RESUMEN
BACKGROUND: Pneumococcal conjugate vaccines have potential to prevent significant proportion of childhood pneumonia. Finnish Invasive Pneumococcal disease vaccine trial was designed to assess the vaccine effectiveness (VE) of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against several outcomes. We now report results for pneumonia. METHODS: In this nationwide, cluster-randomised, double-blind trial, children younger than 19â¯months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants younger than 7â¯months at the first vaccination received either 3+1 or 2+1 vaccination schedule, children aged 7-11â¯months received 2+1, and those 12-18â¯months of age two-dose schedule. All hospitalizations and outpatient visits to hospital associated with ICD-10 codes compatible with pneumonia were identified through the National Care Register and 1-3 frontal chest X-ray images per event were collected. External readers who were unaware of the patients' vaccination status retrospectively interpreted the images. The evaluated outcomes were hospital-diagnosed, hospital-treated pneumonia as primary diagnosis, and radiologically confirmed pneumonia during the blinded, intention-to-treat follow-up period from the first vaccination to the end of 2011. Total VE was calculated as 1 minus rate ratio of all pneumonia episodes. RESULTS: 47 366 children were enrolled from February 2009, to October 2010. VE against all episodes of hospital-diagnosed pneumonia was 27% (95% confidence interval [CI]: 14%, 38%), 32% (95% CI: 3%, 52%), and 23% (95% CI: -5%, 44%) in subjects enrolled at age <7, 7-11, and 12-18â¯months, respectively. Corresponding rate reductions were 3.4, 4.7, and 2.5 per 1000 person-years. VE estimates against pneumonia with alveolar consolidation or pleural effusion (WHO criteria) in the three cohorts were 45% (95% CI: 26%, 60%), 56% (95% CI: 14%, 77%), and 48% (95% CI: 2%, 73%), respectively. CONCLUSION: PHiD-CV10 vaccination remarkably reduced disease burden due to pneumonia in infants and young children. CLINICAL TRIAL REGISTRATION: Main trial NCT00861380, nested carriage and otitis media trial NCT00839254 (ClinicalTrials.gov).
Asunto(s)
Proteínas Bacterianas/inmunología , Proteínas Portadoras/inmunología , Inmunoglobulina D/inmunología , Lipoproteínas/inmunología , Otitis Media/prevención & control , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Neumonía/prevención & control , Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Método Doble Ciego , Femenino , Finlandia/epidemiología , Haemophilus influenzae , Humanos , Esquemas de Inmunización , Inmunoglobulina D/genética , Lactante , Lipoproteínas/genética , Masculino , Otitis Media/microbiologíaRESUMEN
BACKGROUND: Some people report a near-death experience (NDE) after a life-threatening crisis. We aimed to establish the cause of this experience and assess factors that affected its frequency, depth, and content. METHODS: In a prospective study, we included 344 consecutive cardiac patients who were successfully resuscitated after cardiac arrest in ten Dutch hospitals. We compared demographic, medical, pharmacological, and psychological data between patients who reported NDE and patients who did not (controls) after resuscitation. In a longitudinal study of life changes after NDE, we compared the groups 2 and 8 years later. FINDINGS: 62 patients (18%) reported NDE, of whom 41 (12%) described a core experience. Occurrence of the experience was not associated with duration of cardiac arrest or unconsciousness, medication, or fear of death before cardiac arrest. Frequency of NDE was affected by how we defined NDE, the prospective nature of the research in older cardiac patients, age, surviving cardiac arrest in first myocardial infarction, more than one cardiopulmonary resuscitation (CPR) during stay in hospital, previous NDE, and memory problems after prolonged CPR. Depth of the experience was affected by sex, surviving CPR outside hospital, and fear before cardiac arrest. Significantly more patients who had an NDE, especially a deep experience, died within 30 days of CPR (p<0.0001). The process of transformation after NDE took several years, and differed from those of patients who survived cardiac arrest without NDE. INTERPRETATION: We do not know why so few cardiac patients report NDE after CPR, although age plays a part. With a purely physiological explanation such as cerebral anoxia for the experience, most patients who have been clinically dead should report one.