This review focuses on the burden of respiratory syncytial virus (RSV) infection in preterm infants with and without chronic lung disease (bronchopulmonary dysplasia, BPD). of lower respiratory tract infection is not different in term and preterm babies, but rates of apnoeas are significantly improved in preterms, FLN ranging from 4.9 to 37.5 percent with reducing rates observed in more recent studies. Until a RSV vaccine is definitely developed and will be available, prophylaxis with palivizumab is the only preventative strategy other than hand hygiene and contact actions that significantly reduces RSV hospitalization rates in preterm babies both with and without BPD. [15] during the 1999/2000 RSV time of year in Switzerland with 36% of hospitalisations happening after April 1, 2000 that would not have been preventable by palivizumab prophylaxis initiated in November 1. Overall you will find major variations between regions throughout the northern hemisphere [16-22]. In the southern hemisphere, for example in Gambia, RSV activity peaked during the summer OSI-906 months between August and September over a 4-yr (1993 C 1996) period [23]. Therefore, knowledge about local RSV epidemics is definitely required for targeted prophylaxis with palivizumab in high-risk babies. In Austria an epidemiological monitoring system has been founded in OSI-906 2002 called RSV-hotline incorporating data of babies hospitalized due to RSV disease that are came into into the system voluntarily by Austrian pediatricians (https://hc4you.hcsolutions.at/rsv). The seasonal distributions of RSV attributed hospitalizations of preterm babies in Austria over the seasons 1998 to 2001 and 2001 to 2003 are demonstrated in Fig. (?1a1a, ?bb), respectively [11, 24]. Fig. (1) (a). Seasonal distribution of rehospitalisations due to respiratory illness (verified RSV and non-RSV infections) in premature babies of 29C36 weeks gestational age [24]. (b). Seasonal distribution of RSV hospitalizations (n=38) in premature babies … CLINICAL FEATURES OF RSV Illness IN PRETERM Babies The most common infection caused by RSV is definitely of the top respiratory tract; such infections are characterised by rhinitis, cough, and sometimes fever. OSI-906 Acute OSI-906 otitis press happens in up to a third of children with RSV illness; both RSV and bacterial pathogens have been isolated from the middle ears of children with RSV. Croup also happens with RSV illness, but bronchiolitis and pneumonia are the most common manifestations in children. Indications of upper-respiratory-tract involvement generally precede those of the lower respiratory tract by a few days, and fever, when present, is usually low grade. Dyspnoea, lower chest-wall indrawing, and difficulty in feeding characterise lower-respiratory-tract illness. In bronchiolitis, wheeze may be audible with or without a stethoscope, and a prolonged expiratory phase and crackles are characteristic. Air flow trapping results in very fast breathing and a palpable liver and spleen. The typical radiographic pattern includes hyperinflation with diffuse interstitial markings and peribronchial thickening. Segmental atelectasis, which usually clears spontaneously, is often seen. Children with pneumonia, on the other hand, have good crackles and a radiographic pattern of alveolar, segmental, or lobar consolidation. Severe bronchiolitis may lead to acute respiratory failure associated with severe bronchospasm, moderate to severe hypoxia, and carbon dioxide retention. With lung function checks [25] two patterns of severe disease are seen: in about two-thirds of instances there is obstructive small airways disease (bronchiolitis), and in the remainder there is a restrictive pattern (pneumonia). Most of the second option cases meet the criteria for acute respiratory distress OSI-906 syndrome. They tend to become younger, have more predisposing underlying disease, and are ventilated for longer. In severely ill children, complications include pulmonary hypertension and cardiovascular compromise requiring inotropic support [26]. Although bacterial superinfection is definitely rare in developed countries, it is more common in developing countries. This may partly explain the higher fatality rates seen in developing nations [4]. Over a five years period we observed a general low total rate of bacterial co-infection of 1 1.9% excluding ICU individuals [27]. The risk of concurrent bacterial infection in preterm babies hospitalized due to respiratory syncytial disease infection was three times higher compared to term babies (9.5 Haemophilus influenzae[30] examined the hypothesis that dysregulation of mucosal immune responses to respiratory infections is a critical event, which could be causal in respiratory arrest of some previously healthy infants..
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Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent
Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. had faster progression to AML versus patients with dose modifications (= .004). Without dose modifications patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. = .013). Patients with cycle delays or dose reductions received a median of 6 cycles of decitabine compared with those without cycle delays or dose reductions who received a median of 2 cycles of decitabine. Adverse events disease progression lost to follow-up patient choice and investigator decision were the main reasons given for patients discontinuing therapy. Table II Patients receiving decitabine who had myelosuppression and required dose modifications In both studies measurement of hematologic values (hemoglobin lymphocytes neutrophils platelets and white blood cells) over time showed that the incidence of grade 3 or 4 4 toxicities was highest in cycle 1 of decitabine therapy then generally decreased over time with subsequent cycles although all were frequent events likely a result of the underlying disease. The nadir in hematologic values in cycle 1 was expected from the known myelosuppressive effects of decitabine and the improvement in Gata1 mean nadir over successive cycles suggests an absence of cumulative hematologic toxicity. Effects of Dose Modifications on Response Patients who had dose modifications patients who had cycle delays or dose reductions and patients who had cycle delays had significantly higher ORRs compared with those who had none of these (≤ .015) (Table III). Table III Overall response rate for patients receiving decitabine by subgroups with or without dose modifications There was no significant difference in time to OSI-906 initial dose modification between responding and nonresponding patients. The median time for responders was 2.07 months and the median for nonresponders was OSI-906 2.10 months. Effects of Dose Modifications on Survival Patients who had dose modifications (Figure 1) and patients who had cycle delays or dose reductions (Figure 2) had median OS values similar to those of patients who had neither. Median OS was 16.1 months in patients who had dose modifications and 16.3 months in those who had cycle delays and/or dose reductions compared with 15.3 months and 15.2 months respectively in patients who had neither dose modifications nor cycle delays or dose reductions. Figure 1 Kaplan-Meier curves for overall survival in patients receiving decitabine with and without dose modifications adjusted for a time-dependent covariate Figure 2 Kaplan-Meier curves for overall survival in patients receiving decitabine with and without dose delays or dose reductions adjusted for a time-dependent covariate Effects of Dose Modification on Transformation to AML Of the 182 patients in the pooled analysis 46 (25.3%) underwent transformation to AML. No significant differences were observed in time to AML transformation between patients with and without dose modifications (Figure 3A) and between patients with and without dose delays or dose reductions (Figure 3B). Figure 3 Kaplan-Meier curves for time to AML progression in patients receiving decitabine: (A) with and without dose modifications and (B) with and without dose delays or dose reductions adjusted for a time-dependent covariate Predictors of Dose OSI-906 Modifications and Death Cox regression analysis including baseline covariates and time-dependent covariates identified several OSI-906 predictors of decitabine dose modification and death (Table IV). Platelet dependence at baseline was a significant predictor for dose modification (= .006) dose reduction or delay OSI-906 (= .011) and death (= .003). Study effect (DACO-020 5 regimen) was also a significant predictor for dose modification and dose reduction or delay (< .0001 in both cases). In addition IPSS-1 (= .002) and red blood cell dependence at baseline (= .0001) were also significant predictors for death. Table IV Predictors of dose modification dose reduction or delay progression OSI-906 to AML or death DISCUSSION The findings of this retrospective analysis of a pooled subset of data from patients with MDS enrolled in 2 clinical trials of decitabine suggest that the effects of decitabine dose modification or cycle delay or dose reduction may be beneficial for decitabine response although no significant effect on patient survival was found. In the pooled analysis dose modifications cycle delays or dose reductions and.