Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations.

OBJECTIVES: Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. METHODS: Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). RESULTS: Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. CONCLUSIONS: Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.

Comparison of anthropometric indicators to predict mortality in a population-based prospective study of children under 5 years in Niger.

OBJECTIVE: In the present study, we aimed to compare anthropometric indicators as predictors of mortality in a community-based setting. DESIGN: We conducted a population-based longitudinal study nested in a cluster-randomized trial. We assessed weight, height and mid-upper arm circumference (MUAC) on children 12 months after the trial began and used the trial's annual census and monitoring visits to assess mortality over 2 years. SETTING: Niger. PARTICIPANTS: Children aged 6-60 months during the study. RESULTS: Of 1023 children included in the study at baseline, height-for-age Z-score, weight-for-age Z-score, weight-for-height Z-score and MUAC classified 777 (76·0 %), 630 (61·6 %), 131 (12·9 %) and eighty (7·8 %) children as moderately to severely malnourished, respectively. Over the 2-year study period, fifty-eight children (5·7 %) died. MUAC had the greatest AUC (0·68, 95 % CI 0·61, 0·75) and had the strongest association with mortality in this sample (hazard ratio = 2·21, 95 % CI 1·26, 3·89, P = 0·006). CONCLUSIONS: MUAC appears to be a better predictor of mortality than other anthropometric indicators in this community-based, high-malnutrition setting in Niger.

Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial.

In a large community-randomized trial, biannual azithromycin distributions significantly reduced postneonatal childhood mortality in sub-Saharan African sites. Here, we present a prespecified secondary analysis showing that much of the protective effect was in the first 3 months postdistribution. Distributing more frequently than biannually could be considered if logistically feasible. Clinical Trials Registration. NCT02047981.

Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II).

BACKGROUND: The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment. METHODS AND FINDINGS: In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions. CONCLUSIONS: In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

Risk of cardiovascular disease in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of clinical and demographic factors was performed. The Atherosclerotic Cardiovascular Disease (ASCVD) calculator was used to predict 10-year risk of a cardiovascular event. RESULTS: Of the 233 women, 19 women had intact ovaries (median age 56.0) and 214 had undergone risk-reducing salpingo-oophorectomy (RRSO). Among the 108 women with RRSO under age 50 (median age 51.0), compared to the 106 women who had RRSO at or over age 50 (median age 63.5) 6.5% vs 10.4% reported diabetes (p = 0.30), 23.2% versus 28.3% had elevated fasting blood glucose (p = 0.39), 21.3% versus 34.0% reported hypertension (p = 0.04) with median systolic blood pressure of 118 mmHg versus 125.5 mmHg (p < 0.009), 25% versus 32% reported hyperlipidemia (p = 0.40), and 42% versus 49% had any abnormal lipid test (p = 0.28). An elevated 10-year ASCVD risk of over 10% was seen in 6.1% versus 24.8% respectively (p = 0.0001). CONCLUSION: Women who underwent RRSO at age of 50 and over, had higher ASCVD 10-year risk than women who underwent RRSO at younger ages most likely owing to older age at study entry. The ASCVD risks for women with BRCA mutation who had RRSO did not suggest increased risk associated with being a BRCA mutation carrier.

Bone loss in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence and identify risk factors for bone loss in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified from the Breast Cancer Surveillance database at Kaiser Permanente Northern California were invited to participate and undergo a dual-energy x-ray absorptiometry scan to assess for bone loss (osteopenia or osteoporosis). Multivariable logistic regression analysis was performed to assess clinical factors associated with bone loss. RESULTS: Of the 238 women in the final cohort, 20 women had intact ovaries (median age 54.5years) and 218 had undergone risk reducing salpingo-oophorectomy (RRSO) (median age 57). The prevalence of bone loss was 55% in the no RRSO group and 72.5% in the RRSO group (P=0.10). In multivariable analysis, only higher body mass index (OR 0.6 per 5kg/m2, 95% CI: 0.4-0.7) and nonwhite race compared to white (OR 0.5, 95% CI: 0.2-0.9) were protective for bone loss while older age (OR 1.5 per 10years, 95% CI: 1.1-2.1) and selective estrogen receptor modulator use (3.1, 95% CI: 1.2-10.1) were associated with increased odds of bone loss. Among women with RRSO, bone loss was more frequent in women who had postmenopausal (n=106) compared to women who had premenopausal RRSO (n=112), (82.1% and 63.4% respectively, P=0.002). In multivariable analysis, only BMI was protective of bone loss (OR 0.5, 95%, CI: 0.4-0.7) but neither age nor menopausal status at RRSO were associated with bone loss. CONCLUSION: Bone loss is common in women with BRCA mutations who undergo RRSO.

A Cluster-Randomized Trial to Assess the Efficacy of Targeting Trachoma Treatment to Children.

Background: The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection. Methods: Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0-12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction. Results: The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%-28.0%) at baseline to 5.8% (95% CI, 3.2%-9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%-25.3%) to 3.8% (95% CI, 2.2%-6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%-2.7%) to 0.3% (95% CI, .0%-.7%) and in the biannual arm from 1.2% (95% CI, .5%-2.2%) to 0.0% (95% CI, .0%-.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, -.04% to .02%) and adults (95% CI, .9%-2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively). Conclusions: Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages. Clinical Trials Registration: NCT00792922.

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial.

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).

Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma.

Twelve trachoma-hyperendemic communities were treated with 3 annual mass azithromycin distributions. Children aged 0-9 years were monitored 1 year following the third treatment. An RNA-based test detected ocular chlamydial infection in more children than did a DNA-based test (6.9% vs 4.2%), and in a larger number of communities (8 vs 7).

Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial.

BACKGROUND: Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions. METHODS: In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972. FINDINGS: At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04). INTERPRETATION: Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable. FUNDING: National Institutes of Health.

Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial.

CONTEXT: Mass oral azithromycin distribution to affected communities is a cornerstone of the World Health Organization's trachoma elimination program. Antibiotics are provided to target the ocular strains of chlamydia that cause trachoma, but may also be efficacious against respiratory disease, diarrhea, and malaria--frequent causes of childhood mortality in trachoma-endemic areas. OBJECTIVE: To compare mortality rates of participants aged 1 to 9 years in treated communities with those in untreated communities. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cluster-randomized clinical trial of mass azithromycin administration for trachoma control. Forty-eight communities (known as subkebeles) were randomized into 1 of 3 treatment schedules (annual treatment of all residents [15,902 participants], biannual treatment of all residents [17,288 participants], or quarterly treatment of children only [14,716 participants]) or into 1 group for which treatment was delayed by 1 year (control, 18,498 participants). Twelve subkebeles were randomized to each of the 4 schedules with all children in each of the 3 communities being eligible for treatment. The trial was conducted in a field setting in rural Ethiopia, May 2006 to May 2007. INTERVENTIONS: A single dose of oral azithromycin (adults, 1 g; children, 20 mg/kg) was administered for treatment of ocular Chlamydia trachomatis infection. Antibiotic coverage levels for children aged 1 to 9 years exceeded 80% at all visits. MAIN OUTCOME MEASURE: The main outcome measure was the community-specific mortality risk for children aged 1 to 9 years over the course of 1 year. Mortality was measured by enumerative census at baseline and again after 1 year. Comparison of the risk of mortality was a prespecified outcome for the clinical trial. RESULTS: The odds ratio for childhood mortality in the intervention communities was 0.51 (95% confidence interval, 0.29-0.90; P = .02; clustered logistic regression) compared with the control group. In the treated communities, the estimated overall mortality rate during this period for children aged 1 to 9 years in the untreated group was 8.3 per 1000 person-years (95% confidence interval, 5.3-13.1), while among the treated communities, the estimated overall mortality rate was 4.1 per 1000 person-years (95% confidence interval, 3.0-5.7) for children aged 1 to 9 years. CONCLUSION: In a trachoma-endemic area, mass distribution of oral azithromycin was associated with reduced mortality in children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00322972.

Adverse Childhood Experiences and Mental and Behavioral Health Conditions During Pregnancy: The Role of Resilience.

INTRODUCTION: Little is known about how exposure to adverse childhood experiences (ACEs) and protective factors, such as resilience, influence prenatal mental and behavioral health. This study examined associations between exposure to ACEs and mental and behavioral health during pregnancy overall and among women with high versus low levels of resilience. MATERIALS AND METHODS: Women in two Kaiser Permanente Northern California medical centers were screened for ACEs and resilience during prenatal care (∼14-23 weeks of gestation; N = 355). Multivariable logistic regression analyses examined associations between ACEs and prenatal mental and behavioral health conditions overall and for women with low (≤32) versus high (>32) resilience on the 10-item Connor-Davidson Resilience Scale. RESULTS: Overall, 54% of women reported 0 ACEs, 28% 1-2 ACEs, and 18% 3+ ACEs. Relative to women with 0 ACEs, those with 1-2 ACEs had higher odds of an anxiety or depressive disorder and intimate partner violence (IPV) (odds ratios [ORs] 2.42-3.12, p < 0.05), and those with 3+ ACEs had higher odds of an anxiety or depressive disorder, depression symptoms, and IPV (ORs 3.08-4.71, p < 0.05). In stratified analyses by high (56%) and low (44%) resilience, having one or more ACEs (vs. 0 ACEs) was only associated with worse mental and behavioral health in women with low resilience. CONCLUSIONS: ACEs predicted mental and behavioral health conditions among pregnant women, and associations were the strongest among women with low levels of current resilience. Longitudinal research is needed to understand the causal mechanisms underlying these associations.

Community-level Association between Clinical Trachoma and Ocular Chlamydia Infection after MASS Azithromycin Distribution in a Mesoendemic Region of Niger.

Purpose: The clinical sign trachomatous inflammation - follicular (TF) is used to monitor indication for and response to mass azithromycin distribution in trachoma-endemic communities. Here, we assess the relationship between TF, trachomatous inflammation - intense (TI), and infection with ocular Chlamydia trachomatis over time during annual mass azithromycin distribution. Methods: We used data from a cluster-randomized trial of mass azithromycin distribution for trachoma control in a mesoendemic region of Niger. This study includes 24 communities that received 3 years of annual mass azithromycin distribution. TF, TI, and ocular chlamydia infection were monitored among children aged 0-5 years. We assessed the correlation between the prevalence of ocular chlamydia infection and 1) TF and 2) TI prevalence over time. Results: At baseline, ocular chlamydia prevalence was 21.2% (95% CI 14.3-28.1%), TF prevalence was 27.7% (95% CI 21.2-34.2%), and TI prevalence was 8.3% (95% CI 5.2-11.5%). The prevalence of all three measures decreased significantly over time (P < 0.001). At baseline, ocular chlamydia infection prevalence was strongly correlated with both TF (rho = 0.78, P < 0.0001) and TI (rho = 0.76, P < 0.0001). The correlation between ocular chlamydia infection and both TF and TI was weak at months 12 and 24. At 36 months, when TF prevalence had dropped below 10%, ocular chlamydia infection and TF were moderately correlated (rho = 0.70, P= 0.0002). Conclusions: Both TF and TI are good indicators of infection prevalence prior to mass azithromycin distribution. However, this relationship may be affected by repeated rounds of mass azithromycin distribution.

Linear growth in preschool children treated with mass azithromycin distributions for trachoma: A cluster-randomized trial.

BACKGROUND: Mass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children. METHODS AND FINDINGS: 24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial. Communities were randomized in a 1:1 ratio to either continuation of biannual oral azithromycin (20mg/kg for children, 1 g for adults) or to no programmatic antibiotics over the 36 months of the study period. All community members 6 months and older were eligible for the intervention. The primary outcome was ocular chlamydia; height and weight were measured as secondary outcomes on children less than 60 months of age at months 12 and 36. Study participants were not masked; anthropometrists were not informed of the treatment allocation. Anthropometric measurements were collected for 282 children aged 0-36 months at the month 12 assessment and 455 children aged 0-59 months at the month 36 assessment, including 207 children who had measurements at both time points. After adjusting for age and sex, children were slightly but not significantly taller in the biannually treated communities (84.0 cm, 95%CI 83.2-84.8, in the azithromycin-treated communities vs. 83.7 cm, 95%CI 82.9-84.5, in the untreated communities; mean difference 0.31 cm, 95%CI -0.85 to 1.47, P = 0.60). No adverse events were reported. CONCLUSIONS: Periodic mass azithromycin distributions for trachoma did not demonstrate a strong impact on childhood growth. TRIAL REGISTRATION: The TANA II trial was registered on clinicaltrials.gov #NCT01202331.

Community-level chlamydial serology for assessing trachoma elimination in trachoma-endemic Niger.

BACKGROUND: Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. METHODS: A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1-5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation-follicular [TF] and trachomatous inflammation-intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. RESULTS: Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. CONCLUSION: Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. TRIAL REGISTRATION: ClinicalTrials.gov NCT00792922.

Feasibility and Acceptability of Screening for Adverse Childhood Experiences in Prenatal Care.

INTRODUCTION: Adverse childhood experiences (ACEs) are common among pregnant women and contribute to increased risk for negative perinatal outcomes, yet few clinicians screen prenatal patients for ACEs. The purpose of this study was to evaluate the feasibility and acceptability of screening for ACEs in standard prenatal care. METHODS: We evaluated a 4-month pilot (March 2016-June 2016) to screen pregnant women (at ∼14-23 weeks of gestation) for ACEs and resiliency in two Kaiser Permanente Northern California medical centers (N = 480). We examined the acceptability of the screening to patients through telephone surveys (N = 210) and to clinicians through surveys and focus groups (N = 26). RESULTS: Most eligible patients (78%) were screened. Patients who received the screening were significantly more likely to be non-Hispanic White, Asian, or of "Other" or "Unknown" race/ethnicity than African American or Hispanic race/ethnicity (p = 0.02). Among those screened, 88% completed the questionnaires; 54% reported 0 ACEs, 28% reported 1-2 ACEs, and 18% reported ≥3 ACEs. Most patients were somewhat or very comfortable completing the questionnaires (91%) and discussing ACEs with their clinician (93%), and strongly or somewhat strongly agreed that clinicians should ask their prenatal patients about ACEs (85%). Clinicians reported significant pre- to postpilot increases in comfort discussing ACEs, providing education, and offering resources (ps < 0.01). Clinicians' willingness to screen for ACEs was contingent on adequate training, streamlined workflows, inclusion of resilience screening, and availability of mental health, parenting, and social work resources. CONCLUSION: ACEs screening as part of standard prenatal care is feasible and generally acceptable to patients. Women's health clinicians are willing to screen patients for ACEs when appropriately trained and adequate behavioral health referral resources are available.

School-Based versus Community-Based Sampling for Trachoma Surveillance.

Trachoma surveillance is typically performed via random sampling of endemic districts. This strategy minimizes bias and allows examination of preschool children, but is also expensive. Surveillance for some other neglected tropical diseases is carried out in schools, which is logistically easier. In the present study, the prevalence of trachomatous inflammation-follicular (TF) from a population-based sample of children from each of 70 communities in Ethiopia was compared with the corresponding school-based estimate, which was calculated for each community by performing examinations in all primary schools in the district. The overall prevalence of TF was 39.1% (95% confidence interval [CI]: 35.0-43.1%) among children aged 1-9 years in the community-based sample and 18.8% (95% CI: 15.9-21.7%) among children in grades 1-3 of the school-based sample. School-based estimates of TF explained 35% of the variation in the community-based prevalences (P < 0.001). When TF prevalence was used as a diagnostic test for detecting a community with > 5% prevalence of ocular chlamydia, the area under the receiver operating characteristic curve was 0.73 (95% CI: 0.60-0.85) for the school-based sample and 0.71 (0.58-0.83) for the community-based sample (P = 0.76). Thus, although school-based monitoring was necessarily biased relative to population-based monitoring of 1- to 9-year olds, the two methods provided a similar amount of information about the community burden of ocular chlamydia in this trachoma-hyperendemic setting. The generalizability of these findings to areas with less prevalent trachoma is unclear.

Comparison of Mass Azithromycin Coverage Targets of Children in Niger: A Cluster-Randomized Trachoma Trial.

Repeated oral azithromycin distribution targeted only to children has proven effective in reducing the ocular Chlamydia that causes trachoma. Here, we assess whether an enhanced coverage target of at least 90% of children is superior to the World Health Organization recommendation of at least 80%. Twenty-four trachoma-endemic communities in Matamèye, Niger, were randomized to a single day of azithromycin distribution aiming for at least 80% coverage or up to 4 days of treatment and > 90% coverage of children under age 12. All distributions were biannual. Children < 5 years of age and adults > 15 years were monitored for ocular Chlamydia infection by polymerase chain reaction every 6 months for 36 months in children and at baseline and 36 months in adults. Ocular Chlamydia prevalence in children decreased from 24.9% (95% confidence interval [CI] 15.9-33.8%) to 4.4% (95% CI 0.6-8.2%, P < 0.001) at 36 months in the standard coverage arm and from 15.6% (95% CI 10.0-21.2%) to 3.3% (95% CI 1.0-5.5%; P < 0.001) in the enhanced coverage arm. Enhanced coverage reduced ocular Chlamydia prevalence in children more quickly over time compared with standard (P = 0.04). There was no difference between arms at 36 months in children (2.4% lower with enhanced coverage, 95% CI 7.7-12.5%; P = 0.60). No infection was detected in adults at 36 months. Increasing antibiotic coverage among children from 80% to 90% may yield only short term improvements for trachoma control programs. Targeting treatment to children alone may be sufficient for trachoma control in this setting.

Childhood Mortality After Mass Distribution of Azithromycin: A Secondary Analysis of the PRET Cluster-randomized Trial in Niger.

BACKGROUND: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality. METHODS: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression. RESULTS: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported. CONCLUSIONS: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Anthropometry and Malaria among Children in Niger: A Cross-Sectional Study.

The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6-60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00-1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02-1.11) for HAZ and 1.09 (95% CI: 1.01-1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria.