Community-based Controls Research Articles

Neuronal pentraxin-2 (NPTX2) serum levels during an acute psychotic episode in patients with schizophrenia

Neuronal pentraxin-2 (NPTX2, an immediate-early gene), which regulates synapse activity and neuroplasticity, plays an essential role in the neurodevelopmental process. NPTX2 possibly enhances the accumulation of amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPAR) on the postsynaptic membranes and stimulates excitatory synaptogenesis. We aimed to evaluate the plasma concentrations of NPTX2 of patients with schizophrenia in acute psychotic episodes compared with matched community-based controls. Ninety-three (93) patients diagnosed with schizophrenia according to DSM-5 and 83 healthy controls were included. The patients, all of which were in acute psychotic episodes, were recruited from the inpatient clinic. The patients were assessed by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression- Severity (CGIS) scale, whereas the healthy subjects were evaluated with Structured Clinical Interview for DSM-5 (SCID-5) to exclude any major psychiatric diagnoses. NPTX2 serum concentrations were significantly higher in the schizophrenia group (p < 0.001). NPTX2 levels negatively correlated with age (p = 0.004) and PANSS-positive symptom scores (p < 0.001). The most determinant factors in predicting the change in NPTX2 levels were PANSS-positive symptom and general psychopathology scores. We conclude that NPTX2 could be involved in schizophrenia pathophysiology and valuable as a synapse-derived and glutamate-related biomarker. Further studies in larger samples assessing NPTX2 levels in remitted schizophrenia patients and combining neuroimaging techniques and cognitive evaluations with blood samples are needed.

The incidence, baseline predictors, and outcomes of dementia in an incident cohort of Parkinson’s disease and controls

BackgroundThere are few long-term data on the incidence, baseline predictors, and outcomes of dementia in Parkinson’s disease (PD) from prospective community-based incident cohorts.MethodsThe PINE study prospectively identified all incident PD patients in Aberdeen along with age–sex-matched, community-based controls who consented to standardized annual life-long follow-up. Each year, a clinical expert reviewed the diagnosis of PD and the presence of dementia according to DSM-IV-based criteria. Age–sex stratified incidence rates for dementia in PD and controls were calculated and compared with hazard ratios (HR) adjusted for age, sex, education, and socioeconomic status. Cox proportional-hazard modelling was used to assess baseline predictors for PD dementia and the influence of dementia on survival and institutionalization.Results201 patients (mean age 72.6yrs) and 260 controls (mean age 75.4yrs) were followed for median 9.5 years. The incidence of dementia was 7.4 (PD) versus 2.1 (controls) per 100 person-years (adjusted HR 6.0, 95%CI 4.1–8.7), with a sixfold increase from under 60 to over 80 years in PD but no sex difference. Independent baseline predictors of PD dementia were older age at diagnosis, self-reported cognitive symptoms, dream enactment, lower MMSE scores, worse motor UPDRS scores, and the ApoE genotype. PD dementia increased the rates of subsequent death and institutionalization (32.0 and 26.9 per 100 person-years, respectively).ConclusionThe incidence of dementia in PD is high, increases markedly with age, is increased in those with baseline subjective cognitive symptoms as well as other established risk factors, and is associated with high rates of death and institutionalization.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma

BackgroundThe relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk.MethodsThis case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model.ResultsWhen comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21–0.51), PUFA (OR: 0.32, 95% CI: 0.20–0.51), and TFA (OR: 0.44, 95% CI: 0.28–0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19–0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC.ConclusionsThis study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Diagnostic and therapeutic characteristics of diabetes mellitus and risk of out-of-hospital cardiac arrest

