Opportunities for Tuberculosis Diagnosis and Prevention among Persons Living with HIV: A Cross-Sectional Study of Policies and Practices at Four Large Ryan White Program-Funded HIV Clinics

Objective

We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics.

Methods

We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008–2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices.

Results

Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008–2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101–165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6–9.5), and employment (aOR = 1.9, 95% CI = 1.0–3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4–3.3), non-black race (aOR = 1.7, 95% CI = 1.3–2.5), and unemployment (aOR = 1.5, 95% CI = 1.1–2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention.

Conclusions

Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention.     

HIV Testing and Tolerance to Gender Based Violence: A Cross-Sectional Study in Zambia

This paper explores the effect of social relations and gender-based conflicts on the uptake of HIV testing in the South and Central provinces of Zambia. We conducted a community-based cross-sectional study of 1716 randomly selected individuals. Associations were examined using mixed-effect multivariable logistic regression. A total of 264 men (64%) and 268 women (56%) had never tested for HIV. The strongest determinants for not being tested were disruptive couple relationships (OR = 2.48 95% CI = 1.00–6.19); tolerance to gender-based violence (OR = 2.10 95% CI = 1.05–4.32) and fear of social rejection (OR = 1.48 95% CI = 1.23–1.80). In the Zambian context, unequal power relationships within the couple and the community seem to play a pivotal role in the decision to test which until now have been largely underestimated. Policies, programs and interventions to rapidly increase HIV testing need to urgently address gender-power inequity in relationships and prevent gender-based violence to reduce the negative impact on the lives of couples and families.     

The Continuum of Maternal Sepsis Severity: Incidence and Risk Factors in a Population-Based Cohort Study

Objective

To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.

Methods

This retrospective cohort study used linked hospital discharge and vital statistics records data for 1,622,474 live births in California during 2005–2007. Demographic and clinical factors were adjusted using multivariable logistic regression with robust standard errors.

Results

1598 mothers developed sepsis; incidence of all sepsis was 10 per 10,000 live births (95% CI = 9.4–10.3). Women had significantly increased adjusted odds (aOR) of developing sepsis if they were older (25–34 years: aOR = 1.29; ≥35 years: aOR = 1.41), had ≤high-school education (aOR = 1.63), public/no-insurance (aOR = 1.22) or a cesarean section (primary: aOR = 1.99; repeat: aOR = 1.25). 791 women progressed to severe sepsis; incidence of severe sepsis was 4.9 per 10,000 live births (95% CI = 4.5–5.2). Women had significantly increased adjusted odds of progressing to severe sepsis if they were Black (aOR = 2.09), Asian (aOR = 1.59), Hispanic (aOR = 1.42), had public/no-insurance (aOR = 1.52), delivered in hospitals with <1,000 births/year (aOR = 1.93), were primiparous (aOR = 2.03), had a multiple birth (aOR = 3.5), diabetes (aOR = 1.47), or chronic hypertension (aOR = 8.51). Preeclampsia and postpartum hemorrhage were also significantly associated with progression to severe sepsis (aOR = 3.72; aOR = 4.18). For every cumulative factor, risk of uncomplicated sepsis increased by 25% (95% CI = 17.4–32.3) and risk of progression to severe sepsis/septic shock increased by 57% (95% CI = 40.8–74.4).

Conclusions

The rate of severe sepsis was approximately twice the 1991–2003 national estimate. Risk factors identified are relevant to obstetric practice given their cumulative risk effect and the apparent increase in severe sepsis incidence.     

Utilization of HIV and Tuberculosis Services by Health Care Workers in Uganda: Implications for Occupational Health Policies and Implementation

Background

Access to HIV testing and subsequent care among health care workers (HCWs) form a critical component of TB infection control measures for HCWs. Challenges to and gaps in access to HIV services among HCWs may thus compromise TB infection control. This study assessed HCWs HIV and TB screening uptake and explored their preferences for provision of HIV and TB care.

Methods

A cross-sectional mixed-methods study involving 499 HCWs and 8 focus group discussions was conducted in Mukono and Wakiso districts in Uganda between October 2010 and February 2011.

Results

Overall, 5% of the HCWs reported a history of TB in the past five years. None reported routine screening for TB disease or infection, although 89% were willing to participate in a TB screening program, 77% at the workplace. By contrast, 95% had previously tested for HIV; 34% outside their workplace, and 27% self-tested. Nearly half (45%) would prefer to receive HIV care outside their workplace. Hypothetical willingness to disclose HIV positive status to supervisors was moderate (63%) compared to willingness to disclose to sexual partners (94%). Older workers were more willing to disclose to a supervisor (adjusted prevalence ratio [APR] = 1.51, CI = 1.16–1.95). Being female (APR = 0.78, CI = 0.68–0.91), and working in the private sector (APR = 0.81, CI = 0.65–1.00) were independent predictors of unwillingness to disclose a positive HIV status to a supervisor. HCWs preferred having integrated occupational services, versus stand-alone HIV care.

Conclusions

Discomfort with disclosure of HIV status to supervisors suggests that universal TB infection control measures that benefit all HCWs are more feasible than distinctions by HIVstatus, particularly for women, private sector, and younger HCWs. However, interventions to reduce stigma and ensuring confidentiality are also essential to ensure uptake of comprehensive HIV care including Isoniazid Preventive Therapy among HCWs.     

Gender,Migration and HIV in Rural KwaZulu-Natal,South Africa

Objectives

Research on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women''s migration contributes to their high infection risk.

Design

Data on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15–49 and men aged 15–54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003–04.

Methods

Logistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.

Results

Relative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49–1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07–3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23–1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02–1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12–1.32]) and 46% for female migrants (aOR = 1.46 [1.25–1.69]).

Conclusions

Higher risk sexual behavior in the context of migration increased women''s likelihood of HIV infection.     

Ethnic Variations in Severe Maternal Morbidity in the UK– A Case Control Study

Background

Previous studies showed a higher risk of maternal morbidity amongst black and other minority ethnic (BME) groups, but were unable to investigate whether this excess risk was concentrated within specific BME groups in the UK. Our aim was to analyse the specific risks and to investigate reasons for any disparity.

Methods

Unmatched case-control analysis using data from the United Kingdom Obstetric Surveillance System (UKOSS), February 2005-January 2013. Cases were 1,753 women who experienced severe morbidity during the peripartum period. Controls were 3,310 women who delivered immediately before the cases in the same hospital. Multivariable logistic regression modelling was used to adjust for known confounders and to understand their effects.

Results

Compared with white European women, the odds of severe maternal morbidity were 83% higher among black African women (adjusted odds ratio (aOR) = 1.83; 95% Confidence Interval (CI) = 1.39–2.40), 80% higher among black Caribbean (aOR = 1.80; 95% CI = 1.14–2.82), 74% higher in Bangladeshi (aOR = 1.74; 95% CI = 1.05–2.88), 56% higher in other non-whites (non-Asian) (aOR = 1.56; 95% CI = 1.05–2.33) and 43% higher among Pakistani women (aOR = 1.43; 95% CI = 1.07–1.92). There was no evidence of substantial confounding. Anaemia in current pregnancy, previous pregnancy problems, inadequate utilisation of antenatal care, pre-existing medical conditions, parity>3, and being younger and older were independent risk factors but, the odds of severe maternal morbidity did not differ by socioeconomic status, between smokers and non-smokers or by BMI.

Discussion

This national study demonstrates an increased risk of severe maternal morbidity among women of ethnic minority backgrounds which could not be explained by known risk factors for severe maternal morbidity.     

A Prospective Controlled Trial of Routine Opt-Out HIV Testing in a Men's Jail

Background

Approximately 10 million Americans enter jails annually. The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these settings. The logistics for performing routine opt-out HIV testing within jails, however, remain controversial. The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy.

Methods

This prospective, controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban men''s jail in New Haven, Connecticut. 298 sequential entrants to the men''s jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 103), early (next day, n = 98), or delayed (7 days, n = 97). The primary outcome was the proportion of men in each group consenting to testing.

Results

Routine opt-out HIV testing was significantly higher for the early (53%: AOR = 2.6; 95% CI = 1.5 to 4.7) and immediate (45%: AOR = 2.3; 95% CI = 1.3 to 4.0) testing groups compared to the delayed (33%) testing group. The immediate and early testing groups, however, did not significantly differ (p = 0.67). In multivariate analyses, factors significantly associated with routine opt-out HIV testing were assignment to the ‘early’ testing group (p = 0.0003) and low (bond ≥$5,000, immigration or federal charges or pre-sentencing >30 days) likelihood of early release (p = 0.04). Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive.

