Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

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.

Effects of long-chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age.

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.

The Groningen LCPUFA study: no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years.

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 enrollment 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.

The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features. MATERIALS AND METHODS: A retrospective, descriptive, comparative histopathological study was completed utilizing step sections of 43 biopsies of 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies of 19 cases with an established diagnosis of GPP. RESULTS: In AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. Comparing AGEP and GPP, the presence of eosinophils, necrotic keratinocytes, a mixed interstitial and mid-dermal perivascular infiltrate and absence of tortuous or dilated blood vessels were in favor of AGEP. Moreover, chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in our study was higher than that of psoriasis in the general population. However, histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from the other AGEP patients. CONCLUSIONS: The spectrum of histopathological features of both AGEP and GPP is presented. Despite considerable overlap, subtle consistent histopathological differences and the grade of severity of specific features can help in differentiation. We could neither substantiate earlier reports that follicular pustules exclude AGEP nor did we see vasculitis as a specific feature in AGEP. Our study also supports the concept that AGEP is a separate entity that is distinct from GPP.

Construct validity of the Infant Motor Profile: relation with prenatal, perinatal, and neonatal risk factors.

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 40.1 wks, range 37.6-42 wks) and 59 preterm infants (25 females, 34 males; median gestational age 29.7 wks, range 25-34.7 wks). 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 haemorrhage 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<0.001, <0.002, and <0.042 respectively). In the subgroup of preterm infants, IMP scores were significantly affected by brain lesions on neonatal ultrasound (p<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.

The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities.

BACKGROUND: 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. METHOD: 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. FINDINGS: 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. CONCLUSIONS: 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.

Relation of the weather and the lunar cycle with the incidence of trauma in the Groningen region over a 36-year period.

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.

Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization.

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.

Prognostic classification with laboratory parameters or imaging techniques in small-cell lung cancer.

PURPOSE: Our aim in this study was to compare prognostic models based on laboratory tests with a model including imaging information in small-cell lung cancer. PATIENTS AND METHODS: A retrospective analysis was performed on 156 consecutive patients. Three existing models based on laboratory tests and performance status (PS) and a model based on disease stage assessed by imaging techniques and PS were tested with Cox regression analysis. RESULTS: The 3 laboratory-based models and the imaging-based model were significant in predicting prognosis in our patient group, with hazard ratios of 1.6-3 for medium prognosis groups and 2.6-6.1 for poor prognosis groups compared with good prognosis groups. Models based on laboratory tests appear to predict survival probabilities at least as well as a model with information from imaging techniques. CONCLUSION: Prognostic models using PS and laboratory tests provide a similar estimation of survival of patients with small-cell lung cancer as the combination of PS and disease stage assessed by imaging tests.

Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers.

BACKGROUND: Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC. PATIENTS AND METHODS: Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer. RESULTS: Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37-0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR(10) (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89-0.99), p53 (RR(10) = 0.94, 95% CI, 0.89-0.99) and FasL (RR(10) = 0.92, 95% CI, 0.86-0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response. CONCLUSION: Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.

Increased intima-media thickness after early-onset preeclampsia.

OBJECTIVE: Preeclampsia is associated with cardiovascular atherosclerotic events later in life. However, little is known about earlier subclinical signs of atherosclerosis. We aimed to investigate whether women who recently had preeclampsia show increased intima-media thickness (IMT), as marker of early atherosclerosis, compared with women with normal pregnancies or nulliparous women. METHODS: Intima-media thickness of carotid and femoral arteries measured by ultrasonography, and possible confounding risk factors as body mass index, blood pressure, serum lipids, smoking status, and family history of cardiovascular disease were compared among 22 nulliparous women, 22 primiparous women with normal pregnancy, and 22 primiparous women with early-onset preeclampsia at least 3 months postpartum and 6 weeks after ending lactation RESULTS: Except for slightly higher values for blood pressure, triglycerides, and homocysteine in the formerly preeclamptic women, no other clinical or biochemical differences were observed. The preeclampsia group showed an increased IMT (mean +/- standard deviation, 0.63 +/- 0.14 mm) of the common femoral artery compared with the normal pregnancy group (0.55 +/- 0.06 mm, P = .005) and to the nulliparous group (0.52 +/- 0.06 mm, P < .001). These differences remained significant after correction for possible confounders by multiple linear regression analyses. An increase in IMT of the common carotid artery between the normal pregnancy and the nulliparous group was observed, which became significant after adjustment for confounders. CONCLUSION: Preeclampsia and, to a lesser degree, normal pregnancy are associated with increased IMT. The association between increased IMT and (preeclamptic) pregnancy leads to the question of which comes first, which should be addressed in follow-up studies. LEVEL OF EVIDENCE: II-2.

Can kinesiophobia predict the duration of neck symptoms in acute whiplash?

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.

Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.

BACKGROUND: For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population. METHODS AND RESULTS: In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality. CONCLUSIONS: Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.

Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients.

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.

Estimating a Logistic Discrimination Functions When One of the Training Samples Is Subject to Misclassification: A Maximum Likelihood Approach.

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.

The effect of a managerial-based intervention on the occurrence of out-of-range-measurements and mortality in intensive care units.

PURPOSE: To evaluate the effect of an organization-based managerial intervention on performance of intensive care units (ICUs). METHODS AND PARTICIPANTS: Prospective multicentre cluster-randomized study with an intervention at the level of ICU staff was carried out. The intervention comprised a set of managerial changes, concerning the nurses' level of skill discretion and participation in decision-making introduced during a period of six months. The ICU-performance was monitored before, during and after the intervention, in terms of mortality and occurrence of out-of-range-measurements (ORMs). The ORMs were defined as a derangement of systolic blood pressure (BP), heart rate (HR), oxygen saturation (SaO2) and urine output (Diur). Data were statistically analyzed by logistic regression with random effects due to ICUs. RESULTS: The overall ICU and hospital mortalities were 14% and 20%, the incidence of BP, HR, O2 and Diur ORM was respectively 46%, 38%, 28% and 48%. After adjusting for SAPSII, admission type and age the regression analyses revealed a positive effect of the intervention for all the six outcome variables. CONCLUSIONS: The intervention reduced both the ICU and hospital mortalities and the incidences of the out-of-range measurements. Registering ORMs provides a feasible method for evaluating ICU performance and could help to optimize individual patient care.

Causal inference algorithms can be useful in life course epidemiology.

OBJECTIVES: Life course epidemiology attempts to unravel causal relationships between variables observed over time. Causal relationships can be represented as directed acyclic graphs. This article explains the theoretical concepts of the search algorithms used for finding such representations, discusses various types of such algorithms, and exemplifies their use in the context of obesity and insulin resistance. STUDY DESIGN AND SETTING: We investigated possible causal relations between gender, birth weight, waist circumference, and blood glucose level of 4,081 adult participants of the Prevention of REnal and Vascular ENd-stage Disease study. The latter two variables were measured at three time points at intervals of about 3 years. RESULTS: We present the resulting causal graphs, estimate parameters of the corresponding structural equation models, and discuss usefulness and limitations of this methodology. CONCLUSION: As an exploratory method, causal graphs and the associated theory can help construct possible causal models underlying observational data. In this way, the causal search algorithms provide a valuable statistical tool for life course epidemiological research.

The Mantel-Haenszel procedure revisited: models and generalizations.

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.

Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial.

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.

Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis.

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.