Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of <it>Candida </it>in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth.</p> <p>Methods</p> <p>We used a prospective, randomized, open-label, blinded-endpoint (PROBE) study design. Pregnant women presenting at <20 weeks gestation with singleton pregnancies self-collected a vaginal swab. Those who were asymptomatic and culture positive for <it>Candida </it>were randomized to 6-days of clotrimazole vaginal pessaries (100mg) or usual care (screening result is not revealed, no treatment). The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth <37 weeks gestation was also assessed.</p> <p>Results</p> <p>Of 779 women approached, 500 (64%) participated in candidiasis screening, and 98 (19.6%) had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03.</p> <p>Conclusions</p> <p>A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609001052224.aspx">ACTRN12609001052224</a></p

An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

<p>Abstract</p> <p>Background</p> <p>Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk.</p> <p>Methods</p> <p>We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System.</p> <p>Results</p> <p>Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; <it>P </it>= .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; <it>P </it>= .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy.</p> <p>Conclusions</p> <p>Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.</p

Protocol for a randomised controlled trial of treatment of asymptomatic candidiasis for the prevention of preterm birth [ACTRN12610000607077]

<p>Abstract</p> <p>Background</p> <p>Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple <it>Candida </it>testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases.</p> <p>Methods/Design</p> <p>Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care <20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth <37 weeks gestation.</p> <p>The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases.</p> <p>A sample size of 3,208 women with <it>Candida </it>colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat.</p> <p>Discussion</p> <p>For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with <it>Candida </it>may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design.</p> <p>This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12610000607077.aspx">ACTRN12610000607077</a></p

The Role of Repetitive Negative Thoughts in the Vulnerability for Emotional Problems in Non-Clinical Children

The current study examined the role of repetitive negative thoughts in the vulnerability for emotional problems in non-clinical children aged 8–13 years (N = 158). Children completed self-report questionnaires for assessing (1) neuroticism and behavioral inhibition as indicators of general vulnerability (2) worry and rumination which are two important manifestations of repetitive negative thoughts, and (3) emotional problems (i.e., anxiety, depression, and sleep difficulties). Results demonstrated that there were positive correlations between measures of general vulnerability, repetitive negative thoughts, and emotional problems. Further, support was found for a model in which worry and rumination acted as partial mediators in the relation between neuroticism and symptoms of anxiety and depression. In the case of sleep difficulties, no evidence was obtained for such a mediation model. In fact, data suggested that sleeping difficulties are better conceived as an epiphenomenon of high symptom levels of anxiety and depression or as a risk factor for the development of other types of psychopathology. Finally, besides neuroticism, the temperamental trait of behavioral inhibition appeared to play a unique direct role in the model predicting anxiety symptoms but not in the models predicting depressive symptoms or sleep difficulties. To conclude, the current findings seem to indicate that worry and rumination contribute to children’s vulnerability for anxiety and depression

Acupuncture and chiropractic care for chronic pain in an integrated health plan: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Substantial recent research examines the efficacy of many types of complementary and alternative (CAM) therapies. However, outcomes associated with the "real-world" use of CAM has been largely overlooked, despite calls for CAM therapies to be studied in the manner in which they are practiced. Americans seek CAM treatments far more often for chronic musculoskeletal pain (CMP) than for any other condition. Among CAM treatments for CMP, acupuncture and chiropractic (A/C) care are among those with the highest acceptance by physician groups and the best evidence to support their use. Further, recent alarming increases in delivery of opioid treatment and surgical interventions for chronic pain--despite their high costs, potential adverse effects, and modest efficacy--suggests the need to evaluate real world outcomes associated with promising non-pharmacological/non-surgical CAM treatments for CMP, which are often well accepted by patients and increasingly used in the community.</p> <p>Methods/Design</p> <p>This multi-phase, mixed methods study will: (1) conduct a retrospective study using information from electronic medical records (EMRs) of a large HMO to identify unique clusters of patients with CMP (e.g., those with differing demographics, histories of pain condition, use of allopathic and CAM health services, and comorbidity profiles) that may be associated with different propensities for A/C utilization and/or differential outcomes associated with such care; (2) use qualitative interviews to explore allopathic providers' recommendations for A/C and patients' decisions to pursue and retain CAM care; and (3) prospectively evaluate health services/costs and broader clinical and functional outcomes associated with the receipt of A/C relative to carefully matched comparison participants receiving traditional CMP services. Sensitivity analyses will compare methods relying solely on EMR-derived data versus analyses supplementing EMR data with conventionally collected patient and clinician data.</p> <p>Discussion</p> <p>Successful completion of these aggregate aims will provide an evaluation of outcomes associated with the real-world use of A/C services. The trio of retrospective, qualitative, and prospective study will also provide a clearer understanding of the decision-making processes behind the use of A/C for CMP and a transportable methodology that can be applied to other health care settings, CAM treatments, and clinical populations.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01345409">NCT01345409</a></p

The Specification and Global Reprogramming of Histone Epigenetic Marks during Gamete Formation and Early Embryo Development in C. elegans

In addition to the DNA contributed by sperm and oocytes, embryos receive parent-specific epigenetic information that can include histone variants, histone post-translational modifications (PTMs), and DNA methylation. However, a global view of how such marks are erased or retained during gamete formation and reprogrammed after fertilization is lacking. To focus on features conveyed by histones, we conducted a large-scale proteomic identification of histone variants and PTMs in sperm and mixed-stage embryo chromatin from C. elegans, a species that lacks conserved DNA methylation pathways. The fate of these histone marks was then tracked using immunostaining. Proteomic analysis found that sperm harbor ?2.4 fold lower levels of histone PTMs than embryos and revealed differences in classes of PTMs between sperm and embryos. Sperm chromatin repackaging involves the incorporation of the sperm-specific histone H2A variant HTAS-1, a widespread erasure of histone acetylation, and the retention of histone methylation at sites that mark the transcriptional history of chromatin domains during spermatogenesis. After fertilization, we show HTAS-1 and 6 histone PTM marks distinguish sperm and oocyte chromatin in the new embryo and characterize distinct paternal and maternal histone remodeling events during the oocyte-to-embryo transition. These include the exchange of histone H2A that is marked by ubiquitination, retention of HTAS-1, removal of the H2A variant HTZ-1, and differential reprogramming of histone PTMs. This work identifies novel and conserved features of paternal chromatin that are specified during spermatogenesis and processed in the embryo. Furthermore, our results show that different species, even those with diverged DNA packaging and imprinting strategies, use conserved histone modification and removal mechanisms to reprogram epigenetic information