Family history and breast cancer hormone receptor status in a Spanish cohort

Background

Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women.

Materials and Methods

A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles.

Results

Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER−&PR−. Women with a family history of breast cancer were more likely to have ER−&PR− tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91–2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34–5.81).

Conclusions

An increased proportion of ER−&PR− breast cancer was observed among younger Spanish women with a family history of the disease.     

Smoking during pregnancy is associated with a decreased incidence of obstetric anal sphincter injuries in nulliparous women

Background

Smoking is a modifiable lifestyle factor that has been shown to be associated with adverse perinatal outcomes and to have adverse health and dose-dependent connective tissue effects. The objective of this study was to examine whether smoking during pregnancy was associated with the incidence of obstetric anal sphincter injuries (OASIS) among six birthweight groups in singleton vaginal deliveries, considering nulliparous and multiparous women separately between 1997 and 2007 in Finland.

Methodology

A retrospective population-based register study. Populations included women with spontaneous singleton vaginal deliveries, consisting of all 213,059 nulliparous and all 288,391 multiparous women. Incidence of OASIS (n = 2,787) between smoking status groups was adjusted using logistic regression analyses.

Principal Findings

Of the nulliparous women, 13.1% were smokers, 3.6% had given up smoking during the first trimester of their pregnancy and 81.1% were non-smokers. Among these groups 0.7%, 0.9% and 1.1%, respectively suffered OASIS (p≤0.001). Nulliparous women who smoked had a 28% (95% CI 16–38%, p≤0.001) lower risk of OASIS compared to non-smokers, when adjusting for background variables. In multiparous women, the overall frequencies of OASIS were much lower (0.0–0.2%). A similar inverse relationship between OASIS rates and smoking was significant in pooled univariate analysis of multiparous women, but multivariate analysis revealed statistically insignificant results between non-smokers and smokers.

Conclusions

Nulliparous women who were smokers had a 28% lower incidence of OASIS. However, smoking during pregnancy cannot be recommended since it has shown to be associated with other adverse pregnancy outcomes and adverse health effects. The observed association warrants clinical repetition studies and, if confirmed, also in vitro studies focusing on connective tissue properties at a molecular and cellular level.     

Perinatal mortality in eastern Uganda: a community based prospective cohort study

Background

To achieve a child mortality reduction according to millennium development goal 4, it is necessary to considerably reduce neonatal mortality. We report stillbirth and early neonatal mortality risks as well as determinants of perinatal mortality in Eastern Uganda.

Methods

A community-based prospective cohort study was conducted between 2006 and 2008. A total of 835 pregnant women were followed up for pregnancy outcome and survival of their children until 7 days after delivery. Mother''s residence, age, parity, bed net use and whether delivery took place at home were included in multivariable regression analyses to identify risk factors for perinatal death.

Results

The stillbirth risk was 19 per 1,000 pregnancies and the early neonatal death risk 22 per 1,000 live births. Overall, the perinatal mortality risk was 41 [95%CI: 27, 54] per 1,000 pregnancies. Of the deaths, 47% followed complicated deliveries and 24% preterm births. Perinatal mortality was 63/1,000 pregnancies among teenage mothers, 76/1,000 pregnancies among nulliparous women and 61/1,000 pregnancies among women delivering at home who, after controlling for potential confounders, had a 3.7 (95%CI: 1.8, 7.4) times higher perinatal mortality than women who gave birth in a health facility. This association was considerably stronger among nulliparous women [RR 8.0 (95%CI: 2.9, 21.6)] than among women with a previous live birth [RR 1.8 (95%CI: 0.7, 4.5)]. All perinatal deaths occurred among women who did not sleep under a mosquito net. Women living in urban slums had a higher risk of losing their babies than those in rural areas [RR: 2.7 (95%CI: 1.4, 5.3)].

Conclusion

Our findings strengthen arguments for ensuring that pregnant women have access to and use adequate delivery facilities and bed nets.     

Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren

Background

Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT.

Methods

Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens.

Results

Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).

Conclusions

DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00852371","term_id":"NCT00852371"}}NCT00852371     

Does a Family Meetings Intervention Prevent Depression and Anxiety in Family Caregivers of Dementia Patients? A Randomized Trial

Background

Family caregivers of dementia patients are at increased risk of developing depression or anxiety. A multi-component program designed to mobilize support of family networks demonstrated effectiveness in decreasing depressive symptoms in caregivers. However, the impact of an intervention consisting solely of family meetings on depression and anxiety has not yet been evaluated. This study examines the preventive effects of family meetings for primary caregivers of community-dwelling dementia patients.

Methods

A randomized multicenter trial was conducted among 192 primary caregivers of community dwelling dementia patients. Caregivers did not meet the diagnostic criteria for depressive or anxiety disorder at baseline. Participants were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions and four family meetings which occurred once every 2 to 3 months for a year. Outcome measures after 12 months were the incidence of a clinical depressive or anxiety disorder and change in depressive and anxiety symptoms (primary outcomes), caregiver burden and quality of life (secondary outcomes). Intention-to-treat as well as per protocol analyses were performed.

Results

A substantial number of caregivers (72/192) developed a depressive or anxiety disorder within 12 months. The intervention was not superior to usual care either in reducing the risk of disorder onset (adjusted IRR 0.98; 95% CI 0.69 to 1.38) or in reducing depressive (randomization-by-time interaction coefficient = −1.40; 95% CI −3.91 to 1.10) or anxiety symptoms (randomization-by-time interaction coefficient = −0.55; 95% CI −1.59 to 0.49). The intervention did not reduce caregiver burden or their health related quality of life.

Conclusion

This study did not demonstrate preventive effects of family meetings on the mental health of family caregivers. Further research should determine whether this intervention might be more beneficial if provided in a more concentrated dose, when applied for therapeutic purposes or targeted towards subgroups of caregivers.

Trial Registration

Controlled-Trials.com ISRCTN90163486     

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk

Background

There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol (‘polypills’) to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.

Methods

We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.

Findings

At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.

Conclusions

This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12607000099426     

Distribution systems of insecticide-treated bed nets for malaria control in rural Burkina Faso: cluster-randomized controlled trial

Background

Insecticide-impregnated bed nets (ITNs) have been shown to be a highly effective tool against malaria in the endemic regions of sub-Saharan Africa (SSA). There are however different opinions about the role of ITN social marketing and ITN free distribution in the roll-out of ITN programmes. The objective of this study was to evaluate the effects of free ITN distribution through antenatal care services in addition to an ITN social marketing programme in an area typical for rural SSA.

Methods

A cluster-randomised controlled ITN trial took place in the whole Kossi Province in north-western Burkina Faso, an area highly endemic for malaria. Twelve clusters were assigned to long-term ITN (Serena brand) social marketing plus free ITN (Serena brand) distribution to all pregnant women attending governmental antenatal care services (group A), and 13 clusters to ITN social marketing only (group B). The intervention took place during the rainy season of 2006 and thereafter. The trial was evaluated through a representative household survey at baseline and after one year. Serena ITN household ownership was the primary outcome measure.

Findings

A total of 1052 households were visited at baseline in February 2006 and 1050 at follow-up in February 2007. Overall Serena ITN household ownership increased from 16% to 28% over the study period, with a significantly higher increase in group A (13% to 35%) than in group B (18% to 23%) (p<0.001).

Interpretation

The free distribution of ITNs to pregnant women through governmental antenatal care services in addition to ITN social marketing substantially improved ITN household ownership in rural Burkina Faso.

Trial registration

Controlled-Trials.com ISRCTN07985309     

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic

Background

Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use.

Methods

1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.

Findings

Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN''s use was more than 90% in both groups.

Conclusions

Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

Fetal movement counting improved identification of fetal growth restriction and perinatal outcomes--a multi-centre, randomized, controlled trial

Background

Fetal movement counting is a method used by the mother to quantify her baby''s movements, and may prevent adverse pregnancy outcome by a timely evaluation of fetal health when the woman reports decreased fetal movements. We aimed to assess effects of fetal movement counting on identification of fetal pathology and pregnancy outcome.

Methodology

In a multicentre, randomized, controlled trial, 1076 pregnant women with singleton pregnancies from an unselected population were assigned to either perform fetal movement counting from gestational week 28, or to receive standard antenatal care not including fetal movement counting (controls). Women were recruited from nine Norwegian hospitals during September 2007 through November 2009. Main outcome was a compound measure of fetal pathology and adverse pregnancy outcomes. Analysis was performed by intention-to-treat.

Principal Findings

The frequency of the main outcome was equal in the groups; 63 of 433 (11.6%) in the intervention group, versus 53 of 532 (10.7%) in the control group [RR: 1.1 95% CI 0.7–1.5)]. The growth-restricted fetuses were more often identified prior to birth in the intervention group than in the control group; 20 of 23 fetuses (87.0%) versus 12 of 20 fetuses (60.0%), respectively, [RR: 1.5 (95% CI 1.0–2.1)]. In the intervention group two babies (0.4%) had Apgar scores <4 at 1 minute, versus 12 (2.3%) in the control group [RR: 0.2 (95% CI 0.04–0.7)]. The frequency of consultations for decreased fetal movement was 71 (13.1%) and 57 (10.7%) in the intervention and control groups, respectively [RR: 1.2 (95% CI 0.9–1.7)]. The frequency of interventions was similar in the groups.

Conclusions

Maternal ability to detect clinically important changes in fetal activity seemed to be improved by fetal movement counting; there was an increased identification of fetal growth restriction and improved perinatal outcome, without inducing more consultations or obstetric interventions.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00513942","term_id":"NCT00513942"}}NCT00513942     

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study

Background

Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.

Method

We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.

Results

Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.

Conclusions

We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.

Trial Registration

Trialregitser.nl NTR1040     

A randomized placebo-controlled trial of acetaminophen for prevention of post-vaccination fever in infants

Background

Fever is common following infant vaccinations. Two randomized controlled trials demonstrated the efficacy of acetaminophen prophylaxis in preventing fever after whole cell pertussis vaccination, but acetaminophen prophylaxis has not been evaluated for prevention of fever following contemporary vaccines recommended for infants in the United States.

Methods

Children six weeks through nine months of age were randomized 1∶1 to receive up to five doses of acetaminophen (10–15 mg per kg) or placebo following routine vaccinations. The primary outcome was a rectal temperature ≥38°C within 32 hours following the vaccinations. Secondary outcomes included medical utilization, infant fussiness, and parents'' time lost from work. Parents could request unblinding of the treatment assignment if the child developed fever or symptoms that would warrant supplementary acetaminophen treatment for children who had been receiving placebo.

Results

A temperature ≥38°C was recorded for 14% (25/176) of children randomized to acetaminophen compared with 22% (37/176) of those randomized to placebo but that difference was not statistically significant (relative risk [RR], 0.63; 95% CI, 0.40–1.01). Children randomized to acetaminophen were less likely to be reported as being much more fussy than usual (10% vs 24%) (RR, 0.42; 95% CI, 0.25–0.70) or to have the treatment assignment unblinded (3% vs 9%) (RR, 0.31; 95% CI, 0.11–0.83) than those randomized to placebo. In age-stratified analyses, among children ≥24 weeks of age, there was a significantly lower risk of temperature ≥38°C in the acetaminophen group (13% vs. 25%; p = 0.03).

Conclusion

The results of this relatively small trial suggest that acetaminophen may reduce the risk of post-vaccination fever and fussiness.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00325819","term_id":"NCT00325819"}}NCT00325819     

Estimating the magnitude of genetic factors by calculating the genetic relative risk of stroke in first-ever lacunar stroke patients

Background

Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke.

Methods

By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated.

Principal Findings

We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45–3.53) for overall first-degree relatives, 4.52 (95%CI 3.61–5.65) for patients'' parents and 2.10 (95%CI 1.63–2.69) for patients'' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size.

Conclusions

We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke.     

Is There Evidence for Aetiologically Distinct Subgroups of Idiopathic Congenital Talipes Equinovarus? A Case-Only Study and Pedigree Analysis

Background

Idiopathic congenital talipes equinovarus (CTEV) is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV.

Methods

Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history.

Results

The male∶female ratio was 2.3∶1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19–12.62) and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38–1.01); and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12–0.89). Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands.

Conclusions

These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the ‘Carter effect’, suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor ‘load’, and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.     

Completeness and changes in registered data and reporting bias of randomized controlled trials in ICMJE journals after trial registration policy

Objective

We assessed the adequacy of randomized controlled trial (RCT) registration, changes to registration data and reporting completeness for articles in ICMJE journals during 2.5 years after registration requirement policy.

Methods

For a set of 149 reports of 152 RCTs with ClinicalTrials.gov registration number, published from September 2005 to April 2008, we evaluated the completeness of 9 items from WHO 20-item Minimum Data Set relevant for assessing trial quality. We also assessed changes to the registration elements at the Archive site of ClinicalTrials.gov and compared published and registry data.

Results

RCTs were mostly registered before 13 September 2005 deadline (n = 101, 66.4%); 118 (77.6%) started recruitment before and 31 (20.4%) after registration. At the time of registration, 152 RCTs had a total of 224 missing registry fields, most commonly ‘Key secondary outcomes’ (44.1% RCTs) and ‘Primary outcome’ (38.8%). More RCTs with post-registration recruitment had missing Minimum Data Set items than RCTs with pre-registration recruitment: 57/118 (48.3%) vs. 24/31 (77.4%) (χ² ₁ = 7.255, P = 0.007). Major changes in the data entries were found for 31 (25.2%) RCTs. The number of RCTs with differences between registered and published data ranged from 21 (13.8%) for Study type to 118 (77.6%) for Target sample size.

Conclusions

ICMJE journals published RCTs with proper registration but the registration data were often not adequate, underwent substantial changes in the registry over time and differed in registered and published data. Editors need to establish quality control procedures in the journals so that they continue to contribute to the increased transparency of clinical trials.     

Community risk factors for ocular Chlamydia infection in Niger: pre-treatment results from a cluster-randomized trachoma trial

Background

Trachoma control programs utilize mass azithromycin distributions to treat ocular Chlamydia trachomatis as part of an effort to eliminate this disease world-wide. But it remains unclear what the community-level risk factors are for infection.

Methods

This cluster-randomized, controlled trial entered 48 randomly selected communities in a 2×2 factorial design evaluating the effect of different treatment frequencies and treatment coverage levels. A pretreatment census and examination established the prevalence of risk factors for clinical trachoma and ocular chlamydia infection including years of education of household head, distance to primary water source, presence of household latrine, and facial cleanliness (ocular discharge, nasal discharge, and presence of facial flies). Univariate and multivariate associations were tested using linear regression and Bayes model averaging.

Findings

There were a total of 24,536 participants (4,484 children aged 0–5 years) in 6,235 households in the study. Before treatment in May to July 2010, the community-level prevalence of active trachoma (TF or TI utilizing the World Health Organization [WHO] grading system) was 26.0% (95% CI: 21.9% to 30.0%) and the mean community-level prevalence of chlamydia infection by Amplicor PCR was 20.7% (95% CI: 16.5% to 24.9%) in children aged 0–5 years. Univariate analysis showed that nasal discharge (0.29, 95% CI: 0.04 to 0.54; P = 0.03), presence of flies on the face (0.40, 95% CI: 0.17 to 0.64; P = 0.001), and years of formal education completed by the head of household (0.07, 95% CI: 0.07 to 0.13; P = 0.03) were independent risk factors for chlamydia infection. In multivariate analysis, facial flies (0.26, 95% CI: 0.02 to 0.49; P = 0.03) and years of formal education completed by the head of household (0.06, 95% CI: 0.008 to 0.11; P = 0.02) were associated risk factors for ocular chlamydial infection.

Interpretation

We have found that the presence of facial flies and years of education of the head of the household are risk factors for chlamydia infection when the analysis is done at the community level.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00792922","term_id":"NCT00792922"}}NCT00792922     

The diaphragm and lubricant gel for prevention of cervical sexually transmitted infections: results of a randomized controlled trial

Background

We evaluated the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens®) and condoms compared to condoms alone on the incidence of chlamydial and gonococcal infections in an open-label randomized controlled trial among women at risk of HIV/STI infections.

Methods

We randomized 5045 sexually-active women at three sites in Southern Africa. Participants who tested positive for curable STIs were treated prior to enrollment as per local guidelines. Women were followed quarterly and tested for Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) infection by nucleic-acid amplification testing (Roche Amplicor®) using first-catch urine specimens. STIs detected at follow-up visits were treated. We compared the incidence of first infection after randomization between study arms in both intent-to-treat (ITT) and per-protocol populations.

Findings

Baseline demographic, behavioral and clinical characteristics were balanced across study arms. Nearly 80% of participants were under 35 years of age. Median follow-up time was 21 months and the retention rate was over 93%. There were 471 first chlamydia infections, 247 in the intervention arm and 224 in the control arm with an overall incidence of 6.2/100 woman-years (wy) (relative hazard (RH) 1.11, 95% Confidence Interval (CI): 0.93–1.33; p = 0.25) and 192 first gonococcal infections, 95 in the intervention arm and 97 in the control arm with an overall incidence of 2.4/100wy (RH 0.98, 95%CI: 0.74–1.30; p = 0.90). Per protocol results indicated that when diaphragm adherence was defined as “always use” since the last visit, there was a significant reduction in the incidence of GC infection among women randomized to the intervention arm (RH 0.61, 95%CI: 0.41–0.91, P = 0.02).

Interpretation

There was no difference by study arm in the rate of acquisition of CT or GC. However, our per-protocol results suggest that consistent use of the diaphragm may reduce acquisition of GC.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00121459","term_id":"NCT00121459"}}NCT00121459 [{"type":"clinical-trial","attrs":{"text":"NCT00121459","term_id":"NCT00121459"}}NCT00121459]     

Safety of the Recombinant Cholera Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy

Introduction

Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.

Methodology/Principal Findings

From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.

Conclusions/Significance

We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00709410","term_id":"NCT00709410"}}NCT00709410     

Reduction of claustrophobia with short-bore versus open magnetic resonance imaging: a randomized controlled trial

Background

Claustrophobia is a common problem precluding MR imaging. The purpose of the present study was to assess whether a short-bore or an open magnetic resonance (MR) scanner is superior in alleviating claustrophobia.

Methods

Institutional review board approval and patient informed consent were obtained to compare short-bore versus open MR. From June 2008 to August 2009, 174 patients (139 women; mean age = 53.1 [SD 12.8]) with an overall mean score of 2.4 (SD 0.7, range 0 to 4) on the Claustrophobia Questionnaire (CLQ) and a clinical indication for imaging, were randomly assigned to receive evaluation by open or by short-bore MR. The primary outcomes were incomplete MR examinations due to a claustrophobic event. Follow-up was conducted 7 months after MR imaging. The primary analysis was performed according to the intention-to-treat strategy.

Results

With 33 claustrophobic events in the short-bore group (39% [95% confidence interval [CI] 28% to 50%) versus 23 in the open scanner group (26% [95% CI 18% to 37%]; P = 0.08) the difference was not significant. Patients with an event were in the examination room for 3.8 min (SD 4.4) in the short-bore and for 8.5 min (SD 7) in the open group (P = 0.004). This was due to an earlier occurrence of events in the short-bore group. The CLQ suffocation subscale was significantly associated with the occurrence of claustrophobic events (P = 0.003). New findings that explained symptoms were found in 69% of MR examinations and led to changes in medical treatment in 47% and surgery in 10% of patients. After 7 months, perceived claustrophobia increased in 32% of patients with events versus in only 11% of patients without events (P = 0.004).

Conclusions

Even recent MR cannot prevent claustrophobia suggesting that further developments to create a more patient-centered MR scanner environment are needed.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00715806","term_id":"NCT00715806"}}NCT00715806     

Hypertension in women of reproductive age in the United States: NHANES 1999-2008

Objective

To examine the epidemiology of hypertension in women of reproductive age.

Methods

Using NHANES from 1999–2008, we identified 5,521 women age 20–44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use.

Results

The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%–8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%–4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007–2008 did not differ significantly from 1999–2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers.

Conclusion

Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U.S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable.