Frenotomy with breastfeeding support versus breastfeeding support alone for infants with tongue-tie and breastfeeding difficulties: the FROSTTIE RCT.

Background: Tongue-tie can be diagnosed in 3-11% of babies, with some studies reporting almost universal breastfeeding difficulties, and others reporting very few feeding difficulties that relate to the tongue-tie itself, instead noting that incorrect positioning and attachment are the primary reasons behind the observed breastfeeding difficulties and not the tongue-tie itself. The only existing trials of frenotomy are small and underpowered and/or include only very short-term or subjective outcomes. Objective: To investigate whether frenotomy is clinically and cost-effective to promote continuation of breastfeeding at 3 months in infants with breastfeeding difficulties diagnosed with tongue-tie. Design: A multicentre, unblinded, randomised, parallel group controlled trial. Setting: Twelve infant feeding services in the UK. Participants: Infants aged up to 10 weeks referred to an infant feeding service (by a parent, midwife or other breastfeeding support service) with breastfeeding difficulties and judged to have tongue-tie. Interventions: Infants were randomly allocated to frenotomy with standard breastfeeding support or standard breastfeeding support without frenotomy. Main outcome measures: Primary outcome was any breastmilk feeding at 3 months according to maternal self-report. Secondary outcomes included mother's pain, exclusive breastmilk feeding, exclusive direct breastfeeding, frenotomy, adverse events, maternal anxiety and depression, maternal and infant NHS health-care resource use, cost-effectiveness, and any breastmilk feeding at 6 months of age. Results: Between March 2019 and November 2020, 169 infants were randomised, 80 to the frenotomy with breastfeeding support arm and 89 to the breastfeeding support arm from a planned sample size of 870 infants. The trial was stopped in the context of the COVID-19 pandemic due to withdrawal of breastfeeding support services, slow recruitment and crossover between arms. In the frenotomy with breastfeeding support arm 74/80 infants (93%) received their allocated intervention, compared to 23/89 (26%) in the breastfeeding support arm. Primary outcome data were available for 163/169 infants (96%). There was no evidence of a difference between the arms in the rate of breastmilk feeding at 3 months, which was high in both groups (67/76, 88% vs. 75/87, 86%; adjusted risk ratio 1.02, 95% confidence interval 0.90 to 1.16). Adverse events were reported for three infants after surgery [bleeding (n = 1), salivary duct damage (n = 1), accidental cut to the tongue and salivary duct damage (n = 1)]. Cost-effectiveness could not be determined with the information available. Limitations: The statistical power of the analysis was extremely limited due to not achieving the target sample size and the high proportion of infants in the breastfeeding support arm who underwent frenotomy. Conclusions: This trial does not provide sufficient information to assess whether frenotomy in addition to breastfeeding support improves breastfeeding rates in infants diagnosed with tongue-tie. Future work: There is a clear lack of equipoise in the UK concerning the use of frenotomy, however, the effectiveness and cost-effectiveness of the procedure still need to be established. Other study designs will need to be considered to address this objective. Trial registration: This trial is registered as ISRCTN 10268851. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (project number 16/143/01) and will be published in full in Health Technology Assessment; Vol. 27, No. 11. See the NIHR Journals Library website for further project information. The funder had no role in study design or data collection, analysis and interpretation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Many mothers and babies experience difficulties in establishing breastfeeding. In some babies it is thought that their difficulties may be linked to a condition called tongue-tie, in which a piece of skin tightly joins the middle part of the underside of the tongue to the base of the baby's mouth. This can be treated by an operation to divide the tight part/skin in the middle of the underneath of the tongue. We planned to carry out a trial of 870 babies to find out whether an operation together with breastfeeding support helps more mothers and babies with tongue-tie to continue breastfeeding until the baby is 3 months old compared to breastfeeding support on its own and whether the costs were different between the two groups of mothers and babies. We were only able to recruit 169 babies as the trial was stopped because of slow recruitment, changes to services in the COVID-19 pandemic and a high proportion of the babies in the breastfeeding support group going on to have an operation. There were no differences in the rate of breastfeeding at 3 months between the babies in the group who had an operation straightaway and those in the group that had breastfeeding support alone, or had an operation later. More than four in every five babies in both groups were still breastmilk feeding at 3 months. Three babies who had an operation, around 1 in 50 babies, had a complication of the operation (bleeding, scarring or a cut to the tube that makes saliva). Because of the small size of the study, we cannot say whether an operation to divide a tongue-tie along with breastfeeding support helps babies with tongue-tie and breastfeeding difficulties or has different costs. We will need to try different types of research to answer the question.

