Stress-related psychopathology after cardiac surgery and intensive care treatment

Objective: Cardiac surgery patients are at risk for psychopathology. Symptoms of post-traumatic stress disorder (PTSD) and depression occur in 10–20% of these patients and affect their quality of life. The aim of this study was to assess factors associated with psychopathology after cardiac surgery. Methods: We followed participants of the multi-center randomized clinical trial Dexamethasone for Cardiac Surgery (DECS), on a single, intravenous dose of dexamethasone (1 mg/kg) or placebo during cardiac surgery, using validated questionnaires to assess PTSD and depressive symptoms after 1.5 to 4 years, as well as childhood trauma, trait anxiety, pre-existing psychopathology, and substance use. Saliva was used for genotyping of the hypothalamic-pituitary-adrenal-axis (HPA axis) glucocorticoid receptor gene. Linear backward regression analysis was performed with these factors, including pre-specified interaction terms of dexamethasone with sex and genotype. Results: Complete data was available for 90% of cases (n = 1111). The model including trait anxiety and the [dexamethasone x female sex] interaction explained 57% of variance in PTSD symptoms (Model fit F (2;4.817)=643.043, p<.001; R2=0 0.57). Similar explained variance was seen for depressive symptoms, where age, trait anxiety and the [dexamethasone x female sex] interaction provided the optimal model (Model fit F (3;4.261)=435,960, p<.001; R2=0.58). Limitations: In this study psychopathology was assessed through validated questionnaires. Variability in data collection detail was present. Conclusion: This study suggests that the occurrence of psychopathology after cardiac surgery is influenced by higher trait anxiety. Female cardiac surgery patients may benefit from intra-operative dexamethasone administration

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

<p>Abstract</p> <p>Background</p> <p>Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis.</p> <p>Methods</p> <p>Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots.</p> <p>Results</p> <p>A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein).</p> <p>Conclusions</p> <p>A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.</p

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. METHODS: Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. RESULTS: PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. LIMITATIONS: The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. CONCLUSIONS: In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery

Psychopathology after cardiac surgery and intensive care treatment

In this thesis, the occurrence of stress-related psychopathology after cardiac surgery and intensive care treatment is assessed. We primarily focused on post-traumatic stress disorder (PTSD) and depression symptomatology, but the effects of benzodiazepine administration, delirium, anxiety, and cognitive impairment were discussed as well. Psychopathology might hamper full recovery after cardiac surgery and intensive care treatment. Therefore, factors that are potentially associated with the development of psychopathology were explored. The possible association between benzodiazepine use in the intensive care unit (ICU) and the occurrence of various forms of psychopathology - both during ICU admission and after discharge - was investigated. Most evidence was found for an association between benzodiazepines and delirium. The effect of benzodiazepines on long-term types of psychopathology was less clear. Moreover, it remains uncertain how benzodiazepines exert their effects for a considerable period of time after discharge. The extent to which dosage, duration, and administration of other GABAergic medication is of influence, is still unknown as well. Furthermore, we focused on the development of PTSD and depression in cardiac surgery patients who were subsequently admitted to the ICU, examining various potentially associated factors. First, the long-term effects of dexamethasone administration during cardiac surgery versus placebo on the occurrence of PTSD and depression were assessed. Overall, dexamethasone did not have beneficial, nor detrimental effects on psychopathology up to four years after surgery. Second, the role of high trait anxiety, a common personality trait reflecting high neuroticism, was investigated in these patients. We evaluated the possible relation between stress exposure during life and vulnerability to stress-related psychopathology. Trait anxiety was found to be an important mediator of this relationship, and therefore a candidate screening measure in this setting. Third, investigation of common genetic variation in main hypothalamic-pituitary-adrenal axis receptors showed that the protective effect of dexamethasone on symptoms of PTSD was dependent on polymorphisms (i.e., rs41423247, rs10052957, and rs6189) of its main target, the glucocorticoid receptor. Further, no effect on symptoms of depression, nor involvement of genetic variation of the mineralocorticoid receptor or FK506 binding protein was found. Combined, our data supports partial involvement fo trait anxiety in the development of stress-related psychopathology, and a potential beneficial effect of dexamethasone in female patients after cardiac surgery and ICU admission

Läroboksstyrd eller problemlösningsbaserad undervisning : En studie om elevers uppfattningar om matematikundervisningen

Detta är ett forskningsarbete där jag har undersökt elevernas upplevelser av en läroboksstyrd- respektive problemlösningsbaserad undervisning. Dessutom har elevernas åsikter om viktiga aspekter för en stimulerande matematikundervisning undersökts. Empirin har samlats in genom kvalitativa intervjuer med elever i årskurs 2. Resultatet visar att eleverna inte alltid vet vad de gör på matematiklektionerna och att de har svårt att uttrycka och beskriva vad matematikämnet innebär. Eleverna uttrycker en önskan om att få en variation i undervisningen, där de får arbeta både individuellt och i grupp och med en mängd olika material och matematiska områden. Något som eleverna anser är viktigt är också att de får uppgifter med ett tydligt syfte och där det finns ett sammanhang att knyta an till

Reducing unnecessary referrals for colposcopy in hrHPV-positive women within the Dutch cervical cancer screening programme: A modelling study

Background: With the implementation of primary high-risk human papillomavirus (hrHPV) screening in the Netherlands, an increase was observed in the number of unnecessary referrals (≤Cervical Intraepithelial Neoplasia (CIN) 1) to colposcopy. We aimed to investigate which alternative triage strategies safely reduce unnecessary referrals in HPV-based cervical cancer screening programmes. Methods: Microsimulation model MISCAN was used to simulate an unvaccinated cohort of ten million 30-year old Dutch women. We calculated unnecessary referrals, cervical cancer incidence, mortality, costs and QALYs for 24 triage strategies. Condition for direct referral (atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), conditional on HPV-genotype 16/18/other high risk (OHR)), type of triage test (cytology alone or combined with hrHPV) and time to triage test (6 or 12 months) was varied. Results: The 24 triage strategies had varying effects on the number of unnecessary referrals ranging from −72% to +35%. Adjusting conditions for referral to ‘HPV16/18+ and ASC-US+’ and ‘HPVOHR+ and HSIL+’ and extending the interval between tests to 12 months resulted in a reduction in unnecessary referrals of 40% (incidence +0%, mortality −1%). Reduction in unnecessary referrals without genotyping was achieved by adjusting conditions for direct referral to LSIL (12 months to repeat test) (unnecessary referrals −37%, incidence +2%, mortality +0%). Conclusions: To reduce the number of unnecessary referrals without increasing incidence and mortality by more than 2% in the Dutch cervical cancer screening programme, genotyping for HPV16 or HPV16/18 should be implemented with 12 months to repeat testing

Benzodiazepine Use and Neuropsychiatric Outcomes in the ICU : A Systematic Review

OBJECTIVES: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. DATA SOURCES: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. STUDY SELECTION: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. DATA EXTRACTION: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. DATA SYNTHESIS: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods. CONCLUSIONS: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication