Systemic effects of epidural Methylprednisolone injection on glucose tolerance in diabetic patients.

ABSTRACT: BACKGROUND: Several studies have shown that in diabetic patients, the glycemic profile was disturbed after intra-articular injection of corticosteroids. Little is known about the impact of epidural injection in such patients. The goal of this study was double, at first comparing the glycaemic profile in diabetic patients after a unique injection of 80 mg of acetate methylprednisolone either intra-articular or epidural and secondly to compare the amount of systemic diffusion of the drug after both procedures. METHODS: Seventeen patients were included. Glycemic changes were compared in 9 diabetic patients following intra-articular (4 patients) and epidural injections (5 patients). Epidural injections were performed using the sacral route under fluoroscopic control in patients with lumbar spinal stenosis. Diabetes control had to stable for more than 10 days and the renal function to be preserved. Blood glucose was monitored using a validated continuous measuring device (GMS, Medtronic) the day before and for two days following the injection. Results were expressed in the form of daily glycemic profiles and as by mean, peak and minimal values +/ SD. The urinary excretion of methylprednisolone after the 2 routes of injection was analyzed in 8 patients (4 in each group). Urine samples were cropped one hour before the injections, then 4 times during the first day and 3 times a week for 2 weeks. The measurements included the free and conjugated fraction RESULTS: The glycaemic profile remains unchanged with no significant changes in the group of the 5 diabetic patients receiving epidural injections. On the other end, the average peak and mean values were enhanced up to 3 mmol/l above baseline two days after the infiltration in the groups of the 4 diabetic patients infiltrated intra-articular. The mean urinary excretion of the steroid was about ten times higher in the intra-articular versus epidural group: 7000 ng/ml versus 700 ng/ml. Looking at each individual there were marked differences especially after intra-articular injections. CONCLUSION: This is the first study to show that a single epidural steroid injection of 80 mg depot methylprednisolone had no effect on the glycemic control in diabetic patients. The absence of glycemic control changes correlated well with the very low urinary excretion of the drug after epidural injection. Trial registration NCT01420497.

Antibody isotypes, including IgG subclasses, in Ecuadorian patients with pulmonary Paragonimiasis

An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074) and IgM (0.303, SEM: 0.033) were significantly elevated (P<0.05). Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116) and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047). The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P<0.001). The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.

Abnormal sensitivity to negative feedback in late-life depression.

AIMS: The purpose of the present study was to probe sensitivity to potentially misleading negative feedback on cognitive tasks as a possible mechanism of cognitive impairment in elderly patients with mild depression. METHODS: A total of 22 mildly depressed elderly subjects were compared to 22 healthy controls, using a computerized Tower-of-London task. RESULTS: Failure and magnitude of failure were significantly worse after negative but not positive feedback. Depression predicted failure after negative feedback but not the magnitude of failure. Neither failure nor magnitude of failure increased as a consequence of repeated negative feedback. CONCLUSIONS: Altered sensitivity to negative feedback occurs in mild late-life unipolar depression and may represent a subtle context-specific phenomenon.

Is the absence of spiritual well-being at the facit-sp equivalent to spiritual distress in older patients?

Objective: Although initially developed to assess spiritual well-being,the FACIT-Sp is increasingly used to assess the other end of the spectrum,i.e. spiritual distress. This study intends to investigate whether theFACIT-Sp could really contribute to this aim in older patients. Method:Patients (N=135, 81.47.1 years, 68.3% women) aged 65 years and over,with MMSE score>19, admitted consecutively in post-acute rehabilitationwere enrolled. The FACIT-Sp (12 items, score 0 to 48, high spiritualwell-being defined as score_36) was administered and commentswere systematically retrieved. Results: Overall, 32(23.7%) patients hadhigh spiritual well-being. FACIT-Sp internal consistency was good(Cronbach's 0.85) and a confirmatory factorial analysis was consistentwith Meaning and Faith proposed subscales. Qualitative analysisshowed that negative answers (score=0) to "My illness has strengthenedmy faith or spiritual beliefs" (N=76/135) could equally reflect theabsence of impact (49/76, 64.5%) or a negative impact (religious struggle,27/76, 35.5%) of illness on faith. However, former patients had significantlyhigher FACIT-Sp scores than the latter (30.35.6 vs 20.97.9,P<.001). Similarly, among patients (N=73/135) with negative answers(score<3) to "I feel a sense of purpose in my life" those mentioning their"old age" to explain their answer (N=34/73, 46.6%) had higher FACITSpscores than those who did not (26.47.7 vs 22.58.1,P=.02). Conclusion:The FACIT-Sp identifies older people with high spiritual wellbeingbut could underestimate well-being in some older patients. Lowscores on some items could have very different meanings and interpretationof FACIT-Sp global scores below the usual cut-off should becautious.

