Childhood cerebellar tumours mirror conserved fetal transcriptional programs.

Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin+ stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.

Prediction of acute myeloid leukaemia risk in healthy individuals.

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

Intrauterine adhesion in ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA): a randomised controlled trial.

BACKGROUND: Intrauterine adhesion (IUA) can arise as a potential complication following uterine surgery, as the surgical procedure may damage the endometrial stratum basalis. The objective of this study was to assess and compare the occurrence of IUA in women who underwent ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA) for managing first-trimester miscarriage. METHODS: This was a prospective, single-centre, randomised controlled trial conducted at a university-affiliated tertiary hospital. Chinese women aged 18 years and above who had a delayed or incomplete miscarriage of ≤ 12 weeks of gestation were recruited in the Department of Obstetrics and Gynaecology at the Prince of Wales. Recruited participants received either USG-MVA or EVA for the management of their miscarriage and were invited for a hysteroscopic assessment to evaluate the incidence of IUA between 6 and 20 weeks after the surgery. Patients were contacted by phone at 6 months to assess their menstrual and reproductive outcomes. RESULTS: 303 patients underwent USG-MVA or EVA, of whom 152 were randomised to 'USG-MVA' and 151 patients to the 'EVA' group. Out of the USG-MVA group, 126 patients returned and completed the hysteroscopic assessment, while in the EVA group, 125 patients did the same. The incidence of intrauterine adhesion (IUA) was 19.0% (24/126) in the USG-MVA group and 32.0% (40/125) in the EVA group, showing a significant difference (p < 0.02) between the two groups. No significant difference in the menstrual outcomes at 6 months postoperatively between the two groups but more patients had miscarriages in the EVA group with IUA. CONCLUSIONS: IUAs are a possible complication of USG-MVA. However, USG-MVA is associated with a lower incidence of IUA postoperatively at 6-20 weeks. USG-MVA is a feasible, effective, and safe alternative surgical treatment with less IUA for the management of first-trimester miscarriage. TRIAL REGISTRATION: The study was registered with the Centre for Clinical Research and Biostatics- Clinical Trials Registry (CCRBCTR), which is a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) (Unique Trial Number: ChiCTR1900023198 with the first trial registration date on 16/05/2019).

Incidence of intrauterine adhesion after ultrasound-guided manual vacuum aspiration (USG-MVA) for first-trimester miscarriages: a prospective cohort study.

PURPOSE: Ultrasound-guided manual vacuum aspiration (USG-MVA) is a feasible and effective outpatient treatment to treat early pregnancy loss. METHODS: This was a prospective observational study at a university-affiliated hospital. All women undergoing either a USG-MVA or electric vacuum aspiration (EVA) were invited to return 3-6 months later for follow-up at which women completed a questionnaire to document their post-evacuation menstrual and reproductive history, and underwent a hysteroscopy if they were not pregnant. The severity of intrauterine adhesion (IUA), if present, was graded (Stage I-III) according to the American fertility society classification. RESULTS: A total of 292 women had a hysteroscopy after their initial surgical evacuation, USG-MVA 169(57.9%) versus EVA 123(42.1%). Women undergoing EVA as opposed to a USG-MVA had a 12.9% higher incidence of IUA (24.1% vs. 37.0%, p = 0.042) equivalent to 1.84 times higher risk (95% CI 1.01-3.34; p = 0.048). Women having EVA continued to show an increased but not statistically significant trend towards an increased risk of IUA after adjusting for the type of miscarriage (aOR = 1.3; 95% CI 0.66-2.50; p = 0.46). CONCLUSION: There were no significant differences in their reproductive outcomes and fewer women post-USG-MVA complained of hypomenorrhea. IUA may still occur in women undergoing USG-MVA but it is lower than the rate in women undergoing EVA. Clinical trials registry The trial was registered with the Centre for Clinical Research and Biostatistics - Clinical Trials Registry (CCRBCTR), a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) with a Unique Trial Number: CUHK_CCRB00541 on 22 Dec 2016.

Seeking a Relevant Description of Major Trauma Bleeding: Comparison of Four Major Bleeding Definitions.

