This gave us the opportunity to prospectively study how different aspects of quality of care change, as a country changes its health financing options from user charges to free services, in a developing country setting. The outcome of the study may then provide insights into policy actions to maintain quality of care following removal of user fees.It has been argued that quality improvements that result from user charges reduce their negative impact on utilization especially of the poor. In Uganda, because there was no concrete evidence for improvements in quality of care following the introduction of user charges, the government abolished user fees in all public health units on 1A population cohort and representative health facilities were studied longitudinally over 3 years after the abolition of user fees. Quantitative and qualitative methods were used to obtain data. Parameters evaluated in relation to quality of care included availability of drugs and supplies and; health worker variables.Different quality variables assessed showed that interventions that were put in place were able to maintain, or improve the technical quality of services. There were significant increases in utilization of services, average drug quantities and stock out days improved, and communities reported health workers to be hardworking, good and dedicated to their work to mention but a few. Communities were more appreciative of the services, though expectations were lower. However, health workers felt they were not adequately motivated given the increased workload.The levels of technical quality of care attained in a system with user fees can be maintained, or even improved without the fees through adoption of basic, sustainable system modifications that are within the reach of developing countries. However, a trade-off between residual perceptions of reduced service quality, and the welfare gains from removal of user fees should guide such a policy change. It has been argued that there are quality improvements that result from user charges -5, whichst March 2001, with hospitals allowed to operate a paying window for those who could afford to pay. The policy aim was not to discourage payment for services, as prepayment mechanisms are not abolished, but rather to limit the financial barriers clients face in accessing health services by removing charges placed by government. In addition, fees continue to be charged in Private For Profit [PFP] and Private Not For Profit [PNFP] [predominantly church owned] facilities.In Uganda, following the introduction of user charges, evidence for improvements in quality of care was mixed. It was argued that the presence of user fees led to an improvement in the morale of the health workers, improved drug availability, and general maintenance of the health units , and the†. Therefore, the additional release represented an increment of 22.3% on the expected drug expenditure by districts. As part of the budget process for the following financial year [starting 4 months after the policy change], there was an increase in the Ministry of Health allocations by US$ 12.5 million [0.52 US$ per capita]. This amount was felt to be adequate to compensate for the loss in revenue due to the policy change‡. The Primary Health Care [PHC] allocations to health units for recurrent expenditures increased. Non-wage allocations for the 2002/03 FY reflected a 165% and 66% increase for lower level health facilities and hospitals respectively on the 2000/01 financial year§. New guidelines were instituted for management of government grants, with increased flexibility to reflect the need to channel resources to areas previously supported by user fees revenue. A pull system for commodity supplies and management was also instituted. Wages for health workers were increased in the 2001/02 financial year by 14% – 63% across the different cadres of workers and in addition management of health workers pay roll was greatly improved, to ensure better human resources management.A number of measures were instituted to counter the expected effects of this policy change. There was an immediate release of US$ 526,315 [US$ 0.02 per capita] from the Finance Ministry to the districts to allow them purchase drugs. The total Government Primary Health Care [PHC] non-wage disbursement* to districts for the financial year [FY] 2000/01 was US$ 4,454,545, [US$ 0.19 per capita], with 50% recommended for drug expenditureThis policy change provided the opportunity to study the effects of abrupt removal of direct costs of health services in Government facilities on quality of health services. We however note that there are indirect costs associated with seeking health care, but since the policy change was targeted at reducing direct costs, this study therefore focused on abolition of user fees, which is a direct cost, and its impact on quality of care. We studied how the different aspects of quality of care change as a country changes its health financing options away from user fees, with an aim to provide insights into policy actions countries could take to maintain quality of care immediately following the removal of formal user fees.The public sector services are delivered in a Primary Health Care approach through a highly decentralized system, with the sub national units [districts] responsible for service delivery since 1996. The health system is further decentralized into functional health zones , designed around the World Health Organization [WHO] Health District concept and functionally similar to the Close to Client system. At the time of the policy change [2001], there were 56 districts, and 214 HSD's. Services are provided through public, PFP, and PNFP facilities. The Health system is organized hierarchically, and is administratively managed at the national, regional and district levels. Service delivery is organized such that national and regional level facilities are equipped to respond to referrals from lower levels. At the district level, services are delivered at Health Sub Districts [HSD]**. HSDs are the implementation levels within a district and carry out planning, in-service training, coordinate service delivery and undertake supervision of lower level health units within their areas of responsibility. These HSD's are headed by HSD referral facility, which is a hospital or upgraded Health Centre IV.The National referral hospitals provide comprehensive specialist services and, in addition, they are involved in teaching and research. Regional referral hospitals provide general curative and preventive services and specialist services. They provide technical supervision, on the average, to five districts. A general hospital provides general curative and preventive services, in-service training, consultation and research to community based health care programmes. A HC IV provides general preventive and curative services, emergency surgery and blood transfusion services. HC III and II, which are categorized lower level health units/facilities [LLU], provide mainly ambulatory services as included in the Uganda Minimum Health Care Package of services [UMCP].The facilities providing these services are either Public, or PNFP facilities.The policy change was targeted at the public facilities only. As there is close collaboration with, and direct support given to PNFP facilities at the time of the policy change, these too were assessed.††; and varying poverty indices [PI]. The districts were: Rukungiri  and Soroti  for districts had well-established schemes; Nebbi , Mubende  and Rakai  with ordinary user charges scheme. Poverty Indices in Uganda range from 0.894 for the least poor district which is Kampala in the central region to 1.055 for Kotido district which is the poorest in the northern region [Qualitative and quantitative research methods were applied. The effects of the policy change were investigated longitudinally over 36 months after the abolition user fees. Information was obtained on the 12 months preceding the policy change where feasible [data for 2000 was retrospectively reviewed]. The study took place between April 2001 and June 2004. Study sites were in 5 districts. These were selected purposively, with an aim to provide regional representation, the user fee schemen region .In each district, multistage random sampling was done within categories of health facilities, [public and PNFP] and the different levels of care to determine facilities, and sites for investigative follow up. First stage sampling was for selection of HSD referral facilities based on ownership [public/PNFP] and type [hospital/upgraded Health Center IV]. The targeted output was selection of an equal number [except for districts with limited numbers of PNFP referral facilities] of referral facilities from public, and PNFP sub sectors that were either hospitals or upgraded HC IV's. Second stage was for public and PNFP LLU within the areas of responsibility of the selected stage I facilities. The total number of health facilities was 85. Of these, 14 were referral facilities , and 71 were LLU . From the catchment area of each selected LLU, one village with the highest utilization was selected in the first phase of the study amongst those with 30 or more new OPD attendants. Table Each site had a study team of six people assigned to it. They visited their study sites from a central coordinating unit every 3 months starting 1 month after the policy change. Consistency of methodology within each study site was maintained by having the same team in the same site for the entire study period. It was felt that consistency in data collection would override any limitations relating to maintaining the same team over the study period.Qualitative information was collected through Key Informant [KIs] interviews with key district and health facility officials representing the political, administrative and technical authorities respectively. A total of 140 KI interviews were conducted. A total of 71 Health Unit Management Committee members [HUMCs] at HC III and II were interviewed. Community views were sought through Focus Group Discussions [FGD's]. FGDs were conducted in public and PNFP facility catchment areas, which were determined by reviewing health facility registers and the village with the highest number of patients attending the facility was selected. FGD's, which comprised of a maximum of 12 participants each were conducted at each investigative phase. These were constituted by identifying the village chairman who provided a guide. Criteria for selection of participants were: knowledge of village issues, and representation of men, women, elderly, youth and disabled people. They must have lived in the village for the last five years and of voting age. A total of 71 FGDs were conducted. Information was collected on the therapeutic path followed by people when ill, with an attempt to track people's health care seeking behavior. Eight respondents were selected in identified villages. The starting point was the centre of the village, a pen was spinned to determine whether to start in the right or left direction. Once the direction was determined, four households were systematically selected and a questionnaire was administered to an adult [head of household or spouse] who was available and willing to be interviewed. After these four respondents, the team went back to the centre where they had started and systematical identified four households in the opposite direction. In instances where there was no adult, the next household was selected until the required number of respondents was met. We interviewed 587 persons from the communities we were investigating. Both users and non-users of facilities being investigated were interviewed, in villages served by public and by PNFP units. The purpose was not representativeness, but getting a synopsis of health seeking behavior among sampled communities.Qualitative data was collected on the following variables:Health worker variables , and1) Client behavior in the absence of user charges [changes in health seeking patterns among users and non users of health facilities.]2) Drugs and supplies: Community and health worker's views [through KIs and FGDs] on drug availability and management were sought.3) Quantitative data was collected from health records in all the sampled health facilities, to provide additional information on impact on quality of care. Proxy variables used to provide information on quality were:Drugs and supplies: Data on quantities of drug receipts and average number of stock out days per month was collected from health facility stock cards. The two drugs most commonly used in outpatients, cotrimoxazole and chloroquine, were used as proxies.1) The tools were pre-tested and translated into the local languages, and retranslated to English to ensure consistency. Transcription of qualitative data was done on the same day and data was entered into pre-designed matrix. Manifest content analysis technique was applied. Quantitative data was entered into pre-designed spreadsheets, with insignificant data entry error rates [<1%] and analysis done with significance tests done in STATA.The study was reviewed and approved by a committee constituted by the Ministry of Health department of planning and WHO country office Uganda. This committee also drew membership from the Ministry of Finance, planning and economic development and Makerere University School of Public Health, Department of Community Health and Behavioural Sciences. Permission was sought from the five district administration authorities as well as Community leaders to allow us carryout the study. Informed consent was obtained from the study participants after explaining the goals and objectives of the study, confidentiality safeguards and potential risks and benefits of the study were fully explained. The informed consent document was translated into the different local languages in the districts of study.We followed trends in drug quantities from the drug stock cards at the health facilities. These are presented here as average [averaged for LLU and referral facilities] annual quantities received and average number of days in a month the drug is out of stock for the years of the study and; drugs in relation to number of OPD cases. The findings are presented for a period of 1 year prior to the policy change, up to 3 years after for the different levels of care , and public and PNFP facilities.There was an increase in drug receipts following the abolition of the user fees in both LLU and referral public facilities as shown in Figure Regression Analysis was also undertaken, to determine if there was any significant change in drug availability after the abolition of cost sharing, in the various health care facilities.‡‿.Table It was demonstrated that the indicator of abolition of cost sharing was not significant for both the OLS regression and the random effects model. The only significant correlates of drug availability were whether the facility is publicly owned. Specifically, the public variable [where government ownership is the default category] indicates that overtime; there was a significant increase in drugs availability in public health facilities as compared to PNFP facilities. This may be partly explained by the fact that it was public facilities that lacked the essential inputs prior to the abolition of costs sharing. Thus, the increased health spending was used to increase drug availability while in the PNFP facilities, the increased spending may have been used to pay for other recurrent costs.Further investigation was done by looking at perceptions related to drug availability from the community. Almost all FGD respondents from both the public and PNFP units, throughout the study period, reported that health workers prescribe the needed drugs. FGDs in public facility catchment areas reporting that patients received prescribed drugs improved progressively during the study period. Forty four percent [44%] of HUMC and 60% of KI respondents also reported that drug availability was better in 2003 compared to 2001. In the PNFP catchment areas, majority of FGDs consistently reported that patients received prescribed drugs throughout the study period.Average annual stocks out days were much higher in public facilities compared to PNFP facilities as shown in Figure FGDs from half of public health facility catchment areas confirmed the finding that some patients do not get the prescribed drugs because they are not available. Twenty three percent [23%] of HUMC reported there were inadequate stocks of drugs although improvements in drug availability were noted in 2003 compared to 2001."Drugs are brought here but not very frequently, the quantity delivered is inadequate, the patients are too many and so these drugs can not sustain them, especially the injectable drugs" Member HUMC, public health facility June,2004.When drugs were not provided at the health unit, the users reported employing a variety of coping mechanisms. The most commonly reported coping strategy was to visit private clinics or buy drugs from drug shops. This was reported both in areas served by both PNFP and public health units, and didn't change over the period investigated."We get drugs when they are available and this has been rare since the abolition of user fee charges. We [now] normally purchase them from clinics or nearby drug shops. The poor of course go without drugs" FGD, public health facility January 2001.We get the prescribed drugs if they are there. If they are not there, they tell us to go and buy from the private drug shops because they are out of stock and are still waiting for more stock to come" FGD, public health facility June, 2004.On the average, about 80% of the health unit staff from the public facilities reported not receiving drugs and supplies on time both before and after the abolition of user fees. For PNFP facilities, this was much less as only 12–16%; of PNFP facilities did not receive drugs on time over the study period."We receive our drugs on time since purchasing is done by the dispensary. We have also been getting delegated funds, which contribute towards the purchase of drugs. We have no problem towards drug availability" KI interview, PNFP facility, October 2001.The reasons noted for non-receipt of drugs and supplies on time were further explored. District level bureaucracy was clearly a major problem hindering the availability of drugs and supplies at the public health units, and was increasingly reported over the year after the abolition of the user fees."...we don't get drugs and supplies in time. Government takes so long to deliver these necessities but during the time we had cost sharing buying of drugs was easier because we had money at hand" KI interview, public facility July 2001.However, for the PNFP units, absence of funds is also quite prominently mentioned over the years. District bureaucracy was also noted, but was not as much a problem as in public units.The quantity of drugs prescribed per case remained fairly constant in both public and PNFP facilities except for cotrimoxazole in the Public lower levels where a slight increase is noted. This is shown in Figure Health worker behavior is an important component of quality health care provision. Qualitative information was sought from FGD's and KI interviews related to the health worker attitudes, motivation and availability. The majority of FGD's in public facility catchment areas reported that health workers were hardworking, good, and dedicated to their work consistently throughout the period assessed. This was also observed in the PNFP throughout the study period."They are good staff, they advise us on the right drugs to use, the only problem is that the unit doesn't have drugs yet at the clinics we cant afford the charges" FGD, public facility, July 2001.A few negative responses made in public facility catchment areas included staff being too few, rude, not available when required, and were unqualified."The health workers don't care. The one prescribing is slow, does his own things. You can go there at 9:00 am and leave at 2:00 pm [when] you end up giving up and go back home" FGD, public facility, October 2001."And they are also very rude, there is also segregation among the nurses, those who are known are treated properly and first, but those who are not known may end up mourning for the children" FGD, Public facility, 2004.The most common problems staff at the health unit reported when carrying out their duties were lack of transport, inadequate staff numbers, and poor support services like water, lighting, inadequate allowances and drugs. These made up 68% of all the responses, with the trend in reporting similar over the study period.In public facilities, most of the staff had noted an increase in their income just after the abolition of user fees. However, the proportion of those with the view that their salaries had increased reduced over the study period. The main reason that could be attributed to the perceived reduction in income just after the abolition of user fees was a reduction in allowances they received."I no longer participate in outreaches, hence no allowances for that. Completely no allowances in the last 3 months except for lunch allowances, no fuel to facilitate my movements" KI Rakai hospital, Rakai district. July 2001.However, in the later part of the study, salary delays were the prominent issue among the staff.Staff motivational issues were further explored among HUMC members. About 50% of the HUMC's reported that staff were not motivated in any way. However, of those that reported some form of motivation, there was a significant drop [from close to 60% to below 10%] in reporting of allowances as means of motivating staff, with verbal appraisal and encouragement increasing [from close to 30% to over 50%] over the study period as the main method of staff motivation.Verbal appraisal was less used as a motivational means in the PNFP facilities. The array of methods used to motivate the staff in PNFP facilities was wide. These included ensuring staff are paid timely, offering free treatment to staff and allowing them to work elsewhere such as teaching during their free periods.During the fourth investigative phase [12 months after the policy change], we studied the therapeutic path patients take when seeking care in the absence of user charges. This was aimed at exploring the numbers of health care options people in the community use and the average time spent at each option. Both users and non-users of the public, and PNFP health facilities were interviewed. It was demonstrated that, health care seeking options were numerous. However, during analysis, health care seeking options were stratified into public or PNFP facilities, private clinics, drug shops and traditional providers.Of all the respondents, 285 and 136 persons from areas served by public and PNFP facilities respectively reported being users of these facilities, while 86 and 80 reported not using them. The majority [90%] reported favorable final illness outcomes from care sought in areas served by both public, and PNFP facilities.The number of providers seen in order to achieve the illness outcomes they had by the different categories was reviewed and is shown if Figure Among the people that reported not using the health facilities under investigation, we reviewed the providers of choice. Private clinics were the most used health care option among those not seeking care from the public facilities [41%]. These were however only used by 17% for the PNFP facilities among whom the more common health care providers were tertiary care providers.Finally, we reviewed the time spent with each provider. The respondents were asked how long they spent with each provider they went to, before choosing to move on to the next provider.The average time spent at each provider increases with the number of providers seen as shown in Figure Regarding utilization of health facilities, there were marked in increases in utilization in public facilities and slight increases were also noted in PNFP facilities. Percapita utilization of Out Patients Department in government and PNFP facilities increased from 0.43 in 2000, to 0.6 in 2001 to 0.8 in 2004 .We have reviewed some aspects of quality of care that are likely to provide insights into overall quality changes following the abolition of user charges in health facilities in a developing country setting. There are two aspects of quality of care in any health system; observed [technical] and perceived/consumer assessed . TechnicThe findings show that although drug receipts were improved after the abolition of user charges, community views showed that many patients were not able to obtain their prescriptions. However, a small number of people in the communities were able to. As this was the similar situation before the policy change, we can say that in spite of charging communities fees, they felt few were receiving drugs. This situation is similar to what had been observed in other areas where the ability of user fees to effect meaningful quality improvements have been challenged ,11,14. TIt was observed that the general view of the public was that there was no availability of drugs in the health centers. Although this view is contrary to the actual data obtained since there was an increase in drug receipts, it should be noted that there was an increase in visits to the health centre resulting in proportionately fewer people receiving their drugs and an increase in the number of disgruntled clients. The observations from this study does not also support the fact that there was rationing of drug by the health care workers as there was no reduction in drugs per/OPD case.With user fees, health facilities were able to make drug purchases outside the public system that were based on their requirements. The policy change implied a shift to predominantly purchase through the public system with a resultant reduction in flexibility and unnecessary delays. This is seen by the high reporting of district bureaucracy as the main cause of delays in getting supplies to the health facilities.During the era of user fees, many support staff and technical staff were receiving wages [for those who were not on the public service payroll] and or allowances from user fee revenues. At the abolition of user fees, many of the support staff had to be laid off and in many cases the income of some of the technical staff dropped. This resulted in human resource crisis in some of the centers, as the limited staff had to deal with increased load of patients since the services and especially the drugs were now free to the population. To mitigate against this, there was an attempt at accelerated recruitment of health workers by the centers. The effect of the accelerated recruitment of health workers was not easily discernable due to lack of credible information on health work force data before and after the policy change. However, indirect evidence  suggests two situations. The health workers either adapted to the increased workload favorably, or the increased recruitment was adequate to cover the increased needs due to the higher client load.Health workers attitudes were poorer in the public health units as opposed to the PNFP units possibly as result of a poorer incentive structure. The policy change had the potential to even make this worse. Presence of use fees implied that health workers had resources available for use when required, as opposed to the public resources that have stringent guidelines for spending and accountability attached to them. The government response to the abolition of user fees included an increase in resources to the health workers, at levels much better than before the abolition of user fees. Continued health worker disgruntlements after the pay increases were therefore due to two possibilities. The loss of a source of resources that were readily available as needed  or the amounts of fees that were being collected were significantly more than was being reported, and so there was a real decrease in the health workers income that wasn't compensated for adequately by the pay increases.When the present health care seeking patterns of communities is examined, it was observed that the inability to satisfy clients was not a characteristic of the public facilities only. This is because, all the significant health care providers presently offering services to the communities are not able to holistically manage the medical needs of their clients. Thus, the clients have adjusted their expectations in line with the services available from the different providers. This implies that, from the consumer's point of view, there is wholesome low quality of care among all providers of care, not just the public facilities. The presence of user charges [which all the other care providers still employ] does not imply there will be improved care quality from the consumers' viewpoint.From these findings, we can conclude that the levels of technical quality of care attained in a system with user fees are not necessarily a result of the user fee policy, as this quality can be maintained, or even improved without the fees. Such quality can be achieved through adoption of basic system modifications, coupled with marginal increases in funding that are within the reach of developing countries. This is based on targeted increases in allocation to health, with the focus on ensuring more resources are available at the implementation level, and a systemic change in the way in which health services are managed particularly regarding flexibility in the use of public funds at the service delivery level to allow them adjust the required inputs in line with locally determined requirements. The initial response should commence before the actual policy change. Other mechanisms for providing financing to the financing intermediaries that would strengthen quality of care can also be explored, such as Output Based Aid approaches.The policy change was aimed at limiting financial constraints to users, but is not the only option available for countries. These other financing options, such as community based insurance schemes have the potential to achieve the similar aims, if they are able to have equitable involvement of vulnerable persons. Many of the schemes in Uganda operating through public facilities had to shut down, as the policy change was able to provide most of the benefits they were providing, but in a more equitable and efficient manner.However, the residual implications of perceived reduction in quality, particularly relating to the reported reduced motivation, and a potential for increase in unofficial payments among health workers illustrates the residual implications of such a policy change. A trade-off between these residual effects, and the welfare gains by the population should guide move towards such a policy change by a country. Further analytical work is needed to quantify the impacts of these options in more detail.Finally, we conclude by stating that the management of quality in any system is a sub function of the overall management process. As such, improvements in management of quality are usually heavily driven by improvements in overall management. This was seen in that the responses to the policy change that led to quality improvements were designed to also lead to overall improvements in management of services in a holistic manner. Targeted and patchy changes focusing only on quality issues may not lead to the same outputs as we have demonstrated. What are needed are comprehensive changes across different facets of management of health services to maintain quality.The authors declare that they have no competing interests.JN-O participated in conceptualization of the study, data collection and analysis and, led the drafting of the manuscript; HK participated in conceptualization of the study, data collection, analysis and drafting of the manuscript; LA participated in conceptualization of the study, data collection and analysis and, drafting of the manuscript; FB participated in data collection, analysis and reviewed the manuscript; SAO participated in data analysis and reviewed the manuscript, OW participated in conceptualization of the study, data analysis and writing of the manuscript.* Public resources are disbursed in form of grants to different intermediaries† Guidelines for utilization of PHC conditional grants; MoH; 1998.‡ Background to the budget MoFPED; 2001/02§ Background to the budget MoFPED; 2002/03** A HSD, which is headed by a hospital or an upgraded HC IV and located at a country level, serves an average population of 100,000 population. It is a network of community-based health centers, which provides support to the lower-level health centers and manages referral cases. A HC III is located at a Sub country level and serves an average population of 50,000. A HC II is located at a parish level and serves an average population of 25,000.†† Some districts in the country were implementing a fee-for-service scheme [Bamako initiative type of cost recovery], some had normal user fees, while a few had not/were just starting to implement any form of cost sharing.‡‡ We also tried estimating the fixed effects model which unfortunately was dropping two key variables size and ownership of the facility.The pre-publication history for this paper can be accessed here:


Sir,British Journal of Cancer, October 18, p 1580). These researchers described the development of a genetic model for familial breast cancer, named BOADICEA, which takes into account the simultaneous effects of BRCA1, BRCA2 and other genes. There is a considerable need for such predictions for purposes of management of women referred to genetic clinics and for the considerations of eligibility of any prophylactic interventions in both the clinical and research settings.With much interest we read the paper by Antoniou and colleagues  family. The risk for breast cancer in these families is increased because of the combination of both breast and ovarian cancers in the family, which highly points to BRCA1 mutations. The BRCA1 mutation probability as predicted by the BOADICEA model is high, 40.9%. The model then predicted her risk of breast cancer at only 13%. For a clinician, this risk estimation is hard to understand and feels illogical. It seems that in the risk prediction by et al model, the familial clustering of breast and ovarian cancer is explained by three genes, BRCA1, BRCA2 and a hypothetical third gene BRCAu. This third gene was modelled to explain all familial clustering of breast cancer unaccounted for by the BRCA1 and BRCA2 genes. The model parameters were estimated using published estimates of population incidence and relative risks.Recently, et al model is not easy to use in clinical practice. For this reason, we extended the easy-to-use Claus tables into the ‘Claus plus method’ based on the Jonker model (As well as the BOADICEA model, the Jonker The authors have mentioned several improvements to be made for their multi-purpose BOADICEA model like genotype-specific incidence rates, risk for other cancers and allele frequencies. Besides this, we would like to recommend paying attention to the applicability for clinical practice. To attain full development for the BOADICEA model, the authors should be in close contact with the ultimate users in clinical practice.


Child mental health is a goal of high priority for parents in post-modern society, as many stressors may threaten the psychological well-being of the few children that are born in the so-called developed countries. By noting the high prevalence of mental disorders during childhood and adolescence parents are aware how fragile the psychosocial development of their child may be. Aiming at these parental concerns, many programs claiming to improve the mental health of children are marketed by different vendors outside of the professional mental health services. Such programs comprise sports activities, mental training programs, dietary programs, and other complementary interventions.According to their professional guidelines, psychiatrists and psychotherapists are used to base their interventions on evidence, e.g. randomized controlled studies showing the efficacy and effectiveness of a specific intervention and the absence of harm caused by this intervention. Outside of the mental health field, many programs and interventions are offered by claiming to maintain or improve the mental health of children; however, no empirical evidence is presented. Parents seek the advice of therapists about the usefulness of such programs to support their child, and even more parents may expect that such interventions may be equivalent to professional child psychotherapy or child psychiatry, if their child has behavioural or emotional symptoms. On the other hand, therapists may tend to counsel patients to utilize additional programs and activities, thus suggesting a positive effect on mental health, social competence, etc. Usually the impact of these interventions on behavior and psychosocial development is not investigated.Child and Adolescent Psychiatry and Mental Health offers an innovative empirical approach to measuring the impact of participation in martial arts on child mental health. One would expect benefits of such an intervention for a variety of children, regardless of specific diagnoses, therefore the authors' decision to conduct a secondary analysis of a large population-based longitudinal cohort study guarantees results of high external validity. Based on the Early Childhood Longitudinal study, the authors were able to analyse teacher reports of several thousand children's classroom behavior at two time points - 3rd grades and 5th grades - in relation to previous participation in martial arts. The proportion of about 6 to 7 per cent of U.S. children participating in martial arts training is striking. Although martial arts as defined in this study is a heterogeneous type of intervention and the dosage of this activity is not controlled for, the external validity of the study is high due to the large and quite representative sample. The study design is innovative for a program evaluation, as it used epidemiological data for a program evaluation. The results indicate that effects of martial arts as provided in the U.S. on the children's classroom-behavior are absent, at least from the teachers' perspective. It can be concluded from this study, that the proposed broadband impact of martial arts training cannot be demonstrated.Martial arts are an example of an activity claimed to improve child mental health, but whose possible therapeutic benefits remain obscure. The study of Strayhorn and Strayhorn  publisheThis study provides preliminary results on the effectiveness of martial arts for the general mental health of children. More studies are necessary to determine the effectiveness for children with special needs. E.g., differential effects might be found for healthy children, children with internalizing disorders, and children with externalizing disorders. These questions can be optimally addressed in prospective, randomized controlled studies of treatment as usual alone vs. combined treatment as usual and participation in martial arts vs. no treatment.Further studies of complementary or supportive programs and interventions are needed to inform clinicians and families on the usefulness of specific activities or programs to enhance the psychosocial development of children. Research of this kind builds bridges to the daily challenges that are faced in routine clinical work with children, adolescents and their families. Therefore, the editors of CAPMH would like to encourage researchers from all disciplines to submit papers relevant to this still under-investigated area.


Medicine access is an important goal of medicine policy; however the evaluation of medicine access is a subject under conceptual and methodological development. The aim of this study was to describe quantitative methodologies to measure medicine access on household level, access expressed as paid or unpaid medicine acquisition.Searches were carried out in electronic databases and health institutional sites; within references from retrieved papers and by contacting authors.Nine papers were located. The methodologies of the studies presented differences in the recall period, recruitment of subjects and medicine access characterization.The standardization of medicine access indicators and the definition of appropriate recall periods are required to evaluate different medicines and access dimensions, improving studies comparison. Besides, specific keywords must be established to allow future literature reviews about this topic. Universal medicine access is a major goal of the World Health Organization (WHO) and of most countries with respect to medicine policy. This goThe global situation of access to essential medicines is still considered critical. Although the access to health care is a fundamental human right and includes essential medicine access, the World Health Organization (WHO) estimates that nearly two billion people (1/3 of world population) are not receiving regularly all medicines they need. In developing countries the budget for medicines corresponds to 24-66% of national health expenses, supporting the monitoring of access to medicines in these countries /drug utilization [any field], more than 9000 titles and/or abstracts were retrieved until July, 2008. After reading titles/abstracts, nearly 8750 papers were excluded because data collection was not home based. The papers were mostly about demand, medicine availability, in the public/private sector, medicine pricing/expenditure in the public/private sector, medicine prescription studies, health insurance coverage (based on secondary data), co-payments impact or qualitative studies. From the remaining papers, around 180 were excluded because did not evaluate access or were review papers. In about 70 papers we could not identify by the abstract if the approach was the desired (home-based data collection about access), and in those cases full texts were read and even if medicine access was not the main outcome the study could be included.The references of selected studies were checked to find other articles that could be included in the review. Besides, author searches were carried out using relevant names in the field. When more than one study was originated from the same data collection, only one study was included in the review.After manual search, impaired by the lack of specific keywords to evaluate medicine access, nine studies were included in this review ,11-18.In Additional file Medicine access was the main outcome of six out of nine presented studies ,11,15-18Nearly half of the studies assessed the outcome by instruments developed by the researchers ,15,16,18Additional file The criterion employed to include subjects in the specific medicine access evaluation was not similar between studies. Some studies recruited individuals based on the need for the prescribed medicine ,15,17, oIn terms of assessed medicines, six studies investigated all medicines types -14,17,18With respect to the definition of access, the studies presented distinct approaches and distinct recall periods, from 15 days to 12 months. Two studies defined access as obtaining medicines that were prescribed in the last visit to the doctor during the 15  days priAdditional file From all studies, only one relied on internet information (self-administered questionnaire) , eight sThe acknowledgment of methodologies available to evaluate medicine access on household level is the first step to establish strategies that will increase the understanding of individual barriers to medicine access. However, when summarizing methodologies, the first obstacle is the search itself that demanded different strategies and intense manual work. The literature about medicine access on household level is sparse. Besides, the available studies relied on distinct methodologies, impairing comparison. The following is a discussion of obstacles to the review, and adjustments to methodological approaches that could allow future comparisons. Although our intention was not to evaluate or to suggest new sampling methods to measure medicine access, adequate sampling techniques and high response rates are fundamental methodological aspects to assure precision and validity in any quantitative study.The terms "medicine access" are not recognized as keywords, making the search about this topic even more complicated. The search for studies about medicine access on household level results in many health services and/or medicine access/use studies. However, chronic users (chronic diseases medicines) or regular users  may have medical indications to use drugs without recent or regular visits to a doctor. Besides, some medicines sold over the counter (antithermic medicines) are not evaluated by this approach. Therefore, a specific keyword to describe medicine access is needed, to detect studies about this theme avoiding manual searches.The study of medicine access as a secondary goal -14 may r"obtaining the needed medicine" [One of the biggest obstacles to gather studies about this topic is the diversity of indicators and dimensions used in different definitions of the outcome, with no agreement between studies. Even though during selection of the studies for this review, a single definition was adopted - edicine" , an atteedicine" , we obseedicine" , to evalMedicine adherence was the definition of access used in one study , consideThis review did not include studies about medicine access for treatment of STD/AIDS and those designed to evaluate only people covered by health insurances - most studies carried out in the US. We also restricted the search to home-based data collections. This strategy may explain the high number of South American publications retrieved.Three studies carried out in Brazil belonged to the World Health Survey, a multicenter (71 countries); to the SABE project , a study that took place in six Latin American countries and The Caribbean; and to the National Pharmaceutical Evaluation, using the methodology suggested by the World Health Organization for all countries,13. We cThe increase in publications after 2004 may indicate the concern of researchers with the monitoring of medicines national policies, attempting to reach the goals of WHO for the period 2004/2007 in response to the challenges in essential medicine access .Studies on national, state, regional or city level result in different conclusions about medicine access. Distinct levels may evaluate either national drug policies assistance or specific national, regional or local programs . BroaderThe lack of consistency between instruments used to evaluate medicine access and the large variability of approaches poses difficulties to compare the studies and confirms the subject as an area under major conceptual and methodological building .Most studies recruited individuals using as starting point a visit to the doctor (during a certain period) and investigated if the prescribed medicine was obtained. Therefore, some instruments reveal more about health services access than medicine access . This kiThus, the choice for an instrument to study this topic must consider the population type ; the age group to be evaluated ; and the kind of medicine that will be evaluated , only then the recall period and recruitment methodology can be established. Those aspects will influence the structure of the question(s) about access; the chosen strategy to administer the questionnaire (face-to-face or self administered); and the respondent definition . The quality of information will depend on such characteristics and on the dropout rate of the study.The kind of sample to be studied  will determine the kind of question about access to be included in the study. When the general population is interviewed, the study can describe how medicines are obtained by all socioeconomic groups. When studying public health services users and/or when the population belongs to low socioeconomic groups, the main aspect to be investigated is medicine free supply.In addition to the kind of sample to be studied, age groups must be considered as well. Many studies evaluated all age groups and all included the elderly population. Elderly people present high prevalence of chronic conditions and constantly need to take more medicines continuously, while children and adolescents mostly need medicines to treat acute health problems.A great limitation found in the reviewed studies is the use of the same methodology to investigate access to different types of medicines (prescribed for chronic/acute diseases and even not prescribed), hindering the quality of information. The evaluation of medicine access to treat chronic or acute conditions must rely on different recall periods. Besides, during the planning of the study, the goals of the research must be clear to define the inclusion or not of over the counter medicines, adapting the question for this definition. When asking if the individual restrict medication during a certain period, over the counter medicines will be included as well.In studies about medicine access recall bias is a potential source of error; respondents may recall better information of the medicines they had access to. In an attempt to control such problem, the recall period to be used in medicine access studies depends on the medicine access characterization, on the type of medicine to be evaluated and on the studied age group.As described previously, each medicine access definition considers different aspects. The access, defined as obtaining prescription drugs, is employed to investigate prescriptions from the last visit to the doctor during a certain period (15-30 days), which is useful to measure medicine access to acute health problems, and also to evaluate chronic use of long-term medicines (12 months), as long as restricted to the medicine type for specific conditions. On the other hand, the underuse showed by one of the studies , was basUsually, to measure medicine access for acute problems, a short recall period can be used and for chronic conditions longer periods may be indicated to evaluate problems affording prescriptions to continue treatment. Therefore, in studies investigating medicine access for the treatment of chronic and acute health problems, the adoption of distinct recall periods must be considered.Often before measuring access it is necessary to define inclusion criteria or use filter questions in order to allow or restrict the type of medicine evaluated. Medicine access studies are usually carried out within studies about health services utilization because there is a need for a diagnosis and consequent prescription. Because of that, many times the recruitment of individuals for the study takes place after the diagnosis of a specific illness and treatment prescription or after a doctor visit that resulted in a prescription. Another approach is to ask about medicine use to treat specific diseases or to consult a list of health service/facility users that attended the service during a specific period. Consequently, the whole population investigated by such studies may be much larger than the sample considered during the evaluation of medicine access.The questions to evaluate access focus mainly on two aspects: medicine use/acquisition and underuse (due to costs). According to the indicators suggested by WHO, these evaluation strategies may actually measure the following access dimensions: availability, affordability or both . The queMost studies had large samples. On the other hand, the two studies based on phone or internet interviews presented high refusal rates ,17. DespWhen the name of medicine is collected two different analysis are possible: the first uses as denominator the individuals and evaluates the amount of medicines obtained compared to the needed number categorizing the result as total, partial or no access; the second uses the number of medicines as denominator and measures access to each pharmacologic group or chemical name of the medicine. Even incomplete information can be used, for example, if there is report of a medicine prescription for a specific condition but the name of the medicine is not available, the questions about medicine access can still be answered or the reason for the lack of access, linking these data to the condition that the medicine was prescribed for.On household surveys, to collect the name of the medicine demands good training of the staff, considering that interviewees usually are not able to inform it accurately. When this is the case, to ask for the medicine packaging or prescription and use help from other informers aware of medicine regimen may increase the quality of data.When study subjects are children or elderly people, usually they are not aware of the details of medicine use and access. For children, one of the parents needs to provide the information while among the elderly usually a proxy or a person in charge of care is interviewed. Some reviewed studies do not allow identifying the respondent; however this information is extremely important to evaluate the accuracy of information. Another group of studies excluded individuals unable to respond to the questionnaire, and these individuals may need to take regularly many medicines, presenting higher risk of access barriers.This review summarized methodologies employed to evaluate medicine access on household level. In spite of the increasing number of publications in the last five years, due to the relevance of the theme, it is surprising that such small number of studies was detected.This paper revealed the variety of methodologies to evaluate medicine access with respect to recall period, sampling and characterization of the outcome - medicine access.Therefore, the standardization of medicine access indicators such as acquisition, expenses and categorization according to the dimension of evaluation  is needed, as well as the establishment of the appropriate recall period to assess each medicine type and each access dimension, increasing comparability across studies. Thus, as there is no standard methods to evaluate household-level medicine access, as defined previously in this review, we propose studies targeted on population access to all medicines, regardless of consumption pattern (chronic or acute). Although both consumption patterns are assessed together, specific questions must be employed for on each situation. For acute problems, a 15-day recall is appropriate, linking the question to the acute health problem (including self-medication) or to the medical appointment within this period  always asking for the package and prescription, to obtain the medicine's name accurately. With respect to chronic problems, a longer recall period (from 30 days to twelve months) would be appropriate to investigate underuse of the medicine and the reasons for it. On those situations, the question must be linked to the disease and package and prescription should be used as well. However, on both approaches the goals of the study, population and age groups to be studied must be established, to define the respondent of the interview. Besides, specific keywords must be used to allow future studies about medicine access.The authors declare that they have no competing interests.VMVP worked on the project, literature review and writing of the paper. AGF worked on the project and writing of the paper. ADB worked on the project and writing of the paper. MFSM worked on the literature review. MRD worked on the writing of the paper and translation into English. All authors were involved in the final review of the manuscript and all authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/146/prepubTable 1. Description of studies measuring medicines access on household level.Click here for fileTable 2. Population/medicines studied and definition of medicines access on household level.Click here for fileTable 3. Question/Logistics of instrument's administration in studies evaluating medicines access on household level.Click here for file


Hairdressers often come into contact with various chemical substances which can be found in hair care products for washing, dyeing, bleaching, styling, spraying and perming. This exposure can impair health and may be present as skin and respiratory diseases. Effects on reproduction have long been discussed in the literature.A systematic review has been prepared in which publications from 1990 to 2010 were considered in order to specifically investigate the effects on fertility and pregnancy. The results of the studies were summarised separately in accordance with the type of study and the examined events.A total of 2 reviews and 26 original studies on fertility disorders and pregnancy complications in hairdressers were found in the relevant databases, as well as through hand searches of reference lists. Nineteen different outcomes concerning fertility and pregnancy are analysed in the 26 original studies. Most studies looked into malformation (n = 7), particularly orofacial cleft. Two of them found statistically significant increased risks compared to five that did not. Small for gestational age (SGA), low birth weight (LBW) and spontaneous abortions were frequently investigated but found different results. Taken together the studies are inconsistent, so that no clear statements on an association between the exposure as a hairdresser and the effect on reproduction are possible. The different authors describe increased risks of infertility, congenital malformations, SGA, LBW, cancer in childhood, as well as effects from single substances.On the basis of the identified epidemiological studies, fertility disorders and pregnancy complications in hairdressers cannot be excluded. Although the evidence for these risks is low, further studies on reproductive risks in hairdressers should be performed as there is a high public health interest. People in many occupations are exposed to different requirements and stresses in their everyday working life. In hairdressing, women and men are exposed to physical and mental stress, as they have to stand for a long time. Moreover, they often come into contact with chemicals which are components in hair care products. The substances can be found in applications for dyeing or bleaching hair, for permanent waving and in styling products. The use of these preparations is an essential component of the occupation as hairdresser. Health can be impaired by the exposure to these chemicals. For example, widely used agents such as persulfates, organic solvents and endocrine disrupting chemicals were described in various reviews -3. The cFor example, in 2007, 277,000 people were employed in the hairdressing occupation in Germany. Of these, 75% were 45 years old or younger. 90% of them were women; thus hairdressers are a significant group of employed women . Once ocThis systematic review gives an overview of publications of epidemiological studies on the association between occupational exposure in the hairdressing profession and their effects on the fertility and pregnancy of women in this occupational group.hairdresser/s, hair stylist/s, hairdressing occupation, hairdressing profession, professional hairdressing or professional hair care in combination with reproductive disorders, reproductive outcomes, fertility, infertility, subfertility, menstrual disorders, pregnancy outcomes, malformations, preterm birth, stillbirth, perinatal death, low birth weight/LBW, small for gestational age/SGA, spontaneous abortion, as well as time to pregnancy/TTP.A search in MEDLINE from 1990-2010 was performed to search for epidemiological studies on health risks in hairdressers; the most recent update was performed on 31 May 2010. The key words refer to the occupational designations as well as to the different reproductive disorders. Diagnoses related to reproduction are especially unfavourable events, such as infertility and subfertility, prolonged time to pregnancy (TTP), spontaneous abortion, preterm birth, stillbirth, low birth weight (LBW < 2500g), small for gestational age (SGA), congenital malformations and delayed development of children. This led to the following search terms: Subsequently, further publications were identified from the lists of literature and used for the work.The studies were selected in accordance with the following a priori defined inclusion criteria:- Study design: Limitation to original studies - reviews and empirical studies- Study content: With respect to the occupation as a risk factor and the occupational exposure- Study population: Occupation as male or female hairdresser- Outcome: Job-related health risks in reproductionThe studies are classified into occupational studies and hairdresser studies. Occupational studies examine multiple sections of the working population for a defined disease or exposure and differentiate the risks for different occupational groups. On the other hand, hairdresser studies define hairdressers as the study population and compare them with other populations or occupational groups with respect to health risks.The most important characteristics and data of all included studies are shown in Tables Additionally, the risk estimate for the target diagnosis of each study is presented in Table The search query resulted in a total of 34 literature entries. 21 original studies from this were used for the review. The remaining studies did not fulfil the inclusion criteria and therefore could not be considered. Additionally, 7 relevant studies from the lists of literature in identified studies were used for the review. Therefore, a total of 28 publications on fertility disorders and pregnancy complications in hairdressers fulfilled the inclusion criteria. Mainly women were included in the examinations.One review, as well as 11 original studies, concerns general occupational studies Table .Thulstrup et al. examined in their review the risks of specific birth defects in relation with maternal occupational exposure during pregnancy . 26 studA French prospective cohort study pursued the question of the risk of malformations due to exposure to solvents . In thisA Canadian case control study dealt with the question of whether an occupational chemical exposure during pregnancy increases the risk of stillbirth . The expIn three American federal states, it was examined whether there is a link between the occupation of the parents and brain tumours in their offspring (astrocytoma) . If the In contrast to this, in a study coordinated by the International Agency for Research on Cancer (IARC) in Europe, no association between brain tumours in children and the occupation of the parents as a hairdresser was found .In another case control study, the risk of developing a neuroblastoma was examined in correlation with the occupation of the parents . ChildreBianchi et al. examined whether there was a possible association between the mother's occupation and teratogenic risks during pregnancy . IncreasA multinational European study examined the risk of oral clefts in childhood in relation to the mother's workplace exposure . PossiblNguyen et al. came to a similar result: they found that the children of hairdressers had an increased risk of the malformation orofacial clefts . HoweverIn an English study, the occupational exposure of the mother to endocrine disrupting chemicals (EDCs) was examined with respect to hypospadias . The resAn increased incidence of renal cancer in the children of male hairdressers was found during an evaluation conducted by the Swedish Cancer Register on cancer in childhood and the occupation of the parents . In contVrijheid et al. analysed data from the National Anomaly Register of Wales and England for the risk of hypospadias in correlation with the occupation of the mother and the exposure to potential endocrine disrupting chemicals . All neoIn summary, 11 occupational studies were carried out in which hairdressers were included. Four of them showed a statistically significant risk of developing a reproductive disorder. However, these disorders are very different: an increase in risk was found for renal carcinoma if the father is a hairdresser , as wellKersemaekers et al. focused their review on the question of reproductive disorders in hairdressers through the exposure to chemicals . In thisA retrospective cohort study performed in the Netherlands has analysed possible reproductive disorders in 4,236 hairdressers and 2,932 assistants in clothing shops . The subIn another assessment of this cohort, Kersemaekers et al. compared the neurological development of children by using the age when they reached certain significant developmental phases: first step, first word and first sentence . FurtherFor the period from 1973 to 1994, a Swedish cohort study examined the reproductive outcomes of hairdressers with a control group from the general population . In thisPregnancy outcomes among hairdressers and the developmental milestones of their children were examined in a Danish population-based prospective cohort study . The expIn the Netherlands, Blatter et al. examined menstrual disorders through chemical exposure as an indicator for reproductive disorders . In thisThe aim of the study of Gan et al. was the examination of menstrual disorders in relation to permanent waving and exposure to the ingredient thioglycolic acid (TGA) . They coIn Spain, the effects of occupational activities on the reproductive health of hairdressers were examined in comparison to assistants in clothing shops and office employees . The stuIn a further analysis of this data Ronda et al. showed results in pregnancy outcomes of hairdressers . IncreasAxmon et al. examined whether occupational exposure as a hairdresser negatively influences fertility, as measured by the time until the beginning of pregnancy or the risk of spontaneous abortion . In compThe association between hairdressing and smoking and infertility and spontaneous abortion was examined in Norway . The anaIn an American study on premature ovarian failure (POF), Gallicchio et al. compared the workplace exposure of hairdressers with other occupational groups . The autData from the Swedish Birth Register for the period 1983-2001 was used to examine the pregnancy outcomes of women who worked as hairdressers during pregnancy . In thisIn Denmark, Hougaard et al. selected women with the diagnosis of infertility for a hospital-based study . This diFor a Swedish cohort of women who had graduated from vocational schools for hairdressers between 1970 and 1995 the parents were initially identified and subsequently the sisters through a register data search . For theIn Finland, the data from hairdressers, beauticians and teachers was selected from the National Birth Register and their risks of negative results of pregnancy were analysed in relation with the occupation . As littIn summary, a statistically significant increase in risks to reproductive health, as well as a lack of association or a non-significant association can be shown Table  for the This systematic review focuses on the effects of occupational exposure to chemical substances in hair care products on fertility and pregnancy in hairdressers. The review shows that the results of the included studies are inconsistent. No unambiguous association between the exposure in the workplace and the risk of reproductive disorders can be derived from the described studies. However, evidence for a possible increase in risks has been found repeatedly.Studies on reproduction in hairdressers often target specific outcomes and the occurrence and frequency are compared with other population groups. The effects of specific substances on fertility and pregnancy in hairdressers are rarely the main focus.Pregnancy outcomes were investigated in several studies with a wide range of different diagnoses. One of the most frequently examined outcomes in this context was the risk of spontaneous abortion among hairdressers. Increased risks were found in the study by Baste  and a DuAs shown in the review, the reports present varying results as regards reproductive disorders. Therefore, it is still possible that the health of hairdressers is at risk with respect to fertility and pregnancy.Similar results were found in a review by Kersemaekers et al. 15 years ago . To our Thirdly, factors which explain the inconsistent results could include differences in treatments and fashion trends, differences in education and training between countries, changes in occupational environment, as well as different study designs and different reference populations.Two different examination methods are used for risk assessment. The occupational studies focus on employees or specific exposure in general. With this study design, many occupational groups are examined, with the consequence that only a few hairdressers are included in the assessment. Small sample sizes lead to a low statistical power. This could be an explanation why in some studies elevated risks occurred in male or female hairdressers, but these were not statistically significant ,20,21. BIn contrast to this, the hairdresser studies focus on the group of hairdressers and compare them with other occupational and/or population groups with respect to their occupational risk as regards reproduction. Assistants in clothing shops are preferred as a control group as they are considered to be rather similar with respect to the level of education, socioeconomic standing, and the physical and mental workloads. Additionally, different exposure in the workplace can be assumed, with the result that health risks for hairdressers can be observed as a factor of the activities typical of their occupation. Differences in age and smoking behaviour are often controlled by adjustment. With the exception of methodological deficiencies, this study design gives clear statements on hairdressers with respect to their risks. Many hairdressers participate in these studies and the exposure can be assessed more exactly.Exposure comparable to that of the hairdressers can be assumed for the group of beauticians. In some countries hairdressers may also called cosmetologists, stylists or beauticians. Some studies have reported increases in the risks of spontaneous abortions , SGA 3838 and loThe exposure assessment is an essential problem in occupational studies. The assessment is used very differently in individual studies and ranges from the simple designation of the occupation "hairdresser" to the differentiated designation of the activity during which individual hair cosmetics are used, as well as their times of use. However, the occupation alone cannot serve as a substitute for data on exposure itself, as this does not permit its exact determination. Occupation only provides a rough measure of exposure, which can vary within the occupational group. Consequently, the assessment of the actual risks for hairdressers is very inaccurate and can possibly underestimate or overestimate the risks of hairdressing. A valid exposure assessment is necessary for an exact assessment of the occupational situation resulting in health risks. Hairdressing work can be associated with a variety of chemical contacts, which arise through the use of hair care products for washing, dyeing, bleaching, styling, spraying, as well as for perming, and media for cleaning and disinfecting the workplaces. In this environment, exposure is predominantly dermal or inhalative and depends in particular on the duration and frequency of the performed activities and their intensity. Precautions can minimise the exposure. If the room is adequately ventilated and the hairdresser wears gloves, the chemical exposure at the workplace can be reduced ,45.Another essential aspect is the study period. The working environment and also the hairdressing occupation are subject to constant change: older products are taken off the market and new formulations are used. Legal regulations and recommendations  are changed due to new knowledge and thus can influence the exposure at the workplace and the health risks of hairdressers. Through the assessment of two time periods before and after changing the regulations in the Netherlands, the study of Kersemaekers et al. shows that the risks of pregnancy complications and developmental disorders was clearly reduced as a result of improved working conditions ,26.In addition to chemical exposure, the daily working time and physical stress, such as standing for a long period of time and unfavourable working postures, additionally influence the health of hairdressers. In a systematic review, Bonzini et al. showed that these factors increased the risk of preterm births and LBW children . A meta-According to the available epidemiological studies, a risk of fertility disorders and pregnancy complications in hairdressers cannot be excluded. However, the evidence for increased reproductive disorders is currently low. Therefore, further studies on specific outcomes or on specific substances used in the hairdressing occupation and their adverse effects on reproductive health are needed.The authors declare that they have no competing interests.MH has made substantial contributions to the interpretation of data and has been involved in revising the manuscript critically for important intellectual content.MD has made substantial contributions to the interpretation of data and has been involved in revising the manuscript critically for important intellectual content.AS has made substantial contributions to the interpretation of data and has been involved in revising the manuscript critically for important intellectual content.JTC has made substantial contributions to the interpretation of data and has been involved in revising the manuscript critically for important intellectual content.AN has made substantial contributions to conception and design, the interpretation of data and has been involved in drafting and revising the manuscript critically for important intellectual content.CP has made substantial contributions to conception and design, acquisition of data, the interpretation of data and has been involved in drafting and revising the manuscript.All authors have read and approved the final manuscript.


The identification of protein coding elements in sets of mammalian conserved elements is one of the major challenges in the current molecular biology research. Many features have been proposed for automatically distinguishing coding and non coding conserved sequences, making so necessary a systematic statistical assessment of their differences. A comprehensive study should be composed of an association study, i.e. a comparison of the distributions of the features in the two classes, and a prediction study in which the prediction accuracies of classifiers trained on single and groups of features are analyzed, conditionally to the compared species and to the sequence lengths.In this paper we compared distributions of a set of comparative and non comparative features and evaluated the prediction accuracy of classifiers trained for discriminating sequence elements conserved among human, mouse and rat species. The association study showed that the analyzed features are statistically different in the two classes. In order to study the influence of the sequence lengths on the feature performances, a predictive study was performed on different data sets composed of coding and non coding alignments in equal number and equally long with an ascending average length. We found that the most discriminant feature was a comparative measure indicating the proportion of synonymous nucleotide substitutions per synonymous sites. Moreover, linear discriminant classifiers trained by using comparative features in general outperformed classifiers based on intrinsic ones. Finally, the prediction accuracy of classifiers trained on comparative features increased significantly by adding intrinsic features to the set of input variables, independently on sequence length .We observed distinct and consistent patterns for individual and combined use of comparative and intrinsic classifiers, both with respect to different lengths of sequences/alignments and with respect to error rates in the classification of coding and non-coding elements. In particular, we noted that comparative features tend to be more accurate in the classification of coding sequences – this is likely related to the fact that such features capture deviations from strictly neutral evolution expected as a consequence of the characteristics of the genetic code. The annotation of whole genomes through the identification of protein coding and regulatory regions is one of the major challenges in the current research in molecular biology. In comparative genomics, the key idea is that sequences, which are highly conserved during evolution, likely correspond to either protein coding exons or regulatory motifs . In our coding potential, i. e. measures of the likelihood that sequences with a particular nucleotide substitution pattern or with a certain bases composition are coding sequences. These metrics aim to capture different signals that distinguish coding and non coding conserved sequences and may use comparative or non-comparative features. The former are based on cross-genomic comparisons, whereas the latter are computed by analyzing single-species sequences. The most common comparative features are based on evolutionary signals which aim to quantify 1) the tendency of nucleotide insertions and deletions to preserve the codon reading frame , , . . . ,  bp. For each classifier and for each species, we constructed learning curves in which the empirical error rate  is plotted as a function of sequence length. As the trends of learning curves related to the non comparative features were very similar for all three species, we reported in Figure Stopm, CG-Content, BL80M and BL80std, the substitution rate ratio scores SRRM and SRRstd and the reading frame conservation RFC. Moreover, our results suggest that these comparative features better discriminate for more genetically distant species. Error rates related to the human/mouse and human/rat comparisons (blue line) are smaller than those obtained in the mouse/rat comparison (green line).For the intrinsic features with statistically significant error rates  of prediction accuracies of comparative and intrinsic classifiers are depicted respectively in Figure P-value < 0.005 and π > 0.88). Although these learning curves exhibit a similar qualitative behavior, they result statistically different. In fact, Kolmogorov-Smirnov tests show that the error rates of comparative classifiers are significantly smaller than ones of non comparative classifiers in 68% of the length classes for the human, in 65% for the mouse and in 94% for the rat.The features depending on the reading frame were evaluated by using the frame suggested by the most accurate univariate classifier, i. e. the classifier based on global classifier is depicted in Figure P-values < 0.05 and π > 0.992. The accuracy increases proportionally to the sequence length up to 97% . Kolmogorov-Smirnov tests, applied for comparing comparative versus global classifiers, show that the error distribution of the global classifier is significantly smaller than the one of the comparative classifier, for all three species in analysis and independently of the sequence length. In other terms, the information related to the intrinsic features is not redundant in the ensemble of all features in order to classify coding from non coding CSEs.Moreover, we investigated if adding the intrinsic features to the comparative ones could improve the performance of the classifier in a statistically significant way. To this end we trained a classifier by using the above features simultaneously and assessed its error rate as a function of the sequence length. For each length class, the empirical distribution (median and interquartile range) of prediction accuracy of this We completed our analysis comparing the global, comparative and intrinsic classifiers in terms of sensitivity  and specificity (the fraction of non-coding sequences correctly predicted as non-coding) , different features function differentially at different evolutionary distances. In general therefore, it should be considered desirable to use multiple species comparisons spanning different levels of divergence – both in order to maximize the proportion of the reference genome which is aligned, and to maximize the discriminatory power of the tools at hand. Such approaches are the subject of ongoing work.The authors declare that they have no competing interests.NA and GP conceived the study. TMC, FM, AD'A and RM designed the algorithms and conduced the experiments and, together with DSH, GP and NA, they evaluated and compared the experimental results. All the authors contributed to the drafting of the article.


Asthma has grown to be one of the leading chronic illnesses throughout the world, affecting more than 300 million people of all ages. When uncontrolled, asthma can place rigorous restrictions on everyday life. On the other hand, there are so many options of therapeutic modalities including both old and more advanced medications for the control of asthma symptoms.In order to effectively combat any chronic illness, one needs to develop and follow strategic guidelines that optimize its diagnosis, management and control. These guidelines are continuously revised and updazted according to the opinions of experts, knowledge of current scientific research, the appearance of more effective drugs or the inappropriateness in the application of a particular guideline on patients in real life.In 1993, the Global Initiative for Asthma (GINA) was formed. Its goals and objectives were described in a 1995 NHLBI/WHO Workshop Report, Global Strategy for Asthma Management and Prevention (GSAMP). This report was revised in 2002 and its companion documents have been widely distributed and translated into many languages.As the GINA committees expanded their work, the report was updated annually. The first update was posted in October 2003, a second in October 2004 and a third in October 2005, each including the impact of publications from January through December of the previous year.All previous GINA reports recommended the categorization of asthmatics according to their clinical severity into four levels: Intermittent, mild persistent . AccordiIn January 2004, the GINA executive committee recommended that the report be revised to emphasize asthma management based on clinical control rather than classification of the patient by severity. This important paradigm shift for asthma care reflects the progress that has been made in understanding the impact of the disease and the pharmacologic care of patients.The entire, newly revised document of November 2006 emphasizes asthma control. There is now good evidence that the clinical manifestations of asthma-symptoms, sleep disturbances, limitations of daily activity, impairment of lung function and use of rescue medications-can be controlled with appropriate treatment.The document now recommends a classification of asthma by level of control: Controlled, partly controlled or uncontrolled . This reAsthma control may be defined in a variety of ways. In general, the term “control” may indicate disease prevention or even cure. However, in asthma, where neither of these are realistic options at present, it refers to control of the manifestations of the disease.Asthma control means that patients should experience no or minimal symptoms (including at night), have no limitations on their activities (including exercise), have no  requirement for rescue medications, have near normal lung function and experience only very infrequent exacerbations Tables  and 2.Some asthma experts are not yet comfortable with the concept of allowing daytime symptoms twice a week or with the need for reliever rescue treatment twice a week. Additionally, classification of asthma based on severity, according to previous guidelines, is now reserved and recommended only for research purposes.The role of the healthcare professional is to establish each patient's current level of control and then adjust treatment to gain and maintain control. The new document encourages channeling asthmatics into one of five, rather than four, treatment steps based on the control level, with somewhat extra flexibility and more pharmacological options than before.This classification based on control level is by far more practical, easier to follow, includes more clinically relevant issues and implies more appropriate decisions on the choice of treatment in a given patient with asthma. In addition, telling the patient that your asthma is controlled or not controlled is more informative than intermittent or persistent asthma, especially when such words are translated into patient's own language.According to the recent GINA document, many attempts have been made to classify asthma according to etiology, particularly with regard to environmental sensitizing agents . However, such a classification is limited by the existence of patients in whom no environmental cause can be identified . Despite this, an effort to identify allergic asthma should be part of the initial assessment to enable, in some uncontrolled patients, the use of avoidance strategies, allergen-specific immunotherapy and anti-IgE therapy.In spite of courageous efforts to improve asthma care over the past decade, a preponderance of patients have not benefited from advances in asthma management and many lack even the rudiments of care. A challenge for the next several years is to work with asthma specialists, primary healthcare providers and public health officials in each country to design, implement and evaluate asthma care programs to meet local needs.Although many doctors dealing with asthma have some skepticism about previous or recent GINA guidelines, nevertheless it is a step forward in winning the fight against asthma.