Analytical Performance Evaluation of a 523-Gene Circulating Tumor DNA Assay for Next-Generation Sequencing-Based Comprehensive Tumor Profiling in Liquid Biopsy Samples.

Next-generation sequencing (NGS)-based comprehensive tumor profiling from liquid biopsy samples can significantly improve diagnosis and monitoring of tumors when high-quality tissue material is difficult to obtain. In addition, it offers the potential to capture the entire complexity of the tumor, which is particularly important for highly heterogeneous or metastatic tumors. Here, we report the findings of an analytical performance evaluation of the TruSight Oncology 500 circulating tumor DNA (ctDNA) assay, a 523-gene NGS panel developed for ctDNA-based comprehensive genomic profiling of tumors, using reference and patient samples. Using 30 ng cell-free DNA, the assay showed high sensitivity and low variant detection variability for single-nucleotide variants, insertions and deletions, and fusions down to a variant allele frequency (VAF) of 0.5% in the reference samples and VAFs that were highly concordant with previous digital droplet PCR results in the patient samples. At reduced input amounts (20, 15, and 5 ng) and below VAFs of 0.5%, sensitivity was considerably lower and variant detection variability increased. Covering 523 tumor-associated genes, the assay demonstrated a convincing performance comparable to NGS-based ctDNA assays with smaller gene panels, highlighting its value to screen large numbers of different genes.

Psychosocial, educational, and somatic factors in chronic nonspecific low back pain.

Analysis of the effect of psychosocial factors and co-morbidities on the health status of patients with chronic nonspecific low back pain and patients with surgical intervention because of disk herniation was performed. One hundred and two nonselected consecutive inpatients with chronic nonspecific low back pain were included in the study. Their average age was 56.7 (SD = 10.9) years. The control group consisted of 199 subjects matched according to age and sex, chosen from the database of the national representative health survey Hungarostudy 2006, which involved 4,527 subjects. We measured quality of life including mental health with the SF-36 questionnaire validated for use in Hungary, the short 9-item version of the Beck Depression Inventory, the WHO-Five Well-Being Index, and the Hospital Anxiety-Depression Scale. We characterized the socio-demographic status with variables on age, sex, marital status, and education. Data on symptoms and signs of low back pain, other musculoskeletal diseases, and their treatments including spinal surgery were recorded. Co-morbidity and body mass index were considered as independent indicators of health. Depression as measured by Beck Depression Inventory and severity of depression did not vary significantly according to marital status, education, hypertension, diabetes, and gastrointestinal disease. Only half of the patients (52 %) were in the normal range of the scale; 22 % suffered from mild, 16 % from moderate, and 12 % from severe depression. Average values for anxiety and depression as measured by Hospital Anxiety-Depression Scale and Beck Depression Inventory were both significantly higher in the patient than in the control group (Hospital Anxiety Scale: p = 0.0001; Beck Depression Inventory: p = 0.0001). According to the WHO Well-Being Index-5 scale, the difference between patients and the control group was significant (p = 0.0001). Furthermore, correlation was found between the incidence of depression and surgery. Depression was demonstrated in 47.4 % of those patients who had no surgery, in 50 % of patients who had one round of surgery, and in 62.5 % of those who had undergone surgery more than once; the contingence coefficient was 0.211. According to different measurements, the psychological state of patients with chronic nonspecific low back pain was significantly altered as compared to the matched Hungarian population. Higher anxiety and depression markers occurred in 48 % of the patients. There was no correlation between the depression of patients with low back pain and variables such as marital status, education, and co-morbidities. Our study is the first to demonstrate that depression runs parallel with the number of surgical procedures. Therefore, if there is a relative indication for surgery, depression and severity of depression should be assessed and considered when deciding on the intervention.

Relationship between religiosity and health: evidence from a post-communist country.

BACKGROUND: The relationship between religiosity and health has been investigated in the western world for decades. However, very little data are available from the post-communist region of Europe, where religion was suppressed for a long time. PURPOSE: The aim of the present study was to lessen this gap. METHODS: In 2002, 13 years after the regime change, 12,643 persons (mean age = 47.6 ± 17.9 years; 44.8 % male) were interviewed in a Hungarian representative survey. The relationship of mental and physical health indicators with religious worship and personal importance of religion-controlling for several psychological and lifestyle characteristics-were analyzed using the general linear model procedure. RESULTS: Our results showed that practicing religion was largely associated with better mental health and more favorable physical health status. However, persons being religious in their own way tended to show more unfavourable results across several variables when compared to those practicing religion regularly in a religious community or even to those considering themselves as non-religious. The personal importance of religion showed a mixed pattern, since it was positively associated not only with well-being but depression and anxiety as well. CONCLUSIONS: We can conclude that even after an anti-religious totalitarian political system practicing religion still remained a health protecting factor.