Association between breastfeeding duration and educational achievement in England: results from the Millennium Cohort Study.

OBJECTIVE: To evaluate the association between breastfeeding duration and educational outcomes at the end of secondary education among children from the Millennium Cohort Study. DESIGN: Cohort study comparing school results at age 16 according to breastfeeding duration. SETTING: England. PARTICIPANTS: Children born in 2000-2002 (nationally representative sample). EXPOSURE: Self-reported breastfeeding duration (categorised). MAIN OUTCOME MEASURES: Standardised school assessments taken at the end of secondary education (General Certificate of Secondary Education (GCSEs), marked 9-1) in English and Mathematics, categorised as: 'fail, marks <4', 'low pass, marks 4-6' and 'high pass, marks ≥7 (equivalent to A-A*)'. Additionally, overall achievement was measured using the 'attainment 8' score (adding the marks of eight GCSEs, English and Mathematics double weighted; 0-90). RESULTS: Approximately 5000 children were included. Longer breastfeeding was associated with better educational outcomes. For example, after full adjustment for socioeconomic markers and maternal cognitive ability, in comparison with children who were never breastfed, those who were breastfed for longer were more likely to have a high pass in their English and Mathematics GCSEs, and less likely to fail the English GCSE (but not the Mathematics GCSE). Additionally, compared with those never breastfed, those breastfed for at least 4 months had, on average, a 2-3 point higher attainment 8 score (coefficients: 2.10, 95% CI 0.06 to 4.14 at 4-6 months; 2.56, 95% CI 0.65 to 4.47 at 6-12 months and 3.09, 95% CI 0.84 to 5.35 at ≥12 months). CONCLUSIONS: A longer breastfeeding duration was associated with modest improvements in educational outcomes at age 16, after controlling for important confounders.

Planned mode of birth after previous cesarean section and risk of undergoing pelvic floor surgery: A Scottish population-based record linkage cohort study.

BACKGROUND: The global rise in cesarean sections has led to increasing numbers of pregnant women with a history of previous cesarean section. Policy in many high-income settings supports offering these women a choice between planned elective repeat cesarean section (ERCS) or planned vaginal birth after previous cesarean (VBAC), in the absence of contraindications to VBAC. Despite the potential for this choice to affect women's subsequent risk of experiencing pelvic floor disorders, evidence on the associated effects to fully counsel women is lacking. This study investigated the association between planned mode of birth after previous cesarean section and the woman's subsequent risk of undergoing pelvic floor surgery. METHODS AND FINDINGS: A population-based cohort study of 47,414 singleton term births in Scotland between 1983 to 1996 to women with 1 or more previous cesarean sections was conducted using linked Scottish national routine datasets. Cox regression was used to investigate the association between planned as well as actual mode of birth and women's subsequent risk of having any pelvic floor surgery and specific types of pelvic floor surgery adjusted for sociodemographic, maternal medical, and obstetric-related factors. Over a median of 22.1 years of follow-up, 1,159 (2.44%) of the study population had pelvic floor surgery. The crude incidence rate of any pelvic floor surgery per 1,000 person-years was 1.35, 95% confidence interval (CI) 1.27 to 1.43 in the overall study population, 1.75, 95% CI 1.64 to 1.86 in the planned VBAC group and 0.66, 95% CI 0.57 to 0.75 in the ERCS group. Planned VBAC compared to ERCS was associated with a greater than 2-fold increased risk of the woman undergoing any pelvic floor surgery (adjusted hazard ratio [aHR] 2.38, 95% CI 2.03 to 2.80, p < 0.001) and a 2- to 3-fold increased risk of the woman having surgery for pelvic organ prolapse or urinary incontinence (aHR 3.17, 95% CI 2.47 to 4.09, p < 0.001 and aHR 2.26, 95% CI 1.79 to 2.84, p < 0.001, respectively). Analysis by actual mode of birth showed these increased risks were only apparent in the women who actually had a VBAC, with the women who needed an in-labor non-elective repeat cesarean section having a comparable risk of pelvic floor surgery to those who had an ERCS. The main limitation of this study is the potential for misclassification bias. CONCLUSIONS: This study suggests that among women with previous cesarean section giving birth to a singleton at term, planned VBAC compared to ERCS is associated with an increased risk of the woman subsequently undergoing pelvic floor surgery including surgery for pelvic organ prolapse and urinary incontinence. However, these risks appear to be only apparent in women who actually give birth vaginally as planned, highlighting the role of vaginal birth rather than labor in pelvic floor dysfunction requiring surgery. The findings provide useful additional information to counsel women with previous cesarean section about the risks and benefits associated with their future birth choices.

Risk factors for hospitalisation in Welsh infants with a congenital anomaly.

OBJECTIVES: To investigate risk factor associated with hospitalisation of infants with a congenital anomaly in Wales, UK. DESIGN: A population-based cohort study. SETTING: Data from the Welsh Congenital Anomaly Register and Information Service linked to the Patient Episode Database for Wales and livebirths and deaths from the Office for National Statistics. PATIENTS: All livebirths between 1999 and 2015 with a diagnosis of a congenital anomaly, which was defined as a structural, metabolic, endocrine or genetic defect, as well as rare diseases of hereditary origin. MAIN OUTCOME MEASURES: Adjusted OR (aOR) associated with 1 or 2+ hospital admissions in infancy versus no admissions were estimated for sociodemographic, maternal and infant factors using multinomial logistic regression for the subgroups of all, isolated, multiple and cardiovascular anomalies. RESULTS: 25 523 infants affected by congenital anomalies experienced a total of 50 705 admissions in infancy. Risk factors for ≥2 admissions were younger maternal age ≤24 years (aOR: 1.17; 95% CI 1.06 to 1.30), maternal smoking (aOR: 1.20; 1.10 to 1.31), preterm birth (aOR: 2.52; 2.25 to 2.83) and moderately severe congenital heart defects (aOR: 6.25; 4.47 to 8.74). Girls had an overall decreased risk of 2+ admissions (aOR: 0.84; 0.78 to 0.91). Preterm birth was a significant risk factor for admissions in all anomaly subgroups but the effect of the other characteristics varied according to anomaly subgroup. CONCLUSIONS: Over two-thirds of infants with an anomaly are admitted to hospital during infancy. Our findings identified sociodemographic and clinical characteristics contributing to an increased risk of hospitalisation of infants with congenital anomalies.

Electronic cigarette use (vaping) and patterns of tobacco cigarette smoking in pregnancy-evidence from a population-based maternity survey in England.

OBJECTIVES: Exposure to tobacco products during pregnancy presents a potential harm to both mother and baby. This study sought to estimate the prevalence of vaping during pregnancy and to explore the factors and outcomes associated with vaping in pregnancy. SETTING: England. PARTICIPANTS: Women who gave birth between 15th and 28th October 2017. METHODS: A cross-sectional population-based postal survey of maternal and infant health, the National Maternity Survey (NMS) 2018. The prevalence of vaping and patterns of cigarette smoking were estimated, and regression analysis was used to explore associations between maternal characteristics and vaping, and between vaping and birth outcomes. OUTCOME MEASURES: Unweighted and weighted prevalence of vaping with 95% confidence intervals, and unadjusted and adjusted relative risks or difference in means for the association of participant characteristics and secondary outcomes with vaping. Secondary outcome measures were: preterm birth, gestational age at birth, birthweight, and initiation and duration of breastfeeding. RESULTS: A total of 4,509 women responded to the survey. The prevalence of vaping in pregnancy was 2.8% (95%CI 2.4% to 3.4%). This varied according to the pattern of cigarette smoking in pregnancy: 0.3% in never-smokers; 3.3% in ex-smokers; 7.7% in pregnancy-inspired quitters; 9.5% in temporary quitters; and 17.7% in persistent smokers. Younger women, unmarried women, women with fewer years of formal education, women living with a smoker, and persistent smokers were more likely to vape, although after adjusting for pattern of cigarette smoking and maternal characteristics, persistent smoking was the only risk factor. We did not find any association between vaping and preterm birth, birthweight, or breastfeeding. CONCLUSIONS: The prevalence of vaping during pregnancy in the NMS 2018 was low overall but much higher in smokers. Smoking was the factor most strongly associated with vaping. Co-occurrence of vaping with persistent smoking has the potential to increase the harms of tobacco exposure in pregnant women and their infants.

Twenty-five-year trends in breastfeeding initiation: The effects of sociodemographic changes in Great Britain, 1985-2010.

BACKGROUND: Data from the UK Infant Feeding Surveys indicate that breastfeeding initiation increased between 1985 and 2010. During this period, societal changes in GB also influenced the sociodemographic characteristics of women in the childbearing population. As breastfeeding behaviour is highly socially patterned in GB, the increasing trend in breastfeeding initiation may have hidden inequalities in breastfeeding practices. This study examines the sociodemographic inequalities in breastfeeding initiation in GB between 1985 and 2010, exploring whether and how this may have been influenced by social and policy changes. METHODS: Data drawn from the nationally representative 1985, 1990, 1995, 2000, 2005 and 2010 Infant Feeding Surveys were used to estimate changes in the proportion of mothers in selected sociodemographic groups over time. Logistic regression models estimated the independent associations between breastfeeding initiation in each survey year and maternal sociodemographic characteristics. Associations were adjusted for maternal sociodemographic, pregnancy-related and support factors. Evidence of a change in the association between breastfeeding initiation and each sociodemographic characteristic over time was assessed using a test for statistical heterogeneity. RESULTS: The sociodemographic characteristics of mothers in GB changed substantially between 1985 and 2010. Mothers were increasingly more likely to be 30 or over; have higher education and socioeconomic status; and be single or cohabiting. An increasing proportion of mothers in GB identified as being of black or minority ethnic origin. Reported smoking in pregnancy declined. These same characteristics independently predicted higher odds of breastfeeding initiation; the associations between these characteristics and breastfeeding initiation did not vary significantly over time. CONCLUSIONS: Marked inequalities in breastfeeding initiation persisted over the study period, hidden among the increasing initiation rate at the population level. The increasing overall rate of initiation was most likely driven by the rising prevalence of those groups of mothers who were, and remain, characteristically most likely to breastfeed.

Phase I study of pemetrexed with sorafenib in advanced solid tumors.

PURPOSE: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors. RESULTS: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer. EXPERIMENTAL DESIGN: A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1-5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks. CONCLUSIONS: Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer.

Women's Longitudinal Patterns of Smoking during the Pre-Conception, Pregnancy and Postnatal Period: Evidence from the UK Infant Feeding Survey.

BACKGROUND: An understanding of women's longitudinal patterns of smoking during the pre-conception, pregnancy and postnatal period and the factors associated with these patterns could help better inform smoking cessation services and interventions. METHODS: Latent class analysis (LCA) was used to empirically identify women's smoking patterns in a sample of 10,768 mothers from the 2010 UK Infant Feeding Survey. Multinomial logistic regression was used to identify characteristics associated with these patterns. RESULTS: LCA identified five distinct smoking patterns during the pre-conception, pregnancy and postnatal period: "non-smokers" (74.1% of women); "pregnancy-inspired quitters" (10.2%); "persistent smokers" (10.1%); "temporary quitters" (4.4%); and postnatal quitters (1.1%). Smoking patterns varied markedly according to socio-demographic variables and parity. After adjusting for these variables, mothers who lived during pregnancy with a partner who smoked were more likely to be temporary quitters (aOR 2.64, 95% CI 1.74-3.99) or persistent smokers (aOR 3.32, 95% CI 2.34-4.72) than pregnancy-inspired quitters. Mothers who lived during pregnancy with someone else other than a partner who smoked were more likely to be persistent smokers (aOR 2.34, 95% CI 1.38-3.97) or postnatal quitters (aOR 2.97, 95% CI 1.07-8.24) than pregnancy-inspired quitters. Mothers given information on how their partner could stop smoking if they lived during pregnancy with a smoking partner were less likely to be persistent smokers (aOR 0.42, 95% CI 0.27-0.65) than pregnancy-inspired quitters. CONCLUSION: Health professionals should ask about smoking at every opportunity, and refer women who self-report as current smokers to an evidence based smoking cessation service.

Breastfeeding in England: time trends 2005-2006 to 2012-2013 and inequalities by area profile.

Breastfeeding rates in England have risen steadily since the 1970s, but rates remain low and little is known about area-based trends. We report an ecological analysis of time trends in area breastfeeding rates in England using annual data on breastfeeding initiation (2005-2006 to 2012-2013) and any breastfeeding at 6-8 weeks (2008-2009 to 2012-2013) for 151 primary care trusts (PCTs). Overall, breastfeeding initiation rose from 65.5% in 2005-2006 to 72.4% in 2012-2013 (average annual absolute increase 0.9%). There was a statistically significantly higher (interaction P < 0.001) annual increase in initiation in PCTs in the most deprived (1.2%) compared with the least deprived tertile (0.7%), and in PCTs with low baseline breastfeeding initiation (2005-2006; 1.4%) compared with high baseline initiation (0.6%). Similar trends were observed when PCTs were stratified by the proportion of teenage mothers and maternal smoking, but not when stratified by ethnicity. Although breastfeeding prevalence at 6-8 weeks also increased significantly over the observed time period (41.2% in 2008-2009, 43.7% in 2012-2013; annual increase 0.7%), there was no difference in the average increase by deprivation profile, ethnicity, teenage mothers and maternal smoking. However, PCTs with low baseline prevalence in 2008-2009 saw a significantly larger annual increase (0.8%) compared with PCTs with high baseline prevalence (0.07%). In conclusion, breastfeeding initiation and prevalence have seen higher increases in areas with low initial breastfeeding, and for initiation, more disadvantaged areas. Although these results suggest that inequalities in breastfeeding have narrowed, rates have plateaued since 2010-2011. Sustained efforts are needed to address breastfeeding inequalities.

Pregnancy-associated outcomes in women who spent some of their childhood looked after by local authorities: findings from the UK Millennium Cohort Study.

OBJECTIVES: There has been very little description of the health and social outcomes at pregnancy and early motherhood of girls who were previously looked after by local authorities. The objectives of this study were to compare the sociodemographic and health profiles of mothers who had spent time in a children's home or with foster parents as a child to mothers who had not. In particular, to examine associations between being looked after and the likelihood of smoking during pregnancy, birth weight, the presence of symptoms of maternal depression and the initiation of breastfeeding. DESIGN: A retrospective cross-sectional study using the baseline questionnaire of the Millennium Cohort Study. SETTING: The UK. PARTICIPANTS: A nationally representative study of 18,492 mothers of babies born in the UK during 2000-2002. EXPOSURE: A history of spending time in a children's home or with foster parents. OUTCOME MEASURES: (1) Smoking during pregnancy; (2) low birth weight; (3) symptoms of maternal depression and (4) initiation of breastfeeding. RESULTS: In univariable analyses, women who had been looked after by local authorities were significantly less likely to be of a higher social class, live in a high-income household or have achieved a high level of education. They were more likely to have a low-birthweight baby and be a single parent. In multivariable analyses, women who had been looked after by local authorities were more likely to smoke during pregnancy (adjusted OR 3.0 95% CI 2.14 to 4.3) and were more likely to have symptoms of depression (adjusted OR 1.98 95% CI 1.4 to 2.7) compared with women who had not been looked after. CONCLUSIONS: Our results suggest that these women carry social disadvantage into motherhood, with the potential of continuing the cycle of deprivation. There is a case for increasing our attention on this group, which can be readily accessed by maternity and early years' services.

Breastfeeding and educational achievement at age 5.

Our aim was to investigate whether the duration of breastfeeding, at all or exclusively, is associated with educational achievement at age 5. We used data from a prospective, population-based UK cohort study, the Millennium Cohort Study (MCS). 5489 children from White ethnic background born at term in 2000-2001, attending school in England in 2006, were included in our analyses. Educational achievement was measured using the Foundation Stage Profile (FSP), a statutory assessment undertaken by teachers at the end of the child's first school year. Breastfeeding duration was ascertained from interviews with the mother when the child was 9 months old. We used modified Poisson's regression to model the association of breastfeeding duration with having reached a good level of achievement overall (≥78 overall points and ≥6 in 'personal, social and emotional development' and 'communication, language and literacy' points) and in specific areas (≥6 points) of development. Children who had been breastfed for up to 2 months were more likely to have reached a good level of overall achievement [adjusted rate ratio (RR): 1.09, 95% confidence interval (CI): 1.01, 1.19] than never breastfed children. This association was more marked in children breastfed for 2-4 months (adjusted RR: 1.17, 95% CI: 1.07, 1.29) and in those breastfed for longer than 4 months (adjusted RR: 1.16, 95% CI: 1.07, 1.26). The associations of exclusive breastfeeding with the educational achievement were similar. Our findings suggest that longer duration of breastfeeding, at all or exclusively, is associated with better educational achievement at age 5.

The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447].

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.

The role of community acceptance over time for costs of HIV and STI prevention interventions: analysis of the Masaka Intervention Trial, Uganda, 1996-1999.

OBJECTIVE: The objective of this study is to estimate the annual costs of information, education, and communication (IEC), both community- and school-based; strengthened public and private sexually transmitted infections treatment; condom social marketing (CSM); and voluntary counseling and testing (VCT) implemented in Masaka, Uganda, over 4 years, and to explore how unit costs change with varying population use/uptake. STUDY: Total economic provider's costs and intervention outputs were collected annually to estimate annual unit costs between 1996 and 1999. RESULTS: In early intervention years, uptake of all activities grew dramatically and continued to grow for public STI treatment, CSM, and VCT. Attendance at IEC performances started to drop in year 4. Unit costs dropped rapidly with increasing uptake of and participation in interventions. CONCLUSIONS: When implementing long-term community-based interventions, it is important to take into account that it takes time for communities to scale up their participation, since this can lead to large variations in unit costs.

Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda.

BACKGROUND: We studied a cohort of human immunodeficiency virus (HIV)-infected adults in Uganda who were not receiving antiretroviral therapy, to explore the impact of helminths on HIV progression in areas where antiretrovirals are not available. METHODS: A total of 663 patients were screened for helminths, treated presumptively with albendazole and selectively with praziquantel, and monitored for 6 months. Blood samples were analyzed for CD4+ cell count and HIV-1 RNA. RESULTS: Schistosoma mansoni, hookworm, Strongyloides stercoralis, and Mansonella perstans were the most prevalent helminths. Helminth infection was not associated with higher viral load, lower CD4+ cell count, or faster decrease in CD4+ cell count preceding antihelminthic therapy. The effect of coinfection on HIV disease progression varied with species. CD4+ cell counts were highest in subjects with hookworm and Mansonella perstans infection. For most helminths, effective treatment was associated with greater decrease in CD4+ cell count than in those in whom infection was still present at follow-up. A highly significant decrease in viral load at 6 months was seen in patients with persistent Mansonella perstans infection at follow-up. Mortality was lower in subjects with hookworm infection at enrollment. CONCLUSION: Helminth infection was not associated with more-advanced HIV disease or faster disease progression. Antihelminthic therapy may not be beneficial in slowing HIV progression in coinfected adults.

A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis.

BACKGROUND: Active tuberculosis may accelerate progression of human immunodeficiency virus (HIV) infection by promoting viral replication in activated lymphocytes. Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology, and their use also might reduce progression of HIV by suppressing immune activation. We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment, in adults with HIV-1-associated pleural tuberculosis. The primary outcome was death. Analysis was by intention to treat. RESULTS: Of 197 participants, 99 were assigned to the prednisolone group and 98 to the placebo group. The mortality rate was 21 deaths/100 person-years (pyr) in the prednisolone group and 25 deaths/100 pyr in the placebo group (age-, sex-, and initial CD4+ T cell count-adjusted mortality rate ratio, 0.99 [95% confidence interval, 0.62-1.56] [P =.95]). Resolution of tuberculosis was faster in the prednisolone group, but recurrence rates were slightly (though not significantly) higher, and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma (4.2 cases/100 pyr, compared with 0 cases/100 pyr [P =.02]). CONCLUSIONS: In view of the lack of survival benefit and the increased risk of Kaposi sarcoma, the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended.