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Background While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. Methods Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. Results Patients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P P P P P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P Conclusions Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Evaluate effects of electro-acupuncture (EA) and hormone therapy (HT) on health-related quality-of-life (HRQoL) and sleep in breast cancer survivors with vasomotor symptoms.Forty-five women, randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months, were followed for up to 2 years. Distress caused by, and numbers of, hot flushes, hours slept and times woken up/night, Psychological and General Well-being Index (PGWB) and Women's Health Questionnaire (WHQ) were registered before and during treatment and at 6, 9, 12, 18 and 24 months after start of treatment.After 12 weeks of EA (n = 19), WHQ improved from 0.32 (IQR 0.23-0.53) at baseline to 0.24 (IQR 0.12-0.39; p 0.001) and PGWB from 78 (IQR 53-89) to 79 (IQR 68-93; p = 0.002). All sleep parameters improved and Hot Flush Score (HFS) decreased by 80%. At 12 months, WHQ, PGWB and all sleep parameters remained significantly improved (n = 14) and HFS decreased by 65%. After 12 weeks of HT (n = 18), WHQ improved from 0.29 (IQR 0.15-0.44) at baseline to 0.15 (IQR 0.05-0.22; p = 0.001), PGWB from 75 (IQR 59-88) to 90 (62-97; p = 0.102) and three of five sleep parameters improved.Both EA and HT increased HRQoL and sleep, probably through decreasing numbers of and distress by hot flushes. Although flushes decreased less in the EA group than in the HT group, HRQoL improved at least to the same extent maybe due to other effects of EA, not induced by HT, e.g. on anxiety, vitality and sleep, supported by subscale analyses. EA should be further evaluated as treatment for women with breast cancer and climacteric complaints, since HT no longer can be recommended for these women.

To examine to what extent availability of social integration affects health-related quality of life (HRQoL) in former intensive care unit (ICU) patients and how it relates to corresponding findings in a general reference group. Controlled, multicenter, prospective, explorative study. HRQoL data (SF-36) were collected from three combined medical and surgical ICUs in the south-east of Sweden. Social integration was assessed by the Availability of Social Integration (AVSI) instrument (seven questions related to the social interaction of the patient). As reference group, a random sample (n = 6,093) of people from the uptake area of the hospitals was used. Social integration (AVSI), HRQoL (SF-36), and comorbidity were examined also in the reference group. None. The level of social integration significantly affected HRQoL for the former ICU patients, whereas no such effect was seen for the general reference group. For the ICU patients, social integration affected HRQoL to a larger extent than age, sex, and the ICU-related factors examined, but to a lower extent than the pre-existing diseases. For a comprehensive assessment of HRQoL in former ICU patients, it is mandatory to include the effect of social integration. The original publication is available at www.springerlink.com: Lotti Orvelius, Carl Bäckman, Mats Fredrikson, Eva Simonsson, Peter Nordlund, Anders Samuelsson and Folke Sjöberg, Social integration: an important factor for health-related quality of life after critical illness, 2011, INTENSIVE CARE MEDICINE, (37), 5, 831-838. http://dx.doi.org/10.1007/s00134-011-2137-0 Copyright: Springer Science Business Media http://www.springerlink.com/

This study investigated the effects of anxiety on nonverbal aspects of speech using data collected in the framework of a large study of social phobia treatment. The speech of social phobics (N = 71) was recorded during an anxiogenic public speaking task both before and after treatment. The speech samples were analyzed with respect to various acoustic parameters related to pitch, loudness, voice quality, and temporal aspects of speech. The samples were further content-masked by low-pass filtering (which obscures the linguistic content of the speech but preserves nonverbal affective cues) and subjected to listening tests. Results showed that a decrease in experienced state anxiety after treatment was accompanied by corresponding decreases in (a) several acoustic parameters (i.e., mean and maximum voice pitch, high-frequency components in the energy spectrum, and proportion of silent pauses), and (b) listeners’ perceived level of nervousness. Both speakers’ self-ratings of state anxiety and listeners’ ratings of perceived nervousness were further correlated with similar acoustic parameters. The results complement earlier studies on vocal affect expression which have been conducted on posed, rather than authentic, emotional speech.

Background New and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients. Methods We analyzed baseline data from 476 men and 244 women who participated in “Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care” study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries. Results During the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41). Conclusions Our data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease. Trial registration ClinicalTrials.gov: NCT01049737.

