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Around half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP − C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C − C = 22) cannabis use. We undertook vertex‐based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p, Cannabis is often associated with the early course of psychotic disorders. The EfCIP study looked at four groups: People with psychosis with cannabis use, people with psychosis without cannabis use, controls with cannabis use and controls without cannabis use. We observe change in subcortical morphology in persons with psychosis with cannabis use versus persons with psychosis without cannabis use in the putamen and thalamus which may be due to compulsive use in this group.

Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups.The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER.We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (50 or ≥50 years) and sex.ER was present in 367 of the 3305 subjects age50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16-3.07) in subjects50 but not in older subjects (interaction between ER and age group, P = .048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41-12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group.ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older.

Schizophrenia patients frequently display an array of abnormal bodily phenomena (ABPs). There is literature to suggest that the presence of ABPs may be representative of a fundamental disruption of the embodied and prereflexive state of selfhood and hence be relevant for the development of schizophrenia spectrum disorders. ABPs have been considered as trait features of vulnerability to psychosis and may have value as potential markers for early detection, target symptoms for prevention and predictors of clinical outcomes. This longitudinal cohort study aimed to explore: (1) the prevalence of ABPs in first episode psychosis, (2) their longitudinal stability, (3) how ABPs compare with data from patients with enduring psychosis, and (4) how aspects of disorders of self-experience (DSEs) and ABPs and the corresponding instruments relate to each other. Sixteen patients were recruited from an early intervention in psychosis service. They were assessed with a series of structured and semi-structured interviews at point of entry, after 6 months and 12 months of follow-up. A variety of ABPs and DSEs were displayed in all study subjects, associated with high levels of core psychotic symptoms and reduced with treatment over time. Compared with findings of both acute and chronic schizophrenia patients, the prevalence of ABPs seems to be representative of severity and acuteness of the illness. Two factors were identified with stable trait characteristics and might be of predictive value for the course of the illness. Further studies with bigger samples are needed to further test the value of ABPs as early markers of detection and predictors of clinical course. The association between DSEs and ABPs warrants further investigation.

Publisher Copyright: © 2021 Elsevier Inc. Background: Negative T-waves are associated with sudden cardiac death (SCD) risk in the general population. Whether flat T-waves also predict SCD is not known. The aim of the study was to examine the clinical characteristics and risk of SCD in general population subjects with flat T-waves. Methods: We examined the electrocardiograms of 6750 Finnish general population adults aged ≥30 years and classified the subjects into 3 groups: 1) negative T-waves with an amplitude ≥0.1 mV in ≥2 of the leads I, II, aVL, V4–V6, 2) negative or positive low amplitude T-waves with an amplitude

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76–0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.

BackgroundCardiac death is one of the leading causes of death and sudden cardiac death (SCD) is estimated to cause approximately 50% of cardiac deaths. Men have a higher cardiac mortality than women. Consequently, the mechanisms and risk markers of cardiac mortality are not as well defined in women as they are in men.AimThe aim of the study was to assess the prognostic value and possible gender differences of SCD risk markers of standard 12-lead electrocardiogram in three large general population samples.MethodsThe standard 12-lead electrocardiographic (ECG) markers were analyzed from three different Finnish general population samples including total of 20,310 subjects (49.9% women, mean age 44.8 ± 8.7 years). The primary endpoint was cardiac death, and SCD and all-cause mortality were secondary endpoints. The interaction effect between women and men was assessed for each ECG variable.ResultsDuring the follow-up (7.7 ± 1.2 years), a total of 883 deaths occurred (24.5% women, p < 0.001). There were 296 cardiac deaths (13.9% women, p < 0.001) and 149 SCDs (14.8% women, p < 0.001). Among those who had died due to cardiac cause, women had more often a normal electrocardiogram compared to men (39.0 vs. 27.5%, p = 0.132). After adjustments with common cardiovascular risk factors and the population sample, the following ECG variables predicted the primary endpoint in men: left ventricular hypertrophy (LVH) with strain pattern (p < 0.001), QRS duration > 110 ms (p < 0.001), inferior or lateral T-wave inversion (p < 0.001) and inferolateral early repolarization (p = 0.033). In women none of the variables remained significant predictors of cardiac death in multivariable analysis, but LVH, QTc ≥ 490 ms and T-wave inversions predicted SCD (p < 0.047 and 0.033, respectively). In the interaction analysis, LVH (HR: 2.4; 95% CI: 1.2–4.9; p = 0.014) was stronger predictor of primary endpoint in women than in men.ConclusionSeveral standard ECG variables provide independent information on the risk of cardiac mortality in men but not in women. LVH and T-wave inversions predict SCD also in women.

The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.

Aims Identifying subjects at high and low risk of atrial fibrillation (AF) is of interest. This study aims to assess the risk of AF associated with electrocardiographic (ECG) markers linked to atrial fibrosis: P-wave prolongation, 3rd-degree interatrial block, P-terminal force in lead V1, and orthogonal P-wave morphology. Methods and results P-wave parameters were assessed in a representative Finnish population sample aged ≥30 years (n = 7217, 46.0% male, mean age 51.4 years). Subjects (n = 5489) with a readable ECG including the orthogonal leads, sinus rhythm, and a predefined orthogonal P-wave morphology type [positive in leads X and Y and either negative (Type 1) or ± biphasic (Type 2) in lead Z; Type 3 defined as positive in lead X and ± biphasic in lead Y], were followed 10 years from the baseline examinations (performed 1978–80). Subjects discharged with AF diagnosis after any-cause hospitalization (n = 124) were defined as having developed AF. Third-degree interatrial block was defined as P-wave ≥120 ms and the presence of ≥2 ± biphasic P waves in the inferior leads. Hazard ratios (HRs) and confidence intervals (CIs) were assessed with Cox models. Third-degree interatrial block (n = 103, HR 3.18, 95% CI 1.66–6.13; P = 0.001) and Type 3 morphology (n = 216, HR 3.01, 95% CI 1.66–5.45; P Conclusion P-wave parameters associate with the risk of hospitalization with AF.

Introduction: Partial and advanced interatrial block (IAB) in the electrocardiographic (ECG) represents inter-atrial conduction delay. IAB is associated with atrial fibrillation (AF) and stroke in the general population. Material and methods: A representative sample of Finnish subjects (n = 6354) aged over 30 years (mean: 52.2 years, standard deviation: 14.6) underwent a health examination including a 12-lead ECG. Five different IAB groups based on automatic measurements were compared to normal P waves using multivariate-adjusted Cox proportional hazard model. Follow-up lasted up to 15 years. Results: The prevalence of advanced and partial IAB was 1.0% and 9.7%, respectively. In the multivariate model, both advanced (hazard ratio (HR): 1.63 (95% confidence interval (CI): 1.00−2.65)) and partial IAB (HR: 1.39 (1.09−1.77)) were associated with increased risk of AF. Advanced IAB was associated with increased risk of stroke or transient ischaemic attack (TIA) independently of associated AF (HR: 2.22 (1.20−4.13)). Partial IAB was also associated with increased risk of being diagnosed with coronary heart disease (HR: 1.26 (1.01−1.58)). Discussion: KEY MESSAGES: Both partial and advanced interatrial block are associated with increased risk of atrial fibrillation in the general population. Advanced interatrial block is an independent risk factor for stroke and transient ischaemic attack. The clinical significance of interatrial block is dependent on the subtype classification.

Obesity is a major risk factor of type 2 diabetes (T2D). Accordingly, weight loss is being used to reduce this risk. Intervention studies have shown a T2D risk reduction due to weight loss in populations with an elevated risk. Data on the prediction of intentional weight loss (IWL) on diabetes occurrence at population level is, however, sparse. Since in observational studies IWL has been shown to predict later weight gain, possibly leading to adverse consequences, this study examined the prediction of IWL on T2D occurrence in a general population. Data from the representative Finnish Health 2000 Survey conducted in 2000–2001 was used. The study sample consisted of 1962 men and 2308 women, aged 30–69. Information on IWL during the previous year was collected with a questionnaire. Data for the covariates was collected with a health examination, interviews and questionnaires. Incident T2D cases during a 15-year follow-up were drawn from national health registers covering information on medication use, hospitalization, and cause of death. The Cox model was used to estimate strength of association between IWL and T2D occurrence. During the follow-up, 417 individuals developed a T2D. After adjusting for socio-demographic and lifestyle factors and the components of metabolic syndrome, IWL predicted an increased risk of T2D occurrence (HR 1.44; 95% CI 1.11–1.87) compared to individuals without IWL. Moreover, in interaction analyses, the risk in individuals with IWL compared to those without IWL was pronounced in younger age group and in those with the lowest quality diet. Furthermore, an elevated risk was consistently found in persons with IWL and overweight (BMI ≥ 25 kg/m2), also in combination with different aspects of poor health (i.e. mental health, self-perceived health, metabolic health). In the present cohort, IWL predicted an increased subsequent risk of developing T2D. This may be due to that in long-term at population level IWL causes an elevated risk of T2D e.g. by acting as a promotor for weight gain or by causing weight cycling resulting in unfavorable changes in metabolic health indicators. Alternatively, it cannot be excluded, that individuals reporting IWL already are at a greater risk of T2D and pursue IWL in response to that. Greater emphasis should be put on the initial prevention of weight gain and on the support on the weight maintenance after weight loss. Further cohort studies with repeated measurements on dieting behavior and changes in weight are needed.

IntroductionObservational and intervention studies have verified that weight loss predicts a reduced type 2 diabetes (T2D) risk. At the population level, knowledge on the prediction of self-report intentional weight loss (IWL) on T2D incidence is, however, sparse. We studied the prediction of self-report IWL on T2D incidence during a 15-year follow-up in a general adult population.Research design and methodsThe study sample from the representative Finnish Health 2000 Survey comprised 4270 individuals, aged 30–69 years. IWL was determined with questions concerning dieting attempts and weight loss during the year prior to baseline. Incident T2D cases during a 15-year follow-up were drawn from national health registers. The strength of the association between IWL and T2D incidence was estimated with the Cox model.ResultsDuring the follow-up, 417 incident cases of T2D occurred. IWL predicted an increased risk of T2D incidence (HR 1.44; 95% CI 1.11 to 1.87, p=0.008) in a multivariable model. In interaction analyses comparing individuals with and without IWL, a suggestively elevated risk emerged in men, the younger age group, among less-educated people and in individuals with unfavorable values in several lifestyle factors.ConclusionsSelf-report IWL may predict an increased risk of T2D in long-term, probably due to self-implemented IWL tending to fail. The initial prevention of weight gain and support for weight maintenance after weight loss deserve greater emphasis in order to prevent T2D.

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with heart failure, stroke, and increased mortality. The myocardial substrate for AF is poorly understood because of limited access to primary human tissue and mechanistic questions around existing in vitro or in vivo models. Methods: Using an MYH6:mCherry knock-in reporter line, we developed a protocol to generate and highly purify human pluripotent stem cell–derived cardiomyocytes displaying physiological and molecular characteristics of atrial cells. We modeled human MYL4 mutants, one of the few definitive genetic causes of AF. To explore non–cell-autonomous components of AF substrate, we also created a zebrafish Myl4 knockout model, which exhibited molecular, cellular, and physiologic abnormalities that parallel those in humans bearing the cognate mutations. Results: There was evidence of increased retinoic acid signaling in both human embryonic stem cells and zebrafish mutant models, as well as abnormal expression and localization of cytoskeletal proteins, and loss of intracellular nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide + hydrogen. To identify potentially druggable proximate mechanisms, we performed a chemical suppressor screen integrating multiple human cellular and zebrafish in vivo endpoints. This screen identified Cx43 (connexin 43) hemichannel blockade as a robust suppressor of the abnormal phenotypes in both models of MYL4 (myosin light chain 4)–related atrial cardiomyopathy. Immunofluorescence and coimmunoprecipitation studies revealed an interaction between MYL4 and Cx43 with altered localization of Cx43 hemichannels to the lateral membrane in MYL4 mutants, as well as in atrial biopsies from unselected forms of human AF. The membrane fraction from MYL4-/- human embryonic stem cell derived atrial cells demonstrated increased phospho-Cx43, which was further accentuated by retinoic acid treatment and by the presence of risk alleles at the Pitx2 locus. PKC (protein kinase C) was induced by retinoic acid, and PKC inhibition also rescued the abnormal phenotypes in the atrial cardiomyopathy models. Conclusions: These data establish a mechanistic link between the transcriptional, metabolic and electrical pathways previously implicated in AF substrate and suggest novel avenues for the prevention or therapy of this common arrhythmia.