Proposal for a short version of the Beck Hopelessness Scale based on a national representative survey in Hungary.

In our study we assessed the frequency of reported hopelessness and suicide attempts in the national representative survey Hungarostudy 2002. The randomly selected sample consisted of 14,000 individuals over the age of 18. We created a short version of the widely used Beck Hopelessness Scale for screening purposes in suicide prevention. The short version of the BHS consists of four items and has high internal consistency (Cronbach's alpha = 0.85). Moreover, we conducted an investigation into psychological, somatic, sociological and socio-economic as well as cultural variables that show a positive or negative correlation with hopelessness and important predictors of suicide. The following psychological variables showing a positive correlation with hopelessness were identified: dysfunctional attitudes, exhaustion, psychological distress, hostility, lack of life goals and inability to cope emotionally. Sense of coherence, social support, perceived self-efficiency, subjective well-being and problem-solving coping showed a negative correlation with hopelessness. Concerning the relationship between hopelessness and suicide attempts, we found that participants who attempted suicide in the last year scored higher (mean = 4.86) than participants who attempted suicide more than 3 years ago (mean = 3.57). These results indicate that applying the short version of the BHS could be very useful in general practice and in psychiatric care.

[Indicators of psychological distress among female physicians in Hungary]. / A psziches distressz mutatói magyarországi orvosnok körében.

INTRODUCTION: Somatic and mental health of physicians have become an issue of growing interest. AIM: To explore the prevalence of anxiety, dysfunctional attitudes and hostility among female physicians and analyse the possible correlation between psychological distress and chronic disease. METHOD: Representative, cross-sectional, quantitative survey on a representative sample of female physicians (N + 408). The control group of female physicians was formed from the professional female group of a national survey conducted by "Hungarostudy 2002" (N = 818). RESULTS: Anxiety,high performance demand, perfectionism and an item of hostility scale were significantly higher among physicians. There was no significant connection between psychical distress and chronic disease. Insomnia showed strong, significant correlation with psychical distress. After controlling the risk factors of insomnia, high performance demand and perfectionism proved to be the most important predictors (OR = 1,832 and OR = 1,504). CONCLUSIONS: Present and earlier results show that high performance and perfectionism are connected with insomnia, and that sleeping disorders influence chronic diseases.

[Sleep disorders and physical abuse: a nation-wide representative study in Hungary]. / Az alvászavarok prevalenciája a fizikailag bántalmazott nok körében: országos reprezentativ minta alapján.

OBJECTIVES: Violence against women has been declared a major public health concern. The relationship between physical abuse and physical and psychological symptoms is well-known, however data regarding the association between physical abuse and sleep disorders are limited. Our aim is to document the prevalence of reported abuse and investigate the association between physical abuse and insomnia among females. METHODS: Cross-sectional analyses were conducted on the female sample (N=6987) of the Hungarostudy 2002, a nationwide representative survey. The survey contained sociodemographic questions and a Hungarian version of Athen Insomnia Scale (AIS). RESULTS: We found higher (>10) AIS scores and all of the items of AIS reported higher prevalence among abused women's group than non-abused women. Physical abuse was found to be associated with sleep disturbances (OR=1,707), problems with staying asleep (OR=1,552) and decrease of daytime performance (OR=2,024) after controlling the potential risk factors. CONCLUSION: Women experiencing physical abuse have a significantly higher risk of sleep disorders. The relationship between physical abuse and insomnia deserves further investigation in order to determine the possible pathways of this association.

Mediators between bereavement and somatic symptoms.

BACKGROUND: In our research we examined the frequency of somatic symptoms among bereaved (N = 185) and non-bereaved men and women in a national representative sample (N = 4041) and investigated the possible mediating factors between bereavement status and somatic symptoms. METHODS: Somatic symptoms were measured by the Patient Health Questionnaire (PHQ-15), anxiety with a four-point anxiety rating scale, and depression with a nine-item shortened version of the Beck Depression Inventory. RESULTS: Among the bereaved, somatic symptoms proved to be significantly more frequent in both genders when compared to the non-bereaved, as did anxiety and depression. On the multivariate level, the results show that both anxiety and depression proved to be a mediator between somatic symptoms and bereavement. The effect sizes indicated that for both genders, anxiety was a stronger predictor of somatic symptoms than depression. CONCLUSIONS: The results of our research indicate that somatic symptoms accompanying bereavement are not direct consequences of this state but they can be traced back to the associated anxiety and depression. These results draw attention to the need to recognize anxiety and depression looming in the background of somatic complaints in bereavement and to the importance of the dissemination of related information.

