Improved Statistical Modeling of Tumor Growth and Treatment Effect in Preclinical Animal Studies with Highly Heterogeneous Responses In Vivo

Conclusions: In general, the modeling framework enables identification of such biologically significant differences in tumor growth profiles that would have gone undetected or had required considerably higher number of animals when using traditional statistical methods. Clin Cancer Res; 18(16); 4385-96. (C) 2012 AACR.</p

Sense of coherence and diabetes: A prospective occupational cohort study

<p>Abstract</p> <p>Background</p> <p>Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes.</p> <p>Methods</p> <p>The relationship between a weak SOC and the incidence of diabetes was investigated among 5827 Finnish male employees aged 18–65 at baseline (1986). SOC was measured by questionnaire survey at baseline. Data on prescription diabetes drugs from 1987 to 2004 were obtained from the Drug Imbursement Register held by the Social Insurance Institution.</p> <p>Results</p> <p>During the follow-up, 313 cases of diabetes were recorded. A weak SOC was associated with a 46% higher risk of diabetes in participants who had been =<50 years of age on entry into the study. This association was independent of age, education, marital status, psychological distress, self-rated health, smoking status, binge drinking and physical activity. No similar association was observed in older employees.</p> <p>Conclusion</p> <p>The results suggest that besides focusing on well-known risk factors for diabetes, strengthening SOC in employees of =<50 years of age can also play a role in attempts to tackle increasing rates of diabetes.</p

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland

Myotonic dystrophy (DM) is the most common adult-onset muscular dystrophy with an estimated prevalence of 1/8000. There are two genetically distinct types, DM1 and DM2. DM2 is generally milder with more phenotypic variability than the classic DM1. Our previous data on co-segregation of heterozygous recessive CLCN1 mutations in DM2 patients indicated a higher than expected DM2 prevalence. The aim of this study was to determine the DM2 and DM1 frequency in the general population, and to explore whether the DM2 mutation functions as a modifier in other neuromuscular diseases (NMD) to account for unexplained phenotypic variability. We genotyped 5535 Finnish individuals: 4532 normal blood donors, 606 patients with various non-myotonic NMD, 221 tibial muscular dystrophy patients and their 176 healthy relatives for the DM2 and DM1 mutations. We also genotyped an Italian idiopathic non-myotonic proximal myopathy cohort (n=93) for the DM2 mutation. In 5496 samples analyzed for DM2, we found three DM2 mutations and two premutations. In 5511 samples analyzed for DM1, we found two DM1 mutations and two premutations. In the Italian cohort, we identified one patient with a DM2 mutation. We conclude that the DM2 mutation frequency is significantly higher in the general population (1/1830; P-value=0.0326) than previously estimated. The identification of DM2 mutations in NMD patients with clinical phenotypes not previously associated with DM2 is of particular interest and is in accord with the high overall prevalence. On the basis of our results, DM2 appears more frequent than DM1, with most DM2 patients currently undiagnosed with symptoms frequently occurring in the elderly population