Patient-Centered Dentinal Hypersensitivity Treatment Outcomes: Results from the National Dental PBRN.

Dentinal hypersensitivity (DH) can have a significant impact on oral health and functioning, and it is a clinical symptom commonly managed by dentists during routine clinical practice. DH symptoms are typically elicited by otherwise innocuous, nonpainful stimuli applied to exposed dentin (e.g., tactile stimuli, warming or cooling temperatures or air puffs). Treatment approaches have sought to directly target the dentinal pulp tissues or close dentinal tubules via dental office care and treatment services (fluoride varnishes, glutaraldehydes, bonding agents, sealants, oxalates, or lasers) or home care services (toothpastes or dentifrices containing fluoride or potassium nitrate compounds). The purpose of this prospective multicenter cohort study was to assess how community-based dentists from the National Dental Practice-Based Research Network (National Dental PBRN) manage DH and whether the effectiveness of DH treatments can be assessed in those settings. A total of 171 dentists recruited 1862 subjects with DH from their existing patients. Dentists then recommended and provided DH treatment as appropriate. Treatment choice was at the discretion of the dentists. Patients rated their DH pain at baseline and 1, 4, and 8 wk during the course of their treatments. They used pain intensity and unpleasantness visual analog scales and 4 labeled magnitude scales and rated their satisfaction with treatment after 8 wk. Patients were provided reminders postbaseline via email, texting, or voice mail. These patient-centered outcomes served as the principal measures for the assessment of treatment because treatments sought to alleviate DH symptoms. The patients with DH who reported pain reduction from dentist-provided treatments (glutaraldehyde/HEMA [hydroxyethyl methacrylate] compounds, oxalates, and bonding agents), dentists' advice and counseling regarding oral habits and diet, and patient-applied fluoride toothpaste reported a concomitant positive rating of satisfaction with DH treatments. The results from this study support the feasibility of engaging network practices to assess the effectiveness of clinical DH treatments. Knowledge Transfer Statement: National Dental PBRN dentists provide a range of procedures to treat dentinal hypersensitivity. In this large nonrandomized study designed to assess clinical care and to capture patient-reported outcomes, about 60% of patients reported improvement in pain. This study demonstrated the feasibility of engaging network dentists and their patients to assess treatment effectiveness. Future studies will explore the feasibility of imposing randomization and measuring patient compliance with treatment in the manner that this treatment is provided.

Differences between reported and actual restored caries lesion depths: results from The Dental PBRN.

OBJECTIVE: The objectives of this research were to: (1) quantify the discordance between the caries lesion depth at which dentists restored initial lesions during a clinical study ("actual depth") and the lesion depth that they reported during a hypothetical clinical scenario ("reported depth"); (2) test the hypothesis that certain practitioner, practice, patient, and caries lesion characteristics are significantly associated with this discordance. METHODS: Practitioner-investigators who perform restorative dentistry in their practices completed an enrollment questionnaire and participated in 2 consecutive studies on caries diagnosis and treatment. The first study was a survey asking about caries treatment. The second study collected data on restorations placed in routine clinical practice due to caries in patients over 19 years of age on occlusal surfaces only or proximal surfaces only. We report results on 2,691 restorations placed by 205 dentists in 1,930 patients with complete data. RESULTS: Discordance between actual depth and reported depth occurred in only about 2% of the restorations done due to proximal caries, but about 49% of the restorations done due to occlusal caries. Practice type, restorative material used and the diagnostic methods used were significantly associated with discordance. CONCLUSION: Dentists frequently restored occlusal caries at a shallower depth as compared to their reported depth, but the discordance was very small for proximal lesions. Discordance for occlusal caries was more common when radiographs were not taken or if a resin restoration was placed.

Cluster Effects in a National Dental PBRN restorative study.

Items in clusters, such as patients of the same clinician or teeth within the same patient, tend to be more similar than items from different groups. This within-group similarity, represented by the intraclass correlation coefficient (ICC), reduces precision, yielding less statistical power and wider confidence intervals, compared with non-clustered samples of the same size. This must be considered in the design of studies including clusters. We present ICC estimates from a study of 7,826 restorations placed in previously unrestored tooth surfaces of 4,672 patients by 222 clinicians in the National Dental Practice-Based Research Network, as a resource for sample size planning in restorative studies. Our findings suggest that magnitudes of ICCs in practice-based research can be substantial. These can have large effects on precision and the power to detect treatment effects. Generally, we found relatively large ICCs for characteristics that are influenced by clinician choice (e.g., 0.36 for rubber dam use). ICCs for outcomes within individual patients, such as tooth surfaces affected by a caries lesion, tended to be smaller (from 0.03 to 0.15), but were still sufficiently large to substantially affect statistical power. Clustering should be taken into account in the design of oral health studies and derivation of statistical power estimates for these studies (ClinicalTrials.gov, NCT00847470).

Differences between reported and actual restored caries lesion depths: results from The Dental PBRN.

OBJECTIVE: The objectives of this research were to (1) quantify the discordance between the caries lesion depth at which dentists restored initial lesions during a clinical study ("actual depth") and the lesion depth that they reported during a hypothetical clinical scenario ("reported depth"); (2) test the hypothesis that certain practitioner, practice, patient, and caries lesion characteristics are significantly associated with this discordance. METHODS: Practitioner-investigators who perform restorative dentistry in their practices completed an enrollment questionnaire and participated in two consecutive studies on caries diagnosis and treatment. The first study was a survey asking about caries treatment. The second study collected data on restorations placed in routine clinical practice due to caries in patients over 19 years of age on occlusal surfaces only or proximal surfaces only. We report results on 2691 restorations placed by 205 dentists in 1930 patients with complete data. RESULTS: Discordance between actual depth and reported depth occurred in only about 2% of the restorations done due to proximal caries, but about 49% of the restorations done due to occlusal caries. Practice type, restorative material used and the diagnostic methods used were significantly associated with discordance. CONCLUSION: Dentists frequently restored occlusal caries at a shallower depth as compared to their reported depth, but the discordance was very small for proximal lesions. Discordance for occlusal caries was more common when radiographs were not taken or if a resin restoration was placed.

Low-density lipoprotein particle size, central obesity, cardiovascular fitness, and insulin resistance syndrome markers in obese youths.

OBJECTIVE: (1) To determine the prevalence of small dense low-density lipoprotein (SDLDL) particles in obese youths and (2) to compare youths with SDLDL and large buoyant LDL (LBLDL) subclass phenotypes in total body and abdominal fatness, cardiovascular (CV) fitness, and markers of the insulin resistance syndrome (IRS). DESIGN: For group comparisons, subjects were dichotomized into either SDLDL phenotype group or LBDL phenotype group based on LDL particle size. SUBJECTS: Obese 13 to 16-y-olds (n=80) who had a triceps skinfold greater than the 85th percentile for gender, ethnicity, and age. MEASUREMENTS: LDL particle size, plasma lipids and lipoprotein concentrations, plasma glucose and insulin concentrations, and blood pressures; percentage body fat, visceral adipose tissue (VAT); VO(2) at a heart rate of 170 bpm as an index of CV fitness. RESULTS: The prevalence of the SDLDL phenotype was 54% among the 80 obese youths. Although overall body fatness (ie BMI and percentage body fat) and CV fitness were similar between the two LDL phenotype groups, the SDLDL phenotype group had significantly higher weight, waist circumference and VAT than the LBLDL phenotype group. With respect to the IRS markers, youths with the SDLDL phenotype had significantly higher triacylglycerol (TAG), very low-density lipoprotein cholesterol (VLDLC), apolipoprotein B (apo B), and total cholesterol-to-high-density lipoprotein ratio (TC/HDLC) than youths with the LBLDL phenotype. LDL particle size as a continuous variable was significantly correlated with TAG, VLDLC, apo B, HDLC, and TC/HDLC. Plasma TAG and HDLC concentrations were independent predictors of LDL particle size. CONCLUSION: (1) The SDLDL phenotype was common in obese youths and (2) the relationships of LDL particle size with several of the IRS markers suggested that already in adolescence the expression of the SDLDL phenotype might be an important risk factor for future coronary heart disease mortality and morbidity.

Cervicography for triage of women with mildly abnormal cervical cytology results.

OBJECTIVE: To estimate the sensitivity and specificity of cervicography in detecting cervical cancer precursor lesions in women participating in the National Cancer Institute's multicenter atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage study (ALTS). STUDY DESIGN: Cervigrams were obtained from 3134 women with a referral Papanicolaou smear diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. Cervigram and cervical histology results were compared by using cervical intraepithelial neoplasia (CIN) 2 and CIN 3 disease end points. RESULTS: Of 3134 women, 444 had histologic findings of more than or equal to CIN 2 and 222 had CIN 3. Cervicography interpretation by using a threshold of greater than or equal to atypical had a sensitivity, specificity, and positive and negative predictive values of 79.3%, 61.0%, 13.4%, and 97.5%, respectively, for detecting greater than or equal to CIN 3. Cervicography was more sensitive (80.8% vs 57.1%), but less specific (55.7% vs 81.8%), for detecting CIN 3 in women younger than 35 years compared with women 35 years or older, respectively. CONCLUSIONS: Cervicography functioned moderately well at detecting CIN 2 or CIN 3 in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Papanicolau smear results. Cervigram sensitivity was better for younger women.

Exercise in sickle cell anemia: effect on inflammatory and vasoactive mediators.

The aim of this study was to determine the response of inflammatory and vasoactive mediators to 3 consecutive days of exercise in African-American women with and without sickle cell anemia (SCA). Circulating inflammatory mediators [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha)] were measured before, and vasoactive mediators [endothelin-1 (ET-1), nitric oxide metabolites (NOx)] before and after each exercise bout in ten subjects with SCA and ten controls. Exercise did not affect ET-1, IL-6 or CRP concentrations (p >.05). TNFalpha was higher in SCA than controls (p < or = .0005) at all times; however, the response pattern was similar for the groups: no change from day 1 to day 2, but a decrease from day 2 to day 3 (p < or = .05). NOx increased significantly after exercise (p < or = .0001) but returned to baseline by 24 h afterward. On the 3rd day, NOx increased after exercise in SCA but not in the controls (p < or = .05). In conclusion, exercise did not cause a harmful inflammatory response in these individuals with SCA. However, NOx increased after exercise on all 3 days in SCA but appeared attenuated after 2 days in controls.

Body composition in women with sickle cell disease.

INTRODUCTION: Adults with sickle cell disease (SCD) have increased morbidity and low perceived health status, similar to patients with other chronic conditions. These patients may be sedentary due to exercise intolerance, physical incapacity due to sickle cell-related complications or medical conservatism. Obesity is an indicator of low health status and overall well-being in the general population, and we hypothesize that adults with SCD will have a high total body fat (%BF). The purpose of this study was to assess body composition in women with SCD using dual-energy X-ray absorptiometry (DXA). METHODS: Baseline medical examination, laboratory assessments, and seven-day activity recall to estimate energy expenditure (EE) were obtained for 22 women with SCD. BMI was calculated and whole body DXA was performed [fat mass (FM), fat-free soft tissue (FFST), and bone mineral content (BMC)]. Descriptive statistics were obtained and associations between body composition indices, total hemoglobin (Hb), treatment with hydroxyurea (HU), and EE were determined. RESULTS: Patient age was 30.5+/-9.3 years and total Hb was 8.85+/-1.92 g/dL (mean+/-SD). Mean body mass index (BMI) (22.6 kg/m2) was in the 'acceptable' range, while DXA measurement of mean % fat (32.6%) indicated obesity. Fat-free mass (FFM) was 40.0+/-5.62 and bone mineral density (BMD) was 1.13+/-0.14 g/cm2 (mean+/-SD). There were no correlations between body composition indices and total Hb, HU, or EE. CONCLUSIONS: This is the first report of high levels of adiposity, low FFM, and low BMD in normal weight women with SCD. The findings were not affected by total Hb, EE, HU. Further studies are needed to better define body composition, body composition determinants, and their impact on overall health status in adults with SCD.

Ototoxicity after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin followed by stem cell transplantation in patients with breast cancer.

Our purpose was to determine the risk of ototoxicity in breast cancer patients receiving a myeloablative regimen consisting of cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2 (CTCb) followed by stem cell transplantation. Fourteen consecutive patients with breast cancer were treated with high dose chemotherapy consisting of the CTCb regimen followed by stem cell transplantation. A pretransplant complete hearing study was obtained which consisted of hearing case history, audiometry and tympanometry. In addition, DPOAE (Distortion Product Otoaccoustic Emissions) was done to evaluate measurable changes in the cochlear (outer hair cell) functioning. Pre-transplant, all patients had no clinical evidence of hearing impairment and hearing studies were normal. Eleven patients had hearing studies and a telephone interview posttransplant. One patient was lost to follow-up and two patients died. One of the 11 patients tested had an abnormal post-transplant hearing study but none of them had clinically detectable hearing impairment. In our prospective study of breast cancer patients treated with the CTCb regimen, we did not observe clinically detectable hearing impairment in any of the patients tested.

The efficacy of liquid-based cervical cytology using direct-to-vial sample collection.

BACKGROUND: Previous studies of liquid-based cervical cytology (LBCC) have used a split sample collection technique that creates a potential negative bias for its evaluation. Thus, the full diagnostic potential of LBCC has not been established. The purpose of our study was to determine rates of specimen adequacy and cervical cytologic and histologically confirmed diagnoses obtained with a liquid-based Papanicolaou (Pap) test using a direct-to-vial sample collection technique and compare these results with those obtained using the conventional Pap test (CPT). METHODS: A total of 1004 nonpregnant women aged 18 years or older with an intact cervix had Pap tests collected with an Ayre spatula and cytobrush, and the sample was placed in a preservative solution. The specimens were processed as thin layer Pap tests according to the manufacturer's specifications. Another group of 2110 women with a similar patient profile had a CPT collected immediately preceding the initiation of the trial. The subjects in each group consisted of an equal percentage of women presenting for a routine Pap test or a colposcopy examination. We compared the distributions of diagnostic categories between the groups using a chi-square test. RESULTS: A significantly greater percentage of satisfactory Pap tests were obtained using LBCC (84.0%) compared with the CPT (60.5%, P < .001). Fewer satisfactory but limited by (SBLB, 14.8%) and unsatisfactory (1.2%) Pap tests were reported using LBCC compared with the CPT (35.7% and 3.8%, respectively, chi2 = 170.7, P < .001). A significantly greater percentage of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Pap test results were reported using LBCC (7.4% and 3.7%, respectively) compared with the CPT (1.7% and 1.7%, respectively, chi2 = 74.4, P < .001). The predictive value of a positive LBCC test (93.9%) was similar to that for a positive CPT (87.8%) when compared with histology results. CONCLUSIONS: Compared with the CPT, LBCC detected a significantly greater percentage of satisfactory Pap tests and significantly reduced the number of unsatisfactory and SBLB tests. Four times the percentage of LSIL and twice the percentage of HSIL Pap test results were obtained using LBCC compared with the CPT. These findings demonstrate that LBCC significantly improves the adequacy of Pap tests and may increase the rate of detection of cervical neoplasia compared with the CPT.

Heart rate variability in obese children: relations to total body and visceral adiposity, and changes with physical training and detraining.

OBJECTIVE: Heart rate variability provides non-invasive information about cardiac parasympathetic activity (PSA). We determined in obese children: (1) relations of baseline PSA to body composition and hemodynamics; (2) effects of physical training (PT) and cessation of PT; and (3) which factors explained individual differences in responsivity of PSA to the PT. RESEARCH METHODS AND PROCEDURES: The root mean square of successive differences (RMSSD) was the index of PSA. Obese children (n = 79) were randomly assigned to groups that participated in PT during the first or second 4-month periods of the study. RESULTS: Baseline RMSSD was significantly (p<0.05) associated with lower levels of: fat mass, fat-free mass, subcutaneous abdominal adipose tissue, resting heart rate (HR), resting systolic blood pressure, and exercise HR. Stepwise multiple regression produced a final model (R2 = 0.36) that included only resting HR. The analysis of changes over the three time points of the study found a significant (p = 0.026) time by group interaction, such that RMSSD increased during periods of PT and decreased following cessation of PT. Greater individual increases in response to the PT (p<0.05) were seen in those who had lower pre-PT RMSSD levels, showed the greatest decreases in resting HR, and increased most in vigorous physical activity. The final regression model retained only the change in resting HR as a significant predictor of the changes in the RMSSD (R2 = 0.23). DISCUSSION: Regular exercise that improved fitness and body composition had a favorable effect on PSA in obese children.

A comparison of colposcopy using optical and video colposcopes.

OBJECTIVE: To compare the colposcopic adequacy, colposcopic impressions, histologic sampling intent, biopsy site location, procedural complications, and difficulty of colposcopic examinations using optical and video colposcopes. MATERIALS AND METHODS: Women and men presenting consecutively for colposcopy were examined independently by two colposcopists using alternately either an optical or video colposcope. Colposcopists individually recorded their exam adequacy, colposcopic impression, biopsy intent and site, procedural complications, and difficulty of examination. Most colposcopists had no prior experience with video colposcopes. RESULTS: Of 300 patients, mean age 35.3 years (±12.2 SD), examined, 29.7% were nulliparous, 4.9% pregnant, 52.5% had a previous biopsy and 34.3% had prior cervical treatment. Agreement between colposcopes was excellent for visualizing the complete squamocolumnar junction (75.6%, x = 6.40, p = 0.09). Colposcopists using the video colposcope had more unsatisfactory exams of the endocervical canal (36.6%, 97/265) than did colposcopists using optical colposcopes (24.9%, 66/265, x = 16.65, p = 0.001). Colposcopic impression agreement with pathology results were not significantly different between the video (58.1%) and optical (57.0%) colposcopes (x = 0.09, p = 0.8). Biopsy intent (79.9% agreement, x = 0.20, p = 0.7) and biopsy site selection by cervical quadrant were not significantly different for the two colposcopes. Both types of colposcopes were rated extremely easy to use, but colposcopy in general (T = 3.97, p < 0.001), visualization (T = 2.98, p = 0.002), assessment (T = 2.76, p = 0.004), and sampling (Wilcoxon = 2.27, p = 0.02) were determined to be easier when using optical colposcopes. CONCLUSIONS: Video colposcopes have similar, clinically relevant outcomes when compared with optical colposcopes. Colposcopists using optical colposcopes reported easier colposcopy exams and fewer unsatisfactory examinations of the endocervical canal. These findings may represent a learning curve effect as colposcopists become familiar with operating the video colposcope.▪.

High-dose chemotherapy followed by reinfusion of a high number of CD34+ progenitor cells is frequently associated with development of fever in the postengraftment period.

Twenty-nine patients received high-dose chemotherapy and autologous stem cell transplantation from June 1997 to December 1998. The number of CD34+ cells reinfused was 2.4 x 10(6) to 69.0 x 10(6)/kg. Twelve patients developed a fever in the immediate postengraftment period. One patient had a documented infection that could account for the fever; a second patient had a rash and biopsy proven acute graft-versus-host disease (GvHD) that responded to steroids. In the other 10 patients (30%) there was no identifiable cause of the fever. One of these patients received 4.2 x 10(6) CD34+ cells/kg. The other nine received 22.0 x 10(6) to 69.0 x 10(6) CD34+ cells/kg. In our series of 29 patients, 9 of the 11 (82%) patients who received > 20 x 10(6) CD34+ cells/kg developed fever in the postengraftment period. There was a significant association between the number of CD34+ cells (<20 vs. >20 x 10(6)) and occurrence of fever (odds ratio = 76.5; p = 0.00005). Even though they engrafted promptly (7 to 9 days), the fever required evaluation for infection, blood cultures, antibiotic treatment, and observation. This required additional hospitalization of 1 to 7 days. These data suggest that a high number of CD34+ cells is frequently associated with post-engraftment fever and prolongation of the hospital stay. Should there be an upper limit in the number of reinfused CD34+ cells is a question that has to be addressed and possibly studied.

Children's dietary recalls: the salience of entree and liking for foods on accuracy and order of reporting.

This study investigated the impact of entree and liking for foods on the accuracy and order of reporting on children's school lunch recalls. Data were collected during a series of studies to investigate children's lunch recalls from a cognitive processing approach to understand better how children remember what they have eaten. Fourth-grade children from four schools were randomly selected, observed eating lunch, and interviewed the same (n = 89) or next (n = 148) day. Foods were classified as matches (observed and reported eaten), omissions (observed but not reported eaten), or phantoms (not observed but reported eaten), and corresponding rates were calculated. Statistical analyses included z tests and permutation tests. For same- and next-day recalls, children were more likely to report entree than other meal components earlier in the interview. For next-day recalls, the phantom rate for the remaining items was lower for children who reported entrees accurately versus inaccurately. For items liked "a lot" compared with items "not liked a lot," match rates were higher for next-day recalls, and phantom rates were lower for both same- and next-day recalls. Because entree and liking for foods appear to play salient roles in children's dietary recalls, these results provide guidance regarding the development of specific prompts to increase the accuracy of children's dietary recalls.

Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?

BACKGROUND: The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports. METHODS: Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS: A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.

Comparison of two tests for detecting carcinogenic HPV in women with Papanicolaou smear reports of ASCUS and LSIL.

BACKGROUND: The detection of cancer-associated types of human papillomavirus (HPV) in cervical specimens predicts the presence and future development of cervical intraepithelial neoplasia (CIN). The purposes of this study were (1) to determine the efficacy of a second-generation assay by hybrid capture (HC II) to detect carcinogenic HPV from residual cervical cells of a liquid-based cervical cytologic specimen, and (2) to compare the performance of this second-generation test with the first-generation hybrid capture (HCT) HPV test of material from direct cervical sampling to detect CIN in women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) smear reports. METHODS: Women with a recent Pap smear report of ASCUS or LSIL had a sampling of the cervix using either an Ayre's spatula and cytobrush or an Accellon device sampling for liquid-based cytologic system HC II HPV testing, followed by a Dacron swab sampling of the cervix for standard HCT HPV testing of the paired specimens. All women received colposcopy examinations including cervical biopsy and endocervical curettage, when indicated, to determine criterion standards for comparison. RESULTS: Paired swabs and liquid-based cervical specimens from 242 women were available for testing by standard HCT and the newer HC II HPV DNA assays. The sensitivity, specificity, and positive and negative predictive values for detecting CIN grade 2 or 3 (CIN 2/3) were 61.9%, 57.0%, 12.0%, and 94.0%, respectively, for the HCT test, and 90.5%, 29.4%, 10.9%, and 97.0%, respectively, for the liquid-based cytology HC II assay. When only women with an initial ASCUS Pap smear report were considered, the HC II test results were 88.9%, 40.3%, 9.1%, and 98.2%, respectively. CONCLUSIONS: Testing for lower genital tract carcinogenic HPV DNA using a cervical cytology liquid transport media residual sample is clinically feasible. The new HC II microplate HPV test achieved a greater test sensitivity for detecting carcinogenic HPV and correspondingly of CIN 2/3 compared with the currently available first-generation HC HPV test. Use of a liquid-based cervical cytology system combined with intermediate triage by HC II testing of residual cells for carcinogenic HPV alone may help to efficiently identify CIN 2/3 in women who have a prior screening Pap smear report of ASCUS.

Colposcopy Quality Control: Establishing Colposcopy Criterion Standards for the National Cancer Institute ALTS Trial Using Cervigrams.

OBJECTIVES: The colposcopy quality control (QC) group of the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesions (ASCUS/ LSIL) Triage Study (ALTS) monitors colposcopists at four clinical centers by direct observation and indirectly by assessment of digitized computer colposcopic images transferred nightly by modem. The purpose of this preclinical study was to determine the agreement among colposcopy QC monitors' colposcopic impressions and biopsy site placement through evaluation of cervical photographic images. MATERIALS AND METHODS: A nonparticipant selected 100 Cervigram slides representing four pathologically confirmed categories: cervical intraepihelial neoplasia 1(CIN), CIN2 and CIN3, normal, and cancer. our colposcopy QC monitors and two certified Cervigram evaluators independently interpreted the images for colpocopic impression on two separate occasions. Measures of agreement were calculated for intraobserver, pairwise interobserver, and observer versus histological diagnoses. Participants also indicated the most severe biopsy site by marking an χ on a 4 × 6-inch color print duplication. Mean distances between biopsy site annotations for each pair of evaluators were calculated. RESULTS: The ALTS observer agreement with histology ranged from 75.3% (K = .66) to 47.4% (K = .36) for the first evaluation and 71.1 % (K = .63) to 50.5% (K = .38) for the second evaluation. ALTS interobserver agreement varied between 71 % and 57% for the first interpretation and 76% and I2% for the second evaluation. ALTS intraobserver agreement varied from 86% (K = .86) to 68.0% (K = .60). The mean listances between biopsy site annotations for each pair of ALTS observers varied from 0.99 ± 0.93 mm to 1.44 ± 1.19 nm. CONCLUSIONS: The ALTS colposcopy QC monitors achieved poor to good observer agreement with histology, fair to excellent interobserver agreement, and good to excellent intraobserver agreement in assessing the severity of cervical images. These levels of agreement are similar to many reported by pathologists for cervical cytology and histology interpretations. Monitors also demonstrated a very narrow variation of distance (< 2 mm) for ideal biopsy site placement.

The efficacy of topical benzocaine gel in providing anesthesia prior to cervical biopsy and endocervical curettage.

OBJECTIVES: Our goal was to determine the effectiveness of topical 20% benzocaine gel in providing anesthesia prior to cervical biopsy and endocervical curettage (ECC) and to identify specific patient characteristics that would predict which patients would be more likely to benefit from the application of benzocaine gel before cervical procedures. MATERIALS AND METHODS: Women requiring cervical biopsy and ECC completed a questionnaire that obtained demographical and pertinent gynecological information, perceived pain thresholds, and anxiety levels prior to the cervical biopsy procedures. Either benzocaine gel or a placebo was applied to the ectocervix and endocervical canal in a doubleblinded fashion. After each procedure, subjects reported the type, intensity, character, and duration of the sensation via visual analog scales (VAS) (0 = no sensation, 100 = maximum sensation). RESULTS: No difference was noted in the mean VAS scores reported by the placebo and benzocaine cohorts for the sensation felt at the time of cervical biopsy (30.1 SD ± 28.2 and 35.3 SD ± 24.3, respectively; p = .33). No significant difference in mean VAS scores was noted after ECC by the placebo cohort (53.0 SD ± 26.8) and the benzocaine cohort (41.0 SD ± 28.2; p = .09). Pain experienced with prior Papanicolaou (Pap) smears correlated significantly with the level of sensation noted during cervical biopsy (r = 0.395; p = .0001). The mean VAS scores for sensation experienced during cervical biopsy also were significantly greater among women who reported a history of dyspareunia (42.2 vs 27.7; p = .0059) and who reported a history of painful pelvic examinations (45.0 vs 29.8; p = .0125) than among women who did not report these painful experiences. CONCLUSIONS: Topical benzocaine gel was ineffective in reducing discomfort reported on cervical biopsy and ECC as compared with a placebo. Biopsy instrument sharpness may be a critically important factor that determines invoked pain. Discomfort associated with prior Pap smears, history of dyspareunia, and history of painful pelvic examinations correlated significantly with a greater perceived biopsy sensation. Prebiopsy recognition of these indicators may help clinicians to determine which women may be more likely to experience greater pain with cervical biopsy and enable them to intervene with other pain prevention measures.

Short-term plasticity in primary somatosensory cortex of the rat: rapid changes in magnitudes and latencies of neuronal responses following digit denervation.

Recordings were made from neurons in primary somatosensory (SmI) forepaw cortex of rats to study the time course of changes in responses beginning immediately following denervation (ligation) of a single digit. Before denervation, neuronal receptive fields (RFs) defined by tactile stimulation varied in size from small regions of one digit to larger areas covering several digits and palmar pads. With electrical stimulation, most neurons responded best to one (on-focus) digit and less to other (off-focus) digits; on-focus stimulation yielded more spikes per stimulus and shorter spike latencies (Lmin) than did off-focus stimulation. After ligation of the on-focus digit, most neurons showed increased responsiveness to stimulating one or several off-focus digits and palmar regions of the forepaw: (1) tactile stimulation showed that the RFs of all but one neuron expanded to include previously "ineffective" skin regions, such as digits or palmar pads adjoining the original RF; (2) electrical stimulation usually evoked stronger responses from neighboring off-focus digits and sometimes elicited novel responses from previously ineffective digits--seven of ten neurons showed increases in spikes per stimulus, which tended to approach stable values within 60-90 min after denervation; three of ten neurons showed decreases in Lmin with time, but most revealed no significant changes. These results suggest that dynamic response properties, as well as RFs, of SmI cortical neurons can be modified rapidly by blocking afferent input from dominant on-focus skin regions. RFs expand and novel responses appear, with concomitant increases in response magnitude and, in some cases, decreases in response latency over time. These findings seem to reflect a rapid increase in synaptic efficacy of weak or previously ineffective inputs from cutaneous afferent nerve fibers.

Women's use of over-the-counter antifungal medications for gynecologic symptoms.

BACKGROUND: Over-the-counter (OTC) antifungal products for vulvovaginal candidiasis (VVC) have gained tremendous popularity, as evidenced by staggering increases in sales since the products were switched from prescription-only to OTC status. The rapid escalation in the sale of these products may imply that women are using them inappropriately. The purposes of this study were to determine (1) whether women could correctly diagnose VVC and common genitourinary tract problems after reading classic case scenarios, (2) whether women could correctly select the appropriate treatment for these cases, and (3) whether a previous diagnosis of VVC by a clinician had any effect on a woman's ability to self-diagnose and self-treat VVC. METHODS: Women 16 years of age and older were recruited from medical and community sites to complete a 63-question survey instrument designed to assess their knowledge of the symptoms and signs of pelvic inflammatory disease, bacterial vaginosis, acute cystitis, vaginal trichomoniasis, and vulvovaginal candidiasis after reading classic case scenarios. RESULTS: A total of 601 women completed the questionnaire, 552 subjects and 49 medically trained women who served as a criterion standard for comparison. Of the 552 subjects, 365 reported a prior diagnosis of VCC and 154 reported no such prior diagnosis. The medically trained cohort was more accurate in diagnosing VVC (83.7% correct) than were subjects who had received a prior diagnosis of VVC (34.5% correct), and more accurate than subjects without a previous diagnosis of VVC (11.0% correct, P < .001). A greater percentage of subjects in whom VVC had been previously diagnosed, as compared with the medically trained cohort, would use OTC agents inappropriately for pelvic inflammatory disease (6.7% vs 4.3%, respectively; P = NS), bacterial vaginosis (14.6% vs 6.4%, respectively; P = .028), urinary tract infection (2.0% vs 0%, respectively; P < .001), and vaginal trichomoniasis (11.8% vs 6.6%, respectively; P = .048). CONCLUSIONS: A minority of women were able to correctly diagnose VVC from a classic case scenario. A prior clinical diagnosis of VVC had only a moderate positive effect on subjects' ability to correctly diagnose a classic case. Based on our findings, women likely use OTC antifungals inappropriately to treat gynecologic conditions that are similar but potentially more severe. Numerous adverse consequences may result from misdiagnosis. Improved patient education by health care providers and the manufacturers of OTC antifungal drugs might improve this diagnostic problem.