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Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
Introduction: Emergency department (ED) physicians strive to provide analgesia, amnesia and sedation for patients undergoing painful procedures through the use of procedural sedation (PS). While, PS is generally safe and effective in the ED, there is institutional variability and clinician disagreement with respect to the bedside equipment required for airway management and the monitoring of adverse events. The primary goal of this research project was to describe the variability of the bedside setup utilized by Canadian ED physicians preforming PS in conjunction with self-reported adverse events. Methods: An electronic survey was distributed through the Canadian Association of Emergency Physicians (CAEP). Practicing physician members of CAEP were invited to complete the survey. The 20 question survey encompassed various aspects of PS including physician choices regarding bedside setup of airway equipment, and prevalence of self-reported adverse events. The primary outcome was the quantification of variability among ED physicians with respect to the above listed aspects of PS. Data was presented with simple descriptive statistics. Results: 278 ED physicians responded to our survey (response rate 20.9%). Respondents were primarily academic (53.2%) or community hospital based (38.2%). With emergency medicine training as: CCFP-EM (55.2%), FRCPC (30.1%), and CCFP (9.0%). The ED area in which PS was carried out varied; bedside (30.5%), procedure room (37.1%), resuscitation area (31.2%). The basic equipment set utilized appears to be a bag valve mask, suction, and an oral airway. These 3 items were present 95.4%, 95.9%, and 86.3% of the time respectively. The preparation of other items such as capnography and difficult airway equipment is highly variable and appears to be physician specific rather than clinical situation specific. The most common physician self-reported adverse events associated with PS appear to be hypoxia (Spo2<90%), hypotension (sBP<90), and prolonged sedation which occurred in 10.7%, 8.3%, and 8.1% of PS performed. Conclusion: There appears to be significant practice variability with respect to the clinical setting as well as the equipment ED physicians prefer when administering PS. Given that causal relationships cannot be inferred between airway/monitoring equipment preferences and adverse events, future studies should be targeted at identifying optimal bedside set ups which minimize adverse events.
Introduction: Emergency department (ED) physicians strive to provide analgesia, amnesia and sedation for patients when performing painful procedures through the use of procedural sedation (PS). Examination of the literature suggests that the application of PS appears to be variable with institutional influences and clinician disagreement on pharmacology, airway management, and monitoring. The primary goal of this research project was to describe the variability of practice with respect to pharmacologic choices and clinical applications of PS among Canadian ED physicians. Methods: An electronic survey was distributed through the Canadian Association of Emergency Physicians (CAEP). Practicing physician members of CAEP were invited to complete the survey. The 20 question survey encompassed various aspects of PS including physician choices regarding PS indications and pharmacology. The primary outcome was the quantification of practice variability among ED physicians with respect to the above listed aspects of PS. The data was presented with simple descriptive statistics. Results: To date, 278 ED physicians responded to our survey (response rate 20.3%). Respondents were primarily academic hospital (53.2%) or community hospital based (38.2%). With emergency medicine training as: CCFP-EM (55.2%), FRCPC (30.1%), and CCFP (9.0%). There was relative agreement on the following interventions requiring PS: 98.4% applied PS for electrical cardioversion and 98.1% for brief (<10 mins) orthopedic manipulations. However, only 36.3% utilized PS for burn debridement in the ED. PS was utilized less frequently (78.1%) for prolonged (>10mins) orthopedic manipulations than brief manipulations. For all procedures aggregated, in hemodynamically stable patients with an American Society of Anesthesiology (ASA) score of 1, ED physicians utilized propofol 76.3% of the time. Additional agents were utilized at the following rates: fentanyl-propofol (7.6%), ketamine (7.6%), and fentanyl (4%). This inclination towards propofol alone appears to be consistent across modality of ER training, type of ER setting (rural vs academic), and volume of PS performed. Conclusion: This study demonstrates that Canadian ED physicians have a clear preference for propofol as a first line pharmacologic agent when administering PS in hemodynamically stable, ASA1 patients. Conversely, there appears to be more variation amongst ED physicians with respect to second line pharmaceutical choices for PS.
Numerous advances in surgical techniques and understanding of single-ventricle physiology have resulted in improved survival. We sought to determine the influence of various demographic, perioperative, and patient-specific factors on the survival of single-ventricle patients following stage 1 palliation at our institution.
We conducted a retrospective study of all single-ventricle patients who had undergone staged palliation at our institution over an 8-year period. Data were collected from the Society of Thoracic Surgeons Congenital Heart Surgery database and from patient charts. Information on age, weight at stage 1 palliation, prematurity, genetic abnormalities, non-cardiac anomalies, ventricular dominance, and type of palliation was collected. Information on mortality and unplanned reinterventions was also collected.
A total of 72 patients underwent stage 1 palliation over an 8-year period. There were 12 deaths before and one death after stage 2 palliation. There was no hospital mortality following Glenn or Fontan procedures. On univariate analysis, low weight at the time of stage 1 palliation and prematurity were found to be risk factors for mortality following stage 1 palliation. However, multivariable Cox regression analysis revealed weight at stage 1 palliation to be a strong predictor of mortality. The type of stage 1 palliation did not have any influence on the outcome. No difference in survival was noted following the Glenn procedure.
Low weight has a deleterious impact on survival following stage 1 palliation. This is mitigated by stage 2 palliation. The type of stage 1 palliation itself has no bearing on the outcome.
In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19–20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.
“Solar X-ray Spectrometer (SOXS)” mission on-board GSAT-2 Indian spacecraft was launched on 08 May 2003 by GSLV-D2 and deployed in geostationery orbit to study the X-ray emission from solar flares with high spectral and temporal resolution. The SOXS consists of two independent payloads viz. SOXS Low Energy Detector (SLD) payload, and SOXS High Energy Detector (SHD) payload. The SLD consists of two solid state detectors Si PIN and CZT, which cover the energy range from 4-60 keV, while the SHD has NaI(Tl)/CsI(Na) sandwiched phoswich detector that covers energy range from 20 keV to 10 MeV. We present very briefly the science objectives and instrumentation of SLD payload. After the successful In-orbit Tests (IOT), the first light was fed into SLD payload on 08 June 2003 when the solar flare was already in progress. We briefly present the first results from the SLD payload.
In most mental illnesses, onset occurs before the age of 25 and the earliest stages are critical. The youth bear a large share of the burden of disease associated with mental illnesses. Yet, Canadian youths with mental health difficulties face delayed detection; long waiting lists; inaccessible, unengaging services; abrupt transitions between services; and, especially in remoter regions, even a complete lack of services. Responding to this crisis, the Canadian Institutes of Health Research announced a 5-year grant that was awarded to ACCESS, a pan-Canadian network of youths, families, clinicians, researchers, policymakers, community organisations and Indigenous communities. Using strategies developed collaboratively by all stakeholders, ACCESS will execute a youth mental healthcare transformation via early detection, rapid access and appropriate, high-quality care. The project includes an innovative, mixed-methods service research component. Similar in many respects to other national youth mental health initiatives, ACCESS also exhibits important differences of scale, scope and approach.
The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009–August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.
Trials on the use of Metarhizium flavoviride Gams and Roszypal conidia in oil-based formulation for the control of grasshoppers, particularly Hieroglyphus daganensis Krauss, in Malanville, north Benin, are described. Preliminary work examined sprayer types, application rate, and time of application. In a trial on 4-ha plots with three replicates, M. flavoviride mycoinsecticide application to H. daganensis nymphs resulted in field population reductions of 70% after 14 days. In samples incubated in cages, mortality was higher in the samples taken 3 or 7 days after application than in the sample taken immediately after application, indicating the possibility of residual pick-up compared with direct spray impact in this environment. Significant mortality was still being observed in samples collected 37 days after application; to investigate this further, a method for bioassaying the spore load in the field was developed and used to monitor the spore load in the field. The possibility that the results indicate the occurrence of secondary infections resulting from horizontal transmission of M. flavoviride is discussed.
The National Institute for Health and Clinical Excellence (NICE) routinely publishes details of the evidence and reasoning underpinning its recommendations, including its social value judgements (SVJs). To date, however, NICE's SVJs relating to equity in the distribution of health and health care have been less specific and systematic than those relating to cost-effectiveness in the pursuit of improved total population health. NICE takes a pragmatic, case-based approach to developing its principles of SVJ, drawing on the cumulative experience of its advisory bodies in making decisions that command respect among its broad range of stakeholders. This paper aims to describe the SVJs about equity in health and health care that NICE has hitherto used to guide its decision making. To do this, we review both the general SVJs reported in NICE guidance on methodology and the case-specific SVJs reported in NICE guidance about particular health care technologies and public health interventions.
Children frequently are the victims of disasters due to natural hazards or terrorist attacks. However, there is a lack of specific pediatric emergency preparedness planning worldwide. To address these gaps, the federal grant-funded New York City Pediatric Disaster Coalition (PDC) established guidelines for creating Pediatric Critical care (PCC) surge plans and assisted hospitals in creating their plans. To date, five hospitals completed plans, thereby adding 92 beds to surge capacity. On 01 May 2010, 18:00h, there was an attempt to detonate a car bomb in Times Square, a large urban attraction in the heart of New York City. The perpetrator was later convicted of the attempted use of a weapon of mass destruction. Had the bomb exploded, given the location and time of day, it is possible that many critically injured victims would have been children.
The unit director or a senior attending of nine major hospitals in the NYC area (five in close proximity and four at secondary sites) were surveyed for the number of their vacant pediatric critical care beds at the time of the event before activation of surge plans.
At the time the car bomb was discovered, the nine hospitals, which have a total of 141 PCC beds, had only 29 vacant approved pediatric critical care beds.
Had the event resulted in many pediatric casualties, the existing PCC vacant beds at these hospitals may not have satisfied the need. Activating surge plans at five of these hospitals would have added 92 to the 29 available PCC beds for a total of 121. In order to provide PCC to a large number of victims, it is crucial that hospitals prepare PCC surge plans.
There remains a lack of comprehensive pediatric emergency preparedness planning worldwide. A disaster or mass-casualty incident (MCI) involving pediatric patients could overwhelm existing pediatric resources within the New York City (NYC) metropolitan region. The NYC Department of Health and Mental Hygiene (DOHMH) recognizing the importance to plan for a MCI with a large number of pediatric victims, implemented a project (the Pediatric Disaster Coalition; PDC), to address gaps in the healthcare system to provide effective and timely pediatric care during a MCI.
The PDC includes experts in emergency preparedness, critical care, surgery, and emergency medicine from the NYC pediatric/children's hospitals, DOHMH, Office of Emergency Management, and Fire Department (FDNY). Two committees addressed pediatric prehospital triage, transport, and pediatric critical care (PCC) surge capacities. They developed guidelines and recommendations for pediatric field triage and transport, matching patients' needs to resources, and increasing PCC Surge Capacities.
Surge recommendations were formulated. The algorithm developed provides specific pediatric triage criteria that identify severity of illness using the traditional Red, Yellow, and Green categories plus an Orange designation for continual reassessments that has been adopted by FDNY that has trained > 3,000 FDNY EMS personnel in its use. Triaged patients can be transported to appropriate resources based on a tiered system that defines pediatric hospital capabilities. The Surge Committee has created PCC Surge Capacity Guideline that can be used by hospitals to create their individual PCC surge plans. 15 of 25 NYC hospitals with PCC capabilities are participating with PDC planning; 5 have completed surge plans, 3 are nea completion, and 7 are in development. The completed plans add 92 surge beds to 244 regularly available PICU beds. The goal is to increase the PCC surge bed capacity by 200 + beds.
The project is an effective, multidisciplinary group approach to planning for a regional, large-scale pediatric MCI. Regional lead agencies must emphasize pediatric emergency preparedness in their disaster plans.