Forecasting Hepatitis C Virus Status for Children in the United States: A Modeling Study.

BACKGROUND: Virtually all cases of hepatitis C virus (HCV) infection in children in the United States occur through vertical transmission, but it is unknown how many children are infected. Cases of maternal HCV infection have increased in the United States, which may increase the number of children vertically infected with HCV. Infection has long-term consequences for a child's health, but treatment options are now available for children ≥3 years old. Reducing HCV infections in adults could decrease HCV infections in children. METHODS: Using a stochastic compartmental model, we forecasted incidence of HCV infections in children in the United States from 2022 through 2027. The model considered vertical transmission to children <13 years old and horizontal transmission among individuals 13-49 years old. We obtained model parameters and initial conditions from the literature and the Centers for Disease Control and Prevention's 2021 Viral Hepatitis Surveillance Report. RESULTS: Model simulations assuming direct-acting antiviral treatment for children forecasted that the number of acutely infected children would decrease slightly and the number of chronically infected children would decrease even more. Alone, treatment and early screening in individuals 13-49 years old reduced the number of forecasted cases in children and, together, these policy interventions were even more effective. CONCLUSIONS: Based on our simulations, acute and chronic cases of HCV infection are remaining constant or slightly decreasing in the United States. Improving early screening and increasing access to treatment in adults may be an effective strategy for reducing the number of HCV infected children in the United States.

Maternal Hepatitis C Virus Infection and Adverse Newborn Outcomes in the US.

OBJECTIVES: We investigated the relationship between maternal hepatitis C virus (HCV) infection and infant health. Furthermore, we evaluated racial disparities with these associations. METHODS: Using 2017 US birth certificate data, we investigated the association between maternal HCV infection and infant birthweight, preterm birth, and Apgar score. We used unadjusted and adjusted linear regression and logistic regression models. Models were adjusted for use of prenatal care, maternal age, maternal education, maternal smoking status, and the presence of other sexually transmitted infections. We stratified the models by race to describe the experiences of White and Black women separately. RESULTS: Maternal HCV infection was associated with reduced infant birthweight on average by 42.0 g (95% CI: -58.81, -25.30) for women of all races, 64.6 g (95% CI: -81.91, -47.26) for White women and 80.3 g (95% CI: -162.48, 1.93) for Black women. Women with maternal HCV infection had increased odds of having a preterm birth of 1.06 (95% CI: 0.96, 1.17) for women of all races, 1.06 (95% CI: 0.96, 1.18) for White women and 1.35 (95% CI: 0.93, 1.97) for Black women. Overall, women with maternal HCV infection had increased odds 1.26 (95% CI: 1.03, 1.55) of having a low/intermediate Apgar score; White and Black women with HCV infection had similarly increased odds of an infant with low/intermediate Apgar score in a stratified analysis: 1.23 (95% CI: 0.98, 1.53) for White women and 1.24 (95% CI: 0.51, 3.02) for Black women. CONCLUSIONS: Maternal HCV infection was associated with lower infant birthweight and higher odds of having a low/intermediate Apgar score. Given the potential for residual confounding, these results should be interpreted with caution.

Transferrin predicts trimethylamine-N-oxide levels and is a potential biomarker of cardiovascular disease.

INTRODUCTION: Trimethylamine-N-oxide (TMAO) is a circulating biomarker associated with cardiovascular disease (CVD). Production of TMAO is facilitated by gut microbiota and dependent on micronutrients such as choline, betaine, and L-carnitine, present in foods such as red meat and eggs. HYPOTHESIS: We sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD using clinical data via an ordinal logistic model. METHODS: Data from participants (n = 127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were tested (with serum TMAO quartiles as the dependent variable), and only variables with P < 0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with P < 0.10. RESULTS: Eight candidate variables were included in the final model, with only transferrin, high-density lipoprotein cholesterol (HDL-C) and race (white vs. non-white) showing significant associations with TMAO. Participants had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) odds of being in a higher TMAO quartile compared with participants in the lowest transferrin quartile. Non-white participants had 2.92 times higher odds of being in the highest TMAO quartile compared to white individuals. Participants in the second quartile of HDL-C had 2.68 times higher odds of being in a higher TMAO quartile compared with participants in the lowest HDL-C quartile. CONCLUSIONS: Transferrin demonstrated a significant predictive association with TMAO and may represent a novel potential biomarker of increased CVD risk worthy of further study. These results warrant further examination of iron, metabolism, homeostasis, and gut microbiome to better understand and mitigate known increased CVD risk.

Hepatitis E seroprevalence in the United States: Results for immunoglobulins IGG and IGM.

BACKGROUND: Previous research identified a decline in hepatitis E virus (HEV) seroprevalence in US in 1988-1994 and 2009-2010. We investigated most recent HEV epidemiology. METHOD: Using a nationally representative sample (7656 persons in the National Health and Nutrition Examination Survey [NHANES] 2013-2014 and 7124 persons in NHANES 2015-2016), we compared the weighted seroprevalence of HEV (immunoglobulin G [IgG]/immunoglobulin M [IgM]) among people from the US (aged ≧ 6 years) between these two time periods. Sampling-weighted multivariate logistic regression models were used to identify factors associated with HEV seropositivity. RESULTS: The median participant age was 37 years (interquartile range = 17-58 years); 51.17% of them were female. Among US-born individuals, HEV seropositivity (IgG/IgM) increased from 4.5% (95% confidence interval [CI] = 3.5%-5.5%) in 2013-2014 to 8.1% (95%CI = 6.5%-9.7%) in 2015-2016. Recent HEV infection (IgM) has nearly doubled in all US-born people. For participants born in and outside of the US, the overall weighted HEV (IgG/IgM) seropositivity increased from 5% (95%CI = 3.9%-6.1%) during 2013-2014 to 7.7% (95%CI = 7.2%-10.5%) during 2015-2016. In "non-Hispanic Asian" females, HEV seropositivity (IgG/IgM) rose from 8.4% (95%CI = 5.6%-11.1%) during 2013-2014 to 20.7% (95%CI = 15.8%-25.7%) during 2015-2016. In "non-Hispanic Asian" males, HEV seropositivity (IgG/IgM) increased from 9.3% (95%CI = 6.9%-11.8%) during 2013-2014 to 16.8% (95%CI = 12.5%-21.2%) during 2015-2016. HEV (IgG/IgM) seropositivity was significantly associated with "non-Hispanic Asian" ethnicity (odds ratio [OR] = 1.69; CI = 1.12-2.56), female (OR = 1.2, CI = 1.06-1.38), and age (OR = 1.058, CI = 1.05-1.06). No clear etiologic agent was found. CONCLUSION: The combined and strata-specific HEV weighted seroprevalence increased from 2013-2014 to 2015-2016. Although prior studies had found increasing age as the only significant factor associated with HEV, the attribute of "non-Hispanic Asian" had a stronger association with HEV seropositivity than the age factor alone.

Statin users have an elevated risk of dysglycemia and new-onset-diabetes.

OBJECTIVE: Statins are one of the most widely prescribed medications in the United States; however, there is a concern that they are associated with new-onset-diabetes (NOD) development. We sought to understand the risk of dysglycemia and NOD for a cohort of individuals that reflect real-world physician prescribing patterns. METHODS: A retrospective cohort study was conducted among individuals with indications for statin use (n = 7064). To examine elevated glycosylated hemoglobin (>6.0%), logistic regression with inverse probability weighting was used to create balance between incident statin users and nonusers. To evaluate the risk of NOD development, Cox PH models with time varying statin use compared NOD diagnoses among statin users and nonusers. RESULTS: A higher prevalence of elevated HbA1c (PD = 0.065; 95% CI: 0.002, 0.129, P = 0.045) occurred among nondiabetic incident users of statins. Additionally, statin users had a higher risk of developing NOD (AHR = 2.20; 95% CI: 1.35, 3.58, P = 0.002). Those taking statins for 2 years or longer (AHR = 3.33; 95% CI: 1.84, 6.01, P < 0.001) were at the greatest risk of developing NOD; no differences were observed by statin class or intensity of dose. CONCLUSION: As lifestyle programs like the Diabetes Prevention Program are promoted in primary care settings, we hope physicians will integrate and insurers support healthy lifestyle strategies as part of the optimal management of individuals at risk for both NOD and cardiovascular disease. The relationships between statin use and glycemic control should be evaluated in large cohort studies, medical record databases, and mechanistic investigations to inform clinical judgment and treatment.

Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.

Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer.

We examined the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA). Mean cyclooxygenase expression (COX1 + COX2) ranked in the upper 99th percentile of all 20,531 genes and surprisingly, the mean expression of COX1 was more than tenfold higher than COX2. Highly significant correlations were observed between COX2 with eight tumor-promoting genes (EGR2, IL6, RGS2, B3GNT5, SGK1, SLC2A3, SFRP1 and ETS2) and between ALOX5 and ten tumor promoter genes (CD33, MYOF1, NLRP1, GAB3, CD4, IFR8, CYTH4, BTK, FGR, CD37). Expression of CYP19A1 (aromatase) was significantly correlated with COX2, but only in tumors positive for ER, PR and HER2. Tumor-promoting genes correlated with the expression of COX1, COX2, and ALOX5 are known to effectively increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the pathogenesis of breast cancer.

Association Between Prediagnostic Serum 25-Hydroxyvitamin D Concentration and Glioma.

There are no previous studies of the association between prediagnostic serum vitamin D concentration and glioma. Vitamin D has immunosuppressive properties; as does glioma. It was, therefore, our hypothesis that elevated vitamin D concentration would increase glioma risk. We conducted a nested case-control study using specimens from the Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed with glioma (n = 592), between 1974 and 2007, were matched to donors without glioma (n = 1112) on date and age at blood collection and sex. We measured 25-hydroxyvitamin D [25(OH)D], an indicator of vitamin D availability, using liquid chromatography coupled with mass spectrometry. Seasonally adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for each control quintile of 25(OH)D using conditional logistic regression. Among men diagnosed with high grade glioma >56, we found a negative trend (P = .04). Men diagnosed ≤ 56 showed a borderline positive trend (P = .08). High levels (>66 nmol/L) of 25(OH)D in men >56 were inversely related to high grade glioma from ≥2 yr before diagnosis (OR = 0.59; 95% CI = 0.38, 0.91) to ≥15 yr before diagnosis (OR = 0.61; 95% CI = 0.38,0.96). Our findings are consistent long before glioma diagnosis and are therefore unlikely to reflect preclinical disease.

Cyclooxygenase and Lipoxygenase Gene Expression in the Inflammogenesis of Colorectal Cancer: Correlated Expression of EGFR, JAK STAT and Src Genes, and a Natural Antisense Transcript, RP11-C67.2.2.

We examined the expression of major inflammatory genes, cyclooxygenase-1, 2 (COX1, COX2), arachidonate-5-lipoxygenase (ALOX5), and arachidonate-5-lipoxygenase activating protein (ALOX5AP) among 469 tumor specimens of colorectal cancer in The Cancer Genome Atlas (TCGA). Among 411 specimens without mutations in mismatch repair (MMR) genes, the mean expression of each of the inflammatory genes ranked above the 80th percentile, and the overall mean cyclooxygenase expression (COX1+COX2) ranked in the upper 99th percentile of all genes. Similar levels were observed for 58 cases with MMR mutations. Pearson correlation coefficients exceeding r = 0.70 were observed between COX and LOX mRNA levels with genes of major cell-signaling pathways involved in tumorigenesis (Src, JAK STAT, MAPK, PI3K). We observed a novel association (r = 0.78) between ALOX5 expression and a natural antisense transcript (NAT), RP11-67C2.2, a long non-coding mRNA gene, 462 base pairs in length that is located within the terminal intron of the ALOX5 gene on chromosome 10q11.21. Tumor-promoting genes highly correlated with the expression of COX1, COX2, ALOX5 and ALOX5AP are known to increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the inflammogenesis of colorectal cancer. These genes and the novel NAT, RP1167C2.2 are potential molecular targets for chemoprevention and therapy of colorectal cancer.

