Paediatric, invasive pneumococcal disease in Switzerland, 1985-1994. Swiss Pneumococcal Study Group.
BACKGROUND: Cost effective use of new vaccines against pneumococcal disease in children requires detailed information about the local epidemiology of pneumococcal infections. METHODS: Data on 393 culture-confirmed cases of invasive pneumococcal infection in children (<17 years) hospitalized in Swiss paediatric clinics were collected retrospectively for the years 1985-1994. RESULTS: Meningitis (42%) was most frequent, followed by pneumonia (28%) and bacteraemia (26%). The overall annual incidence was 2.7 cases per 100000 children <17 years old and 11 cases per 100000 children <2 years old. Annual incidence rates were stable over the study period. Lethality was high for meningitis (8.6%) and bacteraemia (8.9%). A history of basal skull fracture was reported in 3.3% of children with pneumococcal meningitis. Residence in a rural region was associated with an increased risk of pneumococcal infection (relative risk = 1.45, 95% confidence interval: 1.01-2.00). CONCLUSIONS: Paediatric, invasive pneumococcal disease seems to be less frequent in Switzerland than in other European and non-European countries. This may be due to differences in diagnostic strategies and lower frequency of risk factors such as the use of day care. Children with a history of basal skull fracture are at increased risk for pneumococcal meningitis. Further investigation of the association of invasive pneumococcal infection with rural residence and the use of antibiotics for upper respiratory tract infections might give new insight into the dynamics of Streptococcus pneumoniae infection and the development of antibiotic resistance. (+info
Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension.
OBJECTIVE: To investigate the usefulness of hydroxychloroquine (HCQ) dose-loading to increase the percentage of responders or rate of response in treating rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with early RA (mean duration 1.5 years) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/day and then began a 6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n = 71), 800 mg/day (n = 71), and 1,200 mg/day (n = 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day. RESULTS: All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modifying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.97%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related. CONCLUSION: Dose-loading with HCQ increased the degree of response at 6 weeks in this group of patients with early, predominantly seronegative RA. Adverse GI events were dose related, while adverse ocular events were not. (+info
Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins.
OBJECTIVE: Degenerative intervertebral disc disease is common; however, the importance of genetic factors is unknown. This study sought to determine the extent of genetic influences on disc degeneration by classic twin study methods using magnetic resonance imaging (MRI). METHODS: We compared MRI features of degenerative disc disease in the cervical and lumbar spine of 172 monozygotic and 154 dizygotic twins (mean age 51.7 and 54.4, respectively) who were unselected for back pain or disc disease. An overall score for disc degeneration was calculated as the sum of the grades for disc height, bulge, osteophytosis, and signal intensity at each level. A "severe disease" score (excluding minor grades) and an "extent of disease" score (number of levels affected) were also calculated. RESULTS: For the overall score, heritability was 74% (95% confidence interval [95% CI] 64-81%) at the lumbar spine and 73% (95% CI 64-80%) at the cervical spine. For "severe disease," heritability was 64% and 79% at the lumbar and cervical spine, respectively, and for "extent of disease," heritability was 63% and 63%, respectively. These results were adjusted for age, weight, height, smoking, occupational manual work, and exercise. Examination of individual features revealed that disc height and bulge were highly heritable at both sites, and osteophytes were heritable in the lumbar spine. CONCLUSION: These results suggest an important genetic influence on variation in intervertebral disc degeneration. However, variation in disc signal is largely influenced by environmental factors shared by twins. The use of MRI scans to determine the phenotype in family and population studies should allow a better understanding of disease mechanisms and the identification of the genes involved. (+info
Validation of the Rockall risk scoring system in upper gastrointestinal bleeding.
BACKGROUND: Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study. AIMS: To assess internal and external validity of a simple risk scoring system recently developed by Rockall and coworkers. METHODS: Calibration and discrimination were assessed as measures of validity of the scoring system. Internal validity was assessed using an independent, but similar patient sample studied by Rockall and coworkers, after developing the scoring system (Rockall's validation sample). External validity was assessed using patients admitted to several hospitals in Amsterdam (Vreeburg's validation sample). Calibration was evaluated by a chi2 goodness of fit test, and discrimination was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Calibration indicated a poor fit in both validation samples for the prediction of rebleeding (p<0.0001, Vreeburg; p=0.007, Rockall), but a better fit for the prediction of mortality in both validation samples (p=0.2, Vreeburg; p=0.3, Rockall). The areas under the ROC curves were rather low in both validation samples for the prediction of rebleeding (0.61, Vreeburg; 0.70, Rockall), but higher for the prediction of mortality (0.73, Vreeburg; 0.81, Rockall). CONCLUSIONS: The risk scoring system developed by Rockall and coworkers is a clinically useful scoring system for stratifying patients with acute UGIB into high and low risk categories for mortality. For the prediction of rebleeding, however, the performance of this scoring system was unsatisfactory. (+info
Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer.
The aim of the present study was to find out whether increasing malignancy of prostate carcinoma correlates with an overall increase of loss of heterozygosity (LOH), and whether LOH typing of microdissected tumour areas can help to distinguish between multifocal or clonal tumour development. In 47 carcinomas analysed at 25 chromosomal loci, the overall LOH rate was found to be significantly lower in grade 1 areas (2.2%) compared with grade 2 (9.4%) and grade 3 areas (8.3%, P = 0.007). A similar tendency was found for the mean fractional allele loss (FAL, 0.043 for grade 1, 0.2 for grade 2 and 0.23 for grade 3, P = 0.0004). Of 20 tumours (65%) with LOH in several microdissected areas, 13 had identical losses at 1-4 loci within two or three areas, suggesting clonal development of these areas. Markers near RB, DCC, BBC1, TP53 and at D13S325 (13q21-22) showed higher loss rates in grades 2 and 3 (between 25% and 44.4%) compared with grade 1 (0-6.6%). Tumour-suppressor genes (TSGs) near these loci might, thus, be important for tumour progression. TP53 mutations were detected in 27%, but BBC1 mutations in only 7%, of samples with LOH. Evaluation of all 25 loci in every tumour made evident that each prostate cancer has its own pattern of allelic losses. (+info
Incidence and duration of hospitalizations among persons with AIDS: an event history approach.
OBJECTIVE: To analyze hospitalization patterns of persons with AIDS (PWAs) in a multi-state/multi-episode continuous time duration framework. DATA SOURCES: PWAs on Medicaid identified through a match between the state's AIDS Registry and Medicaid eligibility files; hospital admission and discharge dates identified through Medicaid claims. STUDY DESIGN: Using a Weibull event history framework, we model the hazard of transition between hospitalized and community spells, incorporating the competing risk of death in each of these states. Simulations are used to translate these parameters into readily interpretable estimates of length of stay, the probability that a hospitalization will end in death, and the probability that a nonhospitalized person will be hospitalized within 90 days. PRINCIPAL FINDINGS: In multivariate analyses, participation in a Medicaid waiver program offering case management and home care was associated with hospital stays 1.3 days shorter than for nonparticipants. African American race and Hispanic ethnicity were associated with hospital stays 1.2 days and 1.0 day longer than for non-Hispanic whites; African Americans also experienced more frequent hospital admissions. Residents of the high-HIV-prevalence area of the state had more frequent admissions and stays two days longer than those residing elsewhere in the state. Older PWAs experienced less frequent hospital admissions but longer stays, with hospitalizations of 55-year-olds lasting 8.25 days longer than those of 25-year-olds. CONCLUSIONS: Much socioeconomic and geographic variability exists both in the incidence and in the duration of hospitalization among persons with AIDS in New Jersey. Event history analysis provides a useful statistical framework for analysis of these variations, deals appropriately with data in which duration of observation varies from individual to individual, and permits the competing risk of death to be incorporated into the model. Transition models of this type have broad applicability in modeling the risk and duration of hospitalization in chronic illnesses. (+info
Natural history of dysplasia of the uterine cervix.
BACKGROUND: A historical cohort of Toronto (Ontario, Canada) women whose Pap smear histories were recorded at a major cytopathology laboratory provided the opportunity to study progression and regression of cervical dysplasia in an era (1962-1980) during which cervical squamous lesions were managed conservatively. METHODS: Actuarial and Cox's survival analyses were used to estimate the rates and relative risks of progression and regression of mild (cervical intraepithelial neoplasia 1 [CIN1]) and moderate (CIN2) dysplasias. In addition, more than 17,000 women with a history of Pap smears between 1970 and 1980 inclusive and who were diagnosed as having mild, moderate, or severe dysplasia were linked to the Ontario Cancer Registry for the outcome of any subsequent cervical cancers occurring through 1989. RESULTS: Both mild and moderate dysplasias were more likely to regress than to progress. The risk of progression from mild to severe dysplasia or worse was only 1% per year, but the risk of progression from moderate dysplasia was 16% within 2 years and 25% within 5 years. Most of the excess risk of cervical cancer for severe and moderate dysplasias occurred within 2 years of the initial dysplastic smear. After 2 years, in comparison with mild dysplasia, the relative risks for progression from severe or moderate dysplasia to cervical cancer in situ or worse was 4.2 (95% confidence interval [CI] = 3.0-5.7) and 2.5 (95% CI = 2.2-3.0), respectively. CONCLUSION: The risk of progression for moderate dysplasia was intermediate between the risks for mild and severe dysplasia; thus, the moderate category may represent a clinically useful distinction. The majority of untreated mild dysplasias were recorded as regressing to yield a normal smear within 2 years. (+info
Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.
Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time. (+info