A Markov Multi-State model of lupus nephritis urine biomarker panel dynamics in children: Predicting changes in disease activity.

BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). RESULTS: The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. CONCLUSIONS: Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

The Nairobi birth survey. II. Antenatal care in Nairobi.

PIP: Antenatal care is now universally accepted as an essential part of obstetric care and most health authorities in developing countries are trying to offer this service to their populations. This study, part of the Nairobi Birth Survey, looks into the pattern and distribution of antenatal care in the City of Nairobi, particularly to assess the quality and appropriateness of the service. 96.4% of women attended antenatal clinic at least once, the majority (74.7%) being looked after at health center level. There was an overrepresentation of young, single, primigravidae who had received little formal education in the group that received no antenatal care. The quality of care varied from clinic to clinic but on the whole there was a tendency either not to do certain important investigations or failure to obtain the results in the cases where the tests were requested. Nearly 60% of the antenatal women had height between 155 cm and 164 cm, 2.7% had positive tests for syphilis, 10.5% were anemic and 10.3% were hypertensive. The perinatal mortality rate in the group that did not have antenatal care was found to be 4.8 times greater than that in the group that received antenatal care. 1 way of facilitating detection of risk factors is by designing an appropriate record card. An example of such a card has been successfully tested in rural areas of Kenya. The quality of antenatal care can be assessed by maternal height, blood pressure, blood group, hemoglobin, serological test for syphilis and urine examination for protein and sugar. Private doctor antenatal care tended to be inferior to hospital care. Just under 20% of the women were under 20 years old while 44% were 35 and over. A comparatively larger proportion of adolescents did not receive antenatal care. Primigravida and highly parous mothers are also classified as high risk cases. Nearly 15% of the mothers were single and showed a marked tendency for lack of antenatal care and health care center utilization. Anemia existed in 10.5% of a sample of 789 women. Proteinuria was detected in only 3.6%. In about 80% of the antenatal mothers no complications were found. Perinatal mortality and morbidity rates will be reduced as a result of antenatal care.^ieng

The Nairobi Birth Survey 1. the study design, the population and outline results.

PIP: The Nairobi Birth Survey was planned with the following objectives: 1) establish the social, obstetric and epidemiological characteristics of the obstetric population of Nairobi, Kenya; 2) examine the pattern and distribution of antenatal and delivery care; and 3) assess the true incidence of stillbirths and 1st 24-hour neonatal deaths, congenital abnormalities and major obstetric complications. The Survey consisted of 1) a study of all stillbirths and 24-hour neonatal deaths over a period of 7 months (March-September 1981), and 2) recording of all births taking place in Nairobi over a 7 week period (June 15-August 4, 1981). During the 7 week period there were 5,293 single births, including 187 perinatal deaths, with a stillbirth rate of 23/1,000 births and a 24-hour neonatal death rate of 12/1,000. The obstetric population was found to be predominantly young, with 57.8% of all mothers being under 25 years of age. Nearly 20% were teenagers. 23% of the mothers were having their 5th or more children at the time of the Survey. In 79.3% of the mothers the antenatal period was uncomplicated. Hypertensive disease in pregnancy was found to be the leading cause of complications, existing in 10.4% of the pregnancies. The majority of the mothers delivered in public institutions. Together with the student midwives, midwives conducted 79.7% of the births. The 3 maternal deaths in this survey give a maternal mortality rate of .56/1,000 deliveries. 701 perinatal deaths occured in the 7 month study, which corresponds to 71.2%. These deaths were mostly associated with complications of labor, including prolonged and difficult labor. In 40.9% of the cases the deaths could have been avoided with appropriate action. In 436 babies that were autopsied, 33 had congenital abnormalities.^ieng

The relationship between breast and bottle feeding and respiratory illness in the first year of life.

The relationship between breast or bottle feeding and the incidence of bronchitis and pneumonia in the first year of life was examined in a birth cohort of nearly 2000 children born in Harrow, England, in 1963--65. Fewer episodes of acute bronchitis and pneumonia were reported in children who were breast-fed than in children who were bottle-fed. Firstborn children were more likely to be breast-fed than subsequent children. Mothers who smoked were less likely to breast-feed their babies. Although birth order and parental smoking have been shown to be associated with bronchitis and pneumonia in the same cohort, the association between feeding pattern and respiratory illness history persisted when these and other important factors were taken into account.

Assessing functional status among elderly patients: a comparison of questionnaire and service provider ratings.

This paper describes a comparative analysis of questionnaire-based measures of functional status and clinical ratings of disability made by general practitioners and health visitors. Both approaches to functional assessment were used in rating 92 elderly primary care patients in terms of their performance of 13 mobility and self-help activities. Simple dichotomous and more complex trichotomous measures of performance were used to summarize functional ability in both the questionnaire and the provider's evaluation. Agreement between questionnaire-based and rater assessments was greatest for less complex mobility and self-help functions in comparisons using both dichotomous and trichotomous scales.

Change in respiratory symptom prevalence in adults who alter their smoking habits.

The prevalence of chronic cough and phlegm production has been studied in 3916 young married adults, with recent new births and young children in their families, on six consecutive annual occasions. Among those who were smokers, in all years of the study more men than women reported respiratory symptoms. Respiratory symptoms were also reported more commonly among men than among women who did not smoke at all, whereas no sex difference in symptom prevalence was apparent among men and women who changed their smoking habits during the study. Equal numbers of men stopped or started smoking on their own initiative during the second three years of the study, whereas twice as many women started smoking as stopped in the same period. Men who had been smokers in the first three years and who spontaneously stopped smoking during the second three years showed a progressive decline in respiratory symptoms to a level similar to that of nonsmokers.

Respiratory symptom prevalence in adults: the comparative importance of smoking and family factors.

In a study of the prevalence of chronic cough and phlegm production in a group of nearly 4000 young adults, those adults who had several children had a higher prevalvalence of these symptoms than those with few children, especially if the children suffered from bronchitis or pneumonia. Nevertheless, cigarette smoking was the factor most strongly associated with chronic cough and phlegm production in young adults in this study.

Influence of family factors on asthma and wheezing during the first five years of life.

Family factors associated with the incidence of asthma and wheezing during childhood have been studied in a cohort of over 2000 children who, together with their families, were followed-up for five years. Episodes of wheezing not regarded by the parents as asthma had a different pattern of association with family factors to that found for asthma. The outcome of the two conditions in terms of ventilatory function at the age of five years was also different, in that children with a history of asthma had a lower peak expiratory flow rate than did children with a history of non-asthmatic wheezing.

Influence of family factors on the incidence of lower respiratory illness during the first year of life.

In a study of a cohort of over 2000 children born between 1963 and 1965, the incidence of bronchitis and pneumonia during their first year of life was found to be associated with several family factors. The most important determinant of respiratory illness in these infants was an attack of bronchitis or pneumonia in a sibling. The age of these siblings, and their number, also contributed to this incidence. Parental respiratory symptoms, including persistent cough and phlegm, and asthma or wheezing, as well as parental smoking habits, had lesser but nevertheless important effects. Parental smoking, however, stands out from all other factors as the one most amenable to change in seeking to prevent bronchitis and pneumonia in infants.

Influence of personal and family factors on ventilatory function of children.

We wanted to assess the relative influence of various personal and family factors upon the development of ventilatory function in young children. The relationship of several such factors to peak expiratory flow rates measured at the age of five years was studied in 454 children. These children were members of a birth cohort born between 1963 and 1965 in Harrow, north-west London, who were examined regularly from birth through the first five years of life. Beside its expected association with height, peak expiratory flow rate at the age of five years was also related to a lesser extent with peak expiratory flow rate in parents. Children with a history of lower respiratory illness had mean peak flow rates which were lower than those of children who escaped these illnesses. The earlier the onset of the illness and the more frequent its recurrence, the more marked its effect on ventilatory function. The group of children with a history of asthma and bronchitis had the lowest mean peak expiratory flow rate, but a history of bronchitis or pneumonia alone (that is, without asthma) was also associated with reduced ventilatory function. Respiratory illness beginning in the first year of life was the most potentially modifiable determinant of peak expiratory flow rate in children in this study.

Respiratory function of infants in relation to subsequent respiratory disease: an epidemiological study.

Crying ventilatory function was measured in 487 infants shortly after birth. Over the following five years 129 infants suffered attacks of pneumonia or bronchitis. Their initial crying ventilatory function was compared with that of the 358 infants who escaped these illnesses. No statistically significant differences were found in crying ventilatory function between these two groups of infants. This has been interpreted as indicating that newborn infants who subsequently suffer attacks of pneumonia or bronchitis do not start life with deficits in their ventilatory function. In the same study crying ventilatory function was measured in 550 infants at their first birthday; 70 had suffered attacks of pneumonia or bronchitis by that age and made a clinical recovery. Their crying ventilatory function showed no consistent difference from the 480 infants who escaped their illnesses. The reasons for the lack of a difference in crying ventilatory function is discussed.