Case-control Comparison Research Articles

Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia.

Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity. The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63). HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04). Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.

Identification of Candidate Gene Variants in Korean MODY Families by Whole-Exome Sequencing

Aims: To date, 13 genes causing maturity-onset diabetes of the young (MODY) have been identified. However, there is a big discrepancy in the genetic locus between Asian and Caucasian patients with MODY. Thus, we conducted whole-exome sequencing in Korean MODY families to identify causative gene variants. Methods: Six MODY probands and their family members were included. Variants in the dbSNP135 and TIARA databases for Koreans and the variants with minor allele frequencies >0.5% of the 1000 Genomes database were excluded. We selected only the functional variants (gain of stop codon, frameshifts and nonsynonymous single-nucleotide variants) and conducted a case-control comparison in the family members. The selected variants were scanned for the previously introduced gene set implicated in glucose metabolism. Results: Three variants c.620C>T:p.Thr207Ile in PTPRD, c.559C>G:p.Gln187Glu in SYT9, and c.1526T>G:p.Val509Gly in WFS1 were respectively identified in 3 families. We could not find any disease-causative alleles of known MODY 1-13 genes. Based on the predictive program, Thr207Ile in PTPRD was considered pathogenic. Conclusions: Whole-exome sequencing is a valuable method for the genetic diagnosis of MODY. Further evaluation is necessary about the role of PTPRD, SYT9 and WFS1 in normal insulin release from pancreatic beta cells.

Ischaemic stroke or TIA in older subjects associated with impaired dynamic blood pressure control in the absence of severe large artery stenosis.

older subjects may require higher baseline blood pressures to maintain cerebral perfusion. We investigated whether episodic hypotension is associated with tissue infarction in subjects with syncopal symptoms at stroke onset. over 30 months, all acute strokes/TIAs were prospectively screened for symptoms of syncope or presyncope at stroke onset. Subjects with severe large vessel stenosis were excluded, while cases were referred for syncope unit investigation. All underwent 1.5 T MRI acutely, and suspected borderzone infarctions (BZI) were confirmed through Matlab-derived perfusion software. Case-control comparison was derived from stroke controls with no prior syncope history. thirty-eight of 772 stroke patients described presyncope or syncope at stroke onset and had patent large vessels (4.9% of all strokes). Median age was 72 years (IQR 21.4). Twenty-two patients (58%) were prescribed antihypertensive agents at symptom onset. Twenty-six (68.4%) reported focal neurology <24 h in duration. 63.2% (n = 24) of cases reported prior syncope history, compared with 33% (N = 103) of controls, P < 0.001. Cases exhibited greater orthostatic BP drop than controls, P < 0.05 Twenty-four patients were diagnosed with vasovagal syncope through head-up tilt symptom reproduction, 9 with orthostatic hypotension, 4 with cardiac syncope and 1 with carotid sinus syndrome. Nineteen (50%) patients had an acute infarct on MRI, 14 of these were in the arterial borderzone (73.6%). The BZI group were significantly older than the non-BZI group, 79.2 yrs versus 63.3 yrs, P = 0.002. subjects reporting hypotensive symptoms at stroke onset have a higher prevalence of borderzone infarction, despite being normotensive or hypertensive at baseline.

Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison.

Case–control comparison of bacterial and protozoan microorganisms associated with gastroenteritis: application of molecular detection

The introduction of molecular detection of infectious organisms has led to increased numbers of positive findings, as observed for pathogens causing gastroenteritis (GE). However, because little is known about the prevalence of these pathogens in the healthy asymptomatic population, the clinical value of these additional findings is unclear. A case–control study was carried out in a population of patients served by general practitioners in the Netherlands. A total of 2710 fecal samples from case and matched control subjects were subjected to multiplex real-time PCR for the 11 most common bacterial and four protozoal causes of GE. Of 1515 case samples, 818 (54%) were positive for one or more target organisms. A total of 49% of the controls were positive. Higher positivity rates in cases compared to controls were observed for Campylobacter spp., Salmonella spp., Clostridium difficile, enteroinvasive Escherichia coli/Shigella spp., enterotoxigenic E. coli, enteroaggregative E. coli, atypical enteropathogenic E. coli (EPEC), Cryptosporidium parvum/hominis, and Giardia lamblia. However, Dientamoeba fragilis and Shiga-like toxigenic E. coli were detected significantly less frequent in cases than in controls, while no difference in prevalence was found for typical EPEC and enterohemorrhagic E. coli. The association between the presence of microorganisms and GE was the weakest in children aged 0 to 5 years. Higher relative loads in cases further support causality. This was seen for Campylobacter spp., Salmonella spp., enterotoxigenic E. coli, and C. parvum/hominis, and for certain age categories of those infected with C. difficile, enteroaggregative E. coli, and atypical EPEC. For D. fragilis and Shiga-like toxigenic E. coli/enterohemorrhagic E. coli, pathogen loads were lower in cases. Application of molecular diagnostics in GE is rapid, sensitive and specific, but results should be interpreted with care, using clinical and additional background information.

Psychiatric Autoimmunity: N-Methyl-d-Aspartate Receptor IgG and Beyond

Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse. To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice. Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173). In group 1, at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG-positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody positivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 group 1 encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy control subject. A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of comprehensive psychiatric, laboratory, radiologic, and electrophysiologic evaluations.

Feasibility of laparoendoscopic single-site surgery in supracervical hysterectomy: technique and retrospective case-control comparison

One recent innovation in the field of gynecology is laparoendoscopic single-site surgery (LESS). It is associated with reduced postoperative pain and better cosmetic outcome. The present paper aims to explain techniques and instrumentations associated with single-port hysterectomies. A retrospective case-control study is included, comparing LESS with conventional four-port hysterectomies to highlight the feasibility of LESS. This study involved literature search and personal experience regarding single-port hysterectomy and a retrospective case-control study of 34 patients who underwent supracervical hysterectomy between April 2011 and November 2012. Operating time, blood loss, and length of hospital stay were similar in the two groups. Patient’s evaluation of the cosmetic result was in favor of LESS, however not significant. LESS represents a new frontier in minimally invasive surgery. New instrumentation and recommendations have been developed which are expected to make the technique more feasible. This study demonstrates that LESS supracervical hysterectomy has comparable operative outcomes to conventional laparoscopic hysterectomy and is a feasible approach for supracervical hysterectomy. Based on the literature and our experience, a feasible step by step technique for surgeons who are interested in performing supracervical LESS hysterectomy is described. Comparative data and prospective trials are required in order to determine the clinical utility and impact of LESS in treatment of gynecological conditions in the future.

Pattern and risk factors of stroke in the young among stroke patients admitted in medical college hospital, Thiruvananthapuram.

Background:Stroke in the young is particularly tragic because of its potential to create a long-term burden on the victims, their families, and the community. There had been relatively few studies on young stroke in Kerala's socio-economic setup, that too encapsulating the mentioned apparently relevant dimensions of stroke in the young.Objective:To study the prevalence, patterns and risk factors of young stroke.Settings and Design:A cross-sectional study with case control comparison at Government Medical College Hospital, Thiruvananthapuram, Kerala, India.Materials and and Methods:Total 100 stroke patients were identified over a period of 2 months, and data were collected on the basis of questionnaire developed for the purpose.Results:Of 100 stroke patients, 15 had stroke in the young, among which 9 (60%) had ishaemic stroke. Hypertension was the most common risk factor. Smoking, alcohol, atrial fibrillation, and hyperlipidemia were found to be more common in cases (young stroke) when compared with controls. Alcohol use and atrial fibrillation were significantly higher among young stroke patients. Physical inactivity was significantly lesser in those with stroke in the young than elderly. Atrial fibrillation emerged as an independent risk factor of stroke in the young with adjusted odds ratio of 6.18 (1.31-29.21).Conclusion:In all, 15% of total stroke occurred in young adults <50 years. The proportion of hemorrhagic stroke in young adults is higher than in elderly. Atrial fibrillation is identified as an independent risk factor of stroke in the young. Compared with stroke in elderly alcohol use, smoking, hyperlipidemia, and cardiac diseases, which are known risk factors, are higher in young stroke.

Risk of Breast Cancer With CXCR4-Using HIV Defined by V3 Loop Sequencing

Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P values and conditional logistic regression. In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 0.56-0.81). Concordance was similar among cases and controls. HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer.

Community-dwelling female fallers have lower muscle density in their lower legs than non-fallers: evidence from the Saskatoon Canadian Multicentre Osteoporosis Study (CaMos) cohort.

Our objectives were to determine whether peripheral quantitative computed tomography (pQCT)-derived lower leg muscle density and area, and basic functional mobility differ between community-dwelling older women who do and do not report recent falls. Matched case-control comparison. Academic biomedical imaging laboratory. 147 Women, 60 years or older (mean age 74.3 y, SD 7.7) recruited from a longitudinal, population-based cohort representing community-dwelling residents in the area of Saskatoon, Canada. A cross-sectional pQCT scan of the non-dominant lower leg was acquired to determine muscle density and area. Basic functional mobility (Timed Up and Go Test [TUG]) and SF36 health status were also measured. Fallers (one or more falls) and non-fallers (no falls) were grouped according to a 12-month retrospective survey and matched on measured covariates. The muscle density of fallers (n = 35) was a median of 2.1 mg/cm3 lower (P = 0.019, 95% C.I. -3.9 to -0.1) than non-fallers (n = 78) after matching and adjusting for age, body mass index, and SF36 general health scores. Muscle area and TUG did not differ between fallers and non-fallers. Muscle density may serve as a physiological marker in the assessment of lower leg muscular health and fall risk in community-dwelling elderly women. These results are limited to our study population who were mostly Caucasian. Prospective studies are required for verification.

Effects of Siemens Artis Q.zen on radiation dose on patent ductus arteriosus closure: A single centre experience

Objectives: To assess the impact of the Siemens Artis Q.zen on radiation dosage during patent ductus arteriosus (PDA) device closure. Theoretical dose reduction is purported to be delivered by the use of crystalline silicon detectors in combination with the Gigalix x-ray tube that uses flat emitter technology instead of filaments. Both of these allow good image quality at low dose. Methods: Case-control comparison of patients undergoing PDA device closure in two eras – July to October of 2014 in a Siemens Artis zee laboratory (group 1) versus February of 2015 (group 2) in the Siemens Artis Q.zen laboratory. All patients undergoing PDA closure by three operators were included for analysis. Results: Group 1 comprised 11 patients compared to 9 in group 2. Group 1 median age 1.3 years (range 0.6-7 years) and weight 11kg (range 4.8-26.7kg) versus group 2 age 2.6 years (range 0.7-13.3 years) and weight 14.7kg (range 7.6-49kg). Fluoroscopy time was similar in both groups: 6.75min vs 5.73min (ranges 4.2-20min vs 1.4-13.4min). DAP in group 1 was 142uGym2 (range 42-287) versus 64uGym2 (range 32-124) in group 2. Entry dose was 32mGy (range 8-67) in group 1 vs 9 (range 6-25) in group 2. Conclusion: Conversion to the Artis Q.zen laboratory has more than halved radiation dose in children undergoing PDA closure, without any other changes in operators or procedural practice.

Blood Pressure and Heart Rate Variability in Alzheimer's Disease

Background and Purpose Altered blood pressure (BP) and heart rate variations (HRVs) have been reported in Alzheimer’s disease (AD). However, it is unclear how these two manifestations are associated with AD. Therefore, the objective of this study was to investigate BP and heart rate variability in AD compared to that in normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Methods Case-control comparisons were made among AD (n=37), MCI (n=24), SMI (n=17), and controls (n=25). All patients underwent clinical and neuropsychological assessments with 24-h ambulatory BP and Holter monitoring. Results Patients with AD had higher pulse pressures than those in other groups. In addition, AD patients experienced blunted nocturnal BP dipping associated with declining cognitive status. AD patients also had larger ranges of HRV in parasympathetic domains compared to other groups, especially at night. Conclusions Our results suggest that diurnal sympathetic and parasympathetic cardiac variability were significantly disturbed in mild cholinesterase-naive AD patients. This may be an indirect sign of disturbed integrity to the sleep-wake cycle in mild AD.

Prevention of lymphoceles using FloSeal and CoSeal after laparoscopic lymphadenectomy in patients with gynecologic malignancies.

Pelvic ± para-aortic lymphadenectomy (LAE) is an essential element of staging and treatment of different gynecologic malignancies. However, LAE can induce asymptomatic and symptomatic pelvic lymphoceles (LCs) in a considerable percentage of patients. Therapy of symptomatic LCs may cause additional morbidity. The best strategy to reduce the rate of LCs has not established yet. Between January 2011 and May 2012, transperitoneal laparoscopic pelvic ± para-aortic LAE was performed at the Department of Gynecology at Charité University Hospital Berlin in 238 patients with cervical, endometrial, ovarian, or groin-positive vulvar cancer. The application of FloSeal (Baxter, Deerfield, IL) and CoSeal (Baxter) was used in 25 patients (group A) as an alternative to routine pelvic drainage after LAE. A case-control comparison was performed on 25 patients (group B) with bilateral drainage after complete LAE. The primary objective of this pilot study was to evaluate the feasibility and safety of the method. As a secondary objective, we evaluated the incidence of LCs and symptomatic LCs in both groups. The detection of LCs was performed during oncologic follow-up by sonography, computed tomographic imaging, or magnetic resonance imaging. Pelvic (n = 50) or pelvic + para-aortic (n = 42) LAE was performed in 44 patients with cervical, 2 with endometrial, 1 with ovarian, and 2 with groin-positive vulvar cancer, respectively. In group B (n = 25), systematic bilateral pelvic drainage was placed after finishing LAE, whereas in group A (n = 25) LAE areas were sealed with 5 mL FloSeal on each side and sprayed with CoSeal afterward without placing drains. In 14 of 50 patients (28%), LCs were detected. In a subgroup of patients with cervical cancer (88% of the cohort), symptomatic LCs occurred in 11% in group A and 18% in group B. Operative revision of symptomatic LCs was necessary in 5% and 18% in groups A and B, respectively (p = .66). Mean Hospital stay was significant shorter in group A (6 days) versus B (8 days) (p = .027). The results of this case-controlled pilot study indicate that the application of FloSeal and CoSeal after transperitoneal LAE is feasible and safe, may reduce hospital stay, and may potentially decrease the rate of symptomatic LCs in patients with gynecologic malignancies.

Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival.

Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival.

Comparison of early-stage primary serous fallopian tube carcinomas and equivalent stage serous epithelial ovarian carcinomas

ObjectiveTo investigate the outcome of patients with early-stage primary fallopian tube carcinomas (PFTC) and those of patients with equivalent-stage serous epithelial ovarian carcinomas (SEOC). Materials and methodsA balanced and matched, case–control comparison was conducted in a university-based tertiary hospital database between 1978 and 2007. All PFTC and SEOC patients were treated with complete staging surgery followed by multiagent chemotherapy. One SEOC control was matched for each PFTC patient in a very uniform manner (characteristics and treatment). Disease-free survival (DFS) and overall survival (OS) were then compared using Kaplan-Meier analysis. ResultsTwenty-six paired patients were analyzed. Patients with PFTC were significantly older than the SEOC patients (58 years vs. 51 years, p = 0.001). In terms of recurrence, PFTC patients frequently had an extra-abdominal metastasis (3/4, 75%), in contrast to the SEOC patients, who did not (1/5, 20%). The 5-year DFS rate was similar in both groups (85% vs. 81%, p = 0.05), contributing to a similar OS rate (89% vs. 85%, p = 0.50). The median DFS and OS of patients with PFTC and SEOC were also similar without a statistically significant difference (125 months vs. 109 months, and 125 months vs. 122 months, respectively). ConclusionOur study demonstrated that the survival outcome of International Federation of Gynecology and Obstetrics (FIGO) I/II PFTC patients was similar to that of FIGO I/II SEOC patients, and both groups had a >80% 5-year DFS rate after complete staging surgery, followed by multiagent chemotherapy. This finding is worthy of being investigated.

Genome-wide and gene-based association studies of anxiety disorders in European and African American samples.

Anxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540 European American and 849 African American subjects) genotyped on the Affymetrix GeneChip 6.0 array. We applied two phenotypic approaches: (1) categorical case-control comparisons (CC) based upon psychiatric diagnoses, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. Linear and logistic models were used to analyse the association with ADs using FS and CC traits, respectively. At the single locus level, no genome-wide significant association was found. A trans-population gene-based meta-analysis across both ethnic subsamples using FS identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12) with genome-wide significance (false discovery rate (FDR] <5%). At the pathway level, several terms such as transcription regulation, cytokine binding, and developmental process were significantly enriched in ADs (FDR <5%). Our approaches studying ADs as quantitative traits and utilizing the full GWAS data may be useful in identifying susceptibility genes and pathways for ADs.

Genetic-epidemiological evidence for the role of acetaldehyde in cancers related to alcohol drinking.

Alcohol drinking increases the risk for a number of cancers. Currently, the highest risk (Group 1) concerns oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, as assessed by the International Agency for Research on Cancer (IARC). Alcohol and other beverage constituents, their metabolic effects, and alcohol-related unhealthy lifestyles have been suggested as etiological factors. The aim of the present survey is to evaluate the carcinogenic role of acetaldehyde in alcohol-related cancers, with special emphasis on the genetic-epidemiological evidence. Acetaldehyde, as a constituent of alcoholic beverages, and microbial and endogenous alcohol oxidation well explain why alcohol-related cancers primarily occur in the digestive tracts and other tissues with active alcohol and acetaldehyde metabolism. Genetic-epidemiological research has brought compelling evidence for the causality of acetaldehyde in alcohol-related cancers. Thus, IARC recently categorized alcohol-drinking-related acetaldehyde to Group 1 for head and neck and esophageal cancers. This is probably just the tip of the iceberg, since more recent epidemiological studies have also shown significant positive associations between the aldehyde dehydrogenase ALDH2 (rs671)*2 allele (encoding inactive enzyme causing high acetaldehyde elevations) and gastric, colorectal, lung, and hepatocellular cancers. However, a number of the current studies lack the appropriate matching or stratification of alcohol drinking in the case-control comparisons, which has led to erroneous interpretations of the data. Future studies should consider these aspects more thoroughly. The polymorphism phenotypes (flushing and nausea) may provide valuable tools for future successful health education in the prevention of alcohol-drinking-related cancers.

LAT software induced savings on medical costs of alcohol addicts' care--results from a matched-pairs case-control study.

Lesch Alcoholism Typology (LAT) is one of the most widely used clinical typologies of alcohol addiction. Study tested whether introduction of LAT software in clinical practice leaded to improved outcomes and reduced costs. Retrospective matched-pairs case-control cost comparison study was conducted at the Regional Addiction Center of the University Clinic in Serbia involving 250 patients during the four-year period. Mean relapse frequency followed by outpatient detoxification was 0.42±0.90 vs. 0.70±1.66 (LAT/non-LAT; p = 0.267). Adding relapses after inpatient treatment total mean-number of relapses per patient was 0.70±1.74 vs. 0.97±1.89 (LAT/non-LAT; p = 0.201). However, these relapse frequency differentials were not statistically significant. Total hospital costs of Psychiatry clinic based non-LAT addicts' care (€54,660) were significantly reduced to €36,569 after initiation of LAT. Mean total cost per patient was reduced almost by half after initiation of LAT based treatment: €331±381 vs. €626±795 (LAT/non-LAT; p = 0.001). Mean cost of single psychiatry clinic admission among non-LAT treatment group was €320±330 (CI 95% 262–378) and among LAT €197±165 (CI 95% 168–226) (p = 0.019). Mean LAT software induced net savings on psychiatric care costs were €144 per patient. Total net savings on hospital care including F10 associated somatic co-morbidities amounted to €295 per patient. More sensitive diagnostic assessment and sub-type specific pharmacotherapy and psychotherapy following implementation of LAT software lead to significant savings on costs of hospital care.

Maternal risk factors for fetal alcohol spectrum disorders in a province in Italy

BackgroundMaternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. MethodsMaternal interviews (n=905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. ResultsCase control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child's family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95%C.I.=1.6 to 50.7). Sequential multiple regression analysis of the child's neuropsychological performance also identifies alcohol problems in the child's family as the only significant maternal risk variable (p<.001) when controlling for other potential risk factors. ConclusionsUnderreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified.

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA.