Pressure ulcers are a common and serious health care problem in all health care settings. Results from annual national pressure ulcer prevalence surveys in the Netherlands and Germany reveal large differences in prevalence rates between both countries over the past ten years, especially in nursing homes. When examining differences in prevalence and incidence rates, it is important to take into account all factors associated with the development of pressure ulcers. Numerous studies have identified patient related factors, as well as nursing related interventions as risk factors for the development of pressure ulcers. Next to these more process oriented factors, also structural factors such as staffing levels and staff quality play a role in the development of pressure ulcers. This study has been designed to investigate the incidence of pressure ulcers in nursing homes in the Netherlands and Germany and to identify patient related factors, nursing related factors and structural factors associated with pressure ulcer development. The present article describes the protocol for this study.A prospective multicenter study is designed in which a cohort of newly admitted nursing home residents in 10 Dutch and 11 German nursing homes will be followed for a period of 12 weeks. Data will be collected by research assistants using questionnaires on four different levels: resident, staff, ward, and nursing home.The results of the study will provide information on the incidence of pressure ulcers in Dutch and German nursing homes. Furthermore, information will be gathered on the influence of patient related factors, nursing related factors and structural factors on the incidence of pressure ulcers. The present article describes the study design and addresses the study's strengths and weaknesses. Pressure ulcers are a common and serious health care problem in all health care settings -4. A preResults from annual national pressure ulcer prevalence surveys in the Netherlands and Germany, which use the same standardized definitions, instruments and methodology ,8, have When examining differences in prevalence and incidence rates, it is important to take into account all factors associated with the development of pressure ulcers. Various studies have identified a number of patient related factors as risk factors for the development of pressure ulcers. These patient related factors include age ; limitedThis study has been designed to investigate whether the incidence of pressure ulcers differs between nursing homes in the Netherlands and Germany and, if so, to identify which patient related factors, nursing related factors and structural factors are associated with pressure ulcer development. A detailed description of the methodology of this study is given in this paper.This study has been set up as a prospective multicenter cohort study and will be carried out in 10 nursing homes in the Netherlands and 11 nursing homes in Germany. All newly admitted residents in these nursing homes who fulfill the inclusion criteria will be included for participation. In total, 600 residents (300 in each country) will be recruited. Residents who give their informed consent are followed for a period of 12 weeks. This period of 12 weeks was chosen because the national prevalence measurement of care problems in the Netherlands in 2007 showed that 18.3% of nursing home residents developed a pressure ulcer within 12 weeks after admission .The participating nursing homes in the Netherlands were selected through the 2008 national prevalence measurement of care problems database . This daOnly newly admitted nursing home residents are included in this study. Residents are not excluded if they have a pressure ulcer, but are excluded from participation if they have an expected nursing home stay of less than 3 months, if they have been diagnosed with a terminal illness or if their informed consent is received later than three weeks after their admission to the nursing home. All newly admitted residents (and relatives for psycho geriatric residents) who meet the inclusion criteria receive an information package and an informed consent letter during their interview on admission to the nursing home.Data will be collected using questionnaires on four different levels: resident, ward, nursing home and staff level. For the resident, ward and nursing home levels, most questions are adapted from the Dutch LPZ questionnaires . These qOn the resident level, a number of different questionnaires and instruments are used. An overview of the different instruments and time points can be seen in Table The resident questionnaire contains questions about demographic data , diseases, reason for nursing home admission, medication use, care dependency, mental status, existence of pressure ulcer(s) (yes/no), repositioning, mobilization, skin care and skin inspection, use of mattresses and cushions, nutrition and prevention of malnutrition, and incontinence care.Answers are obtained by speaking to the residents directly or, if not possible, by consulting a responsible nurse or nursing assistant and/or the resident documentation. Information about the existence of pressure ulcers is collected by physical examinations conducted by research assistants. The resident questionnaire is filled in weekly for each resident for a period of 12 weeks.The pressure ulcer questionnaire contains questions (per pressure ulcer) about the location and the duration of the pressure ulcer and the setting where the pressure ulcer developed . For pressure ulcer grading, the grading system of the European Pressure Ulcer Advisory Panel is used . The len2 with a scoring range from 0 to 10, the amount of exudate and the tissue type. The total score ranges from 0 to 17 and helps to indicate improvement or deterioration in pressure ulcer healing [The PUSH tool was developed by the National Pressure Ulcer Advisory Panel as a quick, reliable tool to monitor the change in pressure ulcer status over time. The tool has been validated by several studies and includes the length and width of the wound in cm healing . The preThe Braden scale is a scale used for determining the risk of pressure ulcer development in patients. The scale, developed in 1984, is one of the most used pressure ulcer risk scales and has a proved validity and reliability ,33. The The Care Dependency Scale (CDS) provides a framework for the care dependency status of institutionalized elderly people. It was developed in the Netherlands and has proven validity and reliability ,37. The The Mini Nutritional Assessment (MNA) is a validated and reliable instrument, with a high sensitivity and specificity, used to identify elderly residents who are malnourished or who are at risk for malnutrition ,41. The The staff questionnaire was developed to measure the knowledge and practice among nurses and nursing assistants regarding pressure ulcer preventive measures . The queIn the second part of the questionnaire, the respondents are asked to judge all 29 preventive measures whether they would apply these for patients who are at risk for developing a pressure ulcer. The answering categories for each preventive measure are 'always', 'sometimes' and 'never'. In the third part of the questionnaire, the respondents are asked to judge the usefulness of the preventive measures for patients who are at risk for developing a pressure ulcer. Answering categories for each measure are 'useful', 'sometimes useful', 'not useful' or 'do not know'.The ward questionnaire contains questions about the type of ward, the number of residents and rooms on the ward, ward specialization, staffing, presence of pressure ulcer guidelines and whether there is a tissue viability nurse working at the nursing home.The nursing home questionnaire includes questions about the number of residents in the nursing home, type of specialization and certification of the nursing home, staffing , refresher courses in pressure ulcer care , quality control  and presence of pressure ulcer guidelines.Research assistants are responsible for collecting the data among the nursing home residents. In total, three research assistants are responsible for the data collection in the Netherlands and eleven in Germany. All research assistants are nurses or physiotherapists and are educated in the area of pressure ulcer care. All have been trained and instructed to collect the data for this study.The ward questionnaires are to be filled in by the head of the department. The nursing home questionnaires are to be filled in by the nursing home manager. Both questionnaires are to be completed within a month after the start of the study. Both the ward and nursing home questionnaires are sent back to the principal researchers in both countries by means of stamped addressed envelopes. The staff questionnaires are to be completed by nurses and nursing assistants on the participating wards within the first two months of the study. These questionnaires are collected by the research assistants.A sample size calculation was performed to determine the number of people who develop a pressure ulcer. To detect a 5% difference in pressure ulcer incidence between both countries , with a 15% estimated drop-out rate, 562 residents (280 in each country) need to be recruited.Data will be checked for outliers and normality. The analysis includes descriptive frequency distributions for all variables. The level of statistical significance is set at alpha 0.01 (two-tailed). The dependent variable is the development of a pressure ulcer during the 12-week study period for each resident. Bivariate analyses, using cross-tabulations and chi-square tests for nominal data and two sample Wilcoxon tests for continuous data, will be performed to compare each suggested predictor with the dependent variable.The study will use multilevel models in which 12 repeated measures (the level 1 units) are nested within residents (level 2 units). Multilevel models can accommodate data that are unbalanced due to attrition or missing values. Multivariate logistic regression analyses are used to determine the association between resident, treatment, and facility characteristics and the outcome. All statistical analyses will be performed using Predictive Analytics SoftWare (PASW) version 17 from SPSS.The medical ethical committees of the Maastricht University Medical Hospital and the Charité - Universitätsmedizin Berlin have granted full ethical approval for this study. The privacy of the participating residents is protected, and all data is coded and processed anonymously.The nursing homes for this study have already been selected. In the Netherlands, 119 nursing homes met the inclusion criteria. In the first stage, eight of the ten selected nursing homes and, in the second stage, two of the four selected nursing homes were willing to take part in the study. In Germany, 288 nursing homes met the inclusion criteria. In the first stage, six of the ten selected nursing homes were willing to take part in the study; in the second stage one, in the third stage two and in the fourth stage two of the eight selected nursing homes were willing to take part in the study. Resident recruitment began in June 2009 (GER) and August 2009 (NL). The study will be completed in September 2011.This study has been designed to identify whether there are differences in pressure ulcer incidence rates between nursing homes in the Netherlands and Germany. Additionally, the study will reveal whether these differences can be explained by factors related to patients, nursing care or nursing home structure. To date, many studies concerning pressure ulcer care have a cross-sectional or retrospective design; these designs make it difficult to investigate which factors influence the onset of pressure ulcers because they cannot provide insight into causal relationships. The prospective and longitudinal design of this study will allow us to investigate these factors. Moreover, the longitudinal and prospective design is less vulnerable to measurement error, which is a risk in cross-sectional or retrospective studies ,46.To the present authors' knowledge, this study is the first to assess patient related, nursing related and structure related factors in one study. Most previous studies on pressure ulcer care have focused on only one of these factors. The present study makes it possible to gain better insight into all factors related to patients, nursing care and structure that may influence pressure ulcer prevalence and incidence rates, and their interactions. Moreover, many studies on pressure ulcer care obtain data about the existence of pressure ulcers by means of nursing documentation, or analyze data gathered by staff working in the health care institutions. In the present study, all information about the existence of pressure ulcers will be gathered by means of concrete physical examinations carried out by external research assistants to ensure the reliability of the data. Furthermore, the intended sample size and the involvement of multiple nursing homes will improve the reliability of the results.The internal validity of the study results may be limited due to the exclusion criteria. For example, residents who have an expected nursing home stay of less than 12 weeks will not be included. Additionally, it is possible that participating residents have other clinical characteristics than non-participating residents. For example, non-participating residents may have worse physical conditions than participating residents. Nevertheless, the risk for selection bias will be reduced by the participation of multiple nursing homes in both countries. Although nursing homes were selected from specific regions in both countries, the nursing homes are representative for their country as they differ in size, foundation and specialization. Finally, the drop-out rate of residents during the study due to death, admittance to the hospital or transfer to another nursing home may influence the study results. Drop-outs will be documented thoroughly and included in the data analysis to the point of drop-out.The authors declare that they have no competing interests.EM is responsible for the study design, drafting of the manuscript and critical revision of the manuscript; RJGH is responsible for the study design, critical revision of the manuscript and study supervision, and obtained funding for the study; CH is responsible for the study design, critical revision of the manuscript and study supervision in Germany; CL is responsible for the study design and critical revision of the manuscript; JMGAS is responsible for the study design, critical revision of the manuscript and study supervision. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6955/10/8/prepub


There is much evidence demonstrating that psychosocial interventions in caregivers and oncological staff produce an improvement in their patients' quality of life. The aim of this explorative study was to evaluate the effect of a new approach in promoting more functional ways to face stressful situations in the constellation of people around patients: caregivers, physicians and nurses. Thirty-four subjects were divided into three groups: 10 caregivers, 11 physicians, and 13 nurses. A “Balint Group” method modified according to a mindfulness technique was used as the intervention. Three assessment tools were administered to the participants at baseline, during, and after completion of the study: the Response Evaluation Measure (REM-71), the Satisfaction Profile (SAT-P), and the Group Climate Questionnaire (GCQ). Mean values of defense mechanisms determined by the REM-71 were compared with those of the standard population. At baseline, we observed a prevalence of immature defenses in the three groups, with mean values above those in the standard population. After the psychological intervention, a tendency to normalization of the mean values was observed, indicating the development of more adaptive ways of using defense mechanisms and the effectiveness of the intervention. Group climate, assessed through the GCQ, showed an increase in the “Engagement” factor and a decline in the “Conflict” factor in all groups. This study suggests that group treatment focused on changing personal responses to stressful situations can induce more adaptive strategies enabling caregivers, hematologists, and nurses to help patients better and thereby improve their quality of life. There is growing consensus that psychosocial support should be integrated into the routine care of patients with cancer Patients tend to focus on their illness and their body. However, their emotional burden often causes the adoption of strong dysfunctional defense mechanisms that can bring them to deny the idea of being ill and consequently to refuse or not seek the help of medical staff Patients and caregivers are not, however, the only protagonists of the battle against cancer. Oncologists and nurses deal with existential questions of life and death daily, which are always difficult issues to face and manage. It has been demonstrated that medical oncologists are more prone to experience symptoms of depression than other internal medicine physicians and this phenomenon can be observed even during their training Given the prevalence of distress among oncologists and its implications for patients and their care, it could be important to make physicians undergo periodic screening or monitoring for burnout particularly because they often do not look for help. There is now considerable evidence that any intervention in oncological staff and caregivers increases their capacity to bear emotional burdens and consequently improves the patients' quality of life Starting from these observations, we decided to focus on the “constellation” of people  around patients affected by multiple myeloma and designed a pilot study. The project, conducted in the three groups, was focused on the identification of personal responses to stressful situations (defense mechanisms) evaluated through several assessment tools administered to the participants at baseline and after completion of the psychological intervention. The identification of defense mechanisms against illness is of the utmost importance: on the one hand, these mechanisms represent a way of coping with anxiety triggered by threat, on the other hand, they allow people to establish new ways of relating with the world and with themselves. The aim of this explorative study was to evaluate the effect of a group intervention in improving caregivers' knowledge and quality of life, and in promoting among physicians and nurses a different way of facing the difficulties of their job.An explorative study was carried out between caregivers, physicians and nurses of Policlinico San Matteo of Pavia, Italy. Hematologists and nurses participated voluntarily; the caregivers invited to participate were sampled stratifying for phases of disease . The number of participants from each group who dropped out during the study was recorded (early and late dropouts). The study was approved by the Ethics Committee of Policlinico San Matteo of Pavia, and all participants signed a written informed consent.The research was divided into three phases: the preintervention phase (T0), the intervention period, and the follow-up (T1).In the preintervention phase, individual interviews, of 50 min each, were conducted by a clinical psychologist to introduce the topic and the objective of the research, to administer the questionnaires response evaluation measure (REM-71), Satisfaction profile (SAT-P), and to investigate the present level of personal satisfaction and stress. The questionnaires, anonymous and self-compiled, were the same for all participants.In the second phase of the study, the intervention period, each group  was planned to have 30 sessions, each of 60 min, using a “Balint Group” method In the final phase (T1), at the end of all sessions (after 1 year), the same procedure as in the preintervention phase was used.The research was focused on the identification of personal responses to stressful situations and then on the development of more adaptive ways of managing these situations. The assessment tools  were not specific for the populations in the study.immature defenses) and Factor 2 (mature defenses) The REM-71 The SAT-P The GCQ Data were described as means and standard deviations (SD), if continuous, and as counts and percentages, if categorical. Within-subject comparisons of scores were performed by means of a general linear regression model for repeated measures, with calculation of robust standard errors to account for within-subject correlation. Mean changes and 95% confidence intervals (95% CI) were computed. The association between GCQ scores and number of sessions was assessed with Spearman's rho coefficient. For this analysis, data were anonymous and were pooled across groups.P-value <0.05 was considered statistically significant.Stata 12 Thirty-four subjects were enrolled in the study . Four participants  dropped out the study, three within the first 3 months (early dropout) and one after 3 months (late dropout). The three early dropouts, one caregiver, one physician, and one nurse, stopped participating for employment reasons; the other caregiver (the late dropout) withdrew from the study because of the worsening clinical condition and unbearable increased care of the relative.At baseline, the frequency of immature defenses was higher than that of mature ones. As shown in The comparison of the mean values of defense mechanisms in caregivers at baseline with those of the standard population  showed hThe follow-up analysis performed after the intervention showed a general tendency to normalization with a significant increase in mature defense mechanisms  and a decrease in many immature defense mechanisms, in particular, those that had been found to be significantly higher with respect to the standard population . We also observed an increase in one immature defense: suppression. Changes between before and after the group intervention and the 95% CI are illustrated in At baseline, SAT-P results were all within the range of the standard population. This finding conflicted with the information that emerged from the individual interviews which revealed remarkable difficulties in managing everyday life. After the intervention, all scores for quality of life perception increased by 10%–20%, although this improvement just fell short of being statistically significant .As regards the GCQ (assessed at each session), the number of followed sessions showed a direct correlation with the “Engagement” factor and an inverse correlation with the “Conflict” factor .The baseline, preintervention data revealed a predominance of immature strategies Fig. B: fantasThe comparison with the standard population  showed tThe analysis after the intervention highlighted a significant increase in mature defenses , and a decline of many immature defenses, in particular, those identified as being significantly more frequent with respect to the standard population: fantasy, conversion, and projection. There was clear evidence of a general tendency to normalization for all defenses. Changes between before and after the group intervention and the 95% CI are illustrated in The preintervention evaluation of perceived quality of life showed the same discrepancy as in the group of caregivers between what was picked up by the SAT-P results, which were all in the standard population average, and what emerged from the interviews. In this group, the change from baseline was very close to zero, and far from being statistically significant .Climate group evaluation showed a direct correlation between the number of followed sessions and the “Engagement” factor, and an inverse correlation between the number of followed sessions and “Conflict” and “Avoidance” factors . HoweverA high frequency of immature defenses was observed also in this group Fig. B: fantasIn line with the results of the other groups (caregivers and hematologists), at follow-up, mature defenses  increased significantly, while immature defenses tended to decrease. Only one immature defense increased: suppression. Changes between before and after the intervention and their 95% CI are reported in Before the intervention, the SAT-P results were all similar to those in the standard population. As for the hematologists, there were virtually no changes in the SAT-P score in nurses after the intervention . Once agAs for the hematologists, the number of followed sessions showed a direct correlation with the “Engagement” factor and inverse correlations with “Conflict” and “Avoidance” factors, but these relationships were not statistically significant .The emotional burden of caregivers has usually been characterized in previous studies as creating anxiety and depression with a low quality of life . For nurses and physicians who deal with oncological diseases, most studies have focused on burnout and its personal  and professional  consequences. In both cases, well-being and personal growth were measured in terms of specific symptoms and consequently any therapeutic approaches were addressed at eliminating these symptoms.In contrast, the new approach adopted in this explorative study arose from the belief that a reintegration of personal satisfaction cannot be obtained only from reducing symptoms or improving quality of life, but requires the development of more functional and mature ways of facing reality and its stressful situations, such as severe illness.The analysis performed at baseline, prior to the intervention, showed a high frequency of immature defenses in all three groups: this implies less functional and adaptive ways of facing everyday situations and a low acceptance of reality. This was confirmed by the comparison of our sample with the standard population; all three groups showed, as a common finding, three immature defenses: fantasy, conversion, and projection. The use of these mechanisms of defense is consistent with evoking a death fantasy as a consequence of a confrontation with a severe illness. Conversion is a defensive response to death and contamination anxiety evoked by illness. It could be considered as an unconscious identification with the sick role, reproducing somatic symptoms observed in patients to reduce stress. Projection is a way of transferring unacceptable feelings, such as anger, to other people, that is turning the inner danger into an outer one. For example, the hospital environment could be perceived as constantly hostile and dangerous. Fantasy is a way of coping with problems and situations that evoke great impotence through an excessive use of daydreaming as a substitute for human relationships, more direct and effective action, or problem solving. The frequent use of fantasy as a defense in this context could also embellish the interpretation of somatic symptoms, leading to the idea of being affected by a serious illness. Contrariwise, the use of repression as a defense mechanism, which was more common in caregivers than in the standard population, could lead to an inability to remember diseases, shifting attention to specific symptoms of illness or to drug-related side effects. after the intervention. Altruism increased among physicians and nurses especially in solidarity and cooperation with the colleagues. By contrast, altruism remained stable in caregivers, due to its high value at baseline. An increase in mature defenses implies a greater ability to accept and mitigate the unpleasant aspects of reality, with consequent better self-management.The effect of the psychological intervention was evident in all groups. We observed a decrease of immature defenses, including those that were more present in our study groups at baseline than in the standard population and an increase in mature defenses This trend to normalization in the use of defense mechanisms, in common to all the groups, is a clear indication of the effect of the intervention. Of note, in caregivers and nurses, suppression, which was within the normal range for standard adults at baseline, increased after the intervention. This could be due to the short duration of the intervention and so it might indicate a transitional stage, as already well described in psychotherapy literature. This phenomenon is explained by the fact that defense mechanisms are structures that change slowly, requiring time to develop and become stabilized During the intervention, cohesion increased in all three groups and the avoidance of personal responsibility of work group decreased. Cohesion is comparable to therapeutic alliance in individual psychotherapy Quality of life perception did not change significantly after the invention, except for a relevant, but not statistically significant, increase in scores in the caregiver's cohort only. This could be due to the caregivers' greater attendance at sessions, which implied reinforcement of the group treatment, in line with the GCQ results.In conclusion, this study suggests that a work group, promoting sharing and collaboration, leads to the induction of mature defenses enabling reality to be faced in a more adaptive and effective way. As defense mechanisms are unconscious functions, once established, people keep on using them in their everyday life. The development of more adaptive strategies can help caregivers to accept their new stressful condition, and consequently provide better assistance for the people they are caring for, and can help hematologists and nurses foster better ways to face frustration and impotence, in order to prevent burnout and facilitate their relationships with patients. Therefore, results of this study offer a useful starting point for the planning and the development of future studies with the aim to evaluate the efficacy of the “Balint Group” modified method on caregivers' quality of life and on the ability of physicians and nurses to deal with stressful situations.None declared.


Non-adherence to prescribed medication is a pervasive problem that can incur serious effects on patients’ health outcomes and well-being, and the availability of resources in healthcare systems. This study aimed to develop practical consensus-based policy solutions to address medicines non-adherence for Europe.A four-round Delphi study was conducted. The Delphi Expert Panel comprised 50 participants from 14 countries and was representative of: patient/carers organisations; healthcare providers and professionals; commissioners and policy makers; academics; and industry representatives. Participants engaged in the study remotely, anonymously and electronically. Participants were invited to respond to open questions about the causes, consequences and solutions to medicines non-adherence. Subsequent rounds refined responses, and sought ratings of the relative importance, and operational and political feasibility of each potential solution to medicines non-adherence. Feedback of individual and group responses was provided to participants after each round. Members of the Delphi Expert Panel and members of the research group participated in a consensus meeting upon completion of the Delphi study to discuss and further refine the proposed policy solutions.43 separate policy solutions to medication non-adherence were agreed by the Panel. 25 policy solutions were prioritised based on composite scores for importance, and operational and political feasibility. Prioritised policy solutions focused on interventions for patients, training for healthcare professionals, and actions to support partnership between patients and healthcare professionals. Few solutions concerned actions by governments, healthcare commissioners, or interventions at the system level.Consensus about practical actions necessary to address non-adherence to medicines has been developed for Europe. These actions are also applicable to other regions. Prioritised policy solutions for medicines non-adherence offer a benefit to policymakers and healthcare providers seeking to address this multifaceted, complex problem. Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments”.Many patients do not take prescribed medication as advised : the WorHowever, this is not simply a matter of patients choosing not to take medicines as prescribed  or experiencing difficulty with taking medicines , since there are recognised to be a wide variety of factors that shape the landscape within which patients take medicines -8. TheseOne approach that is recognised to be of value in dealing with complex issues like this, where there are known to be numerous highly complex and inter-related factors involved and where uncertainties inevitably remain, is to harness expert opinion through consensus building -13. The The Delphi study proceeded over a series of four rounds held between January and June 2011. All rounds were completed online using Survey Monkey software and participants received feedback electronically via blind carbon copied emails. A consensus meeting with ABC project partners and members of the Delphi Panel took place at the end of the study to further develop the policy solutions. Conduct of the study was compliant with the Helsinki Declaration and the study received ethical approval from Keele University Ethical Review Panel.Purposive sampling ensured that potential participants had expertise relevant to one or more of the five dimensions of adherence in the World Health Organisation model . Panel mThree open-ended questions were presented to the Panel: What do you think the reasons are why people do not take their medicines as prescribed?; What do you think the consequences are of medicines non-adherence?; What do you think the solutions are to medicines non-adherence? Participants were asked to write as much or as little as they wished in response to each question.For each of the three questions posed to the Panel in Round 1, the researchers independently segmented each panellist’s responses into a series of discrete statements. Statements were then coded and assigned to emerging categories in a series of refinements of the categorisation. Statements that were identical or very similar in essence were collapsed to form a single statement. Validation of the categorisation process involved discussing the features of each category to ensure distinctiveness, establishing agreement that category names reflected the statements that they subsumed, and scrutinising statements that were not initially placed in a category for congruence with existing categories. Some statements were not categorised including general introductory text around the subject, humorous remarks, and direct repetition of an earlier statement within the participant’s response. The researchers remained blind to the authorship of statements throughout.All panellists received feedback on the Panel’s responses to the three questions from Round 1 and instructions for the next round. Round 2 focused on the Panel’s proposed solutions to non-adherence from the first round by inviting participants to agree, reject, or amend each proposed solution and offer new solutions that had not been advanced in Round 1.a priori criterion for refining the solutions specified that those rejected by more than 50 per cent of the Panel should not be taken forward to Round 3. Where amendments were proposed, data from Round 1 were revisited to seek examples, clarification, or support for suggested modifications that could be made without changing the core meaning of statements.An Participants received feedback about the Panel’s collective responses to Round 2 and were asked to rate the importance, and operational and political feasibility of each solution. Ratings were made on five-point Likert-type scales, as shown in TableÂ There are no definitive guidelines for establishing consensus in Delphi literature. While some researchers have suggested that 51% agreement among respondents can be interpreted as indicating consensus ,17, otheThe purpose of this round was to seek consensus for ratings on which the Panel had not converged in Round 3, in light of information about panellists previous ratings. Panellists received the potential solutions to non-adherence for which consensus had not previously been reached, alongside the mean ratings of the Panel from the previous round. Participants who had taken part in Round 3 were also provided with a reminder of their own previous ratings for the potential solutions. Participants were asked to re-rate those particular dimensions for which consensus had not been achieved. All participants were invited to comment on their Round 4 ratings.Means and standard deviations were calculated for all ratings made across Rounds 3 and 4. To produce a set of solutions to non-adherence that reflected the priorities of the Panel, only those solutions considered to be “very important” or “extremely important”, i.e., those with an importance rating of 4.00 or higher, were taken forward to the consensus meeting. Overall priority ratings for these policy solutions were calculated by summing the mean importance score and the average of the two mean feasibility scores for each solution.A group of 40 Delphi panellists and ABC Project researchers from 10 countries met at the Royal Society, London in June 2011. All stakeholder groups from the Delphi study were represented. The objective of this meeting was to further develop the policy solutions through group discussion. A plenary session at the end of the meeting enabled the chairs of each discussion group to present key outcomes of the roundtable discussions. The discussions were audio-recorded with participants’ consent.The recordings of the plenary sessions were transcribed verbatim and analysed by two researchers who had not participated in the discussions. Key themes, ideas, and recommendations for policy development were extracted. The policy solutions were amended in light of the recommendations for development that had been agreed within participants’ discussions.The three questions generated a total of 1,142 statements; 531 statements in response to question 1, 256 for question 2, and 355 statements in response to question 3, from which 501, 244 and 343 statements, respectively, were extracted for analysis. Summaries of responses by category for each question are shown in TablesÂ Approximately 43% of the causes of non-adherence concerned aspects of patients’ behaviour, beliefs or characteristics. These included forgetfulness, low health literacy, and negative beliefs about medicines. Patients’ experience and interpretation of treatment, such as perceptions of feeling no benefit from treatment and, conversely, stopping treatment when benefit was experienced, were also perceived as causes of non-adherence. Medication itself was a cause of non-adherence in nearly 20% of statements, because of the complexity of medication regimens, polypharmacy, the cost of medication for the patient, and side effects. Overarching theories about the causes of medicines non-adherence represented a significant minority of statements. These often referred to the multiplicity of factors that together can result in non-adherence, and the notion that medicines non-adherence can be intentional and unintentional.Panellists viewed the consequences of medication non-adherence to be overwhelmingly, but not exclusively, negative. Over half of the consequences listed by the Panel were experienced directly by the patient, positive or negative, through symptom experience, disease progression, quality of life, illness and death. A quarter were experienced by the healthcare system, through waste of money, medication and resources and increased utilisation of healthcare.Although the consequences of medication non-adherence were largely perceived as negative by the Panel, positive consequences of medication non-adherence were also listed. Positive consequences for patients included the avoidance of adverse/side effects resulting from medication use. Patient quality of life was also seen to benefit from medication non-adherence through feeling that one is not dependent on medication, and feelings of control and mastery.More than half of the solutions offered by panellists focused on achieving change in patients’ knowledge and behaviour. There were nearly three times the number of statements relating to changing or adapting patients’ knowledge and behaviour than those relating to changing or adapting healthcare professionals’ education and behaviour. Solutions focusing on change at the healthcare system or government level together amounted to less than 10% of the solutions generated by the Panel.A substantial proportion of statements by panel members emphasised the need to improve patient education and information about treatment to make the information understandable, impartial, evidence-based, and inclusive of details of other forms of treatment. A similar number of statements described improving education and information about the administration of medication. Several statements specified the need to improve education and information on the potential side effects of the medication, while others expressed the importance of improving education and information to inform patients’ risk-benefit analysis.A sub-set of solutions related to changes to medication, including simplification of the regimen, the development of better drugs with reduced side-effects, and improved packaging, and often referred to the tailoring of dosage to individual need and to compatibility with the patient’s lifestyle.Improving education and training for identifying and assessing medication non-adherence was a prominent solution for the Panel. A number of statements focused on improving education and training in patient-centred care to move away from a paternalistic approach to patients. A large number of statements about the input of healthcare professionals related to the provision of ongoing feedback and support with medication-taking. Frequently cited amongst the healthcare professional-focused solutions was the importance of taking a non-judgmental approach and ending the conception of non-adherence as something that should be blamed on patients. The final category of solutions pertaining to healthcare professionals was the use of reviews of medication and included suggestions such as targeting reviews towards patients on multiple medications or complex regimens.Solutions concerning clinician-patient interaction were fewer in number than those relating to healthcare professionals. Ensuring patient involvement and a partnership approach between clinicians and patients, building a partnership between doctors and patients, and the provision of frequent opportunities for open discussion with the patient about medication-taking were frequent statements here. The need to discuss patients’ beliefs about medications, the condition, and the likelihood of taking medications was also expressed. Statements about discussing patient preferences formed another category.A small number of solutions referred to the impact of the health system on adherence behaviour and these fell into four categories. The first was a team approach to treatment by healthcare professionals, for example, the involvement of nurses and pharmacists, and the concept of the ‘Medicines Education Team’. The second category concerned financial investment for supporting adherence. The last two categories within the scope of the healthcare system are in opposition; while the larger of the two contained statements about reducing the cost of medications for patients through the development of reimbursement systems, removing prescription charges, and lowering out of pocket costs for medication, the other encompassed statements about financial penalties for the non-adherent patient.A few solutions related to government involvement in adherence support. Three categories emerged: statements relating to the investment of resources or money in medication adherence, particularly regarding education, research, and access to medicines; increasing public awareness of the issue of medication adherence, for instance through public education campaigns and interventions to improve health literacy; and suggestions for policy development in the field of adherence, for example, elevating patient adherence as a critical healthcare issue.Three overarching themes on solutions to non-adherence emerged from the data. These were not solutions but rather ‘meta-theories’ about the nature of solutions to non-adherence. The most commonly cited theme related to the complex nature of solutions and the need for multifaceted interventions to achieve a comprehensive response to non-adherence. Several panellists also highlighted the lack of long-term effectiveness of current solutions to non-adherence, and the absence of an evidence base for the effectiveness of adherence interventions. The final theme was the need for solutions to correspond to reasons for non-adherence, for example, developing solutions matched to unintentional or intentional causes of non-adherence.For each of the 43 proposed solutions presented in Round 2, the percentage of the Panel that agreed with, rejected, or amended the solution was calculated. Two solutions that did not meet our a priori criterion for inclusion were deleted .The Panel achieved consensus for 64 of the 126 ratings. One solution was removed following feedback from panellists: “Patients need to broadly adjust to their illness and treatment”. This solution represented a suggestion put forward by one member of the panel in the first round and was queried by a number of panellists in Round 2. The Delphi research team therefore modified the wording of this solution to increase its clarity in Round 3. However, as a consequence of the concerns raised by several members of the panel with regard to this recommendation, this item was excluded from Round 4.Means and standard deviations for the 60 ratings that were made in Round 4 were calculated. The criterion used for determining consensus in Round 3 was used in Round 4 to determine consensus . A substantial shift towards convergence of ratings was found, with 58 of the 60 ratings achieving consensus. Overall, 121 of the 123 ratings made across Rounds 3 and 4 achieved consensus.Prioritised solutions were identified and ranked in a two-step process. Only those solutions considered to be “very important” or “extremely important” by the Expert Panel  were retained. The application of this criterion resulted in 25 policy solutions remaining in the final list. In order to determine the level of priority of each of these 25 solutions, the importance and feasibility ratings were combined in a single score by summing the mean importance score and the average of the two mean feasibility scores for each solution, as shown in TableÂ Minor amendments were made to the wording of policy solutions on the basis of themes identified from transcripts of final plenary statements at the consensus meeting and from discussion with the wider ABC project team. The resulting dissemination statement of consensus-based policy solutions for medication adherence is shown in TableÂ The Delphi panellists achieved consensus about a broad range of policy solutions for Europe to address medication non-adherence, and agreed on the relative importance and feasibility of those solutions. This consensus is all the more significant having been obtained with participants from fourteen countries from a diverse range of stakeholder groups who might be expected to have divergent perspectives, experiences and interests in medication adherence. Participation in a Delphi study demands a significant commitment of time and effort over a number of months and the 1,142 separate statements made by this Panel represent a significant resource.Many, but not all, of the solutions target action at the patient and the public, rather than policy interventions at the healthcare provider or systems level. This may well correspond with the Panel’s beliefs, reflected in the wider research literature that the primary cause of non-adherence is patient’s beliefs about illness and treatment ,22. EquaFor the purpose of this task, panellists were instructed to think about each potential solution, and in later rounds, the importance and feasibility of each solution, in isolation. In practice, interventions to support medicines adherence may be multi-faceted, delivered in parallel, and cut across the categories used here to help structure the task for participants. This study does not tell us how policy makers and commissioners might seek to combine interventions for best effect or perhaps stagger the introduction of individual solutions within an overall implementation strategy.The requirement for panellists to communicate in the English language may have prevented some potential panellists from participation. Panellists came from 14 different countries, though a significant minority of the panel were UK based. Nevertheless, the policy solutions represent the combined views of a diverse group of stakeholders with a remit for adherence, rather than the views of a specific interest group or a single professional group ,25.This study improves on previous research initiatives to develop policy recommendations for medicines adherence in several ways. The proposed solutions look beyond the actions and interactions that occur in the clinical setting  to broadOther research in this area, such as systematic reviews of adherence interventions , tends thttp://www.abcproject.eu/) and we hope this paper stimulates further discussion and action. Future efforts should focus on sharing implementation practice to improve our knowledge of the range of policy responses to medication non-adherence across Europe.The solutions to medication non-adherence for Europe are broad and practical in nature. The breadth of the policy solutions enables significant flexibility in national implementation to reflect differences in healthcare systems, health-related culture, available resources, and the level and sophistication of existing implementation. Local implementation of the highest priority item ‘improve patient and education when a medication is newly prescribed’ could, for example, be delivered in a number of ways: as part of a community pharmacy service such as the New Medicines Service in England ; in conjThe authors declare that they have no competing interests.WC participated in the design of the study and was involved in data collection, data analysis, and data interpretation. SW was involved in the design of the study, data analysis, and data interpretation. SM participated in data collection, data analysis, and data interpretation. All authors helped to draft the manuscript and approved the final version.All authors are based in the School of Pharmacy at Keele University. WC is Head of the Medicines Partnership Programme, SW is Lecturer in Pharmacy Practice, and SM is Medicines Partnership Research Assistant.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/425/prepub


The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices.This study surveyed antibiotic use in the community (December 2007-November 2008) using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic.During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed.A very high consumption of antibiotics was observed in both public and private sector outpatients. There was a high use of broad spectrum and newer antibiotics in the community. Suitable and sustainable interventions should be implemented to promote rational use of antibiotics that will help in decreasing the menace of antibiotic resistance. The current worldwide increase in antimicrobial resistance (AMR) and, simultaneously, the downward trend in the development of new antibiotics have serious public health and economic implications. The increased resistance is a result of many factors, but the foremost cause is the overall volume of antibiotic consumption. About 80% of antibiotics are used in the community and the rest are used in hospitals ,2. It isIn collaboration with the World Health Organization (WHO) a pilot project was conducted in New Delhi, India (2002-2005)  and elseSurveillance of antibiotic use was done by collecting data from four municipal wards  of New Delhi, India. The study was done in conjunction with another study (not described here) to measure the antimicrobial resistance pattern for the OPD patients of a private tertiary care hospital located in West Delhi. Hence, the antibiotic use data was collected from four municipal wards around this hospital - the same 4 wards as used in the previous study in private retail pharmacies . The fouBoth the public and private sectors were included in the survey. Medicines are provided free of charge to patients in public sector facilities but must be paid for in private sector facilities. In order to get a complete picture of antibiotic use in the community, three different types of facilities were chosen:1. Public sector - All 10 facilities under the Government of National Capital Territory of Delhi (GNCT Delhi) in our catchment area were enrolled for the survey. The facilities were 8 dispensaries (Primary care facility) and 2 hospitals (Secondary care level);2. Private retail pharmacies - A total of 185 licensed private retail shops were located in the four chosen municipal wards from which 20 well-stocked, private retail shops, willing to cooperate, were chosen for the study;3. A total of 20 private sector doctors, who were willing to cooperate for the study and were practicing in the chosen areas, were chosen and consisted of 4 paediatricians, 3 physicians, 12 general practitioners (GPs), and 1 dermatologist .A convenience sample for private sector facilities was used because many doctors and retail pharmacy shops do not tolerate continued data collection processes. Moreover we wanted to include facilities with a sufficient number of patients per day. A good liaison was maintained with all the participants and their professional associations, who helped in enrolling the facilities throughout the study period.Trained data collectors (pharmacists) collected antibiotic use data by conducting exiting interviews with all patients receiving/purchasing an antibiotic on leaving the facility. For private retail pharmacies any patient purchasing an antibiotic, whether with a prescription, without a prescription, or on the advice of chemist, was interviewed. For public sector facilities and private clinics all the patients interviewed were out-patients. In private facilities, exiting patient interviews were conducted in a part of the waiting room after the patient had left the consultation room. In pharmacies, exiting patient interviews were conducted in a part of the shop or on the street outside. At public facilities, exit interviews were conducted near the pharmacy of the same facility. A pre-designed proforma was used to collect data regarding the name of the antibiotic, the strength, the dose and the number of units prescribed by the doctor, and the number of units dispensed or purchased.30 exit interviews were conducted in each public sector facility and private retail pharmacy in each month. However, only about 10-12 exit interviews were conducted in each private clinic every month as the patient flow was much less and it was not possible to wait the required time to collect the same number of patients due to resource constraints. The rationale for conducting this number of exit interviews is from the WHO manual, "How to investigate drug use in health facilities" which recommends 600 encounters (20 facilities and 30 patients/prescriptions per facility) for one survey [The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD), ATC/DDD (2006), measurement units were assigned to the data . ConsumpAll the data collected was entered into software developed in Visual Basic, SQL Server and Crystal Reports. The same software was used to analyse the data.Ethical approval for the study was obtained from Vallabhbhai Patel Chest Institute, University of Delhi, India and also from WHO Ethics Review Committee. Informed consent was obtained from all participants and facilities involved in the study.In enrolled private retail pharmacies, 7101 patients (39.5%) out of 17995 patients visiting the pharmacies during data collection purchased an antibiotic (and were thus interviewed). In enrolled public facilities, 3615 (39.3%) out of 9205 patients were prescribed an antibiotic. In enrolled private clinics, 2571 (43.4%) out of 5922 patients were prescribed an antibiotic.Table Table Table At public facilities, while the newer members from each class of antibiotic were also used, there was more use of the older antibiotics than in the private sector. Thus, newer antibiotics such as cefuroxime, ofloxacin, and roxithromycin were commonly used as in the private sector but older antibiotics such as cephalexin, erythromycin, cotrimoxazole, and tetracyclines were also commonly used. However, older antibiotics were used sparingly in the private sector Table . For penFigures This is one of the first studies from a developing country that describes a large, comprehensive surveillance of antibiotic use in three facility types over a one-year period to get a complete picture of antibiotic use in an urban community. There is evidence at the national level  as well Surveillance of antimicrobial use in the community for developing countries is difficult because no databases are available and antibiotics can be purchased over-the-counter ,15. The Measuring the percent of antibiotic containing prescriptions is an easy and more reliable method than measuring the DDD/1000 inhabitants in these settings as the data is not collected from all the facilities serving a population. However, data on DDD consumed per 1000 patients can help in providing insight into how antibiotics are used . For exaThe surveillance system was able to track trends and patterns of antibiotic use in all the types of facilities: public facilities, private clinics and private retail pharmacies. Findings from the present survey clearly show the importance of tracking antibiotic use in different facility types as consumption of various classes of antibiotics was clearly different. In the public sector, almost all classes of antibiotics were prescribed while in the private sector virtually only the newer antibiotics were consumed. Comparison of the results of this survey in 2008 with the pilot survey conducted at the private retail pharmacies in the same areas in 2004 [No major differences in the pattern of use of the various antibiotic groups were found between the four wards/areas surveyed for any facility types nor were any major differences found with regard to the percent of patients receiving antibiotics in four areas surveyed. In each of the four areas, the percent of patient receiving an antibiotic was 38%-41% in public facilities and 39%-41% in private retail pharmacies. However, for private clinics the percent of patients who received antibiotics in Rajouri Garden was 34% and in Karol Bagh 38% as compared to Patel Nagar where it was 56% and Rajinder Nagar where it was 50%. It is difficult to determine the reasons for this variation but it may be associated with the general socioeconomic status of the neighbourhoods, as Patel Nagar and Rajinder Nagar are richer than the other areas. As we did not study the sociodemographic profile of the patients visiting the facilities it is not possible to analyse this further. A study conducted in Uttar Pradesh, India showed that higher socioeconomic status of the patients was associated with higher antibiotic use .A small degree of variation was observed in the prescription of different antibiotics over 12 months. In public facilities any variation could have been due to variation in supply of antibiotics to public health facilities from the main central store (though correlation of use with availability was not done). Overall there did appear to be slightly greater use of antibiotics  used for acute respiratory tract infections (ARI) in the winter months and for antibiotics used for diarrhea (fluoroquinolones) in the humid summer months. A survey conducted simultaneously with this study showed that number of diarrhea cases did increase during the rainy summer months and that fluoroquinolones were the most commonly prescribed antibiotic for diarrhea . It is lThe high and increasing use of the newer antibiotics in the community is worrying, as such antibiotics may often not be needed and their use will lead to resistance in the treatment of serious infections. The older antibiotics should be sufficient for many of the common infections seen in the community. While there is a profit-motive in the private sector for using the newer and more expensive antibiotics, the reason for their increased use in the public sector is not clear. There is an essential medicine list (EML) for all public facilities under the Government of National Capital Territory of Delhi, and this list is regularly updated and used for procurement of all medicines. The Delhi state EML has a separate EML for dispensaries and this list has antibiotics, like amoxicillin, ampicillin, ciprofloxacin, norfloxacin, cephalexin (for restricted use), erythromycin, roxithromycin, cotrimoxazole and doxycycline. These antibiotics are the first choice to treat most common infections in the community. Antibiotics like ofloxacin and cefuraxime are added to the hospital list of the EML with an *asterisk indicating that they are reserve antibiotics to be used only in case of significant resistance to other antibiotics . HoweverOur study has successfully captured the pattern of antibiotic use in the community. We did not measure DDD/1000 inhabitants as is generally done by studies in European countries. In our settings this is not an accurate measure of exposure of the population to antibiotics because we have not included all the facilities of our catchment area and complete data  could not be collected from any enrolled facility. The objective was not to measure accurately population exposure to antibiotics, but rather to measure trends in use as part of a surveillance system. Provided the same methodology is used each month, the same degree of error will occur each month and the data collected will be sufficient for trend measurement even though it is not accurate for a one-off exposure measurement. Since the exit interview data only measures use in some of the patients attending some of the health facilities, the total number of DDDs per population would be much less than would be the case if all the facilities were included.The most important strength of the study is that it clearly shows that it is possible to collect useful data for antibiotic use in all types of facility from wherever it is prescribed/dispensed/purchased, at the individual patient level in resource-constrained settings. The study has some inherent weaknesses. Firstly, it was conducted in four residential localities of one urban area, so generalization should be done with caution for the rest of Delhi and cannot be done for other areas of India. Secondly, the presence of data collectors may have changed the prescribing and dispensing habits of doctors and retailers. Doctors may have prescribed fewer antibiotics than normal and retailers may not have dispensed antibiotics over-the-counter as often as normal. Some of the Hawthorn effect may have reduced over the period of one year, as the health workers got used to the presence of the data collectors. In public facilities, the bias on doctors' prescribing may have been less as the data collectors were in the pharmacy area and doctors were not always aware which day and time data collectors were visiting. The reduced sample size of exiting patient interviews in private sector clinics, due to time and resource constraints may have resulted in less accurate estimates of antibiotic use in this facility type as compared to the other facility types. However, the year-long duration of the study should partially compensate for the lesser number of patients interviewed each month. While the methodology used is simple, reproducible, and feasible for collecting data from various facilities in the community over a long period of time, it requires attention to detail particularly with regard to supervision of data collection, data management and maintaining good relations with frequent feedback to participating facilities (in order to maintain their cooperation).Antibiotic use is the key driver of antimicrobial resistance. Antibiotics are overused, particularly for minor infections, misused for self-limiting viral infections and underused due to financial concerns. Extensive surveillance programmes have been used to study patterns of antibiotic resistance and use in developed countries. These systems have made it possible to stimulate the implementation of nationwide interventions to improve antibiotic use . ResultsThe authors declare that they have no competing interests.Both the authors (AK and KH) are responsible for the reported research, and have participated in the concept and design, analysis and interpretation of data, revising of the manuscript, and have approved the manuscript as submitted. AK was also responsible for getting data collected from different public and private facilities, data entry, and drafting the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/11/99/prepub


The radiation doses to humans resulting from a potential release of radionuclides from a geological repository for long-lived waste are assessed over tens or even hundreds of thousands of years. Ingestion is expected to be the major exposure pathway, and the group with the highest exposures will be those that consume the most contaminated food. In this paper, we characterize the group of individuals with the highest exposures by considering the physical and biological characteristics of the contaminated area and human requirements for energy and nutrients. We then calculate intake rates based on land-use scenarios drawn from self-sustained communities spanning prehistoric times to an industrial-age agrarian culture. The approach is illustrated by simulating groundwater release of four radionuclides to an expected discharge area. We argue that the derived intake rates may serve as credible bounding cases when projected doses are evaluated for compliance with regulatory criteria.The online version of this article (doi:10.1007/s13280-013-0400-z) contains supplementary material, which is available to authorized users. The radiation doses to humans resulting from a potential release of radionuclides from an existing or planned repository for long-lived waste are assessed over tens or even hundreds of thousands of years. The assessment involves estimating activity concentrations of radionuclides in the environment  as well as in plants and animals that may serve as food for human inhabitants  is expected to be a dominant source for exposure from the existing and planned geological repositories for low and intermediate radioactive waste  is likely to be a major exposure route for a geological repository for spent nuclear fuel  which is planned in Forsmark, Sweden. The paper focuses on the intake via food per unit contamination, i.e., how human characteristics and habits will affect the amounts of radionuclides that are ingested with food. However, the principles adopted can also be applied to identifying a representative person for other exposure routes . In order to assess intake from contaminated food, we consider different possible uses of land and natural resources, given the constraints set by the physical landscape and human requirements for energy and nutrients. Assumptions on habits are drawn from self-sustained low- and higher-technology societies from prehistoric times to an industrial-age agrarian culture. Thus, we identify stylized exposure scenarios, based on cultures and habits with high intake rates per unit radionuclide concentration. We recognize that the assigned characteristics and habits are unlikely to provide a realistic estimate of the actual characteristics and habits of human beings in the far future, but argue that the scenarios may serve as credible bounding cases when projected doses are evaluated for compliance with regulatory criteria.Geo-hydrological modeling suggests that contaminated groundwater from a geological repository in a coastal area flows primarily to low points in the landscape, e.g., along the shoreline and in shallow parts of sea basins, or to lakes, streams, and mires when the discharge is to the terrestrial environment .The physical landscape governs and sets the limits for human use of land and natural resources. However, human activity may transform the natural landscape (including the most contaminated area) to a cultural landscape, e.g., by conversion of forests or mires into arable land or meadows. Consequently, the number of individuals that can be supported by natural resources from a unit area of land or water will depend on both land-use practice and available technology . Assumptions on group size, land use, productivity, and diet are drawn from self-sustained societies from prehistoric times to an industrial-age agrarian culture , considering the likely size of the most contaminated area and human physiological constraints with respect to energy and nutrients.The extent to which a contaminated area of a natural or cultural landscape can support the food demand of future human inhabitants depends on the physical properties of the landscape, the number and characteristics of the exposed individuals, technology at hand, and cultural preferences. Below we sketch out detailed principles for calculating intake rates of radioactively contaminated food for a person who is representative of the most exposed group. For convenience with respect to dose calculations, food intake rates are expressed as a fraction of the yearly energy demand throughout .The future landscape in Forsmark under conditions of weak human influence would most likely be a mosaic of forests, mires, and lakes, with a decreasing influence of the sea as the shoreline transgresses with time  also to future foragers . With these assumptions most of the central investigation area of Forsmark  would be within the home range of practically any settlement on the coast.The most exposed individuals would be the ones making full use of the contaminated parts of the landscape. Thus, if contaminants were restricted to the sea, the most exposed group would be one with a marine diet, whereas if the contaminated groundwater primarily reached a lake with surrounding mire, the most exposed group would be found in a community with a mixed diet. From the historical record of hunter gatherers it is reasonable to assign a social structure that encompasses 40 members , pike (Esox lucius), and cod ], there is an upper boundary as to how much contaminated fish could possibly be consumed. Excessive protein consumption may lead to toxic effects due to elevated levels of amino acids, ammonia, and insulin (causing nausea and diarrhea), and thus the upper level for healthy consumption of protein is 25 % of the total energy intake , the land-use pattern of Iron-Age farming has been simulated for family-sized groups Widgren . These cIn an Iron-Age infield-outland system, cattle would typically graze pastures and forest on solid ground, whereas hay would be collected from meadows on solid ground and from mires. Thus, a self-sufficient Iron-Age agricultural community of two households could be used as a model for the most exposed group with respect to exposure from contaminated hay and manure for infield cultivation. An upper boundary for exposure would be to assume that the most exposed group fully depended on the contaminated mire for winter fodder. Wet grasslands are more fertile than dry ones, and mires in Central Sweden may produce up to 2400 kg dw grass and sedges per hectare (ha) and year .In the wake of the industrial revolution agricultural was modernized, and the demand of land led to large-scale draining and cultivations of lakes and mires. At the turn of the nineteenth century the majority of the farming population was found on self-sufficient small-scale farms, and we propose that these are a good reference for the most exposed group with respect exposure from draining and cultivating contaminated lake–mire systems . A large part of the arable land was used to produce fodder for animals. In addition to green fodder production, as much as two thirds of the cereal production may have been used as animal fodder Morell .Animals were used as beasts of burden as well as for production of meat and dairy products. Statistics on livestock from the early twentieth century suggests an animal density of approximately 1 cow (or horse) per 1 ha arable land and farms without animals would have been very rare. Cattle were the most common type of livestock and the production of milk (on a wet weight basis) was an order of magnitude larger than the production of meat  and potatoes also grow well on organic soils, and thus it can cautiously be assume that the most exposed group used organic soils for production of all bulk food.Using an annual demand of 110 kg C per individual, a theoretical minimum support area of 6 ha can be calculated for 10 adult individuals, which means that a few farming households could most likely be fully supported by a contaminated mire which was drained for cultivation. Nevertheless, if the contaminated mire were smaller than this support area, the fraction of food items that would be contaminated could easily be adjusted to account for this.−1) to a potential discharge area in the future Forsmark landscape , the discharge area develops from a sea basin, through a lake–mire complex, to a mire where the lake basin has been filled with sediments and peat. The activity concentrations in sea and lake water and in peat and agricultural soils were dynamically simulated , cultivation of contaminated peat yielded the maximum intake rate. However, for 237Np which accumulates strongly in aquatic food webs, foraging the lake for natural food resulted in the peak intake rate of the radionuclide. In the following sections these patterns are examined and discussed in more detail.The results clearly show that radionuclide properties, the development of the surface environment, and the land-use scenario, all have significant effects on the intake rate of activity. For all four radionuclides, the highest intake rate was recorded after lake isolation, and for three of the radionuclides (fcont) is determined by human physiological constraints with respect to protein toxicity . However, the size of the contaminated sea basin is ultimately reduced by land rise . Consequently the bulk of food will be captured or harvested from uncontaminated parts of the landscape even for the most exposed group.The isolation of the lake from the sea spans 650 years, starting around ad 5000) activity concentrations in the contaminated area approach long-term steady-state conditions, but the production of aquatic food decreases as the lake area declines. Thus, for a radionuclide where the primary source of exposure is aquatic food, intake rates decrease in response to the expansion of mire vegetation . Thus, from these points in time there is no dilution in intake rates relating to the size of the contaminated area.Following lake isolation, activity concentrations of the studied radionuclides are fairly stable in mire peat and vegetation, and the concentrations in agricultural soils, fodder, and food items vary little within the agricultural systems. Given industrial-age farming, two family farms can be supported by the contaminated mire from the point in time when sustainable cultivation is possible, whereas the demand for winter fodder of the infield-outland system can be supported at approximately Comparing the two agrarian land-use scenarios, it is clear that intake of radionuclides is higher in the industrial-age system than in the infield-outland system  and 16:24:60 (% energy), respectively. Though these diets are no more than the results from highly stylized calculation scenarios, the diets are fairly balanced and meet the lower value of acceptable macronutrient requirements for both fat . We then used the fraction of unprocessed food (fresh or frozen) as a reasonable upper limit for the potential contribution of contaminated food .For this comparison, we have used a recent summary of Swedish consumption statistics, published by the Swedish Board of Agriculture . Moreover, this relationship does not change significantly if we assume that the total fraction, rather than the non-processed fraction, of the food items is a more reasonable upper limit for consumption of contaminated food today.From the comparison it becomes clear that the consumption of both natural and agricultural contaminated food items are at least five times higher in the historic land-use scenarios, as compared with upper limits based on recent food statistics. That is, for the historical and present-day calculation cases the fraction of contaminated food is 0.10 versus 0.02 for natural food items, and 1.0 versus 0.16 for agricultural food items  in future assessment models, so that we can estimate crop system-specific activity concentrations in agricultural produce from similar initial conditions.In this paper we have sketched out three land-use scenarios that may serve as bounding cases for intake of contaminated food, using three self-sustained historical societies as reference points. From our analysis we conclude that these constructs define a reasonable set of exposure scenarios for food ingestion, when projected doses are to be evaluated for compliance with regulatory criteria in an appropriate context . That is, the scenarios are likely to cover the most exposed group regardless of type of community existing at the site in the future.We believe that consistency and compatibility between estimates of projected doses would benefit from a more explicit framework for identifying exposure scenarios, and hope that the principles outlined in this paper can contribute to this development. However, we recognize that the assigned characteristics and habits of future humans are unlikely to provide a very realistic estimate of the actual characteristics and habits of human beings in the far future. For this and several other reasons, projected doses in the far future should not be used to predict future health effects ICRP .Ingestion is the expected major pathway of exposure from a geological repository, and the most highly exposed individuals will be those that consume contaminated food (and water). The relative contributions of different land-use scenarios to exposure are likely to vary with the properties of released radionuclides, with time and with the stage of development of a contaminated discharge area. Thus, it seems rational to evaluate several plausible sets of land-use scenarios in parallel, when assessing the radiological safety of future generations. We recommend that each such scenario should conform to the physical and biological constraints of the contaminated area, as well as the physiological and nutritional needs of human inhabitants. Moreover, land use should be sustainable and reasonable in the sense that there are historical records supporting the construct, or that it can be observed in existing human cultures.Supplementary material 1 (PDF 213 kb)Below is the link to the electronic supplementary material.


Bothrops asper (family Viperidae), locally known as ‘terciopelo’, ‘barba amarilla’ or ‘equis’. About 1% of the bites are caused by coral snakes of the genus Micrurus (family Elapidae). Despite significant and successful efforts in Central America regarding snakebite envenomings in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and clinical management of bites, and prevention of snakebites, much remains to be done in order to further reduce the impact of this medical condition. This essay presents seven challenges for improving the confrontation of snakebite envenoming in Central America. Overcoming these challenges demands a coordinated partnership of highly diverse stakeholders though inter-sectorial and inter-programmatic interventions.Snakebite envenoming is a serious public health problem in Central America, where approximately 5,500 cases occur every year. Panama has the highest incidence and El Salvador the lowest. The majority, and most severe, cases are inflicted by the pit viper  Bothrops asper, medically the most important snake in the region  include snakes with venom glands and a fang system located in the posterior part of the maxilla. From the biological standpoint these are venomous snakes; however, they rarely bite humans, owing mostly to the difficulty with which they inject their toxic secretions, and also to the low intrinsic toxicity of some of these venoms. Hence, signs and symptoms of bites by colubrids in Central America do not exceed local edema and bruising [The vast majority of the abundant snake species in Central America are non-venomous  -10. Specbruising ,11. In cBothrops asper, locally known as ‘terciopelo’, ‘barba amarilla’ or ‘equis’  present neurotoxic manifestations provoked by a neuromuscular blockage predominantly induced by post-synaptically acting low-molecular-mass neurotoxins [Pelamis platurus, family Elapidae), it is likely that they would be associated with neurotoxic features similar to envenomings by coral snakes [Envenomings by pit vipers, among which the most serious are inflicted by ’ Figure , are charotoxins . Althougl snakes .The severity of snakebite envenomings depends on several factors, namely:•The volume of venom injected.•The anatomical site of injection (bites on the head and trunk tend to be more complicated than those on the feet or hands).•The size and physiological condition of the victim (bites in children tend to be more serious than in adults).•Time elapsed between the bite and medical attention.The only scientifically validated treatment for snakebite envenoming is the administration of safe and effective animal-derived antivenoms . Antivenet al. [Despite the fact that this problem is attended by the public health systems in the region, with the consequent reduction of mortality in the last decades , a numbThere are various studies published on the epidemiology and mortality of snakebite envenoming in Central America, especially in Costa Rica ,15-18. LIn addition to the provision of data on incidence and mortality, this information will allow the identification of vulnerable regions in each country, particularly with regard to vulnerable sectors, such as the indigenous groups. Moreover, there is a need to develop studies of community-based and household surveys that could provide a more realistic view of the magnitude of the problem. This type of research has been undertaken in other parts of the world, such as Bangladesh and India, where it showed that the magnitude of this problem is much larger than what is reflected by hospital-based statistics ,20. FinaThe effect of this disease in specific groups – including children, indigenous communities, agricultural workers etc. – should be investigated in order to discern the particular aspects in which such groups are affected. The incorporation of social research for understanding snakebite envenomings and their implications is of paramount relevance owing to the impact of cultural, sociological, economical and psychological variables in the overall picture of this condition . ClearlyToxicon devoted to Bothrops asper in 2009 [et al.[Since the pioneering work of Clodomiro Picado Twight , a large in 2009  and a re9 [et al. on the p9 [et al.-27 and r9 [et al.. In fact9 [et al.-32.There is a need to characterize the clinical manifestations of envenomings induced by various snakes in the region, with the aim of identifying clinical patterns characteristic of some species. Some pending questions in this area are:•Do envenomings by newborn/neonate and juvenile pit vipers differ from those provoked by adult specimens, as suggested by their different proteomic and toxinological profiles?Bothriechis sp. species induce envenomings with systemic manifestations and, if so, what are these systemic effects?•Can bites by Porthidium, Cerrophidium and Atropoides, which are endemic to Central America?•What is the clinical picture that characterizes envenomings by terrestrial species of the genera Lachesis stenophrys and L. melanocephala characterized by the unique vagal-type effect described in cases by South American bushmasters?•Are envenomings by Micrurus sp. characterized only by neurotoxic manifestations, or do some species provoke other effects, such as those described in bites by some South American coral snakes?•Are envenomings by Agkistrodon bilineatus, although preclinical results may suggest so [Moreover, the therapeutic effect of antivenoms used in the region in envenomings by different pit viper species has to be investigated in the clinical setting. It is not clear, for instance, whether the polyspecific antivenom is effective, at the clinical level, for neutralizing the venom of ggest so . Thus, tAntivenoms for the treatment of pit viper and coral snakebite envenomings have been produced in Costa Rica since 1967, an effort consolidated by the creation of Instituto Clodomiro Picado in 1970 ,35. In avis-à-vis the distribution of health services, and the distances between communities and nearest health clinics  tools should help to identify regions of high vulnerability to snakebites which require improvements in antivenom deployment  required for the management of envenomings. In this regard, and as a matter of example, proposals for snakebite management on an integrated national basis have been presented in Colombia  and in NEffective management of snakebite envenomings at the clinical level demands a proper knowledge on the main aspects of their clinical manifestations and complications, diagnosis, and treatment, not only regarding the use of antivenom (including the management of adverse reactions), but also the ancillary therapy of the cases. The acquisition of this knowledge by health staff requires concerted actions at various levels, such as university courses in Medicine and Nursing schools, and permanent education programs, especially for physicians, nurses and other health staff working in areas of high incidence of envenomings.The preparation of national and regional guidelines is of utmost relevance, in order to ensure a standard management of these cases with a solid scientific basis. Significant advances have been made in Panamá  and Costa Rica, where snakebite management protocols and algorithms have been prepared and where permanent teaching activities take place at universities and health facilities. Seminars and related activities on the subject are regularly organized in some countries in the region, but in others there remains a need to develop permanent training programs; this demands concerted national and regional efforts. In this regard, the use of communication and information technologies, such as those designed for videoconferences, should be promoted. One example is the PAHO-supported platform Elluminate, which has been used for training activities on this subject in Honduras, Costa Rica and Panamá.One of the most neglected aspects of snakebite envenoming is following up on accident victims who develop permanent physical or psychological sequelae, especially those resulting from cases of viperid snakebites. The actual incidence of these sequelae is largely unknown, because survivors leave the hospital and follow-up of these cases is not performed. Since these accidents mostly affect poor and vulnerable people living in rural areas, the impact in their quality of life is likely to be dramatic. On one hand, this greatly affects their physical integrity and, consequently, their ability to perform field work, thus contributing to the vicious cycle of poverty. In addition, the psychological consequences of such a traumatic event are likely to be high, as demonstrated in a study on snakebite victims performed in Sri Lanka .There is a pressing need to study the magnitude and characteristics of this problem in the region through integrated and interdisciplinary research projects. The relevance of social research in this aspect of the snakebite problem cannot be overestimated. The information generated in such studies will serve as the basis for the development of interventions by governmental and non-governmental groups with the aim of alleviating the long-term consequences of envenomings. The examples in which non-governmental organizations of the civil society have been created to improve the management of many diseases and mitigate their impact on the affected population, should serve to stimulate not only learning but also the development of similar organizations in support of snakebite victims.Information gathered on the epidemiology of snakebite envenomings in Central America highlights several trends that are very helpful in designing effective prevention campaigns. The majority of accidents occur in the rural population in people devoted to agricultural work; hence, priority attention should be given to the provision of basic information on preventive measurements in these groups and communities. To this end, it is relevant to work in close coordination with local community organizations, in order to design the most appropriate intervention programs, which should be tailored to the specific cultural and social features of the populations. One important case to consider has to do with indigenous communities; appropriately designed campaigns must be prepared in local languages and should be adapted to the world view of these groups. In Costa Rica, for instance, Instituto Clodomiro Picado and Caja Costarricense del Seguro Social have developed a prevention program for the communities of the Cabécar ethnic group inhabiting the Caribbean region; this program was developed in close collaboration with the communities and with health and educational institutions in the region  Figure .Bothrops asper, are measures that reduce the likelihood of an accident. Finally, but not less important, is the community-based organization of rapid transportation of bitten people to the nearest health center. It is well known that the prognosis of an envenoming is directly related to the time lapse between the bite and the onset of treatment. Therefore, avoiding unnecessary delays due to the performance of ineffective and often harmful first aid interventions, and ensuring rapid transportation to the health post are key components of an adequate strategy to confront this problem. In Nepal, for instance, an effective motorcycle transportation system, together with community education campaigns, has proven highly effective at reducing the incidence and mortality due to snakebite envenomings [Most of the snakebites in Central America occur on the feet (~50%) and hands (~30%) ,4. Thereenomings .The confrontation of snakebite envenoming as a public health problem on a global basis has been greatly hampered by its systematic neglect among public health and political authorities ,44,45. Thttp://www.snakebiteinitiative.org) is to promote the global awareness of the impact of snakebite envenomings [This scenario should be overcome by a concerted advocacy program at various levels. On a worldwide basis, one of the main goals of the Global Snakebite Initiative (GSI –enomings . Coordinenomings .As observed in many regions of Africa, Asia, Latin America and Oceania, snakebite envenomings represent a serious public health problem in Central America. Although valuable efforts have been made in the region to perform research on snakes, venoms, and envenomings, to train health professionals and students in the details of the clinical diagnosis and management of envenomings, to produce and distribute safe and effective antivenoms to all the countries, and to promote the prevention of snakebites – much remains to be done in order to reduce the impact of this medical condition. The challenges discussed in this work present some of the issues that should be considered. Of highest relevance is the need to incorporate stakeholders from a wide spectrum of sectors in the study and solution of the problems associated with snakebites. It is only through concerted inter-programmatic and inter-sectorial interventions by diverse actors that the heavy impact of human suffering inflicted by this condition will be significantly reduced.The author declares that there are no competing interests.


Objective: To present the use of indocyanine green and the LifeCell SpyElite System to confirm perfusion and viability of a forehead flap prior to division and inset, thereby eliminating the question of flap survival based on clinical judgment alone. Methods: A case report of a 67-year-old man with a forehead flap reconstruction following an acquired nasal defect due to resection of an adenoid cystic carcinoma is presented. LifeCell SpyElite System was used to confirm perfusion prior to pedicle division. Results: The LifeCell SpyElite System was used to confirm perfusion to the forehead flap prior to pedicle division during the second stage of the procedure. After confirming perfusion, the pedicle was divided and the flap was inset. The remainder of the patient's operative and postoperative course was uneventful, and he healed without incident. Conclusions: Indocyanine green and the LifeCell SpyElite System is a reliable method to confirm perfusion and viability of staged reconstructive procedures prior to division and inset, thereby eliminating the question of flap survival based on clinical judgment alone. This is a practical application of this technology that has not been previously described in the plastic surgery literature. Final surgical pathology revealed adenoid cystic carcinoma, and he subsequently underwent bilateral lateral rhinotomies, resection of skull base tumor including nasal bones, frontal process of the maxilla, and nasal septum. After intraoperative evaluation of the defect, the defect was reconstructed with a pedicled mucosal lining flap, split calvarial bone graft, and paramedian forehead flap.The design of the paramedian forehead flap was based on a paper template that was created from the defect. A Doppler probe was used to identify the course of the right supratrochlear vessels . The flaincrease in fluorescence when compared with the surrounding tissues. This may represent a similar phenomenon, which is that there are less developed vascular channels to drain the flap, leading to a mild degree of venous congestion. The remainder of the patient's operative and postoperative course was uneventful, and he healed without incident 8Current methods of assessing perfusion are numerous, but previous reviews demonstrate none to be universally accepted.16Indocyanine green, a second-generation fluorescent dye, rapidly binds to plasma proteins when injected intravenously. It is taken up from the plasma almost exclusively by the hepatic parenchymal cells and is secreted entirely into the bile. It does not undergo significant enterohepatic recirculation, and it has a half-life of 2.5 to 3.0 minutes. In the absence of capillary protein leakage, it is exclusively distributed within the intravascular space,13The use of laser-assisted ICG is not without limitations. Indocyanine green should not be given to patients who have an allergy to iodine or shellfish. Currently, the measurement of flap perfusion is not a quantitative measure, but instead, a qualitative one. Perfusion values are given based upon the intensity of the image on the screen, but these values must be interpreted with caution. Variations in hemodynamics, microcirculation, and artifacts are different for each tissue as well as each patient. There are currently ongoing studies that attempt to delineate the numerical values that will correlate with the risk of flap necrosis, but to date, none of these have determined an exact relationship.,The ability to evaluate the perfusion and viability of both pedicled and free flaps has been both a source of innovation and frustration for plastic surgeons. We present the use of ICG and the LifeCell SpyElite System to confirm perfusion and viability of a forehead flap prior to division and inset, thereby eliminating the question of flap survival based on clinical judgment alone. This has applicability to a number of different procedures within plastic surgery, including staged procedures such as the Abbe flap for lip reconstruction, the Hughes flap for eyelid reconstruction, the Waltzing tubed pedicle flap, and the groin flap for upper extremity reconstruction. Further studies such as this and others that use laser-assisted ICG ,15 must