This study aimed to evaluate the risks of diabetes mellitus (DM) on out-of-hospital cardiac arrest (OHCA) and to investigate whether the risks of DM on OHCA varied according to the diagnostic and therapeutic characteristics of diabetes. We conducted a multicenter prospective case–control study in 17 University hospitals in Korea from September 2017 to December 2020. Cases were EMS-treated OHCA patients aged 20 to 79 with a presumed cardiac etiology. Community-based controls were recruited at a 1:2 ratio after matching for age, sex, and urbanization level of residence. A structured questionnaire and laboratory findings were collected from cases and controls. Multivariable conditional logistic regression analyses were conducted to estimate the risk of DM on OHCA by characteristics. A total of 772 OHCA cases and 1544 community-based controls were analyzed. A total of 242 (31.3%) OHCAs and 292 (18.9%) controls were previously diagnosed with DM. The proportions of type I DM (10.7% vs. 2.1%) and insulin therapy (15.3% vs. 6.5%) were higher in OHCAs with DM than in controls with DM. The duration of DM was longer in OHCAs than in controls (median 12 vs. 7 years). DM was associated with an increased risk of OHCA (aOR (95% CI), 2.13 (1.64–2.75)). Compared to the no diabetes group, the risks of OHCA increased in the diabetes patients with type I DM (5.26 (1.72–16.08)) and type II DM group (1.63 (1.18–2.27)), a long duration of DM prevalence (1.04 (1.02–1.06) per 1-year prevalence duration), and a high HbA1c level (1.38 (1.19–1.60) per 1% increase). By treatment modality, the aOR (95% CI) was lowest in the oral hypoglycemic agent (1.47 (1.08–2.01)) and highest in the insulin (6.63 (3.04–14.44)) groups. DM was associated with an increased risk of OHCA, and the risk magnitudes varied according to the diagnostic and therapeutic characteristics.

Neuroimaging cerebrovascular biomarkers in Parkinson's disease.

The cardiovascular risk in Parkinson's disease (PD) remains uncertain and controversial. Some studies suggest PD patients present an increased risk of cerebrovascular disease. We aimed to study the prevalence of neuroimaging cerebrovascular biomarkers in PD patients compared to controls, using an accurate and complete magnetic resonance (MR) imaging evaluation. Neuroimaging sub-study within a larger cross-sectional case-control study. An enriched subgroup of PD patients (≤10 years since diagnosis) with at least a moderate cardiovascular mortality risk based on a Systematic COronary Risk Evaluation (SCORE) was compared to community-based controls regarding neuroimaging biomarkers. Patients underwent a high-resolution T1-weighted MR imaging sequence at 3.0T to visualize neuromelanin. A 3D SWI FFE, sagittal 3D T1-weighted, axial FLAIR and diffusion-weighted image sequences were obtained. The study included 47 patients, 24 with PD and 23 controls. PD patients presented a reduced area and signal intensity of the substantia nigra and locus coeruleus on neuromelanin-sensitive MR. The median SCORE was 5% in both groups. No significant differences regarding white matter hyperintensities (OR 4.84, 95% CI 0.50, 47.06), lacunes (OR 0.43, 95% CI 0.07, 2.63), microbleeds (OR 0.64, 95% CI 0.13, 3.26), or infarcts (0.95, 95% CI 0.12, 7.41) was found. The frequency of these neuroimaging biomarkers was very low in both groups. The present study does not support an increased prevalence of neuroimaging cerebrovascular biomarkers in PD patients.

Abstract 13788: Systematic Review: Utility of Human Immune Responses to Group A Streptococcus Antigens as a Diagnostic Indicator for Acute Rheumatic Fever

Introduction: Previous studies have established that group A streptococcus (GAS) antibody titre is correlated with a diagnosis of acute rheumatic fever (ARF). However, results vary in the usefulness of GAS antibodies, particularly anti-Streptolysin-O (ASO) and anti-DNase B, in confirming a recent GAS infection. Therefore, we sought to provide, from published studies, an evidence-based synthesis of the correlation of streptococcal serology to establish the usefulness of immunological data in aiding the diagnosis of ARF. These findings are anticipated to have implications where echocardiography is not freely available, especially where ARF is rampant. Methods: We conducted a comprehensive search across a number of databases. Applying a priori criteria, we selected articles reporting on studies, regardless of study design, that evaluate the levels of antibodies against GAS-specific antigens in ARF subjects against control values or a published standard. Data were extracted onto data extraction forms, captured electronically and analysed using STATA software. Risk of bias was assessed in included studies using the Newcastle-Ottawa Scale . Results: The search strategy yielded 534 studies, from which 24 met the inclusion criteria, reporting on evaluation of titres for SLO (n=10), DNase B (n=9), anti-streptokinase (ASK) (n=3) amongst others. Elevation in titres was determined by comparison with controls and upper limit of normal (ULN) antibody values as determined in healthy individuals. Meta-analysis of case-controlled studies revealed moderate odds ratio (OR) correlations between ARF diagnosis and elevated titres for SLO (OR=10.57; 95% CI, 3.36 to 33.29; 10 studies) and DNase B (OR=6.97; 95% CI, 2.99 to 16.27; 7 studies). Conclusions: While providing support for incorporating SLO and DNase B in the diagnosis of ARF, we present the following reflections: an elevation in SLO and DNase B levels are not consistently associated with an ARF diagnosis; increasing the number of GAS proteins in the test is warranted to improve sensitivity; paired (acute and convalescent) samples could provide a more accurate indication of a rising titre. Use of community-based controls as a standard is not a reliable marker by which to gauge recent GAS infection

Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study

BackgroundThis study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).MethodsA case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.ResultsExcessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.ConclusionExcessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

Respiratory Outcomes of Firefighter Exposures in the Fort McMurray Fire: A Cohort Study From Alberta Canada.

Determine effects on respiratory health of firefighters attending a catastrophic wildfire. Within the Alberta Administrative Health Database, we identified five community-based controls for each firefighter in a cohort of 1234 deployed to the 2016 Fort McMurray fire. Spirometry records were identified and a stratified sample assessed clinically. We estimated PM2.5 particles exposure. Firefighters had an increased risk of asthma consultation post-fire (OR new onset asthma = 2.56; 95%CI 1.75 to 3.74). Spirometry showed decreased FEV1 and FVC with increasing exposure. In the clinical assessment, 20% had a positive MCT and 21% BWT. Those with ongoing fire-related symptoms had a higher concurrence of positive MCT and BWT (OR = 4.35; 95%CI 1.11 to 17.12). Lower diffusion capacity related to higher exposure. Massive exposures during a wildfire are associated with non-resolving airways damage.

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis.

Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS. Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.

Plasma amino acids profile in first-episode psychosis, unaffected siblings and community-based controls

Investigations of plasma amino acids in early psychosis and their unaffected siblings are rare. We measured plasma amino acids involved in the co-activation of dopaminergic, GABAergic, glutamatergic, and serotoninergic neurotransmitters in first-episode psychosis (FEP) patients (n = 166), unaffected siblings (n = 76), and community-based controls (n = 166) included in a cross-sectional study. Plasma levels of glutamic acid (GLU), glutamine, glycine, proline (PRO), tryptophan (TRP), tyrosine, serine and GABA were quantified by gas-chromatography-mass spectrometry. We used the generalized linear model adjusted by sex, age, and body mass index for group comparison and paired t-test for FEP-Sibling pairs. FEP had reduced GABA plasma levels compared to siblings and controls (p < 0.05 for both). Siblings had lower GLU, Glx and PRO (p < 0.05 for all) but increased TRP compared to patients and controls (p < 0.05 for both). FEP patients with longer duration of pharmacological treatment and medicated only with antipsychotics had increased GLU compared to FEP with shorter periods, or with those treated with a combination of medications (p < 0.05 for both). Finally, FEP patients treated only with antipsychotics presented higher Glx compared to those with mixed medications (p = 0.026). Our study suggests that FEP have low a GABA plasma profile. Unaffected siblings may be a possible risk group for metabolic abnormalities.

Early-life stress effects on BDNF DNA methylation in first-episode psychosis and in rats reared in isolation

Stressful events during early-life are risk factors for psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is implicated in psychosis pathophysiology and deficits in BDNF mRNA in animal models of psychiatric disease are reported. DNA methylation can control gene expression and may be influenced by environmental factors such as early-life stress. We investigated BDNF methylation in first-episode psychosis (FEP) patients (n = 58), their unaffected siblings (n = 29) and community-based controls (n = 59), each of whom completed the Childhood Trauma Questionnaire (CTQ); BDNF methylation was also tested in male Wistar rats housed isolated or grouped from weaning. DNA was extracted from human blood and rat brain (prefrontal cortex and hippocampus), bisulphite-converted and the methylation of equivalent sequences within BDNF exon IV determined by pyrosequencing. BDNF methylation did not differ significantly between diagnostic groups; however, individuals who had experienced trauma presented higher levels of methylation. We found association between the mean BDNF methylation and total CTQ score in FEP, as well as between individual CpG sites and subtypes of trauma. No significant correlations were found for controls or siblings with child trauma. These results were independent of age, gender, body mass index, BDNF genotype or LINE-1, a measure of global methylation, which showed no significant association with trauma. Isolation rearing resulted in increased BDNF methylation in both brain regions compared to group-housed animals, a correlate of previously reported changes in gene expression. Our results suggest that childhood maltreatment may result in increased BDNF methylation, providing a mechanism underlying the association between early-life stress and psychosis.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study.

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7-17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7–17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

S8. GRIN1 PROMOTER METHYLATION CHANGES IN BLOOD OF EARLY-ONSET PSYCHOTIC PATIENTS AND UNAFFECTED SIBLINGS WITH CHILDHOOD TRAUMA

BackgroundChildhood trauma may lead to impairments in brain development and increases risk at psychiatric disorders. Evidence also suggests that childhood trauma may affect DNA methylation patterns consequently influencing gene expression (Tomassi et al., 2017). Some of this linking may be correlated with N-methyl-d-aspartate receptor (NMDAR) hypofunction, which plays a major role of central aspects of cognitive and negative features of schizophrenia (Lakhan et al., 2013). Specifically, the GRIN1 gene codes the biologically relevant NMDAR subunit involved in the synaptic plasticity which is expressed in a broad of non-neuronal cells (Hogan-Cann et al., 2016).Aims: We investigated DNA methylation in the promoter region of GRIN1 and LINE-1 methylation in first-episode psychosis patients (FEP), their unaffected siblings and community-based controls with and without childhood trauma. We also tested for correlations between GRIN1 methylation and NR1 concentrations in peripheral blood.MethodsThis study is a part of the epidemiological investigation that estimated the incidence of psychosis and the role of environmental and biological factors in psychosis aetiology in the catchment area of Ribeirão Preto, Brazil, from 1st April 2012 to 31st March 2015. The genomic DNA was extracted from blood of 60 FEP patients, 30 of their unaffected siblings and 60 age- and sex-matched community-based controls. Diagnosis and clinical characteristics were assessed using the DSM-IV (First et al., 1997; Del-Ben et al., 2001) and history of childhood trauma was assessed using the Childhood Trauma Questionnaire (Grassi-Oliverira et al., 2006). The genomic DNA was bisulfite converted and pyrosequencing was used to determine methylation levels in three CpGs sites of the GRIN1 gene and of LINE-1, as a measure of global methylation. NR1 plasma concentrations were measured using ELISA (MyBioSource, San Diego, USA). Data were analyzed using General Linear Model with post-hoc Bonferroni correction and Pearson’s correlations.ResultsIndividuals, independent of groups, who had experienced childhood trauma presented higher levels of GRIN1 methylation than those without trauma (CpG1: p=0.004; CpG3: p=0.009). Moreover, individuals with physical neglect demonstrated GRIN1 hypermethylation in comparison to individuals without trauma (CpG1: p=0.027; CpG3: p=0.006). Specifically, siblings with emotional neglect presented increased GRIN1 methylation levels at CpG1 when compared with FEP patients and controls with emotional neglect (p=0.028; p=0.001, respectively) and in relation to siblings without trauma (p=0.004). Siblings with physical neglect also showed increased GRIN1 methylation levels at CpG1 when compared to FEP patients and controls with physical neglect (p=0.010; p=0.003, respectively) and in relation to siblings without physical neglect (p=0.001). Furthermore, FEP patients with emotional neglect showed increased GRIN1 methylation at CpG3 when compared to FEP patients without emotional neglect (p=0.010). No differences were observed in the LINE-1 methylation between individuals with or without childhood trauma.DiscussionThis is the first study demonstrating the association between DNA methylation in GRIN1 and childhood trauma in FEP patients, their unaffected siblings and community-based controls. In addition, the interaction between DNA methylation changes in GRIN1 and childhood trauma may be a predict factor of susceptibility for siblings. All these findings suggest evidence for NMDAR dysfunction in response to trauma, contributing the understanding of some of the epigenetics mechanisms by which early life stress affects the glutamatergic system.

O9.3. CANNABIS CONSUMPTION INCREASES RISK OF PSYCHOSIS IN A SUBGROUP OF PATIENTS WITH HIGH PERIPHERAL BLOOD INFLAMMATION

BackgroundAssociations between cannabis use and psychotic outcomes are consistently reported. Increased innate immune markers have also been suggested as risk factors for psychosis; nevertheless, no study has ever tested whether augmented blood inflammation could be a possible biological mechanism underlying the association between cannabis use and psychosis. We investigated: i) which patterns of peripheral blood cytokines (innate and adaptive immune markers) would be associated with the strongest effect on odds of psychosis; and ii) whether the contribution of cannabis use (lifetime use: yes/no; frequency of use: non-users, less than daily use; daily use) on risk of psychosis would vary between subgroups with low- or high-inflammation.MethodsThe Schizophrenia and Other Psychoses Translational Research: Environment and Molecular Biology (STREAM) is an epidemiological and case-sibling-control study, conducted in Ribeirão Preto catchment area (São Paulo, Brazil) between April 2012 and March 2015, which integrates the international multicentre consortium EU-GEI. We recruited 153 first-episode psychosis patients and 256 community-based controls aged between 16–64 years. Participants answered the Cannabis Experience Questionnaire and plasma cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10, TGF-β) were measured by Multiplex. We firstly investigated which patterns of peripheral blood innate and adaptive immune markers would contribute to the strongest effect on the odds of psychosis. To do that, the sample was divided into quartiles according to cytokine’s percentile distribution (reference group: minimum value – 25th percentile; lower group: 25th – 50th percentile; middle group: 50th – 75th percentile; and upper group: 75th percentile – maximum value). We next investigated whether the effects of the different patterns of cannabis use (lifetime and frequency of use) on the risk of psychosis would differ between subgroups classified as low- or high-inflammatory, using the median (50th percentile) of each cytokine as the cut-off value. All the binary logistic regression analyses were correct for the effects of confounders (gender, age, ethnicity, years of education, body mass index, tobacco smoking, and recreational drugs).ResultsMore than 60% of the patients were classified as high-inflammatory, whereas in the control group, around the same percentage was classified as low-inflammatory. After adjusting for confounders, we observed a dose-response relationship between the percentile’s distribution of IL-10, IL-6, TNF-α, TGF-β and risk of psychosis, with participants classified in the upper percentile having the highest odds ratio when compared with the reference group. The adjusted odds ratio (adj ORs) and 95% CIs range for each cytokine were the following: IL-10 from 4.68 (2.02–10.85) to 11.86 (5.01–28.11), IL-6 from 3.74 (1.61–8.69) to 9.62 (4.15–22.31); TNF-α from 2.18 (1.01–4.73) to 6.88 (3.12–15.17); TGF-β from 2.17 (1.01–4.67) to 3.20 (1.50–6.80). Lifetime cannabis use only increased risk of psychosis in the high-inflammatory subgroup (adj ORs, 95% CIs: IL10: 4.66, 1.62–13.39; IL-6: 2.75, 1.05–7.21). Daily use increased the risk of psychosis even further, and only in the high-inflammatory but not in the low-inflammatory subgroup (adj OR, 95% CIs: IL-10: 14.09, 2.26–87.93; TNF-α: 6.16, 1.28–29.74; IL-6: 4.68, 1.08–20.36), with the exception of TGF-β, for which the effects were seen in the low-subgroup (adj OR, 95% CI: 5.23, 1.17–23.42).DiscussionThe existence of distinct inflammatory profiles indicates possible biological predisposition facilitating immune activation. This would translate into a higher vulnerability to the effects of cannabis use, especially daily use, on risk of psychosis.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (&lt;55 years in men and &lt;65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7–17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Residential Radon Exposure and Cigarette Smoking in Association with Lung Cancer: A Matched Case-Control Study in Korea.

Residential radon exposure and cigarette smoking are the two most important risk factors for lung cancer. The combined effects thereof were evaluated in a multi-center matched case-control study in South Korea. A total of 1038 participants were included, comprising 519 non-small cell lung cancer cases and 519 age- and sex- matched community-based controls. Residential radon levels were measured for all participants. Multivariate logistic regression was used to calculate odds ratios (OR) for lung cancer according to radon exposure (high ≥ 100 Bq/m3 vs. low < 100 Bq/m3), smoking status, and combinations of the two after adjusting for age, sex, indoor hours, and other housing information. The median age of the participants was 64 years, and 51.3% were women. The adjusted ORs (95% confidence intervals [CIs]) for high radon and cigarette smoking were 1.56 (1.03–2.37) and 2.53 (1.60–3.99), respectively. When stratified according to combinations of radon exposure and smoking status, the adjusted ORs (95% CIs) for lung cancer in high-radon non-smokers, low-radon smokers, and high-radon smokers were 1.40 (0.81–2.43), 2.42 (1.49–3.92), and 4.27 (2.14–8.52), respectively, with reference to low-radon non-smokers. Both residential radon and cigarette smoking were associated with increased odds for lung cancer, and the difference in ORs according to radon exposure was much greater in smokers than in non-smokers.

Suspected paracetamol overdose in Monrovia, Liberia: a matched case\u2013control study

BackgroundA cluster of cases of unexplained multi-organ failure was reported in children at Bardnesville Junction Hospital (BJH), Monrovia, Liberia. Prior to admission, children’s caregivers reported antibiotic, antimalarial, paracetamol, and traditional treatment consumption. Since we could not exclude a toxic aetiology, and paracetamol overdose in particular, we implemented prospective syndromic surveillance to better define the clinical characteristics of these children. To investigate risk factors, we performed a case–control study.MethodsThe investigation was conducted in BJH between July 2015 and January 2016. In-hospital syndromic surveillance identified children with at least two of the following symptoms: respiratory distress with normal pulse oximetry while breathing ambient air; altered consciousness; hypoglycaemia; jaundice; and hepatomegaly. After refining the case definition to better reflect potential risk factors for hepatic dysfunction, we selected cases identified from syndromic surveillance for a matched case–control study. Cases were matched with in-hospital and community-based controls by age, sex, month of illness/admission, severity (in-hospital), and proximity of residence (community).ResultsBetween July and December 2015, 77 case-patients were captured by syndromic surveillance; 68 (88%) were under three years old and 35 (46%) died during hospitalisation. Of these 77, 30 children met our case definition and were matched with 53 hospital and 48 community controls. Paracetamol was the most frequently reported medication taken by the cases and both control groups. The odds of caregivers reporting supra-therapeutic paracetamol consumption prior to admission was higher in cases compared to controls (OR 6.6, 95% CI 2.1–21.3). Plasma paracetamol concentration on day of admission was available for 19 cases and exceeded 10 μg/mL in 10/13 samples collected on day one of admission, and 4/9 (44%) collected on day two.ConclusionsIn a context with limited diagnostic capacity, this study highlights the possibility of supratherapeutic doses of paracetamol as a factor in multi-organ failure in a cohort of children admitted to BJH. In this setting, a careful history of pre-admission paracetamol consumption may alert clinicians to the possibility of overdose, even when confirmatory laboratory analysis is unavailable. Further studies may help define additional toxicological characteristics in such contexts to improve diagnoses.

Knowledge, Attitude, and Practices Regarding Dengue Fever among Pediatric and Adult In-Patients in Metro Manila, Philippines.

Background: Knowledge, attitude, and practice (KAP) of in-patients with dengue fever (DF) through hospital-based surveillance has not been done. This study aimed to assess and compare the KAP, identify its predictors, correlation, and protective factors among pediatric and adult patients with DF and community-based controls to structure proactive community-wide DF prevention and control programs. Methods: This case-control study involved clinically or serologically confirmed patients (pediatrics n = 233; adults n = 17) with DF admitted in three public hospitals and community-based controls in Metro Manila, Philippines. A pretested structured KAP questionnaire was administered to participants to assess their KAP. Results: Pediatric and adult patients had significantly lower mean scores in the practice (p < 0.001) domain compared with the pediatric and adult controls. Being in senior high school, having had days in hospital, and rash were predictors of KAP among pediatric patients. Knowledge and attitude of patients with DF did not correlate with their practices against DF. Use of mosquito-eating fish, screen windows, and dengue vaccine were protective factors against DF. Conclusion: The study highlights the importance of behavioral change for knowledge and attitude to have significant effect to practices against DF. Thus, we recommend two comprehensive health programs, Communication for Behavioral Impact (COMBI) and Health Belief Model (HBM).

The U-shaped Relationship Between Serum Methylene Tetrahydrofolate Reductase and Large-artery Atherosclerotic Stroke.

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with ischemic stroke. However, the association between serum MTHFR level and ischemic stroke has not yet been studied. We aimed to examine the association between them in patients with large-artery atherosclerotic stroke and community-based healthy controls. This study includes three hundred ninety-five patients with large-artery atherosclerotic stroke from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and 395 age- and sex-matched healthy controls from Chinese communities. Serum MTHFR concentrations were examined and some conventional risk factors of stroke were collected. The association between serum MTHFR and large-artery atherosclerotic stroke was evaluated. A U-shaped association of serum MTHFR level with large-artery atherosclerotic stroke was observed (p for nonlinearity =0.008). After multivariate adjustment, the odds ratios (95% confidence intervals) of large-artery atherosclerotic stroke associated with the first, second, fourth, and fifth quintiles of MTHFR were 5.62 (1.10-28.87), 2.13 (0.51-8.99), 1.08 (0.21-5.56), and 2.31 (0.57-9.34), respectively, compared with the third quintiles of MTHFR. Adding MTHFR quintiles to a model containing conventional risk factors improved the predictive power for large-artery atherosclerotic stroke (continuous net reclassification improvement=63.78%, p<0.001; categorical net reclassification improvement=2.54%, p=0.012). There is a significant U-shaped relationship between serum MTHFR levels and largeartery atherosclerotic stroke. Our findings raise the possibility that serum MTHFR may have a potential role in the pathogenesis of large-artery atherosclerotic stroke.