Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Lymphedema after pelvic and para-aortic lymphadenectomy-results of a systematic evaluation in patients with cervical and endometrial carcinoma.

BACKGROUND: Lymphedema is a frequent complication after surgical treatment in gynecological oncology with substantial impact on patients´ Quality of Life (QoL). Little is known about screening instruments and prevention. Primary objective was to develop and validate the German version of a 13 items screening questionnaire (SQ) developed by Yost et al. to provide a valid instrument for early diagnosis of lower extremity lymphedema (LEL). METHODS: After translation the SQ was used in pt. with cervical or endometrial cancer who underwent pelvic/paraaortic Lymphadenectomy. Sensitivity and specifity were analysed regarding possible prediction and influencing factors of LEL. RESULTS: 67 pt. had LEL (N = 128). Nearly 50% of women in each group (38 in LEL + e 30 in LEL - ) had a body mass index (BMI) > 30 kg/m2. Number of removed lymphnodes, radiotherapy and were significantly associated with development of LEL. Translated Mayo Clinic questionnaire can be used with reliable specifity and sensitivity. Four additional questions improved the diagnostic accuracy of the SQ. CONCLUSIONS: The translated SQ is a valuable and predictive tool for screening and early detection of LEL in Gynecological cancer surgery and can even improved by adding simple questions.

Correlation of the Patient Reported Outcomes Measurement Information System with legacy outcomes measures in assessment of response to lumbar transforaminal epidural steroid injections.

BACKGROUND AND PURPOSE: The Patient Reported Outcomes Measurement Information System is a newly developed outcomes measure promulgated by the National Institutes of Health. This study compares changes in pain and physical function-related measures of this system with changes on the Numeric Rating Pain Scale, Roland Morris Disability Index, and the European Quality of Life scale 5D questionnaire in patients undergoing transformational epidural steroid injections for radicular pain. MATERIALS AND METHODS: One hundred ninety-nine patients undergoing transforaminal epidural steroid injections for radicular pain were enrolled in the study. Before the procedure, they rated the intensity of their pain by using the 0-10 Numeric Rating Pain Scale, Roland Morris Disability Index, and European Quality of Life scale 5D questionnaire. Patients completed the Patient Reported Outcomes Measurement Information System Physical Function, Pain Behavior, and Pain Interference short forms before transforaminal epidural steroid injections and at 3 and 6 months. Seventy and 43 subjects replied at 3- and 6-month follow-up. Spearman rank correlations were used to assess the correlation between the instruments. The minimally important differences were calculated for each measurement tool as an indicator of meaningful change. RESULTS: All instruments were responsive in detecting changes at 3- and 6-month follow-up (P < .0001). There was significant correlation between changes in Patient Reported Outcomes Measurement Information System scores and legacy questionnaires from baseline to 3 months (P < .05). There were, however, no significant correlations in changes from 3 to 6 months with any of the instruments. CONCLUSIONS: The studied Patient Reported Outcomes Measurement Information System domains offered responsive and correlative psychometric properties compared with legacy instruments in a population of patients undergoing transforaminal epidural steroid injections for radicular pain.

Correlation of the National Institutes of Health patient reported outcomes measurement information system scales and standard pain and functional outcomes in spine augmentation.

BACKGROUND AND PURPOSE: The recently developed National Institutes of Health PROMIS initiative provides reliable and valid measures across many health domains. We correlated changes in pain-related PROMIS measures and changes in both an NRS and the RMDI in patients undergoing spine augmentation. MATERIALS AND METHODS: Fifty patients, composed of 26 women (40-91 years of age; mean, 72.6 years) and 24 men (42-78 years of age, mean, 67.5 years) were enrolled in the study. They were asked at initial presentation and at 30 days to rate the intensity of their pain in the past 24 hours by using a 0-10 pain NRS as well at the 23-item RMDI. Study subjects also completed 3 different PROMIS short forms, including physical function, pain behavior, and pain interference. The Spearman correlation was used to assess the correlation between the scales. The RCI × 1.96 was calculated for each measurement tool as an indicator of change. RESULTS: All instruments were responsive to detection of change during 1 month (all, P < .0001). Correlations between changes in physical function, pain interference, and pain behavior PROMIS scores and changes in RMDI scores were 0.37, 0.44, and 0.42, respectively. Direction of changes (declines versus improvements) in RMDI and other scales were the same in approximately 60% of patients. CONCLUSIONS: All measures evaluated had adequate and comparable psychometric properties. The choice of which measure to use depends on the clinical intent of the intervention.

