Bacterial immunotherapy is highly effective in reducing recurrent upper respiratory tract infections in children: a prospective observational study.

PURPOSE: Whilst immunotherapy is an appealing option as it could reduce the burden of recurrent pediatric respiratory tract infections (RTI), there is limited evidence on its effectiveness and more research was requested in order to better understand this therapeutic modality. METHODS: We performed a prospective cohort study involving 57 subjects to assess the safety and effectiveness a 3-month regimen of either typified or patient-specific bacterial lysates could have in reducing the number of RTIs in children aged 0 to 11 years with histories of recurrent episodes. RESULTS: After a 6-month follow-up, the number of RTIs and school absenteeism dropped sharply and significantly, from an adjusted mean (standard error) of 0.6 (0.04) episodes/month to 0.1 (0.03) episodes/month (74.7% reduction, P < 0.001), and from an adjusted mean score of 4.6 (1.06) points to 0.0 (0.01) points over 10 (99.5% reduction, P < 0.001), respectively. There was also a significant decrease in the severity of symptoms. No adverse reactions were observed. CONCLUSION: The use of the study product is associated with a decreased risk of recurrent RTIs in children, with a very favorable safety profile that warrants further investigation in randomized clinical trials.

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

RATIONALE: Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome. OBJECTIVES: To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers. METHODS: Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated. MEASUREMENTS AND MAIN RESULTS: In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota. CONCLUSIONS: We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

Tongue peak pressure: a tool to aid in the identification of obstruction sites in patients with obstructive sleep apnea/hypopnea syndrome.

Purpose of this study was to evaluate whether tongue peak pressure measured using the Iowa Oral Performance Instrument is correlated with the topographic site of obstruction in patients with obstructive sleep apnea/hypopnea syndrome observed during drug-induced sleep endoscopy. Thirty-five consecutive adult patients (29 men, 6 women) were prospectively enrolled after having been diagnosed with severe obstructive sleep apnea/hypopnea syndrome by polysomnography. An apnea-hypopnea index > 30 was confirmed, and age, gender, and body mass index were recorded by Epworth Sleepiness Scale questionnaire, and a thorough evaluation of the upper airway by video-flexible endoscopy. Twenty healthy controls according to age and sex were chosen for IOPI measurements. After drug-induced sleep endoscopy, a topographic diagnosis was done using the VOTE classification. Tongue and lip peak pressures were both measured using the Iowa Oral Performance Instrument in all patients and in 20 healthy controls. Main outcomes and measures: the correlations between office findings, Iowa Oral Performance Instrument measures, and the VOTE tongue classification during drug-induced sleep endoscopy (T0, T1, T2) were then investigated. RESULTS: The average Iowa Oral Performance Instrument tongue and lip pressure were 44.02 ± 12.29 and 15.03 ± 3.71 kPa, respectively. The Iowa Oral Performance Instrument scores were both significantly lower than values in healthy controls (P < 0.001). The VOTE classification referring to the tongue position was T0 in 13 cases (37.1%), T1 in 12 cases (34.3%), and T2 in 10 cases (28.6%). A significant correlation was found between the Iowa Oral Performance Instrument tongue pressure and the T size during drug-induced sleep endoscopy (Kruskal-Wallis χ2 25.82; P ≤ 0.001). CONCLUSIONS: In our experience, the Iowa Oral Performance Instrument is a useful tool for evaluating tongue collapse for the topographic diagnosis of patients with obstructive sleep apnea/hypopnea syndrome.

Visual field defects and retinal nerve fiber imaging in patients with obstructive sleep apnea syndrome and in healthy controls.

BACKGROUND: To assess the retinal sensitivity in obstructive sleep apnea hypopnea syndrome (OSAHS) patients evaluated with standard automated perimetry (SAP). And to correlate the functional SAP results with structural parameters obtained with optical coherence tomography (OCT). METHODS: This prospective, observational, case-control study consisted of 63 eyes of 63 OSAHS patients (mean age 51.7 ± 12.7 years, best corrected visual acuity ≥20/25, refractive error less than three spherical or two cylindrical diopters, and intraocular pressure < 21 mmHg) who were enrolled and compared with 38 eyes of 38 age-matched controls. Peripapillary retinal nerve fiber layer (RNFL) thickness was measured by Stratus OCT and SAP sensitivities and indices were explored with Humphrey Field Analyzer perimeter. Correlations between functional and structural parameters were calculated, as well as the relationship between ophthalmologic and systemic indices in OSAHS patients. RESULTS: OSAHS patients showed a significant reduction of the sensitivity for superior visual field division (p = 0.034, t-student test). When dividing the OSAHS group in accordance with the severity of the disease, nasal peripapillary RNFL thickness was significantly lower in severe OSAHS than that in controls and mild-moderate cases (p = 0.031 and p = 0.016 respectively, Mann-Whitney U test). There were no differences between groups for SAP parameters. We found no correlation between structural and functional variables. The central visual field sensitivity of the SAP revealed a poor Pearson correlation with the apnea-hipopnea index (0.284, p = 0.024). CONCLUSIONS: Retinal sensitivity show minor differences between healthy subjects and OSAHS. Functional deterioration in OSAHS patients is not easy to demonstrate with visual field examination.

Upper airway and systemic inflammation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment.We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h-1), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay.In PHAL, CD4+ T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p<0.05). The AHI correlated with CD4+, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery.In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found.

Retinal and optic nerve evaluation by optical coherence tomography in adults with obstructive sleep apnea-hypopnea syndrome (OSAHS).

OBJECTIVE: To assess the peripapillary retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) morphologic parameters, and macular thickness and volume in patients affected by obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This prospective, observational case-control study consisted of 96 eyes of 50 OSAHS patients (mean age of 50.9 ± 12.4 years, best-corrected visual acuity ≥ 20/20, refractive error less than 3 spherocylindrical diopters, and intraocular pressure <21 mmHg) who were enrolled and compared with 64 eyes of 33 age-matched controls. Peripapillary RNFL thickness, ONH parameters, macular thickness and volume were measured by optical coherence tomography (OCT). RESULTS: OSAHS patients showed a significant reduction of the nasal quadrant RNFL thickness (74.7 ± 15.8 µm) compared with those values observed in control patients (81.1 ± 16.6 µm, p=0.047, Student's t-test). No differences in peripapillary RNFL thickness were observed when dividing the OSAHS group in accordance with disease severity. Vertical integrated rim area (VIRA) (0.67 ± 0.41 mm(3) in OSAHS vs 0.55 ± 0.29 mm(3) in controls; p=0.043, Student's t-test), horizontal integrated rim width (HIRW) (1.87 ± 0.31 mm(2) in OSAHS vs 1.8 ± 0.25 mm(2) in controls; p=0.039, Student's t-test) and disc area (2.74 ± 0.62 mm(2) in OSAHS vs 2.48 ± 0.42 mm(2) in controls; p=0.002, Student's t-test) showed significant differences, all of them being higher in the OSAHS group. Severe OSAHS had significant higher disc area (2.8 ± 0.7 mm(2)) than controls (2.5 ± 0.4 mm(2); p=0.016, ANOVA test). Temporal inner macular thickness was significantly higher in mild-moderate OSAHS patients (270 ± 12 µm) than in severe OSAHS patients (260 ± 19 µm; p=0.021, ANOVA test). CONCLUSIONS: OSAHS patients showed decreased peripapillary nasal RNFL thickness, and increased ONH area and volume parameters when they were evaluated by OCT. These findings suggest that neuronal degeneration might be present in the retina of OSAHS patients, as previously observed in some neurodegenerative disorders.

Association between treated and untreated obstructive sleep apnea and risk of hypertension.