Influence of inflammation on total energy expenditure in hemodialysis patients.

Background and Objectives: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients.Design: This was a cross-sectional study.Setting: This study was conducted from Hopital Edouard Herriot, Lyon, France.Patients: This study included 24 HD patients and 18 healthy subjects.Main Outcome Measure: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein,5 mg/L, aged 67.0 +/- 6 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 +/- 6 18.0 years) and compared with 18 healthy subjects (62.3 +/- 6 15.3 years).Results: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 +/- 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 +/- 6.7 kcal/kg/day) and with healthy subjects (31.8 +/- 6 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 +/- 5,419 and 6,016 +/- 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 +/- 2,754 steps/day, P = .001).Conclusion: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.

Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.

IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Exploration of immune competencies of viral-specific CD8+T cells in MS patients using tetramers and functional CTL assays

Introduction: Epstein-Barr Virus(EBV) has been repeatedly associatedwith multiple sclerosis (MS). Wehave previously shown that there is ahigh peripheral as well as intrathecalactivation of EBV-, but not cytomegalovirus(CMV)-specific CD8+ Tcells, early in the course of MS,strengthening the link between EBVand MS. However, the trigger of thisincreased EBV-specific CD8+ T cellresponse remains obscure. It could resultfrom a higher EBV viral load. Alternatively,it could be due to an intrinsicallydeficient EBV-specificCTL response, cytotoxic granulesmediated.Thus, we performed anin-depth study of the phenotype of exvivo EBV- and CMV-specific CD8+T cells in MS patients and control patients,assessing their cytotoxic activity.Methods:We analyzed the profileof cytotoxic granules in EBV- andCMV-specific CD8+ T cells in a cohortof 13 early MS patients, 20 lateMS, 30 other neurological diseases(OND) patients and 7 healthy controlsubjects. Ex vivo analysis of EBV- orCMV-specific CD8+ T cells was performedusing HLA class I/tetramercomplexes coupled to CCR7 andCD57 markers in conjunction withperforin, granzymes A, BandKstaining.In a sub-cohort of MS patientsand controls, cytotoxic activity ofEBV- and CMV-specific CD8+ Tcells was investigated using a functionalCFSE CTL assay. Results: UsingHLA Class I tetramers for EBVand CMV, we found that the frequencyof EBV- or CMV-specificCD8+ T cells were similar in all studysubjects. Most of EBV- and CMVspecificCD8+Tcells were highly differentiated(CCR7-) and a variousproportion expressed the exhaustionmarker CD57. MS and OND patientshad increased perforin expression inEBV-specific CD8+ T cells. Most importantly,we found that MS patientswith longer disease duration tended tohave lower CTL cytotoxicity as comparedto earlyMSpatients or controls.Conclusions: Effector EBV-specificCD8+ T cells are increased in earlyMS, however their cytotoxic granuleprofile does not seem to be fully alteredand the cytotoxic activity ofthese cells is normal. However, thecytotoxic activity of CTL decreasedin late MS patients suggesting an exhaustionof EBV-specific CD8+ Tcells possibly due to EBV reactivation.This work was supported by theSwiss National Foundation PP00B3-124893, the Swiss Society for MS,and the Biaggi Foundation to RADP.

Catastrophic reaction in acute stroke: a reflex behavior in aphasic patients.

Twelve patients with a catastrophic reaction (CR) (an outburst of frustration, depression, and anger when confronted with a task) were identified in a prospective cohort population (n = 326) with first-ever stroke admitted within 48 hours from onset. The authors' findings suggest that CR is a rare though not exceptional phenomenon in acute stroke and is associated with nonfluent aphasias and left opercular lesions. CR, poststroke depression, and emotionalism are distinct but related disorders.

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes.

BACKGROUND: In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial. PATIENTS AND METHODS: Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy, followed by pleuropneumonectomy and subsequent radiotherapy. QoL was assessed at baseline, at day 1 of cycle 3, and 1, 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist (RSCL) and the Schedule for the Evaluation of Quality of Life-Direct Weighting (SEIQoL-DW), a measure that is based on five individually nominated and weighted QoL-domains. RESULTS: Completion rates were 98% (RSCL) and 92% (SEIQoL) at baseline and 98%/89% at cycle 3, respectively. Of the operated patients (N=45) RSCL and SEIQoL were available from 86%/72%, 93%/74%, and 94%/76% at months 1, 3, and 6 post-surgery. Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL. Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinically significant deterioration (change>or=8 points) 1 month after surgery (median change of -66 and -14 for RSCL and SEIQoL, respectively). RSCL QoL overall scores improved thereafter, but remained beneath baseline level until 6 months after surgery. SEIQoL scores improved to baseline-level at month 3 after surgery, but worsened again at month 6. RSCL QoL overall score and SEIQoL index were moderately correlated at baseline (r=.30; p<or=.05) and at 6-month follow-up (r=.42; p<or=.05) but not at the other time points. CONCLUSION: The SEIQoL assessment seems to be feasible within a phase II clinical trial, but may require more effort from staff. More distinctive QoL changes in accordance with clinical changes were measured with the RSCL. Our findings suggest that the two measures are not interchangeable: the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest.

Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients.

BACKGROUND: Enterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization. OBJECTIVES: To assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM. STUDY DESIGN: Observational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A=no PCR or negative PCR (n=17), group B=positive real-time PCR (n=20), and group C=positive GXEA (n=22). Clinical, laboratory and health-care costs data were compared. RESULTS: Clinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60h (IQR (interquartile range) 44-87) in group B to 5h (IQR 4-11) in group C (p<0.0001). Median duration of antibiotics was 1 (IQR 0-6), 1 (0-1.9), and 0.5 days (single dose) in groups A, B, and C, respectively (p<0.001). Median length of hospitalization was 4 days (2.5-7.5), 2 (1-3.7), and 0.5 (0.3-0.7), respectively (p<0.001). Median hospitalization costs were $5458 (2676-6274) in group A, $2796 (2062-5726) in group B, and $921 (765-1230) in group C (p<0.0001). CONCLUSIONS: Rapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs.

Health services utilization associated with cognitive impairment and dementia in older patients undergoing post-acute rehabilitation.

OBJECTIVE: To investigate the relationship between levels of cognitive impairment and health services utilization in older patients undergoing post-acute rehabilitation. DESIGN: Cross-sectional study. SETTING: Post-acute rehabilitation facility. PARTICIPANTS: Patients (N = 1764) aged 70 years and older admitted over 3 years. MEASUREMENTS: Sociodemographic, medical, and functional data were collected upon admission. Based on discharge diagnoses, patients were classified as cognitively intact, cognitively impaired with no dementia (CIND), and demented. RESULTS: Dementia and CIND were diagnosed in 425 (24.1%) and 301 (17.1%) patients, respectively. Gradients from cognitively intact to cognitively impaired to demented patients were observed in median length of stay (19, 22, and 25 days, P < .001), and institutionalization rates at discharge (4.2%, 7.6%, and 28.8%, P < .001). Among patients discharged home, similar gradients were observed in utilization of home care (68.2%, 79.7%, and 83.3%, P < .001) and day care (3.1%, 7.1%, and 14.3%, P < .001). After adjustment, compared with cognitively intact patients, only those with dementia still had longer stays (+2.7 days) and increased odds of institutionalization (adjOR 6.1, 95% CI 4.0-9.3, P < .001). Among patients discharged home, use of home and day care remained higher in those with dementia (adjOR 1.8, 95% CI 1.2-2.7, P = .005, and adjOR 1.8, 95% CI 1.2-2.7, P = .005, respectively), while CIND patients had higher odds of using home care (adjOR 1.6, 95% CI 1.1-2.4, P = .028). CONCLUSION: Among patients undergoing post-acute rehabilitation, those with dementia had increased use of both institutional and community care, whereas those with CIND had increased use of home care services only. Future studies should investigate specific strategies susceptible to reduce the related burden on health care systems.