Maternal hepatitis C virus infection and three adverse maternal outcomes in the United States.

BACKGROUND: Hepatitis Virus C (HCV) infection rates have trended upwards among pregnant people in the USA since 2009. Existing evidence about HCV infections and maternal outcomes is limited; therefore, we used birth certificate data to investigate the association between HCV infection and maternal health outcomes. METHODS: We used the 2017 US birth certificate dataset (a cross-section of 1.4 million birth records) to assess the association between prevalent HCV infection and gestational diabetes, gestational hypertension, and eclampsia. Potential confounding variables included prenatal care, age, education, smoking, presence of sexually transmitted infections (STIs), body mass index (BMI), and weight gain during pregnancy. We restricted our analysis to only women with a first singleton pregnancy. Odds ratios were estimated by logistic regression models and separate models were tested for white and Black women. RESULTS: Only 0.31% of the women in our sample were infected with HCV (n = 4412). In an unadjusted model, we observed a modest significant protective association between HCV infection and gestational diabetes (Odds ratio [OR]: 0.83; 95% CI: 0.76-0.96); but this was attenuated with adjustment for confounding variables (Adjusted odds ratio [AOR]: 0.88; 95% CI: 0.76, 1.02). There was no association between HCV and gestational hypertension (AOR: 1.03; 95% CI: 0.91, 1.16) or eclampsia (AOR: 1.15; 95% CI: 0.69, 1.93). Results from the race stratified models were similar to the non-stratified summary models. CONCLUSION: We observed no statistically significant associations between maternal HCV infection with maternal health outcomes. Although, our analysis did indicate that HCV may lower the risk of gestational diabetes, this may be attributable to confounding. Studies utilizing more accurately measured HCV infection including those collecting type and timing of testing, and timing of infection are warranted to ensure HCV does not adversely impact maternal and/or fetal health. Particularly in the absence of recommended therapy for HCV during pregnancy.

Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors.

BACKGROUND: Epidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 326 incident colon cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003-2004 and compared with 652 controls with no history of cancer and matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and colon cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR) and 95% confidence intervals. RESULTS: Results showed significant risk reductions for selective COX-2 inhibitors (OR = 0.31, 95% CI = 0.16-0.57), regular aspirin (OR = 0.33, 95% CI = 0.20-0.56), and ibuprofen or naproxen (0.28, 95% CI = 0.15-0.54). Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no significant change in the risk of colon cancer. CONCLUSION: These results suggest that both non-selective and selective COX-2 inhibitors produce significant reductions in the risk of colon cancer, underscoring their strong potential for colon cancer chemoprevention.

Cyclooxygenase-2 (cox-2) and the inflammogenesis of cancer.

Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that aberrant induction of COX-2 and up-regulation of the prostaglandin cascade play a significant role in carcinogenesis, and reciprocally, blockade of the process has strong potential for cancer prevention and therapy. Supporting evidence includes the following: [1] expression of constitutive COX-2-catalyzed prostaglandin biosynthesis is induced by most cancer-causing agents including tobacco smoke and its components (polycylic aromatic amines, heterocyclic amines, nitrosamines), essential polyunsaturated fatty acids (unconjugated linoleic acid), mitogens, growth factors, proinflammatory cytokines, microbial agents, tumor promoters, and other epigenetic factors, [2] COX-2 expression is a characteristic feature of all premalignant neoplasms, [3] COX-2 expression is a characteristic feature of all malignant neoplasms, and expression intensifies with stage at detection and cancer progression and metastasis, [4] all essential features of carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis, and immunosuppression) are linked to COX-2-driven prostaglandin (PGE-2) biosynthesis, [5] animal studies show that COX-2 up-regulation (in the absence of genetic mutations) is sufficient to stimulate the transformation of normal cells to invasive cancer and metastatic disease, [6] non-selective COX-2 inhibitors, such as aspirin and ibuprofen, reduce the risk of human cancer and precancerous lesions, and [7] selective COX-2 inhibitors, such as celecoxib, reduce the risk of human cancer and precancerous lesions at all anatomic sites thus far investigated. Results confirming that COX-2 blockade is effective for both cancer prevention and therapy have been tempered by observations that some COX2 inhibitors pose a risk to the cardiovascular system, and more studies are needed in order to determine if certain of these drugs can be taken at dosages that prevent cancer without increasing cardiovascular risk. It is emphasized that the "inflammogenesis model of cancer" is not mutually exclusive and may in fact be synergistic with the accumulation of somatic mutations in tumor suppressor genes and oncogenes or epigenetic factors in the development of cancer.

Cancer chemoprevention by cyclooxygenase 2 (COX-2) blockade: results of case control studies.

Significant use of selective cyclooxygenase-2 (COX-2) blocking agents prescribed for the treatment of arthritis during 1999 to 2005 facilitates epidemiologic investigations to illuminate their chemopreventive effects against human cancer. We therefore conducted a set of case control studies of selective COX-2 blocking agents to determine their chemopreventive potential for the four major cancers: breast, prostate, colon, and lung. Newly diagnosed cases (323 breast cancer patients, 229 prostate cancer patients, 326 colon cancer patients, and 486 lung cancer patients) were ascertained during 2002 to September 30, 2004, at The James Cancer Hospital and Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio. All cases of invasive cancer were confirmed by examination of the pathology report. Healthy controls without cancer were ascertained from hospital screening clinics during the same time period. Controls were frequency matched at a rate of 2:1 to the cases by age, gender, and county of residence. We collected information on type, frequency, and duration of use of selective COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Other potentially important risk factors (smoking, drinking, body mass, medical history, blood pressure and cholesterol medications, family history of cancer, occupational history, and reproductive history for women) were also recorded for each subject. Estimates of odds ratios were obtained with adjustment for age and other potential confounders using logistic regression analysis. Use of selective COX-2 inhibitors resulted in a significant risk reduction for each type of cancer (71% for breast cancer, 55% for prostate cancer, 70% for colon cancer, and 79% for lung cancer) and an overall 68% risk reduction for all four cancers. This investigation demonstrates that COX-2 blocking agents have strong potential for the chemoprevention of cancers of the breast, prostate, colon and lung.

Anaerobic muscle strengthening physical activity and depression severity among USA adults.

We investigated the association between depression and anaerobic physical activity (while controlling aerobic physical activity), using a nationally representative sample of USA adults (n = 7354) who participated in the cross sectional National Health and Nutrition Examination Survey (NHANES, 1999-2006). We defined depression using the validated "Patient Health Questionnaire" (PHQ9) scale of 0-27 as PHQ9 ≥ 10. Severity of depression was classified by clinically established PHQ9 levels: mild (5-9), dysthymic (10-14), moderate (15-19), and major depression (≥20). We used logistic regression to estimate adjusted odds ratios of depression associated with distinct types of activity (only aerobic, only anaerobic, combined regime). We used multinomial logistic regression to examine associations of anaerobic activity with various severity levels of depression (mild, dysthymic, moderate, and major depression) with adjustment for aerobic activity. Women had higher prevalence of depression than men (8.4% versus 5.7%), whereas anaerobic muscle strengthening activity was more common in men than women (35% versus 24%). Adjusting for aerobic activity, anaerobic activity was inversely associated with depression (PHQ9 ≥ 10) in women under 50 (OR = 0.57; 95%CI = 0.41-0.81), all women (OR = 0.59; 0.43-0.80), men under 50 (OR = 0.85; 0.58-1.2), and all men (OR = 0.72; 0.51-1.01). Anaerobic activity was inversely associated with severity level of depressive symptoms in women and men. The combined regimen of anaerobic muscle strengthening activity and meeting the Physical Activity Guideline for America (PAGA) was related to the lowest odds ratio of depression in women (OR = 0.50; 95%CI = 0.33-0.75) and men (OR = 0.39; 95%CI = 0.23-0.62). Independent of aerobic physical activity, anaerobic muscle strengthening activity is significantly and inversely associated with depression among USA adults.

An Evaluation of Reach for a Work Site Implementation of the National Diabetes Prevention Program Focusing on Diet and Exercise.

PURPOSE: Our objective is to evaluate the "reach" component of the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework by comparing prediabetics who were and were not interested in enrolling in a free work site diabetes prevention program (DPP) during the first year of the program. Reach is defined as the proportion of eligible participants who enroll in a health program. DESIGN: A cross-sectional study design was used. SETTING: The setting was a large health system in the Midwest. PARTICIPANTS: Prediabetic health plan enrollees and spouses (N = 2158). MEASURES: An online health survey, annual voluntary biometric screenings delivered by a trained health-care professional using standardized protocols via point-of-care testing, and records from the DPP office were the sources of data for this study. ANALYSIS: Health behaviors and biometric screening results were simultaneously compared using multivariable logistic regression. RESULTS: The study population was 63% female, 79% white, and 16% black, and the mean age was 50.2 years (SD = 10.2). The reach of this program was 10%. Prediabetics were more likely to express interest in the DPP, if they were female (adjusted odds ratio [AOR]: 2.4; 95% confidence interval [95% CI]: 1.55-3.72; P < .001), black (AOR = 2.23; 95% CI: 1.43-3.47; P < .001), older in age (AOR: 1.08; 95% CI: 0.99-1.17; P = .05), or had a high-risk waist circumference (AOR = 1.44; 95% CI: 0.98-2.13; P = .07), lower self-efficacy to make healthy changes (AOR = 0.48; 95% CI: 0.26-0.91; P = .03), and 5 or more doctor visits in the last year (AOR = 2.13; 95% CI: 0.99-4.57; P = .05), after controlling for other covariates. CONCLUSION: Current recruitment and implementation strategies are reaching only a small group of individuals who are not representative of the larger prediabetic population. These findings inform future engagement strategies, and we recommend that public health practitioners evaluate reach to ensure that health promotion programs are of high value.

Estrogen plus progestin and colorectal cancer in postmenopausal women.

BACKGROUND: Although the Women's Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants. METHODS: In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication. RESULTS: There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006). CONCLUSIONS: Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.

Evaluation of root coverage with two connective tissue grafts obtained from the same location.

The purpose of this study was to compare the clinical root coverage achieved with two connective tissue grafts that were removed from the same donor area at different times and used in subepithelial grafts for root coverage. Sixty patients, each of whom had two connective tissue grafts removed from the same donor area at different times, were included in this study. The connective tissue grafts were used in two different subepithelial grafts for root coverage. The subepithelial grafts with both the first and second connective tissue grafts produced statistically significant changes in recession, probing depth, width of keratinized tissue, and attachment level. The changes obtained in the clinical measurements were not statistically significantly different between the first and second connective tissue grafts. The mean percentages of root coverage with the first and second connective tissue grafts were 95.4% and 98.2%, respectively, a statistically significant difference. None of the factors evaluated (sex, age, smoking history, and time between the two surgeries) could be related to statistically significant differences in the mean root coverage obtained. In this study, the second connective tissue graft produced greater mean root coverage than the first connective tissue graft.

Clinical evaluation of a combined regenerative technique with enamel matrix derivative, bone grafts, and guided tissue regeneration.

The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations.