Search

Aim: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy. Method: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n = 169) and another group received standard formula supplemented with LCPUFAs (n = 146). A breastfed group (n = 159) served as an additional reference. At 9 years of age, 72% of the children (control group: n = 123; 71 males, 52 females; LCPUFA group: n = 91; 42 males, 49 females; breastfed group: n = 127, 64 males, 63 females) underwent extensive cognitive and behavioural testing. Results: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p = 0.007) and learning and memory (p = 0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p = 0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p = 0.001). Breastfeeding was associated with better performance on IQ (p = 0.005). Interpretation: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition. (Contains 2 tables and 1 figure.)

Aim: The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour of infants aged 3 to 18 months. The aim of this study was to investigate construct validity of the IMP through the relation of IMP scores with prenatal, perinatal, and neonatal variables, including the presence of brain pathology indicated by neonatal ultrasound imaging of the brain. Method: A longitudinal prospective study was performed in a group of 30 term infants (12 females, 18 males; median gestational age 40.1wks, range 37.6-42wks) and 59 preterm infants (25 females, 34 males; median gestational age 29.7wks, range 25-34.7wks). IMP assessments were performed at (corrected) ages of 4, 6, 10, 12, and 18 months. Socio-economic and perinatal data were collected, which, in the case of preterm infants, included information on periventricular leukomalacia and intraventricular hemorrhage based on neonatal cranial ultrasound. Data were analysed by fitting mixed-effects models. Results: Gestational age, socio-economic status, and 5-minute Apgar scores were significant determinants of IMP scores in the total group of infants (p less than 0.001, less than 0.002, and less than 0.042 respectively). In the subgroup of preterm infants, IMP scores were significantly affected by brain lesions on neonatal ultrasound (p less than 0.001) and by socio-economic status (p = 0.001). Interpretation: The findings support the construct validity of the IMP: IMP scores are clearly associated with relevant determinants of neuromotor function.

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient-years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO-identical and 23 (6.1%) ABO-compatible. The 5-year cumulative incidence of death was 11.2% ( SE 1.4%), and of transplantation 72.5% ( SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation. [ABSTRACT FROM AUTHOR]

The problem of discrimination and classification is central to much of epidemiology. Here we consider the estimation of a logistic regression/discrimination function from training samples, when one of the training samples is subject to misclassification or mislabeling, e.g. diseased individuals are incorrectly classified/labeled as healthy controls. We show that this leads to zero-inflated binomial model with a defective logistic regression or discrimination function, whose parameters can be estimated using standard statistical methods such as maximum likelihood. These parameters can be used to estimate the probability of true group membership among those, possibly erroneously, classified as controls. Two examples are analyzed and discussed. A simulation study explores properties of the maximum likelihood parameter estimates and the estimates of the number of mislabeled observations. [ABSTRACT FROM AUTHOR]

Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented. [ABSTRACT FROM AUTHOR]

Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age. A prospective, double-blind, randomised control study was performed in two groups of healthy term infants: a control group with standard formula (n 169) and a LCPUFA-supplemented group (LF; n 146). A breast-fed group (BF; n 159) served as a reference. At age 9 years, children were neurologically assessed according to Touwen, resulting in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction (MND). Information on potential confounders was collected at enrolment and follow-up. Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders. Attrition (28 %) was selective: drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months. Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups. Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children. In conclusion, LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age. The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants. [ABSTRACT FROM PUBLISHER]

It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a model that predicts the outcome of su pervised exercise for intermittent claudication. The authors present an example of the use of autoregressive logistic regression for modeling observed longitudinal data. Data were collected from 329 participants in a six-month exercise program. The levels of the polytomous outcome variable correspond to states they defined in a Markov de cision model comparing treatment strategies for intermittent claudication. Autoregres sive logistic regression can be used to fit multistate transition models to observed longitudinal data with standard statistical software. The technique allows exploration of alternative assumptions about the dependence in the outcome series and provides transition probabilities for different covariate patterns. Of the alternatives examined, a Markov model including two preceding responses, time, age, ankle brachial index, and duration of disease best described the data. Key words: longitudinal data analysis; autoregressive models; logistic regression; Markov models; peripheral arterial occlu sive disease; intermittent claudication; exercise. (Med Decis Making 1998;18:52- 60) [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcomes in children. Design: Prospective, assessor-blinded, follow-up study of children born to women randomly assigned to in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) with or without PGS. Setting: University Medical Center, Groningen, and Academic Medical Center, Amsterdam, the Netherlands. Patient(s): Fifty-four PGS children and 77 controls. Intervention(s): PGS. Main Outcome Measure(s): Mental, psychomotor, neurologic, and behavioral outcomes in 2-year-old children as measured with the Bayley Scales of Infant Development, the Hempel neurologic examination, and the Child Behavior Check List. Result(s): The mental, psychomotor, and behavioral outcomes at 2 years in children born after IVF with and without PGS were similar overall. The PGS children showed lower neurologic optimality scores than the control children. Scores on all tests were within the normal range. Conclusion(s): Conception with PGS does not seem to be associated with impaired mental, psychomotor, or behavioral outcomes by age 2. However, the lower neurologic optimality scores found in the PGS children may signal less favorable long-term neurologic outcomes in PGS children. Our findings stress the need for safety evaluations with new assisted reproductive techniques before large-scale implementation. [ABSTRACT FROM AUTHOR]

