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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.
The liver is the ‘central laboratory’ of a chicken's body, responsible for sorting and transforming digested compounds as well as dealing with waste products. It is essential that this organ is kept in an excellent condition in order to maintain a healthy bird. Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families, including fowl adenoviruses (FAdV), avian hepatitis E virus (HEV), duck hepatitis virus (DHV), and turkey hepatitis virus (THV). Although, these viruses target the liver primarily, they each possess unique clinical and biological features. Hydropericardium syndrome (HPS) is a highly infectious disease caused by FAdV serotype 4 (FAdV-4) affecting poultry, especially broilers, and is characterised by the accumulation of fluid in the pericardial sac and hepatitis. Inclusion body hepatitis (IBH) was recognised firstly in the US, and the disease has now been reported in many countries. FAdV, the causative agent of inclusion body hepatitis, is a Group I avian adenovirus in the genus Aviadenovirus. The affected birds have a pale, swollen, friable, and haemorrhagic liver with pathognomonic histological lesions including intranuclear inclusion bodies in the nuclei of the hepatocytes. Avian HEV naturally infects chickens and is associated with hepatitis-splenomegaly syndrome, although the majority of the infected birds are subclinical. THV is a picornavirus that is likely the causative agent of turkey viral hepatitis. Currently there are more questions than answers about THV, and pathogenesis and clinical impact remains largely unknown. Future research into viral hepatic diseases of poultry is warranted to develop effective vaccines, specific diagnostic assays, and identify suitable cell culture systems for virus propagation. This review covers the common and unique features of major hepatitis causing viruses, with emphasis on FAdV, HEV and THV in an effort to identify the knowledge gaps and aid prevention and control of poultry viral hepatitis.
This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status.
A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test.
Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators.
The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.
National organisations in several countries have recently released more restrictive guidelines for infective endocarditis prophylaxis, including the American Heart Association 2007 guidelines. Initial studies demonstrated no change in infective endocarditis rates over time; however, a recent United Kingdom study suggested an increase; current paediatric trends are unknown.
Children (<18 years) hospitalised with infective endocarditis at 29 centres participating in the Pediatric Health Information Systems Database from 2003 to 2014 were eligible for inclusion. Our primary analysis focussed on infective endocarditis most directly related to the change in guidelines and included community-acquired cases in those >5 years of age. Interrupted time series analysis was used to evaluate rates over time indexed to total hospitalisations.
A total of 841 cases were identified. The median age was 13 years (interquartile range 9–15 years). In the pre-guideline period, there was a slight increase in the rate of infective endocarditis by 0.13 cases/10,000 hospitalisations per semi-annual period. In the post-guideline period, the rate of infective endocarditis increased by 0.12 cases/10,000 hospitalisations per semi-annual period. There was no significant difference in the rate of change in the pre- versus post-guidelines period (p=0.895). Secondary analyses in children >5 years of age with CHD and in children hospitalised with any type of infective endocarditis at any age revealed similar results.
We found no significant change in infective endocarditis hospitalisation rates associated with revised prophylaxis guidelines over 11 years across 29 United States children’s hospitals.
“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.
The emergence and evolution of viral pathogens cause a major problem in the poultry industry. Mutation and recombination processes are involved in the genetic and phenotypic variations of infectious bronchitis virus (IBV) in chickens, leading to the emergence of new variant strains, and give rise to virus population diversity to be modelled by the host, particularly by the immune system. The consequence is the continuous emergence of new variants with regard to pathotypes, serotypes, and protectotypes. The viral genes encoding the spike, replicase and nucleocapsid proteins can be considered the main genomic regions, which indicate the evolution processes of IBV. Despite the use of vaccination, new IBV variants are evolving and circulating in the field and should be considered as initial candidates for vaccine development. The new generation vaccines developed against locally prevailing IBV strains may be more helpful and avoid the reversion of virulence in live vaccine viruses. Understanding the mechanisms underlying the evolution of IBV has basic relevance and, without doubt, is essential to appropriately control and prevention of the disease.
Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.
To report the International Nosocomial Infection Control Consortium surveillance data from 40 hospitals (20 cities) in India 2004–2013.
Surveillance using US National Healthcare Safety Network’s criteria and definitions, and International Nosocomial Infection Control Consortium methodology.
We collected data from 236,700 ICU patients for 970,713 bed-days
Pooled device-associated healthcare-associated infection rates for adult and pediatric ICUs were 5.1 central line–associated bloodstream infections (CLABSIs)/1,000 central line–days, 9.4 cases of ventilator-associated pneumonia (VAPs)/1,000 mechanical ventilator–days, and 2.1 catheter-associated urinary tract infections/1,000 urinary catheter–days
In neonatal ICUs (NICUs) pooled rates were 36.2 CLABSIs/1,000 central line–days and 1.9 VAPs/1,000 mechanical ventilator–days
Extra length of stay in adult and pediatric ICUs was 9.5 for CLABSI, 9.1 for VAP, and 10.0 for catheter-associated urinary tract infections. Extra length of stay in NICUs was 14.7 for CLABSI and 38.7 for VAP
Crude extra mortality was 16.3% for CLABSI, 22.7% for VAP, and 6.6% for catheter-associated urinary tract infections in adult and pediatric ICUs, and 1.2% for CLABSI and 8.3% for VAP in NICUs
Pooled device use ratios were 0.21 for mechanical ventilator, 0.39 for central line, and 0.53 for urinary catheter in adult and pediatric ICUs; and 0.07 for mechanical ventilator and 0.06 for central line in NICUs.
Despite a lower device use ratio in our ICUs, our device-associated healthcare-associated infection rates are higher than National Healthcare Safety Network, but lower than International Nosocomial Infection Control Consortium Report.
Infect. Control Hosp. Epidemiol. 2016;37(2):172–181
In the present study, oocytes retrieved from cross bred Karan Fries cows by ovum pick-up technique were graded into Group 1 and Group 2, based on the morphological appearance of the individual cumulus–oocyte complexes (COCs). To analyze whether the developmental potential of the COCs bears a relation to morphological appearance, relative expression of a panel of genes associated with; (a) cumulus–oocyte interaction (Cx43, Cx37, GDF9 and BMP15), (b) fertilization (ZP2 and ZP3), (c) embryonic development (HSF1, ZAR1 and bFGF) and (d) apoptosis and survival (BAX, BID and BCL-XL, MCL-1, respectively) was studied at two stages: germinal vesicle (GV) stage and after in vitro maturation. The competence was further corroborated by evaluating the embryonic progression of the presumed zygotes obtained from fertilization of the graded COCs. The gene expression profile and development rate in pooled A and B grade (Group 1) COCs and pooled C and D grade (Group 2) COCs were determined and compared according to the original grades. The results of the study demonstrated that the morphologically characterized Group 2 COCs showed significantly (P<0.05) lower expression for most of the genes related to cumulus–oocyte interplay, fertilization and embryonic development, both at GV stage as well as after maturation. Group 1 COCs also showed greater expression of anti-apoptotic genes (BCL-XL and MCL1) both at GV stage and after maturation, while pro-apoptotic genes (BAX and BID) showed significantly (P<0.05) elevated expression in poor quality COCs at both the stages. The cleavage rate in Group 1 COCs was significantly higher than that of Group 2 (74.46±7.06 v. 31.57±5.32%). The development of the presumed zygotes in Group 2 oocytes proceeded up to 8- to 16-cell stages only, while in Group 1 it progressed up to morulae (35.38±7.11%) and blastocyst stages (9.70±3.15%), indicating their better developmental potential.
There is limited evidence and lack of consensus whether second-hand smoke (SHS) increases risk of tuberculosis (TB), which has substantial implications for unrestricted smoking indoors and TB control policies. We aimed to establish the association between SHS and the risk of acquiring and worsening of TB in non-smokers. We identified 428 articles in the initial search and 12 comparative epidemiological studies met our inclusion criteria. Exposure to SHS was found to have a higher risk of TB infection [risk ratio (RR) 1·19, 95% confidence interval (CI) 0·90–1·57] compared to non-exposure; however, this did not reach statistical significance. There was marked variability (I2 = 74%, P = 0·0008) between studies’ results, which could be explained by the differences in the diagnostic criteria used. Exposure to SHS was found to be statistically significantly associated (RR 1·59, 95% CI 1·11–2·27) with the risk of TB disease. There was significant heterogeneity (I2 = 77%, P = 0·0006) between studies’ results, which was sourced to the internal characteristics of the studies rather than combining different study designs. We did not find any studies for SHS and TB treatment-related outcomes. Thus, we conclude that SHS exposure may increase the risk of acquiring TB infection and progression to TB disease; however, the evidence remains scanty and weak.