BACKGROUND: The traditional definition of massive transfusion is 10 red blood cell units transfused within 24 hr. This definition has been faulted for excluding patients who die early from exsanguination. Alternative major bleeding definitions in the trauma literature include time-based (e.g., Resuscitation Intensity) and event based (e.g., Sharpe) transfusion thresholds. OBJECTIVE: The study objective was to compare four definitions of major bleeding, including a modification to the Sharpe definition, on clinically relevant processes and outcomes. METHODS: This is a retrospective cohort study of adult trauma patients admitted from the field to a Level I trauma center from 2014 to 2019. Data sources were the trauma registry, blood bank, and electronic medical records. Transfusion thresholds were defined as follows: Resuscitation Intensity-4 units of any combination of crystalloids, colloids, or blood products within the first 30 min of arrival; Sharpe-10 red blood cell units from trauma bay presentation to inpatient admission (a proxy for the interval of hemorrhage control); Modified Sharpe-10 units of any combination of blood products during the same interval. The study analysis consisted of descriptive statistics. RESULTS: The cohort contained 187 subjects. Of 39 deaths, 28 (72%) occurred within 6 hr following arrival. Modified Sharpe captured 27 (96%) of these 28 subjects, whereas Resuscitation Intensity captured 20 (71%). Sharpe and the traditional definition each captured 22 subjects (79%). Modified Sharpe captured 17%-25% of deaths missed by the other definitions. CONCLUSION: Modified Sharpe may optimally indicate major bleeding during trauma resuscitation.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 male patients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted by potentially clinically significant variants were correlated with single-cell gene expression profiles of human fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were made in 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient with non-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.

Reducing Sedative-Hypnotics Among Hospitalized Patients: a Multi-centered Study.

BACKGROUND: Sedative-hypnotics are frequently prescribed for insomnia in hospital but are associated with preventable harms. OBJECTIVE, DESIGN, AND PARTICIPANTS: We aimed to examine whether a sedative-hypnotic reduction quality improvement bundle decreases the rate of sedative-hypnotic use among hospitalized patients, who were previously naïve to sedative-hypnotics. This interrupted time series study occurred between May 2016 and January 2019. Control data for 1 year prior to implementation and intervention data for at least 16 months were collected. The study occurred on 7 inpatient wards (general medicine, cardiology, nephrology, general surgery, and cardiovascular surgery wards) across 5 teaching hospitals in Toronto, Canada. INTERVENTION: Participating wards implemented a sedative-hypnotic reduction bundle (i.e., order set changes, audit-feedback, pharmacist-enabled medication reviews, sleep hygiene, daily sleep huddles, and staff/patient/family education) aimed to reduce in-hospital sedative-hypnotic initiation for insomnia in patients who were previously naïve to sedative-hypnotics. Each inpatient ward adapted the bundle prior to sustaining the intervention for a minimum of 16 months. MAIN MEASURES: The primary outcome measure was the proportion of sedative-hypnotic-naïve inpatients newly prescribed a sedative-hypnotic for sleep in hospital. Secondary measures include prescribing rates of other sedating medications, fall rates, length of stay, and mortality. KEY RESULTS: We included 8,970 patient discharges in the control period and 10,120 in the intervention period. Adjusted sedative-hypnotic prescriptions among naïve patients decreased from 15.48% (95% CI: 6.09-19.42) to 9.08% (p<0.001) (adjusted OR 0.814; 95% CI: 0.667-0.993, p=0.042). Unchanged secondary outcomes included mortality (adjusted OR 1.089; 95% CI: 0.786-1.508, p=0.608), falls (adjusted rate ratio 0.819; 95% CI: 0.625-1.073, p=0.148), or other sedating drug prescriptions (adjusted OR 1.046; 95% CI: 0.873-1.252, p=0.627). CONCLUSIONS: A sedative-hypnotic reduction quality improvement bundle implemented across 5 hospitals was associated with a sustained reduction in sedative-hypnotic prescriptions.

A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.

Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

Supporting community overdose response planning in Ontario, Canada: Findings from a situational assessment.

