Marie Reilly

The Effect of Treatment of Vaginal Infections on Shedding of Human Immunodeficiency Virus Type 1

To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells, HIV-1-seropositive women were examined before and after treatment of Candida vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1 RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90 log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8; 95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating Candida and Trichomonas, respectively. These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation.

Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: A population‐based Swedish cohort study

There is accumulated evidence for genetic influences on preeclampsia. However, no study has been able to separate the effects of maternal and fetal genetic factors from environmental factors, and there are still uncertainties about the origin and magnitude of the genetic effects. We used the population‐based Swedish Birth and Multi‐Generation Registries to identify a cohort of women who gave birth from 1987 through 1997. In order to separate the genetic and environmental contributions to preeclampsia, we analyzed pregnancy outcomes from families joined by full siblings. We included information from 244,564 sibling pairs (62,236 sister pairs, 63,288 brother pairs, and 119,040 sister–brother pairs), who had 701,488 pregnancies. We found that 35% of the variance in liability of preeclampsia was attributable to maternal genetic effects, 20% to fetal genetic effects (with similar contribution of maternal and paternal genetic effects), 13% to the couple effect, less than 1% to shared sibling environment, and 32% to unmeasured factors. Among women and men without a history of preclampsia, partner change reduced the risk of preeclampsia (odds ratio, 0.6; 95 percent confidence interval, 0.4–0.9). Genetic factors account for more than half of the liability of preeclampsia, and maternal genes contribute more than fetal genes. We suggest that the couple effect is due to a genetic interaction between mother and father.

Socioeconomic determinants of infant mortality: A worldwide study of 152 low-, middle-, and high-income countries

Background: To reach the Millennium Development Goals for health, influential international bodies advocate for more resources to be directed to the health sector, in particular medical treatment. Yet, health has many determinants beyond the health sector that are less evident than proximate predictors. Aim: To assess the relative importance of major socioeconomic determinants of population health, measured as infant mortality rate (IMR), at country level. Methods: National-level data from 152 countries based on World Development Indicators 2003 were used for multivariate linear regression analyses of five socioeconomic predictors of IMR: public spending on health, GNI/capita, poverty rate, income equality (Gini index), and young female illiteracy rate. Analyses were performed on a global level and stratified for low-, middle-, and high-income countries. Results: In order of importance, GNI/capita, young female illiteracy, and income equality predicted 92% of the variation in national IMR whereas public spending on health and poverty rate were non-significant determinants when adjusted for confounding. In low-income countries, female illiteracy was more important than GNI/capita. Income equality (Gini index) was an independent predictor of IMR in middle-income countries only. In high-income countries none of these predictors was significant. Conclusions: The relative importance of major health determinants varies between income levels, thus extrapolating health policies from high- to low-income countries is problematic. Since the size, per se, of public health spending does not independently predict health outcomes, functioning health systems are necessary to make health investments efficient. Potential health gains from improved female education and economic growth should be considered in low- and middle-income countries

Duration of red blood cell storage and survival of transfused patients (CME)

BACKGROUND: Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.

Incidence and Prognosis of Synchronous and Metachronous Bilateral Breast Cancer

PURPOSE Because the incidence of breast cancer is increasing and prognosis is improving, a growing number of women are at risk of developing bilateral disease. Little is known, however, about incidence trends and prognostic features of bilateral breast cancer. PATIENTS AND METHODS Among 123,757 women with a primary breast cancer diagnosed in Sweden from 1970 to 2000, a total of 6,550 developed bilateral breast cancer. We separated synchronous (diagnosed within 3 months after a first breast cancer) and metachronous bilateral cancer, and analyzed incidence and mortality rates of breast cancer using Poisson regression models. RESULTS The incidence of synchronous breast cancer increased by age and by 40% during the 1970s, whereas the incidence of metachronous cancer decreased by age and by approximately 30% since the early 1980s, most likely due to increasing use of adjuvant therapy. Women who developed bilateral cancer within 5 years and at age younger than 50 years were 3.9 times (95% CI, 3.5 to 4.5) more likely to die as a result of breast cancer than women with unilateral cancer. Women with a bilateral cancer diagnosed more than 10 years after the first cancer had a prognosis similar to that of a unilateral breast cancer. Adjuvant chemotherapy of primary cancer is a predictor of poor survival after diagnosis of early metachronous cancers. CONCLUSION We found profound differences in the incidence trends and prognostic outlook between synchronous and metachronous bilateral breast cancer diagnosed at different ages. Adjuvant chemotherapy therapy has a dual effect on metachronous cancer: it reduces the risk, while at the same time it seems to worsen the prognosis.

Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: a comparative population-based study in Singapore and Sweden.

Breast cancer incidence in Sweden has always been approximately twice as high as in Singapore. In recent years, this difference is limited to postmenopausal women. The aim of this study was to explore the reasons behind these differences through the use of age‐period‐cohort modeling. This population‐based study included all breast cancer cases reported to the Swedish and the Singapore cancer registries from 1968 to 1997, with a total of 135,581 Swedish and 10,716 Singaporean women. Poisson regression using age‐period and age‐cohort models was used to determine the effects of age at diagnosis, calendar period and birth cohort. Incidence rate ratios were used to summarize these effects. An age‐cohort model provided the best fit to the data in both countries, indicating that changes over lifetime, rather than recent differences in medical surveillance, might account for the observed differences in these 2 populations. The changes over birth cohort were much greater among Singaporean women. The relative effect of age was very similar in the 2 countries. Analyses show that age and cohort effects may explain the differences in trends of female breast cancer incidence between Sweden and Singapore. The larger cohort effect seen in Singaporean women may be attributed to more rapid changes in reproduction and lifestyle patterns than that of Swedish women during the period studied. The incidence of breast cancer in postmenopausal women in Singapore will probably continue to rise in the coming decades to match the current Swedish rates.

Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction

Objective—Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. Approach and Results—We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P<0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Conclusions—Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.

The effect of hormonal contraception on genital tract shedding of HIV-1.

Objective: A previous cross-sectional study reported that hormonal contraception may be associated with increased infectivity in HIV-1 infected women. We conducted a prospective study to determine if cervical shedding of HIV-1 increased after initiating hormonal contraception. Design: Shedding of HIV-1 DNA (a marker of HIV-1 infected cells) and HIV-1 RNA were measured before and after initiating hormonal contraception. Methods: HIV-1 seropositive women were recruited from a Kenyan family planning clinic. At baseline, cervical secretions were collected for HIV-1 DNA and RNA assays in women initiating hormonal contraception; follow-up samples were collected a median of 64 days later. Results: One-hundred and one women chose depot medroxyprogesterone (Depo), 53 chose low-dose oral contraceptives (OC), seven high-dose OC, and 52 progesterone-only OC. At follow-up, there was a significant increase in the prevalence of cervical HIV-1 DNA detection [from 42% to 52%, odds ratio (OR), 1.62; 95% confidence interval (CI), 1.03–2.63) for all hormonal contraception combined, and a trend for an increase for each individual type. Although the prevalence of cervical HIV-1 RNA increased slightly (from 82% to 86%; OR, 1.56; 95% CI, 0.83–3.03), the concentration of cervical HIV-1 RNA did not change significantly overall (from 2.81 to 2.84 log10 copies/swab; P = 0.77) or for individual contraception types. Conclusions: A modest but significant increase in shedding of HIV-1 DNA but not of HIV-1 RNA was detected after starting hormonal contraception. Our results may have important implications regarding the infectivity of women using hormonal contraception, and highlight the need for epidemiologic studies of transmission rates from women using and not using hormonal contraception.

Maternal Effects for Preterm Birth: A Genetic Epidemiologic Study of 630,000 Families

This study was undertaken to disentangle the maternal genetic from the fetal genetic effects for preterm birth and to study the possibility of these effects being explained by known risk factors. By cross-linking of the population-based Swedish Multigeneration and Medical Birth registers, 989,027 births between 1992 and 2004 were identified. Alternating logistic regression was applied to model the familial clustering with pairwise odds ratios (PORs), and covariates were included to evaluate if the familial aggregation was explained by exposure to shared risk factors. Generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. Sisters of women who had a preterm delivery had themselves an increased odds of having a preterm delivery (POR = 1.8, 95% confidence interval: 1.5, 2.1), while there was no corresponding increase in odds in families joined by brothers (POR = 1.1, 95% confidence interval: 0.9, 1.4). Twenty-five percent of the variation in preterm birth was explained by maternal genetic factors, whereas fetal genetic factors only marginally influenced the variation in liability. The increased odds ratio between offspring of sisters was independent of maternal risk factors for preterm birth, suggesting that the relative importance of maternal effects is not explained by these well-known risk factors.

Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese populations, 1973-1997

Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of world, but rather common in Southern China and Southeast Asia. This study used IARC published datasets to explore the secular trends of incidence rates of NPC among different Chinese populations in Singapore, Hong Kong and Los Angeles, over the time period 1973–1997. We observed great disparity in the risks and time trends of NPC in those selected Chinese populations. The highest risk was in Hong Kong where the incidence rates have declined rapidly throughout the whole study period in both males and females. For Singapore Chinese, the incidence rates also dropped recently in both genders, but the low incidence rates in Los Angeles Chinese have remained essentially unchanged over time. We further assessed the contribution of period and cohort effects to the observed trends in Hong Kong and Singapore populations through age-period-cohort modeling and found that an age-cohort model provided the best fit to the data in both populations, although for Singapore females a simple age-drift model fit the data well. There was a statistically significant decrease in the drop in incidence of NPC for cohorts born around 1940 in Hong Kong and 1958 in Singapore. This indicates that environmental and lifestyle changes play an important role in the declining incidence of NPC over time.