Sleep apnea syndrome: improved detection of respiratory events and cortical arousals using oxymetry pulse wave amplitude during polysomnography

Respiratory events (RE) during sleep induce cortical arousals (A) and marked changes in autonomic markers in sleep apnea syndrome (SAS). The aims of the study were double. First, we assessed whether pulse wave amplitude (PWA) added to polysomnography (PSG) could improve RE and A detection; second, we wanted to know whether the quality of detection of these two parameters could be improved using PWA. Respiratory disturbance index (RDI) and A were randomly scored twice by the same observer in 12 male patients with SAS. The first scoring was done using conventional PSG signals, the second scoring adding PWA to PSG. We also measured interobserver agreement by randomly selecting and reading 100 PSG sequences of 5 min with and without PWA by two observers. Adding PWA to PSG parameters allowed to detect significantly more RDI (53.9 ± 21.6 h⁻¹ versus 48.3 ± 22.3 h⁻¹, p < 0.001) and more A (68.0 ± 14.4 versus 59.4 ± 16.5, p < 0.001). Moreover, after using PWA, there was no significant disagreement between two observers for detecting RE, showing better quality of RE detection. PWA is a simple and cheap parameter that improves the diagnostic value of conventional PSG in sleep apnea syndrome by better detecting respiratory events and A.     

Gene transfer by guanidinium-cholesterol cationic lipids into airway epithelial cells in vitro and in vivo

Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis(guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system.     

Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly

Molecular and supramolecular diversity may be generated, respectively, by reversible, covalent or noncovalent self-assembly of basic components whose various potential combinations in number and nature represent a virtual combinatorial library. This concept is applied to the induction of inhibitors of carbonic anhydrase (CA) by reversible recombination of aldehyde and amine components. It is found that the presence of CA favors the formation of those condensation compounds that may be expected to present the strongest binding to the CA active site. The virtual combinatorial library approach may represent a powerful methodology for the discovery of substrates, inhibitors, receptors, catalysts, and carriers for a variety of processes.     

The impact of introducing new vaccines on the health system: Case studies from six low- and middle-income countries

Objective

We aimed to explore the impacts of new vaccine introductions on immunization programmes and health systems in low- and middle-income countries.

Methods

We conducted case studies of seven vaccine introductions in six countries (Cameroon, PCV; Ethiopia, PCV; Guatemala, rotavirus; Kenya, PCV; Mali, Meningitis A; Mali, PCV; Rwanda, HPV). Interviews were conducted with 261 national, regional and district key informants and questionnaires were completed with staff from 196 health facilities. Routine data from districts and health facilities were gathered on vaccination and antenatal service use. Data collection and analysis were structured around the World Health Organisation health system building blocks.

Findings

The new vaccines were viewed positively and seemed to integrate well into existing health systems. The introductions were found to have had no impact on many elements within the building blocks framework. Despite many key informants and facility respondents perceiving that the new vaccine introductions had increased coverage of other vaccines, the routine data showed no change. Positive effects perceived included enhanced credibility of the immunisation programme and strengthened health workers’ skills through training. Negative effects reported included an increase in workload and stock outs of the new vaccine, which created a perception in the community that all vaccines were out of stock in a facility. Most effects were found within the vaccination programmes; very few were reported on the broader health systems. Effects were primarily reported to be temporary, around the time of introduction only.

Conclusion

Although the new vaccine introductions were viewed as intrinsically positive, on the whole there was no evidence that they had any major impact, positive or negative, on the broader health systems.     

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A french multicenter study

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9 years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5 years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36 months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6 mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.     

A study on clinical and radiological features and outcome in patients with posterior reversible encephalopathy syndrome (PRES)

Posterior reversible encephalopathy syndrome (PRES) is characterized clinically by headaches, seizures, vomiting, nausea, visual abnormalities, and altered mental function and is often (but not invariably) accompanied by parieto-occipital imaging features. The aim of this study is to describe the clinical and radiological features and outcome following PRES in a paediatric cohort. From a retrospectively identified cohort, case records were studied to confirm a diagnosis of PRES. Neuroimaging was reviewed again to assign to recently described radiological subtypes parieto-occipital pattern, holohemispheric watershed pattern, dominant superior frontal sulcus pattern, and asymmetrical or partial expression of the three primary patterns (A/P). Patient outcome was measured by the modified Rankin scale (mRS) scores. Nine boys and three girls with mean age of 12 were identified. Hypertensive episodes (n?=?11), tacrolimus toxicity (n?=?4), and autoimmunity (n?=?1) were identified as potential risk factors/etiologies. Their median mRS at the peak of illness was 2 (range 2–5); three children required intensive care support. After mean follow-up of 35 months (median 37 months; range 3–60 months), all patients improved significantly with mean mRS of 1 (median 1; range 0–1). Conclusion: PRES is easily recognizable by the clinical and radiological features. Although severe at presentation, the outcome from this condition is favorable.