The outcome of childhood Haemophilus influenzae meningitis. A population based study.
TL;DR: To determine the morbidity and mortality from childhood Haemophilus influenzae type b (Hib) meningitis in a well defined population, a large number of cases are diagnosed with Hib.
Abstract: OBJECTIVE To determine the morbidity and mortality from childhood Haemophilus influenzae type b (Hib) meningitis in a well defined population. DESIGN Retrospective survey 1985-1987 and prospective surveillance of hospital laboratories 1989-1990. Information on outcome of meningitis was obtained from hospital records and attending physicians and, in 1989-1990, from a survey of the children's parents. SETTING Sydney Statistical Division, which had a population of children aged 0-4 years of 229,165 in 1986 and 263,758 in 1990. PATIENTS Eligible children were aged from one month to four years and had clinical and microbiological evidence of Hib meningitis on standard criteria. RESULTS There were 229 eligible children. Twelve were excluded (seven died and five had pre-existing neurological deficits). A neurological deficit was detected at the time of hospital discharge in 45 patients (21%) and persisted for 12 months or longer in 29 patients (13%). Follow-up information was available for 165 (96%) children who were normal at the time of hospital discharge and persistent deficits were recorded in 12 (7%) of these children. Forty-one children (19%) had readily recognisable neurological or hearing problems: nine (4%) had persistent severe neurological deficits and seven (3%) had severe hearing loss requiring hearing aids or a cochlear implant. Age had a significant influence on outcome. The youngest children were significantly more likely to be admitted to intensive care. Severe neurological deficits showed a significant negative trend with increasing age (P = 0.03). Severe unilateral or bilateral sensorineural loss (odds ratio [OR] 8.0, 95% confidence interval [CI] 1.5-81) and ataxia at discharge (OR 13.3, 95% CI 2.8-128) were noticeably more common in children over two years of age, with a significant positive trend (P < or = 0.001) with increasing age. Patients requiring intensive care were much more likely to have an adverse outcome, particularly if positive pressure ventilation was needed. CONCLUSIONS These data provide population-based estimates of the minimum incidence of adverse outcomes from Hib meningitis in an urban community with good access to medical services. This is important in assessing the impact of Hib vaccination, as meningitis is responsible for most of the long-term morbidity from childhood invasive Hib disease. Determination of the relationship between morbidity and age is important for assessing alternative vaccine strategies.
Citations
More filters
TL;DR: It is shown that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour.
Abstract: 12 Pathology and Microbiology, and 13 Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.
9,493 citations
[...]
01 Feb 2009
TL;DR: This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale, and what might be coming next.
Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?
5,234 citations
TL;DR: Information is provided about CRP as a protein and an acute-phase reactant, and a knowledge-based framework for interpretation and analysis of clinical observations of CRP in relation to cardiovascular and other diseases, that identifies it as a possible therapeutic target.
Abstract: In the mid 1990s, immunoassays for C-reactive protein (CRP), with greater sensitivity than those previously in routine use, revealed that increased CRP values, even within the range previously considered normal, strongly predict future coronary events. These findings triggered widespread interest, especially, remarkably, in the US, where the clinical use of CRP measurement had been largely ignored for about 30 years. CRP production is part of the nonspecific acute-phase response to most forms of inflammation, infection, and tissue damage and was therefore considered not to provide clinically useful information. Indeed, CRP values can never be diagnostic on their own and can only be interpreted at the bedside, in full knowledge of all other clinical and pathological results. However, they can then contribute powerfully to management, just as universal recording of the patient’s temperature, an equally nonspecific parameter, is of great clinical utility.
The present torrent of studies of CRP in cardiovascular disease and associated conditions is facilitated by the ready commercial availability of automated CRP assays and of CRP itself as a research reagent. However, unlike the earlier rejection in the US of CRP as an empirical test because of its perceived lack of specificity, the current enthusiasm over CRP in cardiovascular disease is widely characterized by failure to recognize appropriately the nonspecific nature of the acute-phase response, and by lack of critical biological judgment. Quality control of the source, purity, and structural and functional integrity of the CRP, and the relevance of experimental design before ascribing pathophysiological functions, are also often ignored.
This article provides information about CRP as a protein and an acute-phase reactant, and a knowledge-based framework for interpretation and analysis of clinical observations of CRP in relation to cardiovascular and other diseases. We also review the properties of CRP, its possible role in pathogenesis of disease, and our own observations that identify it as a possible therapeutic target.
3,814 citations
TL;DR: The prevalence of sleep-disordered breathing in the United States for the periods of 1988-1994 and 2007-2010 is estimated using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study with participants randomly selected from an employed population of Wisconsin adults.
Abstract: Sleep-disordered breathing is a common disorder with a range of harmful sequelae. Obesity is a strong causal factor for sleep-disordered breathing, and because of the ongoing obesity epidemic, previous estimates of sleep-disordered breathing prevalence require updating. We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988–1994 and 2007–2010 using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study that was established in 1988 with participants randomly selected from an employed population of Wisconsin adults. A total of 1,520 participants who were 30–70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing. Participants were invited for repeat studies at 4-year intervals. The prevalence of sleep-disordered breathing was modeled as a function of age, sex, and body mass index, and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey. The current prevalence estimates of moderate to severe sleep-disordered breathing (apnea-hypopnea index, measured as events/hour, ≥15) are 10% (95% confidence interval (CI): 7, 12) among 30–49-year-old men; 17% (95% CI: 15, 21) among 50–70-year-old men; 3% (95% CI: 2, 4) among 30–49-year-old women; and 9% (95% CI: 7, 11) among 50–70 year-old women. These estimated prevalence rates represent substantial increases over the last 2 decades (relative increases of between 14% and 55% depending on the subgroup).
3,301 citations
TL;DR: This work discusses the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response, and many ERBB inhibitors used in the clinic.
Abstract: ERBB receptor tyrosine kinases have important roles in human cancer. In particular, the expression or activation of epidermal growth factor receptor and ERBB2 are altered in many epithelial tumours, and clinical studies indicate that they have important roles in tumour aetiology and progression. Accordingly, these receptors have been intensely studied to understand their importance in cancer biology and as therapeutic targets, and many ERBB inhibitors are now used in the clinic. We will discuss the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response.
3,083 citations
References
More filters
TL;DR: A prospective, laboratory-based surveillance project obtained accurate data on meningitis in a population of 34 million people during 1986, suggesting that improvements in early detection and antibiotic treatment may have occurred since that time.
Abstract: A prospective, laboratory-based surveillance project obtained accurate data on meningitis in a population of 34 million people during 1986. Haemophilus influenzae was the most common cause of bacterial meningitis (45%), followed by Streptococcus pneumoniae (18%), and Neisseria meningitidis (14%). Rates of H. influenzae meningitis varied significantly by region, from 1.9/100,000 in New Jersey to 4.0/100,000 in Washington state. The overall case fatality rates for meningitis were lower than those reported in several studies from the early 1970s, suggesting that improvements in early detection and antibiotic treatment may have occurred since that time. Concurrent surveillance was also performed for all invasive disease due to the five most common causes of bacterial meningitis. Serotypes of group B streptococcus other than type III caused more than half of neonatal group B streptococcal disease and mortality, suggesting that an optimal vaccine preparation must be multivalent. Of the organisms evaluated, group B streptococcus was the second most common cause of invasive disease in persons greater than 5 years old.
785 citations
TL;DR: It is concluded that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.
Abstract: We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.
557 citations
TL;DR: In the present analysis, estimates of completeness of the registry as a whole were remarkably similar using either two or three data sources, and site-specific comparisons differed by at most 7%.
527 citations
"The outcome of childhood Haemophilu..." refers background in this paper
...This study was conducted with the support of the Ontario Institute for Cancer Research and Cancer Care Ontario (CCO) through funding provided by the Government of Ontario, and through provision of data by the Institute for Clinical Evaluative Sciences (ICES) and CCO....
[...]
...Diabetes status was determined by linking subjects to the validated Ontario Diabetes Database, an administrative database registry of diabetes patients....
[...]
...Specific comorbidities were determined at baseline and derived from Discharge Abstraction Database and Ontario Health Insurance Program databases....
[...]
...The Ontario health care databases do not contain clinical data; thus, we were not able to adjust for BMI in our analyses....
[...]
...The primary outcome was all-cause mortality, based on death certificate records from the Registered Persons Database, which contains demographic and residential data on all Ontario residents but does not include information on cause of death....
[...]
TL;DR: The number of days of illness before hospitalization and institution of antibacterial treatment was not correlated with the development of sensorineural deafness, and the site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected.
Abstract: As part of a prospective study of acute bacterial meningitis in children, we studied for five years the hearing of 185 infants and children who had acute bacterial meningitis when they were more than one month of age. Nineteen (10.3 per cent) of the patients had persistent bilateral or unilateral sensorineural hearing loss. The incidence of hearing loss as determined by electric-response audiometry and conventional tests was 31 per cent with Streptococcus pneumoniae, 10.5 per cent with Neisseria meningitidis, and 6 per cent with Hemophilus influenzae infections. Transient conductive hearing impairment was found in 16 per cent of the sample, but in no case was there apparent improvement in a sensorineural deficit over time. The site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected. The number of days of illness (symptoms) before hospitalization and institution of antibacterial treatment was not correlated wit...
320 citations
TL;DR: The increased incidence of unprovoked seizures was highest during the first 5 years after the CNS infection but remained elevated over the next 15 years of follow-up, and the type of CNS infection and the presence or absence of seizures during the acute phase of the CNS infections greatly influenced the risks of subsequent unprovoke seizures.
Abstract: A population-based cohort of 714 survivors of encephalitis or meningitis between 1935 and 1981 was followed in order to evaluate the risks of unprovoked seizures after CNS infections. The 20-year risk of developing unprovoked seizures was 6.8%, and the ratio of observed to expected cases of unprovoked seizures was 6.9. The increased incidence of unprovoked seizures was highest during the first 5 years after the CNS infection but remained elevated over the next 15 years of follow-up. The type of CNS infection and the presence or absence of seizures during the acute phase of the CNS infection greatly influenced the risks of subsequent unprovoked seizures. The 20-year risk of developing unprovoked seizures was 22% for patients with viral encephalitis and early seizures, 10% for patients with viral encephalitis without early seizures, 13% for patients with bacterial meningitis and early seizures, and 2.4% for patients with bacterial meningitis without early seizures. The 20-year risk of 2.1% for patients with aseptic meningitis was not increased over the general population incidence of unprovoked seizures.
270 citations