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M J Clarke

Publications and source records attributed to M J Clarke.

At least 55 records · Page 3Linked to original sources

The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden.

The decision to develop rotavirus vaccines was predicated on the extensive burden of rotavirus disease among children worldwide. US reports on nationwide hospitalizations (1979-1992) and deaths (1968-1991) due to diarrhea and weekly reports of rotavirus infection by 74 laboratories were reviewed to estimate the burden of rotavirus disease, identify epidemiologic trends, and consider methods for evaluating an immunization program when a vaccine becomes available. From 1968 to 1985, diarrhea-related deaths among US children <5 years old declined from 1100 to 300/year. This decline was associated with the disappearance of winter peaks for diarrhea-related deaths previously associated with rotavirus infection among children 4-23 months old. From 1979 to 1992, however, hospitalizations for diarrhea averaged 186,000/year and retained their winter peaks, which have been linked to rotavirus infections. Each year an estimated 54,000-55,000 US children are hospitalized for diarrhea, but <40 die with rotavirus. A rotavirus vaccine program will require improved surveillance, including the timely collection of data from sentinel hospitals, in which a diagnosis of rotavirus can be established or ruled out for all children hospitalized for diarrhea.

Child↗

Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus.

OBJECTIVES: To examine trends in the hospitalizations of children for diarrheal disease in the U.S. and to provide estimates for the burden of disease associated with rotavirus diarrhea. METHODS: Data for diarrheal hospitalizations among U.S. children ages 1 month through 4 years were compiled from the National Hospital Discharge Survey for the years 1979 through 1992. Between 1979 and 1992, 12% of all hospitalizations of U.S. children 1 month through 4 years of age had an International Classification of Diseases code for diarrhea listed in one of the top three positions on the discharge diagnosis. RESULTS: The annual rate of diarrheal hospitalizations, 97 per 10 000 persons (average, 185 742 per year), did not change substantially during the 14-year study period and accounted annually for 724 394 inpatient days (3.9 days per hospitalization). For most diarrheal hospitalizations (75.9%) no causative agent was specified in the National Hospital Discharge Survey records; of the remaining 24.8%, viruses were most commonly reported (19.3%), followed by bacteria (5.1%) and parasites (0.7%). The proportion of hospitalizations associated with viral diarrheas rose from 13% to 27% during the 14-year study period, whereas the proportion of hospitalizations for noninfectious diarrhea declined from 79% to 60%. Every year the number of hospitalizations peaked from November through April, the "winter" months, among children ages 4 through 35 months; this peak began in the West during November and December and reached the Northeast by March. CONCLUSIONS: Diarrhea continues to be a common cause of hospitalization among children in the United States and the winter seasonality estimated to be caused in large part by rotavirus would be expected to decrease if rotavirus vaccines currently being developed were introduced. Our analysis of temporal trends in diarrheal hospitalizations provides a unique surrogate with which to estimate the disease burden associated with rotavirus diarrhea.

Bacterial Infections↗

Practical methodology of meta-analyses (overviews) using updated individual patient data. Cochrane Working Group.

Meta-analyses using updated individual patient data may provide the most reliable means of combining data from similar randomized controlled trials. The benefits of this approach to systematic reviews are described. Guidance, based on the experience of several groups who have undertaken such projects, is given. This includes practical advice on initiating and maintaining collaboration, the time and resources required to undertake these usually international projects and methods of data checking and validation. Example proforma are included.

Data Collection↗

Trends of diarrheal disease--associated mortality in US children, 1968 through 1991.

OBJECTIVES: To describe temporal patterns in mortality related to diarrheal disease in US children and to assess progress toward its prevention and control. DESIGN: Retrospective analyses of death certificate data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. PATIENTS: Children aged 1 month through 4 years who died with diarrhea. SETTING: United States, 1968 through 1991. RESULTS: A total of 14 137 deaths associated with diarrhea among children were reported in the United States between 1968 and 1991. Of these, 78% occurred in infants (ie, aged 1 to 11 months); the median age at the time of death has declined from 5 to 1.5 months. Diarrheal disease mortality dropped by approximately 75% during the first 18 years of the study, but no decline has occurred since 1985. Infant mortality due to diarrhea (per 100 000 live births) averaged 12.8 and was found to be high for blacks (33.1) and for residents of the southern United States (18.5). The infant mortality due to diarrhea from 1986 through 1991 is 5.9. Peaks in winter deaths previously associated with rotavirus were prominent in the early years among infants aged 4 through 11 months. Such peaks have virtually disappeared since 1985. Diarrhea was the principal cause of death, as the leading associated diagnoses (electrolyte disorders [30%], cardiac arrest [16%], shock [8%], and nausea/vomiting [4%]) were commonly recognized complications of diarrhea. Since 1979, prematurity has emerged as a common associated diagnosis. CONCLUSIONS: Diarrheal deaths nationwide have declined 75% from 1968 to 1985 but stabilized since then at about 300 deaths per year. Because many of these deaths may still be preventable by early rehydration, future prevention efforts should be directed at educating health care providers about the continuing problem and recognition of the high-risk infant and at teaching mothers of such infants to begin rehydration early and to seek medical attention when their infant develops diarrhea.

Cause of Death↗

Systematic reviews of randomized controlled trials: the need for complete data.

If the relative effectiveness of different treatments that might be used in clinical practice is to be evaluated reliably, it is very important that the evaluation is carried out in an appropriate manner. This is especially true where the differences between treatments are expected to be moderate, and so easily obscured by the play of chance or systematic bias. Although such differences are often of considerable clinical importance, they can be difficult to assess and require a large amount of randomized evidence. This evidence can be obtained through prospective randomized controlled trials, meta-analysis of results from past randomized trials, or ideally a combination of the two, with prospective trials contributing to future meta-analyses. Whichever technique is adopted, all possible biases must be minimized through the collection of as much randomized evidence as possible. In meta-analyses, this is best achieved by ensuring that all relevant trials, and all randomized participants in these trials, are included in the analysis. The gold standard for this might be a meta-analysis of individual patient data, in which details for each participant in every trial are collected and analysed centrally. This approach requires considerable time and effort. However, it will add to the analyses that can be performed and will remove many of the problems associated with a reliance on published data alone and some of the problems that can arise from the use of aggregate data. This paper sets out some of the reasons for this and some of the techniques used for individual patient data-based meta-analysis.

Bias↗

National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome.

Between 1981 and 1992, the Centers for Disease Control collected and summarized 9,223 cases of Rocky Mountain spotted fever (RMSF) reported from 46 states. Four states (North Carolina, Oklahoma, Tennessee, and South Carolina) accounted for 48% of the reports. The annual incidence per million U.S. population decreased from a high in 1981 of 5.2 to a low in 1992 of 2.0, primarily due to decreased incidence in the southeast. Case report forms were filed on 7,650 patients, of whom 4,217 had laboratory-confirmed RMSF. The age group with the highest incidence was those 5-9 years of age. Most cases (90.0%) occurred between April 1 and September 30 and included a history of tick attachment (59.6%). Reported symptoms included fever (94.0%), headache (86.2%), myalgia (82.5%), and rash (80.2%). The case-fatality ratio was 4.0%. Risk factors associated with death included older age, delay in treatment or no treatment, and treatment with chloramphenicol (compared with tetracycline); however, insufficient data existed to fully assess the confounding effect of severity of illness on antibiotic choice.

Adolescent↗

Obtaining data from randomised controlled trials: how much do we need for reliable and informative meta-analyses?

Many randomised controlled trials compare treatments that will produce only moderate differences in outcome, but these differences can be clinically important. However, they are difficult to assess reliably and require a large amount of randomised evidence. This can be achieved through large prospective randomised trials which will accrue future patients, the meta-analysis of results from randomised trials involving patients from the past, or--ideally--both. The techniques require that all possible biases are minimised, and in meta-analyses this can best be achieved by ensuring that all of the randomised evidence--both trials and participants in those trials--is included. The meta-analysis of individual patient data has been described as the gold standard for this approach. It will remove many of the problems associated with relying solely on published data and some of the problems arising from a reliance on aggregate data, and will also add to the analyses that can be performed. Such projects, however, require considerable time and effort.

Bias↗

Changes in longevity and causes of death among persons with hemophilia A.

To examine recent changes in longevity and the causes of death among persons with hemophilia A, we evaluated death certificate data for persons who died in the United States from 1968 through 1989 and had hemophilia A or congenital Factor VIII disorder (ICD code 286.0) listed on the death certificate as one of the multiple causes of death. Multiple-cause-of-death mortality data for the United States from 1968 to 1989 were examined to compare death rates by year, focusing on death rates and causes of death for 1979-1981, 1983-1985, and 1987-1989. Gender, age group, race, geographic region, and median age at death of persons with hemophilia A and human immunodeficiency virus (HIV)-related disease listed as a cause of death were compared with those with hemophilia A without HIV-related disease. From 1968 through 1989, 2,792 hemophilia A deaths were reported. The death rate increased from 0.5 to 1.3 per 1,000,000 persons. From 1979-1981 through 1987-1989, mortality increased in all age groups above 9 years of age and age at death shifted markedly to lower ages. Median age at death decreased from 57 years in 1979-1981 to 40 years in 1987-1989. The percentage of deaths due to hemorrhage or diseases of the circulatory system decreased markedly as the result of the increase in deaths associated with HIV infection or infections other than HIV infection. Spread of HIV-1 infection in persons with hemophilia A has disrupted the reduction in mortality seen with factor replacement therapy, implementation of home care, and use of comprehensive hemophilia treatment centers. It is hoped that advances in the care of HIV-infected persons will improve survival in the hemophilia community.

Adolescent↗

Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the United States: comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood-transfusion recipients with AIDS.

From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and greater than or equal to 30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS.

Acquired Immunodeficiency Syndrome↗

Inhibition of mitochondrial calcium ion transport by an oxo-bridged dinuclear ruthenium ammine complex.

Ruthenium red is a well-known and effective inhibitor of the mitochondrial Ca2+ uniporter; however, Reed and Bygrave [(1974) FEBS Lett. 46, 109-114] tentatively attributed this inhibition to a colorless impurity present in commercial samples of ruthenium red (RR). This component has now been isolated and a derivative, (mu-O) [(HCO2)(NH3)4Ru]2Cl3, structurally characterized. The active species in solution appears to be the symmetrical oxo-bridged ion, [X(NH3)4Ru-O-Ru(NH3)4X]3+, where X = Cl- or OH-. Its absorption spectrum shows a maximum at 360 nm. The dinuclear ruthenium ammine complex inhibits Ca(2+)-stimulated respiration of rat liver mitochondria with an I50 of 3.5 pmol/mg of protein compared to the value of 60 pmol of RR/mg of protein. The inhibition by the dinuclear compound is noncompetitive with Ca2+. Respiration-linked swelling of mitochondria induced by Cd2+ also responds similarly to both the dinuclear complex and RR. A close correlation was observed between binding to mitochondria as monitored with 103Ru-labeled dinuclear complex and inhibition of Ca2+ transport. A Scatchard plot yielded estimates of maximum specific binding and dissociation constant of 7.5 pmol/mg of protein and 1.3 nM, respectively. The inhibitor has the characteristics of a satisfactory affinity ligand for purification of the uniporter.

Animals↗

A sibling-controlled study of intelligence and academic performance following Reye syndrome.

The authors compared the intellectual, cognitive and academic abilities of 22 survivors of Reye syndrome attending normal schools with the sibling nearest in age as control. The British Ability Scales, visual and verbal IQ, short-term memory scales and attainment tests were administered to all children. Reye syndrome children as a group differed significantly from the controls only on the basic number skills test. However, children with severe encephalopathy and those whose illness occurred in infancy had significant deficits on many of the tests. 18 children recovered without requiring 'additional educational provision'; the mean IQ of the 22 Reye syndrome children was 101. Nonetheless, these children's poor performance on the basic number skills test has important implications for teachers, and careful monitoring of future educational performance is essential.

Achievement↗

Binding of the transition metal ion [(H2O)(NH3)5Ru(II)]2+ to nucleosomal core and internucleosomal DNA.

The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases.

Air↗

An unusual case of mosaic Down's syndrome involving two different Robertsonian translocations.

A baby girl with some of the stigmata of Down's syndrome was found to be a mosaic with three different cell lines: 45,XX,-13,-21,+t(13q21q)/(46,XX/46,XX, -21,+t(21q21q). The chromosome rearrangements detected in this patient appear to have arisen de novo. In the normal cell line the terminal end of the p arm of one chromosome 21 is thought to have been damaged. It seems probable that this is related to the other chromosomal anomalies found.

Chromosome Banding↗