Conclusions

In this men''s jail where attrition was high, routine opt-out HIV testing was not only feasible, but resulted in the highest rates of HIV testing when performed within 24 hours of incarceration.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00624247","term_id":"NCT00624247"}}NCT00624247     

Understanding Providers’ Offering and Patients’ Acceptance of HIV Screening in Emergency Departments: A Multilevel Analysis. ANRS 95008, Paris,France

Objective

We assessed the EDs’ characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France’s new HIV cases are diagnosed annually.

Methods

EDs nurses offered testing to all patients 18–64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS’ characteristics collected included structural characteristics (location, type, size), daily workload (patients’ number and severity, length of stay in hours), staff’s participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling.

Results

Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773–0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581–0.667) and decreased over time (OR = 0.978, 95% CI = 0.975–0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623–0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142–2.038).The EDs’ characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate.

Conclusion

Our findings suggest the need for taking into account EDs’ characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources’ utilization such as HIV targeted screening in the EDs might be privileged.     

Beneficial Effect of Isoniazid Preventive Therapy and Antiretroviral Therapy on the Incidence of Tuberculosis in People Living with HIV in Ethiopia

Background

IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.

Objectives

To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.

Methods

A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.

Results

Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.

Conclusions

IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.     

Global Burden of HIV among Men Who Engage in Transactional Sex: A Systematic Review and Meta-Analysis

Background

Men who engage in transactional sex, the exchange of sex for money, goods, or other items of value, are thought to be at increased risk of HIV, but there have been no systematic attempts to characterize HIV burden in this population. We undertook a systematic review and meta-analysis to quantify the burden in this population compared with that of men in the general population to better inform future HIV prevention efforts.

Methods

We searched seven electronic databases, national surveillance reports, and conference abstracts for studies of men who engage in transactional sex published between 2004–2013. Random effects meta-analysis was used to determine pooled HIV prevalence and prevalence ratios (PR) for the difference in HIV prevalence among men who engage in transactional sex as compared to general population men.

Findings

Of 66 studies included representing 31,924 men who had engaged in transactional sex in 28 countries, pooled biological assay-confirmed HIV prevalence was 10.5% (95% CI = 9.4 to 11.5%). The highest pooled HIV prevalence was in Sub-Saharan Africa (31.5%, 95% CI = 21.6 to 41.5%), followed by Latin America (19.3%, 95% CI = 15.5 to 23.1%), North America (16.6%, 95% CI = 3.7 to 29.5%), and Europe (12.2%, 95% CI = 6.0 to 17.2%). Men who engaged in transactional sex had an elevated burden of HIV compared to the general male population (PR = 20.7, 95% CI = 16.8 to 25.5).

Conclusions

The global burden of HIV is disproportionately high among men who engage in transactional sex compared with the general male population. There is an urgent need to include this population in systematic surveillance as well as to scale-up access to quality HIV prevention programs.     

Lack of an Association between CYP11B2 C-344T Gene Polymorphism and Ischemic Stroke: A Meta-Analysis of 7,710 Subjects

Background

The association between aldosterone synthase (CYP11B2) C-344T gene polymorphism and ischemic stroke remains controversial and ambiguous. To better explain the association between CYP11B2 polymorphism and ischemic stroke risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of Medline, Embase, Web of Science, CNKI and CBM databases, we identified and abstracted outcome data from all articles to evaluate the association between CYP11B2 polymorphism and ischemic stroke. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed in all genetic models. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg''s funnel plot and Egger''s regression test.

Results

A total of 12 studies including 3,620 ischemic stroke cases and 4,090 controls were identified. There was no statistical evidence of association between CYP11B2 C-344T polymorphism and ischemic stroke in all genetic models (allelic model: OR = 1.19, 95% CI = 0.95–1.49; additive model: OR = 1.43, 95% CI = 0.91–2.27; dominant model: OR = 1.30, 95% CI = 0.89–1.89; and recessive model: OR = 1.24, 95% CI = 0.96–1.60). On subgroup analysis by ethnicity, similarly results were found in both Asians and non-Asians. For Asians, the combined ORs and 95% CIs were (allelic model: OR = 1.07, 95% CI = 0.87–1.32; additive model: OR = 1.15, 95% CI = 0.77–1.71; dominant model: OR = 1.13, 95% CI = 0.92–1.38; and recessive model: OR = 1.09, 95% CI = 0.84–1.40). For none-Asians, the combined ORs and 95% CIs were (allelic model: OR = 1.58, 95% CI = 0.90–2.76; additive model: OR = 2.37, 95% CI = 0.79–7.05; dominant model: OR = 1.79, 95% CI = 0.77–4.19; and recessive model: OR = 1.80, 95% CI = 0.96–3.36).

Conclusion

The present meta-analysis suggested that CYP11B2 C-344T polymorphism was unlikely contribute to ischemic stroke susceptibility.     

HIV Prevalence and Associated Factors among Foreign Brides from Burma in Yunnan Province,China

Background

Many Burmese women have migrated to Yunnan Province and married local residents over the past few decades; however, limited information is available on their HIV prevalence and ability to cope with HIV. This study aims to assess the prevalence of HIV and knowledge related to AIDS, as well as to discover possible risk factors of HIV infection among foreign brides from Burma in Yunnan Province.

Methods

A cross-sectional study was taken of all Burmese cross-border wives residing in Tengchong County using standardized questionnaires. HIV and syphilis testing was conducted at the same time.

Results

Among 600 Burmese brides, the HIV prevalence was 2.17%. Those aged 21–30, those with higher education levels and those who had resided in China less than one year had higher infection rates. The AIDS awareness rate of 39.50% was very low in this population. Only 28.67% of participants had ever been involved in prevention services. The rate of condom use was low. Classification by age, education, occupation, prior HIV testing and prior use of HIV prevention services showed a statistically significant association with mean knowledge score (p<0.05). Residing in China less than one year (OR = 3.86, 95% CI = 1.09–13.70) and having casual sex in the last year (OR = 10.49, 95% CI = 1.20–91.59) were risk factors for HIV infection.

Conclusions

Burmese brides in China are not only exposed to a high risk of HIV infection, but also seriously lack response capabilities. Educational interventions and control efforts are practical approaches that need to be strengthened among this population.     

Men Who Have Sex with Men (MSM) and Factors Associated with Not Using a Condom at Last Sexual Intercourse with a Man and with a Woman in Senegal

Background

Men who have sex with other men (MSM) are a vulnerable population in Africa that has been insufficiently explored. Given the high rate of bisexuality among MSM (73% in the past year), it is important to understand their risk-taking behaviors regarding both men and women.

Methodology/Principal Findings

A socio-behavioral survey was carried out in 2007 among 501 MSM recruited using the snowball sampling method. We explore in this article why a condom was not used during last sexual intercourse with a man and with a woman, taking into account the respondent''s characteristics, type of relationship and the context of the sexual act. In the survey, 489 men reported that they had had sexual intercourse at least once with another man during the previous year, and 358 with a man and with a woman. The main risk factors for not using a condom at last sexual intercourse with another man were having sex in a public place (aOR = 6.26 [95%CI: 2.71–14.46]), non-participation in an MSM prevention program (aOR = 3.47 [95%CI: 2.12–5.69]), a 19 years old or younger partner (aOR = 2.6 [95%CI: 1.23–4.53]), being 24 years or younger (aOR = 2.07 [95%CI: 1.20–3.58]) or being 35 years or over (aOR = 3.08 [95%CI:1.11–8.53]) and being unemployed (aOR = 0.36 [95%CI: 0.10–1.25]). The last sexual intercourse with the respondent''s wife was hardly ever protected (2%). With women, the other factors were a 15 years or younger partner (aOR = 6.45 [95%CI: 2.56–16.28]), being educated (primary: aOR = 0.45 [95%CI: 0.21–0.95], secondary or higher: aOR = 0.26 [95%CI: 0.11–0.62]), being a student (aOR = 2.20 [95%CI: 1.07–4.54]) or unemployed (aOR = 3.72 [95%CI: 1.31–10.61]) and having participated in a MSM prevention program (aOR = 0.57 [95%CI: 0.34–0.93]).

Conclusion

Having participated in a prevention program specifically targeting MSM constitutes a major prevention factor. However, these programs targeting MSM must address their heterosexual practices and the specific risks involved.     

Association of Germline Variation in CCNE1 and CDK2 with Breast Cancer Risk,Progression and Survival among Chinese Han Women

Background

Somatic alterations of cyclin-dependent kinase 2 (CDK2)-cyclin E complex have been shown to contribute to breast cancer (BC) development and progression. This study aimed to explore the effects of single nucleotide polymorphisms (SNPs) in CDK2 and CCNE1 (a gene encoding G1/S specific cyclin E1 protein, formerly called cyclin E) on BC risk, progression and survival in a Chinese Han population.

Methodology/Principal Findings

We herein genotyped 6 haplotype-tagging SNPs (htSNPs) of CCNE1 and 2 htSNPs of CDK2 in 1207 BC cases and 1207 age-matched controls among Chinese Han women, and then reconstructed haplotype blocks according to our genotyping data and linkage disequilibrium status of these htSNPs. For CCNE1, the minor allele homozygotes of three htSNPs were associated with BC risk (rs3218035: adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI] = 1.69–6.67; rs3218038: aOR = 1.81, 95% CI = 1.22–2.70; rs3218042: aOR = 2.64, 95% CI = 1.31–5.34), and these three loci showed a dose-dependent manner in increasing BC risk (P _trend = 0.0001). Moreover, the 5-SNP haplotype CCGTC, which carried none of minor alleles of the 3 at-risk SNPs, was associated with a favorable event-free survival (hazard ratio [HR] = 0.53, 95% CI = 0.32–0.90). Stratified analysis suggested that the minor-allele homozygote carriers of rs3218038 had a worse event-free survival among patients with aggressive tumours (in tumour size>2 cm group: HR = 2.06, 95% CI = 1.06–3.99; in positive lymph node metastasis group: HR = 2.41, 95% CI = 1.15–5.03; in stage II–IV group: HR = 2.03, 95% CI = 1.09–3.79). For CDK2, no significant association was found.

Conclusions/Significance

This study indicates that genetic variants in CCNE1 may contribute to BC risk and survival in Chinese Han population. They may become molecular markers for individual evaluation of BC susceptibility and prognosis. Nevertheless, further validation studies are needed.     

Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

Background

In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.

Methods and Findings

A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%).

Conclusions

For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors'' Summary     

Routine HIV Testing in Adolescents and Young Adults Presenting to an Outpatient Clinic in Durban,South Africa

Objectives

Although youth (12–24 years) in Sub-Saharan Africa have a high HIV risk, many have poor access to HIV testing services and are unaware of their status. Our objective was to evaluate the proportion of adolescents (12–17 years) and young adults (18–24 years) who underwent HIV testing and the prevalence among those tested in an urban adult outpatient clinic with a routine HIV testing program in Durban, South Africa.

Design

We conducted a retrospective cross-sectional analysis of adolescent and young adult outpatient records between February 2008 and December 2009.

Methods

We determined the number of unique outpatient visitors, HIV tests, and positive rapid tests among those tested.

Results

During the study period, 956 adolescents registered in the outpatient clinic, of which 527 (55%) were female. Among adolescents, 260/527 (49%, 95% CI 45–54%) females underwent HIV testing compared to 129/429 (30%, 95% CI 26–35%) males (p<0.01). The HIV prevalence among the 389 (41%, 95% CI 38–44%) adolescents who underwent testing was 16% (95% CI 13–20%) and did not vary by gender (p = 0.99). During this period, there were 2,351 young adult registrations, and of these 1,492 (63%) were female. The proportion consenting for HIV testing was similar among females 980/1,492 (66%, 95% CI 63–68%) and males 543/859 (63%, 95% CI 60–66%, p = 0.25). Among the 1,523 (65%, 95% CI 63–67%) young adults who underwent testing, the HIV prevalence was 22% (95% CI 19–24%) in females versus 14% in males (95% CI 11–17%, p<0.01).

Conclusions

Although the HIV prevalence is high among youth participating in an adult outpatient clinic routine HIV program, the uptake of testing is low, especially among 12–17 year old males. There is an urgent need to offer targeted, age-appropriate routine HIV testing to youth presenting to outpatient clinics in epidemic settings.     

High Rates of HIV Seroconversion in Pregnant Women and Low Reported Levels of HIV Testing among Male Partners in Southern Mozambique: Results from a Mixed Methods Study

Introduction

Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner''s HIV testing.

Methods

Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2–3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94) with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing.

Results

HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33–7.16). Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04–13.78, p = 0.04) and living in Maputo Province (RR 4.35, 95%CI: 0.97–19.45, p = 0.05). Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner), 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator.

Conclusions

HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners'' HIV status remains low. Knowledge of both partners'' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS.     

Association between the XRCC1 Polymorphisms and Thyroid Cancer Risk: A Meta-Analysis from Case-Control Studies

Background

The previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies).

Methodology/Principal Findings

PubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77–1.15; dominant model: OR = 0.89, 95% CI = 0.75–1.05; homozygote model: OR = 0.92, 95% CI = 0.69–1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80–1.03; additive model: OR = 0.93, 95% CI = 0.81–1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62–3.23; dominant model: OR = 1.01, 95% CI = 0.77–1.34; homozygote model: OR = 1.42, 95% CI = 0.55–3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85–1.26; additive model: OR = 1.08, 95% CI = 0.81–1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56–2.10; dominant model: OR = 1.01, 95% CI = 0.84–1.22; homozygote model: OR = 1.00, 95% CI = 0.51–1.96; Heterozygote model: OR = 1.04, 95% CI = 0.75–1.42; additive model: OR = 1.03, 95% CI = 0.86–1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms.

Conclusions/Significance

In summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.     

Preparing for PrEP: Perceptions and Readiness of Canadian Physicians for the Implementation of HIV Pre-Exposure Prophylaxis

Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, but concerns persist around its use. Little is known about Canadian physicians'' knowledge of and willingness to prescribe PrEP. We disseminated an online survey to Canadian family, infectious disease, internal medicine, and public health physicians between September 2012–June 2013 to determine willingness to prescribe PrEP. Criteria for analysis were met by 86 surveys. 45.9% of participants felt “very familiar” with PrEP, 49.4% felt that PrEP should be approved by Health Canada, and 45.4% of respondents were willing to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95% confidence interval, CI = 1.6–10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3–19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5–10.5) were positively associated with willingness to prescribe PrEP on univariable analysis. The latter two were the strongest predictors on multivariate analysis. Participants cited cost and efficacy as major concerns. 75.3% did not feel that information had been adequately disseminated among physicians. In summary, Canadian physicians demonstrate varying levels of support for PrEP and express concerns about its implementation. Further research on real-world effectiveness, continuing medical education, and clinical support is needed to prepare physicians for this prevention strategy.     

Factors Impacting Early Mortality in Tuberculosis/HIV Patients: Differences between Subjects Na?ve to and Previously Started on HAART

Background

Mortality among patients with tuberculosis (TB)/HIV is highest during the first few months of antituberculous therapy. The objective of this study was to assess the factors associated with early mortality among TB/HIV patients and whether these factors are similar for HAART naïve and those with prior HAART initiation.

Methods

Prospective cohort study including HIV patients with tuberculosis confirmed by culture, cared for at a referral center in Rio de Janeiro, Brazil. Multivariable Cox analysis was used to assess predictors of mortality within 3 months of antituberculous therapy.

Results

Among 227 patients included, 90 (40%) started HAART before TB diagnosis. The median time to TB diagnosis after ARV initiation was 5.9 months (interquartile range [IQR] 3.0–8.9 months). Fourteen patients (6%) died within the first 3 months. Mortality was not different between patients previously started on HAART and those who were naïve to it. In the overall adjusted analysis, HAART use during TB treatment (hazard ratio [HR] = 0.21, 95% confidential interval [CI] = 0.06–0.72) and CD4 lymphocyte count >100 cells/mm3 (HR = 0.21, 95% CI = 0.04–0.99) were associated with lower mortality, while subjects with unknown baseline CD4 lymphocyte count (HR = 9.39, 95% CI = 2.56–34.5) had higher mortality. In subgroup analysis, among HAART naïve subjects, disseminated TB (HR = 5.32, 95% CI = 1.09–25.8) and unknown baseline CD4 lymphocyte count (HR = 13.2, 95% CI = 2.71–64.5) were associated with significantly higher mortality, while HAART (HR = 0.14, 95% CI = 0.03–0.69) predicted a better outcome. Among subjects previously started on HAART, mortality was significantly associated with duration of TB symptoms >120 days (HR = 6.15, 95% CI = 1.15–32.9).

Conclusions

Predictors of early mortality among TB/HIV patients may vary according to the timing of HAART initiation. Among HAART naïve patients, mortality was influenced by baseline clinical severity, HAART use and, possibly, the quality of care preceding TB diagnosis. For patients with prior HAART initiation, longer delays in TB diagnosis predicted a significantly higher mortality.