Background: Determining the stage of non–small-cell lung cancer often requires multiple preoperative tests and invasive procedures. Whole-body positron-emission tomography (PET) may simplify and improve the evaluation of patients with this tumor. Methods: We prospectively compared the ability of a standard approach to staging (computed tomography [CT], ultrasonography, bone scanning, and, when indicated, needle biopsies) and one involving PET to detect metastases in mediastinal lymph nodes and at distant sites in 102 patients with resectable non–small-cell lung cancer. The presence of mediastinal metastatic disease was confirmed histopathologically. Distant metastases that were detected by PET were further evaluated by standard imaging tests and biopsies. Patients were followed postoperatively for six months by standard methods to detect occult metastases. Logistic-regression analysis was used to evaluate the ability of PET and CT to identify malignant mediastinal lymph nodes. Results: The sensitivity and specificity of PET for the detection of mediastinal metastases were 91 percent (95 percent confidence interval, 81 to 100 percent) and 86 percent (95 percent confidence interval, 78 to 94 percent), respectively. The corresponding values for CT were 75 percent (95 percent confidence interval, 60 to 90 percent) and 66 percent (95 percent confidence interval, 55 to 77 percent). When the results of PET and CT were adjusted for each other, only PET results were positively correlated with the histopathological findings in mediastinal lymph nodes (P<0.001). PET identified distant metastases that had not been found by standard methods in 11 of 102 patients. The sensitivity and specificity of PET for the detection of both mediastinal and distant metastatic disease were 95 percent (95 percent confidence interval, 88 to 100 percent) and 83 percent (95 percent confidence interval, 74 to 92 percent), respectively. The use of PET for clinical staging resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42. Conclusions: PET improves the rate of detection of local and distant metastases in patients with non–small-cell lung cancer. (N Engl J Med 2000;343:254-61.) [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether including a test for faecal calprotectin, a sensitive marker of intestinal inflammation, in the investigation of suspected inflammatory bowel disease reduces the number of unnecessary endoscopic procedures., Design: Meta-analysis of diagnostic accuracy studies., Data Sources: Studies published in Medline and Embase up to October 2009. Interventions reviewed Measurement of faecal calprotectin level (index test) compared with endoscopy and histopathology of segmental biopsy samples (reference standard). Inclusion criteria Studies that had collected data prospectively in patients with suspected inflammatory bowel disease and allowed for construction of a two by two table. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data to account for a possible negative correlation within studies., Results: 13 studies were included: six in adults (n=670), seven in children and teenagers (n=371). Inflammatory bowel disease was confirmed by endoscopy in 32% (n=215) of the adults and 61% (n=226) of the children and teenagers. In the studies of adults, the pooled sensitivity and pooled specificity of calprotectin was 0.93 (95% confidence interval 0.85 to 0.97) and 0.96 (0.79 to 0.99) and in the studies of children and teenagers was 0.92 (0.84 to 0.96) and 0.76 (0.62 to 0.86). The lower specificity in the studies of children and teenagers was significantly different from that in the studies of adults (P=0.048). Screening by measuring faecal calprotectin levels would result in a 67% reduction in the number of adults requiring endoscopy. Three of 33 adults who undergo endoscopy will not have inflammatory bowel disease but may have a different condition for which endoscopy is inevitable. The downside of this screening strategy is delayed diagnosis in 6% of adults because of a false negative test result. In the population of children and teenagers, 65 instead of 100 would undergo endoscopy. Nine of them will not have inflammatory bowel disease, and diagnosis will be delayed in 8% of the affected children., Conclusion: Testing for faecal calprotectin is a useful screening tool for identifying patients who are most likely to need endoscopy for suspected inflammatory bowel disease. The discriminative power to safely exclude inflammatory bowel disease was significantly better in studies of adults than in studies of children.

Background and Objectives: Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition., Design, Setting, Participants, & Measurements: Thirty-nine GSD I patients that visited our clinic were studied. GFR and effective renal plasma flow (ERPF) were measured by means of I(125) iothalamate and I(131) hippuran clearance and corrected for body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06 mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450 micromol/L., Results: Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbuminuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition., Conclusions: This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the development of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the GFR, especially in GSD I patients with glomerular hyperfiltration.

Background: The time distribution of injuries is not random. To assess the potential impact of weather and the phase of the moon on accidents, adjustment for known periodic and nonperiodic factors may be important. We compared the incidence of injuries with quantitative and qualitative weather variables as well as the lunar cycle, after correction for calendar and holiday-related factors., Methods: We extracted the daily number of trauma patients treated at the emergency department over 36 years (1970-2005) from the trauma database of our regional hospital. For each patient, age, sex, cause of injury, and severity of injury were recorded. This was combined with daily meteorological data including temperature, precipitation, sunshine, humidity, air pressure, and wind as well as the lunar phase. We also related the rate of change of these parameters with the incidence of injuries. A qualitative weather variable derived from temperature, sunshine duration, and precipitation was defined as bad, normal, or good. Periodicities were adjusted for with Poisson regression spline fitting analysis., Results: Several weather variables were related with the number of injuries. For most of these, better weather conditions were associated with an increase in trauma incidence. Good weather, which was present on 16.5% of the days, resulted in 10.1% (9.3-11.4 95% CI) more traumas compared with normal weather. Full moon was associated with a 2.1% (1.1-3.0 95% CI) lower trauma incidence than new moon., Conclusions: Better weather conditions contribute to an increased incidence of trauma. Full moon is associated with a slightly lower trauma incidence.

Objective: To study the impact of perineural growth as a prognostic factor in periampullary adenocarcinoma (pancreatic head, ampulla of Vater, distal bile duct, and duodenal carcinoma)., Summary Background Data: Pancreatic head carcinoma is considered to have the worst prognosis of the periampullary carcinomas. Several other prognostic factors for periampullary tumors have been identified, eg, lymph node status, free resection margins, tumor size and differentiation, and vascular invasion. The impact of perineural growth as a prognostic factor in relation to the site of origin of periampullary carcinomas is unknown., Methods: Data of 205 patients with periampullary carcinomas were retrieved from our prospective database. Pancreaticoduodenectomy was performed in 121 patients. Their clinicopathological data were reviewed and analyzed in a multivariate analysis., Results: Perineural growth was present in 49% of the cases (37 of the 51 patients with pancreatic head carcinoma; 7 of the 30 patients with ampulla of Vater carcinoma; 7 of the 19 with distal bile duct carcinoma; and 8 of the 21 with duodenal carcinoma). Overall 5-year survival was 32.6% with a median survival of 20.7 months. Median survival in tumors with perineural growth was 13.1 months compared with 36.0 months in tumors without perineural growth (P < 0.0001) Using multivariate analysis, the following unfavorable prognostic factors were identified: perineural growth (RR = 2.90, 95% CI 1.62-5.22), nonradical resection (RR = 2.28, 95% CI 1.19-4.36), positive lymph nodes (RR = 1.96, 95% CI 1.11-3.45), and angioinvasion (RR = 1.79, 95% CI 1.05-3.06). Portal or superior mesenteric vein reconstruction and tumor localization were not of statistical significance., Conclusion: Perineural growth is a more important risk factor for survival than the primary site of periampullary carcinomas.

Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express the vascular endothelial growth factors, VEGFA and VEGFC, as well as kinase insert domain-containing receptor (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. This study investigates the role of the VEGFR inhibitor PTK787/ZK 222584 in leukemic cell death, and the possibility of an additional effect on cell death by a chemotherapeutic drug, amsacrine. In three AML cell lines and 33 pediatric AML patient samples, we performed total cell-kill assays to determine the percentages of cell death achieved by PTK787/ZK 222584 and/or amsacrine. Both drugs induced AML cell death. Using a response surface analysis, we could show that, in cell lines as well as in primary AML blasts, an equal magnitude of leukemic cell death could be obtained when lower doses of the more toxic amsacrine were combined with low dosages of the less toxic VEGFR inhibitor. This study shows that PTK787/ZK 222584 might have more clinical potential in AML when combined with a chemotherapeutic drug such as amsacrine. In future, it will be interesting to study whether the complications and the long-term effects of chemotherapy can be reduced by lowering the dosages of amsacrine, and by replacing it with other drugs with lower toxicity profiles, such as PTK787/ZK 222584.

Objectives: In low back pain, clinical studies suggest that kinesiophobia (fear of movement/(re)injury) is important in the etiology of chronic symptoms. In this prospective cohort study, the predictive role of kinesiophobia in the development of late whiplash syndrome was examined., Methods: Victims of car collisions with neck symptoms who initiated compensation claim procedures with a Dutch insurance company were sent a questionnaire containing symptom-related questions and the Tampa Scale of Kinesiophobia (TSK-DV). Follow-up questionnaires were administered 6 and 12 months after the collision. Survival analysis was used to study the relationship between the duration of neck symptoms and explanatory variables., Results: Of the 889 questionnaires sent, 590 (66%) were returned and 367 used for analysis. The estimated percentage of subjects with neck symptoms persisting 1 year after the collision was 47% (SE 2.7%). In a regression model without symptom-related variables, kinesiophobia was found to be related to a longer duration of neck symptoms (P=0.001). However, when symptom-related information was entered into the model, the effect of kinesiophobia did not reach statistical significance (P=0.089)., Conclusions: Although a higher score on the TSK-DV was found to be associated with a longer duration of neck symptoms, information on early kinesiophobia was not found to improve the ability to predict the duration of neck symptoms after motor vehicle collisions.

Background: The axillary nodal status may influence the prognosis and the choice of adjuvant treatment of individual breast cancer patients. The variation in number of reported axillary lymph nodes and its effect on the axillary nodal stage were studied and the implications are discussed., Methods: Between 1994 and 1997, a total of 4,806 axillary dissections for invasive breast cancers in 4,715 patients were performed in hospitals in the North-Netherlands. The factors associated with the number of reported nodes and the relation of this number with the nodal status and the number of positive nodes were studied., Results: The number of reported nodes varied significantly between pathology laboratories, the median number of nodes ranged from 9 to 15, respectively. The individual hospitals explained even more variability in the number of nodes than pathology laboratories (range in median number 8-15, P < 0.0001). The number of reported nodes increased gradually during the study period. A decreasing trend was observed with older patient age. A higher number of reported nodes was associated with a markedly increased chance of finding tumor positive nodes, especially more than three nodes. The frequency of node positivity increased from 28% if less than six nodes to 54% if >/=20 nodes were examined, the percentage of tumors with >/=4 positive nodes increased from 4 to 31%. Multivariate analysis confirmed these results., Conclusions: This population-based study showed a large variation in the number of reported lymph nodes between hospitals. A more extensive surgical dissection or histopathological examination of the specimen generally resulted in a higher number of positive nodes. Although the impact of misclassification on adjuvant treatment will have varied, the impact with regard to adjuvant regional radiotherapy may have been considerable., (Copyright 2004 Wiley-Liss, Inc.)

Substantial improvements in long-term survival have been made with acute myeloid leukemia (AML). However, the overall success rate in treatment of AML is around 50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be related to vascular endothelial growth factor (VEGF). The purpose of this study was to investigate whether VEGF production by AML cells is a prognostic factor for therapeutic outcome and whether this is independent of known prognostic factors such as WBC count, French-American-British (FAB) classification, and risk assessment in which the presence of t(8;21), t(15;17), and inv(16) or FAB M3 defines a low-risk group. Pretreatment levels were measured in the supernatant of AML cells obtained from 47 children with newly diagnosed AML treated between 1988 and 1998. All patients were treated with intensive chemotherapeutic protocols from the Dutch Childhood Leukemia Study Group [DCLSG (DCLSG-ANLL87, DCLSG-ANLL92/94, and DCLSG-ANLL97)]. VEGF was measured at the mRNA level with reverse transcription-PCR and at the protein level using a VEGF immunoassay. VEGF in the supernatant from AML cells was highly variable and in concordance with reverse transcription-PCR results. The low-risk group had significantly lower VEGF levels compared with all others (P = 0.002). VEGF levels were significantly increased in AML FAB M4/M5 versus AML patients with FAB M1/M2/M3/M4eo (P = 0.011), who are reported to have a longer remission duration. Subsequently, the influence of different variables on therapeutic outcome was analyzed. No differences were found in overall survival. But within the limits of the small patient population, VEGF levels as well as age at diagnosis had an independent significant effect on relapse-free survival (P = 0.032 and P = 0.029, respectively) in multivariate analysis.