ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

Increasing access to pain management: Feasibility of a self-compassion psychoeducational website using a minimally monitored delivery model.

Self-compassion has been associated with several positive pain-related outcomes. However, little is known about the impact of targeting self-compassion on pain management. This study assesses the feasibility of a self-compassion psychoeducation website among adults with chronic pain using a minimally monitored delivery model. Participants (N = 26) were recruited online and a single group pre-test and post-test design with a 3-month follow-up was used. The intervention was a 6-week program comprised of a video, writing exercises, guided meditations and automated emails. Feasibility outcome measures were grouped into the following categories: study engagement (ease of recruitment, attrition, adherence, satisfaction), pain vulnerability variables (intensity, interference, catastrophizing, mood) and protective pain variables (self-compassion, resilience and acceptance). Challenges pertaining to uptake were encountered. Attrition was higher (n = 11/26; 42%) and adherence to the full treatment protocol lower (n = 6/26; 23%) than expected. Treatment satisfaction was high with nearly all study completers (93%) reporting that they would recommend the program to a friend. Intent-to-treat mixed effects models showed a significant and large increase of self-compassion (d = 0.92) and a significant impact on several outcome variables (ds from 0.24 to 1.15) with most gains either maintained or increased at follow-up. The recruitment strategy may have negatively impacted participant engagement. Methodological modifications are proposed to improve the feasibility of the program. Minimally monitored web-based programs targeting self-compassion may benefit adults with chronic pain who may have limited access to traditional psychological services or who prefer online-based interventions.

Atypical phenotype associated with reported GCK exon 10 deletions: Clinical judgement is needed alongside appropriate genetic investigations.

BACKGROUND: Maturity-onset diabetes of the young (MODY) caused by heterozygous mutations in the glucokinase (GCK) gene typically presents with lifelong, stable, mild fasting hyperglycaemia. With the exception of pregnancy, patients with GCK-MODY usually do not require pharmacological therapy. We report two unrelated patients whose initial genetic test results indicated a deletion of GCK exon 10, but whose clinical phenotypes were not typical of GCK-MODY. CASE REPORTS: In case 1, the patient was hyperglycaemic at diagnosis (glucose > 30 mmol/l) and elevated glucose levels > 10 mmol/l persisted after withdrawal of insulin therapy. The patient in case 2 was also hyperglycaemic at diagnosis [HbA1c > 86 mmol/mol (10%)], which improved with the introduction of oral hypoglycaemic agents. These clinical features were not consistent with GCK-MODY. Both patients had a single nucleotide variant that prevented multiplex ligation-dependent probe analysis, which generated a false positive result of a GCK exon 10 deletion. CONCLUSION: False positive genetic results in these two unrelated cases were attributable to the presence of a rare single nucleotide variant that prevented ligation of the probe in the multiplex ligation-dependent probe analysis kit used and falsely indicated deletion of exon 10 within GCK. Both cases had clinical features that did not tally with the typical GCK-MODY phenotype. These cases emphasize the need to interpret the results of definitive genetic tests within the specific clinical context. Increased medical sequencing is likely to lead to more reports of novel mutations of uncertain significance. If genetic investigations do not agree with the clinical picture, clinicians should exercise caution when making therapeutic changes based on these results.

Green roof valuation: a probabilistic economic analysis of environmental benefits.

Green (vegetated) roofs have gained global acceptance as a technologythat has the potential to help mitigate the multifaceted, complex environmental problems of urban centers. While policies that encourage green roofs exist atthe local and regional level, installation costs remain at a premium and deter investment in this technology. The objective of this paper is to quantitatively integrate the range of stormwater, energy, and air pollution benefits of green roofs into an economic model that captures the building-specific scale. Currently, green roofs are primarily valued on increased roof longevity, reduced stormwater runoff, and decreased building energy consumption. Proper valuation of these benefits can reduce the present value of a green roof if investors look beyond the upfront capital costs. Net present value (NPV) analysis comparing a conventional roof system to an extensive green roof system demonstrates that at the end of the green roof lifetime the NPV for the green roof is between 20.3 and 25.2% less than the NPV for the conventional roof over 40 years. The additional upfront investment is recovered at the time when a conventional roof would be replaced. Increasing evidence suggests that green roofs may play a significant role in urban air quality improvement For example, uptake of N0x is estimated to range from $1683 to $6383 per metric ton of NOx reduction. These benefits were included in this study, and results translate to an annual benefit of $895-3392 for a 2000 square meter vegetated roof. Improved air quality leads to a mean NPV for the green roof that is 24.5-40.2% less than the mean conventional roof NPV. Through innovative policies, the inclusion of air pollution mitigation and the reduction of municipal stormwater infrastructure costs in economic valuation of environmental benefits of green roofs can reduce the cost gap that currently hinders U.S. investment in green roof technology.

Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation.

BACKGROUND/AIMS: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. METHODS: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves. RESULTS: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001). CONCLUSION: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

A review of the relationship between depression and diabetes in adults: is there a link?

OBJECTIVE: To review the support for two hypotheses concerning the interrelationship between depression and diabetes and to identify areas in which more research is needed. RESEARCH DESIGN AND METHODS: A review was conducted using primarily electronic databases. Articles relating to diabetes and depressive symptomatology, depressive disorder, and dysthymic disorder were selected. The study focuses mainly on adults with diabetes. RESULTS: The initial onset of major depressive disorder (MDD) seems to be independent of the onset of type 2 diabetes, but results remain equivocal for type 1 diabetes. However, in both type 1 and type 2 diabetes, diabetes-related psychological and physiological processes may be involved in the higher recurrence and longer duration of MDD and depressive symptomatology CONCLUSIONS: The hypotheses that the initial occurrence of clinically significant depression, MDD, results from either biochemical changes directly due to type 2 diabetes or its treatment or from the psychosocial demands imposed by the illness or its treatment do not seem to be supported. MDD in diabetic individuals represents a multidetermined phenomenon resulting from interactions between biologic and psychosocial factors. This interaction may increase the probability of developing type 2 diabetes in otherwise healthy individuals.

Functional and dysfunctional perfectionists: are they different on compulsive-like behaviors?

Both perfectionism and excessive responsibility have been linked to obsessive compulsive disorder (OCD). Up to now however, a greater number of studies have focused on the role of responsibility. The present study compared compulsive-like behavior of people with different styles of perfectionism. Sixteen functional perfectionists (FP) and 16 dysfunctional perfectionists (DP) were compared on three different tasks in order to explore OC type behavior such as doubting, checking and intrusions. Results show that DP participants, compared to FP participants, scored higher on an OC behavior scale, took significantly more time to complete a precision task and precipitated their decision when confronted with ambiguity. The two groups also tended to differ in their intrusive thoughts following an unsolved problem; FP participants were more preoccupied about solving the problem than about the quality of their performance, contrary to DP subjects. Results are discussed according to theoretical models of OCD.

Relations of diabetes intrusiveness and personal control to symptoms of depression among adults with diabetes.

The generalizability of a model linking illness characteristics to psychosocial well-being was tested in a cross-sectional study of 237 adults with type 2 diabetes. It was hypothesized that diabetic complications increase illness intrusiveness, which in turn increases depressive symptomatology either directly or indirectly by reducing personal control over health outcomes. Illness intrusiveness was defined as the result of disruptions of valued activities and interests due to constraints imposed by the illness. An excellent fit of this model to the data was found using structural equation modeling. The model explained 65% of the variance in depressive symptomatology. Assessment of an alternative model excluding personal control suggested that the extent to which diabetes intrudes in life, rather than diabetic complications per se or personal control, is a key factor in relation to depressive symptomatology in individuals with diabetes.

Evidence for an heterogeneous glycosylation of the Clostridium tyrobutyricum ATCC 25755 flagellin.

Glycosylation analysis of the flagellin from the Gram-positive species Clostridium tyrobutyricum has been supplemented. Amino acid analysis of the glycopeptides obtained after pronase digestion of flagellin indicated that O-glycosylation which was previously demonstrated after nonreductive beta-elimination, probably occurred via the hydroxyl group of serine. Otherwise, beta-elimination partly deglycosylated flagellin. After this treatment carbohydrates were still linked to protein as shown by a digoxigenin-hydrazide labelling. Therefore, in addition to linkages via serine, alkaline resistant linkages exist on the flagellin and some glycans may be linked to the protein core via the amide nitrogen of asparagine or via the hydroxyl group of tyrosine. Furthermore, according to an immunological analysis, glycans attached to flagellin via alkaline sensitive linkages may be different from those attached via alkaline resistant linkages.

Validation of the French translation of the agoraphobic cognitions questionnaire.

BACKGROUND: The goal of the present study was to validate the French version of the Agoraphobic Cognitions Questionnaire (ACQ). METHODS: Subjects consisted of 115 patients with panic disorder and agoraphobia, 54 obsessive-compulsive patients and 72 normal controls. Patients were referred for outpatient treatment. They filled in the questionnaire before and after entering treatment. The control group consisted of people taken from the general population. It was matched with the clinical groups on age, sex and education. RESULTS: The ACQ appears to have a constant factor structure across US, Dutch and French samples. Results support the validity of the total score of the ACQ. Patients with panic disorder and agoraphobia scored significantly higher than obsessive-compulsive patients and control subjects. On the ACQ physical concerns subscale agoraphobic patients were significantly different from obsessive-compulsive patients and control subjects. On the social/behavioural subscale agoraphobic patients and obsessive-compulsive patients were significantly different from control subjects. The French translation of the ACQ was found to be stable over an interval of 15 days in the control group. The Cronbach coefficients of both subscales were also satisfactory. These results support the stability and the internal consistency of the questionnaire. In addition, the French translation of the ACQ was sensitive to changes with cognitive-behavioural therapy. CONCLUSIONS: These results support the findings of Chambless and Gracely [Cogn Ther Res 1989;13:9-20]. The ACQ physical concerns subscale is a specific feature for the anxiety status experienced by patients with panic disorder and agoraphobia. The ACQ social/behavioural subscale seems to be a more general feature of anxious patients.

Partial analysis of the flagellar antigenic determinant recognized by a monoclonal antibody to Clostridium tyrobutyricum.

In order to count Clostridium tyrobutyricum spores in milk after membrane filtration, murine 21E7-B12 monoclonal antibody was produced. Elution of the monoclonal antibody from this antigen, the flagellar filament protein, by carbohydrate ligands was used to study the epitope structure. A competitive elution of an anti-dextran monoclonal antibody by carbohydrate ligands served as a control in order to validate the immunological tool applied to flagellin epitope study. The carbohydrate moiety of flagellin contained D-glucose and N-acetyl-glucosamine in a molar ration of 11:1 as determined by gas-liquid chromatography and 2 low-abundancy unidentified compounds. In ELISA, D-glucose and N-acetyl-glucosamine did not dissociate the antibody-flagellin complex contrary to maltose, maltotriose, maltotetraose and maltopentaose. The efficiency of elution increased from the dimer to the pentamer and became nil for maltohexaose and maltoheptaose. The fact that the hexamer and heptamer could not react with the 21E7-B12 monoclonal antibody could be explained by a drastic conformational change. The over-all stretched maltopentaose switch to a helical-shaped maltoheptaose which could not fit the 21E7-B12 monoclonal antibody antigen-combining site. Thus, flagellin epitope may contain alpha (1-->4) linked glucose residues plus either N-actyl-glucosamine or an unidentified compound that maintain it in an extended shape.

Biochemical and immunological analyses of the flagellin of Clostridium tyrobutyricum ATCC 25755.

The monoclonal antibody 21E7-B12 (IgG3) can be used in a direct method of Clostridium tyrobutyricum detection based on an immunoenzymatic assay. Immunoelectron microscopy demonstrated that the 21E7-B12 antibody recognized the surface-exposed epitopes on the flagellar filaments of C. tyrobutyricum. After flagellar extraction, the purified flagellin showed an apparent molecular mass of 46 kDa with an isoelectric point of 3.6. Sugar staining, mild periodate oxidation and beta-elimination experiments showed that the flagellin was glycosylated and that the 21E7-B12 epitope was located in the sugar moiety. Amino acid composition showed that the flagellar filament protein contained a high percentage of serine and threonine, while proline was absent. The first 23 residues of the N-terminal were determined and sequence homology with other flagellins was found.

Behavioral expressions of intolerance of uncertainty in worry. Experimental findings.

Intolerance of uncertainty has been related to increased worry in recent conceptual models of Generalized Anxiety Disorder (GAD). The present study examines the relationship between a measure of intolerance of uncertainty, the Intolerance of Uncertainty scale (IU), and behaviors associated with GAD, such as slowness of execution and amount of evidence required before decision making. A total of 49 individuals participated in the study. Three experimental tasks varying in level of ambiguity and difficulty were used. The analyses show a positive correlation between scores on the IU and number of cues required before responding in a moderately ambiguous inference task. However, scores on the IU were not significantly related to responses in an unambiguous task (regardless of the level of difficulty) or in a highly ambiguous task. The results suggest that high worriers have a lower threshold of tolerance of uncertainty for intermediate levels of ambiguity. The results are discussed in terms of theoretical models of GAD.

Pericranial muscle tenderness and exteroceptive suppression of temporalis muscle activity: a blind study of chronic tension-type headache.

The aim of the present study was to examine the ability of pericranial muscle tenderness and the second exteroceptive suppression period to distinguish chronic tension-type headache sufferers, migraine sufferers, and controls in a young adult population utilizing a blind design. The second exteroceptive suppression periods were assessed using the methodology recommended by the European Headache Federation and were scored with an automated computer software program designed in our laboratory to provide reliable, standardized, and precise quantification of exteroceptive suppression periods and eliminate any influence of experimenter bias that may occur with manual scoring. Our sample consisted of 45 subjects diagnosed according to IHS criteria: 25 with chronic tension-type headache and 20 with migraine without aura. Twenty-three headache-free controls were recruited. Consistent with our previous findings, abnormalities in pericranial muscle tenderness, but not in the second exteroceptive suppression period distinguished chronic tension-type headache sufferers from controls. The chronic tension headache sufferers exhibited the highest pericranial muscle tenderness and the control group exhibited the lowest tenderness (P < .001). Pericranial muscle tenderness was quite successful in distinguishing recurrent headache sufferers from controls, but failed to distinguish chronic tension-type headache sufferers from migraineurs. Our findings raise the possibility that pericranial muscle tenderness is present early in the development of chronic tension-type headache and migraine without aura, and thus might contribute to the etiology of headache disorders. Our findings also indicate that a shortened second exteroceptive suppression period is not a reliable marker for chronic tension-type headache in young adults.

The assessment of diabetes-related cognitive and social factors: the Multidimensional Diabetes Questionnaire.

The purpose of this study was to examine the psychometric properties of the recently developed Multidimensional Diabetes Questionnaire (MDQ). The MDQ, which is theoretically linked to a social learning perspective of diabetes, was designed to provide a comprehensive assessment of diabetes-related cognitive and social factors. It includes 41 items grouped into three sections: (1) perceptions related to diabetes and related social support, (2) positive and misguided reinforcing behaviors related to self-care activities, and (3) self-efficacy and outcome expectancies. Confirmatory factor analyses, conducted on a sample of 249 patients with non-insulin-dependent diabetes mellitus, supported the construct validity of the MDQ. Adequate internal consistency and significant demographic, psychological, behavioral, and disease-related correlates were found. The MDQ may prove valuable in understanding individual differences in adjustment to diabetes.

Monoclonal antibody detection of Clostridium microcolonies directly on membrane used for milk filtration.

The normal procedure for bacterial colony detection requires a nitrocellulose transfer step after membrane filtration and culture to prevent the development of a high background during the immunodetection. In this paper, we describe a modification of the basic protocol that omits the transfer step and reduces the risk of background. Previous observations indicated that interactions between milk components (principally cream) and membrane are responsible for the high non-specific staining observed. Experiments were performed to remove lipid components or to block the membrane binding sites before milk filtration. Samples of milks of different origin (collected at different times of the year) and different membranes were tested. The results obtained showed that removing lipids did not significantly improve the test but, on the contrary, led to an antigen diffusion. Incubation of the membrane in 0.1% (w/v) of Tween 20 in phosphate-buffered saline before milk filtration prevented non-specific binding, and allowed performance of the detection without any noticeable background.

The development of an empirical psychosocial taxonomy for patients with diabetes.

The main purpose of this study was to develop and to cross-validate an empirically derived psychosocial taxonomy of patients with diabetes. In the first study, 101 patients with Type I or Type II diabetes completed the Multidimensional Diabetes Questionnaire. Cluster analysis identified three clusters, labeled adaptive copers, low support-low involvement, and spousal overinvolvement. In the second study, the taxonomy was cross-validated using an independent sample of 132 patients with long-standing Type II diabetes. The results confirmed that the multivariate classification system was unique and highly accurate. External validation, using general psychological as well as diabetes-specific measures, supported the validity and distinctiveness of the patients' profiles. These findings help establish a multiaxial psychosocial taxonomy of diabetes and may have significant implications for the management of patients with diabetes.

Assessing the dimensions of pain: a multitrait-multimethod evaluation of seven measures.

A multitrait-multimethod design was used to examine the convergent and discriminant validity of seven pain measures from three widely used self-report instruments designed to assess the sensory, affective and intensity dimensions of pain. The instruments were the McGill Pain Questionnaire, the Pain Perception Profile and Numerical Ratings. Three distinct factor models, each corresponding to a different hypothesis about how these pain measures are related, were tested using confirmatory factor analysis in a sample of 419 headache sufferers. A three-factor model, postulating three correlated factors defined by the three assessment instruments best explained the correlations between the pain measures. Measures of sensory, affective and intensity dimensions from the three instruments failed to exhibit convergent or discriminant validity. Rather, instrument variance obscured the pain qualities the three pain instruments were designed to assess. These findings suggest that greater attention needs to be paid to how formal characteristics of pain assessment instruments influence patients' descriptions of their pain.

Is health locus of control a 3-factor or a 2-factor construct?

Although the Multidimensional Health Locus of Control (MHLC) scales are commonly used, uncertainty about their factorial validity still remains. In the present study, confirmatory factor analyses of a French-Canadian adaptation of the Multidimensional Health Locus of Control scales (MHLC) were conducted to compare in a non-clinical group of 224 adults two factor models. Multigroup analyses were also conducted using this group and a clinical group of 132 diabetics to assess the equivalence of the MHLC factor structure across these two groups. A 3-factor model postulating an internal, external, and chance dimension, and accounting for measurement errors provided the best fit to the data. Multigroup analyses failed to support the equivalence of the MHLC factor loadings across the non-clinical and clinical group. These findings suggest that comparisons of MHLC scores across such groups may be problematic.