding aripiprazole to ADT.
To characterize the safety and tolerability of desvenlafaxine succinate (DVS) in patients with major depressive disorder (MDD).
Pooled data from 7 double-blind, placebo-controlled studies were analyzed. Adult outpatients with DSM-IV MDD received DVS or placebo for 8 weeks. Four studies employed flexible dosing of DVS (100-200mg/d [1 study]; 200-400mg/d [3 studies]); 3 studies evaluated fixed doses (100/200/400mg/d [1 study]; 200/400mg/d [2 studies]). Vital signs and treatment-emergent adverse events (TEAEs) were evaluated. In the fixed-dose subset of studies, dose-related effects were analyzed.
The overall safety population consisted of 2014 patients (DVS: n=1211; placebo: n=803); 60% were women. Adverse events were responsible for discontinuations in 4% of placebo-treated patients and 15% of DVS-treated patients. Discontinuation rates increased with dose (10% with 100mg/d to 17% with 400mg/d) in the subset of fixed-dose studies. TEAEs were consistent with the serotonin-norepinephrine reuptake inhibitor (SNRI) class. Nausea was generally mild to moderate with a median duration less than or = to 6 days; the incidence decreased to placebo-like rates after week 1. With all doses of DVS, small but statistically significant changes in mean blood pressure were observed. Mean changes in pulse rate and the proportion of potentially clinically important increases in sustained elevations in supine diastolic blood pressure were higher for patients receiving 200/400mg/d than among placebo-treated subjects; values for these parameters with the 100mg/d dose did not differ from placebo.
DVS treatment exhibited a safety and tolerability profile that was generally consistent with the SNRI class.
This article provides practical guidance for researchers who wish to enroll and collect data from pediatric research participants through online and mobile platforms, with a focus on the involvement of both children and their parents in the decision to participate.