Self-Critical Perfectionism Predicts Lower Cortisol Response to Experimental Stress in Patients With Chronic Fatigue Syndrome

Previous studies have shown that self-critical perfectionism (SCP) is implicated in Chronic Fatigue Syndrome (CFS). However, to date, no studies exist that have examined whether SCP is related to a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis, which has been shown to be a key factor in the pathophysiology of CFS. We conducted a quasi-experimental study to examine the effects of SCP (as measured with the Depressive Experiences Questionnaire) on stress reactivity in a sample of 41 female CFS patients. Participants were exposed to the Trier Social Stress Test (TSST). Both subjective stress and salivary cortisol levels were measured until 90 minutes after the TSST. We also examined the relationship between stress reactivity and illness characteristics (i.e. duration and severity of symptoms). The results showed that SCP was associated with increased subjective stress reactivity, but with decreased HPA-axis reactivity as indicated by a blunted cortisol response to the TSST. Reduced cortisol reactivity was associated with greater symptom severity. There was no relationship between cortisol reactivity and illness duration. Our findings suggest that SCP is associated with loss of resilience of the neurobiological stress response system in CFS

Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies

properly cited. Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population

Cortisol and Subjective Stress Responses to Acute Psychosocial Stress in Fibromyalgia Patients and Control Participants

OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may play a role in fibromyalgia (FM) pathogenesis, but remains understudied in this disorder. Furthermore, early childhood adversities (ECA) are common in FM, but whether they moderate stress reactivity is unknown. Hence, we investigated cortisol and subjective responses to acute psychosocial stress in FM and controls, while adjusting for ECA. METHODS: Twenty-seven female FM patients and 24 age-matched female controls were recruited in a tertiary care center and through advertisements, respectively. The Childhood Trauma Questionnaire was used to measure ECA history. Salivary cortisol levels and subjective stress ratings were measured at multiple time points before and after the Trier Social Stress Test (TSST) was administered. RESULTS: Significant main effects of group [F(1,43)=7.04, p=0.011, lower in FM] and ECA [F(1,43)=5.18, p=0.028, higher in participants with ECA] were found for cortisol responses. When excluding controls with ECA (n=5), a significant group-by-time interaction was found [F(6,39)=2.60, p=0.032], driven by a blunted response to the stressor in FM compared with controls (p=0.037). For subjective stress responses, a significant main effect of group [F(1,45)=10.69, p=0.002, higher in FM] and a trend towards a group-by-time interaction effect [F(6,45)=2.05, p=0.078, higher in FM 30 minutes before and 30 and 75 minutes after the TSST, and impaired recovery (difference immediately after - 30 minutes after the TSST) in FM] were found. CONCLUSIONS: Blunted cortisol responsivity to the TSST was observed in FM patients compared with controls without ECA. FM patients had higher subjective stress levels compared with controls, particularly at baseline and during recovery from the TSST. In FM patients, ECA history was not associated with cortisol or subjective stress levels, or with responsivity to the TSST. Future research should investigate the mechanisms underlying HPA axis dysregulation in FM

Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients

Although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (CFS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and trauma in early childhood. Consistent with findings suggesting that early life stress-induced DNA methylation changes may underlie dysregulation of the HPA axis, we previously found evidence for the involvement of glucocorticoid receptor (GR) gene (NR3C1) methylation in whole blood of CFS patients. Methods In the current study, we assessed NR3C1-1F region DNA methylation status in peripheral blood from a new and independent sample of 80 female CFS patients and 91 female controls. In CFS patients, history of childhood trauma subtypes was evaluated using the Childhood Trauma Questionnaire short form (CTQ-SF). Results Although absolute methylation differences were small, the present study confirms our previous findings of NR3C1-1F DNA hypomethylation at several CpG sites in CFS patients as compared to controls. Following multiple testing correction, only CpG_8 remained significant (DNA methylation difference: 1.3% versus 1.5%, p < 0.001). In addition, we found associations between DNA methylation and severity of fatigue as well as with childhood emotional abuse in CFS patients, although these findings were not significant after correction for multiple testing. Conclusions In conclusion, we replicated findings of NR3C1-1F DNA hypomethylation in CFS patients versus controls. Our results support the hypothesis of HPA axis dysregulation and enhanced GR sensitivity in CFS

Recognition of patients with medically unexplained physical symptoms by family physicians: results of a focus group study

BACKGROUND: Patients with medically unexplained physical symptoms (MUPS) form a heterogeneous group and frequently attend their family physician (FP). Little is known about how FPs recognize MUPS in their patients. We conducted a focus group study to explore how FPs recognize MUPS and whether they recognize specific subgroups of patients with MUPS. Targeting such subgroups might improve treatment outcomes. METHODS: Six focus groups were conducted with in total 29 Dutch FPs. Two researchers independently analysed the data applying the principles of constant comparative analysis in order to detect characteristics to recognize MUPS and to synthesize subgroups. RESULTS: FPs take into account various characteristics when recognizing MUPS in their patients. More objective characteristics were multiple MUPS, frequent and long consultations and many referrals. Subjective characteristics were negative feelings towards patients and the feeling that the FP cannot make sense of the patient's story. Experience of the FP, affinity with MUPS, consultation skills, knowledge of the patient's context and the doctor-patient relationship seemed to influence how and to what extent these characteristics play a role. Based on the perceptions of the FPs we were able to distinguish five subgroups of patients according to FPs: 1) the anxious MUPS patient, 2) the unhappy MUPS patient, 3) the passive MUPS patient, 4) the distressed MUPS patient, and 5) the puzzled MUPS patient. These subgroups were not mutually exclusive, but were based on how explicit and predominant certain characteristics were perceived by FPs. CONCLUSIONS: FPs believe that they can properly identify MUPS in their patients during consultations and five distinct subgroups of patients could be distinguished. If these subgroups can be confirmed in further research, personalized treatment strategies can be developed and tested for their effectiveness

Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies

Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population

Unraveling the role of perfectionism in chronic fatigue syndrome: Is there a distinction between adaptive and maladaptive perfectionism?

In the current study, we investigated whether the distinction between adaptive (i.e. high personal standards) and maladaptive (i.e. concern over mistakes and doubt about actions) perfectionism that has been found in the literature, is also valid in patients with chronic fatigue syndrome (CFS). We hypothesized that maladaptive, but not adaptive, perfectionism would be significantly and positively related to severity of fatigue and depression in CFS. We examined this hypothesis in a sample of 192 CFS patients using structural equation modelling (SEM). Although the two perfectionism dimensions were related to each other, results supported a model in which only maladaptive perfectionism was positively related to severity of fatigue and depression. Further, we found that depression fully mediated the effect of maladaptive perfectionism on fatigue. The results suggest that adaptive and maladaptive perfectionism are two distinct, albeit related, dimensions in CFS. Findings of this study have important implications for theory and treatment of CFS, particularly for cognitive-behavioral treatment. (C) 2010 Elsevier Ireland Ltd. All rights reserved