American health plans can make a substantial contribution to the control of cardiometabolic risk (CMR), a condition associated with both adverse health outcomes and increased cost of care. Our goal was to determine health plan interest in and ability to provide CMR control services.In January 2008, America's Health Insurance Plans, in collaboration with the HealthPartners Research Foundation, surveyed the chief medical officers of 74 member health insurance plans that offer commercial health maintenance organization, point of service, and preferred provider organization insurance. The response rate was 47%.The 35 responding chief medical officers reported that their plans identify members with CMR through referral from case or care management (89%), health risk assessment data (86%), claims data (82%), and pharmaceutical use data (79%). Nearly all (97%) plans currently offer interventions for tobacco use, obesity/overweight, and nutrition. Ninety-four percent of plans offer interventions to increase physical activity. All plans offer health risk appraisal or assessment with feedback and education, 91% use Web-based tools, and 85% use health coaching to help plan members lower their risk. Perceived barriers to broader implementation of risk control programs included lack of resources (79%), limited available enrollee data (74%), and lack of reporting systems (79%). Few health plan officers viewed lack of purchaser interest to be a barrier to program implementation.Health plans appear to be positioned to provide CMR control services that could improve health outcomes, reduce health care costs, and increase workplace productivity in the United States. Cardiometabolic risk (CMR) refers to a condition characterized by standard cardiovascular risk factors, such as blood pressure, cholesterol levels, and tobacco use, and metabolic risk factors, such as obesity, glucose intolerance, and insulin resistance. The path to CMR appears to start with the combination of inadequate physical activity and a diet that is low in fiber and high in saturated fat. Although CMR increases with body mass index (BMI), people with a normal BMI can develop it . UntreatPhysical, social, and economic environments can affect CMR because they promote or hinder participation in physical activity and adoption of healthy eating habits . Some exWe surveyed medical leaders of health plans to assess whether they have the capability and motivation to provide health management services to people and communities to prevent and reduce CMR. The United States Preventive Services Task Force (USPSTF) concluded that evidence is insufficient to recommend for or against routine behavioral counseling to promote either physical activity or a healthy diet for unselected patients in primary care settings ,10. HoweIn addition to efficacy, HRA has the advantage of flexibility because it does not need to be delivered in the doctor's office. When sponsored by employers and delivered either over the Internet or at the work site, HRA can reach groups — for example, young adult men — who visit a physician only when ill or injured. Health management services based on HRA with feedback and additional services can generate a favorable return on investment for employers -17.Two critical components of any intervention program are the proportion of people in the population that the program reaches and the frequency at which the program engages participants. Because most Americans work or live with someone who does and because an even higher proportion have some type of health insurance, health plans, working with employers, have an opportunity to systematically reach a large proportion of the population with tailored health management services . We descThe sample for this survey was drawn from health insurance plans in the United States that were members of America’s Health Insurance Plans (AHIP) as of November 15, 2007. Eligible health plans were identified from the AHIP member organization database. Eligibility requirements were 1) being an AHIP member health insurance plan that offered health maintenance organization (HMO), point-of-service (POS), or preferred provider organization (PPO) services and 2) having a combined enrollment of 50,000 members or more. Plans that did not provide commercial HMO, POS, or PPO health insurance products; leased network PPOs; subsidiary commercial plans; and plans with a combined commercial HMO, POS, or PPO enrollment of less than 50,000 were excluded. Leased network PPOs were excluded because they are typically used by self-funded employers who are seeking only discounted access to a provider network and are unlikely to provide health management or disease management services. Subsidiary commercial plans were excluded because employees of their parent companies were asked to answer on their behalf. Plans with fewer than 50,000 members were excluded because their disease and care management programs are often less developed than those of medium-sized and large health plans, and they are unlikely to have enough staff to respond to the industry surveys. These small plans make up only 0.9% of the aggregate HMO, POS, and PPO enrollment . AccordiThe initial survey sample was 76 health insurance plans. In January 2008, the chief medical officers of each health plan were asked to either complete the survey or designate appropriate staff to the task. Two plans were excluded during the fielding of the survey because respondents indicated that their health plans did not meet the survey selection criteria. The final survey sample frame was 74 health insurance plans.Medical officers from 35 health plans responded to the survey. Twenty health plans were HMOs, 8 were PPOs, and 2 were POS plans . Two plaEighty percent of responding health plans reported that they identified members with elevated CMR. The methods used most frequently included referral from case or care management (89%), HRA data (86%), claims data (82%), and pharmacy use data (79%). However, medical officers of more than 70% of the plans also reported that they use provider referral to identify members with elevated CMR. Data from enrollment forms are rarely used.More than 80% of medical officers of health plans reported that they address CMR among their enrollees as part of both a wellness/prevention domain and as part of a chronic care management domain. Nearly two-thirds of the plans reported that they also address CMR as part of a management or treatment domain.Nearly all plans reported that they offer wellness, health promotion, or prevention programs to members for tobacco use, obesity/overweight, nutrition, and physical activity . AlthougNearly all of the plans address nutrition, cholesterol control, hypertension, tobacco use, physical activity, and obesity/overweight as part of their existing diabetes and cardiovascular disease chronic care programs. Approximately half of the plans address CMR as part of obesity programs. The proportions were lower for cancer, asthma, and chronic obstructive lung disease programs.Medical officers of responding health plans reported using multiple strategies to assist enrollees in managing elevated CMR . All heaThe 5 strategies that health plans reported using most frequently to assist clinicians to evaluate and manage CMR were evidence-based guidelines, feedback to providers , care coordination, pay for performance, and pharmacy programs . Most frMore than 80% of medical officers of health plans cited the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), USPSTF recommendation, and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure as guidelines that they use to identify, manage, or treat enrollees with elevated CMR. Approximately half of the health plan medical officers also reported using other guidelines. Other guidelines that were used included those developed by the National Institutes of Health, United States Public Health Service, American Heart Association, and American Diabetes Association, as well as guidelines developed by regional and local groups. Health plan medical officers reported infrequently using international, European, and subspecialty guidelines to identify, manage, or treat enrollees with CMR.Approximately half of the health plans advocated a risk assessment tool to members or clinicians. When a risk calculator was advocated, it was approximately equally likely to be the NCEP tool or the Framingham risk calculator. Risk calculators that included CMR factors, for example Diabetes PHD , Reynolds Risk Score, and the PROCAM (Prospective Cardiovascular Münster) score, were recommended infrequently or not at all to members, clinicians, or employers. Approximately one-third of health plans recommended 1 or more of the risk assessment tools to address CMR.Medical officers of health plans most frequently reported shortage of resources, lack of reporting systems, and lack of enrollee-level data as barriers that they face in addressing CMR . These sRegarding plans to address CMR, medical officers of 57% of health plans reported that they are planning to expand their activities in the next 2 years, 29% reported being unsure of their plans, and the remaining 14% indicated that they have no plans to expand activities in this area.Many factors limit the interpretation of these data. The survey response rate of 47% may have resulted from the possibility that responding medical officers were more likely than nonresponding medical officers to represent health plans that have active programs to manage CMR. Therefore, the data presented here may represent a best-case scenario, and the true activity levels of all plans may be substantially lower than those that may be inferred from the survey results. Furthermore, all data were self-reported, and no attempt was made to verify the responses from medical officers of the health plans. However, the medical officers who responded to the survey have the training and clinical insight to understand the concept of CMR and accurately respond to the survey questions. A search of PubMed failed to reveal results of similar surveys of health plans.A notable finding is that health plans address traditional cardiovascular risk factors more aggressively than they do CMR. Therefore, much less attention is given to the CMR components of insulin resistance, glucose intolerance, and high triglycerides than it is to blood pressure control, control of low-density lipoprotein cholesterol, or interventions to increase physical activity and improve nutrition. Fortunately, by addressing poor nutrition and inadequate physical activity, health plans are addressing the root causes of CMR. People who are physically active and eat a diet high in fiber and low in saturated fat are less likely than those who are inactive and have a poor diet to develop high triglycerides, glucose intolerance, insulin resistance, obesity, or hypertension ,21.Moreover, most health plans can already administer HRA, and the fact that nearly all of the health plans use the Internet to communicate with their members is a positive sign from the perspective of program delivery. HRAs and the Internet create the capability to interact frequently with a large proportion of health plan members at relatively low cost. Although the effect is modest, interventions to increase physical activity and improve diet help people achieve these goals -27. The Our results suggest 2 principal strategies that health plans can adopt to help members reduce their CMR. First, the influence of insulin resistance, glucose intolerance, obesity, and high triglycerides in creating adverse cardiovascular outcomes should be emphasized to leaders of health plans. This task is primarily an informational and educational challenge for clinical and administrative leaders.The second strategy is to develop effective communication strategies and tools to reach people with an intervention that is strong enough to change behavior. Many adults covered by a health insurance plan work or are living with an adult who works. Therefore, the scope of HRA and similar programs includes the employer in the intervention program. For a large proportion of Americans, the work site is their major locus of social interaction. Therefore, the broader involvement of employers and work sites could reinforce attempts by people to control their CMR. Health plans are well-positioned to encourage and educate physicians and medical groups to 1) more effectively deliver both lifestyle advice and support and 2) more systematically control risk factors such as high cholesterol and high blood pressure. These strategies would allow office-based physicians to focus on illness care and clinical preventive services while still having the opportunity to reinforce the crucial behavior change message.Our results indicate that most health plans can deliver HRA with feedback and provide Internet and telephone-based intervention services. Because most Americans either have health insurance through their employer or live with someone who is employed, creating the conditions that encourage employers to purchase CMR health management services from health plans could have a substantial effect on health outcomes, health care costs, and workplace productivity in America.


Cancer survivors face numerous medical and psychosocial challenges, which the medical and public health systems are ill-equipped to deal with. In May 2008, the Massachusetts Comprehensive Cancer Control Coalition conducted a Survivorship Summit to elicit input from cancer survivors and professionals on developing system-level action plans for cancer survivorship issues. We describe how health care and public health professionals can implement similar events. Our results suggest that a cancer survivorship summit can be a valuable tool for cancer coalitions and advocacy organizations in determining survivorship agendas and action plans. From Cancer Patient to Cancer Survivor: Lost in Transition, the Institute of Medicine addresses the medical and psychosocial issues faced by cancer survivors and makes recommendations for improving the health and quality of life of cancer survivors. Cancer survivors face medical and psychosocial late effects   -10. SuchThe MCCCC is responsible for decreasing deaths and suffering caused by cancer in the state of Massachusetts through a comprehensive approach. The MCCCC comprises more than 300 organizational and individual members. Its priorities are guided by a statewide plan , which wThe goal of the SWG is to ensure that all cancer survivors in Massachusetts have equal access to information and follow-up medical, rehabilitative, and psychosocial services. The group includes 25 people from 12 organizations, representing academic, community, medical, and nonprofit voluntary sectors. Survivorship begins on the day of diagnosis and includes others who are affected by the diagnosis, including family members, friends, and caregivers  survey in Massachusetts by the Massachusetts Department of Public Health. The BRFSS monitors disease, prevention, and quality of life through telephone interviews. BRFSS data confirmed that a substantial proportion of the state's adult population (20% of respondents aged 55 or older) had received a cancer diagnosis, with 52% of these occurring more than 5 years before the survey. Cancer survivors had similar behavioral risk factor rates  compared with the general population. However, rates of chronic diseases and disability were substantially higher among cancer survivors than among the general population.The SWG then implemented a Web- and telephone-based qualitative survey to determine what barriers, issues, and concerns Massachusetts cancer survivors experienced; 1,377 survivors responded to the survey. The SWG then completed a thematic analysis to identify common experiences, which include the following: 1) the need for a central source of information on resources available in respondents' geographic area, without having to rely on support groups; 2) financial struggles that result from a cancer diagnosis, particularly among people older than 60; 3) loss of health insurance; 4) workplace discrimination; 5) lack of information about clinical trials; and 6) lack of awareness of the need for advanced care planning.Survey participants did not broadly represent all cancer survivors. Most responses (63%) came from women, more than 97% of whom were breast cancer survivors. The survey also did not show how the common problems could be solved. The SWG determined that a statewide cancer survivorship summit was needed to develop a deeper understanding of the issues and how they could be faced through devising specific short- and long-term action steps.The Summit Planning Committee (SPC)The Summit Planning Committee (SPC), which comprised SWG members, realized that 1) specific problems faced by Massachusetts cancer survivors and their caregivers need to be clarified, and 2) the strategies to solve these problems need to be well-defined action plans. The SWG wanted the summit to include everyone involved in cancer survivorship . Summit participants would be asked to define problems faced by cancer survivors and caregivers in Massachusetts and to outline potential solutions. Additionally, the summit would allow participants to interact with keynote presenters, workshop session leaders, and attendees representing health care organizations and community service organizations from around the state.The summit planning and development process lasted from November 2006 through May 2008. SPC volunteers served in planning groups, which were chaired by the 1 or 2 people most experienced in the area. The SPC met regularly to ensure that the planning groups were functioning effectively, meeting objectives on time, and getting needed resources. Meetings occurred mostly via conference calls; informal communications occurred via e-mail and telephone. The Massachusetts Department of Public Health coordinated the planning process, organized meetings, produced and circulated meeting minutes via e-mail, and helped all planning groups.Four planning groups were formed . The AgeThe summit was a 1-day event that included keynote sessions and morning and afternoon working group sessions. Keynote speakers were 4 local and national experts, advocates, and supporters of cancer survivorship. Topics were patient navigation, advocacy, a review of the work by the MCCCC that led to the summit, and personal stories.Ten working group session topics were identified . The goaThe Table describes the problems and action plans identified by each working group. Overall, 26 system-level action plans were identified and categorized into 5 major domains: 1) providing services within patient navigation programs; 2) offering formal training programs for providers, volunteers, and human resources; 3) providing ready access to information; 4) advocating for policy changes; and 5) developing standardized protocols and documents, such as treatment summaries and care plans.At the end of the summit, participants completed a brief survey to rate their experiences. The survey assessed participants' 1) demographic characteristics, 2) role in cancer survivorship , and 3) reasons for coming to the summit. They were asked if the summit met their expectations, if their voices were heard, and if the summit helped them advocate for cancer survivorship issues. Participants also rated each summit session and the summit overall.In total, 220 participants attended the summit, 144 of whom (65%) completed an evaluation form. Most were female (93%), aged 50 or older (64%), and non-Hispanic white (85%); approximately 11% of participants were non-Hispanic black. Approximately 61% of participants identified themselves as cancer survivors, and 66% indicated that they attended the summit in a professional role . Approximately one-third of participants (34%) were both cancer survivors and professionals.The most common reasons that participants attended the summit were wanting to learn more about cancer survivorship issues (65%), having an interest in a specific topic on the summit agenda (55%), wanting to network (48%), and wanting to make a difference (42%).Participant ratings of the summit were positive. The majority reported the following: the summit met their expectations (90%), there was opportunity for their voices to be heard (81%), and attending the summit would better help them advocate for cancer survivorship issues (84%). The strategies chosen at the working group sessions were rated excellent or very good (81% for the morning session and 76% for the afternoon session). Eighty-nine percent rated the summit overall as excellent or very good.P = .006) and in the afternoon session , 2) rate as excellent the extent to which the summit met their expectations , 3) rate as excellent the extent to which the summit would help them advocate for cancer survivorship issues , and 4) rate the summit overall as excellent . There were no differences between the groups in reporting as excellent the extent to which they believed their voices were heard.Ratings of the summit did not vary by participant demographics. However, there were differences according to professional versus nonprofessional status. Compared with professionals, nonprofessionals were less likely to 1) say they were extremely satisfied with the strategies decided on in the morning session  develop patient navigation programs that meet the needs of cancer survivors; 2) improve access to information and services for cancer survivors and caregivers; 3) train health care and other service providers and volunteers to help cancer survivors and caregivers during all phases of survivorship, including posttreatment phases; 4) advocate for policy changes; and 5) develop standardized protocols and documents . The priority areas include changes in policies that highlight the importance of advocacy and the need for training in this area.Several lessons learned can improve the success of future similar efforts. Sufficient resources and highly committed personnel are necessary to help develop each component and to conduct activities at the summit. Investment of coalition members is essential, and a planning period of at least 1 year is required. Adequate personnel are needed particularly at crunch time to ensure the smooth running of summit plans. In the MCCCC summit, graduate students were available to assist with the workload through the academic affiliations of some summit planners.Achieving geographic representation from across the state was difficult, even though Massachusetts is a small state and the summit was near a major highway. Most participants were from within the county where the summit was held or the 3 adjacent counties. Participants from more distant counties were more likely to be professionals than nonprofessionals. To achieve geographic representation, summit planning efforts should include finding resources to pay for transportation for people who are not geographically close and coordinating with local organizations and advocacy groups to promote options . In larger states, regional summits may be more appropriate to assure that different geographic regions are represented.The summit was not as well received by nonprofessionals as it was by professionals. We may not have adequately communicated the purpose of the summit. The goal was for participants to identify coalition priorities, not to provide information or resources. To prevent misunderstandings, all correspondence regarding such a summit should include clear objectives for the summit, state what the expectations are for participants, and pilot test these materials with the intended audience.The evaluation protocol for this summit has limitations. Evaluation was conducted only immediately after the summit concluded. Longer-term evaluation of the summit's effects on attendees would have been useful. For the SWG, the summit has been translated into long-term work plans, but no separate evaluation of effects of the identified action plans on the work and advocacy priorities of SWG members were conducted.The MCCCC Survivorship Summit can guide future efforts of this coalition. The summit also allowed the coalition to recruit additional members; attendees who volunteered to work on any action plans were noted during the summit and will be contacted to participate in the implementation of these plans. After the summit, action plans were disseminated to all summit participants via e-mail and mail. During the next 5 years, the SWG will implement these action plans across Massachusetts.Funding for the MCCCC Survivorship Summit was provided in part by a cooperative agreement from Centers for Disease Control and Prevention, National Cancer Prevention and Control Program grant to the Massachusetts Comprehensive Cancer Prevention and Control Program. Funding was also provided by the American Cancer Society, Massachusetts Department of Public Health Women's Health Network and Men's Health Partnership and Bureau of Communicable Disease Control, Bayer HealthCare, Dana-Farber Cancer Institute, Lance Armstrong Foundation, Massachusetts Cancer Prevention Community Research Network, New England Coalition for Cancer Survivorship, and Pfizer Oncology.We thank Snaltze Pierre, coordinator of the MCCCC, for assistance in coordinating work of the SWG and the SPC. We thank the other members of the SPC for implementing this program, including Janice McGrath, SWG cochair; Zana Baruch; Cindy Blood; Lila Brady; Diane Cotting; Carol Curtiss; Kathy Hart; Lynne Graziano Morin; Marcie Saganov; and Palmira Santos. We thank Green Associates, LLC, for assistance in coordinating summit planning and implementation. We thank Joyce Kulhawik, Harold P. Freeman, Palmira Santos, Harriet Chandler, and Susan Quinones for participating as keynote speakers. We thank Seana Quental, Sarah Hunt, and Italo Brown for their assistance with preparing and implementing activities; Andrew Prout for his technical assistance; Jane Hilbert Davis for training facilitators; the volunteers who served as local content experts, working group facilitators, and recorders; and summit participants.


Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies . Benign breast biopsy slides were reviewed by pathologists and CCL presence assessed. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between CCL and breast cancer risk.P for interaction between CCL presence and BBD category = 0.77).Women with CCL  had an increased risk of breast cancer compared with those without CCL , although this was attenuated and became non-significant after adjustment for the histologic category of BBD . CCL presence was associated with the greatest risk of breast cancer for those with nonproliferative BBD  and the lowest risk for those with atypical hyperplasia (AH) ; however, this apparent heterogeneity in risk across BBD categories was not significant (These results provide evidence that CCL may be an important marker of breast cancer risk in women with BBD but suggest that CCL do not increase breast cancer risk independently of concurrent proliferative changes in the breast. In fact, these lesions have been reported to be present in nearly half of biopsies performed for mammographic microcalcifications and have been identified as the source of three-quarters of biopsy-detected microcalcifications . CCL is u (DCIS) . Althougu (DCIS) ,4, "clinu (DCIS) ,6, "coluu (DCIS) , "atypicu (DCIS) , "atypicu (DCIS) -10, and u (DCIS) . The incu (DCIS)  is facilSome of the earliest evidence suggesting that CCL may be premalignant was their frequent detection near known precancerous and cancerous changes in the breast. Several studies have reported a high frequency of CCL and low-grade DCIS in the same breast ,8,12, wiMounting histopathologic and molecular evidence indicates that CCL may indeed be early precursors to low-grade invasive breast carcinomas. CCL have been proposed as breast cancer precursors largely because of the cytologic and architectural similarities of more advanced CCL to atypical hyperplasia (AH), a suspected precancerous abnormality, and DCIS, a well-established precursor to invasive carcinoma ,8,10. Inet al. did find some suggestion of an increased risk of breast cancer subsequent to CCL, as 9 out of 63 participants with advanced CCL (14.3%) developed subsequent infiltrating carcinomas after eight years of follow-up [et al. found that none of 84 patients with advanced CCL alone developed subsequent breast cancer over a 10-year follow-up [et al. [Descriptive studies among patients with advanced CCL, although unable to quantify the elevation in breast cancer risk associated with CCL, suggest that CCL are unlikely to be a strong risk factor for subsequent breast cancer. While Martel ollow-up , most otollow-up . Similarollow-up  or amongThe very limited epidemiologic evidence on CCL suggests that CCL may be markers for concurrent atypical proliferative changes in the breast rather than breast cancer precursors -27. GiveThe NHS is an ongoing prospective cohort study that began in 1976, when 121,700 female registered nurses between ages 30 and 55 years completed a mailed, self-administered questionnaire regarding their health behaviors, lifestyle factors, and medical histories. Follow-up questionnaires have been sent to participants every two years to obtain updated information. The biennial questionnaires have assessed a variety of known and suspected risk factors for breast cancer, including history of BBD. On the 1976, 1978, and 1980 questionnaires, participants were asked if they had ever been diagnosed with fibrocystic or other BBD and whether this diagnosis had required hospitalization; from 1982 onward, the questionnaires have inquired specifically about BBD confirmed by biopsy. Deaths are reported by family members and the postal service, and regular searches of the computerized National Death Index are also conducted . The NHSin situ were included in the study. Eligible controls were women who completed the questionnaire for the same year that the breast cancer case was reported and had a previous diagnosis of biopsy-confirmed BBD, but were free from breast cancer; within each NHS cohort, they were matched to breast cancer cases on year of birth and year of diagnosis of BBD. We attempted to identify four matched controls for each case, but this was not always possible for logistical reasons. Informed consent was obtained from all participants. The study was approved by the Human Research Committee of Brigham and Women's Hospital, Boston, Massachusetts.We conducted a nested case-control study to assess morphological changes in benign breast lesions and breast cancer risk among participants in the NHS and NHS II who had reported a previous diagnosis of BBD that was confirmed by biopsy. Within this subcohort, eligible cases were women who reported a first diagnosis of breast cancer between 1976 and the return of the 1996 questionnaire in the NHS or between 1989 and return of the 1995 questionnaire in the NHS II. Self-reported breast cancers were confirmed by review of medical records, and both invasive breast cancer and carcinoma et al. [in situ or invasive carcinoma, invalid dates of diagnosis, or insufficient information on laterality, there were a total of 395 cases and 1,610 controls [Eligible cases and controls were contacted for permission to obtain their BBD pathology records and biopsy specimens, and specimens then were obtained from hospital pathology departments when possible. These methods have been described in detail elsewhere ,30. Brieet al. ,32, whicet al. ,33,34. Acontrols ,30. AlthDuring histologic review of benign breast biopsies for breast cancer cases reported in the 1976 through 1996 questionnaires in the NHS and in the 1991 through 1995 questionnaires in the NHS II and for matched controls, the presence of CCL was recorded on the pathology worksheets as "columnar alteration of lobules." At the time these benign breast biopsies were reviewed, CCL were not considered to be of particular interest and were usually not further stratified; thus, the categorization of these lesions as "columnar alteration of lobules" was in keeping with the standard of practice of the time. For the 42 cases and 116 controls from the NHS 1996 questionnaire cycle, presence of CCL subtypes  was assessed rather than the overall presence of CCL. These women with only subtype information were re-categorized by presence or absence of CCL to allow their inclusion in analyses. After exclusion of five subjects having lesions without adjacent tissue for evaluation, the final sample for this analysis included 394 cases and 1,606 controls. Given the small number of cases and controls in which CCL were further classified with regard to the presence or absence of atypia, CCL were considered as a single group for these analyses.The distributions of breast cancer risk factors were examined according to CCL presence among the controls, adjusting for age at benign biopsy when appropriate. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk according to CCL presence. Unconditional rather than conditional logistic regression was used because this analytic approach allowed us to use all cases and controls for whom we had histologic information. We first adjusted only for the matching factors, which were age at breast cancer diagnosis or index date , year of benign breast biopsy , and time since benign biopsy . In another set of models, additional adjustment was made for histologic category of BBD , which is a strong predictor of breast cancer risk . We also2), postmenopausal hormone use , and oral contraceptive use . Because BMI at age 18 appeared to be more strongly related to breast cancer risk than current BMI, we chose to consider adjustment for BMI at age 18 and change in weight since age 18 rather than current BMI. Individual adjustment for these covariates did not change the estimated OR substantially, nor did simultaneous adjustment for the four factors having the strongest influence on the OR . We examined relationships between CCL and estrogen receptor (ER) status, grade, and ipsilaterality in additional unconditional logistic regression models. All statistical analyses were performed using the SAS software package . All tests were two-sided, with P < 0.05 indicating statistical significance.The following covariates were considered as potential confounding factors: first-degree family history of breast cancer , age at menarche , menopausal status , jointly classified parity and age at first birth , BMI at age 18 . We also assessed breast cancer risk factors by case-control status and found that established breast cancer risk factors were associated with breast cancer in our study population, although most of these associations were non-significant. Compared with controls, cases had a higher prevalence of family history of breast cancer, lower mean parity and older mean age at first birth among parous women, higher mean alcohol consumption, and a higher prevalence of postmenopausal hormone use , and the mean time since biopsy was 10.0 years (SD = 7.2 years). Compared with women with no CCL, women with CCL were older at the time of their biopsy and had less time since their biopsies  or when proliferative disease without atypia and AH were collapsed into a single category (P = 0.93).When women were jointly classified according to histologic category and CCL presence, all groups had an elevated breast cancer risk compared with the reference category, nonproliferative BBD and no CCL. Women with both AH and CCL were at highest risk , but this risk was not significantly different from that among those with AH without CCL. Within all BBD histologic categories, breast cancer risk was elevated for women with CCL, with the risk higher for those with less severe BBD . However, there was no evidence of an interaction between CCL and BBD histologic category when either three histologic categories were used , although this analysis excluded those with AH, who have been shown to be at highest risk of subsequent breast cancer. Given the strong correlation between CCL and concurrent AH found by Boulos et al. (P < 0.0005), it is possible that the relative risk for presence of CCL would have been somewhat higher had women with AH been included in the main analysis. As in our study, Boulos et al. found that the elevated risk of breast cancer among those with AH was not further increased among those who additionally had CCL, suggesting that CCL are not an independent breast cancer risk factor among women with AH [et al. that assessed subsequent breast cancer risk from a broad range of benign breast lesions found a non-significantly elevated risk of breast cancer among a small number of women with multiple CCL compared with those with non-proliferative disease and no breast pathology , although no increased risk was found for focal CCL  [et al. because this study used a different pathologic classification scheme in which CCL were considered a proliferative disease rather than a separate entity that could exist in conjunction with either nonproliferative or proliferative BBD.Few previous epidemiologic analyses have evaluated the risk of subsequent breast cancer following detection of CCL, but the magnitude of risk associated with the presence of CCL found in our study is consistent with that reported by Boulos  with AH . Anotherto 1.39) . HoweverOur study is the largest nested case-control study of CCL and breast cancer to date and therefore yields important clues into the relationship between presence of CCL and breast cancer risk. However, given the heterogeneity of CCL, it is possible that assessing risk of breast cancer for all CCL subtypes combined masks an effect of advanced CCL subtypes, which are less common. Histopathologic and molecular evidence suggests that CCL displaying low-grade cytologic atypia, recently termed "flat epithelial atypia" (FEA) by the World Health Organization Working Group on the Pathology and Genetics of Tumors of the Breast , may be However, the malignant potential of FEA remains equivocal, as descriptive and epidemiologic studies fail to support molecular findings, just as they do for overall CCL risk. Most descriptive follow-up studies among women with what would now be classified as FEA, including one with an average follow-up of nearly 20 years, have found progression to invasive carcinoma to be uncommon ,11,23,24et al., only 52 biopsies contained FEA without AH [Although we considered performing a CCL subtype-specific analysis, information on subtype  was collected for only 157 women whose breast cancer or index date was reported on the 1996 NHS questionnaire. We chose not to re-review the biopsy slides for the presence of FEA, as prevalence of FEA appeared very low from the 1996 questionnaire cycle, with only 4 of the women out of 53 with CCL from this cycle having FEA. Because FEA is a rare occurrence, many thousands of breast biopsies would be needed for adequate power to study its relationship with subsequent breast cancer. Moreover, to study the association between FEA and breast cancer independent of AH, an adequate number of women with FEA but not AH would be required. This would only be possible in an extremely large study, as FEA commonly occurs in conjunction with AH. Even in the largest previous epidemiologic study of CCL by Boulos thout AH .The strengths of the study include its prospective design, the confirmation of breast cancer cases through review of medical records, the centralized pathology review of specimens from benign biopsies before the development of breast cancer, and the detailed information on other breast cancer risk factors. Furthermore, ours is the first observational study to compare the risk of subsequent breast cancer by BBD histologic category. Although power was limited to test for heterogeneity by histologic category, our findings suggest that CCL may be a marker of increased risk among those with non-proliferative disease. Such a differential effect of CCL on breast cancer risk across BBD categories could have important implications for clinical management of patients with CCL, especially given that women with non-proliferative disease are typically considered to be at no elevated risk for breast cancer compared with women from the general population.In light of these findings, large epidemiologic studies assessing CCL subtype-specific risks are needed to inform clinical guidelines for the management of CCL. In particular, better understanding is needed as to whether CCL with atypia in the absence of more advanced lesions require treatment similar to that for DCIS. Additionally, adequately powered epidemiologic studies might help elucidate whether CCL are of concern only among women without proliferative disease. Regardless of whether particular CCL subtypes are simply markers for premalignant changes in the breast or precancerous histologic changes themselves, recognition of these lesions is nevertheless important, as detection of CCL via biopsy should prompt additional scrutiny for other pathologic changes in breast tissue that may signal the early development of DCIS or invasive carcinoma.in situ; ER: estrogen receptor; FEA: flat epithelial atypia; NHS: Nurses' Health Study; OR: odds ratio.AH: atypical hyperplasia; BBD: benign breast disease; BMI: body mass index; CCL: columnar cell lesions; CI: confidence interval; DCIS: ductal carcinoma The authors declare that they have no competing interests.SA participated in the study design, data analysis and interpretation, and manuscript drafting. LC participated in the study design, data collection, and manuscript revision. SS and JC reviewed the BBD biopsy slides and participated in the study design and manuscript revision. GC participated in the study design, data collection, and manuscript revision. RT participated in study design, data collection, manuscript revision, and study supervision. All authors read and approved the final manuscript.Supplementary table S1. A Word document containing a table that lists the means and percentages of characteristics by case-control status among participants with benign breast disease (BBD).Click here for file


The periods of fetal and child development arguably represent the stages of greatest vulnerability to the dual impacts of fossil fuel combustion: the multiple toxic effects of emitted pollutants  and the broad health impacts of global climate change attributable in large part to carbon dioxide released by fossil fuel burning.In this commentary I highlight current scientific evidence indicating that the fetus and young child are at heightened risk of developmental impairment, asthma, and cancer from fossil fuel pollutants and from the predicted effects of climate disruption such as heat waves, flooding, infectious disease, malnutrition, and trauma. Increased risk during early development derives from the inherently greater biologic vulnerability of the developing fetus and child and from their long future lifetime, during which early insults can potentially manifest as adult as well as childhood disease. I cite recent reports concluding that reducing dependence on fossil fuel and promoting clean and sustainable energy is economically feasible.Although much has been written separately about the toxicity of fossil fuel burning emissions and the effects of climate change on health, these two faces of the problem have not been viewed together with a focus on the developing fetus and child. Adolescence and old age are also periods of vulnerability, but the potential for both immediate and long-term adverse effects is greatest when exposure occurs prenatally or in the early years.Consideration of the full spectrum of health risks to children from fossil fuel combustion underscores the urgent need for environmental and energy policies to reduce fossil fuel dependence and maximize the health benefits to this susceptible population. We do not have to leave our children a double legacy of ill health and ecologic disaster. Lancet on energy and health , sulfur and nitrogen oxides, benzene and mercury emitted by coal-burning power plants, and diesel and gasoline-powered vehicles have been variously linked to infant mortality, lower birth weight, deficits in lung function, respiratory symptoms, childhood asthma, developmental disorders, and cancer . The manonal age . The samonal age . Air polonal age . There ional age .These health effects represent a major societal and public health burden. A significant proportion of U.S. children 6–17 years of age are reported to have developmental problems including learning disabilities (11.5%), attention-deficit/hyperactivity disorder (8.8%), and behavioral problems (6.3%) . Asthma in utero or in childhood. For example, exposure to air pollution in childhood may result in a reduction in lung function and ultimately to increased risk of chronic respiratory illness (in utero as a result of air pollution exposure (Insults sustained early in development can have lifelong consequences. Some adult diseases can be launched  illness  and grea illness . Similarexposure . Such tyexposure .in utero environmental exposures can lead to reproductive disorders and adult onset diseases such as cancer (Epigenetic effects of developmental exposure to air pollutants have been less well studied. However, exposure to PAHs has been associated with epigenetic effects experimentally , and pres cancer .A recent report from the American Lung Association noted that, although ozone levels have decreased in the United States since 2002, particle pollution has increased over that period, and coal-fired power plants are responsible for much of the increase in particle pollution in the eastern United States . The aut2 concentrations since the preindustrial period (2 emissions from burning fossil fuels [2 equivalent (Children are also particularly vulnerable to the effects of global warming . Anthropl period . In the il fuels . More thuivalent . The aveuivalent . A tempeuivalent . As a reuivalent .Global warming also compounds the direct toxicity of fossil-fuel pollutants such as ozone, an important trigger of childhood asthma . Ozone fThe fetus and child are especially susceptible to air pollution and many other environmental contaminants because of their rapid development and immature defense systems; thus, they may be affected by levels of exposure that have no apparent effects in adults , 2006a. Poverty and racism compound the susceptibility of the fetus and child. Poor children, especially those in urban areas and developing countries, are most at risk, because the effects of toxic exposures are magnified by inadequate nutrition and psychosocial stress due to poverty or racism . The shoAlthough more has been written about the heightened susceptibility of the fetus and child to toxic exposures, children also are likely to be especially susceptible to dehydration and heat stroke, malnutrition, diarrhea, allergies, malaria and encephalitis, and psychological trauma , 2007. T2 equivalents using tested approaches and high-potential emerging technologies. The report stated: “Our research suggests that the net cost of achieving these levels of GHG abatement could be quite low on a societal basis” (The most recent IPCC concluded that significant progress toward stabilizing or reducing global warming emissions can be achieved at relatively low cost using known technologies and practices currently available . A recenl basis” .These reports indicate that the cost of acting now to make power generation, transport, buildings, and appliances more efficient and to invest in alternative fuels and technologies would be minimal compared with the cost of doing nothing. The benefits of reducing air pollution and global warming would offset a substantial fraction of mitigation costs. These benefits include the individual and societal benefits of health and security extending multigenerationally and the monetary savings from fewer cases of children with asthma, developmental delay, cancer, heat stroke, drowning, malnutrition, diarrhea, allergies, and infectious disease.Lancet, Richard Horton notes that “Policies to improve access to affordable clean energy should be pro-poor,” and that “Policies to reduce the progress and impact of climate change should explicitly aim to maximise health benefits and minimise health risks” (all the impacts of fossil fuel combustion on child health and development and maximize the health benefits to this susceptible population. Our addiction can be cured. We do not have to leave our children a double legacy of ill health and ecologic disaster.Summarizing the recent series of articles in h risks” . Based o


VEGF expression, bFGF expression and expression of pimonidazole, a marker of hypoxic cells, were investigated by immunohistochemistry. An association between high VEGF and bFGF expression and high angiogenic potential was detected, suggesting an important role for VEGF/bFGF in the angiogenesis of melanomas. High VEGF/bFGF expression was also related to low hypoxic fraction and high vascular density. Thus, the constitutive, genetically determined level of VEGF was probably more important than hypoxia-induced upregulation in the angiogenesis of the melanoma xenografts. © 2000 Cancer Research CampaignAngiogenesis of tumours might develop as a result of environmental conditions, such as hypoxia, and/or as a result of genetic alterations specific for tumour cells. The relative contributions of these mechanisms were investigated by comparing the in vivo expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to the hypoxic fraction, the angiogenic potential and the vascular density of four human melanoma lines  grown intradermally in Balb/c


Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations.Five cases of severe neutropenia  identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in AlbertaOur findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the differential diagnosis will assist clinicians with case timely detection and appropriate management. The modification of illicit drugs is not an uncommon phenomenon. In efforts to enhance the profitability and acceptability of a product, illicit drugs typically undergo processes such as: substitution (replacement of one drug for another with similar pharmacologic properties); dilution (addition of inert substance to reduce the content of the active drug); contamination ; and/or adulteration similar pharmacologic properties or ii)properties which attenuate the effects of the parent drug). AdverseSince 2004, the emergence of a cocaine modifier called levamisole has been reported in Canada , United In 2008-2009, both Alberta and British Columbia public health officials investigated clusters of severe neutropenia associated with levamisole modified cocaine use; particularly in association with the smoking of crack cocaine. We present the findings from our investigations to increase awareness in clinicians and to improve the identification of cases.In 2008, clinicians notified public health officials of five cases of severe neutropenia in Northern Alberta; cocaine and levamisole were detected in the urine of all five cases . On NoveDynaLIFEDX in Edmonton began to append a clinical alert on all laboratory reports testing positive for cocaine. This alert highlighted the relationship between neutropenia and cocaine tainted with levamisole. Identification of levamisole in urine was limited to a few facilities in Alberta and none in British Columbia. The University of Alberta Hospital Toxicology Laboratory in Edmonton agreed to conduct levamisole testing on behalf of British Columbia. A literature review was performed to inform the investigation.On November 18, 2008, the Clinical Toxicology Laboratories at the University of Alberta Hospital and This investigation focused on observational prospective and retrospective case reports of neutropenic patients associated with cocaine use in Alberta and British Columbia between January 1, 2006 and March 31, 2009.9 cells/L), and recent cocaine use in Alberta or British Columbia between January 1, 2006 and March 31, 2009 were identified as cases of Neutropenia Associated with Tainted Cocaine ("NATC"); specifically, levamisole tainted cocaine. Cases were categorized as confirmed, probable, or suspect NATC cases (see Appendix 1). Only confirmed and probable NATC cases are presented in this paper.Patients presenting with severe neutropenia .Alberta performed retrospective chart review using laboratory and medical examiner data. Retrospective laboratory data was obtained from the Edmonton, Calgary, Chinook, East Central and Peace areas of Alberta between January 1, 2006 and March 31, 2009. NATC cases identified through the laboratory and medical examiner data review processes involved searching for potential cases with concurrent laboratory results indicative of severe neutropenia and positive cocaine, cocaine metabolites and/or levamisole screens. Where possible these NATC cases were further cross-referenced with electronic medical records, to determine any NATC exclusion factors and documented risk factors.Health Canada Drug Analysis Service provided testing for cocaine and levamisole markers in suspected cocaine samples and paraphernalia. Toxicology Laboratories in Edmonton and Calgary tested urine for cocaine, its metabolites, and levamisole; the University of Alberta Hospital Toxicology Laboratory also tested drug paraphernalia related to current patients. Clinicians were requested to collect urine specimens for toxicology testing from identified neutropenic patients if within 48 hours of cocaine consumption. Typically, neutrophil counts were performed when patients sought medical care.Forty-two cases of NATC were identified in Alberta and British Columbia from January 1, 2008 to March 31, 2009. In this time period, 16 confirmed, and 26 probable, NATC cases were identified. Eighteen (43%) NATC cases had recurrent episodes of neutropenia associated with cocaine use (range: 2 to 8 episodes). The dates of NATC case identification are shown in Figure Bacterial and fungal infections reported in patients with neutropenia included: abscesses, bacteremia, cellulitis, urinary tract infection, pneumonia, invasive group A streptococcus, septic shock, epiglottitis, ulcers, and thrush. Of the 15 NATC cases who underwent bone marrow biopsy assessment, 12 (80%) cases had the procedures prior to distribution of the public health advisories.Reported history of cocaine use varied from occasional use to chronic use and binging. Ten of the 16 confirmed NATC cases (63%) used crack cocaine within two days of seeking medical care, some within hours of seeing a physician. Five NATC cases indicated heavy crack cocaine usage (1 to 3 grams per day) just prior to admission.NATC cases resided in both large urban centres and rural communities  NATC cases of aboriginal heritage, four cases (17%) in Alberta were identified as Aboriginal. In Alberta, one death was associated with the consumption of levamisole tainted crack cocaine. One NATC case in Alberta was tested for and produced anti-neutrophil antibodies, both IgG and IgM subtypes, as detected by flow cytometry and HLA Class I antigens. For another five NATC cases, anti-neutrophil cytoplasmic antibody (ANCA) tests were conducted; four NATC cases were positive .The contents of two used crack pipes obtained from NATC cases verified the presence of cocaine and levamisole. One sample of cocaine was tested for levamisole and found to be positive; quantifying the percentage of levamisole in the sample was not possible in Canada at that time.st 2006 to December 31st 2007. The earliest confirmed NATC case dated back to July 2007 and the earliest probable NATC case dated back to June 2006.A further 18 cases (20 episodes) were identified through the retrospective review of laboratory and medical examiner data in Alberta between January 1We identified a total of 60 NATC cases and 108 episodes of neutropenia associated with levamisole-tainted cocaine, in Alberta and British Columbia since June, 2006. Most cases were related to smoking crack, and some cases reported heavy use prior to seeking medical care; though we were unable to confirm a dose response.Literature suggests that levamisole remains stable when heated , but maySome patients may be genetically predisposed to develop levamisole-related neutropenia. Prior studies found people with levamisole-related neutropenia were more likely to have HLA-B27, an HLA class I antigen . As routLevamisole is known to have immunostimulating effects with the production of auto-antibodies . Anti-neDespite public health notification and media interest in both provinces the true burden of NATC is likely underestimated by voluntary reporting of NATC cases by clinicians. As levamisole has a short half-life (approximately 5 to 6 hours) and little (2 to 5%) is excreted unchanged in urine, specimens should be collected within 48 hours of exposure ,26. ThusClinicians should be aware that severe neutropenia may be caused by levamisole in cocaine. If fever or infection is present, empiric intravenous broad spectrum antibiotics and supportive care is recommended and treatment with granulocyte-colony stimulating factor (G-CSF or filgastrim) should be considered . The majWe also recommend that clinicians inquire about patients' recent cocaine use (see Appendix 2) and request levamisole testing if urine is obtained within 48 hours of last cocaine use. The diagnosis should still be considered when patients present with other coexisting health conditions (e.g. HIV).Further research is needed to establish methods for cocaine users to detect the presence of levamisole and studies to quantify the levamisole dose required to produce neutropenia.In conclusion, neutropenia associated with levamisole-tainted cocaine presents a significant, emerging public health problem in Canada. For clinicians, the awareness of the differential diagnosis for neutropenia can ensure timely diagnosis and appropriate management of cases.The authors declare that they have no competing interests.LK lead the public health investigation in Alberta, was primary author, developed the concept and design of study; collected, analyzed and interpreted the data; drafted and approved the final manuscript. JB lead the public health investigation in British Columbia, was secondary author, developed the concept and design of study; collected, analyzed and interpreted the data; and revised and approved the final manuscript. NS conducted the public health investigation in British Columbia, developed the concept and design of study; collected, analyzed and interpreted the data; and revised and approved the final manuscript. IA conducted the public health investigation in Alberta, collected, analyzed and interpreted the data; and revised and approved the final manuscript. DL discovered the association between cocaine, levamisole and neutropenia, collected, analyzed and interpreted the data; and revised and approved the final manuscript. SF conducted the public health investigation in Alberta, collected, analyzed and interpreted the data; and revised and approved the final manuscript. NZ discovered the association between cocaine, levamisole and neutropenia, and revised and approved the final manuscript. JT supervised the public health investigation in Alberta, developed the concept and design of study; analyzed and interpreted the data; and revised and approved the final manuscript.Confirmed case: laboratory confirmed exposure to cocaine and levamisole and neutropenia (neutrophil counts less than 0.5 per 109 cells/L).• Probable case: laboratory confirmed or a history of exposure to cocaine and neutropenia; or levamisole positive and serious infection determined post-mortem.• Suspect case: signs and symptoms common to neutropenia and a history of exposure to cocaine or levamisole.• • What type of cocaine  did you use?• Did you smoke, snort, or inject?• How long did you use (Number of days)?• How often did you use ?• How much did you use (Number of grams/day)?• Was there anything different in the look, taste, texture, smell, effect of the cocaine when last used?


An early dispersal of biologically and behaviorally modern humans from their African origins to Australia, by at least 45 thousand years via southern Asia has been suggested by studies based on morphology, archaeology and genetics. However, mtDNA lineages sampled so far from south Asia, eastern Asia and Australasia show non-overlapping distributions of haplogroups within pan Eurasian M and N macrohaplogroups. Likewise, support from the archaeology is still ambiguous.In our completely sequenced 966-mitochondrial genomes from 26 relic tribes of India, we have identified seven genomes, which share two synonymous polymorphisms with the M42 haplogroup, which is specific to Australian Aborigines.Our results showing a shared mtDNA lineage between Indians and Australian Aborigines provides direct genetic evidence of an early colonization of Australia through south Asia, following the "southern route". Homo sapiens) begins in Africa with a group of hunter-gatherers, perhaps just a few hundred strong and ends some 150 – 200 thousand years (ky) later with their six and a half billion descendants spread across the occupied world. Most of the DNA and archaeological evidence are in agreement of the proposition. However, route(s) and time of such spread, undertaken by the anatomically modern Africans to populate the world has been the greater untold part of the story. Recent genetic studies  suggest single "southern route" dispersal of modern humans, extended from the Horn of Africa, across the mouth of the Red Sea into Arabia and southern Asia some time before 50 ky  an anet al.t al. [[[ for the atistics  and usin an anet atistics . The sevky: Kilo Years; kyBP: Kilo Years Before Present: mtDNA: Mitochondrial DNA; rCRS: Revised Cambridge Reference Sequence; np: Nucleotide Position; PCR: Polymerase Chain Reaction.SK, RRR and PK carried out initial screening and complete mtDNA sequencing of the data. SK and RRR did sequence alignment, data base search and all the phylogenetic analysis. AC, BNS and BPU contributed samples. SK drafted the manuscript. VRR conceived the study, participated in its design and coordination also helped to improve the manuscript. All authors read and approved the final manuscript.


For example, a Ugandan study comparing home-based and facility-based antiretroviral therapy (ART) delivery found that both delivered equivalent clinical outcomes, but home-based delivery resulted in substantial cost savings to patients; and a retrospective cohort analysis of an HIV care programme in Lesotho demonstrated that devolving routine patient management to nurses and trained counsellors resulted in impressive gains in annual enrolment, retention in care and other clinical indicators.Studies also demonstrated how the use of trained counsellors and public health advisors could effectively expand both clinical and public health capacity in low-income settings. Studies evaluating the impact of integrating HIV and TB care resulted in improved treatment outcomes in coinfected populations, the development of environmental interventions to reduce TB transmission, and uncovering of the extent of multi-drug-resistant and extremely drug-resistant tuberculosis (MDR-TB and XDR-TB) in KwaZulu-Natal, South Africa.Some mathematical modelling and cost-effectiveness studies presented at this meeting addressed interventions to increase retention in care, and strengthened the evidentiary basis for universal voluntary testing and immediate ART on reducing HIV transmission; debate continued about the relative merits of clinical versus laboratory monitoring. Finally, a provocative plenary presentation outlined the shortfalls of current prevention interventions and argued for more cost-effectiveness analyses to guide the selection of interventions for maximum benefit. The new operations research track at IAS 2009 reflects a growing recognition of the need for applied research to inform the scale up of HIV programmes. The wide range and quality of presentations from a variety of disciplines exemplified one of the challenges for the conference: how to clearly define the operations research field in order to improve understanding of its role among investigators and other HIV professionals. In his summary report, Track D lead rapporteur George Schmid  defined operations research as research that “provides decision makers with information to improve the performance of their programmes ... including identifying service delivery problems and evaluating a variety of delivery interventions” .Key research presented in Track D included: programme evaluations; evaluations of various service delivery models; epidemiology; mathematical modelling; and cost-effectiveness studies. A pre-conference workshop convened by the International AIDS Society (IAS) provided concrete information on how to use operations research methodologies to strengthen HIV prevention, care and treatment scale up. The need for new operations research to further build the evidence base for the health systems strengthening effects of HIV investments also dominated discussion at a two-day pre-conference meeting convened by the IAS.Several studies highlighted how task shifting and the decentralization of HIV services can leverage scarce health care resources to support scale-up efforts. Shabbar Jaffar  compared traditional facility-based delivery of ART with home-based care delivered by trained lay people  in Uganda, and found that both resulted in excellent and equivalent clinical outcomes based on mortality, CD4+ count and virologic response. While the cost of service provision was similar for both models, the home-based care intervention resulted in substantially reduced costs for patients . 3 was reduced from 27% to 13%, and 80% of patients were retained in care [Lipontso Makakole  presented encouraging results from a retrospective cohort analysis of a country programme that devolved routine patient management to nurses and referred patients coinfected with HIV and TB to specially trained counsellors. After two years, annual enrolment more than doubled, the proportion of adults presenting with less than 50 CD4 cells/mmOther presenters offered additional examples of strategies to expand health system capacity. In Rwanda, Alphonse Kayinanga (Catholic Relief Services/AIDS Relief) and colleagues documented a programme that trained community volunteers to screen 3340 HIV-positive individuals for TB, successfully referring 400 for clinical assessment .Operations research also demonstrated how to better integrate service delivery among HIV programmes and among HIV and non-HIV health services. In his plenary presentation, Gerald Friedland  described how an integrated HIV and TB treatment programme in KwaZulu-Natal, South Africa – where more than 90% of TB cases are coinfected with HIV – not only resulted in substantially better clinical outcomes, but also uncovered the extent of multi-drug- and extremely drug-resistent TB prevalence and their effect on morbidity and mortality . FriedlaThe importance of using a combination of approaches to deliver HIV and related health services was echoed in other Track D studies on service integration, including a study of Family Health International programmes in five African countries that assessed the extent to which reproductive health services were integrated into counselling and testing, and care and treatment programmes. The results suggest that, beyond condom provision, more work needs to be done to better integrate HIV with sexual and reproductive health services for women .Not all task-shifting interventions are created equal, however, as demonstrated by a study presented by Charity Kabondo  where trained traditional birth attendants (used by 44% of pregnant women) were used to expand the delivery of antiretroviral (ARV) prophylaxis to prevent vertical transmission. Although the use of traditional birth attendants expanded the use of ARV prophylaxis beyond traditional facility-based care, fewer than half of the pregnant women were identified as HIV positive and less than one-quarter of infants diagnosed as HIV positive received nevirapine prophylaxis from traditional birth attendants .3 results in substantial reductions in morbidity and mortality. Such evidence is expected to change World Health Organization normative guidelines (released in November 2009), thereby making many more people eligible for treatment and reducing treatment coverage figures [Yves Souteyrand  presented encouraging data on increases in ART coverage in 2008, including an almost 50% one-year increase in coverage among children in sub-Saharan Africa . Global  figures .Against this backdrop, several studies addressed the vexing problem of ART programme retention. Kenneth Freedberg  presented a modelling and cost-effectiveness study of four lost-to-follow-up interventions , which indicated that such interventions would be highly cost effective . Based oIn an excellent overview of male circumcision delivery in sub-Saharan Africa, Agot Kawango emphasized that while most countries have completed the necessary situation analyses and taken steps to develop political support and community messaging for male circumcision roll out, health care worker shortages and health facility preparedness remain significant barriers to scale up.Encouragingly, she noted a number of operations research studies underway aimed at evaluating several issues related to roll out, including safety, impact on sexual risk behaviours, HIV incidence and the comparisons of different intervention models, such as physician versus non-physician delivery. One study on male circumcision implementation in Uganda, included in Kawango’s overview, indicated no significant difference in adverse event rates by technique, health facility or cadre of health care worker .In other HIV prevention-related operations research, a promising modelling study on universal voluntary testing and treatment, presented by Reuben Granich , demonstrated the potential preventive effects of this strategy at a population level . QuestioWhile there is consensus regarding the need for a baseline CD4+ count to guide initial clinical decisions, the frequency of subsequent CD4+ counts and the use of viral load monitoring was the subject of substantial debate at IAS 2009. Peter Mugyenyi  reported on final results from the five-year Development of Anti-Retroviral Therapy in Africa (DART) study, which compared clinical to laboratory monitoring using progression to WHO Stage 4 event or death as endpoints. There was no statistically significant difference between the two arms within the first two years and a small, but statistically significant difference from year three onwards, explained by slightly later switch rates in the clinical monitoring arm. Nevertheless, survival rate was excellent in both arms, at 87% and 90% for clinical and laboratory monitoring, respectively  strategy ,17. A moA number of speakers referenced concerns regarding the potential impact of the global economic recession on HIV commitments from both government and private donors. In a provocative plenary presentation, Stefano Bertozzi  argued that while the HIV field has been successful in securing more money for AIDS in recent years, it has been less successful in getting “less AIDS for the money”. He pointed out that few cost-effectiveness studies have been conducted on many common prevention interventions  presented the results of a cost-effectiveness analysis of ACTG 5164, a trial in which patients with opportunistic infections were randomized to receive either early or deferred ART . While tMarielle Bemelmans  presented a landmark cost-effectiveness study of the Médecins Sans Frontières-Ministry of Health ART programme in Malawi, demonstrating that a variety of measures, including task shifting, decentralization of care to health centres and community involvement, helped that country meet universal access targets (with 78% programme retention by the end of 2007) while keeping the marginal cost of the ART programme to €2.6 per inhabitant per year due to economies of scale .There is some evidence that new operations research studies presented at IAS 2009 had an immediate impact on some policy makers in the conference’s host country; an article published after the conference noted that the South African National AIDS Council would be meeting to discuss issuing guidance for earlier ART initiation, treatment for all infants diagnosed with HIV, and better integration of TB and HIV programmes . The eviIAS 2009 was a promising debut for the new operations research track. However, some important programme gaps remain. For example, the critical issues of drug and other medical commodity supply and procurement predictability and forecasting were barely touched on. In addition, the vast majority of data presented in this track related to vertical transmission and ART programmes , with substantially less attention given to prevention interventions beyond circumcision. This is in part due to the research focus of submitted abstracts, as well as the IAS conference’s general focus on biomedical, rather than behavioural prevention interventions.However, without rigorous cost effectiveness, modelling and programme evaluation studies to help identify the most effective prevention interventions, the evidence base for prevention will continue to lag behind that for care, treatment and support, and questions such as those posed by Bertozzi will continue to be raised about whether the HIV field is making the best use of its hard-won financing.MTCT: Mother to child transmission; VCT: Voluntary counselling and testing; STI: Sexually transmitted infection; IEC: Information, education and communication; IDU: Injecting drug userRodney Kort is an independent consultant contracted by the International AIDS Society for the purpose of drafting this section of the IAS 2009 Impact Report: Summary of Key Research and Implications for Policy and Practice.RK drafted the initial text, adapted it for publication in a peer-reviewed journal, and approved the manuscript for publication.


This case-control study aimed to determine critical factors influencing the use of clinical breast examination and mammography among women workers in Monterrey, Mexico.We determined case and control status from survey results. Cases were defined in accordance with the guidelines of the Official Mexican Standard as lack of at least one clinical breast examination during the past year by surveyed women. For women older than 40 years, cases were further defined as lack of at least one mammogram in the previous 2 years and, for women older than 50, lack of a mammogram in the previous year. Controls were defined as adherence by surveyed women to these guidelines. Participants (N = 306 clerks aged 18–60) provided information about their practices, knowledge, and perceptions regarding breast cancer screening. Factors identified by odds ratio analysis as significantly different between cases and controls were analyzed by multivariate logistic regression.Survey participants' knowledge about the utility of breast self-examination , perception that the health care system has enough equipment and personnel for clinical breast examination , and perception that they have enough time to wait for and receive clinical breast examinations  significantly predisposed women to use screening services independent of years of formal education, number of pregnancies, number of living children, hours worked per week, and monthly family income.Perception of organizational and structural factors played a significant role in screening use. Our findings have implications for the general population, provider practices, community interventions, and future development of strategies to increase use of screening services in similar locales. Two decades ago, breast cancer was not a major health concern in the developing world . HoweverWith the goal of formulating recommendations for early detection of breast cancer in developing countries, the 2002 Global Summit Consensus Conference on International Breast Health Care focused on several key issues, including educating and empowering women to adhere to guidelines for breast screening, developing infrastructure for diagnosing and treating breast cancer, and educating primary health care professionals. The 2002 Global Summit also identified social and cultural variables that may be barriers to use of breast cancer screening services, including beliefs that cancer is invariably fatal, spouse/partner lack of acceptance of screening, fear of lack of social support, and preference for traditional medicine .Mexico exemplifies a country caught in this demographic and epidemiologic transition. With socioeconomic development, urbanization, and increased entrance of women into the labor market have come trends linked to increased breast cancer incidence, including obesity, sedentary lifestyle, late parity, nulliparity, and oral contraceptive use ,6. BreasMonterrey, the capital of the state of Nuevo León, is one of many urban areas where chronic diseases such as diabetes, heart disease, and cancer are leading causes of morbidity and mortality . MonterrThe Health Belief Model describes and predicts preventive actions related to cancer by focusing on interactions among health behaviors, practices, and use of services . The modTherefore, we identified and quantified critical factors related to use of breast cancer screening services among women workers in Monterrey, generating novel results for understanding patterns of advanced-stage diagnosis and for modeling strategies to increase early breast cancer detection.This case-control study included formally employed female store clerks working and residing in Monterrey, Mexico. Clerks were selected on the basis of their ability to be surveyed in their place of work away from family and peer influences that could interfere with accurate questionnaire response. The majority of women surveyed (94%) were the only workers present at the place of business; when more than one female worker was present and eligible to be surveyed, we emphasized the importance of each woman responding individually.Women aged 18 years or older were eligible to participate because BSE and CBE are recommended for women starting at this age, and screening at young ages offers an opportunity for women and their doctors or nurses to discuss changes in their breasts, methods of early detection, and factors in the woman's history that might predict future breast cancer. We excluded women with a history of cancer. A minimum sample size of 149 cases and 149 controls was established for 95% confidence in the results and 80% power to detect an odds ratio (OR) of 2.Norma Oficial Mexicana, 041-SSA2-2002) as lack of at least one CBE during the previous year. For women older than 40, we further defined cases as lack of at least one mammogram in the previous 2 years and, for women older than 50, in the previous year. We defined controls as adherence to the Official Mexican Standard guidelines by surveyed women  in Monterrey approved study methodology and protocol measures.We determined case-control status from survey results. Cases were defined in accordance with the Official Mexican Standard  and revised to increase participant comprehension and compliance. The first author (KMW) visited 312 randomly selected businesses throughout Monterrey, accounting for districts of various sizes, and distributed one-third of surveys during each of the three work shifts. Six businesses did not have at least one eligible female clerk on shift. In businesses with eligible participants, the first author explained the purpose of the study and survey, including its anonymous and voluntary nature. The first author left surveys with participants in their place of work and collected them later the same day at a time requested by the participant, usually within 1 hour, to allow for adequate response time during shift breaks or lulls. At collection, respondents were asked if they needed clarification on any of the questions.Of the 379 women asked to participate, 330 (87.1%) agreed and gave informed consent, and 49 (12.9%) declined. Those who declined most frequently cited lack of time (92%), followed by the belief that cancer is invariably fatal, therefore negating the utility of the survey (8%). We excluded the six (1.8%) participants who did not complete at least 80% of the survey.The survey asked about sociodemographic, sociocultural, educational, and organizational and structural factors related to the health care system. Sociodemographic variables included respondent's age, age at first childbirth, number of pregnancies and living children, hours worked per week, and monthly family income. Other variables determined the repeat breast cancer screening practices of the respondents, including the number of BSEs in the previous year and lifetime number of CBEs and mammograms. Response types were 1) open-ended, 2) categorical yes/no, or 3) ranked on a 5-point Likert scale.Sociocultural variables were defined as beliefs and values ingrained in a culture. Respondents provided answers on a 5-point Likert scale (from "very little" to "very much") to the following questions: Are you afraid/feel embarrassed to have your breast examined/receive a mammography from health care personnel? Does your spouse/partner accept that health care personnel examine your breasts/perform a mammography? Do you believe cancer is always fatal?Educational factors included years of formal education and knowledge about breast cancer screening utility and guidelines. Respondents answered the questions: Do you feel BSE/CBE/mammography is important for good health ? Do you know how often you should examine your breasts ? Do you know the screening recommendations for CBE/mammography ?Organizational and structural factors related to the health care system are built into medical encounters that may influence use of services, such as availability of heath resources and quality of care. The survey focused on the respondent's subjective point of view, given that perceptions can be barriers to screening regardless of the objective state of the health care system. Respondents answered the following questions: Did you feel health care personnel and equipment were sufficient for providing CBE/mammography tests ? Did you feel the quality of service provided for CBE/mammography testing was sufficient ? Other structural factors related to the health care system encompass an individual's resources and opportunities to obtain medical attention, such as costs and waiting times. All formally employed persons in Mexico are provided government-funded health insurance covering CBE and mammography screening services, thus removing financial problems as a barrier to screening. Respondents answered how they felt about the waiting time for obtaining CBE and mammography the last time they solicited such services and the waiting time for receiving examinations.We created two education-related indices, each comprising three variables. The first assessed participant knowledge of BSE, CBE, and mammography utility ("screening utility index"). This index coded for accurate versus inaccurate knowledge of the utility of all three detection methods. However, because of an unacceptable level of internal consistency (Cronbach α = 0.48), items could not be combined and were retained in the analysis as separate variables. The second index evaluated participant knowledge of BSE, CBE, and mammography screening guidelines ("screening guidelines index"). This index coded for accurate versus inaccurate knowledge of screening guidelines for all three detection methods. This index reached an acceptable level of internal consistency (Cronbach α = 0.75) and was retained in the analysis along with the individual variables comprising the index.t tests. Univariate OR analysis evaluated the strength of association between participants' knowledge and misperceptions of breast cancer screening and service use. Factors identified as significantly different between cases and controls were entered into multivariate logistic regression models.Survey data were entered directly into SPSS 10.0 for Windows (1999) . Sociodemographic data and quantitative information concerning cancer screening practices were analyzed by descriptive statistics and Significantly more control women than case women had a formal education of high school or more, had at least one pregnancy and at least one living child, and worked 40 hours per week or more . SignifiVariables most strongly associated with use of CBE and mammography were related to educational factors . ControlFour survey variables (data not shown) were not significantly associated with case-control status as determined by OR analysis. These were the belief that cancer is not invariably fatal , spouse/partner acceptance of CBE , spouse/partner acceptance of mammography , and perceptions of reasonable waiting time to receive results of mammography .R2 = 0.292).Variables identified as significantly associated with screening use were entered into multivariate logistic regression analysis . ParticiOur study directly linked the use of breast cancer screening services with years of formal education and accurate knowledge of early detection guidelines. A principal factor for use of screening services was knowledge about BSE screening guidelines, a well-documented indicator in studies of Hispanic women -17. Our Survey participants who perceived that enough equipment and personnel were available for CBE were more inclined to adhere to national screening guidelines for both CBE and mammography. Previous studies indicate the importance of these organizational factors to use of preventive services . Indeed,Social change and epidemiologic transition, especially regarding changes in fertility and breast cancer incidence and awareness in Mexico, also may influence perceptions of the accessibility and quality of medical care concerning sufficient equipment and personnel for CBE. As educational and workforce opportunities improve for women, health awareness and the consequent demand for quality health services increase . HoweverIn addition, participants who perceive they have enough time to wait for and obtain an annual CBE were more inclined to adhere to both CBE and mammography in accordance with national screening guidelines. Structural barriers, such as lack of time, have been described in relation to breast cancer screening, especially the inability of employed women to take work leave or pay child care expenses during an absence . This peFinally, we investigated the influence of fear and embarrassment with regard to CBE and mammography, spouse/partner acceptance of CBE and mammography, and cancer fatality beliefs. Although the sociocultural profile of a population must be considered if a cancer-detection program is to be effective  − and seOur study is subject to information bias because of participants' potential inability to quantitatively recall screening practices and the inaccurate disclosure of personal information such as sexual and reproductive history. To minimize this bias, we surveyed participants away from family and peer influence, assured them of response anonymity, and gave them enough time to carefully consider and answer all questions. Because of these considerations and the high participant response rate, we believe our data are generalizable and have reliably determined critical factors related to use of the breast cancer screening service by this population.We based our study on the assumption that misperceptions can be barriers to screening, regardless of the objective state of the health care system. Therefore, we aimed to determine how users and potential users perceived this system. For example, perceptions of inadequacies in equipment and personnel for CBE may represent actual deficiencies of the system or may result from misconceptions by the general population. The actual state of the breast cancer screening program must be evaluated in terms of these perceptions to determine whether community interventions to increase breast cancer education, screening awareness, and breast health priority are enough or whether macro-level policy interventions aimed at organizational reform of the current system also are necessary.Accurate information and perceptions of the availability of sufficient resources  most strongly determined use of breast cancer screening services. Hypothesized sociocultural factors did not play a significant role. Our findings describing the lack of use of screening services by women workers in Monterrey have implications for the general population, provider practices, community interventions, and future development of strategies to increase use of screening services in similar locales.