Minimally important differences were estimated for the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) instrument using a combination of distribution- and anchor-based approaches.

OBJECTIVE: To estimate minimally important differences (MIDs) on the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) instrument using anchor- and distribution-based methods. STUDY DESIGN AND SETTING: Preliminary MIDs were generated for FACT-C scores based on published results for two samples (n = 60 and n = 63) from the FACT-C validation study. Preliminary MIDs were confirmed using data from a Phase II randomized controlled clinical trial (n = 104) and a population-based observational study (n = 568). MIDs were estimated for the colorectal cancer subscale (CCS); the FACT-C Trial Outcome Index (TOI-C), which is the sum of the CCS, physical well-being, and functional well-being subscales; and the FACT-C total score. Both cross-sectional and longitudinal analyses were used. RESULTS: MIDs were stable across the different patient samples. The recommended MIDs ranged from 2 to 3 points for the CCS, 4 to 6 points for the TOI-C, and 5 to 8 points for the FACT-C total score. CONCLUSIONS: MIDs can enhance the interpretability of FACT-C scores, and they can be used to provide a basis for sample size estimation and to determine clinical benefit in combination with other measures of efficacy. General guidelines for estimating MIDs for other FACT instruments are suggested.

Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1.

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC(50) = 0.003 microM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.

Socioeconomic status and breast cancer incidence in California for different race/ethnic groups.

OBJECTIVE: The majority of research on breast cancer risk and socioeconomic status (SES) has been conducted for blacks and whites. This study evaluates the relationship between SES and breast cancer incidence in California for four race/ethnic groups. METHODS: Principal component analysis was used to create an SES index using 1990 Census data. Untracted cases were randomly allocated to census block groups within their county of residence. A total of 97,227 female breast cancer cases diagnosed in California between 1988 and 1992 were evaluated. Incidence rates and rate ratios (RRs) were estimated and a chi2 test for trend across SES levels was performed. RESULTS: SES was positively related to breast cancer incidence, and this effect was stronger for Hispanics and Asian/others than for whites and blacks. Adjusting by SES did not eliminate the differences in breast cancer rates among race/ethnic groups. RR differences between the race/ethnic groups were greatest in the lowest SES category and attenuated with increasing SES. An increasing trend over SES was statistically significant for all race/ethnic groups. Including randomly allocated cases affected RR estimates for white women only. CONCLUSIONS: Our results are consistent with similar findings for the Los Angeles area but differ from previous results for the San Francisco Bay area.

Regeneration of catalytic activity of glutamine synthetase mutants by chemical activation: exploration of the role of arginines 339 and 359 in activity.

In order to understand the nature of ATP and L-glutamate binding to glutamine synthetase, and the involvement of Arg 339 and Arg 359 in catalysis, these amino acids were changed to cysteine via site-directed mutagenesis. Individual mutations (Arg-->Cys) at positions 339 and 359 led to a sharp drop in catalytic activity. Additionally, the Km values for the substrates ATP and glutamate were elevated substantially above the values for wild-type (WT) enzyme. Each cysteine was in turn chemically modified to an arginine "analog" to attempt to "rescue" catalytic activity by covalent modification; 2-chloroacetamidine (CA) (producing a thioether) and 2,2'-dithiobis (acetamidine)(DTBA) (producing a disulfide) were the reagents used to effect these chemical transformations. Upon reaction with CA, both R339C and R359C mutants showed a significant regain of catalytic activity (50% and 70% of WT, respectively) and a drop in Km value for ATP close to that for WT enzyme. With DTBA, chemically modified R339C had a greater kcat than WT glutamine synthetase, but chemically modified R359C only regained a small amount of activity. Modification with DTBA was quantitative for each mutant and each modified enzyme had similar Km values for both ATP and glutamate. The high catalytic activity of DTBA-modified R339C could be reversed to that of unmodified R339C by treatment with dithiothreitol, as expected for a modified enzyme containing a disulfide bond. Modification of each cysteine-containing mutant to a lysine "analog" was accomplished using 3-bromopropylamine (BPA).(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory evaluations of toothbrush interproximal penetration ratios.

Access to interproximal tooth surfaces by toothbrush bristles has been associated with plaque removal. The ability of toothbrushes to assess the interproximal area was assessed with a new laboratory apparatus by measuring the extent of bristle-to-tooth contact in simulated toothbrushing with ink-coated toothbrush bristles. Toothbrush types evaluated were the bi-level trim Advanced Design Reach Soft, the ripple trim Crest Complete Large Soft, the flat trim Colgate Plus Full Head Adult Soft, and the flat trim Oral-B 35. Six replicates of each toothbrush were tested. Denture teeth in a Columbia Dentoform, mounted at 45 degrees, were brushed at a 300 g brushing weight for 15 horizontal strokes. Tooth #15 (upper left second molar) was then removed for measurement and the interproximal distance of ink deposition was determined under 10x magnification from the plane of the buccal contour, along the mesial side of the tooth in the lingual direction at the approximate vertical midpoint of the proximal surface. This was compared in ratio to the same measurement from the buccal contour to the midline. Mean penetration ratios were 0.84 for the Advanced Design Reach, 0.79 for Crest Complete, and 0.78 for both Colgate Plus and Oral-B 35 (overall standard error = 0.01). A one-way ANOVA showed a highly significant difference (p < 0.001) demonstrating that Advanced Design Reach penetrated significantly farther than the toothbrushes with flat or ripple trim bristle patterns. The data suggest the bi-level trim in the Advanced Design Reach toothbrush offers better penetration into the area between teeth, and may provide superior clinical or plaque removal compared to the other toothbrushes tested.

Comparison of a chlorhexidine rinse and a wooden interdental cleaner in reducing interdental gingivitis.

The purpose of this study was to evaluate the effectiveness of an antimicrobial rinse (chlorhexidine) compared to a positive control of mechanical oral hygiene in reducing interdental gingival inflammation. The mechanical group showed a significantly greater reduction in interdental gingivitis as determined by bleeding compared to the chemical rinse. Even though the chemical rinse has been shown to be effective in reducing inflammation on the visible buccal and lingual gingival surfaces, it is significantly less effective than the mechanical device in reducing bleeding in the interdental area.

Mechanical devices versus antimicrobial rinses in plaque and gingivitis reduction.

The effectiveness of mechanical oral cleaning and oral antimicrobial rinses was compared for gingivitis and bacterial plaque control in 158 subjects. Teeth were brushed ad lib throughout; four of the five groups used either an interdental cleaner, dental floss, an essential oil mouthwash or a cetypyridinium mouthwash. Gingival bleeding (EIBI), visual inflammation (VGI), and tooth plaque coverage were evaluated at zero, six and 12 weeks of product use. After six weeks, bleeding reduction was 42% greater for the interdental cleaner and 21% greater for the dental floss than for the control. All groups showed a further decrease after 12 weeks, but only the 49% reduction of the interdental cleaner was significantly greater than the control. The rinses showed no more reduction in bleeding sites than the control throughout the study. VGI scores were no different from the control for any of the groups. However, the EIBI proved much more sensitive than the visual method finding three times as many inflamed sites. Plaque was reduced by both antimicrobial rinses 27% more than the control over 12 weeks; the interdental cleaner and dental floss groups showed no significant incremental plaque reductions. The results suggest antimicrobial rinses reduce plaque on visible tooth surfaces, but do not penetrate sufficiently between teeth to affect interdental plaque and thus interdental inflammation. However, by disturbing interdental plaque, both dental floss and the interdental cleaner have little effect on visible tooth surface plaque accumulation, yet produce a significant reduction in gingival inflammation.

The prevalence of interdental gingival inflammation: a report from the 1986 ADA annual health screening.

This study screened 1986 ADA annual session participants for interdental gingival inflammation by using the Eastman Interdental Bleeding Index (EIBI). The EIBI provides a sensitive and objective measure of interdental gingival inflammation, and has been shown to be reliable. At least one bleeding site was found in 81% of the 435 dentists examined. This study showed that in a dental population, the prevalence of gingival inflammation was high when the health of interdental tissues was assessed.

Pollutant sources and flows in a municipal sewage system.

The flow of heavy metals (Cu, Ni, Cr, Cd, Zn, Pb) and cyanide in the Kokomo, Indiana collection system and wastewater treatment plant is analyzed. The primary objective is to determine the relative contributions of domestic and non-domestic sources to the total pollutant load in the system, and to assess the levels of discharge control required for the disposal of municipal sludge by landfill or agricultural landspreading. Sampling was conducted at point source locations, in major sewer trunk-and feeder lines, and at the treatment plant. Production and waste treatment data are presented for point sources sampled for the purpose of characterizing metal and cyanide discharges as a function of these parameters. A heavy metal mass balance is attempted for the treatment plant. Metal removal factors are presented for various plant operations.A simple statistical approach is presented for the design of a cost-effective sampling program for correlating point source and trunkline pollutant sampling. The purpose is to minimize the amount of sampling required to account for pollutants seen in trunkline and treatment plant streams in terms of discharges from specific point sources.

The sexually liberated college student--fact or fancy.

PIP: This paper examines the sexual experiences and behavior of a college student population. The target population was 21,677 full-time single female and male undergraduates at Rutgers University in New Brunswick, New Jersey. A random sample of 1627 students were selected and given questionnaires. 622 (38%) of the students responded; 321 were single females and 235 were single males. 41% of the students were Catholic; 89% were white; and 89% of the students were 23 years of age or younger. The questionnaire contained questions concerning social and demographic background, sources of sexual information, sexual behavior and attitudes, contraceptive usage and parental attitudes. 1/3 of the women had never had intercourse. 10% of those who had had intercourse had it only once prior to the preceding 12 months. 20% had had intercourse 2-11 times in the last year; 47% had intercourse 1 or more times a week. Only 5% reported they were currently having sex with more than one partner. 23.7% indicated they were dating but not engaging in intercourse. 1/5 of the males had not had intercourse while 10% of those who had had intercourse in the last 12 months had it only once. 29% had intercourse 2-11 times in the last year. 1/3 of those who had had intercourse had it 1 or more times a week. The men reported having had slightly fewer current sexual relationships than the women. Sex with more than 1 partner was reported by 8.3% of the men. Only 9% of the women reported having orgasm with penile thrusting alone. 36% of the sexually active females had difficulty achieving orgasm all or most of the time. 19% of the males who had had intercourse reported problems in sexual functioning. 22% of the women had had unwanted pregnancies of which most were terminated by abortion. Only 23% of the sexually active females and their partners had used an effective method of contraception. Only 9% of the males used an effective method. Women reported that condoms (44%), withdrawal (43%), abortion (32%), luck (36%), nothing (33%), the diaphragm (22%), and rhythm (25%) were used sometimes. 19% reported consistent use of a diaphragm while 10% reported consistent use of the pill. Men reported use of the condom (45%), withdrawal (46%), the pill (32%), luck (30%), and rhythm (24%) some of the time. 17% reported consistent use of the pill while 13% reported consistent use of the condom. Students are found to not be as sexually active and certainly not as promiscuous as their "sexually liberated" press implies.^ieng

Lipoprotein-hyaluronate associations in human aorta fibrous plaque lesions.

Lipoproteins and glycosaminoglycans were isolated from human aorta fibrous plaque lesions by isotonic saline extraction and treatment with elastase. Hydrolysis by elastase, using suitable inhibitors of nonspecific proteases, yielded about twice the amount of cholesterol and four times more GAG than saline extraction. Bio-Gel A-50m column chromatography of elastase-solubilized materials gave a fraction which contained lipoproteins of 1.006 and 1.063 floating densities and hyaluronic acid. Immunologically the lipoproteins resembled serum apoB-containing lipoproteins. Two species of hyaluronates with estimated molecular weights of 400,000 and 75,000 were observed. In addition to hyaluronate, elastase solubilized other GAG which were not associated with lipoproteins. Association of hyaluronate as the only GAG in the elastase-solubilized lipoprotein fraction emphasizes the important role that hyaluronate may play in the aggregation or entrapment of macromolecules such as lipoproteins in the arterial connective tissue matrix.

A spectrofluorometric protein assay of plaque on dentures and of denture cleaning efficacy.

A spectrofluorometric method of protein analysis using fluorescamine was shown to be a meaningful method of evaluating denture cleanser efficacy. This assay was useful in the presence of most currently used denture cleanser ingredients, materials which cause other protein assay methods to fail. The determination of dental plaque protein was shown to be an adequate measure of dental plaque dry weight.

Some aspects of cadmium flow in the U.S.

A team of Purdue University engineers and scientists has been involved in studying sources, translocation mechanisms, and fate of cadmium in the environment. One of the principal results of this work has been the development of a cadmium flow model for the U. S. which involves simulating sources, use patterns, waste treatment and recovery techniques, waste disposal options, and environmental flow mechanisms. A series of model calculations performed specify cadmium environmental flow, fate, and human exposure for a variety of use pattern, waste treatment/recovery, and disposal scenarios over a ten-year-simulation period.