Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren

<STRONG>Background</STRONG> Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. <STRONG>Methods and Findings</STRONG> We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37–39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12–1.20; 33–36 wk adjusted OR 1.53, 95% CI 1.43–1.63; 28–32 wk adjusted OR 2.66, 95% CI 2.38–2.97; 24–27 wk adjusted OR 6.92, 95% CI 5.58–8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37–39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. <STRONG>Conclusions</STRONG> Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery

Examining the BMI-mortality relationship using fractional polynomials

<p>Abstract</p> <p>Background</p> <p>Many previous studies estimating the relationship between body mass index (BMI) and mortality impose assumptions regarding the functional form for BMI and result in conflicting findings. This study investigated a flexible data driven modelling approach to determine the nonlinear and asymmetric functional form for BMI used to examine the relationship between mortality and obesity. This approach was then compared against other commonly used regression models.</p> <p>Methods</p> <p>This study used data from the National Health Interview Survey, between 1997 and 2000. Respondents were linked to the National Death Index with mortality follow-up through 2005. We estimated 5-year all-cause mortality for adults over age 18 using the logistic regression model adjusting for BMI, age and smoking status. All analyses were stratified by sex. The multivariable fractional polynomials (MFP) procedure was employed to determine the best fitting functional form for BMI and evaluated against the model that includes linear and quadratic terms for BMI and the model that groups BMI into standard weight status categories using a deviance difference test. Estimated BMI-mortality curves across models were then compared graphically.</p> <p>Results</p> <p>The best fitting adjustment model contained the powers -1 and -2 for BMI. The relationship between 5-year mortality and BMI when estimated using the MFP approach exhibited a J-shaped pattern for women and a U-shaped pattern for men. A deviance difference test showed a statistically significant improvement in model fit compared to other BMI functions. We found important differences between the MFP model and other commonly used models with regard to the shape and nadir of the BMI-mortality curve and mortality estimates.</p> <p>Conclusions</p> <p>The MFP approach provides a robust alternative to categorization or conventional linear-quadratic models for BMI, which limit the number of curve shapes. The approach is potentially useful in estimating the relationship between the full spectrum of BMI values and other health outcomes, or costs.</p

Childhood body mass index trajectories: modeling, characterizing, pairwise correlations and socio-demographic predictors of trajectory characteristics

Background: Modeling childhood body mass index (BMI) trajectories, versus estimating change in BMI between specific ages, may improve prediction of later body-size-related outcomes. Prior studies of BMI trajectories are limited by restricted age periods and insufficient use of trajectory information. Methods: Among 3,289 children seen at 81,550 pediatric well-child visits from infancy to 18 years between 1980 and 2008, we fit individual BMI trajectories using mixed effect models with fractional polynomial functions. From each child's fitted trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and velocity and area under curve between 1 week, infancy peak, adiposity rebound, and 18 years. Results: Among boys, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1) and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity rebound were positively correlated (r = 0.76). Blacks had earlier adiposity rebound and greater velocity from adiposity rebound to 18 years of age than whites. Higher birth weight z-score predicted earlier adiposity rebound and higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ by birth year or type of health insurance, after adjusting for other socio-demographics and birth weight z-score. Conclusions: Childhood BMI trajectory characteristics are informative in describing childhood body mass changes and can be estimated conveniently. Future research should evaluate associations of these novel BMI trajectory characteristics with adult outcomes

Four-Year Treatment Outcomes of Adult Patients Enrolled in Mozambique's Rapidly Expanding Antiretroviral Therapy Program

BACKGROUND: In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004-2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4(+) T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3-1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6-2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. CONCLUSIONS: ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed

Procalcitonin Predicts Response to Beta-Lactam Treatment in Hospitalized Children with Community-Acquired Pneumonia

BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in children remains mostly empirical because clinical and paraclinical findings poorly discriminate the principal causes of CAP. Fast response to beta-lactam treatment can be considered a proxy of pneumococcal aetiology. We aimed to identify the best biological predictor of response to beta-lactam therapy in children hospitalized for CAP. METHODS: A retrospective, single-centre cohort study included all consecutive patients 1 month to 16 years old hospitalized in a teaching hospital in Paris, France, because of CAP empirically treated with a beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to study the ability of routine biological parameters available in the Emergency Department to predict a favourable response to beta-lactam (defined as apyrexia within 48 hours of treatment onset). RESULTS: Among the 125 included patients, 85% (106) showed a favourable response to beta-lactam. In multivariate logistic regression, we found procalcitonin (PCT) the only independent predictor of apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT was 4.3 (95% CI 1.5-12.7). At ≥ 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3), 78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2% negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42) and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT level ≥ 3 ng/mL and who showed no response to beta-lactam treatment, secondary pleural effusion had developed in 3, and viral co-infection was documented in 1. CONCLUSIONS: PCT is the best independent biologic predictor of favourable response to beta-lactam therapy in children hospitalized for CAP. Thus, a high PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut-off does not seem compatible with daily medical practice, and additional research is needed to further define the role of PCT in managing CAP in children

Tamoxifen resistance in early breast cancer: statistical modelling of tissue markers to improve risk prediction

BACKGROUND: For over two decades, the Nottingham Prognostic Index (NPI) has been used in the United Kingdom to calculate risk scores and inform management about breast cancer patients. It is derived using just three clinical variables - nodal involvement, tumour size and grade. New scientific methods now make cost-effective measurement of many biological characteristics of tumour tissue from breast cancer biopsy samples possible. However, the number of potential explanatory variables to be considered presents a statistical challenge. The aim of this study was to investigate whether in ER+ tamoxifen-treated breast cancer patients, biological variables can add value to NPI predictors, to provide improved prognostic stratification in terms of overall recurrence-free survival (RFS) and also in terms of remaining recurrence free while on tamoxifen treatment (RFoT). A particular goal was to enable the discrimination of patients with a very low risk of recurrence. METHODS: Tissue samples of 401 cases were analysed by microarray technology, providing biomarker data for 72 variables in total, from AKT, BAD, HER, MTOR, PgR, MAPK and RAS families. Only biomarkers screened as potentially informative (i.e., exhibiting univariate association with recurrence) were offered to the multivariate model. The multiple imputation method was used to deal with missing values, and bootstrap sampling was used to assess internal validity and refine the model. RESULTS: Neither the RFS nor RFoT models derived included Grade, but both had better predictive and discrimination ability than NPI. A slight difference was observed between models in terms of biomarkers included, and, in particular, the RFoT model alone included HER2. The estimated 7-year RFS rates in the lowest-risk groups by RFS and RFoT models were 95 and 97%, respectively, whereas the corresponding rate for the lowest-risk group of NPI was 89%. CONCLUSION: The findings demonstrate considerable potential for improved prognostic modelling by incorporation of biological variables into risk prediction. In particular, the ability to identify a low-risk group with minimal risk of recurrence is likely to have clinical appeal. With larger data sets and longer follow-up, this modelling approach has the potential to enhance an understanding of the interplay of biological characteristics, treatment and cancer recurrence. British Journal of Cancer (2010) 102, 1503 - 1510. doi:10.1038/sj.bjc.6605627 www.bjcancer.co

Perceptions of surgical specialists in general surgery, orthopaedic surgery, urology and gynaecology on teaching endoscopic surgery in The Netherlands

BACKGROUND: Specific training in endoscopic skills and procedures has become a necessity for profession with embedded endoscopic techniques in their surgical palette. Previous research indicates endoscopic skills training to be inadequate, both from subjective (resident interviews) and objective (skills measurement) viewpoint. Surprisingly, possible shortcomings in endoscopic resident education have never been measured from the perspective of those individuals responsible for resident training, e.g. the program directors. Therefore, a nation-wide survey was conducted to inventory current endoscopic training initiatives and its possible shortcomings among all program directors of the surgical specialties in the Netherlands. METHODS: Program directors for general surgery, orthopaedic surgery, gynaecology and urology were surveyed using a validated 25-item questionnaire. RESULTS: A total of 113 program directors responded (79%). The respective response percentages were 73.6% for general surgeons, 75% for orthopaedic surgeon, 90.9% for urologists and 68.2% for gynaecologists. According to the findings, 35% of general surgeons were concerned about whether residents are properly skilled endoscopically upon completion of training. Among the respondents, 34.6% were unaware of endoscopic training initiatives. The general and orthopaedic surgeons who were aware of these initiatives estimated the number of training hours to be satisfactory, whereas the urologists and gynaecologists estimated training time to be unsatisfactory. Type and duration of endoscopic skill training appears to be heterogeneous, both within and between the specialties. Program directors all perceive virtual reality simulation to be a highly effective training method, and a multimodality training approach to be key. Respondents agree that endoscopic skills education should ideally be coordinated according to national consensus and guidelines. CONCLUSIONS: A delicate balance exists between training hours and clinical working hours during residency. Primarily, a re-allocation of available training hours, aimed at core-endoscopic basic and advanced procedures, tailored to the needs of the resident and his or her phase of training is in place. The professions need to define which basic and advanced endoscopic procedures are to be trained, by whom, and by what outcome standards. According to the majority of program directors, virtual reality (VR) training needs to be integrated in procedural endoscopic training course