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Gary R Cutter

Publications and source records attributed to Gary R Cutter.

At least 19 recordsLinked to original sources
PubMed2022

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 &#xd7; 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 &#xd7; 10-5) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

Humans↗
PubMed2006

Randomized trials on consider this, a tailored, internet-delivered smoking prevention program for adolescents.

The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools containing Grades 6 through 9. Australian children using Consider This reported reduced 30-day smoking prevalence. This reduction was mediated by decreased subjective norms. The amount of program exposure was low in many classes, but program use displayed a dose-response relationship with reduced smoking prevalence. American children only reported lower expectations for smoking in the future. Intervening to prevent smoking is a challenge, and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation. Implementation remains the major challenge to delivering interventions via the Internet, both for health educators and researchers.

Adolescent↗
PubMed2006

Early inhaled nitric oxide therapy in premature newborns with respiratory failure.

BACKGROUND: The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain. METHODS: We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly. RESULTS: Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P=0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events. CONCLUSIONS: Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov].).

Administration, Inhalation↗
PubMed2006

Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis.

PURPOSE: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes. DESIGN: Cross-sectional study. PARTICIPANTS: Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes). METHODS: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness measured by OCT, and visual function test results. RESULTS: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum. CONCLUSIONS: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.

Acute Disease↗
PubMed2006

Effects of the Sunny Days, Healthy Ways curriculum on students in grades 6 to 8.

BACKGROUND: There are few effective sun-safety education programs for use in secondary schools. Project aims were to create a sun-safety curriculum for grades 6 to 8, and to test whether exposure to the curriculum would increase children's sun-protection behavior. DESIGN: A pair-matched, group-randomized, pre--post test, controlled trial was performed with middle schools as the unit of randomization. Teachers implemented the six-unit sun-safety curriculum in 2001-2003, and analyses were performed in 2003-2004. SETTING/PARTICIPANTS: A total of 2038 children from 30 middle schools in Colorado, New Mexico, and Arizona. MAIN OUTCOME MEASURES: Self-reported sun-protection behavior using frequency ratings and diary. RESULTS: Compared to control schools, children receiving the curriculum reported more frequent sun protection (p=0.0035), and a greater proportion wore long-sleeved shirts during recess (p<0.0001) and applied sunscreen (p<0.0001). Exposure to the curriculum improved knowledge (p<0.0001), decreased perceived barriers to using sunscreen (p=0.0046), enhanced self-efficacy expectations (p=0.0577) about sun safety, and reduced favorable attitudes toward sun tanning (p=0.0026 to <0.0001). In intent-to-treat analyses, the treatment effect was eliminated only under the most conservative assumptions about dropouts. CONCLUSIONS: Educational approaches to sun safety in middle school may be effective for improving children's sun safety. Potential trial limitations include measuring short-term outcomes, focusing on young adolescents, using active parental consent, and testing in the American Southwest.

Adolescent↗
PubMed2006

Mediation of a middle school skin cancer prevention program.

This study tested potential mediators of a school-based skin cancer prevention intervention for middle school children (6th-8th grades; N = 1,788). Ten variables were tested on 4 criteria to establish mediation, including (a) intervention related to outcome, (b) intervention related to mediators, (c) mediators related to outcome, and (d) mediated effect statistically significant. Sun-safe behaviors (e.g., sunscreen use) and potential mediators were measured with a self-report questionnaire. All criteria were met for Barriers--Sunscreen, Perceived Self-Efficacy, and Knowledge when the mediators were tested separately. In multiple mediator analyses, barriers to sunscreen use and self-efficacy satisfied Criteria 1-3 but were not statistically significant (Criterion 4). Barriers to sunscreen use, perceived self-efficacy for sun-safe behavior, and knowledge may serve as mediators.

Adolescent↗
PubMed2005

Current realities of delivering mammography services in the community: do challenges with staffing and scheduling exist?

PURPOSE: To evaluate the current (2001-2002) capacity of community-based mammography facilities to deliver screening and diagnostic services in the United States. MATERIALS AND METHODS: Institutional review board approvals and patient consent were obtained. A mailed survey was sent to 53 eligible mammography facilities in three states (Washington, New Hampshire, and Colorado). Survey questions assessed equipment and staffing availability, as well as appointment waiting times for screening and diagnostic mammography services. Criterion-related content and construct validity were obtained first by means of a national advisory committee of academic, scientific, and clinical colleagues in mammography that reviewed literature on existing surveys and second by pilot testing a series of draft surveys among community mammography facilities not inclusive of the study facilities. The final survey results were independently double entered into a relational database with programmed data checks. The data were sent encrypted by means of file transfer protocol to a central analytical center at Group Health Cooperative. A two-sided P value with alpha = .05 was considered to show statistical significance in all analyses. RESULTS: Forty-five of 53 eligible mammography facilities (85%) returned the survey. Shortages of radiologists relative to the mammographic volume were found in 44% of mammography facilities overall, with shortages of radiologists higher in not-for-profit versus for-profit facilities (60% vs 28% reported). Shortages of Mammography Quality Standards Act-qualified technologists were reported by 20% of facilities, with 46% reporting some level of difficulty in maintaining qualified technologists. Waiting times for diagnostic mammography ranged from less than 1 week to 4 weeks, with 85% performed within 1 week. Waiting times for screening mammography ranged from less than 1 week to 8 weeks, with 59% performed between 1 week and 4 weeks. Waiting times for both diagnostic and screening services were two to three times higher in high-volume compared with low-volume facilities. CONCLUSION: Survey results show shortages of radiologists and certified mammography technologists.

Breast Neoplasms↗
PubMed2005

Association between mammography timing and measures of screening performance in the United States.

PURPOSE: To evaluate whether there is an association between the number of months since previous mammography (MSPM) and performance measures (sensitivity, specificity, recall rate, cancer detection rate, and positive predictive value) in women who underwent U.S. community-based screening mammography. MATERIALS AND METHODS: Data from seven registries (Breast Cancer Surveillance Consortium) and mammographic data and cancer outcome in regard to 1 213 754 screening mammographic examinations performed in 680 641 women who were 40-89 years old for the years 1996-2000 were used in this study. These data are submitted annually in a standard format to a central statistical coordinating center that is subject to institutional review board approval, quality control, and confidentiality standards. Performance measures were calculated for first and subsequent screening mammography. For subsequent mammography, performance measures were calculated according to categories of MSPM (9-15, 16-20, 21-27, and >/=28 months). Receiver operating characteristic and multivariable logistic regression analyses were conducted to test the association between the number of MSPM and performance measures. RESULTS: With increasing MSPM in each category from 9-15 to 28 months or more and for first mammographic examinations, respectively, there was increased sensitivity (70.9%, 75.7%, 85.4%, 82.5%, and 88.6%), decreased specificity (93.3%, 92.7%, 91.6%, 91.0%, and 85.9%), increased recall rate (7.0%, 7.6%, 8.8%, 9.4%, and 14.7%), and increased cancer detection rates (3.2, 3.5, 4.5, 4.6, and 6.1 per 1000 mammographic examinations). When the category of 9-15 MSPM was compared with that of 21-27 MSPM, there was a slight increase in positive predictive value from 4.6% to 5.1%. Confidence intervals were narrow and did not overlap. Age affected these associations for all performance measures except sensitivity. CONCLUSION: Performance measures increased as MSPM increased, except for specificity, which decreased. Time between mammograms is an important factor to consider when audits are reviewed or screening performance measures are compared.

Adult↗
PubMed2005

Does litigation influence medical practice? The influence of community radiologists' medical malpractice perceptions and experience on screening mammography.

PURPOSE: To assess the relationship between radiologists' perception of and experience with medical malpractice and their patient-recall rates in actual community-based clinical settings. MATERIALS AND METHODS: All study activities were approved by the institutional review boards of the involved institutions, and patient and radiologist informed consent was obtained where necessary. This study was performed in three regions of the United States (Washington, Colorado, and New Hampshire). Radiologists who routinely interpret mammograms completed a mailed survey that included questions on demographic data, practice environment, and medical malpractice. Survey responses were linked to interpretive performance for all screening mammography examinations performed between January 1, 1996, and December 31, 2001. The odds of recall were modeled by using logistic regression analysis based on generalized estimating equations that adjust for study region. RESULTS: Of 181 eligible radiologists, 139 (76.8%) returned the survey with full consent. The analysis included 124 radiologists who had interpreted a total of 557 143 screening mammograms. Approximately half (64 of 122 [52.4%]) of the radiologists reported a prior malpractice claim, with 18 (14.8%) reporting mammography-related claims. The majority (n = 51 [81.0%]) of the 63 radiologists who responded to a question regarding the degree of stress caused by a medical malpractice claim described the experience as very or extremely stressful. More than three of every four radiologists (ie, 94 [76.4%] of 123) expressed concern about the impact medical malpractice has on mammography practice, with over half (72 [58.5%] of 123) indicating that their concern moderately to greatly increased the number of their recommendations for breast biopsies. Radiologists' estimates of their future malpractice risk were substantially higher than the actual historical risk. Almost one of every three radiologists (43 of 122 [35.3%]) had considered withdrawing from mammogram interpretation because of malpractice concerns. No significant association was found between recall rates and radiologists' experiences or perceptions of medical malpractice. CONCLUSION: U.S. radiologists are extremely concerned about medical malpractice and report that this concern affects their recall rates and biopsy recommendations. However, medical malpractice experience and concerns were not associated with recall or false-positive rates. Heightened concern of almost all radiologists may be a key reason that recall rates are higher in the United States than in other countries, but this hypothesis requires further study.

Adult↗
PubMed2005

Randomized trial testing a worksite sun protection program in an outdoor recreation industry.

Health communication campaigns intended to reduce chronic and severe exposure to ultraviolet radiation in sunlight and prevent skin cancer are a national priority. Outdoor workers represent an unaddressed, high-risk population. Go Sun Smart (GSS), a worksite sun safety program largely based on the diffusion-of-innovations theory, was evaluated in a pair-matched, group-randomized, pretest-posttest controlled design enrolling employees at 26 ski areas in Western North America. Employees at the intervention ski areas were more aware of GSS (odds ratio [OR] = 8.27, p < .05) and reported less sunburning (adjusted OR = 1.63, p < .05) at posttest than employees at the control areas. A dose response was evident (OR = 1.46, p < .05) with greater observed program implementation associated with fewer sunburns among employees. Program awareness per se was not predictive (p > .05) of reduced sunburning in a mediational analysis. Analyses of nonrespondents, including intent-to-treat analyses, further supported the success of GSS.

Adolescent↗
PubMed2005

Community-based mammography practice: services, charges, and interpretation methods.

OBJECTIVE: The purpose of our study was to accurately describe facility characteristics among community-based screening and diagnostic mammography practices in the United States. MATERIALS AND METHODS: A survey was developed and applied to community-based facilities providing screening mammography in three geographically distinct locations in the states of Washington, Colorado, and New Hampshire. The facility survey was conducted between December 2001 and September 2002. Characteristics surveyed included facility type, services offered, charges for screening and diagnostic mammography, information systems, and interpretation methods, including the frequency of double interpretation. RESULTS: Among 45 responding facilities, services offered included screening mammography at all facilities, diagnostic mammography at 34 facilities (76%), breast sonography at 30 (67%), breast MRI at seven (16%), and nuclear medicine breast scanning at seven (16%). Most facilities surveyed were radiology practices in nonhospital settings. Eight facilities (18%) reported performing clinical breast examinations routinely along with screening mammography. Only five screening sites (11%) used computer-aided detection (CAD) and only two (5%) used digital mammography. Nearly two thirds of facilities interpreted screening mammography examinations on-site, whereas 91% of facilities interpreted diagnostic examinations on-site. Only three facilities (7%) interpreted screening examinations on line as they were performed. Approximately half of facilities reported using some type of double interpretation, although the methods of double interpretation and the fraction of cases double-interpreted varied widely across facilities. On average, approximately 15% of screening examinations and 10% of diagnostic examinations were reported as being double-interpreted. CONCLUSION: Comparison of this survey's results with those collected a decade earlier indicates dramatic changes in the practice of mammography, including a clear distinction between screening and diagnostic mammography, batch interpretation of screening mammograms, and improved quality assurance and medical audit tools. Diffusion of new technologies such as CAD and digital mammography was not widespread. The methods of double-interpretation and the fraction of cases double-interpreted varied widely across study sites.

Breast Neoplasms↗
PubMed2004

CCR2-64I polymorphism and CCR5Delta32 deletion in patients with Alzheimer's disease.

Monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as their related receptors, have been shown to be involved in Alzheimer's disease (AD) pathogenesis. Genes for their related receptors, CCR2 and CCR5, respectively, are characterized by the presence of two polymorphisms: a conservative change of a valine with an isoleucine at codon 64 of CCR2 (CCR2-64I) and a 32-bp deletion in the coding region of CCR5 (CCR5Delta32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Delta32 polymorphisms was determined in 290 AD patients and in 222 controls. A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found, thus suggesting a protective effect of the mutated allele on the occurrence of AD. However, these findings must be cautiously interpreted as the overall significance was found without adjustment for multiple comparisons and is coming from the complete absence of the genotype 64I/64I in AD patients. Conversely, no different distribution of the CCR5Delta32 deletion in the two populations was shown. Stratifying by the presence of ApoE varepsilon4 allele, gender or age at onset, no differences in either allele frequencies were observed.

Adult↗
PubMed2004

The association between obesity and screening mammography accuracy.

BACKGROUND: Obesity is increasing among American women, especially as they age. The influence of obesity on the accuracy of screening mammography has not been studied extensively. METHODS: We analyzed 100 622 screening mammography examinations performed on members of a nonprofit health plan. The relationship between body mass index (weight in kilograms divided by the square of height in meters) and measures of screening accuracy was assessed. Body mass index was categorized as underweight or normal weight (<25), overweight (25-29), obesity class I (30-34), and obesity classes II to III (> or =35). RESULTS: Compared with underweight or normal weight women, overweight and obese women were more likely to be recalled for additional tests after adjusting for important covariates, including age and breast density (overweight odds ratio [OR], 1.17; 95% confidence interval [CI], 1.11-1.23); obesity class I OR, 1.27; 95% CI, 1.19-1.35; obesity classes II-III OR, 1.31; 95% CI, 1.22-1.41). As body mass index increased, women were more likely to have lower specificity (overweight OR, 0.86; 95% CI, 0.81-0.90; obesity class I OR, 0.79; 95% CI, 0.74-0.84; and obesity classes II-III OR, 0.77; 95% CI, 0.71-0.82). No statistically significant differences were noted in sensitivity. Adjusted receiver operating characteristic analysis showed statistically significant improvement in the area under the curve (AUC) for underweight or normal weight women (AUC = 0.941) vs overweight women (AUC = 0.916, P =.02) and underweight or normal weight women vs obesity classes II and III women (AUC = 0.904, P =.02). CONCLUSIONS: Obese women had more than a 20% increased risk of having false-positive mammography results compared with underweight and normal weight women, although sensitivity was unchanged. Achieving a normal weight may improve screening mammography performance.

Adult↗
PubMed2003

Enhancing antimelanoma immune responses through apoptosis.

We examined the feasibility of using tumor apoptosis at accessible sites to enhance antimelanoma immune responses in a model of spontaneous canine melanoma. We show that priming peripheral blood mononuclear cells with apoptotic melanoma cells significantly enhanced autologous and allogeneic lymphokine-activated killing of tumor cells. Since various pathways required for intrinsic apoptosis are often inactivated in melanoma, we used Fas ligand (FasL) overexpression to promote extrinsic apoptosis. FasL induced apoptosis in five of six cell lines. Each of the susceptible lines, but not the resistant one, expressed Fas mRNA. In addition, direct intratumoral administration of FasL DNA to tumor-bearing dogs was safe, with no adverse events reported over 7 days of observation. A reduction of tumor burden was seen in three of five dogs treated. The reduction of tumor volume was correlated with Fas expression by the tumors, although one dog with a Fas-negative tumor survived for 82 weeks after treatment. Our data show that overexpression of FasL is suitable to promote apoptosis of Fas(+) melanomas, and support the notion that priming immune responder cells with apoptotic tumor cells may enhance antitumor responses. The results also suggest that intratumoral administration of FasL offers a safe route for therapeutic gene delivery.

Animals↗
PubMed2003

The prevalence and predictors of helmet use by skiers and snowboarders at ski areas in western North America in 2001.

BACKGROUND: Helmets may protect the heads of skiers and snowboarders. The prevalence of helmet use by these groups was estimated. METHODS: Helmet use was observed in face-to-face surveys (N = 2,978) on sun protection at 28 ski areas in Alaska, California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and British Columbia (0.7% refusal rate) from January to April 2001. RESULTS: Helmets were worn by 12.1% (95% confidence interval [CI], 11.0-13.3) of the sample. Use was highest among guests who skied or snowboarded more frequently (fourth quartile vs. first quartile, odds ratio [OR] = 11.998 [95% CI, 6.774-21.251]; third vs. first, OR = 5.556 [95% CI, 3.119-9.896]; second vs. first, OR = 2.186 [95% CI, 1.162-4.112]), were experts (OR = 3.326 [95% CI, 1.297-8.528]), used snowboards (OR = 2.301 [95% CI, 1.731-3.058]), and were more educated (college graduate, OR = 2.167 [95% CI, 1.271-3.695]; some college, OR = 1.969 [95% CI, 1.130-3.431]). CONCLUSION: Helmet use was generally low but may be high enough by experts, snowboarders, and in the central Rocky Mountains to produce a norm stimulating further adoption.

Adult↗