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Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
Aims
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Method
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
Results
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
Conclusions
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
To test in first-episode schizophrenia (FES) patients whether early treatment improvement accurately predicts subsequent treatment outcome and to develop a valid definition for early improvement.
Methods
188 first episode schizophrenia inpatients were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and biweekly until discharge within a randomized, double-blind trial. 93 patients were treated with risperidone, 95 with haloperidol. Response was defined as a 40% improvement in PANSS total score from admission to discharge, remission according to the recently proposed consensus criteria and early improvement as an improvement in the PANSS total subscore after the second week. Receiver operator characteristic (ROC) analyses were used to evaluate predictive validity of early improvement and to find the most reasonable cutoff definition according to specificity and sensitivity. A confidence interval for the optimum cutoff was furthermore estimated.
Results
ROC analyses revealed reasonable predictability for response (AUC=0.707) and remission (AUC=0.692) concerning early improvement as a predictor for response/remission. No significant differences were found between the two treatment groups. Early improvement defined as a 46% PANSS total score reduction for response and a PANSS total score reduction of 50% for remission obtained the best results in terms of sensitivity and specificity.
Conclusion
We were able to confirm that early improvement is a valid predictor of subsequent treatment response and remission. FES patients should at least improve up to 30% in the PANSS total score at week 2 to achieve treatment response and remission.
The increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were mahed for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in ouome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
Method
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Results
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Conclusions
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.
To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.
Methods
Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.
Results
Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) and response (AUC = 0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%).
Conclusion
The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms.
Methods:
Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient’s symptoms.
Results:
The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of > 6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors.
Limitations:
The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms.
Conclusion:
Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.
The role of H2 in forming interstellar complex organics is still not clear due to the high activation energies required for “non-energetic” association reactions. In this work, we investigated the potential contribution of H2 to the hydrogenated species (HnNCO) formation on dust grains when the “energetic” processing is involved. The goal is to test whether an additional hydrogenation pathway is possible upon UV irradiation of a CO:H2 ice mixture. It is proposed that the electronically excited carbon monoxide (CO*) induced by UV-photons can react with a ground-state H2 to form HCO, ultimately enhancing the production of COMs in ice mantle.
The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7–54·4] and 44·6 (95% CI 41·6–47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4–45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9–54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.
To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight.
Methods
Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients.
Results
Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p = 0.0004), less suicidality (p = 0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p = 0.0012) at admission were identified to be significant predictors of poor insight at discharge.
Conclusion
The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.
Infrared spectroscopy is the best astronomical tool for studying the composition of cosmic dust. Thanks to the Herschel satellite, dust properties from the FIR to mm wavelength range will be sampled in different astrophysical environments. In the laboratory, the study of the temperature and structural dependence of FIR absorption of cosmic dust analogs including agglomeration is essential to interpret observational spectra. For crystalline materials, FIR single phonon bands are temperature dependent due to the anharmonicity of the vibrational potentials. This strong temperature dependence of the FIR bands’ positions can be used as a thermometer of the dust temperature. In amorphous material, the FIR absorption is dominated by disorder-induced single phonon processes and in the submillimeter and millimeter range by highly temperature-dependent low energy processes, e.g. tunneling transitions in two-level systems. The effect of these processes on the FIR absorptivity in amorphous silicates will be demonstrated.
Shiga toxin-producing Escherichia coli (STEC) bacteria can cause outbreaks and sporadic cases of gastroenteritis in humans. Ruminants are seen as the main reservoir. The aim of this study was to evaluate the spatial association between reported human STEC O157 infections in The Netherlands and different livestock densities. Data were collected at the municipality level and a spatial regression analysis was performed. Between April 1999 and December 2008, 409 symptomatic sporadic cases were registered. Adding an interaction term between season, age, and livestock density showed an increased risk of STEC cases in summer for living in areas with cattle, in particular for young children. In conclusion, cattle, but not pigs or poultry, are indicated as an important source for human STEC O157 infections in rural areas. The association is probably due to direct or indirect contact with cattle, resulting in symptomatic infections, especially in young children.
Early improvement with treatment is thought to be important in patients with first-episode schizophrenia, yet a valid definition is still outstanding.
Aims
To develop a valid definition of early improvement and test its predictive validity regarding response and remission.
Method
We examined 188 in-patients with first-episode schizophrenia. Early improvement was defined as improvement in Positive and Negative Syndrome Scale (PANSS) total score at week 2, response as a 40% PANSS total score improvement at end-point, and remission according to consensus criteria.
Results
Reasonable predictive validity of early improvement was found for a 46% PANSS total score improvement at week 2 and a 50% improvement for remission (area under the curve: response 0.707, remission 0.692). Estimated confidence intervals ranged from 26 to 62% PANSS reduction for response and remission.
Conclusions
Patients with a first episode of schizophrenia should improve by at least 30% in PANSS total score at week 2 to achieve response and remission.
Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.
A model for the unsteady thermal boundary-layer development at the end wall of a shock tube, in partially ionized atmospheric argon, is proposed. Consideration is given to ionization and thermal relaxation processes. In order to obtain some insight into the influence of the relaxation processes on the structure of the boundary layer, a study of the frozen and equilibrium limits has been carried out. The transition from a near-equilibrium situation in the outer part of the boundary layer towards a frozen situation near the wall has been determined numerically. Experimental data on the electron and atom density profiles obtained from laser schlieren and absorption measurements are presented. A quantitative agreement between theory and experiment is found for a moderate degree of ionization (3 %). At a higher degree of ionization the structure of the boundary layer is dominated by the influence of radiation cooling, which has been neglected in the model.
In 2002, in The Netherlands a national study of gastroenteritis outbreaks was performed. Epidemiological information was collected by the Public Health Services (PHS) and the Food Inspection Services (FIS) using standardized questionnaires. Stool samples were collected for diagnostic testing. For foodborne outbreaks, food samples were taken. In total, 281 gastroenteritis outbreaks were included, mainly from nursing homes and homes for the elderly (57%), restaurants (11%), hospitals (9%) and day-care centres (7%). Direct person-to-person spread was the predominant transmission route in all settings (overall 78%), except for restaurant outbreaks where food was suspected in almost 90% (overall in 21% of outbreaks). The most common pathogen was norovirus (54%), followed by Salmonella spp. (4%), rotavirus group A (2%), Campylobacter spp. (1%) and only incidentally others. In conclusion, most outbreaks were reported from health and residential institutions, with norovirus as the dominant agent. Control should aim at reducing person-to-person spread. In foodborne outbreaks norovirus was common, due to contamination of food by food handlers. Salmonella, as the second foodborne pathogen, was mainly associated with raw shell eggs. These results stress the continuous need for food safety education, complementary to governmental regulation.
Los datos cada vez más numerosos de que los trastornos afectivos bipolares y unipolares tienen causas biológicas y cursos de enfermedad diferentes se han asociado con una intensificación del interés en los regímenes de tratamiento específicos para ambos trastornos durante la última década. En este contexto, surgió la cuestión de si los antidepresivos ejercen una eficacia similar en el tratamiento agudo de la depresión bipolar comparado con la unipolar. Aunque la impresión clínica no indica diferencias sustanciales en la eficacia de los antidepresivos entre estos grupos de pacientes, las bases de datos empíricas con respecto a esta cuestión son poco frecuentes. El presente estudio comparó la eficacia de los antidepresivos en 50 pacientes hospitalizados deprimidos unipolares y 50 bipolares (criterios de la CIE-9) en condiciones de tratamiento naturalistas. Se emparejó a ambos grupos de pacientes en cuanto a la edad, el género y la duración de la enfermedad. Se utilizaron las evaluaciones clínicas del estado en el momento de la admisión y en el alta para evaluar la respuesta al tratamiento antidepresivo. Los análisis de los datos revelaron que ambos grupos de pacientes necesitaban el mismo tiempo para la respuesta al tratamiento y no mostraban diferencias significativas en las medidas de evolución en el alta. Estos hallazgos no están de acuerdo con la hipótesis formulada por algunos expertos en el campo de los trastornos afectivos de que los antidepresivos son menos efectivos en el tratamiento agudo de los pacientes deprimidos bipolares comparado con los pacientes deprimidos unipolares.
We compared gastroenteritis cases that consulted a general practitioner (GP) with those who did not in a community-based study and also with those in a GP-based study. We aimed to identify factors associated with consultation, and with inclusion of cases by GPs, and secondly to study the effects on the frequency of detection of pathogens. Furthermore, we estimated the under-ascertainment by GPs. Both studies were performed in The Netherlands in the same population in an overlapping time-period. Overall, 5% of community cases consulted a GP. Cases who consulted suffered from more severe episodes than non-consulting cases. Inclusion of cases by GPs, instead of a study team, caused a selection of more severe cases with more chronic symptoms. When extrapolating data from GP-based studies, it should be taken into account that, in general practice, gastroenteritis due to bacteria and Giardia lamblia is a relatively large proportion of that in the community and gastroenteritis due to Norwalk-like viruses is a relatively small proportion. The incidence of gastroenteritis in general practices was estimated between 14 and 35 per 1000 person years.