[Are oppressive dreams indicators in bereavement?]. / Van-e a nyomasztó almoknak indikátorszerepük a gyászban?

OBJECTIVES: It is widely believed that oppressive dreams are frequent in bereavement--despite the lack of scientific investigations of the subject. The aims of our study were the analysis of dream quality as well as the correlates of oppressive dreams in bereavement. METHOD: Participants with (N = 473) and without bereavement were compared upon the database of a national representative study (Hungarostudy Epidemiological Panel Survey 2006, N = 4329). Dream contents were assessed with the Dream Quality Questionnaire (DQQ). Depressive symptoms (BDI-S) and the presence anxiety were also investigated. RESULTS: Oppressive dreams occurred significantly higher frequency in the first year of bereavement (men: F = 17.525, p < 0.001, women: F = 8.291, p = 0.004). Oppressive dreams were significantly associated with anxiety (F = 37.089, p < 0.001) and with depressive symptoms (F = 50.562, p < 0.001). DISCUSSION: Oppressive dreams are significantly more frequent in the first year of bereavement, and may act as indicators of bereavement-linked mental health consequences like depression and anxiety. These are often masked by the symptoms of grief and therefore remain untreated. Our preliminary results could be a starting point for the development of further research aiming to clarify the relationship amongst dream contents, anxiety, and depression in bereavement.

A challenging epigenetic message: telomerase activity is associated with complex changes in lifestyle.

As an outcome of The 2009 Nobel Prize in Physiology or Medicine, a connection has been highlighted between the length of telomeres and epigenetic effects, such as intensive changes in lifestyle and nutrition as well as behavioural and psychological factors. In this review, the various elements of molecular, cell biological, nutritional and lifestyle changes are introduced and discussed.

Socio-demographic characteristics, health behaviour, co-morbidity and accidents in snorers: a population survey.

OBJECTIVE: We assessed the socio-demographic correlates of snoring and also the patterns of health behaviour and co-morbidity associated with different types of snoring in the Hungarian population. We wanted to study whether different types of snoring are associated with high-risk health behaviour, chronic illnesses, daytime consequences of poor sleep, and with frequent accidents compared with non-snoring individuals. METHOD: This is a cross-sectional study. Interviews were carried out in the homes of 12,643 people. This was the largest nationally representative study in Central Europe about health behaviour. In the Athens Insomnia Scale, questions about snoring and sleep behaviour, life-style factors and health behaviour, as well as questions on their history and current medical treatment were included in the questionnaire. RESULTS: Thirty-seven percent of males and 21% of females reported loud snoring with breathing pauses. We found a significant increasing trend for the consumption of alcohol and coffee as well as smoking among non-snorers, habitual snorers and loud snorers, respectively. In an ordinal regression model male gender, the presence of smoking, the presence of three or more co-morbid conditions and alcohol consumption were independent predictors of snoring (OR [95% CI], 1.99 [1.85-2.1], 1.76 [1.60-1.92], 1.45 [1.30-1.62] and 1.22 [1.04-1.43], respectively, P < 0.001) after controlling for multiple socio-demographic and clinical variables. The frequency of accidents was higher in the loud snoring group than among non-snoring individuals (24% vs 17%, P < 0.0001). CONCLUSIONS: Snoring is common in the Hungarian adult population. Snoring, especially loud snoring with breathing pauses, is strongly associated with high-risk health behaviour, higher co-morbidity and a higher frequency of accidents.

Drug suicide: a sex-equal cause of death in 16 European countries.

BACKGROUND: There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). METHODS: Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. RESULTS: No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. CONCLUSIONS: Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.

Gender patterns of socioeconomic differences in premature mortality: follow-up of the Hungarian Epidemiological Panel.

