Uric acid and cardio-metabolic risk factors : an epidemiological approach

The role of serum uric acid (SUA) in cardio-metabolic conditions has long been contentious. It is still unclear if SUA is an independent risk factor or marker of cardio-metabolic conditions and most observed associations are not necessarily causal. This study aimed to further understand and explore the causal role of SUA in cardio-metabolic conditions using genetic and non-genetic epidemiological methods in population-based data. In the first part of this study, we found moderate to high heritability estimates for SUA and fractional excretion of urate (FEUA) suggesting the role of genetic factors in the etiology of hyperuricemia. With regards to the role of SUA on inflammatory markers (IMs), a strong positive association of SUA with C-reactive protein (CRP) and a weaker positive association with tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was observed, which was in part mediated by body mass index (BMI). These findings suggest that SUA may have a role in sterile inflammation. In view of the inconsistency surrounding the causal nature and direction of the relation between SUA and adiposity, we applied a bidirectional Mendelian randomization approach using genetic variants to decipher the association. The finding that elevated SUA is a consequence rather than a cause of adiposity was not totally unexpected and is compatible with the hypothesis that hyperinsulinemia, accompanying obesity, enhances renal proximal tubular reabsorption of uric acid. The fourth part of this study examined the relationship between SUA and blood pressure (BP) in young adults. The association between SUA and BP, significant only in females, was strongly attenuated upon adjustment for BMI. The possibility that BMI lies in the causal pathway may explain the attenuation observed in the associations of SUA with BP and IMs. Finally, a significant hockey-stick shaped association of SUA with social phobia in our data suggests a protective effect of SUA only up to a certain concentration. Although our study findings have shed some light on the uncertainty underlying the pathophysiology of SUA, more compelling evidence using longitudinal designs, randomized controlled trials and the use of robust genetic tools is warranted to increase our understanding of the clinical significance of SUA.

An epidemiological study of dental agenesis in a primary health area in Spain: estimated prevalence and associated factors

Objectives: To evaluate the prevalence of dental agenesis and its possible association with other developmental dental anomalies and systemic entities. Setting and Sample Population: Descriptive transversal study, for which 1518 clinical records, of patients visited by the Odontological Service of the Primary Health Centre of Cassà de la Selva (Girona-Spain) between December 2002 and February 2006 were reviewed. The data were recorded in relation to the oral and dental anomalies and the associated systemic entities, between the ones referred as concomitant in literature. Results: Values of 9.48% (7.25% excluding the third molars) for dental agenesis and 0.39% for oligodontia were obtained. The presence of dental agenesis concomitant with some other forms of oral and dental anomalies was observed. Attention must be drawn to the fact that a greater number of concomitant systemic entities were observed in those patients that presented a severe phenotypical pattern of dental agenesis. Conclusions: The results of the present study do not differ from the ones reported in studies of similar characteristics among Occidental and Spanish populations. The relationship observed between certain systemic entities and developmental dental anomalies suggest a possible common genetic etiology

An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.

BACKGROUND: Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort. METHODS: Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF). RESULTS: For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001). CONCLUSION: Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures.

Patient with hepatocellular carcinoma related to prior acute arsenic intoxication and occult HBV: epidemiological, clinical and therapeutic results after 14 years of follow-up

Little is known about the long-term survivors of acute arsenic intoxication. We present here a clinical case report of a man with chronic hepatitis B virus (HBV) infection who developed hepatocellular carcinoma four years after acute arsenic poisoning. HBsAg was detected in serum in 1990 when he voluntarily donated blood. In 1991, the patient suffered from severe psychological depression that led him to attempt suicide by massive ingestion of an arsenic-containing rodenticide. He survived with polyneuropathy and paralysis of the lower limbs, and has been wheelchair-bound since then. During participation in a follow-up study conducted among HBV carriers, abdominal ultrasound detected a two-centimeter liver mass consistent with hepatocellular carcinoma. The tumor was confirmed by computed tomography (CT) and magnetic resonance image (MRI). Because of his significant comorbidity, the patient received palliative treatment with transarterial lipiodol chemoembolization (TACE) on three occasions (1996, 1997 and 1999). At his most recent visit in May 2005, the patient was asymptomatic, liver enzymes were normal and the tumor was in remission on ultrasound.

Prevention of cutaneous melanoma: an epidemiological evaluation of the Swiss campaign.

A national information program, focusing on the main recognized risk factors (primary prevention) and on the potential benefits of early detection (secondary prevention) of cutaneous malignant melanoma, was launched in Switzerland in May 1988. The first campaign, based on a pilot study conducted in 1986 in the canton of Basel, was followed by a recall campaign in July 1989. This report describes the organization of this program and presents an assessment of its initial impact. The number of newly diagnosed cases increased more than twofold (+ 116%) in the two months following the launch of the first campaign (May to June 1988). This trend was accompanied by a statistically significant shift of case distribution towards younger ages (< 60 years; p = 0.003), and a non-significant shift was observed towards less advanced lesions (thickness < or = 1.5 mm). The incidence decreased quickly, though in the twelve month period between the two campaigns it remained 21% higher than before the inception of the program. No appreciable effects were detected from the recall campaign and no difference was seen among regions or between sexes.

Predictors of substance use reduction in an epidemiological first-episode psychosis cohort.

AIM: To assess the predictors of a significant decrease or cessation of substance use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHOD: Participants were FEP patients of the Early Psychosis Prevention and Intervention Centre in Australia. Patients' medical files were reviewed using a standardized file audit. Data on 432 patients with FEP and baseline co-morbid substance use disorder (SUD) were available for analysis. Predictors of reduction/cessation of SU at follow up were examined using logistic regression analyses. RESULTS: In univariate analyses, a reduction/cessation of SU was predicted by baseline measures reflecting higher education, employment, accommodation with others, cannabis use disorder (CUD) only (rather than poly-SUDs), better global functioning and better premorbid social and occupational functioning, later age at onset of psychosis, and a diagnosis of non-affective psychosis. In multivariate analysis, CUD alone and better premorbid social and occupational functioning remained significant predictors. CONCLUSIONS: Addressing SUDs and social and occupational goals in people with FEP may offer opportunities to prevent SUDs becoming more severe or entrenched. Further longitudinal research on recovery from SU and FEP is needed to disentangle directions of influence and identify key targets for intervention.

Investigation of classical epidemiological links between patients harbouring identical, non-predominant meticillin-resistant Staphylococcus aureus genotypes and lessons for epidemiological tracking.

According to molecular epidemiology theory, two isolates belong to the same chain of transmission if they are similar according to a highly discriminatory molecular typing method. This has been demonstrated in outbreaks, but is rarely studied in endemic situations. Person-to-person transmission cannot be established when isolates of meticillin-resistant Staphylococcus aureus (MRSA) belong to endemically predominant genotypes. By contrast, isolates of infrequent genotypes might be more suitable for epidemiological tracking. The objective of the present study was to determine, in newly identified patients harbouring non-predominant MRSA genotypes, whether putative epidemiological links inferred from molecular typing could replace classical epidemiology in the context of a regional surveillance programme. MRSA genotypes were defined using double-locus sequence typing (DLST) combining clfB and spa genes. A total of 1,268 non-repetitive MRSA isolates recovered between 2005 and 2006 in Western Switzerland were typed: 897 isolates (71%) belonged to four predominant genotypes, 231 (18%) to 55 non-predominant genotypes, and 140 (11%) were unique. Obvious epidemiological links were found in only 106/231 (46%) patients carrying isolates with non-predominant genotypes suggesting that molecular surveillance identified twice as many clusters as those that may have been suspected with classical epidemiological links. However, not all of these molecular clusters represented person-to-person transmission. Thus, molecular typing cannot replace classical epidemiology but is complementary. A prospective surveillance of MRSA genotypes could help to target epidemiological tracking in order to recognise new risk factors in hospital and community settings, or emergence of new epidemic clones.

Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients.

OBJECTIVES: High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort. METHODS: The Early Psychosis Prevention and Intervention Centre admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. A total of 704 files were available, 43 excluded because of a nonpsychotic diagnosis at end point and 3 due to missing data regarding past stressful events; 658 patients were analyzed. RESULTS: A total of 83% patients had been exposed to at least one stressful event and 34% to SPA. SPA patients were more likely to have presented other psychiatric disorders before psychosis onset (posttraumatic stress disorder, substance use disorder), to have made suicide attempts in the past, and to have had poorer premorbid functional levels. Additionally, SPA patients had higher rate of comorbid diagnosis at program entry and were more likely to attempt suicide during treatment. CONCLUSIONS: SPA prevalence is high in FEP patients and must be explored by clinicians considering its durable impact on psychological balance and link with long-lasting suicidal risk. More research is warranted to better understand mechanisms involved between trauma and its potential consequences, as well as to develop psychological interventions adapted to this very sensitive and complex issue.

Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort.

INTRODUCTION: To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS: Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION: Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.

Two different epidemiological scenarios of border disease in the populations of Pyrenean chamois (Rupicapra p. pyrenaica) after the first disease outbreaks

Since 2001 several outbreaks of a new disease associated with Border disease virus (BDV) infection have caused important declines in Pyrenean chamois (Rupicapra pyrenaica) populations in the Pyrenees. The goal of this study was to analyze the post-outbreak BDV epidemiology in the first two areas affected by disease with the aim to establish if the infection has become endemic. We also investigated if BDV infected wild and domestic ruminants sharing habitat with chamois. Unexpectedly, we found different epidemiological scenarios in each population. Since the disease outbreaks, some chamois populations recuperated quickly, while others did not recover as expected. In chamois from the first areas, prevalence was high (73.47%) and constant throughout the whole study period and did not differ between chamois born before and after the BDV outbreak; in all, BDV was detected by RT-PCR in six chamois. In the other areas, prevalence was lower (52.79%) and decreased during the study period; as well, prevalence was significantly lower in chamois born after the disease outbreak. No BDV were detected in this population. A comparative virus neutralisation test performed with four BDV strains and one Bovine viral diarrhoea virus (BVDV) strain showed that all the chamois had BDV-specific antibodies. Pestivirus antibodies were detected in all the rest of analyzed species, with low prevalence values in wild ruminants and moderate values in domestic ruminants. No viruses were detected in these species. These results confirm the hypothesis that outbreaks of BDV infection only affect the Pyrenean chamois, although other wild ruminants can occasionally be infected. In conclusion, two different scenarios have appeared since the first border disease outbreaks in Pyrenean chamois: on the one hand frequent BDV circulation with possible negative impact on population dynamics in some areas and on the other, lack of virus circulation and quick recovery of the chamois population.

Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). FUNDING: Medical Research Council, Cancer Research UK.