Background

To investigate the effect of helminth infections and their treatment during pregnancy on HIV load, we conducted a 2×2 factorial randomised controlled trial of albendazole versus placebo and praziquantel versus placebo in pregnant women in Entebbe, Uganda

Methods

Two hundred and sixty-four HIV-infected women from the Entebbe Mother and Baby Study (ISRCTN32849447) were included in this analysis. Women were tested for helminth infections at enrolment and mean HIV load was compared between infected and uninfected groups. The effect of anthelminthic treatment on HIV load was evaluated at six weeks post-treatment and at delivery using linear regression and adjusting for enrolment viral load.

Results

Hookworm and Trichuris infections were associated with higher mean viral load at enrolment (adjusted mean difference 0.24log10 copies/ml, 95% confidence interval (CI): 0.01 to 0.47, p=0.03 and 0.37log10 copies/ml, 95%CI: 0.00 to 0.74, p=0.05, respectively). There were no associations between viral load and other helminth species. There was some evidence that albendazole reduced viral load at six weeks post-treatment (adjusted mean difference −0.17, 95% CI: −0.36 to 0.01, p=0.07), however this effect did not differ according to mother’s hookworm infection status and had diminished at delivery (adjusted mean difference −0.11, 95% CI: −0.28 to 0.07, p=0.23). There was no effect of praziquantel treatment on HIV load at any time point.

Conclusions

Infection with some soil-transmitted helminth species is associated with increased HIV load in pregnancy. Treatment with albendazole causes a small decrease in HIV load, however this may not represent a direct effect of worm removal.

Relatively little is known about the clinical importance of symptoms not presented to healthcare services. Using data from a community survey we examined the health status among those with chronic pain who reported using or not using healthcare services. Individuals with chronic pain who had used healthcare services in the previous year had poorer health than symptomatic responders who had not used services, irrespective of the severity of chronic pain. The findings suggest that there is little point in trying to detect and treat individuals not currently presenting to healthcare services with their pain.

Background

Symptom characteristics are strong drivers of care seeking. Despite this, incongruous consultation behaviour occurs and has implications for both individuals and health-care services. The aim of this study was to determine how frequently incongruous consultation behaviour occurs, to examine whether it is more common for certain types of symptoms and to identify the factors associated with being an incongruous consulter.

Methods

An age and sex stratified random sample of 8,000 adults was drawn from twenty UK general practices. A postal questionnaire was used to collect detailed information on the presence and characteristics of 25 physical and psychological symptoms, actions taken to manage the symptoms, general health, attitudes to symptom management and demographic/socio-economic details. Two types of incongruous consultation behaviour were examined: i) consultation with a GP for symptoms self-rated as low impact and ii) no consultation with a GP for symptoms self-rated as high impact.

Results

A fifth of all symptoms experienced resulted in consultation behaviour which was incongruous based on respondents' own rating of the symptoms' impact. Low impact consultations were not common, although symptoms indicative of a potentially serious condition resulted in a higher proportion of low impact consultations. High impact non-consultations were more common, although there was no clear pattern in the type of associated symptoms. Just under half of those experiencing symptoms in the previous two weeks were categorised as an incongruous consulter (low impact consulter: 8.3%, high impact non-consulter: 37.1%). Employment status, having a chronic condition, poor health, and feeling that reassurance or advice from a health professional is important were associated with being a low impact consulter. Younger age, employment status, being an ex-smoker, poor health and feeling that not wasting the GPs time is important were associated with being a high impact non-consulter.

Conclusions

This is one of the first studies to examine incongruous consultation behaviour for a range of symptoms. High impact non-consultations were common and may have important health implications, particularly for symptoms indicative of serious disease. More research is now needed to examine incongruous consultation behaviour and its impact on both the public's health and health service use.

Highlights

► Largest study comparing BCG strains and first to assess strain effects on non-specific responses. ► Cytokine responses to both mycobacterial and non-mycobacterial stimuli are strain-dependent. ► BCG-Denmark causes higher cytokine levels and more scars and adverse events than two other strains. ► Sex may interact with the effect of strain; non-specific responses are not associated with scars. ► BCG strain choice may be important and should be evaluated in novel vaccine strategies using BCG.

Background

Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses.

Methods

Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-γ), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders.

Results

Both specific and non-specific IFN-γ, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p < 0.001). Scarred infants had higher IFN-γ and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p = 0.025). Mortality differences were not significant.

Conclusions

Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-γ and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime–boost sequences, or as a vector for other vaccine antigens.