Background Sudden cardiac death (SCD) remains a major cause of premature mortality worldwide, so there has been an ongoing pursuit for tools for SCD risk stratification. Coronary artery disease is the major cause for SCD in adults, but the level of risk associated with multiple cardiovascular risk factors is not well established. Purpose To create a clinical risk score for estimating SCD risk in the general population. Methods Using data from a Finnish general population cohort of 7200 adults (mean age 51y, 46% male) with a mean follow-up of 24±11 years, we assessed the incremental SCD risk associated with the presence of several cardiovascular risk factors. SCD events were adjudicated based on death certificates according to the established criteria (autopsy was performed on 48% of SCD cases). Hazard ratios (HR) for SCD and all-cause mortality were calculated using the Cox proportional hazards model. Of the multiple parameters analysed, male sex, increasing age, diabetes, hypertension, smoking and previously diagnosed cardiac disease were independently associated with SCD in a multivariable model. Based on the magnitude of risk, a SCD risk score was created (2 points: age >70y; 1 point: male sex, age 60–70y, diabetes, hypertension, smoking, cardiac disease). Results 75.2% of the study subjects had 0–2 risk points, 12.8% 3 risk points, and 12.0% >3 risk points. During the follow-up, 400 SCDs occurred. Increasing risk score was associated with a progressively greater risk for SCD (Figure). Compared with subjects without risk factors, those with a risk score of 3 had a HR of 21.2 (95% CI 12.7–35.4, p3 had a HR of 52.6 (95% CI 31.3–88.3, p3 [95% CI 27.6–35.9, p Risk of SCD according to the risk score Conclusions Accumulation of multiple cardiovascular risk factors is associated with a markedly elevated risk for SCD in the general population. This highlights the need for SCD prevention efforts with lifestyle interventions and medical therapy in the high-risk subjects. Studies on focused SCD risk stratification may be warranted in the subjects at highest risk.

Background A substantial portion of the risk of atrial fibrillation (AF) remains unexplained by the established risk markers. However, accurate assessment of AF risk would be beneficial, especially among stroke patients and subjects with symptoms attributable to arrhythmia. Purpose To study the associations of P-wave indices with AF risk in the general population. Methods Electrocardiograms, including orthogonal leads, of 7217 Finnish subjects aged over 30 years who took part in the baseline examinations of the Mini-Finland Health Survey in 1978–80, were digitized. P-wave duration, third-degree interatrial block (IAB), and P terminal force (PTF) were assessed manually. PTF was considered abnormal when the amplitude of the negative terminal part of the P wave in lead V1 was ≥0.1mV and duration ≥40ms. Third-degree IAB was defined as P-wave duration ≥120ms and the presence of ≥2 +/− biphasic P-waves in the inferior leads. Orthogonal P-wave morphology, which is related to left atrial breakthrough site and affected by atrial fibrosis (1 being considered benign, 2 borderline, and 3 shown to be associated with adverse events), was assessed with an automated algorithm, and ascertained manually. Subjects were followed 10 years for AF hospitalization and mortality. The risk of AF associated with P wave parameters was assessed using Cox proportional hazards models. Model discrimination improvement was quantified by the change in C index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results There were 5489 subjects (47.8% male, mean age 50.5 years) with a readable ECG, sinus rhythm, no missing data, and a predefined orthogonal P-wave morphology. Type 3 orthogonal P morphology (n=216, multivariate adjusted HR [maHR] 3.01, 95% confidence interval [CI] 1.66–5.45, p Conclusions P-wave indices and orthogonal P-wave morphology can be used to identify subjects at high and low risk for AF and possibly direct extensive AF screening protocols towards high-risk subjects in the general population in order to decrease the risk of cardioembolic stroke. However, more research is needed in this topic. Acknowledgement/Funding Finnish Medical Foundation, Onni and Hilja Tuovinen's Foundation, Orion Research Foundation, Paavo Nurmi's Foundation, Veritas Foundation

ObjectiveWe investigated whether combining several ECG abnormalities would identify general population subjects with a high sudden cardiac death (SCD) risk.MethodsIn a sample of 6830 participants (mean age 51.2±13.9 years; 45.5% male) in the Mini-Finland Health Survey, a general population cohort representative of the Finnish adults aged ≥30 years conducted in 1978–1980, we examined their ECGs, following subjects for 24.3±10.4 years. We analysed the association between individual ECG abnormalities and 10-year SCD risk and developed a risk score using five ECG abnormalities independently associated with SCD risk: heart rate >80 beats per minute, PR duration >220 ms, QRS duration >110 ms, left ventricular hypertrophy and T-wave inversion. We validated the score using an external general population cohort of 10 617 subjects (mean age 44.0±8.5 years; 52.7% male).ResultsNo ECG abnormalities were present in 4563 subjects (66.8%), while 96 subjects (1.4%) had ≥3 ECG abnormalities. After adjusting for clinical factors, the SCD risk increased progressively with each additional ECG abnormality. Subjects with ≥3 ECG abnormalities had an HR of 10.23 (95% CI 5.29 to 19.80) for SCD compared with those without abnormalities. The risk score similarly predicted SCD risk in the validation cohort, in which subjects with ≥3 ECG abnormalities had HR 10.82 (95% CI 3.23 to 36.25) for SCD compared with those without abnormalities.ConclusionThe ECG risk score successfully identified general population subjects with a high SCD risk. Combining ECG risk markers may improve the risk stratification for SCD.

Negative U-waves are a relatively rare finding in an electrocardiogram (ECG), but are often associated with cardiac disease. The prognostic significance of negative U-waves in the general population is unknown. We evaluated 12-lead ECGs of 6,518 adults (45% male, mean age 50.9 +/- 13.8 years) for the presence of U-waves, and followed the subjects for 24.5 +/- 10.3 years. Primary end points were all-cause mortality, cardiac mortality, and sudden cardiac death; secondary end point was hospitalization due to cardiac causes. Negative U-waves (amplitude >= 0.05 mV) were present in 231 subjects (3.5%), minor negative (amplitude 0.30). In conclusion, negative U-waves are associated with adverse events in the general population. In men, this association is independent of cardiovascular risk factors. (C) 2018 Elsevier Inc. All rights reserved.

Background— Prevalence and prognostic significance of abnormal P terminal force (PTF) in the general population are not known. The aim of this study was to assess the prevalence of abnormal PTF and to compare clinical outcomes of middle-aged subjects with and without the PTF. Methods and Results— The presence of PTF was assessed in a cohort of 10 647 middle-aged subjects (mean age [SD], 44 [8] years; 47.2% female). The subjects were followed 35 to 41 years, and data on mortality and hospitalizations were obtained from national registers. Primary outcomes were all-cause mortality, cardiac mortality, and arrhythmic death. Secondary outcomes were hospitalization because of congestive heart failure, coronary heart disease, new onset atrial fibrillation, and stroke. The Cox proportional hazards model was used to assess the risk for death (all-cause), and the Fine and Gray competing risks model was used for other outcomes. The prevalence of PTF 0.04 to 0.049, 0.05 to 0.059, and ≥0.06 mm·s were 4.8%, 1.5%, and 1.2%, respectively. Subjects presenting PTF ≥0.04 mm·s were at increased risk for death, cardiac death, and congestive heart failure, and subjects presenting PTF ≥0.06 mm·s were at increased risk for atrial fibrillation. However, after adjustment for potential confounding factors, an increased risk was observed only for death (hazard ratio, 1.76; 95% confidence interval, 1.45–2.12; P P Conclusions— PTF ≥0.04 mm·s is a relatively common finding in a 12-lead ECG of middle-aged subjects. PTF ≥0.06 mm·s is associated with increased risk for atrial fibrillation and death in the general population.

Background QRS transition zone is related to the electrical axis of the heart in the horizontal plane and is easily determined from the precordial leads of a standard 12-lead ECG. However, whether delayed QRS transition, or clockwise rotation of the heart, carries prognostic implications and predicts sudden cardiac death (SCD) is unclear. Objective The purpose of this study was to study whether delayed transition is associated with mortality and SCD. Methods We evaluated 12-lead ECGs of 10,815 Finnish middle-aged subjects from the general population (52% men, mean age 44 ± 8.5 years) and followed them for 30 ± 11 years. Main end-points were mortality and SCD. Results Delayed QRS transition at lead V 4 or later occurred in 1770 subjects (16.4%) and markedly delayed transition at lead V 5 or later in 146 subjects (1.3%). Delayed transition zone was associated with older age, male gender, higher body mass index, hypertension, baseline cardiovascular disease, leftward shift of the frontal QRS axis, wider QRS-T angle, and ECG left ventricular hypertrophy. After adjusting for several clinical and ECG variables, delayed transition was associated with overall mortality (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.07–1.22, P P = .029). Markedly delayed transition at V 5 or later predicted significantly SCD (HR 1.89, 95% CI 1.18–3.03, P = .008) and all-cause mortality (HR 1.30, 95% CI 1.07–1.58, P = .01). However, further adjustments for repolarization abnormalities attenuated this effect. Conclusion Delayed QRS transition in the precordial leads of an ECG seems to be a novel ECG risk marker for SCD. In particular, markedly delayed transition was associated with significantly increased risk of SCD, independent of confounding factors.

Certain electrocardiographic (ECG) abnormalities are associated with ischemic stroke (IS), especially cardioembolic subtype. Besides atrial fibrillation, markers of left ventricular hypertrophy (LVH) or atrial pathology also reflect elevated risk. We studied the association of ECG markers with IS in young adults.We performed a case-control study including 567 consecutive IS patients aged 15-49 years (inclusion period: 1994-2007) and one or two age- and sex-matched control subjects enrolled during 1978-1980 (n = 1033), and investigated also the stroke aetiologic subgroups. We studied ECGs of all participants for markers of atrial abnormality, i.e. P-terminal force (PTF) on lead V1, interatrial blocks (IAB; P-wave duration ≥110 ms), and LVH. Conditional logistic regression analyses were used.IAB (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.16-2.13) and PTF combined with LVH (HR: 6.83, 95% CI: 1.65-28.31), were independently associated with IS. LVH, abnormal P-wave (HR: 6.87, 95% CI: 1.97-135.29), PTF, IAB, and combinations of these P-wave abnormalities with LVH - were associated with cardioembolic subtype. Abnormal P-wave and IAB were associated with cryptogenic stroke subtype. In unadjusted analysis, LVH was associated with small-vessel disease subtype.P-wave abnormalities on ECG were associated with cardioembolic but also with a cryptogenic subtype of IS. Key messages ECG patterns associated with atrial pathology are markers of increased risk of ischemic stroke in young adults. The ECG markers reflecting atrial pathology were seen in patients with cardioembolic and cryptogenic subtypes of ischemic stroke.

Sudden cardiac death (SCD) causes a high burden of premature deaths in the population affecting subjects of all ages. The identification of subjects at high risk for SCD is of great importance as the prevention of many of these events would be possible with the treatment of underlying cardiac diseases and the use of implantable cardioverter-defibrillators (ICD). However, the current selection of patients for ICD therapy is based solely on left ventricular ejection fraction, and thus a substantial portion of patients at high risk does not qualify for the therapy. Role of the standard electrocardiogram (ECG) in SCD risk stratification has been under active research during the last decade and multiple abnormalities of depolarization and repolarization on the ECG associated with an increased risk of SCD have been identified. In this review, we describe the basic pathophysiological principles behind these changes. We also review the current knowledge of the prognostic significance of ECG predictors of SCD in the general population, and in patients with coronary heart disease (CHD), heart failure, cardiomyopathies, and in inheritable arrhythmia syndromes. Also, insights into the novel digital ECG signal processing techniques are provided.

Background: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. Methods: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose = 9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). Results: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p

Background Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication. Using repetitive transcranial magnetic stimulation (rTMS) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms. Methods We performed a double-blind randomized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia. 17 right-handed patients with prominent negative symptoms (PANSS negative subscore ≥ 20) were randomized to a 10 day course of real ( n = 8) or sham rTMS ( n = 9) applied to the left dorsolateral prefrontal cortex (20 trains per day, 10 s treatment at 10 Hz, 50 s inter-train interval, 110% of motor threshold). The primary outcome measure was PANSS negative symptom score. Secondary outcomes included mood, cognitive function and side-effects. Patients were followed-up two weeks afterwards. The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA. Results All subjects completed the treatment course. There was no significant difference between the two groups on PANSS negative symptom scores at either time point. At the end of treatment, no subjects in either group met the criterion for response (i.e. a 20% reduction in baseline PANSS negative symptom score). The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up. Conclusions Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up.

Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors.

Background: Dysfunction of the prefrontal cortex is implicated in craving for drugs and food. This study explores the effect of prefrontal cortex stimulation on food craving. Methods: In a randomized double-blind parallel group study, 28 women, who reported frequent cravings for food were exposed to foods that typically elicit strong cravings before and after a single session of real or sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex at an intensity of 110% individual motor threshold. Results: Self-reported food craving during exposure to the experimental foods remained stable before and after real stimulation compared with sham stimulation in which cravings increased over the experimental session. Consumption of snack foods within a 5-min period after stimulation did not differ between groups. Conclusions: Prefrontal stimulation inhibits the development of craving. A longer period of observation is necessary to establish whether there is an effect on food consumption.

BackgroundMost studies reporting the gender difference in age at onset of schizophrenia show an earlier onset in males, but vary considerably in their estimates of the difference. This may be due to variations in study design, setting and diagnostic criteria. In particular, several studies conducted in developing countries have found no difference or a reversed effect whereby females have an earlier onset. The aim of the study was to investigate gender differences in age of onset, and the impact of study design and setting on estimates thereof.MethodStudy methods were a systematic literature search, meta-analysis and meta-regression.ResultsA total of 46 studies with 29218 males and 19402 females fulfilled the inclusion criteria and were entered into a meta-analysis. A random-effects model gave a pooled estimate of the gender difference of 1.07 years (95% confidence interval 0.21–1.93) for age at first admission of schizophrenia, with males having earlier onset. The gender difference in age at onset was not significantly different between developed and developing countries. Studies using Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria showed a significantly greater gender difference in age at onset than studies using International Classification of Diseases (ICD) criteria, the latter showing no difference.ConclusionsThe gender difference in age of onset in schizophrenia is smaller than previously thought, and appears absent in studies using ICD. There is no evidence that the gender difference differs between developed and developing countries.

Objective: To investigate if repetitive transcranial magnetic stimulation (rTMS) was as effective as electroconvulsive therapy (ECT) in treating major depressive episodes and to perform a cost-effectiveness analysis. Design: A single-blind pragmatic multicentre randomised controlled trial (RCT) with 6 months of follow-up to test equivalence of rTMS with ECT Setting: The South London and Maudsley NHS Trust and Pembury Hospital in the Invicta Mental Health Trust in Kent. Participants: Right-handed adult patients referred for ECT for treatment of a major depressive episode (DSM-IV) were assessed. During the 2.5-year trial period, 260 patients were referred for ECT, of whom 46 entered the trial. The main reason for not entering the trial was not consenting to ECT while being formally treated under the UK Mental Health Act 1983. Interventions: Patients were randomised to receive a 15-day course of rTMS of the left dorsolateral prefrontal cortex (n = 24) or a course of ECT (n = 22). Main outcome measures: Patients were assessed before randomisation, at end of treatment and at the 6-month follow-up. Primary outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD) and proportion of remitters (defined as HRSD score ≤8) at the end-of-treatment time point. Secondary outcomes included self-ratings for mood on the Beck Depression inventory-II (BDI-II) and visual analogue mood scales (VAMS), the Brief Psychiatric Rating Scale (BPRS), plus subjective and objective side-effects. Low scores on the BDI-II, VAMS and BPRS are positive in terms of health. The results were analysed on an intention-to-treat basis. Cost data were collected using the Client Service Receipt Inventory and the Short Form with 36 Items was used to obtain quality of life measures. Health economic outcomes were cost of treatments, costs incurred during the 6-month follow-up period and gains in quality-adjusted life-years (QALYs). Results: One patient was lost to follow-up at end of treatment and another eight at 6 months. The end-of-treatment HRSD scores were lower for ECT, with 13 (59%) achieving remission compared with four (17%) in the rTMS group. However, HRSD scores did not differ between groups at 6 months. BDI-II, VAMS and BPRS scores were lower for ECT at end of treatment and remained lower after 6 months. Improvement in subjective reports of side-effects following ECT correlated with antidepressant response. There was no difference between the two groups before or after treatment on global measures of cognition. Athough individual treatment session costs were lower for rTMS than ECT, the cost for a course of rTMS was not significantly different from that for a course of ECT as more rTMS sessions were given per course. Service costs were not different between the groups in the subsequent 6 months but informal care costs were significantly higher for the rTMS group and contributed substantially to the total cost for this group during the 6-month follow-up period. There also was no difference in gain in QALYs for ECT and rTMS patients. Analysis of cost-effectiveness acceptability curves demonstrated that rTMS has very low probability of being more cost-effective than ECT. Conclusions: ECT is a more effective and potentially cost-effective antidepressant treatment than 3 weeks of rTMS as administered in this study. Optimal treatment parameters for rTMS need to be established for treating depression. More research is required to refine further the administration of ECT in order to reduce associated cognitive side-effects while maintaining its effectiveness. There is a need for large-scale, adequately powered RCTs comparing different forms of ECT. The next generation of randomised trials of rTMS should also seek to compare treatment variables such as stimulus intensity, number of stimuli administered and duration of treatment, with a view to quantifying an effect size for antidepressant action. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

The study explored patterns of risk behavior and knowledge about HIV and AIDS among patients in an inpatient psychiatric facility in south India. Fifty-nine consecutive patients admitted to a state psychiatric hospital were interviewed using a semistructured questionnaire. Fifty-one percent had a history of recent risk behavior, and 86 percent had inadequate knowledge about AIDS. The most common high-risk behavior was unprotected heterosexual intercourse with a high-risk partner. There was no correlation between knowledge and high-risk behavior. The findings underscore the need to specifically tailor intervention programs.

Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis. Oxidative stress has also been implicated in the extrapyramidal symptoms (EPS) produced by haloperidol. Supporting the oxidative stress hypothesis, vitamin E (antioxidant) has demonstrated therapeutic efficacy in idiopathic parkinsonism. The prophylactic efficacy of vitamin E (antioxidant) on haloperidol-induced EPS was examined in a randomized controlled trial. The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial. All patients received oral haloperidol 10 mg/day. The sample was equally randomized to receive either haloperidol alone or haloperidol + vitamin E (3200 IU/day). EPS was rated at recruitment, both live and with video records, and on days 3, 7, 10 and 14. Psychopathology was rated at recruitment and weekly thereafter. Vitamin E had no prophylactic effect on drug-induced EPS, though it did not interfere with the therapeutic efficacy of haloperidol.