Patients with combat-related posttraumatic stress disorder (PTSD) show altered cognitive and affective processing and symptomatic responding following exposure to trauma reminders. Previous symptom provocation studies using brain imaging have involved Vietnam veterans. In this study neural correlates were investigated in patients with PTSD resulting from trauma in more recent war zones. (15)Oxygen water and positron emission tomography were used to measure regional cerebral blood flow (rCBF) in patients with war- and combat-related chronic PTSD during exposure to combat and neutral sounds. Self-reports and heart rate confirmed symptomatic responding during traumatic stimulation. The war-related condition, as compared to the neutral, increased rCBF in the right sensorimotor areas (Brodmann areas 4/6), extending into the primary sensory cortex (areas 1/2/3), and the cerebellar vermis. RCBF also increased in the right amygdala and in the periaqueductal gray matter adjacent to the pons. During provocation rCBF was lowered in the right retrosplenial cortex (areas 26/29/30 extending into area 23). Symptom provocation in PTSD promote sensorimotor, amygdaloid and midbrain activation. We conclude that perceptually induced symptom activation in PTSD is associated with an emotionally determined motor preparation and propose that subcortically initiated rather than cortically controlled memory mechanisms determine this pattern.

Background Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. Methods We investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann–Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis. Results CXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-κB complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone. Conclusions The CD markers identified in this study further emphasize the significance of components related to NF-κB regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-κB interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD. Electronic supplementary material The online version of this article (doi:10.1186/1471-230X-14-176) contains supplementary material, which is available to authorized users.

Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their antiemetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.

Background: The present study examined the prevalence of social phobia in the Swedish general population and demographic characteristics associated with this anxiety disorder. Methods: Data were obtained by means of a postal survey administrated to 2000 randomly selected adults. A questionnaire, validated against clinical interviews and established social phobia scales, was used to assess social distress in a broad range of phobic situations, as well as the diagnostic criteria for social phobia corresponding to DSM-IV. Interpretable questionnaires were obtained from 1202 respondents (60.1%). Results: The point prevalence of social phobia was estimated at 15.6%, but prevalence rates varied between 1.9 and 20.4% across the different levels of distress and impairment used to define cases. Public speaking was the most common social fear. Social phobia was associated with female gender, low educational attainment, psychiatric medication use, and lack of social support. Conclusions: Although the exact diagnostic boundaries for social phobia are difficult to determine, it can be concluded that social anxiety is a distressing problem for a considerable proportion of the general population.

Based on traditional quality of life scales, it has been suggested that known side-effects of prostate cancer treatment do not influence the quality of life. The present authors have developed an alternative approach to quality of life assessment applying epidemiological methods. Using a self administered questionnaire, we investigated 431 prostate cancer patients and an age stratified sample of 435 randomly selected men. Patients reporting any level of distress due to waning sexual functions (66%) or urine or bowel symptoms (38%), reported a lower psychological well-being compared to patients not reporting these symptoms or patients not distressed by their symptoms. Our results stress that an intact sexual and urinary and bowel functions are important for the quality of life among elderly men with or without prostate cancer.

The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients > or = 55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients > or = 55 years than in those < 55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of "persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.

The objective was to investigate how prostate cancer and its treatment affects sexual, urinary and bowel functions and to what extent eventual complications cause distress. A questionnaire was sent to 431 men aged 50-80 years with prostate cancer diagnosed in 1992 in the Stockholm area (Sweden) and 435 randomly selected men with a similar age distribution. Sexual function, as compared with their youth, was diminished in a majority of all men. The prostate cancer patients were, however, more likely to report low frequency and/or intensity in all aspects of sexual function. A majority of the men were distressed by a waning sexual capacity. The proportion of men with prostate cancer who were severely distressed owing to a decline in sexual function was larger than in the reference group. The willingness to trade off an intact sexual function for long-term survival varied considerably among the men in the reference group. Urinary and bowel symptoms were less common than a waning sexual function in both groups, and few appeared to be severely distressed by urinary or bowel symptoms. A decline in sexual functions was the most common cause of disease-specific distress in men with prostate cancer.

Background Hypothermia in burns is common and increases morbidity and mortality. Several methods are available to reach and maintain normal core body temperature, but have not yet been evaluated in critical care for burned patients. Our unit's ordinary technique for controlling body temperature (Bair Hugger®+ radiator ceiling + bed warmer + Hotline®) has many drawbacks e.g.; slow and the working environment is hampered. The aim of this study was to compare our ordinary heating technique with newly-developed methods: the Allon™2001 Thermowrap (a temperature regulating water-mattress), and Warmcloud (a temperature regulating air-mattress). Methods Ten consecutive burned patients (> 20% total burned surface area and a core temperature < 36.0°C) were included in this prospective, randomised, comparative study. Patients were randomly exposed to 3 heating methods. Each treatment/measuring-cycle lasted for 6 hours. Each heating method was assessed for 2 hours according to a randomised timetable. Core temperature was measured using an indwelling (bladder) thermistor. Paired t-tests were used to assess the significance of differences between the treatments within the patients. ANOVA was used to assess the differences in temperature from the first to the last measurement among all treatments. Three-way ANOVA with the Tukey HSD post hoc test and a repeated measures ANOVA was used in the same manner, but included information about patients and treatment/measuring-cycles to control for potential confounding. Data are presented as mean (SD) and (range). Probabilities of less than 0.05 were accepted as significant. Results The mean increase, 1.4 (SD 0.6°C; range 0.6-2.6°C) in core temperature/treatment/measuring-cycle highly significantly favoured the Allon™2001 Thermowrap in contrast to the conventional method 0.2 (0.6)°C (range -1.2 to 1.5°C) and the Warmcloud 0.3 (0.4)°C (range -0.4 to 0.9°C). The procedures for using the Allon™2001 Thermowrap were experienced to be more comfortable and straightforward than the conventional method or the Warmcloud. Conclusions The Allon™2001 Thermowrap was more effective than the Warmcloud or the conventional method in controlling patients' temperatures.

A pharmacological, behavioural and nursing intervention strategy was evaluated for prevention of cisplatin (50 mg m-2) induced emesis in ovarian cancer patients. 46 patients received metoclopramide 2.5 mg kg-1 i.v., b.i.d., dexamethasone 20 mg i.v., lorazepam and biperiden as well as training in relaxation, nutritional advice and continuity in nursing care. Controls (n = 34) received standard treatment (metoclopramide 10-20 mg i.v. or dixyracin 20 mg i.v.). The intensity and duration of nausea and vomiting were significantly lower and measures of quality of life higher for patients on the experimental ward during the three cycles that were studied. No significant changes in emesis were observed between the cycles. There was no correlation between emesis and any of the parameters of quality of life measured. The reliability and validity of nausea ratings are discussed and we suggest that an underreporting of nausea and vomiting might be common.

Lower pre-chemotherapy night time cortisol excretion predicted more severe cisplatin induced nausea and vomiting in 42 ovarian cancer patients receiving ondansetron as a single antiemetic agent. Dexamethasone administration added to the antiemetic effect of ondansetron principally in patients who had low excretion of cortisol.

Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

Twelve patients with borderline hypertension [less than or equal to 21 X 33/12.6, greater than or equal to 18 X 6/12.0 kPa (less than or equal to 160/95; greater than or equal to 140/90 mm Hg)] participated in an experiment aimed at testing whether they could learn to attenuate heart rate while exercising on a cycle ergometer. Six experimental (E) subjects received beat-to-beat heart-rate feedback and were asked to slow heart rate while exercising; six control (C) subjects received no feedback. Averaged over 5 days (25 training trials) the exercise heart-rate of the E group was 97.8 bt min-1, whereas the C group averaged 107 bt min-1 (P = 0.03). Systolic blood pressure was unaffected by feedback training. Generally, changes in rate-pressure product reflected changes in heart-rate. Oxygen consumption was lower in the E than in the C group late in training. We conclude that neurally mediated changes associated with exercise in patients with borderline hypertension can be brought under behavioral control through feedback training.

The slow or total lack of decrease in some autonomic responses during extinction in aversive conditioning and concomitant verbalization of fear have remained a problem for learning theories and psychophysiology. Removal of the aversive stimulus should result in a rapid decrement in responding, as it does in cognitive and somatic systems. In laboratory analogues of phobia and clinical neurosis, however, such decreases do not occur in some autonomic responses and reported fear. In this article three areas of research are presented in which dissociations occur between cognitive and autonomic responses: 1) relational learning, 2) phobia, and 3) incubation. The data indicate that there are some important distinctions to be made concerning the properties of different psychological and physiological systems. These distinctions pertain to the differences between cognitive and noncognitive systems, between the two branches of the ANS, and between acquisition and extinction processes. These distinctions lead to a number of hypotheses concerning dissociations between response systems and have important implications for the understanding and treatment of neurosis.