BACKGROUND: Gender differences in premature mortality rates and in the size of socioeconomic inequalities in mortality vary across countries. PURPOSE: We aimed to quantify the gender differences in the association between socioeconomic status (SES) and premature all-cause mortality and to analyse whether psychosocial factors might associate between SES and mortality among men and women separately in the middle-aged Hungarian population. METHOD: Men (n = 1130) and women (n = 1529), aged 40-69 years, participants in the Hungarian Epidemiological Panel (2002) were followed up for 3.5 years for total mortality. Cox proportional hazard models were used to evaluate the association between several socioeconomic measures and total death. RESULTS: During the follow-up, 99 men (8.8%) and 53 women (3.5%) died. The age-adjusted hazard ratios and the Rothman's synergy indexes showed that each measure of socioeconomic position was more deleterious in men compared with women. When investigating potential explanatory factors for the SES-mortality association, we found that adjustment for severe depression resulted in the most pronounced reduction in the regression coefficients for the association between most socioeconomic factors and male premature death. There was no indication that depression would mediate between SES and mortality in women. Work stress factors, poor lifestyle and low social support also contributed to the explanation of the link between socioeconomic disadvantage and premature death in men. CONCLUSION: Middle-aged Hungarian men seem to be considerably more vulnerable to the chronic stress of material disadvantage than women. This effect modification by gender might partly be explained by a stronger connection between low SES and depressive symptoms in men.

Early maternal separation, nightmares, and bad dreams: results from the Hungarostudy Epidemiological Panel.

Early maternal separation is a particularly stressful experience. Current models of nightmare production emphasize negative emotionality as having a central role in determining dream affect. Our aim is to test the hypothesis that persons who experienced early maternal separation (before one year of age and lasting at least one month) report more frequent nightmare experiences and bad dreams as adults. In the frame of the Hungarostudy Epidemiological Panel, 5020 subjects were interviewed. Significant associations were found between early maternal separation and both frequent nightmare experience in adulthood and increased frequency of oppressive and bad dreams. Current depression scores fully mediated the association between early separation and nightmares, but not the association between early separation and negative dream affect. We interpret these findings as a trait-like enhancement of negative emotionality in adults who experienced early maternal separation. This enhancement influences the content of dreams and, when it takes the form of depression, also influences the frequency of nightmares.

[Sleep disturbances and nightmares as risk factors for suicidal behavior among men and women]. / Alvászavarok és rémálmok mint az öngyilkossági magatartás férfiak és nok körében.

INTRODUCTION: Today, more and more international studies analyze the connection between sleep disturbances, including nightmares, and the risk of suicide. The majority of these studies focuses on patients with depression and PTSD; a few studies use community samples. The present paper is based on a community sample research; it examines gender differences in the relationship between nightmares and suicidal behavior (ideation and attempt) during the three years preceding the study. METHODS: The database was derived from the data of the national representative survey Hungaro study 2006, the objective of which was the health status of the Hungarian adult population (N=4642). The five-item version of Athens Insomnia Scale was used for the examination of sleep disturbances; depression was measured with the shortened version of the Beck depression questionnaire. The questions dealing with nightmares were part of the Sleep Quality Questionnaire. Sleep problems, nightmares and depression were considered as risk factors for both suicidal ideation and suicide attempts. Associations were analyzed by logistic regression. The data were corrected for age, gender, education, and financial situation. RESULTS: Our analysis verified the connections between suicidal thoughts and attempts, and nightmares. The results show that the frequent occurrence of nightmares is associated with a nearly four times higher risk of suicide attempts among men (OR=3,89) and a threefold increase among women (OR=1,74). For suicidal thoughts, nightmares correlate with a three times higher risk for men (OR=2,97) and one and the half higher risk for women (OR=1,58). In our sample, frequent nightmares and sleep disorders increase the risk of suicidal behavior more than depression. CONCLUSION: After clinical studies proved the influence of sleep problems in various patient groups, our epidemiological study seem to confirm that nightmares have an independent role in the formation of suicidal behavior.

Use of plasma ctDNA as a potential biomarker for longitudinal monitoring of a patient with metastatic high-risk upper tract urothelial carcinoma receiving pembrolizumab and personalized neoepitope-derived multipeptide vaccinations: a case report.

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Only limited data are available concerning therapeutic regimes and potential biomarkers for disease monitoring. Standard therapies often provide only insufficient treatment options. Hence, immunotherapies and complementary approaches, such as personalized neoepitope-derived multipeptide vaccine (PNMV), come into focus. In this context, genetic analysis of tumor tissue by whole exome sequencing represents an essential diagnostic step in order to calculate tumor mutational burden (TMB) and to reveal tumor-specific neoantigens. Furthermore, disease progression is essential to be monitored. Longitudinal screening of individually known mutations in plasma circulating tumor DNA (ctDNA) by the use of next-generation sequencing and digital droplet PCR (ddPCR) might be a promising method to fill this gap.Here, we present the case of a 55-year-old man who was diagnosed with high-risk metastatic UTUC in 2015. After initial surgery and palliative chemotherapy, he developed recurrence of the tumor. Genetic analysis revealed a high TMB of 41.2 mutations per megabase suggesting a potential success of immunotherapy. Therefore, in 2016, off-label treatment with the checkpoint-inhibitor pembrolizumab was started leading to strong regression of the disease. This therapy was then discontinued due to side effects and treatment with a previously produced PNMV was started that induced strong T cell responses. During both treatments, plasma Liquid Biopsies (pLBs) were performed to measure the number of mutated molecules per mL plasma (MM/mL) of a known tumor-specific variant in the MLH1 gene by ddPCR for longitudinal monitoring. Under treatment, MM/mL was constantly zero. A few months after all therapies had been discontinued, an increase of MM/mL was detected that persisted in the following pLBs. When MRI scans proved tumor recurrence, treatment with pembrolizumab was started again leading to a rapid decrease of MM/mL in the pLB to again zero. Treatment response was then also confirmed by MRI.This case shows that use of immunotherapy and PNMV might be a promising treatment option for patients with high-risk metastatic UTUC. Furthermore, measurement of individually known tumor mutations in plasma ctDNA by the use of pLB could be a very sensitive biomarker to longitudinally monitor disease.

[The 2009 Nobel Prize in Medicine and its surprising message: lifestyle is associated with telomerase activity]. / A 2009. évi orvosi Nobel-díj és egy meglepô üzenete: az életmód befolyásolja a telomerázaktivitást.

The 2009 Nobel Prize in Physiology and Medicine was awarded to three scientists for their pioneer research on telomeres - and the enzyme that forms them - telomerase. Their work highlighted the considerable connection between the length of telomeres and intensive changes in lifestyle and nutrition (Ornish method) as well as behavioral and psychological factors. In this review the various elements of molecular, cell biological, nutritional and lifestyle changes are introduced and discussed.

[Psychiatric and somatic morbidity among Hungarian psychiatrists]. / A magyarországi pszichiáterek egészségi állapota.

BACKGROUND: A growing body of evidence in the international literature suggests that the prevalence of psychiatric morbidity including suicide is high among psychiatrists. Based on these data, we hypothesised that the prevalence of psychiatric and somatic morbidity is higher among psychiatrists in Hungary compared to the other graduate population. Aims. To assess the psychiatric and somatic health status of psychiatrists in Hungary. METHODS: Data for this epidemiological study were collected from 160 female and 60 male psychiatrists using questionnaires. 1,754 white collar female and male workers from a representative survey (Hungarostudy 2002) and 407 representative physicians served as controls. RESULTS: We found that the prevalence of chronic somatic morbidity among both female and male physicians was significantly higher than that in the respective control groups. The prevalence of malignancies, diabetes, renal impairment, depression, hypertension, myocardial infarction and cardiovascular diseases, other infectious diseases, allergies and gastrointestinal ulcers was higher among male psychiatrists compared to controls. Female psychiatrists exhibited higher prevalence of malignant diseases, liver disease, depression, hypertension, myocardial infarction, other infectious diseases, bronchial asthma, other pulmonary and cardiovascular diseases, allergies, gastrointestinal diseases including ulcer, ophthalmologic and gynecological disorders compared to the other graduate and female physician population. A significantly higher prevalence of maternal reproductive morbidity including miscarriage, therapeutic termination of pregnancy, high-risk pregnancy among female psychiatrists was found compared to women in the control groups. CONCLUSIONS: The prevalence of psychiatric and somatic morbidity is higher among physicians compared with that in the normative population. Furthermore, female physicians consumed more anxiolytics, reported exhaustion more frequently, and exhibited poorer health maintenance behaviours than male colleagues. Increased mortality among Hungarian physicians may be attributed to high prevalence of somatic and psychiatric morbidity and inattentive health behaviours.

Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors - Results of a Prospective Biomarker Study.

PURPOSE: BRAF and MEK inhibitors significantly improved the prognosis of metastatic melanoma. Nevertheless, initial treatment response may be only temporary. Liquid biopsies (LB) offer a possibility to monitor patients by measuring circulating tumor DNA (ctDNA). We sought to find out whether ctDNA can be used to reliably determine progressive disease under targeted therapy. In addition, we wanted to check whether ctDNA may represent a possible prognostic marker for survival. PATIENTS AND METHODS: We included 19 melanoma patients with BRAF and MEK inhibitor therapy. For each patient, a 710 gene panel was analyzed on the latest available tumor tissue before the start of therapy. Repetitive LB were collected in which BRAF V600E/K mutations were monitored using digital droplet PCR (ddPCR). We correlated radiological staging results and overall survival with ctDNA results. RESULTS: In 13 patients, ctDNA was detectable when starting targeted therapy, whereas in six patients, ddPCR was always negative, which we confirmed with ultra-deep sequencing. All patients with initially detectable ctDNA had ctDNA values declining to zero during follow-up, increasing again at the time of extracerebral progression or even slightly before detection by imaging. Survival was significantly worse for patients with elevated LDH (p=0.034) or detectable ctDNA (p=0.008) at the start of targeted therapy. CONCLUSION: Therapy monitoring by ctDNA seems to be a reliable method for detecting extracranial progression, even more sensitive and specific than LDH or S100B. However, due to the small number of cases in our study, further studies are necessary.

Rapid Next-Generation Sequencing-Based Diagnostics of Bacteremia in Septic Patients.

The increasing incidence of bloodstream infections including sepsis is a major challenge in intensive care units worldwide. However, current diagnostics for pathogen identification mainly depend on culture- and molecular-based approaches, which are not satisfactory regarding specificity, sensitivity, and time to diagnosis. Herein, we established a complete diagnostic workflow for real-time high-throughput sequencing of cell-free DNA from plasma based on nanopore sequencing for the detection of the causative agents, which was applied to the analyses of eight samples from four septic patients and three healthy controls, and subsequently validated against standard next-generation sequencing results. By optimization of library preparation protocols for short fragments with low input amounts, a 3.5-fold increase in sequencing throughput could be achieved. With tailored bioinformatics workflows, all eight septic patient samples were found to be positive for relevant pathogens. When considering time to diagnosis, pathogens were identified within minutes after start of sequencing. Moreover, an extrapolation of real-time sequencing performance on a cohort of 239 septic patient samples revealed that more than 90% of pathogen hits would have also been detected using the optimized MinION workflow. Reliable identification of pathogens based on circulating cell-free DNA sequencing using optimized workflows and real-time nanopore-based sequencing can be accomplished within 5 to 6 hours following blood draw. Therefore, this approach might provide therapy-relevant results in a clinically critical timeframe.

Comorbid depression is associated with increased healthcare utilization and lost productivity in persons with diabetes: a large nationally representative Hungarian population survey.

OBJECTIVE: To estimate the prevalence of depression among people with diabetes and to examine the association of comorbid depression with lost productivity and health resource utilization in persons with and without diabetes. METHODS: Cross-sectional survey, enrolling 12,643 individuals aged >18 years. Clustered, stratified sampling procedure was utilized. This sample represented 0.16% of the Hungarian adult population according to age, gender, and geographic regions. The severity of depressive symptoms was measured by the abbreviated Beck Depression Inventory. RESULTS: The prevalence of diabetes in the sample was 6.2% (95% Confidence Interval (CI) = 5.7-6.6), and 13.4% (95% CI = 12.8-13.9) were classified as depressed. Adults with diabetes were two times more likely to have depression (adjusted odds ratio (OR) = 1.83, 95% CI = 1.53-2.19, p < .001) versus individuals without diabetes. Compared with nondepressed people with diabetes, those with diabetes and comorbid depression were older, less educated, more likely to be female and physically inactive, less likely to be employed, and married and had more comorbidities. In multivariate regression analyses, people with diabetes and depression had significantly greater odds of prolonged bed days due to illness (>or=20 days) (OR = 2.6, 95% CI = 1.69-3.88, p < .001), prolonged length of hospital stay (>or=18 days) (OR = 2.1, 95% CI = 1.27-3.45, p = .004), and multiple hospital admissions (>or=2) (OR = 1.8, 95% CI = 1.13-2.82, p = .01) compared with nondepressed diabetic patients. CONCLUSIONS: These findings further document the association between depression and health resource utilization and lost productivity in people with diabetes. Screening and treating depression are important for everyday clinical care and public health initiatives to improve health outcomes for people with diabetes.