First Episode Of Disease Research Articles

Clinical and Epidemiological Aspects of Multiple Sclerosis in Children.

Overall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children. In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software. Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively. MS is significantly more common among women. The most common age of onset is during the second decades. Sensory and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results.

Antibiotic prescribing and expenditures in outpatient adults in Greece, 2010 to 2013: evidence from real-world practice.

We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad-spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing.

Executive summary: 2013 update of the guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children.

Major recommendations are accompanied by ratings that include a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation (TABLE 1); this rating system is similar to the rating systems used in other USPHS/IDSA guidelines. Because licensure of drugs for children and their application in clinical care often relies on efficacy data from adult trials in combination with pharmacokinetic, safety, and observational data in children, recommendations sometimes rely on data from clinical trials or studies in adults with supporting data in children. Thus, the quality of evidence level is accompanied by an asterisk (*) to indicate that evidence supporting the recommendation is a hybrid of higher-quality adult study evidence and consistent but lower-quality pediatric study evidence. This modification to the rating system is the same as that used by the DHHS Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Table 1 System for grading strength of recommendations and quality of supporting evidence The guidelines discuss opportunistic illnesses that occur in the United States and ones that might occur during international travel, such as malaria. Because the guidelines target HIV-exposed and -infected children in the United States, the opportunistic pathogens discussed are those common to the United States and do not include certain pathogens such as Penicillium marneffei that may be seen almost exclusively outside the United States. They also do not include pathogens that are common but seldom cause chronic infection, or that have the same risk, disease course, and approach to prevention and treatment in all children regardless of HIV status. Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of first episode of disease; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment, including immune reconstitution inflammatory syndrome (IRIS); management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. The most important, rated recommendations are highlighted in boxed major recommendations sections preceding the text for each OI, and a table of dosing recommendations follows the text for each OI. The tables at the end of the document summarize recommendations for dosing of medications used for prevention and treatment of OIs in children; drug preparation and toxicity information for children; and major drug-drug interactions. Vaccination recommendations for HIV-infected children and adolescents are summarized in the section entitled “Preventing Vaccine-Preventable Diseases in HIV-Infected Children and Adolescents” and individual OI sections and detailed in figures at the end of the document.

Is the length of postoperative recurrence on the neo ileum terminal ileum predictable in Crohn's disease?

Crohn's disease (CD) often has a stricturing phenotype on the terminal ileum requiring surgery due to obstruction. Recurrence is frequent, creating a risk of multiple surgeries. We studied patients with ileal or ileo-colic CD who had undergone at least two surgical bowel resections between 1968 and 2008 for obstructive symptoms. Aims The aim of this retrospective study was to determine if the length of the removed diseased bowel varied from one surgical resection to the next. The measurements obtained from radiology (small bowel follow-up), surgery and histology were compared. Results Twenty four patients were included. Seventeen had 2 resections, 5 patients had 3 resections and two had 4 resections. The resected length of the diseased ileum was significantly shorter for the second intervention than for the first as assessed by radiology (median 16 cm vs 37 cm; p = 0.0005), surgery (20 cm vs 40 cm; p = 0.005) and histology (15 cm vs 25 cm; p = 0.02) while there was no difference between the second and third resections (16 cm, 13 cm, 19.5 cm respectively) for the three types of measurements (p = NS). The surgeon's assessment of the diseased segment was longer than the histologist's (p = 0.003). No factor was found to be significantly associated with the length of the diseased bowel on recurrence. Conclusion This study shows that the length of the excised neo-terminal ileum during the first episode of recurrence was shorter than during the first episode of disease and remained stable for the third episode. This is an important prognostic finding that could influence the therapeutic choices for this disease and reduce hesitation to indicate surgery.

S25-04 - Neuroanatomical and neurofunctional correlates of the transition from at-risk state to full-blown psychosis

In early stage psychosis research the identification of neurobiological correlates of vulnerability to schizophrenia is an important hurdle. Structural and functional imaging techniques have shown the potential to clarify the correlates of an increased vulnerability to psychosis and to address the changes underlying transition from a prodromal state to a first episode of disease. sMRI studies found decreased prefrontal, cingulate, insular and cerebellar gray matter volume in high risk subjects with transition(HR-T) as compared to high-risk subjects without transition (HR-NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T compared to HR-NT subjects Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, increased membrane turnover in frontal and cingulate cortex. Structural and neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal and cerebellar cortex might be predictive for development of psychosis within high risk subjects.

Management of Diverticulitis in Younger Patients

This study was designed to evaluate the clinical course of sigmoid diverticulitis patients younger than aged 50 years examined by abdominal CT during the first episode of disease to elucidate whether the criteria used for older patients can safely be followed in their younger counterparts. Retrospective review of patients with sigmoid diverticulitis treated from 1990 to 2003 was performed. patients younger than aged 50 years with sigmoid diverticulitis documented by CT scan. Severity of disease was classified according to radiographic findings. Age, gender, treatment, recurrent disease, and need for colostomy were documented. A total of 5,499 patients were identified with sigmoid diverticulitis: 962 patients were younger than aged 50 years, and 411 had a CT scan on their first episode of disease. Of the 411 patients, 335 were classified as uncomplicated and 76 were complicated. Of the uncomplicated patients, 101 underwent an elective operation and 234 were followed nonoperatively. Of those followed, 67 had a recurrent uncomplicated episode, 10 had a recurrent complicated episode, of whom 5 required emergent operation and colostomy. Of the 76 patients with complicated disease, 23 had an emergent operation with colostomy, and 38 had an elective operation. Fifteen patients were followed without an operation and seven had a recurrent uncomplicated episode. None required emergent operation or colostomy. Younger patients with uncomplicated diverticulitis by CT criteria respond well to medical management and seldom required an emergent operation and colostomy. Young patients with diverticulitis should be treated according to the same criteria used for older patients.

Preemptive Therapy With Intravenous Ganciclovir for the Prevention of Cytomegalovirus Disease in Lung Transplant Recipients

The most effective strategy for the prevention of cytomegalovirus (CMV) disease in lung transplantation has not been conclusively established. The aim of this study was to determine the efficacy of preemptive ganciclovir therapy for this purpose. Twenty-five consecutive adult patients positive for CMV before transplantation and surviving more than 30 days after the procedure were studied. Mean follow-up was 732.2 days (range, 210–1125). All patients received intravenous (IV) ganciclovir prophylaxis for the first 21 days and subsequently underwent frequent CMV antigenemia monitoring: weekly for the first 3 months, every 15 days between 3 and 6 months, and monthly thereafter. IV ganciclovir was given when antigenemia results were greater than 10 infected cells per 100,000 polymorphonuclears. The study group was compared with a historical group of 30 consecutive patients who had received IV ganciclovir prophylaxis and continued on oral ganciclovir up to day 120 posttransplantation. Eighteen of the 25 patients (72.0%) presented episodes of CMV infection. Six of the 25 patients (24.0%) had CMV disease, including 3 viral syndromes and 3 cases of pneumonitis. Four patients debuted with CMV disease, 1 of them with pneumonitis. CMV resistance to ganciclovir was observed in 2 patients. The incidence of infection was higher than in the historical group (72.0% vs 46.7%; P < .05), but there were no significant differences in the incidence of CMV disease (24.0% vs 40.0%; P = not significant [NS]). Mean time before onset of the first episode of disease was lower in the preemptive therapy group than in the comparison patients (82.8 days; range, 42–240 vs 175 days; range, 90–243; P < .05). In conclusion, preemptive therapy for CMV disease is as effective a prevention strategy as oral ganciclovir prophylaxis. However, the early appearance of CMV disease with preemptive therapy can make this approach inadvisable.

Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice

Increased golli MBP (golli) expression has been observed in the peripheral immune system of mice in the relapsing phase of EAE, raising the possibility that golli MBP expression in the periphery may contribute to relapses. Here we describe the generation of golli MBP-deficient mice and a comparison of the clinical course of EAE between heterozygous (golli +/−) and wild-type (golli +/+) mice. There was no difference between the two groups in incidence of disease, severity of the first episode of disease, or remission after the first episode. However, there was a significant reduction in relapses in golli +/− mice vs. controls, suggesting a role for golli proteins in the relapses in EAE.

Meningococcal disease and polymorphism of FcgammaRIIa (CD32) in late complement component-deficient individuals.

