Emanuele Leoncini

Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses.

Introduction PRISMA statement was published in 2009 in order to set standards in the reporting of systematic reviews and meta-analyses. Our aim was to evaluate the impact of PRISMA endorsement on the quality of reporting and methodological quality of systematic reviews and meta-analyses, published in journals in the field of gastroenterology and hepatology (GH). Methods Quality of reporting and methodological quality were evaluated by assessing the adherence of papers to PRISMA checklist and AMSTAR quality scale. After identifying the GH journals which endorsed PRISMA in instructions for authors (IA), we appraised: 15 papers published in 2012 explicitly mentioning PRISMA in the full text (Group A); 15 papers from the same journals published in 2012 not explicitly mentioning PRISMA in the full text (Group B); 30 papers published the year preceding PRISMA endorsement from the same journals as above (Group C); 30 papers published in 2012 on the 10 highest impact factor journals in GH which not endorsed PRISMA (Group D). Results PRISMA statement was referred in the IA in 9 out of 70 GH journals (12.9%). We found significant increase in overall adherence to PRISMA checklist (Group A, 90.1%; Group C, 83.1%; p = 0.003) and compliance to AMSTAR scale (Group A, 85.0%; Group C, 74.6%; p = 0.002), following the PRISMA endorsement from the nine GH journals. Explicit referencing of PRISMA in manuscript was not associated with increase in quality of reporting and methodological quality (Group A vs. B, p = 0.651, p = 0.900, respectively). Adherence to PRISMA checklist, and the compliance with AMSTAR were significantly higher in journals endorsing PRISMA compared to those not (Groups A+B vs. D; p = 0.003 and p = 0.016, respectively). Conclusion The endorsement of PRISMA resulted in increase of both quality of reporting and methodological quality. It is advised that an increasing number of medical journals include PRISMA in the instructions for authors.

Prevalence at Birth of Cleft Lip With or Without Cleft Palate : Data From the International Perinatal Database of Typical Oral Clefts (IPDTOC)

As part of a collaborative project on the epidemiology of craniofacial anomalies, funded by the National Institutes for Dental and Craniofacial Research and channeled through the Human Genetics Programme of the World Health Organization, the International Perinatal Database of Typical Orofacial Clefts (IPDTOC) was established in 2003. IPDTOC is collecting case-by-case information on cleft lip with or without cleft palate and on cleft palate alone from birth defects registries contributing to at least one of three collaborative organizations: European Surveillance Systems of Congenital Anomalies (EUROCAT) in Europe, National Birth Defects Prevention Network (NBDPN) in the United States, and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) worldwide. Analysis of the collected information is performed centrally at the ICBDSR Centre in Rome, Italy, to maximize the comparability of results. The present paper, the first of a series, reports data on the prevalence of cleft lip with or without cleft palate from 54 registries in 30 countries over at least 1 complete year during the period 2000 to 2005. Thus, the denominator comprises more than 7.5 million births. A total of 7704 cases of cleft lip with or without cleft palate (7141 livebirths, 237 stillbirths, 301 terminations of pregnancy, and 25 with pregnancy outcome unknown) were available. The overall prevalence of cleft lip with or without cleft palate was 9.92 per 10,000. The prevalence of cleft lip was 3.28 per 10,000, and that of cleft lip and palate was 6.64 per 10,000. There were 5918 cases (76.8%) that were isolated, 1224 (15.9%) had malformations in other systems, and 562 (7.3%) occurred as part of recognized syndromes. Cases with greater dysmorphological severity of cleft lip with or without cleft palate were more likely to include malformations of other systems.

Treatment of Hyperthyroidism in Pregnancy and Birth Defects

CONTEXT Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are propylthiouracil and methimazole/carbimazole. OBJECTIVES In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research. DESIGN The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure. RESULTS Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphalocele, and total situs inversus ± dextrocardia (P < 0.01). CONCLUSIONS Further studies are required to exhaustively evaluate the associations between propylthiouracil and birth defects because of the low number, the lack of biological plausibility, and the possibility of underdiagnosis. Association between methimazole/carbimazole exposure and omphalocele and choanal atresia is consistent with previous reports and definitely suggests that these malformations could be part of a specific, even if rare, embryopathy.

Survey on Knowledge, Attitudes, and Training Needs of Italian Residents on Genetic Tests for Hereditary Breast and Colorectal Cancer

Objectives. The aim of the study was to assess knowledge and attitudes of medical residents working in Università Cattolica del Sacro Cuore, Rome, Italy, on genetic tests for breast and colorectal cancer. Methods. We distributed self-administered questionnaire to the residents. Logistic regression models were used to evaluate the determinants of knowledge and attitudes towards the tests. Results. Of 754 residents, 364 filled in questionnaire. Around 70% and 20% answered correctly >80% of questions on breast and colorectal cancer tests, respectively. Knowledge on tests for breast cancer was higher among residents who attended course on cancer genetic testing during graduate training (odds ratio (OR): 1.72; 95% confidence interval (CI): 1.05–2.82) and inversely associated with male gender (OR: 0.55; 95% CI: 0.35–0.87). As for colorectal cancer, residents were more knowledgeable if they attended courses on cancer genetic testing (OR: 2.08; 95% CI: 1.07–4.03) or postgraduate training courses in epidemiology and evidence-based medicine (OR: 1.95; 95% CI: 1.03–3.69). More than 70% asked for the additional training on the genetic tests for cancer during the specialization school. Conclusion. The knowledge of Italian residents on genetic tests for colorectal cancer appears to be insufficient. There is a need for additional training in this field.

Risk factors for intraductal papillary mucinous neoplasm (ipmn) of the pancreas: A multicentre case-control study

OBJECTIVES:To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs).METHODS:Multicentre case–control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics.RESULTS:Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08–2.98), CP (OR: 10.10, CI 95%: 1.30–78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17–7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74–20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement.CONCLUSIONS:A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results suggest an overlap between certain risk factors for PDAC and IPMN.

Frequency of holoprosencephaly in the International Clearinghouse Birth Defects Surveillance Systems: Searching for population variations

BACKGROUND Holoprosencephaly (HPE) is a developmental field defect of the brain that results in incomplete separation of the cerebral hemispheres that includes less severe phenotypes, such as arhinencephaly and single median maxillary central incisor. Information on the epidemiology of HPE is limited, both because few population-based studies have been reported, and because small studies must observe a greater number of years in order to accumulate sufficient numbers of births for a reliable estimate. METHODS We collected data from 2000 through 2004 from 24 of the 46 Birth Defects Registry Members of the International Clearinghouse for Birth Defects Surveillance and Research. This study is based on more than 7 million births in various areas from North and South America, Europe, and Australia. RESULTS A total of 963 HPE cases were registered, yielding an overall prevalence of 1.31 per 10,000 births. Because the estimate was heterogeneous, possible causes of variations among populations were analyzed: random variation, under-reporting and over-reporting bias, variation in proportion of termination of pregnancies among all registered cases and real differences among populations. CONCLUSIONS The data do not suggest large differences in total prevalence of HPE among the studied populations that would be useful to generate etiological hypotheses.

Conjoined twins: A worldwide collaborative epidemiological study of the International Clearinghouse for Birth Defects Surveillance and Research†‡

Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32–1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature.

Mannose-Binding Lectin Codon 54 Gene Polymorphism and Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis

Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10–11.15; P for heterogeneity = 0.013; I 2 = 68.6%) and 12.68 (95% CI 3.74–42.92; P for heterogeneity = 0.932, I 2 = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29–5.12; P for heterogeneity = 0.897; I 2 = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the womens innate immunity in response to Candida.

T1ρ magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults.

Study Design. Cross-sectional study using T1&rgr; magnetic resonance imaging (MRI) of lumbar spine in healthy young adults. Objective. To evaluate early intervertebral disc degeneration (IDD) quantified by T1&rgr;- and T2-weighted MRI in asymptomatic young adults and to correlate T1&rgr; value with Pfirrmann degenerative grade, sex, and body mass index (BMI). Summary of Background Data. Intervertebral disc starts early to degenerate losing proteoglycan content in the nucleus pulposus (NP). A potential tool for the study of early stage of IDD is T1&rgr; MRI. T1&rgr; relaxation time of human discs has been correlated to proteoglycan content in previous studies. Methods. T1&rgr;- and T2-weighted images of the lumbar spine were obtained for 63 asymptomatic young subjects (34 men and 29 women; mean age, 22.95 ± 1.8 yr), with a 1.5-T MRI scanner. T1&rgr; mapping and values in the NP and anulus fibrosus (n = 315) were obtained. Degenerative grade was assessed using T2-weighted images, according to the Pfirrmann scale. Differences in T1&rgr; value between sexes, BMI, and linear regression analyses with degenerative grade were determined. Results. T1&rgr; values of NPs were significantly higher than those of anulus fibrosus at all levels. T1&rgr; values were significantly lower in women at L3–L4 and L4–L5 discs (P < 0.05). T1&rgr; values decreased linearly with degenerative grade. However, nondegenerated discs (Pfirrmann grades 1 and 2) showed a wide range of T1&rgr; relaxation time. No significant correlation was observed between T1&rgr; value and BMI. Conclusion. The data of this study showed a significant difference in IDD onset between sexes. T1&rgr; values correlate with Pfirrmann degenerative grade in young adults. However, the wide distribution of T1&rgr; values in healthy intervertebral disc highlights the low sensitivity of Pfirrmann grade to detect the early IDD changes. T1&rgr; can be potentially used as a clinical tool to identify early IDD and to create a reliable quantitative scale.

Microtia‐anotia: A global review of prevalence rates

BACKGROUND There are few published studies on microtia-anotia frequency. METHODS Using data from birth defects surveillance programs around the world, we conducted a systematic review on the frequency of microtia-anotia to further explore the differences in prevalence across countries. Ninety-two birth defects surveillance programs were evaluated with a total of 8917 cases of microtia-anotia. We computed the prevalence per 10,000 births for each surveillance program for total cases of microtia-anotia (microtia types I to IV), microtia (types I to III), and anotia (type IV). Prevalence ratios were calculated by large geographic areas, race/ethnicity, and by surveillance methodologies. RESULTS The overall prevalences were: microtia-anotia, 2.06 (confidence interval [CI], 2.02-2.10); microtia, 1.55 (CI, 1.50-1.60); and anotia 0.36 (CI, 0.34-0.38). Higher prevalences were observed for the Americas, Northern Europe and Asia, among Hispanics and Asians, and among active ascertainment and hospital-based surveillance programs. CONCLUSIONS We observed marked variation in the prevalence of microtia-anotia across surveillance programs and within countries. These results must be interpreted cautiously as this variability may be explained mainly by differences in surveillance methods. However, given the magnitude of some of the differences, other factors may also be involved. This study contributes to the knowledge of the prevalence of microtia-anotia by providing a critical analysis of the existing data. In addition, it supports the need for a coding system that allows complete phenotype characterization of microtia-anotia, including severity and laterality, as well as for further studies on the variation of its frequency related to race and ethnicity.