Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
Abstract Background We evaluated the overall and site-specific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the United States Immune Deficiency Network ...(USIDNET) registry compared with age-adjusted cancer incidence in the Surveillance, Epidemiology and End Results Program (SEER) database. We hypothesized that subjects with PIDD would have an increased incidence of cancer due to impaired immune function. Methods Overall and site-specific cancer incidence rates were evaluated in subjects with PIDD (n = 3,658) enrolled in the USIDNET registry from 2003-2015, and compared with age-adjusted incidence rates in the SEER database. Results We observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared to the age-adjusted SEER population (p<0.001). Men with PIDD had a 1.91-fold excess relative risk of cancer compared to the age-adjusted male population (p<0.001), while women with PIDD had similar overall cancer rates compared to the age-adjusted female population. Of the four most common malignancies in men and women in SEER (lung, colon, breast, and prostate cancers), we found no significant increase in these diagnoses in subjects with PIDD. Significant increases in lymphoma in both men (10-fold increase, p<0.001) and women (8.34-fold increase, p<0.001) with PIDD were observed. Conclusions Excess incidence of cancer occurred in subjects with PIDD. An excess of lymphoma in specific PIDD populations principally drove this increased incidence, while no increased risk of the most common solid tumor malignancies was observed. These data point to a restricted role of the immune system in protecting from specific cancers.
Summary Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of 15 years, more than 90% of them in resource-limited countries. Here, we ...review the key policy issues for the delivery of better care, research, and education of professionals and patients. We present a key list of time-limited proposals focusing on change to health systems and research and development. These include sector and system reforms to make care affordable to all, policies to promote growth of civil society around both cancer and Millennium Development Goals, major improvements to public health services (particularly the introduction of national cancer plans), improved career development, and increased remuneration of specialist health-care workers and government support for childhood cancer registries. Research and development proposals focus on sustainable funding, the establishment of more research networks, and clinical research specifically targeted at the needs of low-income and middle-income countries. Finally, we present proposals to address the need for clinical trial innovation, the complex dichotomy of regulations, and the threats to the availability of data for childhood cancers.
Objective The objective of the study was to determine whether the administration of cefazolin prior to skin incision was superior to administration at the time of umbilical cord clamping for the ...prevention of postcesarean infectious morbidity. Study Design This was a prospective, randomized, double-blind, placebo-controlled trial. Study subjects received cefazolin 15-60 minutes prior to incision and controls received cefazolin at the time of cord clamping. The occurrence of endomyometritis, wound infection, total infectious morbidity, and neonatal complications were compared. Results There were 357 subjects enrolled. No demographic differences were observed between groups. There were decreased total infectious morbidity in the study group (relative risk RR = 0.4, 95% confidence interval CI 0.18 to 0.87), decreased endometritis (RR = 0.2, 95% CI 0.15 to 0.94). No increase in neonatal sepsis ( P = .99), sepsis workups ( P = .96), or length of stay ( P = .17) was observed. Conclusion Administration of prophylactic cefazolin prior to skin incision resulted in a decrease in both endomyometritis and total postcesarean infectious morbidity, compared with administration at the time of cord clamping. This dosing did not result in increased neonatal septic workups or complications.
Antibiotic prophylaxis in obstetrics Sullivan, Scott A., MD; Soper, David, MD
American journal of obstetrics and gynecology,
05/2015, Volume:
212, Issue:
5
Journal Article
Background:. Analyzing outcomes and the minimal clinically important difference (MCID) after anterior cruciate ligament reconstruction (ACLR) is of increased interest in the orthopaedic literature. ...The purposes of this study were to report outcomes after ACLR at medium to long-term follow-up, identify the threshold preoperative outcome values that would be predictive of achieving the MCID postoperatively, and analyze outcome maintenance at medium to long-term follow-up after ACLR. Methods:. Active athletes who underwent ACLR were identified in an institutional ACL registry. Patient-reported outcome measures (PROMs) were administered preoperatively and at the 2-year and >5-year postoperative follow-up; measures included the International Knee Documentation Committee (IKDC) form, the 12-item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS), and Lysholm scale. We calculated the MCID from baseline to each of the 2 follow-up periods (2-year and mean 7.7-year). Logistic regression was performed to investigate factors associated with achievement of the MCID. Results:. A total of 142 patients (mean follow-up, 7.7 years range, 6.6 to 9.1 years) underwent ACLR. The mean age and body mass index at the time of surgery were 27.2 ± 13.0 years and 23.2 ± 3.0 kg/m2, respectively. Final postoperative outcome scores improved significantly from baseline for the IKDC (50.9 ± 14.7 to 87.9 ± 11.2), SF-12 PCS (41.6 ± 8.9 to 55.6 ± 3.2), and Lysholm scale (62.2 ± 17.6 to 90.5 ± 10.3) (p < 0.0001), while the SF-12 MCS did not improve significantly (54.2 ± 8.0 to 54.4 ± 6.0) (p = 0.763). Between 2- and >5-year follow-up, the SF-12 PCS showed significant improvement (54.6 ± 4.5 to 55.6 ± 3.2; p = 0.036), while no change was noted in the IKDC (87.6 ± 11.1 to 87.9 ± 11.2), SF-12 MCS (55.5 ± 5.3 to 54.4 ± 6.0), and Lysholm scale (89.8 ± 10.6 to 90.5 ± 10.3) (p ≥ 0.09). At the time of final follow-up, the MCID was achieved by 94.7% of patients for the IKDC, 80.8% for the Lysholm, 79.0% for the SF-12 PCS, and 28.2% for the SF-12 MCS. At 2-year follow-up, 95.3% of patients were either “very” or “somewhat” satisfied with their surgery, compared with 88.6% at the time of final follow-up. Conclusions:. We found a high level of maintained function following ACLR. The IKDC, SF-12 PCS, and Lysholm scores improved significantly after ACLR at the time of final follow-up and were not significantly different between follow-up periods. Approximately 95% and 89% of patients reported being satisfied with the outcome of surgery at the 2-year and final follow-up, respectively. Level of Evidence:. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Endocrine emergencies Sullivan, Scott A; Goodier, Christopher
Obstetrics and gynecology clinics of North America,
03/2013, Volume:
40, Issue:
1
Journal Article
Peer reviewed
Several potentially fatal endocrine emergencies in relation to obstetrics and gynecology are discussed in the article. Rates of case fatality vary in different series, but range from 10% to 30%. ...Rapid recognition, prompt supportive care, and intervention likely maximize maternal and fetal outcomes.
Objective The objective of the study was to improve the distribution of preterm deliveries in a Medicaid population through a regional perinatal risk assessment and case management initiative. Study ...Design An innovative public/private partnership was initiated in the 8 county Lowcountry (LC) perinatal region to reduce preterm birth (PTB) among Medicaid recipient women. Eligible women were identified and underwent telephonic risk assessment, education, and access to a 24 hours, 7 days per week perinatal hotline. Women with predetermined risk factors for PTB were offered patient-centered case management. Medicaid claims and birth certificate data were used to compare obstetric outcomes for 2006 (intervention) and 2004 (control) in both the Lowcountry (LC; program) and Midlands (ML; nonprogram) perinatal regions. Results There were 6356 Medicaid deliveries in the LC in 2006. Of these, 2111 were referred for telephonic risk assessment; 317 had identifiable PTB risk factors and consented to case management. Compared with 2004, there was a significant improvement in the distribution of preterm birth ( P = .05) in the LC region, primarily confined to deliveries less than 28 weeks (1.6% vs 1.1%; P = .029, relative risk RR 0.75, 95% confidence interval CI, 0.51-0.96). There were also reductions in the frequency (6.7% vs 5.8%; RR 0.86, 95% CI, 0.75-0.98; P = .04) and mean duration (25.0 vs 20.6 days; 95% CI, 1.03-7.77; P = .01) of neonatal intensive care unit (NICU) admissions. No changes were identified in the ML region. Conclusion A regional initiative of telephonic risk assessment and case management of Medicaid recipient women significantly reduced deliveries less than 28 weeks and NICU care.
Purpose We examined symptom variability in men and women with urological chronic pelvic pain syndrome. We describe symptom fluctuations as related to early symptom regression and its effect on ...estimated 1-year symptom change. We also describe a method to quantify patient specific symptom variability. Materials and Methods Symptoms were assessed biweekly in 424 subjects with urological chronic pelvic pain syndrome during 1 year. To evaluate the impact of early symptom regression subjects were classified as improved, no change or worse according to the rate of change using 1) all data, 2) excluding week 0 and 3) excluding weeks 0 and 2. Patient specific, time varying variability was calculated at each interval using a sliding window approach. Patients were classified as high, medium or low variability at each time and ultimately as high or low variability overall based on the variability for the majority of contacts. Results Prior to excluding early weeks to adjust for early symptom regression 25% to 38% and 5% to 6% of patients were classified as improved and worse, respectively. After adjustment the percent of patients who were improved or worse ranged from 15% to 25% and 6% to 9%, respectively. High and low variability phenotypes were each identified in 25% to 30% of participants. Conclusions Patients with urological chronic pelvic pain syndrome show symptom variability. At study enrollment patients had worse symptoms on average, resulting in a regression effect that influenced the estimated proportion of those who were improved or worse. Prospective studies should include a run-in period to account for regression to the mean and other causes of early symptom regression. Further, symptom variability may be quantified and used to characterize longitudinal symptom profiles of urological chronic pelvic pain syndrome.
We report here the sequencing and analysis of the genome of the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. This species is a model for studies of hydrogenogens, which are ...diverse bacteria and archaea that grow anaerobically utilizing carbon monoxide (CO) as their sole carbon source and water as an electron acceptor, producing carbon dioxide and hydrogen as waste products. Organisms that make use of CO do so through carbon monoxide dehydrogenase complexes. Remarkably, analysis of the genome of C. hydrogenoformans reveals the presence of at least five highly differentiated anaerobic carbon monoxide dehydrogenase complexes, which may in part explain how this species is able to grow so much more rapidly on CO than many other species. Analysis of the genome also has provided many general insights into the metabolism of this organism which should make it easier to use it as a source of biologically produced hydrogen gas. One surprising finding is the presence of many genes previously found only in sporulating species in the Firmicutes Phylum. Although this species is also a Firmicutes, it was not known to sporulate previously. Here we show that it does sporulate and because it is missing many of the genes involved in sporulation in other species, this organism may serve as a "minimal" model for sporulation studies. In addition, using phylogenetic profile analysis, we have identified many uncharacterized gene families found in all known sporulating Firmicutes, but not in any non-sporulating bacteria, including a sigma factor not known to be involved in sporulation previously.
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