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The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.

Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2–4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. Local regulatory authorities in France allowed inclusion of up to four children in this phase 1/2 study. Treatment was 16 intraparenchymal deposits (four in the cerebellum) of a recombinant adenoassociated viral vector serotype 2/5 (rAAV2/5) encoding human α-N-acetylglucosaminidase (NAGLU) plus immunosuppressive therapy. We assessed tolerance, neurocognitive progression, brain growth, NAGLU enzymatic activity in CSF, and specific anti-NAGLU immune response for 30 months after surgery. This trial is registered with EudraCT, number 2012-000856-33, and the International Standard Clinical Trial Registry, number ISRCTN19853672. Of seven eligible children, the four youngest, from France (n=2), Italy (n=1), and Greece (n=1), aged 20, 26, 30, and 53 months, were included between February, 2012, and February, 2014. 125 adverse events were recorded, of which 117 were treatment emergent and included six classified as severe, but no suspected unexpected serious adverse drug reactions were seen. Vector genomes were detected in blood for 2 days after surgery. Compared with the natural history of mucopolysaccharidosis type III syndromes, neurocognitive progression was improved in all patients, with the youngest patient having function close to that in healthy children. Decrease in developmental quotient was −11·0 points in patient one, −23·0 in patient two, −29·0 in patient three, and −17·0 in patient four, compared with −37·7 in the natural history of the disease. NAGLU activity was detected in lumbar CSF and was 15–20% of that in unaffected children. Circulating T lymphocytes that proliferated and produced tumour necrosis factor α upon ex-vivo exposure to NAGLU antigens were detectable at 1–12 months and 3–12 months, respectively, but not at 30 months in three of four patients. Intracerebral rAVV2/5 was well tolerated and induced sustained enzyme production in the brain. The initial specific anti-NAGLU immune response that later subsided suggested acquired immunological tolerance. The best results being obtained in the youngest patient implies a potential window of opportunity. Longer follow-up is needed to further assess safety outcomes and persistence of improved cognitive development. Association Française Contre les Myopathies, Vaincre les Maladies Lysosomales, Institut Pasteur, and UniQure.

Purpose Hyperglycemia in the acute phase after trauma could adversely affect outcome in children with severe traumatic brain injury (TBI). The goal of this study was to identify the relationship between acute spontaneous hyperglycemia and outcome in children with severe TBI at hospital discharge and 6 months later. Methods A retrospective analysis of blood glucose levels in children with severe TBI at a Pediatric level I Trauma Center, between January 2000 and December 2005. Hyperglycemia was considered for a cut-off value of 11.1 mmol/l (200 mg/dl). Outcome was measured with Glasgow Outcome Scale (GOS) at hospital discharge and at 6 months. A multiple logistic regression analysis, the Student's t test and the χ 2 test were done. Results Hyperglycemia was noted within the first 48 h in 34% of the patients. Mortality (70% vs 14%, p  < 10 -5 ) was more frequent in hyperglycemic children and bad outcome upon hospital discharge in those who remained hyperglycemic during the first 48 h of hospitalization. GOS after 6 months demonstrated that those normoglycemic children had a better outcome (95%) than those who developed hyperglycemia during the first 48 h (83%, p  = 0.01) after trauma. Conclusion Hyperglycemia could be considered as a marker of brain injury and when present upon admission, could reflect extensive brain damage with frequently associated mortality and bad outcome. The inability to maintain normal blood glucose levels during the first 48 h could be a predictive factor of bad outcome. Avoiding hyperglycemia in the initial phase could be a major issue in children with severe TBI.

To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.

Abstract Background For the elderly population living at home, the implementation of professional services tends to mitigate the effect of loss of autonomy and increases their quality of life. While helping in avoiding social isolation, home services could also be associated to different healthcare pathways. For elderly patients, Emergency Departments (EDs) are the main entrance to hospital where previous loss of autonomy is associated to worst hospital outcomes. Part of elderly patients visiting EDs are still admitted to hospital for having difficulties coping at home without presenting any acute medical issue. There is a lack of data concerning elderly patients visiting EDs assisted by home services. Our aim was to compare among elderly patients visiting ED those assisted by professional home services to those who do not in terms of emergency resources’ use and patients’ outcome. Methods A multicenter, prospective cohort study was performed in 124 French EDs during a 24-h period on March 2016.Consecutive patients living at home aged ≥80 years were included. The primary objective was to assess the risk of mortality for patients assisted by professional home services vs. those who were not. Secondary objectives included admission rate and specific admission rate for “having difficulties coping at home”. The primary endpoint was in-hospital mortality. Cox proportional-hazards regression model was used to test the association between professional home services and the primary endpoint. Multi variables logistic regressions were performed to assess secondary endpoints. Results One thousand one hundred sixty-eight patients were included, median age 86(83–89) years old,32% were assisted by professional home services. The overall in-hospital mortality rate was 7%. Assisted patients had more investigations performed. Home services were not associated with increased in-hospital mortality (HR = 1.34;95%CI [0.68–2.67]), nor with the admission rate (OR = 0.92;95%CI [0.65–1.30]). Assisted patients had a lower risk of being admitted for “having difficulties coping at home” (OR = 0.59;95%CI [0.38–0.92]). Conclusion Professional home services which assist one-third of elderly patients visiting EDs, were not associated to lower in-hospital mortality or to an increased admission rate. Assisted patients were associated to a lower risk of being admitted for «having difficulties coping at home».Professional home services could result in avoiding some admissions and their corollary complications. Trial registration Clinicaltrial.gov - NCT02900391 , 09/14/2016, retrospectively registered