Late complement component-deficient (LCCD) individuals lack plasma bactericidal activity and are highly susceptible to meningococcal disease. Phagocytosis plays a significant role in immune defence against meningococci and involves FcgammaRIIa (CD32) on leucocytes. Two allotypic forms are currently recognized: FcgammaRIIa-R131 and RIIa-H131. Neutrophils with the IIa-H/H131 allotype are more effective in phagocytosis than IIa-R/R131. We studied the distributions of IIa-R131 and IIa-H131 allotypes among 29 Russian LCCD patients who had suffered from recurrent episodes of meningococcal disease. The distribution of IIa-R/R131 to heterozygous IIa-R/H131 to homozygous IIa-H/H131 genotypes was 0.14:0.29:0.57 for LCCD patients who developed the first episode of disease before 10 years of age. The distribution was 0.21:0.64:0.14 for patients who experienced meningococcal disease above the age of 10 years (chi2 = 6, P < 0.05, odds ratio for IIa H/H131 versus R/R131 = 8). Meningococcal disease had a 'grave' course in 14 of 31 disease episodes in patients with IIa-R/R131 and IIa-R/H131 allotypes, in contrast to 1 of 18 episodes in patients with IIa-H/H131 allotype (chi2 = 7, P < 0.01, odds ratio = 14). We conclude that IIa-H/H131 individuals appear to have a higher acquired antibody-mediated phagocytosis-dependent resistance to meningococcal disease above the age of 10 years. Additionally, effective CD32-mediated phagocytosis may restrict the severity of meningococcal disease in LCCD patients with IIa-H/H131 phenotype.

Effects of cyclosporin A treatment on clinical course and inflammatory cell apoptosis in experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by inoculation with myelin basic protein (MBP) and adjuvants. Rats were treated with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease followed by clinical recovery. Rats treated with CsA 16 or 32 mg/kg had minimal signs of EAE at the usual time after inoculation, but developed signs of disease after treatment was ceased. Rats treated with CsA 8 mg/kg had a delayed first episode of disease and then developed a relapsing or a chronic persistent course of disease. CsA 4 mg/kg delayed the onset of disease. To study the effects of CsA on the inflammatory infiltrate, cells were extracted from the spinal cords of rats with EAE, 16 h after a single injection of CsA or saline. Extracted cells were labelled with antibodies to T cells, CD11b/c (macrophages/microglia), CD95 (Fas) and Fas ligand. CsA 4 mg/kg did not alter the composition of the inflammatory infiltrate. Treatment with higher single doses of CsA caused a dose-dependent decline in the percentage of T cell receptor (TCR) αβ + cells in the inflammatory infiltrate. All doses of CsA caused a significant increase in the number and percentage of cells that were apoptotic. CsA treatment caused an increase in the percentages of CD5 + and TCRαβ + cells that were apoptotic. There was a decline in the percentage of apoptotic T cells that were Vβ8.2 +, compared to the percentage of non-apoptotic T cells that were Vβ8.2 +, in CsA treated rats compared to saline-treated controls. This suggests that, while CsA treatment caused a non-specific increase in the overall level of T cell apoptosis in the spinal cord, it abrogated the selective apoptosis of Vβ8.2 + encephalitogenic T cells that normally occurs during spontaneous recovery from acute EAE.

Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

Ureaplasma urealyticum and Mycoplasma hominis in chlamydial and non-chlamydial nongonococcal urethritis.

Urethral specimens from 726 patients with nongonococcal urethritis (NGU) were examined for Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis. Chlamydiae were isolated from 35.9% of ureaplasma-positive patients and from 36.5% of ureaplasma-negative patients. Ureaplasmas were isolated from 52.5% of chlamydia-positive patients and from 53.1% of chlamydia-negative patients, an observation which contrasts with that of some workers who have suggested that ureaplasmas are significantly associated with chlamydia-negative NGU. Furthermore, the numbers of ureaplasmas isolated from patients who did or did not harbour chlamydiae were not significantly different nor was there a particular association of ureaplasmas with chlamydia-negative NGU in patients experiencing their first episode of disease. In addition, M. hominis was not isolated more frequently from those from whom chlamydiae were or were not isolated. The only significant associations were the isolation of M. hominis from patients who were ureaplasma-positive and of ureaplasmas from those who were M. hominis-positive. These findings do not necessarily mitigate against ureaplasmas being responsible for some cases of chlamydia-negative NGU.