Molecular classification of autofluorescence excision margins in oral potentially malignant disorders.

OBJECTIVE: To define molecular differences between autofluorescence and white light defined excision margins in oral potentially malignant disorders (OPMD) using transcriptome expression profiles. MATERIALS AND METHODS: Excisional biopsy specimens were taken from 11 patients at three different sites for each lesion: centre, white light margin and autofluorescence margin. The lesions were diagnosed histopathologically as oral epithelial dysplasia, oral lichenoid dysplasia, oral lichen planus or other. Transcriptome analysis was performed by RNA sequencing, hierarchical clustering, differential expression and biological pathway analysis. RESULTS: For hierarchical clustering, the samples broadly clustered according to histology rather than the margins with lichenoid samples clustering together. Differential expression analysis showed that independent of histology, there was greater molecular dysregulation between the lesion centre and autofluorescence margin compared to the lesion centre and white light margin. Furthermore, the autofluorescence and white light margins were molecularly distinct, indicating the white light margins harboured abnormality. CONCLUSION: Our results indicate that the molecular profile of OPMD changes with divergence away from the centre of the lesion, and that autofluorescence determined margins are superior to the white light margin in achieving a clear molecular margin when excising an OPMD.

Cumulative sum failure analysis of a policy change from on-pump to off-pump coronary artery bypass grafting.

BACKGROUND: Use of the sequential probability cumulative sum (CUSUM) technique may be more sensitive than standard statistical analyses in detecting a cluster of surgical failures. We applied CUSUM methods to evaluate the learning curve after a policy change by a single surgeon from routine on-pump (cardiopulmonary bypass [CPB]) to off-pump coronary artery bypass grafting (OPCAB). METHODS: Fifty-five consecutive first-time coronary artery bypass patients (CPB group) were compared with the next 55 patients undergoing an attempt at routine OPCAB using the same coronary stabilizer. The goal in OPCAB patients was to obtain complete revascularization, albeit with a low threshold for conversion to CPB to maximize patient safety during the learning curve. Preoperative patient risk was calculated using previously validated models of the Cardiac Care Network of Ontario. The occurrence of operative mortality and nine predefined major complications (myocardial infarction, bleeding, stroke, renal failure, balloon pump use, mediastinitis, respiratory failure, life-threatening arrhythmia, and sepsis) was compared between the CPB and OPCAB groups using Wilcoxon, Fisher exact, and two-tailed t tests, as well as CUSUM methodology. An intention to treat analysis was performed. RESULTS: The CPB and OPCAB groups had similar predicted mortality and length of stays (2.2% +/- 2.5%, 8.1 +/- 2.5 days versus 2.4% +/- 3.5%, 8.1 +/- 2.4 days, respectively). The mean number of grafts per patient was 3.1 +/- 0.7 in the CPB group versus 3.0 +/- 0.7 in the OPCAB group (p = 0.45). Two of 55 (3.6%) CPB patients died, as opposed to 1 of 55 (1.8%) OPCAB patients (p = 0.99). Eight of 55 CPB patients (14.5%) incurred major complications, as opposed to 4 of 55 (7.3%) OPCAB patients (p = 0.36). Median hospital length of stay was 6.0 days in the CPB group versus 5.0 days in the OPCAB group (p = 0.28). On CUSUM analysis, the failure curve in CPB patients approached the upper 80% alert line after eight cases, whereas the curve in OPCAB patients reached below the lower 80% (reassurance) boundary 28 cases after the policy change, indicating superior results in the OPCAB group despite the learning curve. CONCLUSIONS: A policy change from coronary artery bypass on CPB to routinely attempting OPCAB can be accomplished safely despite the learning curve. CUSUM analysis was more sensitive than standard statistical methods in detecting a cluster of surgical failures and successes.

Targeted mailed materials and the Medicare beneficiary: increasing mammogram screening among the elderly.

OBJECTIVES: Older women have the highest breast cancer rates but are underscreened relative to their risk. Racial/ethnic minority women especially have low screening rates, often because of financial constraints. In response, Medicare introduced subsidized biennial mammogram benefits in 1991. This study examined the effect on mammography rates of an intervention that informed women about the Medicare benefit. METHODS: A list frame method of subject selection was used to select random samples of eligible women from the Health Care Financing Administration's master beneficiary file. Women were interviewed by telephone in 1991 (N = 917) before the targeted mailing and in 1993 (N = 922). One control and 2 treatment communities participated. RESULTS: Mammogram use increased significantly among minorities in the treatment groups. Among minorities who received the intervention, Black women were twice as likely (odds ratio = 1.97) and Hispanic women were more than twice as likely (odds ratio = 2.33) to undergo screening relative to their untreated cohorts. CONCLUSIONS: A targeted low-cost mailed intervention can help increase screening rates among elderly minority women. The Health Care Financing Administration should promote its benefits aggressively if it expects to reach its target--elderly beneficiaries.

Costs and cost-effectiveness of a church-based intervention to promote mammography screening.

OBJECTIVES: To evaluate the costs of implementing a church-based, telephone-counseling program for increasing mammography use, and to identify the components of costs and the likely cost-effectiveness in hypothetical communities with varying characteristics. DATA SOURCES/STUDY SETTING: An ethnically and socioeconomically diverse sample of 1,443 women recruited from 45 churches participating in the Los Angeles Mammography Promotion (LAMP) program were followed from 1995 to 1997. STUDY DESIGN: Churches were stratified into blocks and randomized into three intervention arms-telephone counseling, mail counseling, and control. We surveyed participants before and after the intervention to collect data on mammography use and demographic characteristics. DATA COLLECTION/EXTRACTION METHODS: We used call records, activity reports, and interviews to collect data on the time and materials needed to organize and carry out the intervention. We constructed a standard model of costs and cost-effectiveness based on these data and the Year One results of the LAMP program. PRINCIPAL FINDINGS: The cost in materials and overhead to the church site was $10.89 per participant and $188 per additional screening. However, when the estimated cost for church volunteers' time was included, the cost of the intervention increased substantially. CONCLUSIONS: A church-based program to promote the use of mammography would be feasible for many churches with the use of volunteer labor and resources.

Dealing with diversity: recruiting churches and women for a randomized trial of mammography promotion.

There is little documentation about the recruitment process for church-based health education programs. In this study, the authors recruit African American, Latino, and white churches and women members (age 50 to 80) for a randomized church-based trial of mammography promotion in Los Angeles County. Efforts to enhance recruitment began 10 months before churches were invited to participate and included a variety of community-based strategies. Subsequently, 45 churches were recruited over a 5-month period through group pastor breakfast meetings and church-specific follow-up. In close collaboration with the 45 churches, the authors administered church-based surveys over 6 months and identified 1,967 age-eligible women who agreed to be contacted by the program team. It was found that an extended resource intensive period of relationship-building and community-based activities were necessary to conduct church-based programs effectively, particularly among older and ethnically diverse urban populations.

Church-based telephone mammography counseling with peer counselors.

Little is published about step-by-step implementation of telephone counseling interventions to promote community-based health activities. This article describes the authors' experience of implementing a church-based telephone mammography counseling intervention with peer counselors representing three principal racial or ethnic groups: African American, Latino, and Anglo (White). Twenty-six women from 12 churches in the Los Angeles area were recruited and trained to deliver the counseling annually over a two-year period to 570 women participants who were recruited from participating churches (n = 15). The counseling sessions were conducted from church-based telephone centers in key geographic locations in our program area. Training and supervision proved challenging: most of the Latino counselors had fewer than seven years of education and spoke only Spanish, while most of the other counselors had at least some college and spoke only English. Culturally specific and small group interactions, role plays, and a more modular approach to training were the most effective ways to enhance counselors' skills. Latina participants' mammography adherence rates were lowest, and their barriers reflected their low socioeconomic status; as Latina counselors shared basic information about mammograms and where to obtain them at little or no cost, the counseling exchanges tended to be nonconflictive and supportive. Black and White participants were generally more knowledgeable and adherent with screening guidelines than Latinas. We found that it was possible to implement this intervention with diverse groups and conclude with lessons learned that may inform others considering such a strategy.

Maintaining mammography adherence through telephone counseling in a church-based trial.

OBJECTIVES: This study assessed the effectiveness of telephone counseling in a church-based mammography promotion intervention trial. METHODS: Thirty churches were randomized to telephone counseling and control conditions; telephone interview data were used in assessing intervention effects on mammography adherence. Separate analyses were conducted for baseline-adherent participants (maintaining adherence) and baseline-nonadherent participants (conversion to adherence). RESULTS: Year 1 follow-up data indicated that the telephone counseling intervention maintained mammography adherence among baseline-adherent participants and reduced the nonadherence rate from 23% to 16%. CONCLUSIONS: Partnerships between the public health and faith communities are potentially effective conduits to promote maintenance of widely endorsed health behaviors such as regular cancer screening.

Problems in recruiting community-based physicians for health services research.

OBJECTIVE: To qualitatively determine factors that are associated with higher participation rates in community-based health services research requiring significant physician participation burden. MEASUREMENTS: A review of the literature was undertaken using MEDLINE and the Social Science Research Index to identify health services research studies that recruited large community-based samples of individual physicians and in which the participation burden exceeded that of merely completing a survey. Two reviewers abstracted data on the recruitment methods, and first authors were contacted to supplement published information. MAIN RESULTS: Sixteen studies were identified with participation rates from 2.5% to 91%. Almost all studies used physician recruiters to personally contact potential participants. Recruiters often knew some of the physicians to be recruited, and personal contact with these "known" physicians resulted in greater participation rates. Incentives were generally absent or modest, and at modest levels, did not appear to affect participation rates. Investigators were almost always affiliated with academic institutions, but were divided as to whether this helped or hindered recruitment. HMO-based and minority physicians were more difficult to recruit. Potential participants most often cited time pressures on staff and themselves as the study burden that caused them to decline. CONCLUSIONS: Physician personal contact and friendship networks are powerful tools for recruitment. Participation rates might improve by including HMO and minority physicians in the recruitment process. Investigators should transfer as much of the study burden from participating physicians to project staff as possible.

Use of cancer screening practices by Hispanic women: analyses by subgroup.

OBJECTIVES: This study compares the use of three cancer screening practices (Pap smear, mammogram, and clinical breast examination) 3 years prior to interview among five subgroups of Hispanic women, and examines whether sociodemographic; access; health behavior, perception, and knowledge; and acculturation factors predict screening practices for any subgroup. METHODS: Descriptive and multiple logistic regression analyses were conducted with data pooled from the 1990 and 1992 National Health Interview Surveys on women who reported that they were Hispanic. The study sample includes 2,391 respondents: 668 Mexican-American, 537 Mexican, 332 Puerto Rican, 143 Cuban, and 711 other Hispanic women. RESULTS: Subgroup profiles reveal differences in education, health insurance, use of English language, and screening use. Mexican women were the least likely to be screened with any procedure. Logistic regression results for each screening practice show that having a usual source of care was a positive predictor for obtaining each of the three screening practices within the last 3 years. Being married, being more than 50 years of age, and having knowledge of breast self-examination were all predictors of having a Pap smear. Having health insurance and ever having had a clinical breast examination and Pap smear were predictors of having a mammography, while age, knowledge of breast self-examination, ever having had a Pap smear and mammogram, and being a nonsmoker all predicted having a clinical breast examination. CONCLUSIONS: We conclude that access factors and prior screening are more strongly associated with current screening than are language and ethnic factors. Our data confirm that a disproportionate percentage of Hispanic women are low income and at risk of being underscreened. Our findings from a nationally representative sample of Hispanics have implications for provider practices, ethnic-specific community interventions, and future development of measures and data collection approaches.

Breast cancer screening adherence: does church attendance matter?

Little is known about the health behaviors of church attendees. This article reviewed telephone interview data of 1,517 women who were church members from 45 churches located in Los Angeles County to determine their breast cancer screening status and to identify the key predictors of screening. Almost all of this sample (96%) reported attending church at least once a month. Key predictors of screening included physician-patient communication, ethnic background, and having medical insurance. Although church-related predictors were not significantly related to screening adherence, the authors compared community-based screening rates from another sample to their sample rates and found that, when controlling for income and education, church members fared better on mammography screening than women who were community residents. This finding suggests that frequent church attendance contributes to better mammography screening status and that the relationship between religious involvement and health behaviors needs further explanation.

Underusers of mammogram screening: stage of adoption in five U.S. subpopulations. The NCI Breast Cancer Screening Consortium.

BACKGROUND: The purpose of this report is to describe the characteristics of women ages 50 to 80 who do not follow commonly accepted mammography screening guidelines. It provides unique understanding of the robustness of characteristics of underusers across five different U.S. subpopulations. METHODS: The data are from the baseline surveys of the five studies of the NCI Breast Cancer Screening Consortium. Stage of adoption of mammography screening and other characteristics of underusers are presented. Polytomous logistic regression analysis was used to explore multivariable associations with stage of adoption in each study site. RESULTS: The five samples studied by the Consortium range in size from 259 to 4,477 women (n = 11,292). The relationship of the perceptions of the pros and cons of mammography with stage of adoption was strikingly similar across the five samples. Other variables consistently associated with stage were a recent receipt of a breast physical examination and recommendation for mammography by a physician. CONCLUSIONS: The findings suggest a need to encourage regular screening through effective communication from a health care provider. Intervention messages should be designed to increase the pros of mammography, decrease the cons, and highlight these differentially according to the woman's stage of adoption.

A trial to increase mammography utilization among Los Angeles Hispanic women.

The objective of this program was to increase mammography screening rates among Hispanic women through a series of targeted community-wide interventions. A diverse array of outreach efforts was offered by the program to increase awareness and use of screening mammography. Before the program, 12 percent of the Hispanic women surveyed in the intervention community had been screened, compared with 27 percent after the program. There was no change in screening among Hispanic women in the control community (23 percent before and 24 percent after the program). The program demonstrated that the awareness and behavior of "hard-to-reach" underscreened Hispanic women can be changed through intensive targeted outreach and that a church-based cancer control program can play an effective role in the process. This finding has national health policy implications.

Confirmatory analysis of opinions regarding the pros and cons of mammography.

This investigation extends prior research to apply decision-making constructs from the transtheoretical model (TTM) of behavior change to mammography screening. Study subjects were 8,914 women ages 50-80, recruited from 40 primarily rural communities in Washington State. Structural equation modeling showed that favorable and unfavorable opinions about mammography (i.e., pros and cons) fit the observed data. Analysis of variance supported the associations between readiness to obtain screening (i.e., stage of adoption) and opinions about mammography (i.e., decisional balance) previously found in research using smaller samples from another geographic region. This report extends these earlier studies by using structural equation modeling, opinion scales based both on principal component analyses and on a priori definitions, a developmental sample and a confirmatory sample, and by sampling from a different geographic region. It is recommended that future research examine whether opinions regarding the cons of mammography are more individually specific than the pros.

Rapid and sensitive genotyping of hepatitis C virus by single-strand conformation polymorphism.

There is an increasing demand for genotyping hepatitis C virus (HCV) isolates due to the rapidly expanding list of distinct HCV genotypes and the mounting evidence of genotype-specific clinical consequences. We describe an SSCP-based assay for determining genotypes in HCV infections. HCV RNA extracted from serum was amplified by a sensitive nested-PCR assay producing a 287 bp fragment of the conserved 5' non-coding region (NCR) and analysed by non-denaturing polyacrylamide gel electrophoresis. Following empirical optimisation of the SSCP assay we identified distinct conformation polymorphisms (characteristic band patterns) corresponding to types 1a, 1b, 2a, 2b, 2c, 3 and 4 found in the Western Australian population. Seventy-three HCV RNA-positive samples were used to evaluate the SSCP genotyping assay for accuracy and efficiency by comparison with the previously established genotyping methods of manual direct sequencing and dideoxy fingerprinting. SSCP genotyping was in concord with control methods while performing more rapidly and at a fraction of the cost. Moreover, SSCP detected two co-infected samples that were not shown by the control methods. The PCR-SSCP assay provides an accurate and rapid method for genotyping of HCV RNA-positive samples at the 5' NCR by type-specific sequence polymorphisms which is applicable to large-scale screening.

Barriers to cancer prevention in the older person.

Barriers to cancer screening are numerous and include both immutable barriers, such as a patient's low income, as well as more mutable barriers; fortunately, most barriers are potentially mutable ones. These encompass, among others, doctor patient communication patterns, inadequate and inaccurate health information, at attitudinal barriers such as patient anxiety, and community barriers, such as the lack of a provider reminder system to patients that prompts compliance. One of the easiest enablers of patient screening to implement is for clinicians to communicate their enthusiastic belief in screening to their older patients. Numerous studies now have documented the effectiveness of the physician's role in increasing patient compliance with screening guidelines.

The influence of risk factors on breast carcinoma screening of Medicare-insured older women. National Cancer Institute Breast Cancer Screening Consortium.

BACKGROUND: It is not certain whether older women with additional breast carcinoma risk factors are adequately screened or whether they are more likely to undergo screening than other older women. This study was conducted to determine whether selected risk factors influence the breast carcinoma screening rates of Medicare-insured older women (i.e., age 65 years or older). METHODS: Self-reported rates of screening mammography and clinical breast examination in the previous year were compared for women with benign breast disease, women with a family history of breast carcinoma, and women lacking these risks, using samples of non-Hispanic white, Medicare-insured women surveyed at the 5 National Cancer Institute Breast Cancer Screening Consortium sites in 1991 (n = 5376, mean age = 69.7 years) and 1994 (n = 5086, mean age = 69.7 years). RESULTS: In 1993, rates of screening mammography reported in the previous year at the 5 Consortium sites had a range of 46-61% for women with a family history of breast carcinoma, 49-66% for women with benign breast disease, and 31-43% for women lacking these risks. Women with a positive family history or a personal history of benign breast disease were also more likely to report having had a clinical breast examination in the previous year and having received a physician's mammography recommendation. A substantial proportion of older women with a positive family history remain inadequately screened, however. Between 25% and 35% of women in this group had not had a screening mammogram in the previous 2 years, while at some Consortium sites more than 20% reported never having had a mammogram in their lives. CONCLUSIONS: Older women with additional risk factors are more likely to undergo screening mammography. This is due partly to more frequent physician recommendations for screening and partly to more frequent provision of clinical breast examinations. However, a substantial proportion of high risk older women remain inadequately screened, despite widespread clinical consensus that these women should be regularly screened. Interventions that target older women with risk factors and their physicians appear warranted. Understanding the mechanisms by which risk factors influence screening is an important area for future research.

Inclusion body myositis: investigation of the mumps virus hypothesis by polymerase chain reaction.

Inclusion body myositis (IBM) is a distinctive form of chronic inflammatory myopathy characterized pathologically by the finding of rimmed vacuoles and 15-18nm microtubular filamentous inclusions in muscle fiber nuclei and cytoplasm. The observation that these filaments resembled nucleocapsids of the paramyxovirus group and showed immunoreactivity with mumps virus (MV) antibodies has led to a long-standing postulate that IBM may be a "slow" mumps infection. We searched for the presence of MV RNA in 34 muscle biopsies (17 frozen and 17 paraffin-embedded) from 18 patients with IBM and 43 control biopsies (mainly from patients with other forms of inflammatory myopathy) using a polymerase chain reaction (PCR). The MV PCR was shown to be sensitive and specific for MV strains (including J-L) and the integrity of muscle RNA extracts was confirmed by PCR detection of constitutive Ableson tyrosine kinase mRNA. MV RNA was not found in any biopsy from the IBM group nor any of the control cases. Our results therefore do not support the mumps hypothesis for IBM.

The effects of health beliefs on screening mammography utilization among a diverse sample of older women.

Screening mammography is particularly effective in detecting breast cancer in elderly women. Yet, although half of all breast cancers are diagnosed in older women, statistics show that women aged 65 and over tend to underutilize screening mammography. Prior research has used the constructs of the Health Belief Model to explore attitudes and beliefs relative to breast cancer screening. Prior studies have also identified health beliefs and concerns relative to screening mammography and race/ethnicity as some of the patient-related predictors of screening mammography utilization among younger women. This study uses the theoretical framework of the Health Belief Model to explore the effects of these variables on utilization in a multiracial, multiethnic, random sample of 1011 women, aged 65 and over. Race/ethnicity, belief that mammograms detect cancer, ease the mind, and provide accurate results; concern over the radiation, pain, and cost associated with receiving a mammogram; and other independent variables were tested as predictors of screening mammography utilization. Regression analysis identified that the belief that having a mammogram eases recipients minds was the most significant predictor of screening mammography utilization. None of the other health beliefs or health concerns were significant predictors. Race/ethnicity had no direct effects on utilization nor was it a confounder in the relationship between health beliefs, concerns and utilization. These results indicate that, along with emphasizing the importance of mammograms in early detection of breast cancer, stressing the reassurance that mammography brings recipients may be an effective health education strategy for elderly women of different racial/ethnic backgrounds.

Physician-reported determinants of screening mammography in older women: the impact of physician and practice characteristics.

OBJECTIVE: Despite having markedly higher breast cancer risk, compliance of older women with screening mammography has been poor. This study was undertaken to determine which physician and patient practice characteristics were associated with high self-reported mammography referral rates for older women. METHODS: Primary care physicians (n = 129) from three socioeconomically diverse communities in Los Angeles were surveyed. Agreement with annual screening and self-reported referral rates were assessed for two groups of women, those 65 to 74 years of age and those 75 years and older. Screening outcomes were compared with physician and patient practice characteristics using bivariate and multivariate techniques. RESULTS: Although 73% of physicians agreed with annual screening of women aged 65 to 74 years, only 24% of physicians reported actually screening most women seen in this age group. Similarly, 57% of physicians agreed that women age 75 years and older should be screened annually, but only 21% reported recommending mammograms for most women seen in this age group. In multivariate analysis, white physicians (adjusted OR = 9.1), younger physicians (adjusted OR = 3.85), and those who used the American Cancer Society's low cost mammography projects (adjusted OR = 5.01) were more likely to report screening the majority of women seen. DISCUSSION: This study suggests that although physicians' intentions to screen older women may be relatively high, a gap exists between intentions and what is reported to be accomplished in practice. Race/ethnicity and physician specialty were the two strongest predictors of high self-reported referral rates, suggesting that targeted interventions may be useful.

Search for persistent infection with poliovirus or other enteroviruses in amyotrophic lateral sclerosis-motor neurone disease.

A longstanding hypothesis proposes that amyotrophic lateral sclerosis-motor neurone disease (ALS-MND) is a late consequence of subclinical poliovirus (PV) infection. In this study, RNA extracts of CNS tissue from 28 patients with ALS-MND and 7 controls were assayed by nested polymerase chain reaction (PCR) using primers to the 5'-untranslated region (UTR) of the enterovirus (EV) genome which is highly conserved between EVs including PV, echovirus and coxsackie viruses. The integrity of RNA extracted from either archival paraffin-embedded or frozen CNS tissue was assessed by detection of constitutive Ableson tyrosine kinase (ABL) mRNA by PCR. Of 63 tissue samples assayed, 81% (51/63) were ABL-positive corresponding to 78% (22/28) of the ALS-MND cases and all controls. None of the 27 ALS-MND cases (i.e. 21 ABL+ and 6 ABL-) in which paraffin-embedded tissue was used nor any of the age and sex matched controls were positive for specific PV/EV RNA. Moreover, CNS tissue from 14 different locations obtained from one patient < 2 hrs after death and immediately frozen, showed no evidence of PV/EV at any site by PCR. Disease duration, degree of tissue autolysis and duration of tissue storage were all excluded as factors which may predispose to negative results. The sensitivity of the PV PCR was determined to be 40-400 copies (12.5 - 125 ag) of synthetic EV RNA transcripts in 1 microgram of cellular RNA and the assay was shown to detect all types of PV and and other EVs tested. Thus it seems unlikely that a persistent PV or related EV infection is implicated in ALS-MND unless there has been alteration in the 5'-UTR of the virus genome.