Background to the debate: The US and Canadian task forces on preventive health recently declared that there is not enough evidence to recommend for or against routine universal screening of women for domestic violence. Yet some experts argue that routine enquiry is justified. Experts from both sides of the Atlantic debate whether screening can be justified based on the available clinical evidence Domestic violence is a misunderstood topic. The context of a trusted health professional talking to a woman is one that provides an important opportunity for providing information to counter misconceptions.asking all women about domestic violence and not in terms of screening women for domestic violence. It is not appropriate or helpful to regard enquiry about being abused as a form of screening. Domestic violence is not a disease present in the body of the person who experiences it—rather it is a health-related risk factor.I deliberately talk about this in terms of As such, knowledge of abuse puts health professionals in a position to respond better to the needs of women affected by it. Professionals can respond by providing information on specialist services—usually provided outside the health service—that women may access if they wish. By giving information to affected women, health professionals can also help to reduce women's sense of isolation and stigmatisation. Asking about experience of domestic violence can be seen as a routine part of history taking, just as health professionals regularly and repeatedly ask patients about their smoking behaviour, alcohol use, weight, and exercise.The prevalence of domestic violence among women is such that, even if it is not a personal issue for the woman concerned, it most likely will be for one or more of her relatives, friends, and neighbours . Since mMost women experiencing domestic violence report that the specialised services that exist to respond to their needs were difficult to find out about . The proStudies have examined women's views on being asked about domestic violence. These studies have shown that once they have experienced being asked, they are usually in favour of being asked. This is true both for those who have experienced or are experiencing abuse, and those who have not . It is oAsking about abuse should be done in a flexible fashion—the particular questions used should respond to the circumstances of the consultation. For example, it is appropriate to ask women about domestic violence as part of a health check in a Well Woman Clinic, but it would be completely inappropriate in a consultation where another adult or a child was present. By being flexible, health professionals can integrate their questioning within a variety of different encounters. Integrating questions about abuse into routine encounters provides for the maintenance of confidentiality and safety. In order to do this, health professionals require training on raising the issue and knowledge about local advice and support services.Committees on both sides of the Atlantic have rejected the notion of screening women for domestic violence, arguing that there is insufficient evidence of the effectiveness of interventions ,5. Part In one example of an excluded study, researchers used a randomised design to evaluate an advocacy service for women experiencing domestic violence ,8. WomenSystematic reviews have also excluded, or devalued, evidence from qualitative studies. For example, a study of 200 women who had used domestic violence outreach services found that about half were living in situations of domestic violence when they first contacted the service. All of these women reported that the outreach services had helped them to leave the abusive relationship—a valued outcome for them .Given the health impacts on women who experience domestic violence (not to mention their children) and the prevalence of the problem, routinely asking women about abuse should be seen as an important form of primary and secondary prevention for a wide range of health problems.Screening tools for domestic violence are abundant, and many are effective at identifying women experiencing abuse ,10. HoweGiven the morbidity and mortality associated with domestic violence, it is tempting to suggest that universal screening for abuse should be integrated into routine clinical care, such that all women, regardless of their reason for presenting to a clinical setting, should be “asked the question.” Some argue that this approach is justified by the need to increase awareness of domestic violence as a significant problem with serious health and social consequences, and to make abused women aware that they are not alone in their experience. These are important considerations.Certainly all women who disclose that they have been exposed to violence should be provided with options regarding seeking help . Good diwithout obvious signs and symptoms of domestic violence—such as a woman who comes to the clinic for assessment of an upper respiratory tract infection? Should such women be prompted to disclose whether they are being abused? The woman who is not being abused will answer to that effect, and the appointment can carry on. But for the woman who is experiencing violence, who has not volunteered this information, several factors must be considered. An important issue is whether she is ready—both psychologically and in terms of taking specific actions—to confront the issue. A number of excellent qualitative studies have examined the process that women undertake in acknowledging that they are “victims” of “abuse” and embarking on the often long and difficult journey to avoid, reduce, and ultimately stop the violence in their lives [However, what about women presenting ir lives ,17. GiveAny potential benefits of screening must then be weighed against its potential harms, including labelling women, prompting potentially premature disclosure, and triggering possible reprisal violence from the abuser if he discovers she has sought help. The last of these might be particularly exacerbated for the woman with the respiratory tract infection who was unprepared to disclose and did not take necessary precautions. Other potential harms include exposure to the ramifications of laws on mandatory child protection reporting, whereby health providers must report such disclosures to child protection authorities. This can lead to an investigation that potentially increases a woman's risk of exposure to violence, and in some cases of having her children placed in foster care. Research has shown that many of these potential harms are of concern to women when mandatory universal screening and/or reporting protocols are in place . FinallyGiven the lack of clear data on the benefits of screening and of the interventions to which women are referred, and the lack of data on potential harms, we and others have concluded the following ,19,20. UI agree entirely with Nadine Wathen and Harriet MacMillan that practice should be based on evidence. There are further areas of agreement. We agree that there is a lack of knowledge on effective interventions for abusers and on harm occurring as a result of enquiry, and that targeted case finding is important.all women about domestic violence. Underlying this difference is the issue about how much evidence we need, and of what type. My position is that the evidence that already exists is sufficient to justify the promotion of routine enquiry, aiming to ask all women about their experience of abuse. There is evidence of actual benefits to women—and their children—from interventions provided by specialised services for domestic violence and from brief discussions with health professionals [The key difference that exists between my viewpoint and theirs is the conclusion about whether health professionals should aim to ask ssionals .Aiming to ask all women has several advantages over targeted case finding . It contThe twin issues of women's safety and harm minimisation are extremely important, for both routine enquiry and targeted case finding. These issues are important reasons why training and protocols for enquiry are necessary. Standard principles of confidentiality should be reinforced in training and protocols, which need to be tailored to relevant legal requirements, such as when child protection issues are involved. Training and protocols also need to emphasise that the role of routine enquiry is to facilitate, and not force, disclosure. It must remain the woman's choice as to if, when, and to whom, she discloses.all women or only in situations where asking about it is part of a specific diagnostic assessment. As with screening for a disease, universal screening for domestic violence should not be implemented unless we are sure that interventions are available to help those identified via screening and that screening plus appropriate treatment will do more good than harm.We agree with Ann Taket that domestic violence is not a disease, and that the paradigm of “screening for disease” is problematic in this context. At issue, however, is the question of whether domestic violence should be “talked about” with Professor Taket outlines the importance of integrating discussions about abuse in consultations to raise community awareness. Unfortunately, there is no evidence that this type of consciousness-raising occurs, or if it does, what benefit it might have. Given the lack of effectiveness of educational campaigns in general, it is difficult to be optimistic about this approach.We disagree with her conclusion that existing systematic reviews have “excluded studies done outside the health service setting….” Our review included interventions such as the post-shelter advocacy counselling approach to which Professor Taket refers . This inFinally, we concur that qualitative studies are invaluable in understanding domestic violence. Such research has provided insight into the complex process that women undertake to address the violence in their lives. Until there is evidence that universal screening actually helps with this process, the focus should be on developing evidence-based approaches to assist women when they do disclose abuse and on training health professionals to respond appropriately to such disclosures.


Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system. Daniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness', which links priority setting to theories of democratic deliberation. Fairness is a key goal of priority setting. According to 'accountability for reasonableness', health care institutions engaged in priority setting have a claim to fairness if they satisfy four conditions of relevance, publicity, appeals/revision, and enforcement. This is the first study which has surveyed the views of hospital decision makers throughout an entire health system about the fairness of priority setting in their institutions. The purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'.160 Ontario hospital Chief Executive Officers, or their designates, were asked to complete a survey questionnaire concerning priority setting in their publicly funded institutions. Eight-six Ontario hospitals completed this survey, for a response rate of 54%. Six close-ended rating scale questions , and 3 open-ended questions  of priority setting in your hospital?) were used.Overall, 60.7% of respondents indicated their hospitals' priority setting was fair. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement (39.5%).For the first time hospital Chief Executive Officers within an entire health system were surveyed about the fairness of priority setting practices in their institutions using the conceptual framework 'accountability for reasonableness'. Although many hospital CEOs felt that their priority setting was fair, ample room for improvement was noted, especially for the enforcement condition. Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system, including governments, funded provincial/territorial agencies, pharmaceutical benefit-management organizations, hospitals and clinical programs . CountriDaniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness' -7, which'Accountability for reasonableness' may be an effective framework for describing the components of priority setting, evaluating the fairness of priority setting in hospitals and identifying 'good' practices and opportunities for improvement. It can help hospitals improve their priority setting practices and can be an effective driver of health care reforms -10.'Accountability for reasonableness' has been used to evaluate priority setting in health systems . HoweverThe purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'.We conducted a survey of Chief Executive Officers, or their designates, of Ontario hospitals. The survey questionnaire covered 102 items, including hospital profile information . In this paper we focus on the results of 9 questions concerning priority setting, fairness, and the four conditions of 'accountability for reasonableness' . There are 160 hospitals in Ontario and all were invited to participate in this study.160 Ontario hospital Chief Executive Officers, or their designates, were asked to participate. 86 Ontario hospitals completed this survey, for a response rate of 54%. The average bed count of the responding hospitals was 250.4, with a range of 18 to 1265 beds. The average operating budget of the hospital sample was $75.8 million, ranging from $3.3 million to $733 million. The sampled hospitals represented a blend of teaching, small, community and specialized service facilities across the province.The survey was pre-tested and mailed to Chief Executive Officers of all Ontario hospitals in January 2001. Data from returned surveys were entered into an electronic database for further analysis. Of the 9 questions analyzed in this study, 6 asked for a rating on a 5-point scale ranging from 'Not Well' or '1' to 'Very Well' or '5', and 3 were open-ended.Close-ended ratings were analyzed statistically , with raOverall, 60.7% of respondents indicated their hospitals' priority setting was fair, while 79% stated their hospitals met their priority setting goals. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement 39.5%). (Refer to Table 9.5%. (Re = 3.94) condition significantly higher than the publicity ( = 3.57), appeals ( = 3.52), and enforcement ( = 3.25) conditions (p < .05) (paired-samples t test). While publicity and appeals conditions were not significantly different, respondents rated these conditions significantly higher than the enforcement condition (p < .05). The distribution of ratings suggested that there was ample opportunity for improvement, with most room for improvement in meeting the enforcement condition.Respondents rated the relevance . Fairness ratings were also positively correlated with each of the 4 'accountability for reasonableness' conditions (p < .01), as were meeting priority setting goals (p < .05).The bivariate correlation between each of the accountability variables of relevance, publicity, appeals/revision and enforcement was strongly positive (p < .01). The Pearson correlation coefficients among the 4 conditions ranged from 0.41 to 0.57. The internal consistency (Cronbach's α) of all of the 'accountability for reasonableness' conditions was very good (α = .78).Bed size  and operating budget  were negatively correlated with the rating of fairness in priority setting.In this section we describe participants' responses to the open-ended questions organized according to themes. We have included verbatim responses to help illustrate the themes.Decision makers emphasized four priority setting goals which were complex, interdependent, and required balancing. Some respondents said that (1) meeting needs existed in relation to delivering (2) quality services, or was constrained by resource availability. Examples of these goals include "quality care within available resources" and "access to high quality service in areas of greatest need". While (3) meeting budgets was identified as a goal by some decision makers, it did not exist in isolation from other goals such as meeting strategic directions or needs. One decision maker said his goal was "ensuring a balanced situation at year end while meeting the direction set out in our strategic plan". Achieving (4) organizational goals was expressed as a limiting, or organizational focusing process, which involved alignment or balancing of multiple goals and values.Decision makers described a deliberative process by which their priority setting goals were operationalized, providing examples of good practices and challenges or barriers for achievement. Overall, decision makers appeared confident that their priority setting goals were the correct ones, in no case did they comment that expressed goals were unrealistic, so contributing to lack of achievement.Decision makers pointed to five factors of importance in meeting their priority setting goals. Review processes (1) were described in which different review processes are brought to bear pointing to areas requiring additional resources. For example, a decision maker said "annually we review and ensure that resources are being allocated to priority programs and services". Leadership (2) was implicated as an important factor in meeting priority-setting goals. For example, a decision maker said "We do not set goals that are pie in the sky, they must be achievable". With respect to (3) stakeholder consultation, some respondents pointed to the need to involve the wider community in decision making. Decision-makers felt that improvements in priority setting were contingent upon (4) access to relevant information. Finally, some decision-makers emphasized the importance of (5) decision making tools, or benchmarking, to improve decision making.Respondents gave information to support their self-evaluation, and provided examples to demonstrate the fairness of priority setting processes from their perspective.In evaluating the fairness of priority setting, decision makers emphasized five themes. Stakeholder consultation raises the level of (1) inclusivity, bringing different points of views and interests to bear in solving common problems. For example, a decision maker said "we have a service providers network in our community that has direct input into resource allocation and program planning". Respondents described review processes (2) involving the deliberation of concerned parties, using relevant data, based on need, cost and other values (e.g. evidence). Reporting systems (3) provide an institutional feedback loop, pointing to areas where limits may be fairly set. With respect to (4) revision/appeals, revising arguments or values based on iterative processes involving various stakeholders is a feature of fairness, and helps to improve buy-in, but may increase organizational tensions. Finally, (5) governance may also be involved in developing decision-making models, and in ensuring the conditions of relevancy, appeals/revision, and publicity are met. For example, a decision maker said "The Board and senior management have developed decision-making models for key program/service changes...our appeals process is informal, but open to access including the Board".To our knowledge, this is the first published survey of hospital decision makers covering an entire health system, using Daniels and Sabin's framework of 'accountability for reasonableness'. It provides data to understand how fair priority setting processes are, what decision makers' priority setting goals are, and how well these goals are met.Several studies, using either survey or qualitative methodologies sometimes in combination with hypothetical "tradeoffs", have examined priority setting from theoretical perspectives aimed at capturing the public or professional's preferences or values in priority setting -24. RelaThis study makes five contributions to knowledge on priority setting. First, there is ample room for improvement in fair practices within Ontario hospitals as described by their Chief Executive Officers. Although many hospital CEOs felt that their priority setting was fair, ample room for improvement was noted, especially for the enforcement condition, followed by publicity, appeals/revision and relevance. While 79% of decision makers felt their hospitals met their priority setting goals, only 60.7% felt their processes were fair. According to decision makers, the perceived 'gap' was greater in meeting fairness than in priority setting goals.Second, it is feasible for decision makers to assess the fairness of priority setting in their institutions on a quantitative basis according to the 'accountability for reasonableness' framework, with greater than half of respondents saying their processes are fair. There is a high degree of association between 'fairness' and the internal components of 'accountability for reasonableness', lending support that fairness can be operationalized through 'accountability for reasonableness'. As well, the internal conditions of 'accountability for reasonableness' are highly related, and positively correlated, suggesting relevance, publicity, appeals/revision, and enforcement are measuring comparable aspects of fairness. Consistent with this, the high Cronbach's α finding is promising for the development of an 'accountability for reasonableness' scale of perceived fairness of priority setting in health care institutions. Measuring decision makers' self-report of their perception in meeting the various conditions of 'accountability for reasonableness', the scale would provide a practical tool for decision makers to assess self-reported views over time, noting progress in meeting conditions, while providing a reference point for needed improvement (i.e. enhance meeting 'publicity' condition). Finally, the finding of a negative relationship between number of hospital beds or budgets and self-report on fairness is consistent with the view that smaller hospitals may be perceived to have fairer processes, with greater involvement of their local communities in decision making and emphasis on transparency and "trust".Third, decision makers' views were surveyed at a health system level to determine what their actual priority setting practices were. Four complex, interrelated priority setting goals were described, suggesting a balance of need, quality, budget and organizational goals in priority determination. In addition, the study points to a close alignment of factors required in the meeting of priority setting goals and in the elements of fairness. In providing decision maker perspectives on characteristics of fairness, this study also adds to previous empirical work suggesting fair priority setting depends on a fair priority setting process . AdditioFour, this study has shown, from a blend of qualitative and quantitative approaches, that it is feasible to operationalize the 'accountability for reasonableness' framework, through the design of survey instruments to facilitate self-evaluation, and identification of good practices. This data can be shared with decisions makers to improve the fairness of their priority setting processes in meeting the four conditions of 'accountability for reasonableness'.Finally, this study expands on the likely relationship between leadership and priority setting in which leadership was found to contribute to perceptions of fairness in two committees engaged in priority setting for new health care technologies. Study results indicate that greatest room for improvement exists in meeting the 'enforcement' condition, with decision-makers describing critical leadership success factors, including: the role of governance in establishing policy and in meeting this condition, the need to set achievable corporate goals, and the significance of a lobbying funding function. Further study is needed to clarify the nature of this leadership contribution.The study is limited, first, in the response rate from hospitals. Only 54% of Ontario's 160 hospital CEO's responded to the survey. It is possible that hospitals responding to this survey were those doing, or perceived doing, better on self-report than others. However, there is no evidence to suggest that this is the case, and the sample did include small, medium and larger teaching hospitals, as well as specialized facilities to mitigate against representative selection bias. Second, social desirability bias was possible in that the views of decision makers expressed in the survey may not have corresponded to what they actually believed, or did. However, unpublished data  based onIn this first survey of Chief Executive Officers within a health region reporting on their assessment of the fairness of priority setting practices in their institutions according to 'accountability for reasonableness', ample room for improvement was observed, especially for the enforcement condition. Additional study is required to understand how application of 'accountability for reasonableness' will vary within and across institutions, and is shaped or influenced by various parameters, including the nature of corporate leadership. These evaluations can help to identify good practice opportunities for improvement that can be shared between local institutions or used within government to drive health care reforms.The author(s) declare they have no competing interests.DR was the primary analyst and principal author of the manuscript. DKM, CK and PAS were involved in study conception, analysis and drafting the manuscript. CK and DKM were involved in data collection. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


We have previously shown that use of an EC brush device in combination with the Rovers Cervex-Brush (SurePath broom) offered no significant improvement in EC recovery. Here we determine if use of additional collection devices enhance the diagnostic utility of the SurePath Pap for gynecologic cytology.After informed consent, 37 women ages 18–56 receiving their routine cervical examinations were randomized into four experimental groups. Each group was first sampled with the SurePath broom then immediately re-sampled with an additional collection device or devices. Group 1: Rover endocervix brush (n = 8). Group 2: Medscand CytoBrush Plus GT (n = 7). Group 3: Rover spatula + endocervix brush (n = 11). Group 4: Medscand spatula + CytoBrush Plus GT (n = 11).Examination of SurePath broom-collected cytology yielded the following abnormal diagnoses: atypia (n = 2), LSIL (n = 5) and HSIL (n = 3). Comparison of these diagnoses to those obtained from paired samples using the additional collection devices showed that use of a second and or third device yielded no additional abnormal diagnoses. Importantly, use of additional devices did not improve upon the abnormal cell recovery of the SurePath broom and in 4/10 cases under-predicted or did not detect the SurePath broom-collected lesion as confirmed by cervical biopsy. Finally, in 36/37 cases, the SurePath broom successfully recovered ECs. Use of additional devices, in Group 3, augmented EC recovery to 37/37.Use of additional collection devices in conjunction with the SurePath broom did not enhance diagnostic utility of the SurePath Pap. A potential but not significant improvement in EC recovery might be seen with the use of three devices. In gynecologic cytology, sampling of both the ecto and endocervix is critical to increasing Pap test sensitivity . ControvAfter study design approval from the Carle Clinic Association Institutional Review Board and informed consent, 37 women ages 18–56 receiving their routine cervical examinations were sampled with the SurePath broom. This device, which is packaged with the SurePath Pap, is the Rovers Cervex-Brush . Its use followed the manufactures recommendations of 5 full clockwise rotations. The same patient was immediately re-sampled with either the Rovers endocervix brush, patient group 1; the Medscand Cytobrush Plus GT , patient group 2: the Rovers endocervix brush + Rovers Spatula, patient group 3; or the Medscand Cytobrush Plus GT + Medscand Pap Perfect Spatula, patient group 4. All devices had "pop-off" heads. The SurePath broom device was collected into CytoRich Preservative vials  and processed routinely using the PrepStain Slide Processor . In samples using multiple collection devices, all devices, including the SurePath broom, were placed in a single collection vial and processed as above.The diagnostic terminology used was derived from the 1991 revision of the Bethesda System (TBS) -9. The dAll cases where the cytology diagnosis was ASC-US or more serious underwent colposcopic-guided cervical biopsy . Cases were excluded from analysis if the: 1) cytology and corresponding tissue diagnosis were separated in time by more than 6 months; 2) cytology and/or corresponding cervical biopsy were not performed and interpreted within the Carle Clinic Association/Hospital system. In cases where multiple cervical biopsies were performed, the cytology closest in temporal relationship to the cervical biopsy was correlated. No cervical biopsies met the exclusion criteria.All analyses were performed using SAS statistical software . Data comparisons were made using the Student's paired t-test, the Sign Test and the Wilcoxon Signed Rank test for analysis of non-parametric data.We have previously shown that use of the Surgipath C-E brush  in combination with the SurePath broom did not increase EC recovery in women undergoing a SurePath Pap . This prWhen group 2 patients were examined by cytology after using the SurePath broom  of SurePath Pap limited by diagnoses are due to lack of an EC component . To overIn this study, we found that 3% of women sampled with just the SurePath broom lacked EC cells. These findings were consistent with but better than our previous report based on 3,994 women in which we found that 6% of SurePath Paps were "satisfactory for evaluation but limited by no EC cells" -16. ThisDebate over cervical sampling devices often focuses on EC sampling. Unfortunately, few studies are available that report both the EC absence rate and the abnormal cell detection rate in studies where multiple devices are compared. The retrospective study by Boon et al  stands oAs with any study, the strength of statistical analysis increases as the sample size is increased. However, even with small sample sizes, compelling results can be obtained if the statistical significance is large. Here the data was analyzed using three different nonparametric statistical tests (for non-continuous or non-numeric data) to ensure stringency. In addition, we chose to include the p-values for each of these statistical tests to show that multiple analyses yield the same result and that no single statistical test was chosen to favor a desired outcome. The hypothesis being tested, in this study, is that the use of additional collection devices in conjunction with the SurePath broom device does not enhance diagnostic utility. Normally, p-values <0.05 indicate that one should reject the hypothesis being tested and conclude enhanced utility. In this study, the large p-values generated from analysis of the data indicate a very high probability that the hypothesis be rejected and that no enhanced diagnostic utility is realized with the use of additional collection devices.Since liquid-based Pap testing is relatively new, little work has been done to examine sampling device effectiveness utilizing this technology. Selvaggi et al compared the ThinPrep broom to the ThinPrep spatula + cytobrush and the ThinPrep broom +cytobrush . These aIn conclusion, the SurePath broom appears to be a very effective cervix sampling device when coupled with the SurePath Pap. In 60 patients examined prospectively  of uncertain significance (ASC-US), endocervical cell (EC), Food and Drug Administration (FDA), high grade SIL (HSIL), low grade SIL (LSIL), Papanicolaou (Pap), quantity not sufficient for diagnosis (QNS), squamous intraepithelial lesion (SIL), SurePath Liquid-Based Pap Test (SurePath Pap), SurePath Liquid-Based Pap Test Broom Device (SurePath broom), The Bethesda System (TBS).SJD coordinated the study and analyzed the study data, DLO collected all samples, JCO performed the statistical analysis. GGF constructed the manuscript.The pre-publication history for this paper can be accessed here:


Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia.International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer.The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns.Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries. Worldwide, over one million people die of lung cancer each year . In the Epidemiological studies have shown that cigarette smoking is the major cause of lung cancer in both sexes -8. HowevLong-term geographical trends in cancer mortality can provide useful information to assist etiological research. However, Asian countries are often excluded from studies of geographical differences in trends in lung cancer mortality. In order to clarify the changing patterns of lung cancer mortality worldwide, we examined lung cancer trends from 1971 to 1995 among men and women for 23 countries including four from Asia – Taiwan, Japan, Singapore, and Hong Kong. In addition, we plotted the pattern of mortality rate in these countries by using the age-period-cohort (APC) model.We used data from the World Health Organization (WHO) and Taiwan to analyze secular trends from 1971–1995 in lung cancer mortality in both men and women. Mortality data provided by WHO were relatively incomplete in some countries, so we analyzed data from 22 countries and Taiwan. The twenty-two countries – Hong Kong, Singapore, Japan, Portugal, Poland, Italy, Cuba, Spain, Hungary, France, Greece, Finland, United States, England and Wales, Netherlands, Belgium, Canada, Australia, New Zealand, Denmark, Norway and Sweden – are members of WHO. The data for Taiwan came directly from the Office of Statistics, Department of Health in Taiwan. Since rates for the under 30-year age group are often based on few deaths, and rates for the over 80-year group might be affected by competitive death effects, only rates for the age range 30 to 79 were considered, so as to ensure adequate reliability of the estimates. Lung cancer mortality rates between 1971 and 1995 were analyzed in five consecutive five year periods  and in five year age groups.1991–1995 - ASMR1971–1975) / (ASMR1971–1975)] × 100.Age-standardized mortality rates (ASMR) were calculated using the world population for 1976 as the reference . PercentIn order to apply the APC model, the matrix of age-specific death rates was calculated for each 5-year calendar period (from 1971–1975 to 1991–1995) and age group (from 30–34 to 75–79). The effect of period of death in the APC model was evaluated by a log-linear Poisson model with a modified method as described by Osmond and Gardner . BrieflyAge-standardized mortality rates from lung cancer per 100 000 population per year in 23 countries for 1971 to 1995 are listed for men in Table Table The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Cuba, Singapore, and Japan were 2.10, 2.39, 2.78, 3.07, and 3.55, respectively, with a range of 0.17 to 0.51 over the five-year periods. These values were not only relatively constant over time, but were also lower than seen in the western countries. For example, the lowest sex ratio of 2.10 was seen in Taiwan, with the sex ratio remaining a relatively constant value over the entire period.Only age is adjusted when the ASMR is calculated. However, both age and cohort effect are adjusted in the APC model. The period effects for males and females from the APC model applied to the data from the 23 countries could be classified into seven patterns: 1) an increasing trend in both sexes, seen in Taiwan  declare that they have no competing interests.YPL was responsible for the development of intellectual content and the study design, collected and analyzed the data, interpretation of the results, manuscript drafting and the critical revisions of manuscript. YCH was responsible for the development of intellectual content, interpretation of the results and manuscript drafting. GWL was responsible for data coding and entry and statistical analyses.The pre-publication history for this paper can be accessed here:


We aimed to determine optimal strategies for complete mortality ascertainment comparing death certificates and United States (US) Veterans Administration (VA) records.We constructed a cohort of California veterans who died in fiscal year (FY) 2000 and used VA services the year before death. We determined decedent status using California death certificates linked to VA utilization data and the VA Beneficiary Identification and Records Locator System (BIRLS) death file. We compared the characteristics of decedents who would not have been identified by either single source  with the rest of the cohort.A total of 8,813 veteran decedents were identified from both VA decedent files and death certificates. Of all decedents, 5,698 / 8,813 (65%) veterans were identified in both source files, but 2,426 / 8,813 (28%) decedents were not identified in VA BIRLS, and 689 / 8,813 (8%) were not identified in death certificates. Compared to the rest of the cohort, decedents whose mortality status was ascertained through either single source differed by race / ethnicity, marital status, and California residence. Clinically, veterans identified from either single source had less comorbidity and were less likely to have been users of VA inpatient or long term care, but equally or more likely to have been users of VA outpatient services.As single sources, VA decedent files and death certificates each provided an incomplete record, and death ascertainment was improved by using both source files. Potential bias may vary depending on analytic interest. Clinicians, healthcare administrators, researchers, regulators and policymakers are concerned with optimizing mortality ascertainment using administrative data. In addition to its clinical importance, mortality informs program planning, quality assessment and improvement, and public reporting -8. VeterIn order to evaluate the implications for improving veterans' end-of-life care, we constructed a population-based decedent cohort . For sucThe VA Beneficiary Identification and Records Locator System (BIRLS) contains records of all beneficiaries including veterans whose survivors applied for burial benefits. It includes records of discharged military veterans post-1973 and recipients of Medals of Honor and VA education benefits. After submission to the Veterans Benefits Administration (VBA), deaths are recorded in the BIRLS Death File. A submission to the VBA is typically triggered by a family claim for death benefits  -19. The We first identified 345,380 decedent veterans who died during FY2000 (30 September 1999 – 1 October 2000) from the BIRLS Death File. We used SSNs to link cases to VA NPCD outpatient, inpatient, or long term care records restricted to recipients of any VA services in California within 12 months of death. We extracted records including any inpatient or long term care admission, or outpatient encounters. Veterans who entered the cohort on the basis of using outpatient services were required to have at least one clinical encounter .In addition, we used California death certificates as second source to identify decedent veterans by linking SSNs from death certificates directly to VA utilization files. California death certificates contained 462,561 records for calendar years 1999 and 2000, and we primarily matched decedents identified through death certificates to BIRLS by SSN. We manually inspected matches on SSN only and we also examined matches on criteria other than SSN . Additional cases we accepted after manual inspection involved transpositions of one and rarely more than one SSN digit but agreement in other fields. Thus, the cohort included recipients of VA clinical services verified as deceased based on either BIRLS or death certificates, and all cases were linked to VA utilization files by SSN.In the final decedent cohort, we excluded cases of non-veterans receiving care at VA facilities by examining indicators of veteran status associated with visits. The VA assigns specific codes to non-veterans rendered care for various reasons . We also considered the possibility of erroneous decedent status by looking for evidence of healthcare utilization during the 12 months after death. We excluded cases with evidence of utilization more than one month after the date of death.We used VA encounters and ICD-9-CM codes to demographically  and clinically characterize decedents -26. We iTo understand the limitations of single source mortality ascertainment, we described decedents who would not have been identified by a strategy using either death certificates alone or VA decedent files alone. We compared these cases with the rest of the cohort based on their demographic and clinical attributes and the settings in which they received care. Based on distributions, we used Wilcoxon tests for continuous and chi-square tests for categorical variables.From 345,380 deaths during the period 30 September 1999 to 1 October 2000 identified in BIRLS, we distinguished 6,071 decedents who were users of VA inpatient, outpatient, or long term care services in California. California death certificates included 227,308 deaths during the same period, including 3,580 additional users of VA inpatient, outpatient, or long term care services in California. Using SSN and other identifiers to match decedent cases to VA utilization data, we excluded non-veterans (n = 365), users of only non-clinical care such as laboratory tests (n = 251), those possibly alive based on subsequent VA encounter data (n = 229), and 3 cases for other reasons. Of the final cohort of 8,813 veteran decedents, 5,698 (65%) cases were identified in both source files, while 689 (8%) were only identified in VA decedent files, and 2,426 (28%) additional cases were only identified through death certificates . Ninety-nine percent of decedents missed by using VA data alone were California residents ; whereas, 62% of those missed by using death certificates alone were out-of-state residents . Relatively fewer veterans of white or black ethnicity and relatively more veterans of missing ethnicity were represented among decedents missed by either single source strategy. The proportion of married or previously married veterans was higher and single or missing marital status lower among those decedents missed using only BIRLS, and relative proportions were reversed for a strategy using only death certificates.Decedents missed by either single source approach were less likely to have been diagnosed with an advanced chronic illness than the identified cohort. Veteran decedents missed by using only BIRLS were less likely to be diagnosed with any condition except HIV and dementia, and those missed by using death certificates alone were less likely to be diagnosed with any condition except HIV. With a BIRLS only approach, 37% of missing cases vs. 35% of the remainder cohort p < 0.001) had no diagnosed chronic illness . Veteran decedents missed by either single source approach were equally or more likely to have been users of the outpatient setting, but missed cases were less likely to have been users of inpatient healthcare settings  were both significantly lower among veterans missed by either single source approach.Our findings are consistent with Washington State where the deaths of 25% of 533 veterans who only used outpatient services were only identified with death certificates, and 5% were only identified in BIRLS.  Using BIOne limitation of our study is that we did not identify cases that were only decedents by virtue of VA utilization files alone rather than BIRLS, although Dominitz, et. al., identified only 2.7% of deaths this way . We did Researchers, managers, and policy makers should understand the limitations of sources of mortality ascertainment. The relationship of missing data to bias is related somewhat to how "missingness" is distributed by the outcome of interest. Our findings suggest these concerns may be relatively more important for studies involving veterans and racial-ethnic disparities, co-morbidity, certain disease comparisons, or settings of care. Additional study is needed to compare BIRLS, death certificates, and the NDI for mortality ascertainment in veterans. If our findings are confirmed, the VA may need to consider improving its system for mortality ascertainment through routine linkages to national mortality data. Studies of end-of-life care using decedent cohorts need to pay particular attention to the incompleteness of VA data as the sole source of mortality information.VA, Veterans Administration; FY, fiscal year; BIRLS, Beneficiary Identification and Records Locator System; NPCD, National Patient Care Database; SSN, Social Security Number; CHF, congestive heart failure; COPD, chronic obstructive lung disease; ESLD, end-stage liver disease; ESRD, end-stage renal disease.The author(s) declare that they have no competing interests.KL originated and oversaw all aspects of the conception, design, analysis, and publication of the study. SA, LR, and EY contributed to conception, design, and analysis. MW contributed to analysis and is responsible for programming. All authors reviewed and approved of the manuscript.


Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'.This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents , and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation.Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement.'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less. As of August 12, 2003 there were 438 probable and suspected cases of Severe Acute Respiratory Syndrome (SARS) in Canada – the majority located in Toronto. In Toronto there were forty-four SARS related deaths and over 100 health care workers contracted SARS, placing intense pressure on Toronto's public health and hospital system [Due to both the importance of hospitals in any health system and the difficulties they face, improving priority setting  within hospitals is crucial. Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as SARS in Toronto in 2003, amplifies the difficulties of hospital priority setting.relevance, publicity, appeals, and enforcement  over two hundred key documents , and (2) 35 interviews with key informants (senior administrators (6), physicians (10), managers (5), nurses (5), a patient (1), family members (2), and other staff (6)). Interviews were audiotaped and transcribed. Interview participants were asked to describe priority setting decisions in relation to SARS and their thoughts about it. We developed an interview guide based on previous research and improved it through pilot interviews with personnel from other hospitals. As is traditional with qualitative studies, the interview guide was modified during the study to explore emerging themes.The data were analyzed concurrent with collection using a modified thematic approach in three phases: open coding, axial coding, and evaluation. In open coding, the data were fractured by identifying chunks of data that relate to a concept or idea. In axial coding, the concepts were organized under overarching themes (i.e. the four conditions of 'accountability for reasonableness'). In evaluation, the descriptive data were compared with the conditions of 'accountability for reasonableness' – correspondence with the framework was considered 'good practice'; instances where the conditions are not met were considered 'opportunities for improvement'. Concepts were formalized and made explicit through the writing of the findings .The validity of the interpretations was enhanced in four ways . First, Approval for this project was obtained from the participating hospital's Research Ethics Board. Written informed consent was obtained from each individual before being interviewed. All data were kept confidential and viewed only by the research team. No individuals have been identified without their explicit agreement.In this section we describe one hospital's priority setting in response to SARS by focusing on the types of decisions, the decision making process, and the supportive reasoning. We then evaluate our findings using the four conditions of 'accountability for reasonableness'. We have also included verbatim quotes from participants to illustrate key points.There were two distinct phases of priority setting at the hospital during the SARS outbreak. First, during the initial days of the outbreak, decisions were made in order to contain the spread of the virus. The Ontario Ministry of Health and Long-Term Care (MOHLTC) directed Toronto acute care hospitals to establish or maintain as necessary a SARS isolation area, restrict patient visits, limit visitors and suspend selected patient transfers. Second, after the initial weeks of the outbreak, was a 'ramp up' phase during which the hospital gradually increased its level of activity. Throughout both phases, priority setting decisions can be organized according to four specific types: decisions relating to staff and patients, beds/rooms, clinical activity, and visitors.Staff were allocated for SARS patients in the SARS unit and ICU, screening at the doors, manning the site command centre, or helping out in occupational health; pregnant and immunosuppressed staff were either redeployed to low-risk activities or sent home; staff deemed non-essential were sent home with pay; students were sent home and educational rounds were cancelled. General medicine patients were transferred to other medical units to maintain the SARS isolation unit; out-patients who had been waiting for non-emergency surgery or clinic appointments were told to wait indefinitely.The SARS isolation unit required negative pressure beds. The hospital created these spaces in a specific isolation unit on a general medicine floor, and in the ICU and Emergency. Admissions to negative pressure beds were decided case-by-case and were based on the assessment of the referring physician, the hospital's infectious disease representative, and the hospital intensivist.All non-emergency surgery and ambulatory care were cancelled during the initial 7–10 days of SARS. During the ramp up phase, clinical activity volumes increased in percentages allowing for urgent cases to be seen as determined by physicians. Operating room time was allotted by division – each individual surgeon reported to their division head the cases they considered urgent. This activity was coordinated by the hospital's command center.A 'no visitors' policy was enforced during the initial stages of SARS except for compassionate grounds as determined by the nurse manager or nurse in charge of the particular unit, in consultation with the attending physician and the hospital command centre. During the ramp up phase, the hospital relaxed the no visitor policy according to changing directives from the MOHLTC and the human resources available for screening at the doors.Priority setting decisions were made across all levels of the institution. We identified four groups of key decision makers: Corporate Command, Hospital Command, Department Management/Chiefs, and Individual Clinicians. MOHLTC directives were interpreted by a team of senior administrators (corporate command) and then communicated to the hospital's command centre. The hospital's command centre implemented the recommendations from the corporate command in accordance with patient population requirements and physical logistics. Department managers and clinical staff also participated in allocating human resources and determining patient care priorities. The corporate command was in constant communication with the hospital's command centre who maintained communication with the managers and other leaders through teleconferencing and email.Throughout each stage of the SARS outbreak, safety was the primary rationale underpinning priority setting. During the early stages of SARS, decisions were made for infection control focused on protecting staff. During the ramp up phase, decisions were based more on a duty to care for patients, emphasizing the hospital's role in the community. However, in addition, there were several other reasons used in support of each decision  staff and patient safety was the primary criterion in decision making, but each decision was based on a cluster of relevant reasons – decision makers' use of clusters of relevant reasons has been identified and discussed in a previous study [opportunities for improvement: 1) patients and families did not have access to the reasons for many decisions, including the visitation policy and ramp-up of clinical activities; 2) a formal revision/appeals mechanism could help improve the quality of decision making and alleviate the unfair reliance on the 'squeaky wheel' phenomenon; 3) OR time was allocated by division, rather than by patient need, and these decisions should be discussed more fully; 4) institutional leaders should maintain two-way contact with front-line staff who are implementing priority setting decisions – this will provide support and enhance accountability for decision making by staff.We identified the following us study , 2) deci'Accountability for reasonableness' is a framework that can be used to guide legitimate and fair priority setting in health care organizations, such as hospitals. It assumes that the time and effort required for meeting the conditions of fairness is justified for two reasons: First, it is important to act ethically and be perceived to be acting ethically – in this case, fairly. Second, acting ethically can help an organization achieve 'goodwill' benefits including, but not limited to, increased trust and satisfaction and decreased complaints. However, it is clear from this scope of decisions examined in this study that time constraints imposed on a health care organization by a highly communicable and potentially fatal infectious disease creates significant priority setting difficulties. It may appear that the conditions of 'accountability for reasonableness' are too demanding to implement in the time constraints – that perhaps containment should take precedence over procedural requirements. We disagree. During the SARS outbreak the hospital's leadership developed and implemented several sophisticated processes to help with their crisis management. Tailoring those processes to meet the four conditions of 'accountability for reasonableness' is not any more difficult or demanding. Moreover, we argue, and some of the participants also argued, that in the midst of a crisis where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.Our findings are limited in that they may not be generalizable to other hospitals. However, generalizability is not the goal of qualitative studies like this. We expect that other hospitals may benefit from the insights provided in this study. For example, this was the first time that 'accountability for reasonableness' has been used to evaluate priority setting in response to an infectious disease outbreak. Other hospitals in similar crises can use 'accountability for reasonableness' to help evaluate and enhance the fairness of their priority setting .The best assurance of fair priority setting in a crisis is fair priority setting everyday. A health care organization that incorporates legitimate and fair decision making everyday, where the decision making culture of the organization is permeated with the conditions of 'accountability for reasonableness', will be primed to meet the challenges of fair priority setting in a crisis. This may be the most important lesson to take from this study.SH and MB are employees of the organization studied here.JB was primarily responsible for acquisition and analysis of data. All authors made substantial contributions to conception and design of the study, data analysis and interpretation, and have been involved in drafting the article or revising it critically for important intellectual content. All authors have given final approval of the version to be published.The pre-publication history for this paper can be accessed here:


There are many different sex-determining systems in plants and animals with separate sexes (dioecious species). In some species, environmental factors activate sex-determining genes that trigger expression of genes leading to male or female development. Other species have evolved specialized sex chromosomes. In the well-known X-Y system of mammals, individuals inheriting a Y chromosome become males, and XX individuals become females.Sex chromosomes have arisen independently in many taxonomic groups. It is an interesting question whether the same mechanisms were involved each time. Similarities in sex chromosome evolution have been reported between birds and mammals . In a new study, Michael Nicolas and colleagues uncover striking parallels in the details of sex chromosome evolution between mammals and a far more distant group: plants.Silene, which includes the White Campion, includes both dioecious and hermaphrodite species. The authors focus on three dioecious species, Silene dioica, S. latifolia, and S. diclinis, which share an X-Y sex-determination system where Y specifies maleness.Sex chromosomes are an oddity in flowering plants. They are limited to dioecious species, a subset of plants that carry male and female organs  on separate individuals (most flowering plants are hermaphrodites). The genus The theory of sex chromosome evolution holds that sex chromosomes were once homologs  that evolved different morphology and gene content because they lost their ability to recombine. Suppression of recombination is thought to start around the sex-determining region, but may eventually affect much of the sex chromosomes. Recombination is a key genetic process in which two chromosomes pair and exchange their sequences. In the absence of recombination, the two chromosomes of a pair evolve separately.Silene species are morphologically distinct, like those of mammals, and they also have a PAR and a nonrecombining region. Nicolas and colleagues' results shed some light on how recombination suppression evolved on the Silene sex chromosomes.In the case of mammals, whose sex chromosomes evolved about 320 million years ago, loss of recombination led to widely diverged X and Y chromosomes that pair only over a very small region, the pseudoautosomal region . The X and Y chromosomes of dioecious Silene X chromosomes that are also present on their Y chromosomes. They mapped the genes relative to the PAR and compared the nucleotide sequences of the X and Y version of each gene in each species. As expected of sequences that no longer recombine, the X and Y versions of each gene have diverged. Strikingly, the extent of nucleotide divergence increases with the gene's distance from the PAR.The authors studied four genes outside the PAR on the Silene data is one of a progressive suppression of recombination, gradually diminishing the PAR. A similar scenario has been proposed in mammals and birds. However, the authors estimate that the Silene sex chromosomes started diverging only 10 million years ago. The Silene chromosomes might therefore offer a better chance to observe recombination suppression in its early stages, and perhaps to get at its mechanisms.Evolutionary biologists use sequence divergence as a clock: the longer two originally identical sequences have been isolated from one another, the more independent mutations they accumulate. The picture that emerges from the Silene Y chromosome genes. Y degeneration is well documented in mammals, in which most X-linked genes have no Y-linked counterparts. Understanding X-Y divergence in Silene species may thus shed light on the evolution of sex chromosomes in vertebrates as well.The authors also report evidence for some degeneration of the


The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets – greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics. The recent awareness of an epidemic of obesity coincides with, and may have contributed to a dramatic increase in the popularity of a variety of low carbohydrate diets. This rapid switch in dietary habits of a significant part of the population, and the virtual revolution in the food industry, is unusual in that it stands in direct opposition to long-standing recommendations of the majority of the nutritional and medical establishment e.g. ,2). Desp. Desp2])was found. In the absence of an identifiable methodological error, experimental data has to be accepted and numerous investigations, in fact, serve as precedents for Greene et al.'s findings .always be independent of macronutrient composition would violate the second law of thermodynamics.In our previous review of metabolic advantage  we showeBecause it is a colloquial phrase, it is important to understand exactly what it is meant by "a calorie is a calorie." The most common meaning is that is it impossible for two isocaloric diets to lead to different weight loss. Frequently, the concept is justified by reference to the "laws of thermodynamics", but an explicit connection has never been spelled out. More recently, Buchholz & Schoeller  appear ts of thermodynamics" it is important to be sure that one is including the second law. The first law is very different in character from the second law [dissipation law: it defines a quantity, the entropy, S, which we traditionally identify with disorder or high probability. The second law says that in any  irreversible process, the entropy must increase (ΔS > 0); balance is not expected. Entropy is, in fact, identifiable with irreversibility.The idea that "a calorie is a calorie" comes from a misunderstanding of the laws of thermodynamics. There are two laws of thermodynamics. (The zeroth law that establishes the concept of temperature and the third law that describes absolute zero are not relevant here). When speaking of "the lawcond law ,11,12. TIt is important to understand that it is the second law that drives chemical reactions. The first law is a bookkeeping law and tells us that the total energy attributed to work, heat and changes in chemical composition will be constant. It does not tell us whether such a reaction will occur, or if it does, what the relative distributions of the forms of energy will be. To predict the tendency of the reaction to occur, we must employ the second law that says the entropy must increase. In a chemical reaction, at constant temperature and pressure, the entropic and energetic effects are combined into the change in the Gibbs free energy, ΔG, whose sign predicts the direction of reaction, and whose magnitude indicates the maximum amount of work realizable from the reaction.in vivo values will differ from standard state values but they are continuous functions of the concentrations and there will be numerous conditions under which ΔG' is not zero. In other words, assuming that protein and carbohydrate are energetically equivalent leads to a contradiction.To understand the implications of "a calorie is a calorie," that energy yield could be path-independent and the same for all diets consider that it implies that carbohydrate and protein are equivalent fuels as shown in Figure is unrecoverable. The efficiency of a machine is dependent on how the machine works and, for a biochemical machine, the nature of the fuel and the processes enlisted by the organism. A simple example is the inefficiency of low-test gasoline in high compression gasoline engines. If a "calorie is a calorie" were true, nobody would pay extra for high test gasoline. . In weight loss diets, of course, inefficiency is desirable and is tied to hormonal levels and enzyme activitiesThe second law was developed in the context of the industrial revolution and the attempt to understand the efficiency of machines. The law describes the theoretical limits on the efficiency of engines and applies as well to living (irreversible) systems. The second law says that no machine is completely efficient. Some of the available energy is lost as heat and in the internal rearrangement of chemical compounds and other changes in entropy. In other words, although the first law holds even in irreversible processes – energy is still conserved – the second law says that something is lost, something possibility of metabolic advantage should not come as a surprise.In nutrition, one component of inefficiency is measured in thermogenesis (thermic effect of feeding), or the heat generated in processing food. There is a large literature on this subject and the general conclusion, as summarized in a recent review by Jéquier , is thatRecommendations for fighting obesity frequently call for small reductions in calories . In facttheoretically required in all cases is mistakenly based on equilibrium, reversible conditions that do not hold for living organisms and an insufficient appreciation of the second law. The second law of thermodynamics says that variation of efficiency for different metabolic pathways is to be expected. Thus, ironically the dictum that a "calorie is a calorie" violates the second law of thermodynamics, as a matter of principle.A review of simple thermodynamic principles shows that weight change on isocaloric diets is not expected to be independent of path (metabolism of macronutrients) and indeed such a general principle would be a violation of the second law. Homeostatic mechanisms are able to insure that, a good deal of the time, weight does not fluctuate much with changes in diet – this might be said to be the true "miraculous metabolic effect" – but it is subject to many exceptions. The idea that this is The analysis above might be said to be over-kill although it is important, intellectually, not to invoke the laws of thermodynamics inappropriately. There are also, however, practical consequences. The seriousness of the obesity epidemic suggests that we attack it with all the means at our disposal. Metabolic advantage with low carbohydrate diets is well established in the literature. It does not always occur but the important point is that it can occur. To ignore its possibilities and to not investigate the precise conditions under which it appears would be cutting ourselves off from potential benefit. The extent to which metabolic advantage will have significant impact in treating obesity is unknown and it is widely said in studies of low carbohydrate diets that "more work needs to be done." However, if the misconception is perpetuated that there is a violation of physical laws, that work will not be done, and if done, will go unpublished due to editorial resistance. Attacking the obesity epidemic will involve giving up many old ideas that have not been productive. "A calorie is a calorie" might be a good place to start.None declared.


This issue of CytoJournal contains an article on screening for anal intraepithelial neoplasia in high-risk male patients. This accompanying Editorial focuses on current understanding of this relatively new disease entity, with insights as to the potential role of screening cytopathology in the epidemiology, pathophysiology and clinical management of this HIV and HPV related anal lesion, which predominates in male patients living long-term with AIDS. Mention is made of techniques of obtaining samples, methods of preparation, and morphologic classification. Issues of anoscopic confirmation, as well as topical and surgical management are emphasized. The similarity of initial experiences in anal screening to problems encountered early in cervical cancer screening programs several decades ago, are highlighted. For corresponding research article please see Arian et al, 2005 The subject of anal screening cytology has entered the epidemiologic and cytopathologic literature as a topic of interest over the last decade, and is highlighted in this issue of CytoJournal in an article by Arain and colleagues. Until recently, anal cancer was not considered to be a neoplasm of major public health concern . It occuDuring the 1990s, in several European and North American cancer centers, an initially unaccountable increase in anal cancers was seen in younger people. It soon became apparent that HIV-positive homosexual males were affected in numbers greatly in excess of those expected. This was first noted in those urban areas in which large concentrations of homosexual men had been treated since the outbreak of the HIV epidemic. The term "males having sex with males" (MSM) was coined to cover these high-risk individuals. Preliminary information gleaned from screening programs in high HIV-positive incidence areas amongst MSM, showed detection rates of intraepithelial and early invasive neoplasia higher than any incidence ever recorded for cervical cancer screening. Further, HIV-negative homosexual MSMs, and HIV positive non-homosexual men (eg drug users) also exhibited an increased incidence of pre-malignant and invasive anal carcinomas. More recently, the syndrome of early onset anal cancer has been extended to include HIV-positive female patients, as well as females who are not HIV-positive, but who have genital HPV. All these groups show a higher incidence of abnormal anal cytopathology, though none quite as high as that found in HIV positive MSM. The unifying factor in most instances is ano-receptive intercourse, or extension of HPV infection from the genital tract to the anal mucosa, most obvious in the face of deficient immunity, or high viral load -6.Epidemiologic studies have indicated that a prolonged preclinical phase precedes the onset of anal cancer in these high-risk groups. Just as in the cervix, there is a transitional zone  in the anus. Rectal mucosa, with goblet cells, ends about one inch proximal to the external sphincter, giving way to a transitional epithelium, which in turn blends into a stratified squamous epithelium at the level of the anus.  Almost all anal cancers develop in the transitional zone, where atypical, dysplastic and in-situ lesions are identifiable histologically. The cytologic counterparts are those of atypical cells of uncertain significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL). Once this natural history had been demonstrated and confirmed, it seemed natural that exfoliative cytology could be investigated as an "anal Pap smear" ,8.As with the cervix, the technique of obtaining the anal sample is critical to the success of screening. Standard colonic preparation is not required, but the rectum should be emptied prior to obtaining the anal sample. Brushes, brooms and Dacron swabs have all been used, the type of spatula probably being less important than the skill of the operator. The instrument is inserted to a depth of one and a half inches beyond the external sphincter, and subsequently withdrawn in a firm downward spiral movement incorporating 10–12 rotations, to ensure the device has made contact with the full surface area of the transformation zone. Some have used direct smears onto glass slides with immediate wet fixation; most centers, however, employ immediate insertion of the scraping device into liquid fixative for thin layer preparation. This appears both to improve adequacy and preservation, and also to eliminate any fecal contamination; residual material in the vial can be used for HPV studies if required, or for the creation of a bank of teaching slides.There has been a relative dearth of literature on the cytomorphology of anal samples -11. ClasExperience over the last decade suggests that anal cancer may be as highly appropriate a target for screening as is the cervix, in selected populations. The neoplasm is frequently encountered in well-defined high-risk groups. It has a detectable pre-malignant phase, and is amenable to easy cytologic sampling. Cytodiagnosis is reasonably sensitive and highly specific, and histologic confirmation is relatively easily obtained by well-trained personnel. If there is a current area of deficiency in such programs, it may well be in the treatment of intraepithelial lesions, which, as yet, has not been adequately assessed in large numbers of patients. It is known that highly active anti-retroviral therapy (HAART) does not appear to alter the pathophysiology of anal lesions once initiated. A variety of topical agents such as podophyllotoxin and imiquimod have been tried, as has intralesional interferon; superficial ablative therapies including liquid nitrogen, electrocautery, laser and LEEP have been attempted with varying success rates. Circumferential surgical resection almost inevitably results in unacceptable loss of sphincter control and soiling, but anoscopy-directed limited excision may prove less morbid. The fact that so many options are available implies perhaps that no single modality is yet considered sufficiently effective, with minimal complication ,13. Thisineffective in these communities. The second feature dictating the institution of screening programs in developing countries relates to antiretroviral therapy. Anal intraepithelial neoplasia and cancer are not encountered early in the progression of HIV/AIDS. Rather, they are late complications of patients living long-term with AIDS, usually implying patients living long-term on HAART [An interesting consideration is whether or not anal cancer, and thereby anal cytopathology screening programs, would be of value in the developing world, particularly in Africa, India and China, where the bulk of the global incidence of HIV resides. This will depend on two very different factors. First is the nature of transmission. Unlike the situation in the developed world, AIDS in these regions is not essentially a disease of homosexual males; thus, without anal intercourse predominating, an upward trend in the incidence of anal cancer would seem unlikely. Anal screening programs would be unnecessary or cost-on HAART . Unless


Self-reported information has commonly been used to monitor mammography utilization across populations and time periods. However, longitudinal investigations regarding the prevalence and determinants of inconsistent responses over time and the impact of such responses on population screening estimates are lacking.Based on longitudinal panel data for a representative cohort of Canadian women aged 40+ years  assessed in the 1994–95 (baseline) and 1996–97 (follow-up) National Population Health Survey (NPHS), we examined the prevalence of inconsistent self-reports of mammography utilization. Logistic regression models were used to estimate the associations between women's baseline sociodemographic and health characteristics and 2 types of inconsistent responses: (i) baseline reports of ever use which were subsequently contradicted by follow-up reports of never use; and (ii) baseline reports of never use which were contradicted by follow-up reports of use prior to 1994–95.Among women who reported having a mammogram at baseline, 5.9% : 4.6–7.3%) reported at follow-up that they had never had one. Multivariate logistic regression analyses showed that women with such inconsistent responses were more often outside target age groups, from low income households and less likely to report hormone replacement therapy and Pap smear use. Among women reporting never use at baseline and ever use at follow-up, 17.4% (95%CI: 11.7–23.1%) reported their most recent mammogram as occurring prior to 1994–95 (baseline) and such responses were more common among women aged 70+ years and those in poorer health.Women with inconsistent responses of type (i), i.e., ever users at baseline but never users at follow-up, appeared to exhibit characteristics typical of never users of mammography screening. Although limited by sample size, our preliminary analyses suggest that type (ii) responses are more likely to be the result of recall bias due to competing morbidity and age. Inconsistent responses, if removed from the analyses, may be a greater source of loss to follow-up than deaths/institutionalization or item non-response. In the absence of organized screening, self-report is often the only means to monitor mammography utilization and to investigate trends in uptake at the population level . In CanaFew evaluations of the reliability of mammography self-report are reported in the literature. Excellent test-retest reliability for having ever had a mammogram was reported in interviews conducted 1 week, 6–30 days, or 6–8 months after an initial interview, while reliability within the past year varied from excellent to good ,23,24. IBased on data from the longitudinal panel of the National Population Health Survey (NPHS), the present study examines the prevalence and determinants of inconsistent self-reports of mammography utilization among Canadian women aged 40 years and older and quantifies the extent that inconsistent self-reports of mammography use contribute to biased estimates of mammography utilization and uptake. To our knowledge, this is one of the first studies of mammography utilization to provide specific longitudinal data on the determinants of inconsistent responses over time and the impact of such responses on population screening estimates.The National Population Health Survey (NPHS) is a survey of the Canadian household population. Initiated in 1994–95 and repeated biennially, it is a split panel survey, combining repeated cross-sectional components with the longitudinal follow-up of a panel of respondents. A representative sample of Canadian household residents aged 12 and older from all ten provinces was sampled using a multistage probability design with stratification and clustering at various stages. The overall response rate for the baseline 1994–95 survey was 89 percent with a 96 percent response rate for the selected panel respondent . On follThis study evaluated data from longitudinal panel respondents of the 1994–95 (baseline) and 1996–97 (follow-up) waves of the NPHS to examine inconsistencies in reported mammography utilization among women aged 40+ years at first contact. Questions about mammography use were administered to female respondents through a personal interview conducted in 1994–95 and repeated by telephone approximately two years later. In both survey years, women were asked the identical question: "Have you ever had a mammogram, that is, a breast x-ray?". Those with positive responses were further probed for the time and reason of their most recent mammogram. All women provided their own health-related information; no proxy responses were allowed.Analyses were restricted to women aged 40 and older (at baseline) who participated in the first two waves of the NPHS and consented to share their information with federal and provincial governments. Two types of inconsistent responses were assessed: (i) baseline reports of ever use which were contradicted by follow-up reports of never use; and (ii) baseline reports of never use which were contradicted by follow-up reports of use prior to 1994–95. Multivariate logistic regression techniques were used to evaluate the associations between women's baseline sociodemographic and health characteristics and type (i) inconsistent responses. Variables significant at p ≤ .05 in age-adjusted analyses were eligible for entry in the multivariate logistic models. Sample size constraints permitted only simple bivariate, rather than multivariate exploration of factors associated with reports reflecting inconsistent timing of most recent use at follow-up (type (ii) response). Estimates were weighted to reflect baseline population characteristics. To account for stratification and clustering in the NPHS sampling design, 95% confidence intervals for parameter estimates were calculated using exact standard errors generated through bootstrap re-sampling methods . All staweighted according to 1994/95 population characteristics whereas the frequency data represent actual numbers of women surveyed.Of the 3,535 women aged 40+ years who responded to the ever/never mammography question in both survey waves Figure . Among wTable Follow-up interviews were completed, on average, 1.98 years from the baseline survey (range 1.19–3.01 years). Of the 293 women who reported never use at baseline and ever use at follow-up, 17.4 percent (95%CI: 11.7–23.1) reported a time for their most recent mammogram at follow-up that was inconsistent with never use at baseline. Despite baseline reports that they had never had a mammogram, approximately half of these women reported having had a mammogram at least 5 years ago. Although limited by small numbers, determinants of such inconsistent responses were assessed with simple bivariate analyses. Inconsistencies in timing occurred more often in older women. Compared to women aged 50–69, those 70 and older were more likely to report (at follow-up) that their most recent mammogram had occurred prior to 1994–95, despite a report of never use at baseline . Women reporting fair or poor self-rated health were also more likely to report a time for their most recent mammogram at follow-up that was inconsistent with never use at baseline .Depending on how inconsistent responses are handled, different measures of use and uptake of mammography may be obtained. The lack of a gold standard such as a medical chart for validation makes the choice of a corrective measure unclear. If inconsistent ever/never responses are included in the analysis unchanged, 67.3 percent (95% CI: 65.1–69.5%) of women would be classified as ever having had a mammogram in 1994–95 while 71.7 percent (95% CI: 69.6–73.7%) would be classified as ever users in 1996–97. Conversely, if it is assumed that inconsistent ever/never responses represent false-positive responses at baseline (an assumption supported by our study findings), the 1994–95 prevalence estimate becomes 63.3 percent (95% CI: 61.0–65.6%), demonstrating an absolute increase in mammography use of 8.4 percent (95% CI: 7.1–9.6%) by this cohort of women by 1996–97.Although a limited number of studies have assessed the reliability of mammography self-report -25, detaAlthough direct comparison with our sample was not possible due to the expectation that behavior might have changed in a 2-year time span, earlier findings from longitudinal studies of fairly affluent  and low-Our analyses of factors associated with inconsistent ever/never responses indicate that women reporting ever having had a mammogram at baseline but never use at follow-up exhibited many of the sociodemographic and health behaviour characteristics  commonly observed among non-participants in mammography screening in previous studies -38. SuchValidation studies also provide support for our assumption that inconsistent ever/never responses  are most likely to be explained by false-positive responses at baseline. Women are more likely to falsely claim having had a mammogram, than not having one ,17,39,40Among women who reported never use at baseline and ever use at follow-up, approximately 17.4 percent reported a time for their most recent mammogram (at follow-up) that was inconsistent with never use at baseline. If respondents truly initiated mammography use subsequent to the baseline interview, they overestimated the time elapsed since their mammogram. Such a finding is relatively inconsistent with previous studies that have generally found that women tend to underestimate the time since their last mammogram -13,15,17Unfortunately, no gold standard was available to assess the validity of the responses women generated. Thus, the proportion of consistent responses that may actually represent invalid responses is unclear. Nor was it possible to distinguish errors in recall of timing from false reports of mammography utilization. Further, the reasons for providing inconsistent responses can only be inferred. The possibility of data entry errors is remote. Although data entry checks for consistency between survey cycles were not included among the comprehensive quality control strategies implemented by Statistics Canada, computer assisted interviewing was used by highly trained interviewers. Also, data entry errors would be expected to occur randomly and not disproportionately among women outside of the target age range or with relatively lower socioeconomic status, as observed in the present study. However, several plausible explanations for the inconsistencies exist, including survey methodology changes and deliberate or inadvertent provision of inaccurate responses by the respondent.We cannot exclude the possibility that interview changes  prompted women who reported ever use in 1994/95 to alter their response in 1996–97. The NPHS used an initial personal interview to foster a good long-term relationship with the panel representative, but the cost and logistics of traveling to different regions was prohibitive. Therefore, unless the respondent objected or had no phone, future interviews (including the 1996–97 cycle) were conducted by telephone . The neeCognitive research has implicated comprehension as a barrier to providing valid, reliable survey responses. Several researchers employ the lead-in question 'Have you ever heard of a mammogram, that is a breast x-ray?' to identify comprehension difficulties ,16,21,42There are several possible explanations for the higher rate of inconsistent responses observed in the present study. The focus of the NPHS questionnaire was not limited to preventive practices nor was it designed for reliability testing. The length and comprehensiveness of the NPHS may have contributed to greater respondent fatigue. Also, the longer time interval between surveys, relative to that observed in other studies, may have contributed to instability in responses. A more favourable level of concordance among responses may be obtained by studies that apply eligibility criteria that ensure more accurate responses  ,10,15. FThe inconsistent data reported here, if removed from longitudinal analyses, could yield losses to follow-up equivalent to or greater than other sources of attrition  over the planned 20 year course of the NPHS. The 1998–99 NPHS included probing questions to reduce inconsistencies and it should alleviate many of the problems evident here . HoweverIn summary, inconsistent responses represent a challenge to longitudinal, population-based evaluations of breast screening practices. Losses from inconsistent data regarding mammography participation are not negligible and may contribute to inaccurate estimates of mammography uptake. Women reporting inconsistent ever/never use in the present study displayed characteristics typical of never users, favoring treatment of women's baseline responses as false-positive. Inconsistent responses regarding the timing of recent mammography practices, however, may be primarily related to the impact of age and competing morbidity on recall.The authors declare that they have no competing interests.CB and CM contributed to the initial and revised analyses of the NPHS panel data, the interpretation of the results and the initial drafting/editing of the manuscript. CB and JS were responsible for the data linkage with Statistics Canada (for the NPHS Share File) and for the revised bootstrap analyses. JS also contributed to the interpretation of the results and editing of the manuscript.The pre-publication history for this paper can be accessed here:


West African Journal of Medicine [In this perspective, Andrew Browning of the Fistula Hospital in Addis Ababa discusses a study on obstetric fistula in Ilorin, Nigeria. The study was originally published in the Medicine . With th Obstetric fistula causes women enormous distress and social isolation in developing countries like Nigeria. What do we know about the condition? The obstetric urogenital fistula has caused women misery ever since they first started delivering children. It was once common worldwide, but with the advent of safe obstetric care during the early part of the last century, the condition has become rare in rich countries. Urogenital fistulae do still occur in developed countries, but unlike in the developing world, they are usually a complication of a difficult pelvic surgery, cancer, or radiation .Obstetric fistula—a urogenital fistula from obstructed labour—is now only encountered in countries where health resources are scarce. The shame associated with incontinence drives affected women further into a life of poverty and begging. Many women with fistula either do not know that they can get medical help, or if they do, they are unable to pay.Furthermore, very little scientific research has been published about obstetric fistula and its management, partly because the people treating patients with this condition are working in remote areas, often with very limited resources for research. What has been written consists largely of personal case series and a few epidemiological studies .To date there has been only one randomised trial in the developing world, involving 79 women operated on by a single surgeon in Benin, which found that intra-operative intravenous antibiotics did not reduce the risk of failed surgical repair or of objective incontinence . There hWhat we do know about the obstetric urogenital fistula is that the women who have these injuries are young, usually illiterate, and of a lower socioeconomic background. They are more often primiparous and short in stature, and they have an average length of labour of some 3.9 days. The labour is usually unattended, or if attended, it is by someone unskilled. The women inevitably deliver a stillborn child. About half of the women with fistula are divorced as a direct result of their incontinence ,5,6,7.The initial injury that leads to a fistula results from ischaemic necrosis of the soft tissues of the pelvis due to an impacted presenting part during the long labour.The ischaemia then affects the bladder and vagina (and sometimes the rectum and vagina), resulting in a fistula. The process also affects other pelvic structures. These include the nerves of the sacral plexus, resulting in foot drop and hamstring compartment weakness . Bony abnormalities are common, separating or obliterating the symphysis pubis.Up to half of patients develop upper renal tract abnormalities: scarring of the ureter can cause obstructive uropathies . Up to tThe continual leakage of urine over the perineal skin can cause local and painful irritation, termed ‘urine dermatitis’. Bladder stones can occur, as women affected by fistula often drink less to try and pass less urine and the concentrated urine can form calculi. The obstetric injury has been termed a ‘field injury’, as the pathology is broad rather than isolated . The resA recently published retrospective case note review provides new data on obstetric urogenital fistula in northern Nigeria. Ijaiya and Aboyeji reviewed 34 cases of fistula managed at the University of Ilorin Teaching Hospital over a two-year period . During ‘[Obstetric fistula] usually occurs when a young, poor woman has an obstructed labour and cannot get a Caesarean section when needed. The obstruction can occur because the woman's pelvis is too small, the baby's head is too big, or the baby is badly positioned. The woman can be in labour for five days or more without medical help. The baby usually dies. If the mother survives, she is left with extensive tissue damage to her birth canal that renders her incontinent.’www.unfpa.org/fistula/about.htm).Source: UNFPA Campaign to End Fistula: “What is Fistula?”  and the International Federation of Gynecology and Obstetrics (www.figo.com) are endeavouring to help. UNFPA has already sponsored training workshops on fistula surgery for surgeons and fledgling fistula units in Bangladesh and some parts of Africa.Resource-rich countries were able to eradicate the obstetric fistula almost 100 years ago, but the challenge to resource-poor countries is enormous. There are an estimated 2 million women with fistula in the world, with anywhere between 100,000 and 500,000 new cases developing each year . At the The obstetric fistula is an entirely preventable condition. Several strategies have been proposed to eradicate this condition in developing countries , just as‘Postpone marriage and pregnancy for young girls‘Increase access to education and family planning services for women and men‘Provide access to adequate medical care for all pregnant women and emergency obstetric care for all who develop complications‘Repair physical damage through medical intervention and emotional damage through counselling' www.unfpa.org/fistula/facts.htm).Source: UNFPA Campaign to End Fistula: “Fast Facts” (Even if such centres are established, women will need to be convinced of the importance of seeking help without delay for a difficult labour. And then, to be able to receive that help, roads need to be built, transport systems need to be put in place, and communications need to be improved. The obstacles are clearly huge, and with currently very little money and very few professionals available, women with obstetric fistula will sadly be with us for many more years to come.Text S1Full Text of Ijaiya and Aboyeji's Study  (234 KB Click here for additional data file.