BACKGROUND: Many communities across North America are coming together to develop comprehensive plans to address and respond to the escalating overdose crisis, largely driven by an increasingly toxic unregulated drug supply. As there is a need to build capacity for successful implementation, the objective of our mixed methods study was to identify the current planning and implementation practices, needs, and priority areas of support for community overdose response plans in Ontario, Canada. METHODS: We used a situational assessment methodology to collect data on current planning and implementation practices, needs, and challenges related to community overdose response plans in Ontario, consisting of three components. Between November 2019 to February 2020, we conducted ten semi-structured key informant interviews, three focus groups with 25 participants, and administered an online survey (N = 66). Purposeful sampling was used to identify professionals involved in coordinating, supporting, or partnering on community overdose response plans in jurisdictions with relevant information for Ontario including other Canadian provinces and American states. Key informants included evaluators, representatives involved in centralised supports, as well as coordinators and partners on community overdose response plans. Focus group participants were coordinators or leads of community overdose response plans in Ontario. RESULTS: Sixty-six professionals participated in the study. The current planning and implementation practices of community overdose response plans varied in Ontario. Our analysis generated four overarching areas for needs and support for the planning and implementation of community overdose response plans: 1) data and information; 2) evidence and practice; 3) implementation/operational factors; and 4) partnership, engagement, and collaboration. Addressing stigma and equity within planning and implementation of community overdose response plans was a cross-cutting theme that included meaningful engagement of people with living and lived expertise and meeting the service needs of different populations and communities. CONCLUSIONS: Through exploring the needs and related supports for community overdose response plans in Ontario, we have identified key priority areas for building local capacity building to address overdose-related harms. Ongoing development and refinement, community partnership, and evaluation of our project will highlight the influence of our supports to advance the capacity, motivation, and opportunities of community overdose response plans.

Retrospective record review on timing of COVID-19 vaccination and cardiac surgery.

BACKGROUND: Novel clinical challenges are faced by cardiac surgeons under the coronavirus disease 2019 (COVID-19) pandemic. Amidst the uncertainties faced due to the socioeconomic and public health impact, there is little evidence surrounding COVID-19 vaccination in patients undergoing cardiac surgery. Timing of vaccination and postvaccination adverse effects are required parameters to discuss with cardiac surgical patients. METHODS: This is a single-center, retrospective observational study. All patients who underwent adult cardiac surgery at the Prince of Wales Hospital, Hong Kong from January 2021 to December 2021 were included. Postoperative clinical outcomes, COVID-19 vaccination status, and vaccination-related adverse effects were collected. RESULTS: A total of 426 patients; 117 (27%) underwent isolated coronary artery bypass grafting, 111 (26%) underwent valvular surgery, and 97 (23%) underwent aortic surgery. Patients received either Sinovac CoronaVac or Pfizer BNT162b2 vaccine. Overall vaccination rate with at least 1 dose was 52% (n = 212), 15% (n = 63) received the first dose before surgery, 36% (n = 149) received the first dose vaccination after surgery. Rate of completion with second and third doses of vaccination were 22% (n = 89) and 4.9% (n = 20), respectively. The mean timing of first dose of vaccine after surgery was 216 ± 84 days from operation. Three (1.4%) patients recorded vaccination-related complications. CONCLUSIONS: COVID-19 vaccination is safe in patients who received major cardiac surgery, with low adverse effects recorded and no vaccine-related mortality observed. A time frame of 3-6 months after cardiac surgery receiving COVID-19 vaccination is reasonable and could serve as a guidance for future COVID-19 vaccination booster programs.

Effect of Volitional Effort on Submental Surface Electromyographic Activity During Healthy Swallowing.

The effortful swallowing technique aims to compensate for or rehabilitate impaired swallowing by using maximal volitional effort to behaviorally modify aspects of swallowing physiology. Given that swallowing is a submaximal task, swallowing at submaximal levels has recently been suggested as a more task-specific therapeutic technique. The aim of this study was to investigate differences in muscle activity during minimum, regular, and maximum effort swallowing of different boluses and across different ages, with the goal of characterizing the task specificity of minimum effort and maximum effort swallowing. Forty-three healthy adults (22 female) representing four age groups (20-39, 40-59, 60-79, and 80 + years) participated in the study. They were verbally cued to swallow saliva and 5 mL water boluses using participant-determined minimum, regular, and maximum levels of effort, in randomized order. sEMG peak amplitude and duration of each swallow were measured. Linear mixed effects analyses demonstrated that compared to regular effort swallowing, maximum effort swallowing resulted in increased sEMG amplitude (p < .001) and prolonged duration (p < .001), while minimum effort swallowing resulted in decreased amplitude (p < .001) but no significant difference in duration (p = .06). These effects occurred regardless of age or bolus type. Differences in sEMG activity were smaller between regular and minimum effort swallowing than regular and maximum effort swallowing. Both increasing and decreasing volitional efforts during swallowing translate to significant modulation of muscle activity. However, regular swallowing is more similar to minimal effort swallowing. Results reinforce the concept of swallowing as a submaximal task, and provide insight into the development of sEMG biofeedback techniques for rehabilitation.

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line.

The SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged, although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available, with nearly 20,000 variants present, most of which were missed by short-read sequencing. Surrounding the important ERBB2 oncogene (also known as HER2), we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the genome and sheds new light on the complex mechanisms involved in cancer genome evolution.

Classification of Stroke Patients With Dysphagia Into Subgroups Based on Patterns of Submental Muscle Strength and Skill Impairment.

OBJECTIVES: To identify and characterize subgroups of stroke patients with clinical signs of dysphagia, based on swallowing-related strength and skill impairments of the submental muscle group. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation centers and community dwellings. PARTICIPANTS: Individuals (N=114), including stroke patients with dysphagia (n=55) and 2 control groups including myopathic patients with dysphagia (n=19) and healthy volunteers (n=40) were included in this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Novel clinical assessment of strength (force generation) and skill (spatial and temporal precision of muscle activation) of the submental muscle group during swallowing and nonswallowing behaviors, using surface electromyography and dynamometry. RESULTS: Hierarchical cluster analysis revealed 4 clusters, which could be broadly characterized as cluster 1: intact strength and skill, cluster 2: poor strength and poor nonswallowing skill, cluster 3: poor strength, and cluster 4: poor strength and poor swallowing skill. Membership in cluster was significantly associated with medical diagnosis (P<.001). The majority of healthy and myopathic participants were assigned to clusters 1 and 3, respectively, whereas stroke patients were found in all 4 clusters. Skill outcome measures were more predictive of cluster assignment than strength measures. CONCLUSIONS: Although healthy and myopathic participants demonstrated predominantly homogeneous swallowing patterns of submental muscle function within their etiology, several subgroups were identified within stroke, possibly reflecting different subtypes of swallowing function. Future research should focus on the nature and rehabilitation needs of these subtypes. Assessment of skill in swallowing may be an important but overlooked aspect of rehabilitation.

A mixed methods evaluation of a 4-week geriatrics curriculum in strengthening knowledge and comfort among orthopaedic surgery residents.

BACKGROUND: In 2014, the University of Toronto Faculty of Medicine implemented a 4-week "Orthogeriatrics" rotation for orthopaedic surgery residents. We sought to assess the rotation's impact on trainees' knowledge, attitudes, and behaviours toward caring for older adults, and explore areas for improvement. METHODS: We used a mixed methods concurrent triangulation design. The Geriatrics Clinical Decision-Making Assessment (GCDMA) and Geriatric Attitudes Scale (GAS) compared knowledge, attitudes, and behaviours between trainees who were or were not exposed to the curriculum. Rotation evaluations and semi-structured interviews with trainees and key informants explored learning experiences and the curriculum's impact on resident physician growth and development in geriatric competencies. RESULTS: Among trainees who completed the GCDMA (n = 19), those exposed to the rotation scored higher in knowledge compared to the unexposed cohort (14.4 ± 2.1 vs. 11.3 ± 2.0, p < 0.01). The following themes emerged from the qualitative analysis of 29 stakeholders: Increased awareness and comfort regarding geriatric medicine competencies, appreciation of the value of orthogeriatric collaboration, and suggestions for curriculum improvement. CONCLUSIONS: These results suggest that the Orthogeriatrics curriculum strengthens knowledge, behaviour, and comfort towards caring for older adults. Our study aims to inform further curriculum development and facilitate dissemination of geriatric education in surgical training programs across Canada and the world.

Comparison of Shock Index With the Assessment of Blood Consumption Score for Association With Massive Transfusion During Hemorrhage Control for Trauma.

BACKGROUND: Hemorrhage is a leading cause of early mortality following trauma. A massive transfusion protocol (MTP) to guide resuscitation while bleeding is definitively controlled may improve outcomes. Prompts to initiate massive transfusion (MT) include shock index (SI) and the Assessment of Blood Consumption (ABC) score. OBJECTIVE: To compare SI with the ABC score for association with transfusion requirement, need for emergency hemorrhage interventions, and early mortality. METHODS: A retrospective cohort analysis of trauma MTP activations at our Level I trauma center was conducted from January 1, 2012, to December 31, 2016. The study data were obtained from the Trauma Registry and the blood bank. An SI cutoff of 1.0 was chosen for comparison with the positive ABC score. RESULTS: The study cohort included 146 patients. Shock index ≥ 1 had significant association with MT requirement (p = .002) whereas a positive ABC score did not (p = .65). More patients with SI ≥ 1 required bleeding control interventions (67% surgery, 47% interventional radiology) than patients having a positive ABC score (49% surgery, 29% interventional radiology). For geriatric patients who received MT, 65% had SI ≥ 1 but only 30% had a positive ABC score. Three-hour mortality following emergency department arrival was similar (60% SI ≥ 1, 62% positive ABC score). CONCLUSION: Shock index ≥ 1 outperformed a positive ABC score for association with MT requirement. Shock index is a simple tool registered nurses can independently utilize to anticipate MT.

Third-generation cephalosporin-resistant urinary tract infections in children presenting to the paediatric emergency department.

BACKGROUND: The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED). METHODS: This was a retrospective cohort study conducted at British Columbia Children's Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis. RESULTS: There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI. CONCLUSIONS: Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI.

Correlation of Nasal Cannula End-Tidal Carbon Dioxide Concentration With Need for Critical Resources for Blunt Trauma Patients Triaged to Lower-Tier Trauma Activation.

Patients assigned lower-tier trauma activation may be undertriaged. Delayed recognition and intervention may adversely affect outcome. For critically injured intubated patients, research shows that abnormally low end-tidal carbon dioxide (EtCO2) values correlate with need for blood transfusion, surgery, and mortality. The purpose of this study was to evaluate EtCO2 monitoring for patients triaged to lower-tier trauma activation. EtCO2 monitoring may aid in the recognition of patients who have greater needs than anticipated. This is a prospective observational study conducted at a Level I trauma center. Potential subjects presenting from the field were identified by lower-tier trauma activation for blunt mechanism. EtCO2 measurements acquired using nasal cannula sidestream technology were prospectively recorded in the trauma bay during the initial assessment. The medical record and trauma registry were queried for demographics, injury data, mortality, and critical resource data defined as intubation, blood transfusion, surgery, intensive care unit admission, and vasoactive medication infusion. EtCO2 data were obtained for 682 subjects during a 10.5-month period. Following exclusions, 262 patients were enrolled for data collection. EtCO2 values less than 30 mmHg were significantly associated with blood transfusion (p = .03) but not with other critical resources or mortality. Although capnography had limited utility for patients triaged to lower-tier trauma activation, EtCO2 values less than 30 mmHg correlated with blood transfusion, consistent with previous studies of critically injured intubated patients. EtCO2 monitoring is noninvasive and may serve as a simple prompt for earlier initiation of blood transfusion, a resource-intensive intervention.

An observational follow-up study on pelvic floor disorders to 3-5 years after delivery.

INTRODUCTION AND HYPOTHESIS: This study aimed to determine the prevalence of urinary incontinence (UI), fecal incontinence (FI), and pelvic organ prolapse (POP) 3-5 years after the first pregnancy and their associated risk factors. METHODS: We assessed 506 women using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-squared test, and logistic regression. RESULTS: The prevalence of UI, FI, and POP, respectively, at a mean of 43 months after first delivery was 40.8, 6.6, and 10.2% following vaginal delivery (VD) and 22.7, 4.5, and 4.5% following cesarean section (CS). Stress urinary incontinence (SUI) was reported by more women following VD than CS (38.7 vs 22.4%, P = 0.010). Compared with 8 weeks' postpartum, more women reported SUI at this later follow-up visit (40.1 vs 19.5%, P < 0.001), but fewer reported FI. More women who had an instrumental delivery reported symptoms of POP compared with those who had a normal VD. Higher body weight and weight gain from first trimester were risk factors of SUI [odds ratio (OR) 1.03] and urge urinary incontinence (UUI) (OR 1.18), respectively. Women who delivered vaginally had higher PFDI subscales scores. CONCLUSIONS: VD increased UI risk. Higher body weight and weight gain from first trimester were risk factors for SUI and UUI, respectively. More women reported symptoms of POP following an instrumental delivery than those who had a normal VD.