Cent CI Research Articles

Trends in childhood and parental asthma prevalence in Merseyside, 1991-1998

To determine changes in childhood and parental asthma prevalence in Merseyside between 1991 and 1998. Three standardized cross-sectional respiratory health surveys using a parent-completed questionnaire were completed in 1991 (n = 1171), 1993 (n = 2368) and 1998 (n = 1964) amongst primary school children (5-11 years) attending the same 10 schools. The main outcome measures were prevalence of reported doctor diagnosed asthma, the symptom triad of cough, wheeze and breathlessness (C+W+B+) and parental asthma. Significant changes in prevalence for all respiratory variables occurred between 1991 and 1998, except for the symptom triad C+W+B+. Between 1991 and 1998 the prevalence of reported doctor diagnosed asthma increased from 17.7 to 29.8 per cent (p < 0.001), history of wheezing increased from 22.5 to 29.4 per cent (p < 0.001). The symptom triad of C+W+B+ changed from 9.6 to 9.9 per cent (p = 0.78). Childhood reported hospital admissions for respiratory illness increased from 5.5 to 10.7 per cent (p < 0.001). Paternal asthma increased from 6.5 per cent in 1991, to 8.6 per cent in 1998 (p = 0.031), and maternal asthma almost doubled in the same period from 6.6 to 11.2 per cent (p < 0.001). Children living in poorer areas (Townsend score 8-11) were more likely to have doctor diagnosed asthma (OR = 2.99, 95 per cent CI, 2.06 to 4.33) and C+W+B+ (OR = 2.17, CI 1.13 to 4.18). Childhood obesity was significantly associated with increased risk of both doctor diagnosed asthma (OR = 1.74, 95 per cent CI, 1.29 to 2.37) and C+W+B+ (OR = 1.88, 95 per cent CI, 1.21 to 2.90). A rising prevalence of reported doctor diagnosed asthma, but not C+W+B+ was observed during the 1990s in a low socio-economic area of Liverpool. Asthma prevalence was related to socio-economic deprivation and was associated with obesity. The rising prevalence of reported doctor diagnosed asthma is likely to be attributable to several factors, including changes in diagnostic labelling and the distribution of factors related to socio-economic status.

Towards a Better Understanding of Exclusive Breastfeeding in the Era of HIV/AIDS: A Study of Prevalence and Factors Associated with Exclusive Breastfeeding from Birth, in Rakai,Uganda

Exclusive breastfeeding (EBF) is being promoted by WHO/UNICEF as the recommended mode of feeding for all infants from birth to around 6 months of age. It is also recommended for the initial few months, for infants born to HIV-positive mothers in the developing world where conditions may not be ideal for replacement feeding. A cross-sectional study was done to find the prevalence and factors associated with EBF from delivery, amongst mothers of infants 0-6 months of age in a rural Ugandan community with a high HIV/AIDS burden. A prevalence of EBF of 35.1 per cent was found. There was a very high use of prelacteal feeds. Factors positively associated with EBF from birth, after logistic regression, were: delivery from a health unit (OR 2.07; 95 per cent confidence interval, 1.2-3.6); and mother having a normal vaginal delivery (OR 10.54; 95 per cent CI, 3.0-36.6). Factors showing negative association were: male gender of child (OR 0.44; 95 per cent CI, 0.3-0.7); and age of child over 3 months (OR 0.48; 95 per cent CI, 0.3-0.7). Mothers knowledge of her HIV serostatus was not associated with EBF (p = 0.78). Breastfeeding is almost universal in this area but it is rarely exclusive from birth.

Secondary post-tonsillectomy haemorrhage and informed consent

This is a prospective incidence study of 250 secondary post-tonsillectomy haemorrhages from a population of 2706 tonsillectomies performed over a seven-year period, which aims to ascertain the incidence and character of post-tonsillectomy secondary haemorrhage. Out of 250 post-tonsillectomy secondary bleeds (9.2 per cent of total; 95 per cent CI = 8.2 per cent - 10.4 per cent), 39 patients had a severe bleed (1.4 per cent; 95 per cent CI = 1.2 per cent - 2.1 per cent). The incidence of secondary tonsillectomy haemorrhage increased with age, peaking at 30-34 years in both men and women (p < 0.001), with no statistically significant difference between the two sexes (p = 0.23). The incidence of serious haemorrhage increases in the older age categories (p = 0.005) but is not influenced by gender (p = 0.50). The majority of secondary tonsillectomy haemorrhages presented between the fourth and seventh day post-operation (69.8 per cent). These results now provide the basis for informed consent for a tonsillectomy in our department.

High Rates of Primary Care and Emergency Department Use Among Injection Drug Users in Vancouver

Frequent use of emergency rooms by injection drug users (IDUs) has been attributed to a lack of access to primary care and barriers to health services. Using a community-based sample of IDUs, we examined rates of primary care and emergency room use among IDUs and identified correlates of frequent emergency department use. From January to November 2003, we enrolled IDUs into a prospective cohort study involving a baseline questionnaire, comprehensive retrospective and prospective health record linkages. We examined rates of primary care and emergency department utilization, and diagnoses upon arrival in the emergency room. Logistic regression was used to determine factors independently associated with frequent emergency room use. Of the 883 IDUs included in this analysis, 687 (78 per cent) accessed a primary care clinic in the previous year, while 528 (60 per cent) participants accessed the emergency room (ER) during the years 2002 and 2003. Abscesses, cellulitis and other skin infections accounted for the greatest proportion of ER use. Factors independently associated with frequent ER use included: frequent crystal methamphetamine injection (AOR = 2.4, 95 per cent CI: 1.0-5.6); non-fatal overdose (AOR = 2.1, 95 per cent CI: 1.4-3.3); HIV-positive status (AOR = 1.5, 95 per cent CI: 1.1-2.1), having been physically assaulted (AOR = 1.5, 95 per cent CI: 1.1-2.1); and primary care utilization (AOR = 1.5, 95 per cent CI: 1.0-2.1). high rates of ER use were observed among IDUs, despite high rates of primary care use among this same population. ER use was due primarily to preventable injection-related complications that are less amenable to primary care interventions, and therefore educational and prevention efforts that encourage and enable sterile injection practices should be promoted.

A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data

We propose a transmission model to estimate the main characteristics of influenza transmission in households. The model details the risks of infection in the household and in the community at the individual scale. Heterogeneity among subjects is investigated considering both individual susceptibility and infectiousness. The model was applied to a data set consisting of the follow-up of influenza symptoms in 334 households during 15 days after an index case visited a general practitioner with virologically confirmed influenza. Estimating the parameters of the transmission model was challenging because a large part of the infectious process was not observed: only the dates when new cases were detected were observed. For each case, the data were augmented with the unobserved dates of the start and the end of the infectious period. The transmission model was included in a 3-levels hierarchical structure: (i) the observation level ensured that the augmented data were consistent with the observed data, (ii) the transmission level described the underlying epidemic process, (iii) the prior level specified the distribution of the parameters. From a Bayesian perspective, the joint posterior distribution of model parameters and augmented data was explored by Markov chain Monte Carlo (MCMC) sampling. The mean duration of influenza infectious period was estimated at 3.8 days (95 per cent credible interval, 95 per cent CI [3.1,4.6]) with a standard deviation of 2.0 days (95 per cent CI [1.1,2.8]). The instantaneous risk of influenza transmission between an infective and a susceptible within a household was found to decrease with the size of the household, and established at 0.32 person day(-1) (95 per cent CI [0.26,0.39]); the instantaneous risk of infection from the community was 0.0056 day(-1) (95 per cent CI [0.0029,0.0087]). Focusing on the differences in transmission between children (less than 15 years old) and adults, we estimated that the former were more likely to transmit than adults (posterior probability larger than 99 per cent), but that the mean duration of the infectious period was similar in children (3.6 days, 95 per cent CI [2.3,5.2]) and adults (3.9 days, 95 per cent CI [3.2,4.9]). The posterior probability that children had a larger community risk was 76 per cent and the posterior probability that they were more susceptible than adults was 79 per cent.

Accounting for leadtime in cohort studies: evaluating when to initiate HIV therapies

Commonly reported comparisons of differences in disease progression according to disease staging at therapy initiation may be subject to bias if they do not account for the time it took the deferred group to reach the latter stage (that is, leadtime) and for previous events in those who initiate therapy at late stage (that is, unseen fast progressors). To estimate the impact of deferring initiation of highly active antiretroviral therapies (HAART) on time to clinical AIDS in the context of data from observational cohort studies, we describe a method that capitalizes on data from a pre-HAART period to multiply impute estimated leadtimes and the unseen events among fast progressors. After accounting for leadtime and the unseen events, data from two large cohort studies (N=739) indicate that deferring HAART initiation until CD4 is below 200 cells/mm3 was detrimental compared to initiating between 201 and 350 (hazard ratio=1.97; 95 percent confidence interval [CI] 1.09, 3.54), and that failure to account for leadtime resulted in a 38 per cent higher hazard ratio. In contrast, initiating HAART between 201 and 350 did not increase the hazard of AIDS compared to initiating with CD4 between 351 and 500 cells/mm3 (hazard ratio=0.70; 95 per cent CI 0.35, 1.42). Methods presented here offer an approach to analysing prevalent cohort studies and provide procedures to maximize the usefulness of observational data.

Does promoting bicycle‐helmet wearing reduce childhood head injuries?

The objectives of the study are to assess the impact of a community‐based bicycle‐helmet program aimed at children aged 5–12 years (about 140,000). A quasi‐experimental design, including a control group, was used. Sex‐ and age‐group‐based changes in the risk of bicycle‐related head injury leading to hospitalisation were measured, using rate ratios. Compared with the pre‐program period, significant risk reductions were observed during the post‐program period among both boys (RR = 0.56, 95 per cent CI = 0.40, 0.77) and girls (RR = 0.52, 95 per cent CI = 0.33, 0.82), and among both younger (RR = 0.46, 95 per cent CI = 0.31, 0.68) and older (RR = 0.63, 95 per cent CI = 0.44, 0.89) children. A significant reduction was also observable during the program phase among the groups most at risk, i.e. boys (RR = 0.94, 95 per cent CI = 0.66, 1.35) and younger children (RR = 1.07, 95 per cent CI = 0.70, 1.63). The population‐based educational program significantly decreased the risk of head injuries among boys and girls despite observable differences in the voluntary adoption rate of bicycle‐helmet wearing. The impact was more pronounced among younger children.

Impact of a Standardized Management Protocol on Mortality of Children with Diarrhoea: An Update of Risk Factors for Childhood Death

In the developing world, diarrhoeal disease is a significant cause of childhood morbidity especially amongst severely malnourished children. As a direct result of improved acute-phase management of this group of patients, there has been a 47 per cent reduction in the death rate among severely malnourished children hospitalized at the ICDDR,B in Bangladesh. The change in the risk factors for death among children aged under 5 years presenting with diarrhoea was reassessed. The charts of 366 children under 5 years of age who were hospitalized for diarrhoeal disease in the year 1998 were retrospectively analysed. One hundred and eighty-three of these patients died and 183 of those who survived acted as controls. Univariate analysis found 12 significant risk factors on admission that impacted outcome. Only two factors, female sex and positive blood culture, remained significant in the multivariate analysis with odds ratios (95 per cent CI) of 2.05 (1.1-4.0) and 4.6 (1.7-12.4), respectively. Prior to the change in the protocol involving the management of severely malnourished children, only severe malnutrition and non-breastfeeding were found to be significant predictors of mortality.

Mother-to-Infant Transmission of Hepatitis C Virus (HCV) in Brazil

Sixty-one women with anti-HCV antibodies, detected by a third-generation enzyme immunoassay (EIA3), were prospectively recruited for investigation of vertical HCV transmission during child-birth, at the University Hospital of the Catholic University of Campinas, Brazil, between January 1994 and July 1998. Six of the women presented coinfection with the human immunodeficiency virus type 1 (HIV-1). All of the 72 children born in this period were followed at least until they were 18 months of age. Analyses of anti-HCV, HCV RNA, and alanine aminotransferase were performed in a minimum of two blood samples during follow-up. One (2.4 per cent; 95 per cent CI, 2.2-7) of the 42 children born to HCV viremic mothers was both anti-HCV and HCV RNA-positive, with altered ALT levels. Passively transferred maternal anti-HCV antibodies became undetectable within 9-12 months. None of the nine infants born to HIV-1 infected mothers were infected either by HIV or HCV. Thus, the mother-infant HCV transmission rate is low and seems to be associated with maternal HCV RNA positivity.

Effect of Giardia infection on growth and psychomotor development of children aged 0-5 years.

Giardiasis, an intestinal protozoan infection caused by Giardia intestinalis, is common in southeastern Anatolia, Turkey. In this cross-sectional survey, to investigate the role of giardiasis on growth and psychomotor development, we studied 160 children aged 0-5 years. Data were collected using a structured questionnaire, anthropometry, Ankara Developmental Screening Inventory, and laboratory analysis of fecal samples. The results showed that 50 per cent of the subjects were infected with at least one pathogen of intestinal parasitic infections. Giardia intestinalis was the most frequent pathogenic parasite. Giardia-infected children had a risk for stunted (OR = 7.67, 95 per cent CI = 2.25-26.16; p = 0.001) and poor psychomotor development (OR = 2.68, 95 per cent CI = 1.09-6.58; p = 0.030). The data indicate that Giardia intestinalis infection has an adverse impact on child linear growth and psychomotor development. In the primary healthcare centers, during the programme of the monitoring growth and developmental status of children, following children in terms of Giardia, diagnosis and treatment will have a positive effect on child health.

Fetal Thrombotic Vasculopathy in the Placenta: A Thrombophilic Connection Between Pregnancy Complications and Neonatal Thrombosis?

Objective Fetal thrombotic vasculopathy (FTV) has been related to pregnancy complications and neonatal thrombosis separately. We assessed whether a relationship existed in our population of women with neonates who were admitted to our Neonatal Intensive Care Unit (NICU). In addition, the presence of thrombophilic factors in children and parents was investigated. Methods Two groups were detected by a search of the departmental databases. Group A was a cohort of 5000 neonates admitted to our NICU (1992–2002). Infants who developed thrombotic complications were selected. Group B was a cohort of placentae from our institution (2000, n=141). Those with a diagnosis of FTV were selected. Case-notes and laboratory results were obtained through the hospital information system. Results Of Group A, thrombosis was reported in 55 children. Of these, 20 matching placentae were available. Eight placentae showed FTV (40 per cent). Of the eight corresponding pregnancies, seven were complicated by pre-eclampsia and/or intra uterine growth restriction (IUGR). Of the 12 placentae without FTV, five of the pregnancies had pre-eclampsia and/or IUGR (odds ratio for relation FTV-Complications: 9.8, 95 per cent CI=0.9–107). In Group B, nine placentae showed FTV (6.4 per cent). Of these nine, six of the pregnancies were complicated by pre-eclampsia and/or IUGR. None of the neonates developed thrombosis. Conclusion Pre-eclampsia and/or IUGR as well as neonatal thrombosis are both associated with fetal thrombotic vasculopathy in the placenta. However, in our selected-tertiary centre-population, FTV did not predict neonatal thrombosis. The thrombophilic investigations of parents and children were incomplete. A standard approach for evaluating parents at risk for FTV and evaluating neonates at risk for thrombosis should be developed.

Case fatality proportions and predictive factors for mortality among children hospitalized with severe pneumonia in a rural developing country setting.

Few large studies have evaluated risk factors for mortality among children hospitalized for pneumonia and this may contribute to suboptimal case management efficiency. To identify useful screening criteria for mortality among children hospitalized for pneumonia in a developing country setting, we conducted a population-based hospital cohort study among children less than 2 years of age admitted for pneumonia during 1999-2001 at one of three major hospitals on Lombok Island, Indonesia. Of 4351 children admitted for pneumonia, 12 per cent died before discharge. Case fatality proportions were seasonal, with peaks occurring immediately after peaks in the proportion of cases positive for respiratory syncytial virus. Children with an oxygen saturation < or = 85 per cent or age younger than 4 months were 5.6 times more likely to die than children with none of these predictive factors (95 per cent CI, 4.5-7.1); 83 per cent of children who died had one of these two risk factors. For children < 4 months old, mortality increased at an oxygen saturation < 88 per cent compared with < 80 per cent for older children. Laboratory, physical examination, and radiological findings were not associated with or did not contribute substantially to mortality prediction. Among children hospitalized for pneumonia, age less than 4 months and hypoxia were identified with those at high risk of death. Age influences cut-off levels for hypoxia.

Predictors and nutritional consequences of intestinal parasitic infections in rural Ecuadorian children.

The study investigated the prevalence, risk factors, and nutritional consequences of intestinal parasitic infections (IPI) in rural Ecuadorian children. A total of 244 children aged 0.2-14 years were studied. The data were collected using a structured questionnaire, anthropometry, and laboratory analysis of blood and fecal samples. The results showed that 90 per cent of the subjects were infected with at least one pathogenic IPI: 51 per cent with helminths, 37.6 per cent with protozoa, and 21.4 per cent with both. Giardia-infected children had a risk for stunted growth that was twice that of other children (51.7 vs. 33.1 per cent; OR = 2.16, 95 per cent CI = 1.13-4.15; p = 0.01). They also had significantly reduced mean hemoglobin levels compared with their non-infected counterparts (11.8 +/- 1.5 vs. 12.2 +/- 1.4 g/dl; p = 0.023). However, the proportion diagnosed with iron-deficiency anemia was slightly, but not significantly, increased (29.4 vs. 24.3 per cent). The most consistent predictor of Giardia and other protozoal IPI risk was a high intra-/peri-domicilliary concentration of domestic animals. Children who lived in such households had an infection risk that was two to five times greater than that of their non-infected counterparts. The data indicate that Giardia intestinalis infection has an adverse impact on child linear growth and hemoglobin. They also suggest that domestic animals may be an important reservoir for Giardia and other intestinal protozoal infections observed in the Ecuadorian children studied.

Use of a proforma for reporting staging CT scans of the thorax

The aim of this study was to devise a simple proforma for reporting staging CT scans of the thorax, to ensure that all essential information is included on the report, in a logical manner, and that a TNM classification and tumour stage is given. Once the design of the proforma had been agreed, its utilisation and effectiveness was audited. In an initial six month period, every proforma filled in had resulted in a TNM classification being given, although in only 20 out of 40 (50 per cent) had a tumour stage been given. In a subsequent six month period, 39 out of 44 patients (89 per cent) with lung cancer undergoing a staging CT scan had proformas completed, and a TNM classification and tumour stage given (95 per cent CI is (0.75, 0.96)). Therefore, a proforma can be a useful aid to reporting staging scans, and is an effective method of ensuring that tumours are staged as fully as possible, radiologically. In addition, relevant information is presented in a clear format that allows accurate collection of data for audit purposes.

Are Placental Lakes of any Clinical Significance?

The aim of this study was to determine prospectively whether an association exists between the finding of placental lakes at the 20 week scan and an increased risk of uteroplacental complications or a poor pregnancy outcome. We studied the placental appearances in 1198 consecutive second trimester ultrasound scans performed for routine foetal abnormality screening at our institution. The placental thickness was measured at its widest diameter in the sagittal plane and the presence or absence of placental lakes was recorded. The birth weight in each case was plotted against the centile charts in use at the hospital and recorded. Specific outcome measures included foetal growth restriction (IUGR) with a birth weight below the 5th centile, pre-eclampsia, placental abruption, and perinatal deaths. Placental lakes were seen in 17.8 per cent of the scans. There was no significant association with either maternal socio-demographic factors or perinatal mortality (OR 0.94, 95 per cent CI 0.35–2.51). No association was seen with maternal cigarette smoking (OR 1.07, 95 per cent CI 0.75–1.52), a birth weight below the 5th centile (OR 0.68, 95 per cent CI 0.39–1.18), the development of pregnancy induced hypertension (OR 0.68, 95 per cent CI 0.35–1.32), severe pre-eclampsia (OR 0.72, 95 per cent CI 0.21–2.50), or placental abruption (OR 1.79, 95 per cent CI 0.46–6.99). A finding of placental lakes was six times more likely with a thick placenta >3cm at 20 weeks gestation (OR 6.30, 95 per cent CI 4.39 to 9.05). A finding of placental lakes during the second trimester ultrasound scan does not appear to be associated with uteroplacental complications or an adverse pregnancy outcome. The lesions are more prevalent with increasing placental thickness.

Changing profile of retinopathy of prematurity.

The aim of this study was to determine the evolving trends of retinopathy of prematurity (ROP) at a tertiary neonatal intensive care unit. In an ongoing screening programme for ROP, we estimated the incidence of ROP among at-risk neonates in a tertiary care unit. We compared our data over the last 12 months (1999-2000; period II) to the previously published data (1993-94; period I) to study changes in the spectrum of the disease. The overall incidence of ROP in period II was not significantly different from the incidence in period I (32 vs. 20 per cent, p > 0.05). However, a decreasing trend in the proportion of severe ROP (stage III) from 46 to 21 per cent in the later period was noted. The need for cryotherapy also dropped significantly compared with the earlier period (8 vs. 46 per cent respectively, p < 0.05). On multivariate analysis, apnea (p < 0.001; RR = 12.5; 95 per cent CI, 3.03-50.9; clinical sepsis (p < 0.001; RR = 5.7; 95 per cent CI, 1.6-20.7); and male sex (p < 0.001; RR = 6.3; 95 per cent CI 1.6-25.5) emerged as significant risk factors. Although the incidence of ROP is static, the more severe form of the disease (stage III) is showing a decline. Our data suggests that efficient management of apnea and sepsis may be crucial in further minimizing the risk of ROP.

Estimation of the time-dependent vaccine efficacy from a measles epidemic.

We present a method to estimate the time-dependent vaccine efficacy from the cohort-specific vaccination coverage and from data on the vaccination status of cases and apply it to a measles epidemic in Germany which involved 529 cases, 88 of whom were vaccinated and 370 unvaccinated (for the remaining 71 cases the vaccination status is unknown). Our epidemiological model takes into account that maternal antibodies prevent successful vaccination and that vaccine immunity may be lost over time. Model parameters are estimated from the data using maximum likelihood. Vaccination coverage, as determined in school surveys, ranged from 27.6 per cent for the cohort born in 1974 to 85 per cent for the 1986 cohort, which is far too low to prevent measles transmission. Cohorts for which no school surveys were performed are omitted from analysis. Thus, sufficient data are available for only 282 cases, 69 of whom are vaccinated. According to our estimates, measles vaccinations provided no immunity before 1978 (95 per cent CI: 0 to 47 percent), for the period 1978-1982, the estimated vaccine efficacy was 80 percent (95 percent CI: 67 to 89 percent), and for 1982-1990 it was 97 percent (95 percent CI: 93 to 99 percent). After 1990, the estimated value dropped to 89 per cent, but its confidence interval widely overlaps with that of the previous period (95 percent CI: 74 to 97 percent). Loss of immunity was estimated to be zero (95 percent CI: 0 to 0.003/year). Several sensitivity analyses were performed with respect to the model assumptions. A modified model which assumed constant efficacy at all vaccination times yielded a high estimate of 96 per cent (95 percent CI: 92 to 98 percent) for primary vaccine efficacy but also a high loss rate of immunity of 0.007/year (95 percent CI: 0.001 to 0.012) to explain the high fraction of vaccinated cases among older individuals. The likelihood score value is however significantly inferior compared to the score value of the model with time-dependent vaccine efficacy.

Paracetamol Versus Paracetamol‐Codeine in the Treatment of Post‐Operative Dental Pain: A Randomized, Double‐Blind, Prospective Trial

Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects. There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg. A randomized, single centre, double-blind prospective parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars, and analysed on an intention-to-treat (ITT) basis. Eighty-two patients were assigned randomly to receive either drug for a maximum of three doses. Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours. The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone (p=0.03) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h (95 per cent CI: 0.18 to 2.08). Of the patients who received the paracetamol codeine combination, 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone (p=0.20). There was no significant difference between the two groups in the proportion of patients experiencing adverse events (p=0.5). A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal, with no significant difference of side effects during the 12 hour period studied.

Altered Plasma Concentrations of Leptin, Transforming Growth Factor-β 1 and Plasminogen Activator Inhibitor Type 2 at 18 weeks of Gestation in Women Destined to Develop Pre-eclampsia. Circulating Markers of Disturbed Placentation?

Background. In many pre-eclamptic women the placentation process seems to be disturbed. Our objective was to investigate if disturbed placentation in pre-eclamptic women may be recognized in early second trimester as altered plasma levels of factors involved in the formation of the uteroplacental unit. Methods. In a prospective study of 2190 pregnant women we compared plasma leptin, transforming growth factor-β 1 (TGF-β 1) and plasminogen activator inhibitor type 2 (PAI-2) concentrations at 18 weeks' gestation in 71 women with subsequent pre-eclampsia and 71 controls matched for age, parity and first trimester body mass index. Results. Leptin and TGF-β 1 concentrations were lower and PAI-2 concentration higher in women destined to develop pre-eclampsia relative to controls (leptin: median (25–75 percentiles): 19.0 (14.5–29.0) vs 25.0 (16.0–35.0) ng/ml (p =0.03), TGF-β 1: 3.2 (2.0–6.1) vs 5.3 (3.8–7.1) ng/ml ( P=0.01) and PAI-2: 78.8 (65.1–118.1) vs 67.6 (61.6–79.6) ng/ml ( P=0.002)). OR (95 per cent CI) for pre-eclampsia for women in the upper quartile compared to women in the lower quartile were: leptin: 0.2 (0.03–0.7), TGF-β 1: 0.2 (0.08–0.7) and PAI-2: 3.1 (1.2–8.2). Conclusions. Altered plasma concentrations levels of factors involved in the process of placentation in women destined to develop pre-eclampsia, indicate that disturbed formation of the uteroplacental unit is reflected in the maternal circulation before 20 weeks' gestation.

The Epidemiology of Placental Infarction at Term

The incidence and associations of placental infarction at term were investigated as part of a population based case-control study of small for gestational age (SGA) infants. 509 placentas from women delivering SGA infants (SGAP) and 529 placentas from women delivering infants with birthweights appropriate for gestational age (AGAP) were examined using fixed protocols for macroscopic identification and microscopic confirmation of infarction. Other information was obtained by maternal interview and from an obstetric database.Infarcts were found in 17.3 per cent of SGAP and 11.7 per cent of AGAP. This difference was in placentas with multiple infarcts not involving the placental margin and was significant in multivariate analysis (OR 1.66; 95 per cent CI 1.12,2.47). Multivariate analysis showed significant associations between the presence of any infarct and maternal hypertension in both SGAP (OR=4.00; 95 per cent CI 1.96,8.16) and AGAP (OR 2.99; 95 per cent CI 1.23,7.32); maternal smoking, associated with a lesser risk in SGAP only (OR=0.31; 95 per cent CI 0.13,0.73); maternal age at first pregnancy in a linear relationship with AGAP only (beta co-efficient 0.09, P=0.0034); and between some ethnic groups. We conclude that at least five factors have independent associations with the incidence of placental infarction and these associations differ by site and age of infarcts.