CONTEXT: Systemic hypertension is prevalent among patients with obstructive sleep apnea (OSA). Short-term studies indicate that continuous positive airway pressure (CPAP) therapy reduces blood pressure in patients with hypertension and OSA. OBJECTIVE: To determine whether CPAP therapy is associated with a lower risk of incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 1889 participants without hypertension who were referred to a sleep center in Zaragoza, Spain, for nocturnal polysomnography between January 1, 1994, and December 31, 2000. Incident hypertension was documented at annual follow-up visits up to January 1, 2011. Multivariable models adjusted for confounding factors, including change in body mass index from baseline to censored time, were used to calculate hazard ratios (HRs) of incident hypertension in participants without OSA (controls), with untreated OSA, and in those treated with CPAP therapy according to national guidelines. MAIN OUTCOME MEASURE: Incidence of new-onset hypertension. RESULTS: During 21,003 person-years of follow-up (median, 12.2 years), 705 cases (37.3%) of incident hypertension were observed. The crude incidence of hypertension per 100 person-years was 2.19 (95% CI, 1.71-2.67) in controls, 3.34 (95% CI, 2.85-3.82) in patients with OSA ineligible for CPAP therapy, 5.84 (95% CI, 4.82-6.86) in patients with OSA who declined CPAP therapy, 5.12 (95% CI, 3.76-6.47) in patients with OSA nonadherent to CPAP therapy, and 3.06 (95% CI, 2.70-3.41) in patients with OSA and treated with CPAP therapy. Compared with controls, the adjusted HRs for incident hypertension were greater among patients with OSA ineligible for CPAP therapy (1.33; 95% CI, 1.01-1.75), among those who declined CPAP therapy (1.96; 95% CI, 1.44-2.66), and among those nonadherent to CPAP therapy (1.78; 95% CI, 1.23-2.58), whereas the HR was lower in patients with OSA who were treated with CPAP therapy (0.71; 95% CI, 0.53-0.94). CONCLUSION: Compared with participants without OSA, the presence of OSA was associated with increased adjusted risk of incident hypertension; however, treatment with CPAP therapy was associated with a lower risk of hypertension.

Assessment of the Effectiveness of Obstructive Sleep Apnea Treatment Using Optical Coherence Tomography to Evaluate Retinal Findings.

Retinal findings may change in patients with obstructive sleep apnea syndrome (OSAS). The present study aims to evaluate several retinal findings, such as macula layer thickness, the peripapillary retinal nerve fiber layer, and the optic nerve head in patients with OSAS, using optical coherence tomography (OCT); it also aims to monitor the result of several types of treatment of OSAS with OCT. A prospective comparative study was designed. Patients were recruited at a Sleep Unit of a University Hospital and underwent comprehensive ophthalmological examinations. Following exclusion criteria, fifty-two patients with OSAS were finally included. Patients were examined by OCT twice: once before treatment, and again after six months of treatment. In mild-moderate patients, where retinal swelling had been demonstrated, retinal thicknesses decreased [fovea (p = 0.026), as did inner ring macula (p = 0.007), outer ring macula (p = 0.015), and macular volume (p = 0.015)]. In severe patients, where retinal atrophy had been observed, retinal thickness increased [fovea (p < 0.001)]. No statistically significant differences in efficacy between treatments were demonstrated. In conclusion, OCT can evaluate the retina in patients with OSAS and help to monitor results after treatment. In severe OSAS, retinal thickness increased six months after treatment.

Medication adherence and persistence in severe obstructive sleep apnea.

STUDY OBJECTIVE: The aim of this study was to compare 2 groups of patients with severe obstructive sleep apnea (OSA) who were taking medication for cardiovascular disease: those who were compliant with nasal continuous positive airway pressure (CPAP) treatment and those who refused treatment or were noncompliant with CPAP treament. METHODS: In a cohort of 2158 patients with severe OSA (apnea-hypopnea index >30) a 2-year prospective longitudinal assessment of adherence and persistence with 3 medication categories (antihypertensives, statins, and antiplatelets) was carried out using the administrative database of the National Health Service. Medication adherence was evaluated by calculating the medication possession ratio (%MPR = days supplylactual days to refill x 100) for each drug. Medication persistency was defined as the proportion of subjects having filled a prescription in the last 30 days of the 2-year period. CPAP use was assessed at every follow-up visit after the treatment was prescribed. Medication adherence was compared between patients who had adequate CPAP adherence (> 4 h/day) and those who declined CPAP therapy or had discontinued CPAP due to an average use of less than 4 hours per day. RESULTS: The average 2-year MPR for antihypertensives, statins, and antiplatelets was not different among patients who used CPAP (88%, 81%, 95%) or did not use CPAP (86%, 77%, 93%). Female sex and increased number of comorbidities were predictors of good medication adherence (MPR > 80%). The rates of persistence for the 3 studied medications after the 2-year observation period were not different between the 2 groups (patients with or without CPAP). CONCLUSIONS: Medication adherence and persistence during a 2-year period for 3 well-known protective cardiovascular medications were not different in patients with severe OSA, whether or not they were treated with CPAP.

Long term management of obstructive sleep apnea and its comorbidities.

Obstructive sleep apnea (OSA) is a worldwide highly prevalent disease associated with systemic consequences, including excessive sleepiness, impairment of neurocognitive function and daytime performance, including driving ability. The long-term sequelae of OSA include and increase risk for cardiovascular, cerebrovascular and metabolic syndrome disorders that ultimately lead to premature death if untreated. To ensure optimal long-term outcomes, the assessment and management of OSA should be personalized with the involvement of the appropriate specialist. Most studies have demonstrated inmediate improvement in daytime somnolence and quality of life with CPAP and other therapies, but the effect of long-term treatment on mortality is still under debate. Currently, the long-term management of OSA should be based on a) identifying physiological or structural abnormalities that are treatable at the time of patient evaluation and b) comprehensive lifestyle interventions, especially weight-loss interventions, which are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. In long-term management, attention should be paid to the clinical changes related to a potential reoccurrence of OSA symptoms and it is also necessary to monitor throughout the follow up how the main associated comorbidities evolve.

La profesionalización en el contexto de las ciencias médicas en Cuba: una mirada desde los artículos científicos publicados por autores cubanos / Professionalization in the context of medical sciences in Cuba: a view from scientific articles published by Cuban authors

RESUMEN Introducción: en la actualidad los estudios sobre profesionalización son un campo abierto a nuevas áreas y a los más diversos abordajes. Fenómeno que se manifiesta de igual manera en el campo de las ciencias de la salud. Objetivo: realizar una revisión sistemática sobre la profesionalización en el contexto de las ciencias médicas en Cuba. Métodos: se realizó una investigación descriptiva de corte transaccional. Se emplearon dos criterios de búsquedas, la base de datos de cada una de las revistas de las ciencias médicas del país y la búsqueda abierta en varios motores de búsquedas y bases de datos. Como instrumento básico de recogida de datos se diseñó una matriz de adyacencia formada por filas y columnas. Resultados: la búsqueda realizada permitió identificar 24 artículos científicos sometidos a la revisión por pares. El comportamiento de las publicaciones en los años registrados reveló de manera general que es muy reducido el número de artículos que sobre el tema se han publicado. Se observó que la centralidad de la red gira en torno a cuatro nodos que tienen la mayor cantidad de concurrencia: profesionalización, profesionalización pedagógica, profesionalización docente y profesionalización científica Conclusiones: se concluye que la profesionalización es una categoría usada en el contexto de las ciencias médicas en Cuba y en la gestión de los diferentes procesos que se llevan a cabo. No obstante, la socialización de artículos científicos no está adecuadamente respaldada dada la totalidad de prácticas que en este campo se realizan.

ABSTRACT Introduction: at present, studies on professionalization continue to be a field open to new areas and to the most diverse approaches. This phenomenon is equally visible in the field of health sciences. Objective: to carry out a systematic review on professionalization in the context of medical sciences in Cuba. Methods: a descriptive-transactional-type research was carried out. Two search criteria were used: the database of each one of the medical sciences journals in the country and the open search in several search engines and databases. An adjacent matrix formed by rows and columns was designed as a basic data collection instrument. Results: the search made it possible to identify 24 scientific articles submitted to peer-review. The behavior of the publications in the years recorded revealed in general that the number of articles published on the subject is very small. It was observed that the centrality of the network revolves around four nodes that have the highest number of concurrence: professionalization, pedagogical professionalization, teaching professionalization and scientific professionalization. Conclusions: it is concluded that professionalization is a category used in the context of medical sciences in Cuba and in the management of the different processes conducted. However, the socialization of scientific articles is not adequately supported given the totality of practices carried out in this field.

Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study.

BACKGROUND: The effect of obstructive sleep apnoea-hypopnoea as a cardiovascular risk factor and the potential protective effect of its treatment with continuous positive airway pressure (CPAP) is unclear. We did an observational study to compare incidence of fatal and non-fatal cardiovascular events in simple snorers, patients with untreated obstructive sleep apnoea-hypopnoea, patients treated with CPAP, and healthy men recruited from the general population. METHODS: We recruited men with obstructive sleep apnoea-hypopnoea or simple snorers from a sleep clinic, and a population-based sample of healthy men, matched for age and body-mass index with the patients with untreated severe obstructive sleep apnoea-hypopnoea. The presence and severity of the disorder was determined with full polysomnography, and the apnoea-hypopnoea index (AHI) was calculated as the average number of apnoeas and hypopnoeas per hour of sleep. Participants were followed-up at least once per year for a mean of 10.1 years (SD 1.6) and CPAP compliance was checked with the built-in meter. Endpoints were fatal cardiovascular events (death from myocardial infarction or stroke) and non-fatal cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, coronary artery bypass surgery, and percutaneous transluminal coronary angiography). FINDINGS: 264 healthy men, 377 simple snorers, 403 with untreated mild-moderate obstructive sleep apnoea-hypopnoea, 235 with untreated severe disease, and 372 with the disease and treated with CPAP were included in the analysis. Patients with untreated severe disease had a higher incidence of fatal cardiovascular events (1.06 per 100 person-years) and non-fatal cardiovascular events (2.13 per 100 person-years) than did untreated patients with mild-moderate disease (0.55, p=0.02 and 0.89, p<0.0001), simple snorers (0.34, p=0.0006 and 0.58, p<0.0001), patients treated with CPAP (0.35, p=0.0008 and 0.64, p<0.0001), and healthy participants (0.3, p=0.0012 and 0.45, p<0.0001). Multivariate analysis, adjusted for potential confounders, showed that untreated severe obstructive sleep apnoea-hypopnoea significantly increased the risk of fatal (odds ratio 2.87, 95%CI 1.17-7.51) and non-fatal (3.17, 1.12-7.51) cardiovascular events compared with healthy participants. INTERPRETATION: In men, severe obstructive sleep apnoea-hypopnoea significantly increases the risk of fatal and non-fatal cardiovascular events. CPAP treatment reduces this risk.

Tongue-base suspension in conjunction with uvulopalatopharyngoplasty for treatment of severe obstructive sleep apnea: long-term follow-up results.

OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of tongue-base suspension (TBS) in addition to uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Long-term prospective case series. SETTING: University tertiary care medical center. METHODS: Fifty-five consecutive patients with severe OSAS (apnea-hypopnea index [AHI] 52.8+/-14.9 events/hr) with multilevel upper airway obstruction who refused treatment with continuous positive airway pressure underwent UPPP plus TBS with the Repose system. All patients were evaluated before surgery by clinical history, Epworth Sleepiness Scale (ESS), fiberoptic nasopharyngoscopy with Müller maneuver, and nocturnal polysomnography (PSG). After 3 years of surgery, all patients were re-evaluated at the clinic and had ESS test and full PSG. Surgical success was defined when the ESS dropped bellow 11, and the AHI decreased below the threshold of 20 events per hour of sleep and at least 50% from the preoperative value RESULTS: There were 42 (78%) patients in which the AHI score decreased more than 50%, the AHI was lower than 20 events/hr in the PSG, and the ESS was lower than 11 after 3-years of follow-up (surgical success index). Logistic regression analysis demonstrated that body mass index at baseline was the only variable with significant statistical power to predict surgical success (odds ratio 0.85; 0.73-0.95, 95% confidence interval, P<.01) CONCLUSION: When associated with UPPP, the TBS technique performed with the Repose system demonstrates a surgical success of up to 78% for patients with severe OSA who refused nasal continuous positive airway pressure.

Identification of 14-3-3-like protein in sugarcane (Saccharum officinarum)

Seqüências completas de três cDNAs que codificam proteínas 14-3-3 de cana-de-açúcar (Saccharum officinarum) foram encontradas no projeto genoma EST de cana-de-açúcar. As proteínas codificadas por essas seqüências foram identificadas baseando-se no agrupamento de ESTs de cana-de-açúcar e, três "clusters" (SCCCLR1022 DO5.g, SCCCRZl001D02.g e SCBFLR1026E02.g) foram similares a proteínas 14-3-3 de outras monocotiledôneas. O cluster SCCCLR1022DO5.g apresentou similaridade de 99 por cento com a proteína 14-3-3 de milho (gi/1345587) e, os clusters SCCCRZ1001D02.g e SCBFLR1026E02.g foram similares a proteína 14-3-3 de arroz (gi/7435022), 96 por cento e 94 por cento, respectivamente. Embora proteínas 14-3-3 têm sido relatadas como sendo específicas a organismos, tecidos e órgäos, todos os "clusters" de cana-de-açúcar correspondentes a 14-3-3 foram provenientes de cDNAs advindos de diferentes tecidos.