Treatment failure in pneumonia: Impact of antibiotic treatment and cost analysis

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p<0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with β-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27-0.68) and was more comparable with a β-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.

The cam-type deformity of the proximal femur arises in childhood in response to vigorous sporting activity

The prevalence of a cam-type deformity in athletes and its association with vigorous sports activities during and after the growth period is unknown.

Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study

Background Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. Methods We computed person-years at risk for children aged 0–15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place of residence at birth and calculated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing the risk of cancer in children born <5 km, 5–10 km and 10–15 km from the nearest NPP with children born >15 km away, using Poisson regression models. Results We included 2925 children diagnosed with cancer during 21 117 524 person-years of follow-up; 953 (32.6%) had leukaemia. Eight and 12 children diagnosed with leukaemia at ages 0–4 and 0–15 years, and 18 and 31 children diagnosed with any cancer were born <5 km from a NPP. Compared with children born >15 km away, the IRRs (95% CI) for leukaemia in 0–4 and 0–15 year olds were 1.20 (0.60–2.41) and 1.05 (0.60–1.86), respectively. For any cancer, corresponding IRRs were 0.97 (0.61–1.54) and 0.89 (0.63–1.27). There was no evidence of a dose–response relationship with distance (P > 0.30). Results were similar for residence at diagnosis and at birth, and when adjusted for potential confounders. Results from sensitivity analyses were consistent with main results. Conclusions This nationwide cohort study found little evidence of an association between residence near NPPs and the risk of leukaemia or any childhood cancer.

Daily Physical Activities and Sports in Adult Survivors of Childhood Cancer and Healthy Controls: A Population-Based Questionnaire Survey

Background Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. Methodology/Principal Findings The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976–2003 at age 0–15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5years and reached adulthood (≥20years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35years: 1.5, 95CI 1.2–2.0), female gender (OR 1.6, 95CI 1.3–1.9), French/Italian Speaking (OR 1.4, 95CI 1.1–1.7), and higher education (OR for university education: 2.0, 95CI 1.5–2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1–1.6), older age (OR for ≥35years: 1.4, 95CI 1.1–1.8), migration background (OR 1.5, 95CI 1.3–1.8), French/Italian speaking (OR 1.4, 95CI 1.2–1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2–2.2), being married (OR 1.7, 95CI 1.5–2.0), having children (OR 1.3, 95CI 1.4–1.9), obesity (OR 2.4, 95CI 1.7–3.3), and smoking (OR 1.7, 95CI 1.5–2.1). Type of diagnosis was only associated with sports. Conclusions/Significance Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.

Alcohol consumption and binge drinking in young adult childhood cancer survivors

Background This study compared frequency of alcohol consumption and binge drinking between young adult childhood cancer survivors and the general population in Switzerland, and assessed its socio-demographic and clinical determinants. Procedure Childhood cancer survivors aged <16 years when diagnosed 1976–2003, who had survived >5 years and were currently aged 20–40 years received a postal questionnaire. Reported frequency of alcohol use and of binge drinking were compared to the Swiss Health Survey, a representative general population survey. Determinants of frequent alcohol consumption and binge drinking were assessed in a multivariable logistic regression. Results Of 1,697 eligible survivors, 1,447 could be contacted and 1,049 (73%) responded. Survivors reported more often than controls to consume alcohol frequently (OR = 1.7; 95%CI = 1.3–2.1) and to engage in binge drinking (OR = 2.9; 95%CI = 2.3–3.8). Peak frequency of binge drinking in males occurred at age 24–26 years in survivors, compared to age 18–20 in the general population. Socio-demographic factors (male gender, high educational attainment, French and Italian speaking, and migration background from Northern European countries) were most strongly associated with alcohol consumption patterns among both survivors and controls. Conclusions The high frequency of alcohol consumption found in this study is a matter of concern. Our data suggest that survivors should be better informed on the health effects of alcohol consumption during routine follow-up, and that such counseling should be included in clinical guidelines. Future research should study motives of alcohol consumption among survivors to allow development of targeted health interventions for this vulnerable group.

Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance

The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals.

Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study

Purpose Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors. Methods We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression. Results Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor. Conclusion We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.

Educational achievement in Swiss childhood cancer survivors compared with the general population

The objective of this study was to describe educational achievements of childhood cancer survivors in Switzerland compared with the general population. In particular, the authors investigated educational problems during childhood, final educational achievement in adulthood, and its predictors.

Quantitative PCR to diagnose Pneumocystis pneumonia in immunocompromised non-HIV patients

The utility of quantitative Pneumocystis jirovecii PCR in clinical routine for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised non-HIV patients is unknown. We analysed bronchoalveolar lavage fluid with real-time quantitative P. jirovecii PCR in 71 cases with definitive PCP defined by positive immunofluorescence (IF) tests and in 171 randomly selected patients with acute lung disease. In those patients, possible PCP cases were identified by using a novel standardised PCP probability algorithm and chart review. PCR performance was compared with IF testing, clinical judgment and the PCP probability algorithm. Quantitative P. jirovecii PCR values >1,450 pathogens·mL(-1) had a positive predictive value of 98.0% (95% CI 89.6-100.0%) for diagnosing definitive PCP. PCR values of between 1 and 1,450 pathogens·mL(-1) were associated with both colonisation and infection; thus, a cut-off between the two conditions could not be identified and diagnosis of PCP in this setting relied on IF and clinical assessment. Clinical PCP could be ruled out in 99.3% of 153 patients with negative PCR results. Quantitative PCR is useful for diagnosing PCP and is complementary to IF. PCR values of >1,450 pathogens·mL(-1) allow reliable diagnosis, whereas negative PCR results virtually exclude PCP. Intermediate values require additional clinical assessment and IF testing. On the basis of our data and for economic and logistical limitations, we propose a clinical algorithm in which IF remains the preferred first test in most cases, followed by PCR in those patients with a negative IF and strong clinical suspicion for PCP.

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is known that overexpression and/or amplification of the MYC oncogene is associated with poor clinical outcome, but the molecular mechanisms and the MYC downstream effectors in MB remain still elusive. Besides contributing to elucidate how progression of MB takes place, most importantly, the identification of novel MYC-target genes will suggest novel candidates for targeted therapy in MB. A group of 209 MYC-responsive genes was obtained from a complementary DNA microarray analysis of a MB-derived cell line, following MYC overexpression and silencing. Among the MYC-responsive genes, we identified the members of the bone morphogenetic protein (BMP) signaling pathway, which have a crucial role during the development of the cerebellum. In particular, the gene BMP7 was identified as a direct target of MYC. A positive correlation between MYC and BMP7 expression was documented by analyzing two distinct sets of primary MB samples. Functional studies in vitro using a small-molecule inhibitor of the BMP/SMAD signaling pathway reproduced the effect of the small interfering RNA-mediated silencing of BMP7. Both approaches led to a block of proliferation in a panel of MB cells and to inhibition of SMAD phosphorylation. Altogether, our findings indicate that high MYC levels drive BMP7 overexpression, promoting cell survival in MB cells. This observation suggests the potential relevance of targeting the BMP/SMAD pathway as a novel therapeutic approach for the treatment of childhood MB.

[Needle in the haystack - potentially dangerous syncope in childhood]

Syncope is a frequently observed symptom in pediatrics with teenagers being the age group most often affected. In contrast to older age, organic cardiac causes of syncope in child-hood are observed in a minority of only 2-5% of cases, in their majority pediatric syncopes thus are neurocardiogenic in origin. The rare organic cardiac causes that may manifest with syncope are all potentially dangerous entities such as cardiomyopathies, genetic primary electrical disease and some forms of structural heart disease, as well as some other rare diseases such as e.g. primary pulmonary hypertension. These diseases have to be actively looked for or excluded. Guidelines recommend patient evaluation including history, physical examination and ECG, which is sufficient to sort out suspect cases after a syncopal episode.