Background

The symptom iceberg describes the phenomenon that most symptoms are managed in the community without people seeking professional health care. The size of the iceberg for many symptoms is unknown, as is their association with personal characteristics, including history of a chronic disease.

Aim

To ascertain the size of the symptom iceberg in the UK.

Design of study

A UK-wide community-based postal survey.

Setting

Urban and rural communities across the UK.

Method

A postal survey was sent to an age- and sex-stratified random sample of 2474 adults, aged 18–60 years, drawn from 20 practices around the UK. Questions were aimed at investigating adults' experiences of 25 different symptoms in the previous 2 weeks.

Results

The number of symptoms experienced by one individual in the previous 2 weeks ranged from 0 to 22 (mean 3.66). Of the symptoms examined, the three most common were: feeling tired/run down; headaches; and joint pain. Univariate analysis found symptom prevalence to be significantly associated with a wide range of participant characteristics. However, after adjustment, many of these associations no longer remained significant for a number of the symptoms. Presence of a chronic condition, age, and employment status were the three factors most commonly associated with the 2-week prevalence of symptoms. Reported symptom characteristics (severity, duration, interference, and time off work) varied little by sex or age.

Conclusion

Symptoms in the UK community are common. Symptom prevalence was associated with a number of participant characteristics, although the extent of this association was less than has been reported in previous research. This study provides an important current baseline prevalence of 25 symptoms in the community for those who do, and do not, have a chronic condition.

SUMMARY

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.

Background

Although many individuals have multiple lifestyle risk factors, few studies have investigated the impact of lifestyle risk factor combinations among women.

Aim

To investigate the relationship between individual and combinations of lifestyle risk factors in middle-aged women with subsequent mortality, and to estimate the associated population attributable risks.

Design of study

Prospective cohort study.

Setting

Royal College of General Practitioners' (RCGP) Oral Contraception Study, UK.

Method

In 1994–1995, women remaining under follow-up in the RCGP Oral Contraception Study were sent a lifestyle survey, from which modifiable risk factors were identified: pack-years smoked, physical inactivity, never drinking versus consuming at least 7 units of alcohol weekly, and being underweight, overweight, or obese. The cohort was followed to December 2006 or death. Population attributable risks were calculated.

Results

Of 10 059 women studied, 896 died. Pack-years smoked (11–20 years: adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.46 to 2.27; >20 years: adjusted HR = 2.34, 95% CI = 2.00 to 2.74); never drinking alcohol (adjusted HR = 1.66, 95% CI = 1.34 to 2.05); being underweight (adjusted = HR 1.66, 95% CI = 1.03 to 2.68); and physical inactivity (<15 hours/week: adjusted HR = 1.73, 95% CI = 1.46 to 2.04) were significantly associated with mortality compared with their respective reference group. Women with multiple lifestyle risk factors had higher mortality risks than those reporting one factor. The population attributable risk of the combination of smoking, physical inactivity, body mass index outside normal range, and alcohol (never drinking or excess intake) was 59% (95% CI = 31% to 78%).

Conclusion

Assuming a causal relationship between lifestyle and mortality, avoidance of four lifestyle risk factors would have prevented 60% of the deaths. The importance of avoiding smoking and undertaking physical inactivity during midlife should continue to be emphasised.

Background

Recent changes in UK primary care have increased the range of services and healthcare professionals available for advice. Furthermore, the UK government has promoted greater use of both self-care and the wider primary care team for managing symptoms indicative of self-limiting illness. We do not know how the public has been responding to these strategies. The aim of this study was to describe the current use of different management strategies in the UK for a range of symptoms and identify the demographic, socio-economic and symptom characteristics associated with these different approaches.

Methods

An age and sex stratified random sample of 8,000 adults (aged 18-60), drawn from twenty general practices across the UK, were sent a postal questionnaire. The questionnaire collected detailed information on 25 physical and psychological symptoms ranging from those usually indicative of minor illness to those which could be indicative of serious conditions. Information on symptom characteristics, actions taken to manage the symptoms and demographic/socio-economic details were also collected.

Results

Just under half of all symptoms reported resulted in respondents doing nothing at all. Lay-care was used for 35% of symptoms and primary care health professionals were consulted for 12% of symptoms. OTC medicine use was the most common lay-care strategy (used for 25% of all symptom episodes). The GP was the most common health professional consulted (consulted for 8% of all symptom episodes) while use of other primary care health professionals was very small (each consulted for less than 2% of symptom episodes). The actions taken for individual symptoms varied substantially although some broad patterns emerged. Symptom characteristics (in particular severity, duration and interference with daily life) were more commonly associated with actions taken than demographic or socio-economic characteristics.

Conclusion

While the use of lay-care was widespread, use of the primary care team other than the GP was low. Further research is needed to examine the public's knowledge and opinions of different primary care services to investigate why certain services are not being used to inform the future development of primary care services in the UK.

Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN-γ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes.

Background:

Praziquantel treatment of schistosomiasis boosts anti-schistosome responses, with ‘type 2 helper T-cell’ bias that may contribute to immunologically mediated killing and to protection against re-infection. Praziquantel treatment during pregnancy was recommended in 2002 but immunological effects of the treatment had not been investigated.

Methods:

A cohort of 387 S. mansoni infected women was recruited within a larger trial of de-worming during pregnancy (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott). Women were randomised to receive either praziquantel or placebo during pregnancy. Six weeks after delivery all women received praziquantel. Whole blood culture cytokine responses to S. mansoni worm and egg antigens were measured before and six weeks after each treatment.

Results:

Schistosome specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in gamma interferon (IFNγ), interleukin (IL)-2, IL-4, IL-5 IL-13 and IL-10 responses to schistosome worm antigen and IFNγ, IL-5 and IL-13 to schistosome egg antigen; but these boosts were not as substantial as those seen for treatment after delivery.

Conclusion:

Pregnancy suppresses potentially beneficial boost in cytokine responses associated with praziquantel treatment. Further studies are needed on the long term effect of treating schistosomiasis during pregnancy on morbidity and resistance to reinfection among treated women and their offspring.

Introduction

Helminth infections and malaria are widespread in the tropics. Recent studies suggest helminth infections may increase susceptibility to malaria. If confirmed, this could be particularly important during pregnancy-induced immunosuppression.

Aim

To evaluate the geographical distribution of Plasmodium falciparum-helminth co-infection, and associations between parasite species in pregnant women in Entebbe, Uganda.

Methods

A cross-sectional study was conducted at baseline in a trial of anti-helminthics during pregnancy. Helminth and P.falciparum infections were quantified in 2507 asymptomatic women; socio-demographic and geographical details were recorded.

Results

Hookworm and Mansonella perstans were associated with P.falciparum but the effect of hookworm was seen only in the absence of M.perstans (OR for P.falciparum, adjusted for age, tribe, socioeconomic status, HIV and location: hookworm without M.perstans 1.53 (95% CI 1.09-2.14); M.perstans without hookworm 2.33 (1.47-3.69), both hookworm and M.perstans, 1.85 (1.24-2.76)). No association was observed between Schistosoma mansoni, Trichuris or Strongyloides and P.falciparum.

Conclusions

Hookworm-P.falciparum and M.perstans-P.falciparum co-infection amongst pregnant women in Entebbe is more common than expected by chance. Further studies are needed to elucidate the mechanism of this association. Helminth-induced increased susceptibility to P.falciparum could have important consequences for pregnancy outcome and responses to malaria in infancy.

Background

Drug-resistant Mycobacterium tuberculosis has emerged as a global threat. In resource-constrained settings, patients with a history of tuberculosis (TB) treatment may have drug-resistant disease and may experience poor outcomes. There is a need to measure the extent of and risk factors for drug resistance in such patients.

Methods

From July 2003 through November 2006, we enrolled 410 previously treated patients with TB in Kampala, Uganda. We measured the prevalence of resistance to first- and second-line drugs and analyzed risk factors associated with baseline and acquired drug resistance.

Results

The prevalence of multidrug-resistant TB was 12.7% (95% confidence interval [95% CI], 9.6%–16.3%). Resistance to second-line drugs was low. Factors associated with multidrug-resistant TB at enrollment included a history of treatment failure (odds ratio, 23.6; 95% CI, 7.7–72.4), multiple previous TB episodes (odds ratio, 15.6; 95% CI, 5.0–49.1), and cavities present on chest radiograph (odds ratio, 5.9; 95% CI, 1.2–29.5). Among a cohort of 250 patients, 5.2% (95% CI, 2.8%–8.7%) were infected with M. tuberculosis that developed additional drug resistance. Amplification of drug resistance was associated with existing drug resistance at baseline (P<.01) and delayed sputum culture conversion (P<.01).

Conclusions

The burden of drug resistance in previously treated patients with TB in Uganda is sizeable, and the risk of generating additional drug resistance is significant. There is an urgent need to improve the treatment for such patients in low-income countries.

Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users.

Design Prospective cohort study started in 1968 with mortality data supplied by participating general practitioners, National Health Service central registries, or both.

Setting 1400 general practices throughout the United Kingdom.

Participants 46 112 women observed for up to 39 years, resulting in 378 006 woman years of observation among never users of oral contraception and 819 175 among ever users.

Main outcome measures Directly standardised adjusted relative risks between never and ever users for all cause and cause specific mortality.

Results 1747 deaths occurred in never users of oral contraception and 2864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5-9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100 000 woman years.

Conclusion Oral contraception was not associated with an increased long term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral contraception usage and background risk of disease.

Background

Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life.

Purpose

To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood.

Methods

The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 X 2(x2) factorial design.

Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed.

Conclusion

This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy. Clinical Trials 2007; 4: 42–57. http://ctj.sagepub.com

Objective

To describe uptake of HIV and syphilis testing in a prevention of mother-to-child HIV transmission programme in Uganda.

Methods

Analysis of data from routine HIV and syphilis testing at Entebbe Hospital antenatal services.

Results

A total of 20 738 women attended antenatal services. Exactly 62.8% of women, but only 1.8% of their male partners, accepted testing for HIV; 82.2% of women, but only 1.1% of their male partners accepted syphilis testing. Partners of women with positive HIV results were more likely to come for subsequent testing. Of 200 couples whose partners accepted HIV-testing within 30 days of one another, 19 (9.5%) were HIV-discordant, representing 65.5% of couples with at least one partner HIV-positive. HIV prevalence was 12.6% for women and 10.8% for men; syphilis prevalence was 4.0% for women and 6.2% for men.

Conclusion

Uptake of HIV and syphilis testing was fairly good among pregnant women attending antenatal clinics at Entebbe Hospital, but very low among their male partners. The level of HIV-discordant couples was high. These clinics should be made more couples-friendly to identify both HIV-positive men for treatment and discordant couples for HIV prevention.

Summary

The objectives of this study were to estimate the prevalence of atopic sensitization, and to identify common aeroallergens associated with atopic sensitization among women in Entebbe, Uganda, and to determine risk factors for atopic sensitization among those with and without a history of asthma or eczema. A case–control study was conducted within a trial of deworming in pregnancy, approximately 2 years after the intervention. Skin prick test reactivity was assessed among 20 women with a history of asthma, 25 with history of eczema and 95 controls. Overall prevalence of reactivity was estimated by adjusting for the prevalence of asthma in the whole cohort. Overall skin prick test prevalence was: any allergen 30.7%, Blomia tropicalis 10.9%, Dermatophagoides mix 16.8%, cockroach 15.8%. The prevalence of a positive skin prick test was significantly associated with a history of asthma (70% to any allergen vs. 32%, P = 0.002) but not with a history of eczema (44% vs. 36%, P = 0.49). Women with Mansonella perstans had significantly reduced odds for atopic sensitization (adjusted odds ratio 0.14, 95% CI 0.03–0.69); women with a history of asthma were less likely to have hookworm (adjusted odds ratio 0.24, 95% CI 0.07–0.81) but this association was weaker for women with a history of eczema. [Clinical Trial No. ISRCTN32849447]

Background

Disparities in perinatal health care occur worldwide. If the UN Millennium Development Goals in maternal and child health are to be met, this needs to be addressed. This study was conducted to facilitate our understanding of the changing use of maternity care services in a semi-urban community in Entebbe Uganda and to examine the range of antenatal and delivery services received in health care facilities and at home.

Methods

We conducted a retrospective community survey among women using structured questionnaires to describe the use of antenatal services and delivery care.

Results

In total 413 women reported on their most recent pregnancy. Antenatal care attendance was high with 96% attending once, and 69% the recommended four times. Blood pressure monitoring (95%) and tetanus vaccination (91%) were the services most frequently reported and HIV testing (47%), haematinics (58%) and presumptive treatment for malaria (66%) least frequently. Hospital clinics significantly outperformed public clinics in the quality of antenatal service. A significant improvement in the reported quality of antenatal services received was observed by year (p < 0.001). Improvement in the range and consistency of services at Entebbe Hospital over time was associated with an increase in the numbers who sought care there (p = 0.038). Although 63% delivered their newborn at a local hospital, 11% still delivered at home with no skilled assistance and just under half of these women reported financial/transportation difficulties as the primary reason. Less educated, poorer mothers were more likely to have unskilled/no assistance. Simple newborn care practices were commonly neglected. Only 35% of newborns were breastfed within the first hour and delayed wrapping of newborn infants occurred after 27% of deliveries.

Conclusion

Although antenatal services were well utilised, the quality of services varied. Women were able and willing to travel to a facility providing a good service. Access to essential skilled birth attendants remains difficult especially for less educated, poorer women, commonly mediated by financial and transport difficulties and several simple post delivery practices were commonly neglected. These factors need to be addressed to ensure that high quality care reaches the most vulnerable women and infants.

Objective To examine the absolute risks or benefits on cancer associated with oral contraception, using incident data.

Design Inception cohort study.

Setting Royal College of General Practitioners' oral contraception study.

Participants Directly standardised data from the Royal College of General Practitioners' oral contraception study.

Main outcome measures Adjusted relative risks between never and ever users of oral contraceptives for different types of cancer, main gynaecological cancers combined, and any cancer. Standardisation variables were age, smoking, parity, social class, and (for the general practitioner observation dataset) hormone replacement therapy. Subgroup analyses examined whether the relative risks changed with user characteristics, duration of oral contraception usage, and time since last use of oral contraception.

Results The main dataset contained about 339 000 woman years of observation for never users and 744 000 woman years for ever users. Compared with never users ever users had statistically significant lower rates of cancers of the large bowel or rectum, uterine body, and ovaries, tumours of unknown site, and other malignancies; main gynaecological cancers combined; and any cancer. The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies, were seen with increasing duration of oral contraceptive use. Reduced relative risk estimates were observed for ovarian and uterine body cancer many years after stopping oral contraception, although some were not statistically significant. The estimated absolute rate reduction of any cancer among ever users was 45 or 10 per 100 000 woman years, depending on whether the main or general practitioner observation dataset was used.

Conclusion In this UK cohort, oral contraception was not associated with an overall increased risk of cancer; indeed it may even produce a net public health gain. The balance of cancer risks and benefits, however, may vary internationally, depending on patterns of oral contraception usage and the incidence of different cancers.

Summary

It is suggested that helminths, particularly hookworm and schistosomiasis, may be important causes of anaemia in pregnancy. We assessed the associations between mild-to-moderate anaemia (haemoglobin >8.0 g/dl and <11.2 g/dl) and helminths, malaria and HIV among 2507 otherwise healthy pregnant women at enrolment to a trial of deworming in pregnancy in Entebbe, Uganda. The prevalence of anaemia was 39.7%. The prevalence of hookworm was 44.5%, Mansonella perstans 21.3%, Schistosoma mansoni 18.3%, Strongyloides 12.3%, Trichuris 9.1%, Ascaris 2.3%, asymptomatic Plasmodium falciparum parasitaemia 10.9% and HIV 11.9%. Anaemia showed little association with the presence of any helminth, but showed a strong association with malaria (adjusted odds ratio (AOR) 3.22, 95% CI 2.43–4.26) and HIV (AOR 2.46, 95% CI 1.90–3.19). There was a weak association between anaemia and increasing hookworm infection intensity. Thus, although highly prevalent, helminths showed little association with mild-to-moderate anaemia in this population, but HIV and malaria both showed a strong association. This result may relate to relatively good nutrition and low helminth infection intensity. These findings are pertinent to estimating the disease burden of helminths and other infections in pregnancy. [Clinical Trial No. ISRCTN32849447]

Background

Associations between symptom experience and mortality have rarely been investigated. One study has suggested that the number of symptoms people experience may be an important predictor of mortality. This novel and potentially important finding may have important implications but needs to be tested in other cohorts.

Methods

858 people aged around 58 years were interviewed by nurses in 1990/1 as part of the West of Scotland Twenty-07 Study. They were asked about the presence of symptoms in the last month from a checklist of 33 symptoms. Measures of morbidity included symptom type (respiratory, musculoskeletal, gastrointestinal, mental health, neurological, systemic) and symptom summary measures looking at the number and impact of symptoms (total number; number participants tended to have; number participants did not tend to have; number which restricted usual activities; number which led to GP consultation). Hazard ratios for thirteen-year all-cause mortality were calculated for symptom types, symptom summary measures, and self-assessed health with and without adjustment.

Results

On unadjusted analysis, and after adjusting for gender, socio-economic status and smoking, mortality was elevated in individuals reporting respiratory, systemic and mental health symptoms. After additional adjustment for chronic conditions and self-assessed health, only the association between mental health symptoms and mortality remained significant. On unadjusted analysis, and after adjusting for gender, socio-economic status and smoking, mortality was elevated in individuals with many (≥ 6) symptoms in four of the symptom summary measures examined. These relationships were no longer significant after additional adjustment for chronic conditions and self-assessed health. A clear trend of increasing mortality as self-assessed health became poorer was observed. This pattern remained statistically significant after adjustment for gender, socio-economic status, smoking, chronic conditions and the total number of symptoms experienced.

Conclusion

Symptoms often thought of as minor may have important consequences later in life especially for those reporting mental health-related symptoms or those experiencing many symptoms. In this study however, self-assessed health appeared to be a better predictor of mortality than the type or number of symptoms experienced, even when the tendency to have and impact of the symptoms were taken into account.

Background

Few qualitative studies of headache have been conducted and as a result we have little in-depth understanding of the experiences and perceptions of people with headache. The aim of this paper was to explore the perceptions and experiences of individuals with headache and their experiences of associated healthcare and treatment.

Methods

A qualitative study of individuals with headache, sampled from a population-based study of chronic pain was conducted in the North-East of Scotland, UK. Seventeen semi-structured interviews were conducted with adults aged 65 or less. Interviews were analysed using the Framework approach utilising thematic analysis.

Results

Almost every participant reported that they were unable to function fully as a result of the nature and unpredictability of their headaches and this had caused disruption to their work, family life and social activities. Many also reported a negative impact on mood including feeling depressed, aggressive or embarrassed. Most participants had formed their own ideas about different aspects of their headache and several had searched for, or were seeking, increased understanding of their headache from a variety of sources. Many participants reported that their headaches caused them constant worry and anguish, and they were concerned that there was a serious underlying cause. A variety of methods were being used to manage headaches including conventional medication, complementary therapies and self-developed management techniques. Problems associated with all of these management strategies emerged.

Conclusion

Headache has wide-ranging adverse effects on individuals and is often accompanied by considerable worry. The development of new interventions or educational strategies aimed at reducing the burden of the disorder and associated anxiety are needed.

Background

Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.

Methods

In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.

Results

Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.

Conclusion

Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.

Objectives To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy.

Design Nested cohort study.

Setting Royal College of General Practitioners' oral contraception study.

Participants 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation).

Main outcome measures Mortality from all causes, cardiovascular disease, and cancer.

Results 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age.

Conclusion Hysterectomy did not increase the risk of death in the medium to long term.

BACKGROUND: Little is known about the clinical importance of disease that is not presented to healthcare services. AIM: To determine the 5-year mortality among those with angina symptoms, known or not known by their general practitioner (GP) to have ischaemic heart disease (IHD). DESIGN: A prospective cohort study. SETTING: The study was conducted in the United Kingdom as part of the Royal College of General Practitioners' Oral Contraception Study. METHOD: In 1994-1995 women (n = 11,797) still under GP observation were sent a questionnaire that inquired about their smoking habits, other lifestyle issues, general health, and selected symptoms (including chest pain, assessed using the Rose angina questionnaire). The main outcome measure was the chances (odds) of dying during the next 5 years, among those with and without exertional chest pain, Rose angina or Rose myocardial infarction (MI), stratified by documented history of IHD. RESULTS: Overall, the lifetime prevalence of any exertional chest pain was 10.1% (95% confidence interval [CI] = 9.5 to 10.8); grade I Rose angina was 6.1% (95% CI = 5.6 to 6.6); grade II Rose angina was 1.3% (95% CI = 1.1 to 1.6); and Rose MI was 4.4% (95% CI = 4.0 to 4.9). The prevalence of each condition tended to increase with age, social class, parity, body mass index, and documented history of IHD. The proportion of women documented as having IHD was 23% among those with any exertional chest pain, 21.7% for grade I Rose angina, 37.7% for grade II Rose angina, and 31.4% for Rose MI. Compared to women without Rose angina, significantly higher odds ratios for all-cause mortality were observed among women with grade I Rose angina and no documented history of IHD (adjusted odds ratio [AOR] = 1.71, 95% CI = 1.05 to 2.79); those with grade II Rose angina and documented IHD (AOR = 3.94, 95% CI = 1.58 to 9.83); and women with grade II Rose angina and no documented history of IHD (AOR = 3.35, 95% CI = 1.47 to 7.62). CONCLUSIONS: Women with angina symptoms that have not been documented by their GP appear to have an increased risk of future mortality. Research is needed to determine the best way of identifying and managing these individuals.