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Biomedical subjects

J A C Sterne

Publications and source records attributed to J A C Sterne.

15 recordsLinked to original sources
PubMed2006

Human papillomavirus and head and neck cancer: a systematic review and meta-analysis.

It has been suggested that the link between human papillomavirus (HPV) and head and neck squamous cell carcinoma (HNSCC) is specific to carcinoma of the tonsil. We systematically reviewed studies that tested for HPV16 exposure in anatomically defined sites in the head and neck and a control group. The association between HPV16 and cancer was strongest for tonsil (OR: 15.1, 95% CI: 6.8-33.7), intermediate for oropharynx (OR: 4.3, 95% CI: 2.1-8.9) and weakest for oral (OR: 2.0, 95% CI: 1.2-3.4) and larynx (OR: 2.0, 95% CI: 1.0-4.2). To investigate heterogeneity, further stratification by method of HPV16 detection, suggested that variation in the magnitude of the HPV-cancer association with cancer site was restricted to studies using ELISA: among studies using PCR, the magnitude of the summary odds ratios was similar across the four sites. The association between HPV16 infection and HNSCC in specific sites suggests the strongest and most consistent association is with tonsil cancer, and the magnitude of this association is consistent with an infectious aetiology. However, the method of viral detection may be an important source of heterogeneity. Resolution of this issue will require further studies using both methods, examining associations separately in different sites.

Carcinoma, Squamous Cell↗
PubMed2006

Incidence of severe reproductive tract complications associated with diagnosed genital chlamydial infection: the Uppsala Women's Cohort Study.

OBJECTIVE: To estimate the cumulative incidence of severe complications associated with genital chlamydia infection in the general female population. METHODS: The Uppsala Women's Cohort Study was a retrospective population based cohort study in Sweden, linking laboratory, hospital, and population registers. We estimated the cumulative incidence of hospital diagnosed pelvic inflammatory disease, ectopic pregnancy, and infertility, and used multivariable regression models to estimate hazard ratios according to screening status. RESULTS: We analysed complete data from 43 715 women in Uppsala aged 15-24 years between January 1985 and December 1989. Follow up until the end of 1999 included 709 000 woman years and 3025 events. The cumulative incidence of pelvic inflammatory disease by age 35 years was 3.9% (95% CI 3.7% to 4.0%) overall: 5.6% (4.7% to 6.7%) in women who ever tested positive for chlamydia, 4.0% (3.7% to 4.4%) in those with negative tests, and 2.9% (2.7% to 3.2%) in those who were never screened. The corresponding figures were: for ectopic pregnancy, 2.3% (2.2% to 2.5%) overall, 2.7% (2.1% to 3.5%), 2.0% (1.8% to 2.3%), and 1.9% (1.7% to 2.1%); and for infertility, 4.1% (3.9% to 4.3%) overall, 6.7% (5.7% to 7.9%), 4.7% (4.4% to 5.1%), and 3.1% (2.8% to 3.3%). Low educational attainment was strongly associated with the development of all outcomes. CONCLUSIONS: The incidence of severe chlamydia associated complications estimated from ours, and other population based studies, was lower than expected. Studies that incorporate data about pelvic inflammatory disease diagnosed in primary care and behavioural risk factors would further improve our understanding of the natural history of chlamydia. Our results provide reassurance for patients, but mean that the benefits of chlamydia screening programmes might have been overestimated.

