Higher Severity Grade Research Articles

CORRELATION BETWEEN FFP TRANSFUSION AND APACHE II SCORE IN ICU PATIENTS

While plasma donation is still necessary as a unique source of human proteins and to treat coagulation disorders, FFP administration seems to have high rate of inappropriate indication. After all, FFP transfusion is not risk free, and is associated with lung injury, infectious disease and circulatory overload in recipients. On the other hand, high severity grade patients may have impaired physical status and increased demand for FFP transfusion.

Assessment of corneal epithelial thickness in dry eye patients.

To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients. In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated. The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017). Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Mo1338 Comparative Evaluation of Abdominal Ultrasound, Endoscopic Ultrasound and Magnetic Resonance Imaging in Detecting Solid Necrotic Debris in Walled off Pancreatic Necrosis

Background Two new classification systems for the severity of acute pancreatitis (AP) have been proposed recently, the determinant based classification (DBC) and revised Atlanta classification (RAC). We aimed to validate and compare these classification systems with original Atlanta classification (OAC). Aims To validate and compare the DBC and RAC with original Atlanta classification (OAC) Methods 469 adult patients with AP admitted to a tertiary care center from January 2009-June 2013 were included in the study. The new classification systems were validated and compared in terms of outcomes (need for interventions, total hospital and intensive care unit (ICU) stay and mortality). Results The mean age of patients was 39.9±13.4 years (331 males) with the commonest etiology being alcohol (161, 34.3%) followed by gall stones (125, 26.6%). There were 119 (25.4%) patients with mild and 250 (74.6%) patients with severe AP as per OAC. Pancreatic necrosis was present in 66.1% and infected pancreatic necrosis in 23.1% patients. 126 (26.9%) patients underwent interventions (endoscopic n= 49, 10.4%, radiological n=95, 20.2% and surgical n=47, 10%). 93 (19.8%) patients died. As per DBC, 97(20.7%), 172 (36.7%), 152 (32.4%), and 48(10.2%) patients were determined to have mild, moderate, severe, and critical AP, respectively. As per RAC, 119 (25.4%), 160 (34.1%), and 190 patients (40.3%) were determined to have mild, moderately severe, and severe AP, respectively. Higher grades of severity were associated with worse outcomes in DBC, RAC and OAC. Predictive accuracies were evaluated using area under the receiver operator characteristics curve (AUROC) and Somer's D co-efficient. The DBC, RAC and OAC were comparable in predicting the need for interventions (AUROC 0.53, 0.55, 0.54, p=0.36) and length of hospital stay (Somer's D, 0.27, 0.26, 0.23, p=0.41). However, both DBC and RAC had comparable but better accuracy than OAC in predicting need for ICU admission (AUROC 0.73 for both vs. 0.62 for OAC, P<0.001), length of ICU stay (Somer's D, 0.35 for both vs. 0.24 for OAC, p<0.001) and mortality (AUROC 0.78 for both vs. 0.61 for OAC, p<0.001). Conclusion Determinant based classification and revised Atlanta classification categorize patients into subgroups that reflect clinical outcomes. Both have comparable and higher predictive accuracy than old Atlanta classification for need for ICU admission, length of ICU stay and mortality.

Mo1335 Systemic Inflammatory Response Syndrome (SIRS) in Acute Pancreatitis (AP): Outcome of Early Fluid Therapy

Background Two new classification systems for the severity of acute pancreatitis (AP) have been proposed recently, the determinant based classification (DBC) and revised Atlanta classification (RAC). We aimed to validate and compare these classification systems with original Atlanta classification (OAC). Aims To validate and compare the DBC and RAC with original Atlanta classification (OAC) Methods 469 adult patients with AP admitted to a tertiary care center from January 2009-June 2013 were included in the study. The new classification systems were validated and compared in terms of outcomes (need for interventions, total hospital and intensive care unit (ICU) stay and mortality). Results The mean age of patients was 39.9±13.4 years (331 males) with the commonest etiology being alcohol (161, 34.3%) followed by gall stones (125, 26.6%). There were 119 (25.4%) patients with mild and 250 (74.6%) patients with severe AP as per OAC. Pancreatic necrosis was present in 66.1% and infected pancreatic necrosis in 23.1% patients. 126 (26.9%) patients underwent interventions (endoscopic n= 49, 10.4%, radiological n=95, 20.2% and surgical n=47, 10%). 93 (19.8%) patients died. As per DBC, 97(20.7%), 172 (36.7%), 152 (32.4%), and 48(10.2%) patients were determined to have mild, moderate, severe, and critical AP, respectively. As per RAC, 119 (25.4%), 160 (34.1%), and 190 patients (40.3%) were determined to have mild, moderately severe, and severe AP, respectively. Higher grades of severity were associated with worse outcomes in DBC, RAC and OAC. Predictive accuracies were evaluated using area under the receiver operator characteristics curve (AUROC) and Somer's D co-efficient. The DBC, RAC and OAC were comparable in predicting the need for interventions (AUROC 0.53, 0.55, 0.54, p=0.36) and length of hospital stay (Somer's D, 0.27, 0.26, 0.23, p=0.41). However, both DBC and RAC had comparable but better accuracy than OAC in predicting need for ICU admission (AUROC 0.73 for both vs. 0.62 for OAC, P<0.001), length of ICU stay (Somer's D, 0.35 for both vs. 0.24 for OAC, p<0.001) and mortality (AUROC 0.78 for both vs. 0.61 for OAC, p<0.001). Conclusion Determinant based classification and revised Atlanta classification categorize patients into subgroups that reflect clinical outcomes. Both have comparable and higher predictive accuracy than old Atlanta classification for need for ICU admission, length of ICU stay and mortality.

Mo1334 Validation and Comparison of the New Severity Classification Systems With Old Atlanta Classification for Severity of Acute Pancreatitis

Background Two new classification systems for the severity of acute pancreatitis (AP) have been proposed recently, the determinant based classification (DBC) and revised Atlanta classification (RAC). We aimed to validate and compare these classification systems with original Atlanta classification (OAC). Aims To validate and compare the DBC and RAC with original Atlanta classification (OAC) Methods 469 adult patients with AP admitted to a tertiary care center from January 2009-June 2013 were included in the study. The new classification systems were validated and compared in terms of outcomes (need for interventions, total hospital and intensive care unit (ICU) stay and mortality). Results The mean age of patients was 39.9±13.4 years (331 males) with the commonest etiology being alcohol (161, 34.3%) followed by gall stones (125, 26.6%). There were 119 (25.4%) patients with mild and 250 (74.6%) patients with severe AP as per OAC. Pancreatic necrosis was present in 66.1% and infected pancreatic necrosis in 23.1% patients. 126 (26.9%) patients underwent interventions (endoscopic n= 49, 10.4%, radiological n=95, 20.2% and surgical n=47, 10%). 93 (19.8%) patients died. As per DBC, 97(20.7%), 172 (36.7%), 152 (32.4%), and 48(10.2%) patients were determined to have mild, moderate, severe, and critical AP, respectively. As per RAC, 119 (25.4%), 160 (34.1%), and 190 patients (40.3%) were determined to have mild, moderately severe, and severe AP, respectively. Higher grades of severity were associated with worse outcomes in DBC, RAC and OAC. Predictive accuracies were evaluated using area under the receiver operator characteristics curve (AUROC) and Somer's D co-efficient. The DBC, RAC and OAC were comparable in predicting the need for interventions (AUROC 0.53, 0.55, 0.54, p=0.36) and length of hospital stay (Somer's D, 0.27, 0.26, 0.23, p=0.41). However, both DBC and RAC had comparable but better accuracy than OAC in predicting need for ICU admission (AUROC 0.73 for both vs. 0.62 for OAC, P<0.001), length of ICU stay (Somer's D, 0.35 for both vs. 0.24 for OAC, p<0.001) and mortality (AUROC 0.78 for both vs. 0.61 for OAC, p<0.001). Conclusion Determinant based classification and revised Atlanta classification categorize patients into subgroups that reflect clinical outcomes. Both have comparable and higher predictive accuracy than old Atlanta classification for need for ICU admission, length of ICU stay and mortality.

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

ObjectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).MethodsA total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model.ResultsA total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART.ConclusionHAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI.

Revised Atlanta and Determinant-Based Classification: Application in a Prospective Cohort of Acute Pancreatitis Patients

Atlanta classification (Atlanta 1992) of acute pancreatitis (AP) has several limitations. Two new classification systems were recently proposed: the Atlanta reclassification (Atlanta 2012) and the determinant-based classification (DBC). The aim of our study was to: (i) determine the association between different severity categories and clinical outcomes and (ii) perform a head-to-head comparison between Atlanta 1992, Atlanta 2012, and DBC in predicting these clinical outcomes. A total of 256 prospectively enrolled patients were assigned a severity category for all three classifications. Five clinical outcomes were evaluated: mortality, intensive care unit (ICU) admission and length of stay (LOS), need for interventions, and hospital LOS. Pairwise testing between severity grades within a classification system was performed using Fisher's exact and Kruskal-Wallis tests. Predictive accuracies were evaluated using area under the ROC curve (AUC) and Somer's D co-efficient. Overall, higher grades of severity were associated with worse clinical outcomes for all three classification systems. Atlanta 2012 and DBC performed better than Atlanta 1992 and were comparable in predicting mortality (AUC 0.89 for both vs. 0.76, P<0.001), ICU admission (AUC 0.91 for both vs. 0.80, P<0.001), and ICU LOS (Somer's D 0.21 and 0.28 vs. 0.07, P<0.05). DBC performed better in predicting need for interventions (AUC 0.93 vs. 0.85, P<0.001), whereas Atlanta 2012 performed better in predicting hospital LOS (Somer's D 0.43 vs. 0.37, P=0.04). Atlanta 2012 and DBC severity categories accurately reflected clinical outcomes in our cohort and were superior to Atlanta 1992. These novel classification systems can guide the selection of homogeneous patient populations for clinical research and provide an accurate spectrum of disease severity categories in the clinical setting.

Plasma NGAL for the Diagnosis of AKI in Patients Admitted from the Emergency Department Setting

The purpose of this study was to determine the accuracy of plasma neutrophil gelatinase-associated lipocalin as a marker of AKI in patients admitted from the emergency department. In this prospective cohort study, patients (n=616) admitted from the emergency department from March to November of 2008 were classified according to clinical criteria as AKI, transient azotemia, stable CKD, and normal function. Plasma neutrophil gelatinase-associated lipocalin was measured serially. A logistic regression model using clinical characteristics was fitted to the data, and a second model included discretized plasma neutrophil gelatinase-associated lipocalin. Performance of the models was evaluated by Hosmer-Lemeshow goodness-of-fit test, area under the receiver operating characteristic curve, net reclassification improvement, integrated discrimination improvement, and predictiveness curve. Twenty-one percent of patients were classified as AKI; the highest median levels of plasma neutrophil gelatinase-associated lipocalin were in the AKI group (146-174 ng/ml at various time points) and increased with AKI severity (207-244 ng/ml for Acute Kidney Injury Network classification stage>2). The discriminative ability of plasma neutrophil gelatinase-associated lipocalin for AKI diagnosis (area under the curve, 0.77-0.82 at various time points) improved with higher grades of severity (area under the curve, 0.85-0.89 for AKIN>2). Plasma neutrophil gelatinase-associated lipocalin discriminated AKI from normal function and transient azotemia (area under the curve, 0.85 and 0.73, respectively). Patients were classified into three grades of AKI risk according to plasma neutrophil gelatinase-associated lipocalin levels (low, moderate [i.e., the gray zone], and high). Patients with plasma neutrophil gelatinase-associated lipocalin in the high-risk category displayed a 10-fold greater risk of AKI (odds ratio, 9.8; 95% confidence interval, 5.6 to 16.9). The addition of plasma neutrophil gelatinase-associated lipocalin to the clinical model yielded a net reclassification improvement of 94.3% and an integrated discrimination improvement of 0.122. Plasma neutrophil gelatinase-associated lipocalin is an accurate biomarker for prediction of AKI in patients admitted from the emergency department. This work proposes a three-grade classification of AKI risk based on plasma neutrophil gelatinase-associated lipocalin levels.

Classifying the severity of paediatric chronic pain – an application of the chronic pain grading

The chronic pain grading (CPG), a standard approach to classify the severity of pain conditions in adults, combines the characteristics of pain intensity and pain-related disability. However, in children and adolescents, the CPG has only been validated in a school sample, but not in the actual target population, i.e., clinical populations with pain. In the present study, we applied the CPG to a tertiary sample of adolescents with chronic pain (n=1242). Construct validity, sensitivity to change and prognostic utility were examined. Results indicate that most adolescents were equally classified into the three higher severity grades. Higher CPG classification was associated with more pain locations, higher pain frequency, longer pain duration, extensive use of health care and more depressive symptoms. Adolescents with a high CPG received recommendations for inpatient treatment more often; however, the prognostic utility for therapy recommendation - as operationalized in this study - was low. Sensitivity to change was assessed via reassessment at follow-up for a subsample of 490 adolescents. The majority of adolescents improved to a less severe CPG; changes were more common in the high severity range. The CPG may be applied to adolescent tertiary care samples and to assess outcomes in clinical trials. However, in this study it was not appropriate to assign adolescent patients to different treatment options. Future work should focus on developing a comprehensive assessment tool for assigning patients to different treatments.

Relationship between the clinical findings and radiographic severity in Osgood-Schlatter disease.

BackgroundOsgood–Schlatter disease (OSD) is one of the common causes of knee pain in active adolescents who play sports. The common age for boys to have OSD is between 12 and 15 years and for girls, between 8 and 12 years. Radiographic studies are helpful in diagnosis and treatment of OSD.PurposeWe examine the age at onset of OSD in detail and investigate the relationship between clinical findings, radiographic bone morphology, and the severity of OSD in adolescents.ResultsThe average age at onset of knee pain was 12 years and 6 months – 12 years and 9 months in boys, and 12 years and 1 month in girls. Boys were significantly older than girls at onset. In addition, there were significant relationships between duration from first onset to visit to the clinic, radiographic bone stage, body morphology, and radiographic severity. The patients who delayed their visit to the clinic from the first onset of pain and who were older showed a later bone stage and more radiographic severity grade of OSD. There was significant differences concerning weight and body mass index between severity grade I and III.ConclusionFor the age at the onset of OSD, the mean age of boys was significantly older than that of girls. The patients at a later bony stage had a higher severity grade. The boys and girls with OSD who had less weight or body mass index showed less severity.

Clinical profile, species-specific severity grading, and outcome determinants of snake envenomation: An Indian tertiary care hospital-based prospective study

Objective:We undertook this study to assess the clinical profile and outcome determinants of different snake envenomation as well as to assign species-specific severity grade to different cases based on clinico – laboratory evidence scale.Materials and Methods:A prospective clinico – epidemiologic evaluation for outcome determinants of snakebite envenomation was carried out based on a clinico – laboratory severity grading scale, among 76 patients over a period of 2 years, in a tertiary care hospital in southern India.Results:Majority of patients were male agricultural workers (53.9%) followed by housewives (19.7%), and students (9.2%). Occurrence of viper snake envenomation with hemotoxic syndrome (73.68%) was highest followed by cobra and krait envenomation with neurotoxic (19.73%) and hemo – neurotoxic (5.3%) syndrome, respectively. On the contrary, maximum mortality and severity was seen in krait (60%) followed by cobra (13.33%) and viper (8.9%) envenomation. The average dose of anti-snake venom (ASV) administered varied from 9.83 (±7.22) to 20.25 (±4.92) vials throughout grade I to IV in all snake species envenomation. An increase in severity grade, ASV dose, and mortality were observed with the corresponding delay in ‘bite to needle time.’ Also, initial traditional treatments and krait species envenomation were significantly associated with higher grades of severity and mortality.Conclusion:There is an urgent need to spread awareness among the community for avoidance of traditional treatment and any delay in medical intervention in snakebite incidents.

Elevated urinary total sialic acid and increased oxidative stress in patients with bladder cancer

Abstract Background: Increased production and release of sialic acid have been reported in many malignant conditions including bladder cancer. 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) have been widely used as oxidative stress biomarkers. Objective: Determine urinary levels of total sialic acid (TSA), 8-OHdG, and MDA in patients with urinary bladder cancer, and evaluate their clinical relevance. Patients and methods: Forty-five patients with histologically proven bladder cancer and 41 healthy subjects were recruited for the study. Morning urine samples were collected from all participants for measurements of TSA, 8-OHdG and MDA using thiobarbituric assay, competitive ELISA and spectrophotometry methods, respectively. Histological examination was performed for all patients. Results: Bladder cancer patients excreted urinary TSA, 8-OHdG, and MDA significantly higher than healthy controls. Based on receiver operating characteristic curve analysis, urinary TSA had adequate diagnostic potential to distinguish patients from healthy populations, and its cutoff value was chosen at 95.26 μg/g creatinine. Sensitivity, specificity, and accuracy of urinary TSA determination were 75.6%, 75.6%, and 75.6%, respectively. Both in patient and healthy groups, urinary TSA was linearly correlated with urinary 8-OHdG. Patients with highseverity grade (n=27) excreted urinary TSA significantly greater than those with low-severity grade (n=18). Conclusion: Urinary TSA, 8-OHdG, and MDA increased in patients with bladder cancer. The elevated urinary TSA was associated with enhanced oxidative stress. In addition, urinary TSA increased with progressiveness of the tumor.

EGF genetic polymorphism is associated with clinical features but not malignant phenotype in neurofibromatosis type 1 patients

Neurofibromatosis type 1 (NF1) is characterized by a wide variation in clinical presentation and in some cases progression to malignant tumor. Epidermal growth factor (EGF) is an important mitogen for Schwann cells and is involved in the development of malignant tumors in NF1 patients. We hypothesized that EGF +61 G/A functional polymorphism, which represents constitutional all-life exposure to higher EGF expression and circulating levels, may predispose for precocious and more aggressive manifestations of disease. We found that clinical findings of intestinal polyps are significantly more frequent in patients with G homozygous genotype (P = 0.023). Those carriers of GG genotype have earlier onset of café-au-lait spots and Lisch nodules appearance (P = 0.030 and P = 0.017, respectively). Nevertheless, the EGF overexpressing genotype-GG, is not associated with higher risk for malignant progression or severity of disease. EGF polymorphism may play a role in the earlier onset of NF1 pigment cell-related manifestations and in intestinal polyps' development. Further studies in larger samples should confirm the absence of risk for having higher severity grade or malignant phenotype in NF1 patients.

Delayed Intracranial Complications After Concussion

The incidence of readmissions because of delayed intracranial complications within 3 weeks after observation for the sole diagnosis of concussion was examined in a national cohort. A nested case-control design was used to analyze the association between clinical factors as well as early computed tomography (CT) scan examination and these complications. Out of 100,784 patients hospitalized because of concussion during ten years, 127 (0.13%) patients were readmitted because of a delayed intracranial complication. High clinical severity grade (odds ratio [OR] 2.0, confidence interval [CI] 1.2-3.6), minor CT scan abnormalities (OR 1.7, CI 0.8-3.4) and male gender (OR 2.2, CI 1.4-3.5) were associated with an increased risk of delayed, intracranial complications. The incidence of delayed intracranial complications after primarily uncomplicated concussion was low. High clinical severity grade and male gender were risk factors. We failed to demonstrate an additional value of the acute CT scan examination to predict these complications.

Specialized Neurocritical Care, Severity Grade, and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage

To evaluate the impact of specialized neurocritical care on the population admitted to a neurovascular center and on the outcome of patients with severe aneurysmal subarachnoid hemorrhage (aSAH). After exclusion of patients treated with endovascular techniques, between 1999 and 2003, 198 patients with aSAH treated with early aneurysm clipping were analysed. In 1999, a new standardized protocol for intensive care treatment was established in the Department of Neurosurgery, University Hospital Zurich. The results were compared to the earlier time period (1993-1994) immediately after introduction of early aneurysm clipping. Out of 198 patients with aSAH, 90 patients (45.5%) suffered from mild aSAH World Federation of Neurosurgical Societies (WFNS) grade 1 and 2, 41 (27.3%) from aSAH WFNS grade 3, 36 (18.2%) from grade 4, and 57 (28.8%) from grade 5. From 1999 to 2003, significantly more patients with severe aSAH WFNS grade 4 and 5 underwent (further) treatment (93 out of 198 patients; 47.0%) compared to the former time-period after introduction of early surgery (23 out of 150 patients; 15.3%) (p < 0.0001). In the early series, 10 out of 23 patients (43.5%) with WFNS 4 recovered with good outcome Glasgow Outcome Score 4 and 5, whereas in the later series 23 out of 36 (63.9%) with WFNS grade 4 survived in a good functional state. Before 1999, all patients with WFNS grade 5 died or survived in a vegetative state. From 1999 to 2003, 20 out of 57 patients (35.1%) with aSAH WFNS grade 5 survived with good outcome. The availability of extended specialized neurocritical care seems to induce a change within the patient population towards a higher severity grade. Patients with highgrade aSAH might benefit most from highly specialized neurocritical care treatment.

Transdermal penetration of topical drugs used in the treatment of acne.

Acne vulgaris is a very common skin disease. Most patients present with mild to moderate acne comedonica or papulopustulosa grade I-II. The first-line treatment for these cases is generally via the topical route, whereas systemic medication is indicated when higher severity grades with small nodes or scarring occur. There are several topical agents available that affect at least one of the main pathogenetic factors responsible for the development of acne: hyperseborrhoea, hyperkeratosis, microbial colonisation and inflammatory and immunological reactions. Topical retinoids have a comedolytic and anticomedogenic activity, and some of them have anti-inflammatory potency. Azelaic acid and benzoyl peroxide have a moderate to strong antibacterial effect without inducing bacterial resistance, which is becoming a significant problem with the increasing use of topical antibacterials. Topical antiandrogens may soon be available for the treatment of the pathogenetic factor hyperseborrhoea. The transdermal penetration and the resulting systemic bioavailability of the various topical agents has not been widely considered. Apart from the retinoids, which can be associated with the risk of embryotoxicity/teratogenicity, and clindamycin, which might cause pseudomembranous colitis, information on the systemic pharmacokinetics of other topical agents is not readily available. There is still no consensus on the safe use of topical retinoids in pregnancy, and the occurrence of pseudomembranous colitis after the topical use of clindamycin does not appear to be of clinical relevance. In general, topical anti-acne agents are well tolerated and, as would be expected from their limited transdermal uptake, other significant safety concerns have not so far arisen.

Long-term clinical outcome of elderly patients with reflux esophagitis: a six-month to three-year follow-up study.

Although the prevalence of reflux esophagitis is known to increase with age, data on the long-term outcome of esophagitis in elderly patients are scarce. We sought to evaluate the clinical outcome of elderly patients with esophagitis 6 months to 3 years after diagnosis and to identify specific prognostic indicators of a poor outcome. This was a long-term (6 months to 3 years) follow-up study. Patients older than 65 years of age diagnosed as having reflux esophagitis healed after acute treatment (2 to 4 months) were included in the study. Clinical examinations and upper gastrointestinal endoscopy were performed every 6 months for the first year and annually thereafter. After healing, no therapy was prescribed; in the event of symptom recurrence, a maintenance therapy consisting either of H2 blockers or proton pump inhibitors (PPI) was prescribed. At baseline and during follow-up, the following clinical parameters were recorded: gender, age, the presence of symptoms (heartburn, acid regurgitation, epigastric/chest pain), type and dose of the maintenance therapy, nonsteroidal antiinflammatory drug use; gastric Helicobacter pylori infection, diagnosis of hiatal hernia, and/or Barrett's esophagus. The chi-square test, the Kaplan-Meier test, and Cox's proportional hazards regression analysis were used for statistical analyses. Included in the final analysis were 138 patients (M/F, 81/57; mean age, 79.7 years; range, 66-97). The numbers of patients in need of maintenance therapy were 47 of 69 (68.1%) after 6 months, 29 of 58 (50%) after 12 months, 17 of 39 (43.6%) after 24 months, and 12 of 26 (46.1%) after 36 months of follow-up. A significantly higher esophagitis relapse rate was found in patients not treated compared with subjects who were in maintenance therapy: 59% versus 8.5% (P <.0001) at 6 months, 65.5% versus 20.7% at 12 months (P <.002), 63.6% versus 11.7% at 24 months (P =.003), and 57.1% versus 8.3% at 36 months (P =.02). No significant difference in relapse rate was found in patients treated with H2 blockers versus PPIs (21.7% versus 10%). The Cox model demonstrated that no maintenance treatment (P =.00001), the presence of typical symptoms (P =.00001), the presence of hiatal hernia (P =.03), and a high severity grade of esophagitis at baseline (P =.009) were risk factors for relapse of esophagitis. In elderly subjects, esophagitis relapse occurs in a high percentage of cases, particularly in patients not treated with antisecretory drugs. The presence of typical symptoms, hiatal hernia, and a severe grade of esophagitis are risk factors for relapse. The most effective measure for minimizing the occurrence of relapse is a maintenance therapy with antisecretory drugs.

Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study.

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.

Guidelines for maintenance treatment of childhood asthma: Development of a score card system by multivariate cluster analysis

Multivariate cluster analysis of data on 128 asthmatic children resulted in the identification of 8 major discriminating variables. Stepwise divisions by this computer programme resulted in the formation of 6 grades of severity. There was significant correlation between higher grades of severity and early onset of the disease ( P < 0.02). There was also significant correlation between higher grades of severity and greater use of interval medications ( P < 0.002). However, 27.3% were receiving inadequate interval medications in respect of their grade of severity. Assignation of a 5-point scale to each of the 8 major discriminating variables resulted in the generation of computer-designated scores commensurate with each grade of severity. This was coupled to current recommendations for stepwise maintenance medications appropriate for each grade. This Score Card system for maintenance management of childhood asthma may prove useful in busy clinical settings.