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.
Imprinting is a well-established technique to induce recognition features in both organic and inorganic materials for a variety of target analytes. In this study, ion imprinted polysiloxanes with varying percentage of coupling agent i.e. 3-chloro propyl trimethoxy silane (CPTM) were synthesized by sol-gel method for imprinting of Cr3+. The imprinting of Cr3+ in cross-linked siloxane network was investigated by FT-IR which indicates the metal ion is coordinated with oxygen atoms of polysiloxanes. SEM images revealed that imprinted polysiloxanes possess uniform particles of submicron size. It was experienced that by increasing the concentration of CPTM up to 10% (v/v) substantially improves the binding capacity of polysiloxanes which allows us to recognized Cr3+ down to 50µg/L. Furthermore, the selectivity of Cr3+-imprinted polysiloxanes was evaluated by treating them with other competing metal ions of same concentration i.e. Cr6+, Pb2+ and Ni2+. In this regard, polysiloxanes showed much higher binding for imprint ion i.e. Cr3+ in comparison to above mentioned metal ions. Finally, the regenerated polysiloxanes were studied in order to reuse them thus, developing cost effective biomimetic sensor coatings.
In general, tuberculosis (TB) is more common in men than women. However, for reasons currently not understood, women are 1·5–2 times more likely to report TB compared to men in Pashtun region (Afghanistan, adjacent provinces Pakistan and Iran). We explored whether or not gender disparity in TB notifications in the Pashtun region of Pakistan can be explained by Pashtun ethnicity. Using an ecological linear regression design, we estimated the effect of Pashtun ethnicity on female-to-male ratio (FMR) in TB notifications after adjusting for other determinants of women's health, in Pakistan. Districts with a high proportion of women of Pashtun ethnicity had a 44% (95% confidence interval 27–61) increase in FMR of notified TB cases compared to those with low proportions, after controlling for confounders. Genetic predisposition and distinct socio-cultural determinants could be possible causative factors. However, these hypotheses need further evaluation through rigorous longitudinal studies.
Objective: To assess the association of mode of conception and sex concordance with neonatal outcomes in very preterm twins. Study design: Twin pairs born at gestational age ≤32 weeks and admitted to a Level 3 neonatal intensive care unit (NICU) in 2010–2011 were retrospectively identified from the Canadian Neonatal Network™ database. A composite outcome representing neonatal mortality or any severe morbidity (intraventricular hemorrhage grades ≥3 or periventricular leukomalacia, retinopathy of prematurity stages ≥3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥2) was compared between twins conceived using assisted reproduction technologies (ARTs) or spontaneously (SP), and tested for association with sex concordance in individual-level and pair-wise multivariable logistic regression analyses. Results: Study subjects included 1,508 twins from 216 ART (53 [25%] male–male, 104 [48%] male–female, and 59 [27%] female–female) and 538 SP (192 [36%] male–male, 123 [23%] male–female, and 223 [41%] female–female) pairs. No statistically significant association was detected between mode of conception and the composite outcome of mortality/morbidities. The composite outcome was significantly higher in same-sex than in opposite-sex twins (OR = 1.68; 95% CI = [1.09, 2.59]). This relationship was most pronounced in ART pairs (OR = 2.25; 95% CI = [1.02, 4.98]), with increased rates in one or both twins from male–male versus opposite-sex ART pairs (OR = 3.0; 95% CI = [1.07, 8.36]). Conclusion: Same-sex pairing was associated with higher mortality/morbidities in very preterm twins admitted to the NICU, and can be used in clinical practice to identify twins at higher risk of adverse neonatal outcomes.
Intranasal teeth are uncommon. Causes include trauma, infection, anatomical malformations and genetic factors. They present mainly in children, and many are asymptomatic.
This report describes the finding of a tooth that had been displaced into the nasal cavity in a six-year-old girl. The history, clinical examination, findings and operative treatment are described.
The child presented with nasal symptoms. Examination revealed a tooth in the right nasal cavity, confirmed by a lateral cephalogram radiograph. It was extracted under general anaesthesia. At follow up, the child was asymptomatic.
This is an unusual case of a child presenting with an intranasal tooth and nasal symptoms following trauma a number of years earlier. The child underwent extraction of the tooth, and recovered well without any complications.