Demographic characteristics and health-related quality of life of patients with moderate-to-severe psoriasis: The VACAP study.

BACKGROUND: Psoriasis is associated with a deterioration in the health-related quality of life (HRQoL) of affected patients. The aim of this study was to assess the HRQoL of patients with moderate-to-severe psoriasis. METHODS: A prospective observational study (the VACAP Study) was carried out in 123 centers in Spain with 1217 patients. Patients were evaluated at baseline (visit 1 [V1]) and again four months later (visit 2 [V2]). The severity of psoriasis was determined using the following indices: (i) Psoriasis Area and Severity Index (PASI) (score range 0-72, higher score indicates more severe disease), (ii) the body surface area (BSA) affected, and (iii) the Physicians Global Assessment (PGA) (range 1-7, higher score indicates more severe disease). Four questionnaires were used for the assessment of the HRQoL: (i) the Short-Form 36 quality-of-life questionnaire (SF-36) (score range 0-100, higher score indicates better HRQoL); (ii) Euroqol (EQ-5D) (range from 1 to 3, lower score indicates better HRQoL); (iii) Dermatology Life Quality Index (DLQI) (ranges 0-30; from best to worst HRQoL); and (iv) Psoriasis Disability Index (PDI) (ranges 0-45; higher score indicates better HRQoL). RESULTS: The mean (SD) age of the patients was 45.11 (13.92) years at V1. The mean age at the onset of psoriasis was 26.08 (14.19) years. The majority of patients were female (61%) and were employed (68%). The mean PASI score was 13.24 (9.50) at V1 and 5.07 (6.03) at V2 (P<.001). Scores from the generic HRQoL questionnaires (EQ-5D, SF-36) showed significant improvement between visits in all dimensions measured (P<.001). The disease-specific questionnaires also revealed overall improvements in quality of life over time: the DLQI mean total score was 8.97 (7.28) at V1 and 4.76 (5.72) at V2 (P<.001), and the PDI mean total score was 9.24 (8.76) V1 and 4.88 (6.65) at V2 (P<.001). Multivariate analysis using PDI as the dependent variable showed that the principal factors related to HRQoL were severity of psoriasis as measured by PASI (P<.001), and gender (P=.048). CONCLUSIONS: The principal factor related to HRQoL in patients with psoriasis is the severity of the disease.

Mental health self-assessment in patients with moderate to severe psoriasis: an observational, multicenter study of 1164 patients in Spain (the VACAP Study).

BACKGROUND: Poor self-assessed mental health appears to be related to the severity of psoriasis. OBJECTIVE: To evaluate the impact of psoriasis severity on mood and anxiety disorders. METHODS: A prospective, observational, multicenter study was conducted by 123 dermatologists in Spain. Patients (n=164; mean [SD] age, 45.11 [13.92] years; 60.8% males) with moderate to severe psoriasis were evaluated at baseline and 4 months later. Psoriasis severity was measured using the Psoriasis Area and Severity Index (PASI), with a score range of 0 (mild) to 72 (severe); body surface area involvement (BSA); and physician global assessment (PGA) scores, with a range of 1 (mild) to 7 (severe). Mental health was assessed using the Hospital Anxiety and Depression Scale (HADS), with a total possible score of 0-42 (higher scores representing worse mental health). Mean first and second visit scores were compared. RESULTS: Mean (SD) scores improved between the first and second visit as follows: 13.24 (9.50) to 5.07 (6.03) for PASI, 12.52 (7.92) to 10.78 (7.32) for overall HADS, 7.83 (4.55) to 6.85 (4.21) for the HADS anxiety subscale, and 4.72 (4.12) to 3.95 (3.76) for the HADS depression subscale (P<.001 in all cases). Multivariate analyses showed that the main factors related to anxiety were psoriasis severity, sex, and completion of graduate studies. The independent variables included in the model for depression were psoriasis severity, sex, and psoriasis located on the head. CONCLUSIONS: Reductions in disease severity improve self-assessed mood and anxiety disorders in patients with moderate to severe psoriasis.

Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home units in Spain.

The aim of this study was to assess the direct healthcare costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH) units in Spain. An observational, multicentre, economic evaluation of retrospective cohorts was conducted. Patients were treated at home by the HaH units of three Spanish hospitals between January 2012 and December 2013. From the cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests and structural), the cost of each outpatient course was obtained following a top-down strategy based on the use of resources. Costs associated with inpatient stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis. There were 1324 HaH episodes in 1190 patients (median age 70 years). The median (interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes, 91.5% resulted in cure or improvement on completion of intravenous therapy. The mean total cost of each infectious episode was €6707 [95% confidence interval (CI) €6189-7406]. The mean cost per OPAT episode was €1356 (95% CI €1247-1560), mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%). The mean cost of inpatient hospitalisation of an infectious episode was €4357 (95% CI €3947-4977). The cost per day of inpatient hospitalisation was €519, whilst the cost per day of OPAT was €98, meaning a saving of 81%. This study shows that OPAT administered by HaH units resulted in lower costs compared with inpatient care in Spain.

Preoperative risk factors associated with mortality in lung biopsy patients with interstitial lung disease.

The objective of this study was to evaluate the risk factors associated with mortality in interstitial lung disease patients. We performed a retrospective study of 722 consecutive patients submitted for lung biopsy during the 1986-1990 period. Twenty-two (3%) died within the 30 days following surgery. Forty-four patients who survived after the surgery for the same time span were randomly chosen as control group. Dyspnea at rest was present in 18/44 of surviving group (SG) and in 18/22 of the nonsurviving group (NSG) (OR 6.5, 95% CI 1.8-22.4,p = .001). Systemic diseases (i.e., diabetes, systemic arterial hypertension)were mainly present in the NSG (OR 7.2, 95% CI 2.3-22.8, p < .001). The SG displayed significantly less respiratory insufficiency with a PaO2 of 52.2 + 8.4 versus 38.5 i 9.4 mm Hg, and PaCO2 of 28.8 i 4.5 versus 38.5 +/- 9.2 mm Hg, respectively (p < .001). Likewise, the SG exhibited a PaCO2/PaO2 ratio of 0.5 - 0.1, while in the NSG it was of 1 +/- 0.4 (p < .001), showing a sensitivity of 84% and specificity of 93% for mortality. Multiple logistic regression analysis for these variables showed that log likelihood was still significant for PaCO2 > 34 mm Hg, PaO2 <48 mm Hg, and comorbid diseases. Logistic regression analysis of these three variables showed the greatest sensitivity and specificity (84 and 750/0,respectively) for prediction of mortality. However, the strongest association was found when PaCO2/PaO2 ratio was analyzed alone (OR 21,073,CI 95% 28-15,946,357, p < .005). These data suggest that PaCO2/PaO2 ratio appears to be a predictor of mortality in this subset of patients. Its prospective use has reduced early mortality after surgery less than 1% in the last decade.

Evidence for a MARCKS-PKCalpha complex in skeletal muscle.

MARCKS (Myristoylated Alanine Rich C Kinase Substrate) is a protein known to cross-link actin filament and consequently, is very important in the stabilization of the cytoskeletal structure. In addition, it has been recently demonstrated that the phosphorylation rate of this protein changes during myogenesis and that this protein is implicated in fusion events. For a better understanding of the biological function of MARCKS during myogenesis, we have undertaken to identify and purify this protein from rabbit skeletal muscle. Three chromatographic steps including an affinity calmodulin-agarose column were performed. The existence of a complex between the two proteins was confirmed by non-denaturing gel electrophoresis and immunoprecipitation. Two complexes were isolated which present an apparent molecular weight of about 600 kDa. Such interactions suggest that MARCKS is either a very good PKCalpha substrate and/or a regulator of PKC activity. These results are supported by previous studies showing preferential interactions and co-localization of PKC isozyme and MARCKS at focal adhesion sites. This is the first time that MARCKS has been purified from skeletal muscle and our data are consistent with a major role of this actin- and calmodulin-binding protein in cytoskeletal rearrangement or other functions mediated by PKalpha. Our results provide evidence for a tight and specific association of MARCKS and PKCalpha (a major conventional PKC isozyme in skeletal muscle) as indicated by the co-purification of the two proteins.

A data management program for the Electra 800 automatic analyser.

The Electra 800 automatic coagulation analyser rapidly performs most chronometric coagulation tests with high precision. To facilitate data handling, software, adaptable to any PC running under MS-DOS, was written to manage the analyser. Data are automatically collected via the RS232 interface or can be manually input. The software can handle 64 different analyses, all entirely 'user defined'. An 'electronic worksheet' presents the results in pages of ten patients. This enables the operator to assess the data and to perform verifications or complementary tests if necessary. All results outside a predetermined range can be flagged and results can be deleted, modified or added. A patient's previous files can be recalled as the data are archived at the end of the day. A 120 Mb disk can store approximately 130,000 patient files. A daily archive function can print the day's work in alphabetical order. A communication protocol allows connection to a mainframe computer. This program and the user's manual are available on request, free of charge, from the authors.

Computer program for connection and data management of an automated coagulation system: the KC 10.

In Europe, the KC 10, manufactured by Amelung Germany, is one of the instruments most commonly found in coagulation laboratories. For facilitating the work of technical validation, we wrote a software adapted to any IBM or compatible PC running under MS-DOS, to manage the analyser performance. Data are automatically collected via the BCD interface from the analyser or keyed in for the other techniques. The software deals with 64 different analyses entirely 'user defined'. An 'electronic worksheet' presents the results, by page of ten patients. This enables the laboratory technician to assess the coherence of the various data and to perform verifications or complementary tests if necessary. As an option, a blinking asterisk can signal all results outside predetermined range. By moving the cursor through the table, a test result can be deleted, modified or added. A function displays the patient's previous files in a window because the data are recorded in long-term archives at the end of the day. This long-term recording allows a search of previous files to decide additional tests if the patient is unknown. A daily archive function classifies and prints the whole day's work in alphabetical order. A protocol of communication allows connection to a mainframe Bayer-Technicon computer. This program and the user's manual are free, available on request from address above.

[Glutamate concentration in diabetic vitreous]. / Concentración de glutámico en el vítreo de diabéticos.

PURPOSE: To investigate the hypothesis that the death of retinal ganglion cells in diabetic retinopathy involves excitotoxic effects from elevated concentrations of vitreal glutamate. MATERIAL AND METHODS: Patients with diabetic retinopathy who had not undergone prior vitreous or intraocular surgery were studied. Undiluted vitreous samples from 75 patients with diabetic retinopathy who underwent pars plana vitrectomy were analyzed. Mean levels of vitreal glutamate were determined in this group and they were compared with the levels in a control group. Glutamate and other free amino acids were determined using high-performance liquid chromatography. Patients were divided into two groups: Group A: Patients with proliferative diabetic retinopathy (PDR) and group B: Patients with PDR and macular edema. RESULTS: The mean level of vitreal glutamate in the diabetic population was 3.9 SD 4.5 mcmol/L which was not significantly different from the concentration in the control group (3.8 SD 5.1 mcmol/L). No statistically significant difference was found in the vitreous concentration of amino acids between the two groups of patients with PDR (p > 0.05). CONCLUSIONS: Vitreal glutamate concentration is not elevated in eyes with diabetic retinopathy. This finding is in contradiction to previous reports that stated that vitreal glutamate increases to toxic levels and probably contributes to diabetic damage of retinal ganglion cells.

[Amino acid concentrations in the vitreous body in control subjects]. / Concentración de aminoácidos en el vítreo en una población control.

PURPOSE: Concentrations of amino acids in the vitreous body of a control group were determined. MATERIAL AND METHODS: Patients who neither had undergone prior vitreous or intraocular surgery nor had a history of intraocular ischemia such as retinal vascular occlusion, diabetic retinopathy glaucoma history were studied. Undiluted vitreous samples were obtained from 64 patients with retinal detachment, preretinal macular membranes and macular holes, who underwent pars plana vitrectomy. Free amino acids were determined using high-performance liquid chromatography. Patients were divided into three groups: A (<50 years old), B (50-65 years old) and C (>65 years old). RESULTS: Glutamine+histidine had the higher concentration with 851.1 D.E. 74.2 mcmol/L, and the vitreous concentration of glutamate was 3.8 D.E. 5.1 mcmol/L and aspartate 3.7 D.E. 4.1 mcmol/L. No statistically significant differences were found in the vitreous concentrations of amino acids between different age groups and no statistically significant differences were found between the 3 pathological groups analysed (retinal detachment, macular hole and epiretinal membrane). CONCLUSIONS: These results show that the concentration of acid amino acids in the vitreous body of a control group was not high and that in mature eyes the concentration of amino acids was maintained at a fairly constant level.

Calpain-PKC inter-relations in mouse hippocampus: a biochemical approach.

In previous studies, we isolated and identified a mu-calpain/PKCalpha complex from rabbit skeletal muscle. Here, we have used specific purification procedures in order to study the interactions between mu-calpain and PKC in mouse hippocampus, a brain structure implicated in memory processes. We observed that mu-calpain and conventional PKCs (alpha, betaII and gamma) are co-eluted after anion exchange chromatography. In contrast to our previous results obtained on skeletal muscle, mu-calpain and PKC isoenzymes were dissociated after gel filtration chromatography. Furthermore, mu-calpain induced the proteolytic conversion of PKCalpha, betaII, and gamma into PKMalpha, betaII, and gamma with a preferential hydrolysis of PKCgamma, a specific isoenzyme of the nervous system. Although the mu-calpain/PKC interactions in the hippocampus are quite different from skeletal muscle, our results however, point out the functional importance of these inter-relations. Moreover, as PKCgamma has been involved in the biochemical events underlying learning and memory, the preferential relationship between mu-calpain and PKCgamma promotes the importance of the role that mu-calpain could play in the cellular mechanisms of memory formation.

Protein kinase Calpha is a calpain target in cultured embryonic muscle cells.

Previously we isolated a micro-calpain/PKCalpha complex from skeletal muscle which suggested tight interactions between the Ca2+-dependent protease and the kinase in this tissue. Our previous studies also underlined the involvement of ubiquitous calpains in muscular fusion and differentiation. In order to precise the relationships between PKCalpha and ubiquitous calpains in muscle cells, the expression of these two enzymes was first examined during myogenesis of embryonic myoblasts in culture. Our results show that calpains and PKCalpha are both present in myotubes and essentially localized in the cytosolic compartment. Moreover, calpains were mainly present after 40 h of cell differentiation concomitantly with a depletion of PKCalpha content in the particulate fraction and the appearance of PKMalpha fragment. These results suggest a possible calpain dependent down-regulation process of PKCalpha in our model at the time of intense fusion. In our experimental conditions phorbol myristate acetate (PMA) induced a rapid depletion of PKCalpha in the cytosolic fraction and its translocation toward the particulate fraction. Long term exposure of myotubes in the presence of PMA induced down-regulation of PKCalpha, this process being partially blocked by calpain inhibitors (CS peptide and inhibitor II) and antisense oligonucleotides for the two major ubiquitous calpain isoforms (m- and micro-calpains). Taken together, our findings argue for an involvement of calpains in the differentiation of embryonic myoblasts by limited proteolytic cleavage of PKCalpha.

Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia.

BACKGROUND: Equilibration of hemoglobin concentration after transfusion has been estimated to take about 24 hours, but some studies have shown that earlier measurements reflect steady-state values in persons who have not bled recently. This study was aimed at assessing the changes over time in hemoglobin concentration after transfusion in acutely anemic patients because of recent bleeding. STUDY DESIGN AND METHODS: Thirty-two normovolemic patients recovering from an acute bleeding episode who were no longer thought to be bleeding and who received a 2-unit red cell transfusion were studied. At baseline and 15, 30, 60, and 120 minutes and 24 hours after transfusion, hemoglobin concentration and hematocrit values were measured. RESULTS: The administration of 2 units of packed red cells elicited a 24-hour increase of 22.4 +/- 6.8 g per L in hemoglobin concentration. Hemoglobin values were not different at any of the defined posttransfusion times. Hematocrit levels experienced similar changes over time. Agreement between 15-minute and 24-hour values was excellent, as only 6 percent of patients exhibited a clinically significant difference (> 6 g/L) between the hemoglobin measurements. CONCLUSION: Hemoglobin and hematocrit values rapidly equilibrate after transfusion in normovolemic patients who are recovering from an acute bleeding episode. This fact would allow a rapid assessment of the effects of transfusion and of the recurrence of bleeding in patients remaining at risk.