Adolescent↗
PubMed2005

Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV is the dominant mode of acquisition of HIV infection for children, currently resulting in more than 2000 new paediatric HIV infections each day worldwide. OBJECTIVES: To assess the effects of antenatal and intrapartum vitamin A supplementation on the risk of MTCT of HIV infection and infant and maternal mortality and morbidity, and the tolerability of vitamin A supplementation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, AIDSLINE, LILACS, AIDSTRIALS, and AIDSDRUGS, using standardised methodological filters for identifying trials. We also searched reference lists of identified articles, relevant editorials, expert opinions and letters to journal editors, and abstracts or proceedings of relevant conferences; and contacted subject experts, agencies, organisations, academic centres, and pharmaceutical companies. There were no language restrictions. SELECTION CRITERIA: Randomised trials comparing vitamin A supplementation with no vitamin A supplementation in known HIV infected pregnant women. Trials had to include an estimate of the effect of vitamin A supplementation on MTCT of HIV and or any other adverse pregnancy outcome to be included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and quality and extracted data. Effect measures (odds ratio [OR] for binary variables and weighted mean difference [WMD] for continuous variables) with their 95% confidence intervals (CI) were estimated for each study and combined using the fixed effect (Mantel-Haenszel) method, by intention to treat. Heterogeneity between studies was examined by graphical inspection of results followed by a chi-square test of homogeneity. MAIN RESULTS: Four trials, which enrolled 3,033 HIV-infected pregnant women, are included in this review. There was no evidence of an effect of vitamin A supplementation on MTCT of HIV infection (OR 1.14, 95% CI 0.93 to 1.38). There was evidence of heterogeneity between the three trials with information on MTCT of HIV (I(2) =75.7%, P=0.02). While the trials conducted in South Africa (OR 0.98, 95% CI 0.67 to 1.42 at three months) and Malawi (OR 0.78, 95% CI 0.53 to 1.15 at 24 months) did not find evidence that the effect of Vitamin A supplementation was different from that of placebo, the trial in Tanzania did find evidence that vitamin A supplementation increased the risk of MTCT of HIV (OR 1.53, 95% CI 1.15 to 2.04 at 24 months). Vitamin A supplementation significantly improved birth weight (WMD 89.78, 95% CI 84.73 to 94.83), but there was no evidence of an effect of vitamin A supplementation on stillbirths (OR 0.99, 95% CI 0.67 to 1.46), preterm births (OR 0.89, 95% CI 0.71 to 1.11), death by 24 months among live births (OR 1.11, 95% CI 0.88 to 1.40), postpartum CD4 levels (WMD -4.00, 95% CI -51.06 to 43.06), and maternal death (OR 0.49, 95%CI 0.04 to 5.40). AUTHORS' CONCLUSIONS IMPLICATIONS FOR PRACTICE: Currently available evidence do not support the use of vitamin A supplementation of HIV-infected pregnant women to reduce MTCT of HIV, though there is an indication that vitamin A supplementation improves birth weight. IMPLICATIONS FOR RESEARCH: The awaited publication of data from a large trial involving 4,495 HIV infected pregnant women in Harare (Zimbabwe Vitamin A for Mothers and Babies Project), will further clarify the effect of vitamin A supplementation on MTCT of HIV. The current review will be updated as soon as the trial is published.

Female↗
PubMed2005

Vaginal disinfection for preventing mother-to-child transmission of HIV infection.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV infection is one of the most tragic consequences of the HIV epidemic, especially in resource-limited countries, resulting in about 650 000 new paediatric HIV infections each year worldwide. The paediatric HIV epidemic threatens to seriously undermine decade-old child survival programmes. OBJECTIVES: To estimate the effect of vaginal disinfection on the risk of MTCT of HIV and infant and maternal mortality and morbidity, as well as tolerability of vaginal disinfection in HIV-infected women. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Cochrane Pregnancy and Childbirth Register, PubMed, EMBASE, AIDSLINE, LILACS, AIDSTRIALS, and AIDSDRUGS, using standardised methodological filters for identifying trials. We also searched reference lists of identified articles, relevant editorials, expert opinions and letters to journal editors, and abstracts and proceedings of relevant conferences, and contacted subject experts and pharmaceutical companies. There were no language restrictions. SELECTION CRITERIA: Randomised trials or clinical trials comparing vaginal disinfection during labour with placebo or no treatment, in known HIV-infected pregnant women. Trials had to include an estimate of the effect of vaginal disinfection on MTCT of HIV and or infant and maternal mortality and morbidity. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial eligibility and quality, and extracted data. Meta-analysis was performed using the Yusuf-Peto modification of Mantel-Haenszel's fixed effect method. MAIN RESULTS: Only two trials that included 708 patients met the inclusion criteria. The effect of vaginal disinfection on the risk of MTCT of HIV (OR 0.93, 95% CI 0.65 to 1.33), neonatal death (OR 1.38, 95% CI 0.30 to 6.33), and death after the neonatal period (OR 1.45, 95% CI 0.47 to 4.45) is uncertain. There was no evidence that vaginal disinfection increased adverse effects in mothers (OR 1.15, 95% CI 0.41 to 3.22), and evidence from one trial showed that adverse effects decreased in neonates (OR 0.14, 95% CI 0.07 to 0.31). AUTHORS' CONCLUSIONS: Currently, there is no evidence of an effect of vaginal disinfection on the risk of MTCT of HIV. Given its simplicity and low cost, there is need for a large well-designed and well-conducted randomised controlled trial to assess the additive effect of vaginal disinfection on the risk of MTCT of HIV in antiretroviral treated women.

Disinfection↗
PubMed2005

Dietary intake of flavonoids and asthma in adults.

Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease. This effect has been attributed to their high flavonoid content, but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly. In a population-based, case-control study of 1,471 adults aged 16-50 yrs in London (UK), the present study examined whether dietary intake of catechins, flavonols and flavones was negatively associated with asthma, asthma severity and chronic sputum production. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997. After controlling for potential confounders, dietary intake of these three flavonoid subclasses was not significantly associated with asthma, (odds ratio per quintile (95% confidence interval) = 0.94 (0.86-1.02); 1.00 (0.92-1.09); 0.98 (0.88 -1.08) for flavones, flavonols and total catechins, respectively) nor was it associated with asthma severity, or chronic sputum production. In conclusion, no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease.

Adolescent↗
PubMed2004

Dietary restraint and the mis-reporting of anthropometric measures by middle-aged adults.

OBJECTIVE: To assess whether levels of dietary restraint are associated with mis-reporting measures of adiposity by middle-aged adults. DESIGN: Cross-sectional study of middle-aged men and women, the parents of a group of young adults followed up since birth. METHODS: In all, 631 couples were mailed questionnaires and asked to record their height, weight and waist circumference. A paper tape measure with instructions for use was attached. Couples also completed the dietary restraint section of the Dutch Eating Behaviour Questionnaire, and provided information on employment and lifestyle habits. A subsample of participants was then invited to attend a clinic where detailed anthropometric measures were taken. RESULTS: In all, 435 women (69%) and 332 men (55%) completed the questionnaire; of those invited, 182 (85%) women and 102 (61%) men attended a clinic session. Regression analyses showed that the dietary restraint score was associated with the mis-reporting of BMI by women (P<0.01), but not men (test for interaction with gender, P=0.11). In women, the difference between the measured and reported BMI increased by 0.36 kg/m(2) (0.11-0.61) per unit increase in restraint score. This association was independent of age, smoking, social class, slimming, exercise frequency or television viewing time, but was attenuated in models controlling for measured BMI. The dietary restraint score was not associated with mis-reporting of waist circumference in men or women. CONCLUSIONS: Dietary restraint score may be a useful tool for identifying individuals more likely to mis-report anthropometric measurements, although associations may vary by gender.

Analysis of Variance↗
PubMed2004

Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study.

OBJECTIVE: To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease. DESIGN: Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months. RESULTS: Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal. CONCLUSIONS: Associations between parents' atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no "parent-of-origin" effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.

Adult↗
PubMed2004

The chlamydia screening studies: rationale and design.

BACKGROUND: Screening has been recommended to reduce the prevalence and morbidity associated with genital chlamydia infection in the United Kingdom. METHODS: We describe the rationale and study design of the Chlamydia Screening Studies (ClaSS), a collaborative project designed to evaluate screening outside genitourinary medicine clinics. A non-selective, active screening approach in 16-39 year olds randomly sampled from 27 general practice lists in the Bristol and Birmingham areas formed the basis of interlinked studies: a case-control study was used to investigate factors to improve the targeting of screening; participants with chlamydia were invited to enroll in a randomised controlled trial to evaluate partner notification conducted in primary care; and laboratory based studies were used to assess the best specimens and tests. We also explored psychosocial effects of screening and partner notification and modelled the cost effectiveness of the programme. CONCLUSION: Results from four pilot practices show that mailing of specimens for chlamydia testing is feasible but that it is difficult to achieve high response rates with postal screening. The high prevalence of asymptomatic infection in men suggests that efforts to screen men for chlamydia should be strengthened.

Adolescent↗
PubMed2004

Investigating ethnic inequalities in the incidence of sexually transmitted infections: mathematical modelling study.

OBJECTIVES: To investigate ethnic differences in rates of gonorrhoea using empirical sexual behaviour data in a simple mathematical model. To explore the impact of different intervention strategies in this simulated population. METHODS: The findings from cross sectional studies of gonorrhoea rates and sexual behaviour in three ethnic groups in south east London were used to determine the parameters for a deterministic, mathematical model of gonorrhoea transmission dynamics, in a population stratified by sex, sexual activity (rate of partner change), and ethnic group (white, black African, and black Caribbean). We compared predicted and observed rates of infection and simulated the effects of targeted and population-wide intervention strategies. RESULTS: In model simulations the reported sexual behaviours and mixing patterns generated major differences in the rates of gonorrhoea experienced by each subpopulation. The fit of the model to observed data was sensitive to assumptions about the degree of mixing by level of sexual activity, the numbers of sexual partnerships reported by men and women, and the degree to which observed data underestimate female infection rates. Interventions to reduce duration of infection were most effective when targeted at black Caribbeans. CONCLUSIONS: Average measures of sexual behaviour in large populations are inadequate descriptors for the epidemiology of gonorrhoea. The consistency between the model results and empirical data shows that profound differences in gonorrhoea rates between ethnic groups can be explained by modest differences in a limited number of sexual behaviours and mixing patterns. Targeting effective services to particular ethnic groups can have a disproportionate influence on disease reduction in the whole community.

Adolescent↗
PubMed2003

Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies.

BACKGROUND: We examined whether the initial virological and immunological response to highly active antiretroviral treatment (HAART) is prognostic in patients with HIV-1 who start HAART. METHODS: We analysed 13 cohort studies from Europe and North America including 9323 adult treatment-naive patients who were starting HAART with a combination of at least three drugs. We modelled clinical progression from month 6 after starting HAART, taking into account CD4 count and HIV-1 RNA measured at baseline and 6 months. FINDINGS: During 13408 years of follow-up 152 patients died and 874 developed AIDS or died. Compared with patients who had a 6-month CD4 count of fewer than 25 cells/microL, adjusted hazard ratios for AIDS or death were 0.55 (95%CI 0.32-0.96) for 25-49 cells/microL, 0.62 (0.40-0.96) for 50-99 cells/microL, 0.42 (0.28-0.64) for 100-199 cells/microL, 0.25 (0.16-0.38) for 200-349 cells/microL, and 0.18 (0.11-0.29) for 350 or more cells/microL at 6 months. Compared with patients who had a 6-month HIV-1 RNA of 100000 copies/mL or greater, adjusted hazard ratios for AIDS or death were 0.59 (0.41-0.86) for 10000-99999 copies/mL, 0.42 (0.29-0.61) for 500-9999 copies/mL, and 0.29 (0.21-0.39) for 6-month HIV-1 RNA of 500 copies/mL or fewer. Baseline CD4 and HIV-1 RNA were not associated with progression after controlling for 6-month concentrations. The probability of progression at 3 years ranged from 2.4% in the patients in the lowest-risk stratum to 83% in patients in the highest-risk stratum. INTERPRETATION: At 6 months after starting HAART, the current CD4 cell count and viral load, but not values at baseline, are strongly associated with subsequent disease progression. Our findings should inform guidelines on when to modify HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Comparison of methods for analysing cluster randomized trials: an example involving a factorial design.

BACKGROUND: Studies involving clustering effects are common, but there is little consistency in their analysis. Various analytical methods were compared for a factorial cluster randomized trial (CRT) of two primary care-based interventions designed to increase breast screening attendance. METHODS: Three cluster-level and five individual-level options were compared in respect of log odds ratios of attendance and their standard errors (SE), for the two intervention effects and their interaction. Cluster-level analyses comprised: (C1) unweighted regression of practice log odds; (C2) regression of log odds weighted by their inverse variance; (C3) random-effects meta-regression of log odds with practice as a random effect. Individual-level analyses comprised: (I1) standard logistic regression ignoring clustering; (I2) robust SE; (I3) generalized estimating equations; (I4) random-effects logistic regression; (I5) Bayesian random-effects logistic regression. Adjustments for stratification and baseline variables were investigated. RESULTS: As expected, method I1 was highly anti-conservative. The other, valid, methods exhibited considerable differences in parameter estimates and standard errors, even between the various random-effects methods based on the same statistical model. Method I4 was particularly sensitive to between-cluster variation and was computationally stable only after controlling for baseline uptake. CONCLUSIONS: Commonly used methods for the analysis of CRT can give divergent results. Simulation studies are needed to compare results from different methods in situations typical of cluster trials but when the true model parameters are known.

Breast Neoplasms↗
PubMed2003

A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0-42 months.

BACKGROUND: There is strong evidence that the incidence and prevalence of atopic diseases is increasing. However, estimates of the prevalence of atopic dermatitis (AD) have varied greatly in the U.K. and most parts of the developed world. OBJECTIVES: The aim of the study was to estimate the prevalence and incidence of AD between the ages of 0 and 42 months in children born in the 1990s in a defined population in the U.K. DESIGN: We used data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a large population-based study in the U.K. that enrolled all pregnant mothers who were resident in Avon and had their delivery date falling between 1 April 1991 and 31 December 1992. Since then ALSPAC has collected a wide range of data from the newborns and their parents. Data reported here were collected at 6, 18, 30 and 42 months using parental reports in a postal questionnaire. Of the 14 009 children originally enrolled 8530 provided information on AD in each of the four follow-up questionnaires. We defined AD as a report of rash in at least two of the four questionnaires. Incidence risk was defined as the percentage of new cases of AD between follow-up questionnaires, out of the total number of children whose parents had not reported that they had AD by the time of the previous follow-up. RESULTS: Period prevalence of 21.0%, 25.6%, 23.2% and 19.9% were observed at ages 0-6, 6-18, 18-30 and 30-42 months, respectively. The corresponding incidence risks were 21.0%, 11.2% and 3.8%, at 0-6, 6-18 and 18-30 months, respectively. There were no gender differences in either the incidence or prevalence of the disease. CONCLUSIONS: Results from this large, prospective study are consistent with recent reports of increased incidence and prevalence of AD. Health planners can use our estimates of incidence and prevalence to project the number of children likely to suffer from AD during infancy and early childhood, and thus to determine the human and financial resources required.

Age Distribution↗
PubMed2002

Attenuation of the virulence of Porphyromonas gingivalis by using a specific synthetic Kgp protease inhibitor.

The Arg- and Lys-gingipains of Porphyromonas gingivalis are important virulence determinants in periodontal disease and may correspond to targets for immune- or drug-based treatment strategies. In this investigation we aimed to determine which of these enzymes represents the most promising molecular target for protease inhibitor-based therapy and to examine the effectiveness of the resultant compound in a murine virulence assay. Isogenic mutants with mutations in rgpA and rgpB (encoding Arg-gingipains) and in kgp (encoding Lys-gingipain) and a double mutant with mutations in rgpA and rgpB were prepared by using P. gingivalis W50. The virulence of these mutants indicated that Kgp is a promising drug target. Combinatorial chemistry was used to define the optimal substrate of Kgp, and from this information a specific slowly reversible inhibitor with a nanomolar K(i) was designed and synthesized. Growth of P. gingivalis W50 in the presence of this compound resembled the phenotype of the kgp isogenic mutant; in both instances bacterial colonies failed to form pigment on blood agar, and only poor growth was obtained in a defined medium containing albumin as the sole protein source. Furthermore, pretreatment of the wild-type organism with the Kgp inhibitor led to a significant reduction in virulence in the murine assay. These data emphasize the conclusion that Kgp is an important factor for both nutrition and virulence of P. gingivalis and that inhibitors of this enzyme may have therapeutic potential for the control of P. gingivalis infections. Protease inhibitors may be a potentially novel class of antimicrobial agents with relevance to the control of other bacterial pathogens.

Adhesins, Bacterial↗
PubMed2002

Maternal periodontal disease and preterm low birthweight: case-control study.

Periodontal disease has been suggested to be an important risk factor for preterm low birthweight (PLBW). Here we report a case-control study of 236 cases (infants < 37 wks and weighing < 2499 g) and a daily random sample of 507 controls (> or = 38 wks and weighing > or = 2500 g). Clinical periodontal indices were measured on the labor wards. Associated risk factors for periodontal disease and PLBW were ascertained by means of a structured questionnaire and maternity notes. The risk for PLBW decreased with increasing pocket depth (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68 to 1.00). After adjustment for maternal age, ethnicity, maternal education, smoking, alcohol consumption, infections, and hypertension during pregnancy, this decreased further (OR 0.78, 95% CI 0.64 to 0.99). We found no evidence for an association between PLBW and periodontal disease. Our results do not support a specific drive to improve periodontal health of pregnant women as a means of improving pregnancy outcomes.

Adolescent↗