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Biomedical subjects

Gary Cutter

Publications and source records attributed to Gary Cutter.

At least 19 recordsLinked to original sources
PubMed2024

Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis.

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS. METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression. RESULTS: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. INTERPRETATION: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Humans↗
PubMed2006

Persistent pain and uncomfortable sensations in persons with multiple sclerosis.

The experience of pain has been documented in small studies of individuals with multiple sclerosis (MS). The present study examines the prevalence of persistent pain and uncomfortable sensations among participants in the large North American Research Committee on MS (NARCOMS) Patient Registry. Registrants (10,176) responded to a questionnaire on pain and 7579 reported experiencing some level of pain during the month prior to the survey. Among the respondents 49% reported mild to severe pain and 49% of those indicated severe pain. Increased pain intensity was positively associated with gender (more women), multiple pain sites (51% of the severe pain group reported four or more pain sites), and constancy of pain (44% among the group with severe pain). There was also a positive association with increased MS-related disability, relapsing-worsening type of MS, and depression. Respondents with severe pain made greater use of the healthcare system and of prescribed analgesics, but were less likely to be satisfied with their doctors' efforts to manage their pain. About one-third of the patients with moderate pain and 18% of those with severe pain reported no consultations for their pain. The effects of pain severity were fully evident in the respondents' daily life, their work, mood, recreational activities and enjoyment of life. Our results indicate that the high prevalence of MS-related severe pain, low satisfaction with management of intense pain, and the perceived interference with quality of life indicators necessitate greater attention by healthcare providers to the management of pain and uncomfortable sensations in the MS population.

Activities of Daily Living↗
PubMed2006

Reality check: perceived versus actual performance of community mammographers.

OBJECTIVE: Federal regulations mandate that radiologists receive regular albeit limited feedback regarding their interpretive accuracy in mammography. We sought to determine whether radiologists who regularly receive more extensive feedback can report their actual performance in screening mammography accurately. SUBJECTS AND METHODS: Radiologists (n = 105) who routinely interpret screening mammograms in three states (Washington, Colorado, and New Hampshire) completed a mailed survey in 2001. Radiologists were asked to estimate how frequently they recommended additional diagnostic testing after screening mammography and the positive predictive value of their recommendations for biopsy (PPV2). We then used outcomes from 336,128 screening mammography examinations interpreted by the radiologists from 1998 to 2001 to ascertain their true rates of recommendations for diagnostic testing and PPV2. RESULTS: Radiologists' self-reported rate of recommending immediate additional imaging (11.1%) exceeded their actual rate (9.1%) (mean difference, 1.9%; 95% confidence interval [CI], 0.9-3.0%). The mean self-reported rate of recommending short-interval follow-up was 6.2%; the true rate was 1.8% (mean difference, 4.3%; 95% CI, 3.6-5.1%). Similarly, the mean self-reported and true rates of recommending immediate biopsy or surgical evaluation were 3.2% and 0.6%, respectively (mean difference, 2.6%; 95% CI, 1.8-3.4%). Conversely, radiologists' mean self-reported PPV2 (18.3%) was significantly less than their mean true PPV2 (27.6%) (mean difference, -9.3%; 95% CI, -12.4% to -6.2%). CONCLUSION: Despite regular performance feedback, community radiologists may overestimate their true rates of recommending further evaluation after screening mammography and underestimate their true positive predictive value.

Biopsy↗
PubMed2005

Physician predictors of mammographic accuracy.

BACKGROUND: The association between physician experience and the accuracy of screening mammography in community practice is not well studied. We identified characteristics of U.S. physicians associated with the accuracy of screening mammography. METHODS: Data were obtained from the Breast Cancer Surveillance Consortium and the American Medical Association Master File. Unadjusted mammography sensitivity and specificity were calculated according to physician characteristics. We modeled mammography sensitivity and specificity by multivariable logistic regression as a function of patient and physician characteristics. All statistical tests were two-sided. RESULTS: We studied 209 physicians who interpreted 1,220,046 screening mammograms from January 1, 1995, through December 31, 2000, of which 7143 (5.9 per 1000 mammograms) were associated with breast cancer within 12 months of screening. Each physician interpreted a mean of 6011 screening mammograms (95% confidence interval [CI] = 4998 to 6677), including a mean of 34 (95% CI = 28 to 40) from women diagnosed with breast cancer. The mean sensitivity was 77% (range = 29%-97%), and the mean false-positive rate was 10% (range = 1%-29%). After adjustment for the patient characteristics of those whose mammograms they interpreted, physician characteristics were strongly associated with specificity. Higher specificity was associated with at least 25 years (versus less than 10 years) since receipt of a medical degree (for physicians practicing for 25-29 years, odds ratio [OR] = 1.54, 95% CI = 1.14 to 2.08; P = .006), interpretation of 2500-4000 (versus 481-750) screening mammograms annually (OR = 1.30, 95% CI = 1.06 to 1.59; P = .011) and a high focus on screening mammography compared with diagnostic mammography (OR = 1.59, 95% CI = 1.37 to 1.82; P<.001). Higher overall accuracy was associated with more experience and with a higher focus on screening mammography. Compared with physicians who interpret 481-750 mammograms annually and had a low screening focus, physicians who interpret 2500-4000 mammograms annually and had a high screening focus had approximately 50% fewer false-positive examinations and detected a few less cancers. CONCLUSION: Raising the annual volume requirements in the Mammography Quality Standards Act might improve the overall quality of screening mammography in the United States.

Adult↗
PubMed2005

Assessing accuracy of mammography in the presence of verification bias and intrareader correlation.

The performance of a medical diagnostic test is often evaluated by comparing the outcome of the test to the patient's true disease state. Receiver operating characteristic analysis may then be used to summarize test accuracy. However, such analysis may encounter several complications in actual practice. One complication is verification bias, i.e., gold standard assessment of disease status may only be partially available and the probability of ascertainment of disease may depend on both the test result and characteristics of the subject. A second issue is that tests interpreted by the same rater may not be independent. Using estimating equations, we generalize previous methods that address these problems. We contrast the performance of alternative estimators of accuracy using robust sandwich variance estimators to permit valid asymptotic inference. We suggest that in the context of an observational cohort study where rich covariate information is available, a weighted estimating equations approach may be preferable for its robustness against model misspecification. We apply the methodology to mammography as performed by community radiologists.

Bias↗
PubMed2005

Validation of the NARCOMS Registry: pain assessment.

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a multiple sclerosis (MS) self-report registry with more than 24,000 participants. Participants report disability status upon enrollment, and semi-annually using Performance Scales (PS), Patient Determined Disease Steps (PDDS) and a pain question. In November 2000 and 2001, we also collected the Pain Effects Scale (PES). Our aim was to validate the NARCOMS pain question using the PES as our criterion measure. We measured correlations between the pain question and age, disease duration, various PS subscales and PDDS to assess construct validity. We correlated pain question responses in participants who reported no change in PDSS or the PS subscales between questionnaires to determine test-retest reliability. We measured responsiveness in participants who reported a substantial change in the sensory, spasticity PS subscales. The correlation between the pain question and PES was r = 0.61 in November 2000, and r = 0.64 in November 2001 (both P < 0.0001). Correlations between the pain question and age, and disease duration were low, indicating divergent validity. Correlations between the pain question and spasticity, sensory PS subscales and PDSS were moderate, indicating convergent validity. Test-retest reliability was r = 0.84 (P < 0.0001). Responsiveness was 70.7%. The pain question is a valid self-report measure of pain in MS.

Adult↗
PubMed2005

Validation of the NARCOMS registry: fatigue assessment.

Participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry report disability using Performance Scales (PS), which assess eight domains. We aimed to validate the PS fatigue subscale (PSF) using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) as external criteria. We measured correlations between the PSF and age, disease duration and PS subscales to assess construct validity. The PSF correlated strongly with the MFIS (r =0.72, P <0.0001) and FSS (r =0.75, P <0.0001). Correlations between the PSF and age, disease duration were low, indicating divergent validity. Correlations between the PSF and spasticity, sensory and mobility PS scales were moderate, indicating convergent validity. The PSF has adequate criterion and construct validity in MS.

Disability Evaluation↗
PubMed2005

Randomized effectiveness trial of a computer-assisted intervention to improve diabetes care.

OBJECTIVE: There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care settings. This report presents 12-month follow-up results from a computer-assisted, patient-centered intervention to improve the level of recommended services patients received from a variety of primary care settings. RESEARCH DESIGN AND METHODS: A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on two primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program (PRP). Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale, lipid and HbA1c levels, and the Patient Health Questionnaire-9 depression scale. RESULTS: The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition. There was overall improvement on secondary outcomes of lipids, HbA1c, quality of life, and depression scores; between-condition differences were not significant. CONCLUSIONS: Staff in small, mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care. Alternative explanations for why these process improvements did not lead to improved outcomes, and suggested directions for future research are discussed.

Colorado↗
PubMed2004

Accuracy of screening mammography interpretation by characteristics of radiologists.

BACKGROUND: Radiologists differ in their ability to interpret screening mammograms accurately. We investigated the relationship of radiologist characteristics to actual performance from 1996 to 2001. METHODS: Screening mammograms (n = 469,512) interpreted by 124 radiologists were linked to cancer outcome data. The radiologists completed a survey that included questions on demographics, malpractice concerns, years of experience interpreting mammograms, and the number of mammograms read annually. We used receiver operating characteristics (ROC) analysis to analyze variables associated with sensitivity, specificity, and the combination of the two, adjusting for patient variables that affect performance. All P values are two-sided. RESULTS: Within 1 year of the mammogram, 2402 breast cancers were identified. Relative to low annual interpretive volume (< or =1000 mammograms), greater interpretive volume was associated with higher sensitivity (P = .001; odds ratio [OR] for moderate volume [1001-2000] = 1.68, 95% CI = 1.18 to 2.39; OR for high volume [>2000] = 1.89, 95% CI = 1.36 to 2.63). Specificity decreased with volume (OR for 1001-2000 = 0.65, 95% CI = 0.52 to 0.83; OR for more than 2000 = 0.76, 95% CI = 0.60 to 0.96), compared with 1000 or less (P = .002). Greater number of years of experience interpreting mammograms was associated with lower sensitivity (P = .001), but higher specificity (P = .003). ROC analysis using the ordinal BI-RADS interpretation showed an association between accuracy and both previous mammographic history (P = .012) and breast density (P<.001). No association was observed between accuracy and years interpreting mammograms (P = .34) or mammography volume (P = .94), after adjusting for variables that affect the threshold for calling a mammogram positive. CONCLUSIONS: We found no evidence that greater volume or experience at interpreting mammograms is associated with better performance. However, they may affect sensitivity and specificity, possibly by determining the threshold for calling a mammogram positive. Increasing volume requirements is unlikely to improve overall mammography performance.

Adult↗
PubMed2004

Effect of breast augmentation on the accuracy of mammography and cancer characteristics.

CONTEXT: Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. OBJECTIVE: To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. MAIN OUTCOME MEASURES: Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. RESULTS: Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval [CI], 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P =.008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P =.052) for women with breast augmentation vs without. CONCLUSIONS: Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.

Adult↗
PubMed2004

A practical randomized trial to improve diabetes care.

OBJECTIVE: There is a well-documented gap between diabetes care guidelines and the services received by patients in almost all health care settings. This project reports initial results from a computer-assisted, patient-centered intervention to improve the level of recommended services received by patients from a wide variety of primary care providers. DESIGN AND SETTINGS: Eight hundred eighty-six patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on 2 primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed. Secondary outcomes were evaluated using the Problem Areas in Diabetes scale and the Patient Health Questionnaire (PHQ)-9 depression scale, and the RE-AIM framework was used to evaluate potential for dissemination. RESULTS: The program was well-implemented and significantly improved both number of recommended laboratory assays (3.4 vs 3.1; P <.001) and patient-centered aspects of diabetes care patients received (3.6 vs 3.2; P <.001) compared to those in randomized control practices. Activities that were increased most were foot exams (follow-up rates of 80% vs 52%; P <.003) and nutrition counseling (76% vs 52%; P <.001). CONCLUSIONS: Patients are very willing to participate in a brief computer-assisted intervention that is effective in enhancing quality of diabetes care. Staff in primary care offices can consistently deliver an intervention of this nature, but most physicians were unwilling to participate in this translation research study.

Attitude of Health Personnel↗
PubMed2003

Effect of relapses on development of residual deficit in multiple sclerosis.

OBJECTIVE: To determine the percentage of patients with residual deficits following multiple sclerosis (MS) exacerbations and the magnitude of those deficits using a database of pooled placebo patients from clinical trials. METHODS: A database of patients assigned to the placebo group in several randomized clinical trials was queried to determine those patients with Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale assessments prior to, at the time of, and after an acute exacerbation of MS. The extent of deficit present at these time points was compared to determine the acute effect of exacerbations and the degree of persistent disability. RESULTS: Forty-two percent of patients had residual deficit of at least 0.5 and 28% had residual of >or=1.0 EDSS units, at an average of 64 days after an exacerbation. The results were reproduced across subsequent exacerbations and were sustained over time. The subgroup of patients with measurable change in EDSS during the exacerbation had more extensive residual impairment on the follow-up visits. Similar results were seen when the Scripps score was examined. CONCLUSION: MS exacerbations produce a measurable and sustained effect on disability.

Adolescent↗
PubMed2003

Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population.

PURPOSE: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. METHODS: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. RESULTS: Compared with nonusers, women using estrogen and progestin for >/= 5 years were at increased risk of breast tumors of stage 0 or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size </= 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77), grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive (RR, 1.72; 95% CI, 1.55 to 1.90). Estrogen-only users were slightly more likely to have estrogen receptor-positive breast cancer compared with nonusers (RR, 1.14; 95% CI, 1.06 to 1.23). CONCLUSION: Use of estrogen and progestin postmenopausal hormone therapy for five years or more increased the likelihood of developing breast cancer, including both tumors with favorable prognostic features and tumors with unfavorable prognostic features.

Aged↗
PubMed2003

A randomized controlled study of the acute and chronic effects of cooling therapy for MS.

BACKGROUND: Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. The therapeutic effects of cooling in patients with MS have not been convincingly demonstrated because prior studies were limited by uncontrolled designs, unblinded evaluations, reliance on subjective outcome measures, and small sample sizes. OBJECTIVE: To determine the effects of a single acute dose of cooling therapy using objective measures of neurologic function in a controlled, double-blinded setting, and to determine whether effects are sustained during daily cooling garment use. METHODS: Patients (n = 84) with definite MS, mild to moderate disability (Expanded Disability Status Scale score < 6.0), and self-reported heat sensitivity were randomized into a multicenter, sham-treatment controlled, double-blind crossover study. Patients had the MS Functional Composite (MSFC) and measures of visual acuity/contrast sensitivity assessed before and after high-dose or low-dose cooling for 1 hour with a liquid cooling garment. One week later, patients had identical assessments before and after the alternate treatment. Patients were then re-randomized to use the cooling garment 1 hour each day for a month or to have observation only. They completed self-rated assessments of fatigue, strength, and cognition during this time, and underwent another acute cooling session at the end of the period. After 1 week of rest, they had identical assessments during the alternate treatment. RESULTS: Body temperature declined during both high-dose and low-dose cooling, but high-dose produced a greater reduction (p < 0.0001). High-dose cooling produced a small improvement in the MSFC (0.076 +/- 0.66, p = 0.007), whereas low-dose cooling produced only a trend toward improvement (0.053 +/- 0.031, p = 0.09), but the difference between conditions was not significant. Timed gait testing and visual acuity/contrast sensitivity improved in both conditions as well. When patients underwent acute cooling following a month of daily cooling, treatment effects were similar. Patients reported less fatigue during the month of daily cooling, concurrently on the Rochester Fatigue Diary and retrospectively on the Modified Fatigue Impact Scale. CONCLUSIONS: Cooling therapy was associated with objectively measurable but modest improvements in motor and visual function as well as persistent subjective benefits.

Adolescent↗
PubMed2003

Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography.

BACKGROUND: The relationships among breast density, age, and use of hormone replacement therapy (HRT) in breast cancer detection have not been fully evaluated. OBJECTIVE: To determine how breast density, age, and use of HRT individually and in combination affect the accuracy of screening mammography. DESIGN: Prospective cohort study. SETTING: 7 population-based mammography registries in North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California. PARTICIPANTS: 329 495 women 40 to 89 years of age who had 463 372 screening mammograms from 1996 to 1998; 2223 women received a diagnosis of breast cancer. MEASUREMENTS: Breast density, age, HRT use, rate of breast cancer occurrence, and sensitivity and specificity of screening mammography. RESULTS: Adjusted sensitivity ranged from 62.9% in women with extremely dense breasts to 87.0% in women with almost entirely fatty breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44 years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity increased from 89.1% in women with extremely dense breasts to 96.9% in women with almost entirely fatty breasts. In women who did not use HRT, adjusted specificity increased from 91.4% in women 40 to 44 years of age to 94.4% in women 80 to 89 years of age. In women who used HRT, adjusted specificity was about 91.7% for all ages. CONCLUSIONS: Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density.

Adipose Tissue↗
PubMed2003

Factors that predict health-related quality of life in patients with relapsing-remitting multiple sclerosis.

Health-Related Quality of Life (HRQoL) research is gaining acceptance in the field of multiple sclerosis (MS). Little is known about what precipitates quality of life change. It was hypothesized that physical aspects of quality of life decline with worsening objective disease measures and psychosocial aspects remain relatively stable regardless of change in objective measures. These assumptions are tested using data from a Phase 3 study of relapsing-remitting MS patients treated with interferon beta-1a and reassessed approximately eight years after study initiation. The Sickness Impact Profile (SIP) questionnaire is the generic quality of life measure used in this study. Three summary scores of the SIP (Physical, Psychosocial, and Total scores), Expanded Disability Status Scores, Multiple Sclerosis Functional Composite, and Brain Parenchymal Fraction were determined at baseline, year 2, and after an average of 8.1 years from study entry. SIP data collected during a clinic visit were available from 137 of the original 172 participants. All objective indicators worsened by follow-up. SIP Physical and Total scores significantly worsened from baseline to follow-up. SIP Psychosocial showed nonsignificant worsening. Regression analysis indicated that final measures of SIP Physical and Total scores were most strongly associated with change in objective measures and follow-up SIP Psychosocial was most strongly related to earlier scores on the same measure.

Adjuvants, Immunologic↗