We report a patient-centered intervention study in 9 municipalities of rural Nicaragua aiming at a reduction of internalized social stigma in new AFB positive tuberculosis (TB) patients diagnosed between March 2004 and July 2005.Five out of 9 municipal teams were coached to tailor and introduce patient-centered package. New TB patients were assigned to the intervention group when diagnosed in municipalities implementing effectively at least TB clubs and home visits.We compared the changes in internalized stigma and TB treatment outcome in intervention and control groups. The internalized stigma was measured through score computed at 15 days and at 2 months of treatment. The treatment results were evaluated through classical TB program indicators. In all municipalities, we emphasized process monitoring to capture contextual factors that could influence package implementation, including stakeholders.TB clubs and home visits were effectively implemented in 2 municipalities after June 2004 and in 3 municipalities after January 2005. Therefore, 122 patients were included in the intervention group and 146 in the control group. After 15 days, internalized stigma scores were equivalent in both groups. After 2 months, difference between scores was statistically significant, revealing a decreased internalized stigma in the intervention group and not in the control group.This study provides initial evidences that it is possible to act on TB patients' internalized stigma, in contexts where at least patient centered home visits and TB clubs are successfully implemented. This is important as, indeed, TB care should also focus on the TB patient's wellbeing and not solely on TB epidemics control. Tuberculosis (TB) is usually presented as a global public health problem: there were an estimated 9 million new TB cases and 2 million TB deaths in 2004 . TB can Some interventions have been reported for their potentiality to reduce tuberculosis social stigma. This has been assessed through qualitative methods, for example in the case of TB clubs ,14 or inWe report hereby an intervention study comparing changes in internalized stigma and treatment outcome between a group of TB patients benefiting from a patient-centered interventions package including at least TB clubs and home visits, and a group control in rural Nicaragua. The basic assumption behind that package design was that, by increasing power-sharing between the health personnel and TB patients , TB patients' internalized stigma would decrease.In this section, we describe the setting, the population, the definition of control and intervention groups, and the data collection. Data collection was not limited to outcome measurement. We emphasized comprehensive documentation of process before and during interventions package implementation. Indeed, we wanted to capture contextual factors  that could influence package implementation.Nicaragua is the second poorest country in America. First-line government health services (FLGHS) consist of health posts and health centers. They are managed by a Ministry of Health (MOH) team at the municipal level, under the regional level MOH authorities. TB care is delivered through a MOH program, strongly organized at the FLGHS level. It ensures the availability and quality of free sputum examination in government health laboratories and free TB treatment provided exclusively in FLGHS. In each health center, a nurse is usually responsible for the TB patients care.This intervention research project involved different stakeholders: (1) it was conceived by the authors of this paper, (2) adapted for its operational design by national TB program coordinator, and MOH team at the municipal and regional level; (3) implemented by MOH teams at municipal level for the operational component and by the authors of this paper for the research component; and (4) it benefited from financial and other supports, for the research component, from Damian foundation project in Nicaragua and Global Fund administrating institution in Nicaragua (NICASALUD).This research project included 9 municipalities of rural Nicaragua, selected by the MOH national TB program coordinator because of their need to be strengthened for the local management of the care to TB patients. Strengthening local management of the TB program was initially mainly foreseen through operational analysis exercise, explained here bellow.It targeted new AFB positive TB patients diagnosed between March 2004 and July 2005. Table The process before implementing the intervention covered 5 out of 9 municipalities: Siuna, Bluefield, Waslala, San Jose de Bocay and Nueva Guinea. It was planned in 3 phases: an operational analysis, a qualitative exploration with the design of an intervention package thereafter introduced in the municipalities.During the first phase, operational analysis was performed. This is a method for identifying problems in the care process for TB patients. It is done through the use of a simple step-by-step model, the operational model. It is based on the passive detection of AFB-positive cases and the main steps that a patient must go through from the first symptoms and up to TB recovery . It makeDuring the second phase, a qualitative exploration of the social stigma meanings and determinants was used as an input for the design of an intervention package in order to reduce internalized stigma.During the third phase, feedback of the exploration, training on self-esteem and tailoring the intervention package through negotiation with stakeholders were planned.We initially designed a set of three types of interventions for internalized stigma reduction. Firstly, we wanted to strengthen TB patients through TB clubs taking the form of self-help groups. Secondly, we wanted health personnel to better know TB patients and their realities through performing patient centered home visits and case discussion centered on the problems experienced by TB patients. The objective of the patient centered home visit was to know better the social network of the patient, identify strength and weaknesses of the network, and plan activities to support the patient. Health professionals were expected to listen to the relatives and neighbours of the patients, identify their feelings towards the patient , and plan with the social network activities to support the patient during his treatment. A specific guide was conceived to assist health care providers. Thirdly, we planned a revised DOT provision through the involvement of a supporter at the first consultation or through reviewing the patient pathway by decreasing unnecessary isolation and decentralizing care where possible.Of the three types of initially designed interventions, at least TB clubs and patient centered home visits were implemented in the intervention municipalities.All these interventions were conceived in their implementation with the full participation of MOH authorities. Furthermore, TB clubs had been included in the 2005 Global Fund grant for Nicaragua although it was initially piloted in the intervention municipios by this research project.We allocated patients in two groups: intervention and control. TB patients were included in the intervention group if diagnosed in a municipality organizing at least the two most consistent interventions of the package: TB clubs and home visits. Others were allocated to control group.We compared both groups in relation to basic socio-economic indicators: age, gender, declared income, literacy, and distance from the TB treatment center. Additionally, we compared their self-esteem, using the Rosenberg scale , at the Researchers performed six monitoring visits between February 2004 and December 2005 in each of the five municipalities where interventions package was introduced. During each visit, they documented the progress in implementing interventions and possible municipal health team's initiatives. They performed care process observations and they systematically interviewed various local stakeholders .Outcomes of this study were TB treatment outcome and TB internalized social stigma.TB treatment outcome classical indicators were computed with data from the municipal TB register crosschecked with the TB patient cards.The internalized social stigma was measured through a scale that has been largely inspired by the scale developed by Boyd Ritsher in the context of mental illnesses ,19. It iUnivariate analysis of TB treatment outcome and internalized TB stigma variable was done using the EPIINFO 2000 program.This proposal didn't pass through a formal ethical review. However, it was selected through an independent peer review process to receive financial support from Damian Foundation. It was further on submitted to Nicaragua Ministry of Health authorities for approval.A total of 268 AFB positive TB patients were enrolled in the study over the 9 municipalities. We report the process that leads or not to the implementation of intervention, the assignment of TB patients in the control or intervention group, the TB treatment results and the internalized stigma changes.The three phases of the process before implementing the intervention were coached by researchers in Siuna, Bluefield, Waslala, San Jose de Bocay and Nueva Guinea. Upon request of the nurse in charge of TB patients in La Dalia, this municipality was also coached. The municipalities of El Rama, Juigalpa and Wiwili were just visited for data collection.The operational analysis was performed before January 2004 in Bluefield, Siuna, Waslala, San Jose de Bocay and Nueva Guinea. The process and results of this exercise were unequal. In Siuna, decentralization from the health center to the health post was quickly successful. For example, some village health workers transferred sputum samples to the health post and patients from a particular area received their treatment directly from a cured TB patient. Some health posts also provided treatment to TB patients. In Bluefield, the decentralization from health center to health post was difficult at first due to a lack of personnel and resources. However, as of July 2004, some patients received their treatment at the health post or even within their families. In Waslala, the decentralization process was slow but some patients had their treatment supervised by their families after July 2004.External researchers (i.e. the authors of this paper) performed a qualitative exploration of the meanings and determinants of social stigma in Siuna, Bluefield, Waslala, San Jose de Bocay and Nueva Guinea at the end of 2003 .This consisted in in-depth interviews and focus groups with key stakeholders involved in the TB patients care. The patient centered package design was inspired by this study results.Workshops were organized in each of the 5 municipality during the first semester 2004. Firstly, training on self-esteem was organized by a psychologist in each of the municipality. Secondly, a draft of the interventions package was discussed in each municipality. Each local health team chose amongst the initial package, the interventions to be implemented.In Bluefield, the whole municipal health team and the TB program regional coordinator participated to the workshop together with nurses from the health center and the health post. They decided to focus on TB patients' clubs and home visits. By the end of the first semester 2004, a meeting was organized by the director of the health center with the whole staff in order to discuss perception and behavior towards TB patients. The regional authorities also organized the broadcast of TB related messages on the local radio.In Siuna, members of the municipal health team, nurses from the health center and the health posts attended the workshop. Initially, the municipal team decided to implement only home visits but very quickly started also TB patients' clubs.In Waslala, the whole nursing staff from the municipality participated in the initial workshop but the municipal health director was partly present. The nurse responsible for the care to TB patients in La Dalia, although not supposed to be involved in the study, participated also. The Waslala municipal health team members committed themselves to start home visits and to improve the first consultation process. In July 2004, a follow-up visit was done by researchers and several problems were encountered. A newly appointed medical doctor was performing the first consultation for TB patients. He did not know about the proposed methodology. Concerning home visits, the nurse in charge of TB patients at the municipal level complained of the lack of resources. He performed only two of them, and did not follow the suggested methodology.In San Jose de Bocay, no authority was present at the initial workshop with the exception of the TB program regional coordinator. The workshop was unprepared and attended only by part of the staff. The decision was taken to decentralize treatment wherever possible. In a second workshop organized in April 2004, few people, different from the first workshop, were present. Many others were involved in the mass vaccination campaign. The follow-up of the February workshop showed little changes and no decentralization. In July 2004, a monitoring visit was done. The municipal director, the nurse and the doctor in charge of TB patients were newly appointed. As a consequence, little changes were observed.In Nueva Guinea, the workshop mainly discussed the involvement of village health workers in TB suspected cases' referrals. In April 2004, a second workshop was organized. There was confusion as community health workers rather than health staff members were invited to the workshop. It was however decided to organize TB cases discussion and to focus on the reorganization of the TB patient's pathway. During 2004 and 2005, only one case discussion was organized during a monitoring visit. It was very much centered on TB control and not much on the difficulties met by TB patients. The revision of the patient's pathway was not really done because of changes in health staff. In May 2005, TB clubs that had been planned were not organized due to the lack of funds.Three groups of municipalities were identified according to the period home visits and TB clubs were effectively implemented. In the first group, composed of Siuna and Bluefield, it was effectively implemented as of July 2004. In the second group, composed of Waslala, La Dalia and San Jose de Bocay, it was implemented as of January 2005. Finally, home visits and TB clubs were never effectively implemented in the third group composed of Nueva Guinea, Juigalpa, El Rama and Wiwili.In Bluefield, TB clubs in their new form that is aiming at a maximum of TB patients interactions started operating early 2004. The director and the doctor in charge of epidemiology at the health center were initially present. Home visits were also performed by two health staff members. The regional level proposed a special format for home visits providing information on the TB patients' psychosocial conditions in addition to the usual contact tracing data. In January 2005, the TB clubs were chaired by TB patients themselves. They also decided to appoint an executive board. In Siuna, home visits were done mainly close by the health center. Quickly after, TB clubs started first in the health center upon the initiative of the nurse in charge of TB patients and the doctor responsible of epidemiology. Later on, a TB club executive board constituted of TB patients was set up. In other areas, two cured TB patients took the initiative of starting a club with 5–6 patients. They actively supported the work of the ministry of health in those areas. Another cured TB patient talked on the radio and on TV about tuberculosis and the ways to cure it. Finally, a local NGO decided to support TB clubs meetings.In Waslala, TB club meetings started to be regularly organized in 2005 with around 20 people present each time. Home visits were done, using the guideline developed in Bluefield. Not all TB patients were systematically visited because some were living too far away. In La Dalia, the nurse in charge of TB patients also started TB patients' club meetings and home visits with the support of the responsible at the regional level. In San Jose de Bocay, a new staff was appointed at the end of 2004. As a consequence, home visits, and TB clubs started. Additionally, the staff of this municipality took the initiative of organizing special counseling for the patients' families, aiming at reducing isolation and increasing support. Finally the decentralization of the diagnosis and treatment at the health post level started for some patients. Some health posts started sputum smear slide preparations for transfer to the health center laboratory.Hundred and twenty two AFB positive TB patients were diagnosed in municipalities implementing TB clubs and home visits at that time. They were assigned to the intervention group. The other 146 TB patients included in the study were assigned to the control group Table .There was no statistically significant difference between the control and intervention groups for socioeconomic variables Table . The meaThe results of the treatment do not show statistically significant difference between the intervention and control groups. Both groups can be considered as having a good outcome: 90% of the TB patients in the control group and 93% of the ones in the intervention group were either cured or completed their treatment; only 5/146 (3%) of the patients in the control group and 4/122 (2%) of the patients in the intervention group abandoned their treatment.Details of the scale are presented on Table We computed the stigma scale score, attributing 5 points when a TB patient completely agrees with a statement and 1 point when he completely disagrees with it. The total of the scale score amounts therefore between 10 and 50 points. We compared the mean rate for the control group with the mean rate for the intervention group. For both groups, we calculated two internalized stigma scores, one for 15 days of treatment and another one for 2 months of treatment. After 15 days, scores were equivalent in both groups. However, after 2 months, difference between scores was statistically significant, revealing a decreased internalized stigma in the intervention group and not in the control group , was prevented in two ways. Firstly, patients were not aware of being part of the intervention or the control group. Secondly, the internalized stigma scale was "self applied" by TB patients with eventually the assistance of a patient's relative, outside of the health care facility and the influence of health care professionals.These results should not be analyzed mechanically, by trying to link a standardized package of intervention to a given outcome. Acting on TB patients' internalized stigma is a complex issue. Successful interventions depend from the context and the stakeholders and quantitative measures only capture part of the TB patients' feelings.Firstly, interventions effect cannot be separated from the context. It would be indeed naïve to believe that any type of TB clubs and home visit independently from the context and the stakeholders would improve internalized stigma in TB patients. Indeed in our study, the implementation of the patient centered package has been highly dependent on the context and more specifically on the stakeholders at the local level. Two central stakeholders were critical for a successful intervention package: the TB patients and the nurse in charge of the TB patients. In the first group of municipalities (Siuna and Bluefield), the TB patients played an active role in the TB club activities and other support activities for TB patients, thanks to some individualities' leadership. In the same municipalities, and also in La Dalia, nurses caring for TB patients where highly motivated, knew the community members very well, and were used to working with TB patients, as they have a long lasting experience in such position. In those cases, nurses were supported by authorities: the nurse of Siuna benefited from a dynamic municipal health management team stable during the time of the research; the nurse of Bluefield benefited from the proximity of an enthusiastic TB program responsible at the regional level. Finally, in both Bluefield and Siuna, the work of the nurse responsible of the TB patients, was supported by local NGO's. These findings are congruent with recent policies and experiences emphasizing the pivotal role of frontline health workers in TB care -31.Secondly, quantitative measures only capture part of the TB patients' feelings. In our study, we used a 10 items scale to measure internalized stigma. The presentation of scales to measure TB social stigma in a context of low HIV prevalence has not yet been published in peer reviewed journals. We identified in the "grey" literature five studies that quantified the TB social stigma: Two studies used only one binomial variable ,33; thremanual de trabajo sobre estigma de la tuberculosis a nivel municipal en Nicaragua." Part of it has already been used in expanding PATB clubs and home visits in all areas of Nicaragua. It has been discussed and validated by a new commission, the "Commission Nacional the Apoyo a Personas Afectadas por Tuberculosis" (CONAPAT) created during, and partly as a consequence of this research project. It involves the main national stakeholders in TB control, i.e. the National TB control program of the Nicaraguan ministry of health, the administrator of the Global Fund , the Damian Foundation, a Belgian NGO and the Centro de Investigaciones y Estudios de la Salud (CIES), a public health school.Further to its local benefits, this project has been able to influence national policies about the care of TB patients in government health services. The final result of this has been the production of a "By its role of coaching, the research team of the CIES has been in a position to support the local implementation of the intervention package, but also to collect information about difficulties and the success in the local processes. This was particularly useful for discussions in the CONAPAT. Indeed, as a consequence of the intertwined process of information collection during coaching activities and discussion of it during CONAPAT meetings, scaling up of tools that were developed in this project was made possible. For example, early 2006, more than 50 municipios created PATB clubs with tools developed by this research.Increased attention is given to the TB social stigma and its consequences on TB patients suffering. This study provides initial evidences that it is possible to act on TB patients' internalized stigma, in contexts where at least patient centered home visits and TB clubs are successfully implemented. Outcomes are not dependant of a standardized set of intervention but also of the context, and mainly the capacity of frontline nurse and TB patient to establish a fruitful dialogue. Our findings are relevant particularly, in context where TB control is already effective. Through this paper, we hope to have contributed to promoting an expanding field of research which is highly needed in order to develop valid instruments to measure the stigma, to understand the optimal mix of contextual factors, stakeholders' interaction and interventions' package.The authors declare that they have no competing interests.JM conceived and designed the study; supervised the data collection; analyzed and interpreted the data and wrote the paper. AS conceived and designed the study; supervised the data collection; analyzed and interpreted the data and participated to the writing of the paper. GM conceived and designed the study; supervised the data collection; analyzed and interpreted the data and participated to the writing of the paper. PM conceived and designed the study; supervised the data collection; analyzed and interpreted the data and participated to the writing of the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Malaria remains a major cause of morbidity and mortality among children under five years of age in Nigeria. Most of the early treatments for fever and malaria occur through self-medication with anti-malarials bought over-the-counter (OTC) from untrained drug vendors. Self-medication through drug vendors can be ineffective, with increased risks of drug toxicity and development of drug resistance. Global malaria control initiatives highlights the potential role of drug vendors to improve access to early effective malaria treatment, which underscores the need for interventions to improve treatment obtained from these outlets. This study aimed to determine the feasibility and impact of training rural drug vendors on community-based malaria treatment and advice with referral of severe cases to a health facility.A drug vendor-training programme was carried out between 2003 and 2005 in Ugwuogo-Nike, a rural community in south-east Nigeria. A total of 16 drug vendors were trained and monitored for eight months. The programme was evaluated to measure changes in drug vendor practice and knowledge using exit interviews. In addition, home visits were conducted to measure compliance with referral.The intervention achieved major improvements in drug selling and referral practices and knowledge. Exit interviews confirmed significant increases in appropriate anti-malarial drug dispensing, correct history questions asked and advice given. Improvements in malaria knowledge was established and 80% compliance with referred cases was observed during the study period,The remarkable change in knowledge and practices observed indicates that training of drug vendors, as a means of communication in the community, is feasible and strongly supports their inclusion in control strategies aimed at improving prompt effective treatment of malaria with referral of severe cases. More than a million people die of malaria each year and most of them occur in Africa . In NigeIn order to treat the disease, people seek treatment from a broad spectrum of public and private healthcare providers ,4. ArounOne of the problems associated with treatment by these patent medicine dealers is that there is poor knowledge and poor dispensing behaviour in relation to childhood malaria episodes . These tIn Nigeria, patent medicine vendors (PMV's) are usually the first choice in health care and are a recognized primary source of orthodox drugs for both rural and urban populations, especially the poor -17. In aThe patent medicine vendor can be defined as a person without formal pharmacy training, who sells orthodox pharmaceutical products on a retail basis for profit . The priIn addition, most of the anti-malarial drugs purchased from PMVs in a study in Nigeria were for children . Since pThe results of the formative stage (pre-intervention phase) of this study  showed tBased on these results an intervention programme was developed to determine the feasibility of training drug vendors to provide appropriate treatment for childhood malaria, to take on an advisory role and to refer severe cases of malaria promptly, with a view to reducing childhood morbidity and mortality and achieving the health related Millennium Development Goals 4.Thus this report is part of a larger study designed to improve home management of childhood malaria and referral of severe malaria at the household and community levels.Anopheles gambiae and Plasmodium falciparum is responsible for more than 90% of all malaria infection [The study area has previously been described . Malarianfection th December 2003 for a period of 18 months, until June 2005. The total number of drug vendors had increased from 13 at time of baseline study[The intervention programme commenced on the 30The main components of the programme were training of drug vendors, community information activities, monitoring and evaluation of the programme. In recognition of the prominent role which traditional, administrative and political leaders play in ensuring community participation and successful implementation of an intervention programme, a series of sensitization meetings were held in the community. Having obtained the support of the community leaders, meetings were then held with the members of drug vendors association to gain their cooperation. Enough trust was built with the drug vendors during the formative phase. In addition, the results of the formative phase were fed back to them and they showed great interest in the intervention.A core group known as Project-Community Communication Group (PCCG) was formed. The composition of the PCCG included women leaders, opinion leaders, representatives of patent medicine vendors and project members. The main aim was to promote community participation and for the group to help in the design, implementation and monitoring of the project and also to act as a link between the research team and the community.Some members of the research team, representatives of drug vendors and a graphic artist worked together to design the job aids which included, age-specific dose guides for treatment of malaria with chloroquine Figure  and paraAge-specific rubber stamps depicting correct doses of chloroquine in children of different ages with different colours of handles for the different age groups for easy recognition were produced. Posters were also produced depicting a child with mild and severe malaria with a list of the clinical symptoms. This was to aid drug vendors in diagnosis of severe malaria requiring referral. It was also to serve as client awareness poster to help caretakers differentiate between mild and severe malariaThe community information activities aimed to create awareness of the programme, give information on recommended anti-malarial drug policy, importance of appropriate early treatment and symptoms of severe disease requiring referral to a health facility. This was done through community meetings, distribution of posters, which were placed in strategic places in the community, and drama groups, which performed regularly. The results of this will be published elsewhere.Drug vendors were trained in a series of two workshops each lasting three days. To ensure full participation, all the training activities took place on days that were not market days, when they were considered very busy. The participatory approach was adopted for the training, which emphasized culturally appropriate methods, such as role play.Training focused on improving their age-specific dispensing practices for chloroquine, which was the recommended anti-malarial at time of study, asking relevant history questions before giving treatment instructions as well as effective communication skills to enable them give accurate verbal advice to caretakers. They were trained to recognize symptoms requiring referral and were taught to record all referrals on a notebook by writing the child's name, the date and reasons for the referral. Referral was facilitated by giving the caretakers referral note stamped with a referral stamp and also by informing nearby hospitals to recognize the referral stamp as that of a child requiring urgent attention.The caretakers were to choose the hospitals of their choice, since baseline results showed the local health centre was not being utilized for reasons that included the lack of a doctor. To measure compliance with referral, some community members chosen by the PCCG, were detailed to follow up the referred patients at home to confirm compliance.In addition, sessions on reading the doctor's prescription was included based on drug vendors request and the fact that patients will eventually end in their shops to purchase drugs. At the end of the workshop, they were given job aids such as age-specific dose guides for malaria treatment to be hung up on the wall of their shops, to serve as reminders before dispensing drugs. They were taught to stamp the dispensing envelopes with the right dose for the age of sick child, to serve as a visual reminder of the verbal advice given to caretakers.At the end of the training, certificates of participation were distributed to all participants. Drug vendors appreciated the certificates as this will elevate their status within the community as well as boost sales of drugs. They were neither charged nor remunerated for their participation.This was carried out by some members of the research team and trained research assistants. Monitoring and face-to-face supportive supervision for drug vendors, designed to reinforce skills was carried out for a period of eight months. Unannounced face-to-face observations were conducted to monitor health care providers performance after training. Later supportive feedback was provided for problems they were not aware of and important issues raised were solved to help them integrate the new knowledge and skills into their daily practices.The programme was evaluated by conducting three rounds of exit interviews on all trained PMVs. Immediately after leaving the PMVs' outlet, the caretaker was interviewed at a location away from the shop, using a pre-structured form, which was developed to record all the behaviours the PMVs were expected to perform at the end of training. This is with regards to history questions asked, treatment given, whether reference was made to the dose guides provided, if stamped envelopes were given and type of verbal advice given if any.In-depth interviews (IDI) were conducted with the PMVs using IDI guide to explore their knowledge, beliefs, and stated treatment practices for mild and severe malaria, as well as the referral practices for severe malaria. The interview was conducted in the morning hours on non-market days  by two community health nurses from the Health Visiting Unit of the Department of Community Medicine, who also conducted the pre-intervention phase interviews. Each interview lasted between 60 and 75 minutes. The interview was tape-recorded and notes taken.In addition, a review of the PMVs' referral records was conducted. The review noted the total number of cases referred during the study period by drug vendors and the main reasons for referral. The places the patients were referred to was also noted. To measure compliance with referral, some community members chosen by the PCCG, were detailed to follow up the referred patients at home to confirm compliance and this information was collected from the PCCG members.Data entry and statistical analysis was conducted using EPI-INFO version 6.04 and SPSS statistical packages version 15. Chi-square test was used to test for any significant differences between proportions before and after intervention.For the qualitative data, the transcriptions was organized under thematic headings and later developed into an ethnographic summary with illustrative quotes. The trajectories of their response to questions were captured with a trajectory tree and then the different ranges of opinions, perceptions and stated practices were noted.Ethical approval was sought and obtained from the Ethical Committee of The University of Nigeria Teaching Hospital, Enugu (UNTH). The research objectives and methods were explained to individual respondents and verbal informed consent to tape-recording the interviews was obtained from the study participants before the interview commenced.Confidentiality of all information obtained from participants was maintained by not allowing information on the respondents' identities to be accessible to non-members of the research team.A total of 16 patent medicine vendors (PMVs), registered with the association were trained. They comprised eleven male and five female practitioners and the age range was from 26 to 42 years. The majority  had attained primary education while only  had secondary education. Only one, who is a trained nurse, had received any formal training in drug use. Generally, they were willing to participate in the programme and all 16 of them were trained giving 100% participation rate.They acknowledged the importance of profit as a motive for their drug dispensing habit, preferring a sale of single tablets (incomplete course) to no sale at all. However, they were advised to sell only full courses of anti-malarials to caretakers and the sale of single tablets was discouraged. They were eager to receive further training and to broaden the scope of their therapeutic activities.The result of the exit interviews is shown in Table the sun can cause malaria when it shines directly on the child". However, after the intervention,  of drug vendors knew mosquitoes as a cause of malaria, , still attributed malaria to eating of oily/fried food. In the pre-intervention, the mode of transmission was also not quite clear. However, in the post-intervention phase, the majority had acquired correct knowledge about mode of transmission. According to one vendor" when mosquito bites a person carrying the parasite already, it carries the parasite and transfers it to a healthy person when it bites that person. In that way it transfers the parasite from a sufferer to a healthy person and malaria starts".During the pre-intervention phase , some ofmalaria gives very high fever and convulsion occurs from very high fever, again when malaria enters the brain of the child, it causes convulsion"During the pre-intervention phase, when asked to discuss the symptoms of malaria, drug vendors correctly identified them to be fever , headache , weakness , loss of appetite  and restlessness  for mild malaria. Other less commonly noted symptoms included deep yellowish discoloration of urine, chills, vomiting, and stomach upset, dreaming, and excessive sweating. However, following training, there was an increase in recognition of malaria as  of vendors identified fever as a major symptom of malaria followed by loss of appetite (68.8%), chills (62.5%), headache (62.5%), weakness (56.3%), and vomiting (50%). They were less knowledgeable about symptoms of severe illness before intervention. Persistent fever and convulsions, which were recognized by 38.5% and 30.8% of vendors, respectively, were the popular answers. Also mentioned were yellowish discoloration of the skin (23.1%) and unconsciousness (15.4%). But the intervention had a positive impact on the recognition of signs of severe malaria. In the post-intervention, most drug vendors could now list the cardinal signs, such as convulsions (87.5%), persistent fever (68.8%), unconsciousness (62.5%), dryness of skin (62.5%), inability to stand/sit (56.3%), yellowish discoloration of the skin (50%), fast breathing (43.7%) and coke-colored urine (43.8%). The relationship between malaria and convulsion, which was previously vague, was also better understood as shown in this quote "During formative research, when asked about how treatment decisions are made  responded they dispensed what customers demand. Only  did take some form of history, by asking about age of the child only, before giving drugs and none gave any verbal advice to caretakers. Furthermore, a majority  used chloroquine as their first-line drug, in addition to analgesics in the form of paracetamol, as an adjunct to specific anti-malarial drugs for the treatment of mild malaria. In general the knowledge with regards to drug dosages and duration of treatment was grossly inadequate and none dispensed anti-malarial drugs correctly.you do not commence treatment immediately, you first take history, if he has not received any treatment you then give them some drugs and tell them how to take it." The majority also refered to their age-specific dose guides before administering any treatment, as one of them noted "when the mother brings the child, I will welcome the mother, sit her down, ask the mother when the sickness started, what type of treatment she has given. Then after this I will bring the chart so that I will give the correct dose according to the age of the child. Yet another remarked "I look at the drug guides you gave us to treat these children". Commenting on the efficacy of treatment one of them observed that "if they bring the child on time this treatment works fast and the child recovers immediately after 3 days".However, the intervention resulted in an increase in knowledge and correct practices as shown by results of exit interviews in Table The percentage of anti-malarial drug sales where an adequate amount of chloroquine was sold rose from 42.1% one month after training to 69% after four months and to 90.9% after 8 months. It was noted that the same drug vendors who made reference to their dose guides also dispensed chloroquine correctly. Generally there was a steady increase in correct practices over the months with regards to history questions asked, reference to dose guides, treatment given, verbal advice and stamping of dispensing envelopes. All these observed differences were statistically significant (p < 0.05) as shown in table "if it is severe malaria it is above my scope, I will tell them to go to the hospital. You cannot treat this type because it is beyond my scope". Yet another explained "when we use the system we learnt from the training and treat mild malaria, if it does not respond, we refer them to the hospital on time".Prior to the intervention, most drug vendors indicated that they also made use of chloroquine and paracetamol as the major drugs for the treatment of severe malaria. None did refer a child with severe malaria to a health facility, unless he starts convulsing. There was a gap in knowledge of severe symptoms requiring referral. After the intervention, most had learnt that severe cases should be referred immediately. As one vendor remarked A total of 132 cases were referred during the study period by drug vendors out of which 115 (80%) complied. The main reasons for referral were high fever, weakness and vomiting. A majority 50 (47.6%) of the referred patients went to Parklane General hospital, while 37 (35.2%) of them went to the University of Nigeria Teaching Hospital, both situated in the urban area about 20 kilometers away. Nine (8.6%) used private clinics and the community health center. All severe cases were referred.The training interventions were aimed at building the knowledge and skills that will enable PMVs to provide better treatment for malaria and refer severe malaria cases. This study shows that the training improved their knowledge and correct practices. These results are rather encouraging, considering the difficulty involved in changing private sector practices. As noted by a WHO study group, achieving rational prescribing in the private sector is "notoriously difficult" due to influences from patient demand, drug advertising and profit margins .A majority of them were able to provide anti-malarials in the right dose and for the right duration. No doubt this is likely to improve the effectiveness of anti-malarial treatment, and hence reduce the development of drug resistant and eventual cost of treatment. The result is similar to what was obtained in Kenya , where pThe intervention also showed that drug vendors were able to give correct verbal advice to their patients in such a way that the customers understand and can follow the advice. However, as has been noted in Nigeria , there mThe referral of severe cases of malaria to a health facility also improved. This is particularly encouraging as increased trend in morbidity from severe malaria has been noted in Nigeria  and earlThe training programme focused on chloroquine because at the time of the study it was the recommended first-line treatment and the only anti-malarial drug available in the majority of shops in the study area. The new policy, which recommended a change to artemisinin-based combination therapy (ACT), was officially inaugurated in May 2005 , by whicThe improvement in the knowledge of the vendors suggests that they are very receptive and that their training is feasible. They are, therefore, likely to be useful in health interventions when given the appropriate training.The interpretation of results of this study is limited by the fact that it lacks randomization. Nevertheless the data shows a highly probable relationship between the introduction of a specific training programme and changes in PMV's behavioural practices, which are strongly related to the content of the intervention. In addition there were no other local sources of information on anti-malarials during the study period, other than biased information from pharmaceutical companies.Generally the advantages of training to drug vendors would be a possible increase in prestige and OTC sales, especially if certificates were issued at the end of the training as was the case in our study. The advantages to rural communities, would be that they would receive more reliable advice when they purchase OTC drugs. If carried out effectively such a programme could reduce morbidity and mortality in these communities, by initiating prompt appropriate treatment of malaria with early referral of severe cases to a health facility. The potential role of private retailers as partners for malaria control has long been recognized -33 and sThe primary goal of malaria control is to reduce morbidity and mortality through prompt diagnosis and adequate treatment. The focus of delivery of such service has been through the formal health facilities. However, such settings, where treatment is provided by trained personnel, represents only a small part of the providers of care for malaria patientsThe retail sector seems to have the greatest potential in improving access to anti-malarials. This is because this sector is generally more accessible geographically and treatment from this source is cheap and involves less time.The findings of this study strongly support the inclusion of patent medicine vendors in malaria control strategies in form of public private partnership and are in line with the philosophy of primary health care, which is noted for advocating incorporation of local human resources into healthcare efforts. This was demonstrated in Tanzania  and in NWith the newly introduced high cost ACT, a policy option to improve diagnosis and prescribing pattern in private sectors will be to train PMVs in the appropriate use of ACT, using pictorial aids and dose guide as in this study. Although there is no guarantee that the PMVs will perform as well as with chloroquine, it is believed that If well taken by the PMVs, it is likely to decrease inappropriate drug prescribing, use, costs and resistance to ACT. It may also enhance the delivery of ACT for malaria treatment.The authors declare that they have no competing interests.OT and UB conceived and designed the study, collected the data, analysed and wrote up the manuscript.


Population-based perception studies on potential causes and triggers of intimate partner violence against women (IPVAW) may enlighten context-relevant primary preventive actions in settings where data are limited. This study, conducted in one specific city, deals with married women's opinions concerning potential causes and triggers of IPVAW and seeks to highlight areas of consensus and divergence in the views.A convenient sample of women aged 25–45 years and married for at least 5 years was consecutively recruited in the 48 public health centres of Kermanshah city, where free health services are provided to mothers and children under 6 years old. Respondents were individually interviewed on site by trained and experienced female interviewers (response rate 94.3%). A structured pilot-tested questionnaire was used that consisted mainly of closed questions about individual assessment of the extent to which various items could be regarded as a potential cause, a potential trigger or a potential consequence of IPVAW. Individual item frequencies were compiled and the association between socio-demographic attributes of the spouses and also respondents' prior exposure to violence and women answers was explored.For most factors covered, women mainly "agreed" or "agreed very much" about their potential as a trigger or a cause of IPVAW; agreements were stronger for individual-related potential causes. Generally, women's socio-demographic characteristics and prior victimisation did not much affect the opinions they expressed. For some triggers however, women's own occupation and their husband's educational level affected how much in agreement they were.The women interviewed consider that most potential causes and triggers proposed may, at some point in a relationship, engender IPVAW. In the main, their views are not much altered by their own and their husbands' socioeconomic position or their prior victimisation. It remains to be seen whether married men and, for that matter, even women married for a shorter duration or from other settings will answer in a similar manner. Domestic violence is acknowledged as the most common and hidden form of violence against women , one of IPVAW affects women from every cultural, social and economic group ,5,9. Preindividual potential causes are young age of the perpetrator  and alciewed in ,14-18; miewed in ,14,16,18iewed in  are acknl causes ,18.The ecological approach stresses the importance of taking into account the global context of occurrence of IPVAW in order to better understand why it occurs and – perhaps more importantly – how preventive efforts can be tailored to different groups. In that respect, the perception of various community members about the potential causes and triggers of IPVAW could constitute an important part of preventive efforts, in particular in settings where knowledge is limited and data are scarce and difficult to access . Indeed,This paper presents the results of a social diagnosis investigation gathering the views of married Iranian women from Kermanshah city concerning what may cause or trigger IPVAW. The study forms part of a broader community-based project ultimately aiming at the prevention of IPVAW in new couples and of which the first part is a wide-ranging social assessment that gathers the opinions of women and men currently married as well as those of a number of key informants in the community so as to better understand the social context of the intervention that will be developed later on. The approach is inspired from the Green model for the modification of health behaviour [developed in 1991] and where various community-specific assessments ought to be made prior to an intervention and the first step is a social assesment ,22.A wide range of factors  are covered, including both attitudes and values that may need to be altered and are modifiable in an educational programme helping new married couples to reflect upon their attitudes and also solve their conflicts in a non-violent and non-aggressive manner. This approach felt necessary as Iranian studies on this topic and on IPVAW in general are still limited and scattered -27. AlsoKermanshah city, where the study was conducted, is the capital of the province Kermanshah and has a population of about 800,000 inhabitants. In the city, the three main ethnic groups called the Kurds (in majority), the Fars and the Laks (minority) cohabit. The Kurds, who also live in Iraq and Turkey, and the Laks live only in the western part of Iran – where Kermanshah is situated – and the Fars are in the majority in most of the rest of the country. Kermanshah is considered to have a patriarchal culture stronger than that of many other Iranian cities and the divorce rate is 3.4% .The interviews were conducted during August 2005 in the city of Kermanshah, seeking married women of reproductive age co-habiting with an intimate male partner. As the average age of marriage for women in the city is 20.3 years , women The sample size was estimated at 460 women, considering the Cochran formula allowing about 15% attrition. Interviews were conducted in all 48 centres, in proportion to each centre's population coverage. Women were recruited consecutively, on site, by trained interviewers (see below). In total, 435 of the 460 eligible women approached were interviewed (non-response rate: below 6%); none of them was accompanied by her husband.A questionnaire in five parts consisting mainly of closed questions was developed and pre-tested. Part I covered the spouses' socio-demographics and Part II addressed women's prior exposure to IPVAW. Here, a set of questions focusing on non-physically abusive acts including moderate forms of violence , like shFor each single item presented in Part III and Part IV, respondents were asked to state the extent to which they agreed that it could cause (or trigger) the occurrence of IPVAW alternatively be a consequence of its occurence. The answer alternatives were: completely disagree, disagree, don't know, agree and completely agree.Three trained female interviewers, all of which were experienced and university graduates (BSc degree) collected the data consecutively and in a convenient manner. Interviews were conducted privately at each health centre on every day of the week. Upon arrival at the centre, women were asked by the interviewer whether they would be willing to participate in the study. They were informed about the study goals, briefed about the content of the questionnaire, received assurance of confidentiality and notified of the possibility to withdraw from the interview at any time.Univariate frequencies for each response alternative were compiled and arranged in descending order of agreement , all respondents aggregated (using SPSS version 14). Also, item by item, comparisons were made between groups of respondents considering selected socio-demographics , and spouses' ethnic group), education level and employment, and also prior exposure to violence. Two by two comparisons were made and the significance of the difference was estimated with 95% confidence intervals, using a test for two independent proportions .The study was reviewed and approved by the Iranian National Ethics Committee of Medical Research.The 13 potential triggers presented in the questionnaire are listed in Table Over 80% of the women completely agreed with the triggering effect of the first two items, both of which can imply a husband losing face in front of others: unpleasant verbal communication and unsuitable clothes (88.5% and 86.9% respectively). Items related to home chores and household matters  score 80% when both "agree completely" and "agree" are considered. Lowest on the list are potential triggers related to leisure time activities and, otherwise, women asking questions about husband's friends. For those items, the proportion of women having "no idea" is also the highest.Table Table Table *°. Items which have significant differences with more than one other item are underlined.Table The order of the items from the three parts  is quite consistent among the sub-groups considered, but with some noteworthy differences. Among the most consensual potential triggers, all but the first one, "unpleasant verbal communication", show some significant inter-group differences. Also, women's occupation and husband's education level are descriptors where substantial differences are observed: housewives' scores are systematically higher than those of women who work/study. Furthermore, women whose husbands are less educated have higher scores than those whose husbands are university graduates (see for instance "arguing back"). There are also some differences based on the husband's ethnic group, particularly for "infidelity", where the consensus is higher among Laks' wives than Kurds' or Fars'. For arguing back, not obeying and quarrelling about in-laws, consensus is higher among women who experienced violence.Inter-group differences are not very pronounced as regards the potential causes of IPVAW. When significant, they are similar to the differences found for potential triggers. Two items divide the respondents when comparing housewives and women working/studying: mental disorder of the husband and his work-related problems. Husband's work problems also score differently when women are stratified based on their husband's education.The categories of women's occupation and husband's education also divide the respondents when it comes to the consequences of IPVAW, in particular inability of the wife to do her duties. More women married to Fars are in complete agreement as regards "children's learning problems" being a possible consequence than those married to Kurds or Laks. Also, for this item, women who have experienced violence scored higher than those who have not.It has been stated that the prevention of IPVAW requires a community-wide response to individual risk factors, personal relationship, and larger cultural, societal and economic factors ,32. AlthUltimately, the combination of the assessments made among various community members  will help determine the attitudes and behaviours that can be targeted by an intervention and the potential barriers to be dealt with ,22. The The study shows that, in the study area, among the women surveyed, most potential causes and triggers proposed receive considerable agreement. We interpret this as an indication that the women interviewed believe that most potential causes and triggers proposed may, at some point in a relationship, engender IPVAW and we regard this as something essential to address in the development of a prevention programme (i.e. reducing "victim blaming"). Individual-related factors are the ones that attain the highest levels of agreement. The top two potential triggers, "unpleasant verbal communication in front of others" and "unsuitable clothes in front of others" are behaviours that, in the Iranian context, are likely to put down the male partner in front of others . This hiAs the first intervention planned for is educational, individual and relational factors will be possible to address, although in ways that are yet to be identified. Factors of that kind are among those more easily dealt with in the family. It is also known that male partners are more able to control outbursts of IPVAW than one might think . For theThese results are not easy to compare to those of other studies, as opinion surveys about potential causes of IPVAW are uncommon. One conducted in the USA reports findings consistent with the current one in that social and cultural factors were not as much mentioned as potential factors and substance abuse and men's mental problems ranked high. This isFurthermore, in this study, the order of agreement for potential causes, triggers or consequences of IPVAW is quite similar among the socio-demographic sub-groups and even groups of victimised women. Of the socio-demographic characteristics measured, being a housewife and being married to a low-educated husband, though not affecting the ranking of potential causes/triggers that much, does significantly push the level of agreement upwards. Even one's prior experience of moderate forms of violence has little effect on the ranking. For their part, marriage duration, number and sex of children and age have little – if any – effect on women's opinions. As suggested by others, the diversity of opinions about IPVAW can to a limited extent be accounted for by the diversity in people's background or experiences .The women surveyed seem also to be very aware of the multifaceted potential consequences of IPVAW: we found very high consensus on all consequences listed, except for economic problems in the family unit.The convenient sampling strategy used yielded a high response rate (94.5%), which could be attributed to the precautions taken to secure individual confidentiality ,30 and rAs mentioned above, we interpret the high level of consensus obtained overall as an indication that the married women interviewed do consider that most potential causes and triggers of IPVAW covered may, at some point in a relationship, engender IPVAW, although not necessarily in theirs. Although confidentiality was guaranteed and the questionnaires were anonymous, a social desirability bias may have come into play. The lower acknowledgement of the absence of a male child and of the  size of the dowry as potentially linked to the perpetration of IPVAW might, we feel, be a case in point.A drawback of the study is its descriptive character and the fact that the sample may not be representative of the whole target population. Let us emphasise that, for safety reasons (that primarily of the participants) ,30, it fThough the findings ought to be considered with caution, we believe the views reported herein may be regarded as a reasonable representation of those of married women in the target community. As there are few studies of this kind in the published literature, it remains difficult to assess how much the results are specific for those women or whether they are similar to those from other settings, in or outside the country.Our social diagnosis of women's opinions reveals that most factors proposed receive considerable agreement as potential causes and triggers of IPVAW. Although being a housewife (women's occupation) and having a relatively low-educated husband push the women's score upwards, socio-demographic characteristics and prior victimisation to non-physical violence have, in the main, little effect on the opinions of women about the causes, triggers and consequences of IPVAW. This is more so for potential causes and consequences than for potential triggers. Yet, the highest consensus is attained on potential triggers that tend to have a humiliating effect on a husband in front of other people. These results reveal attitudes and behaviours that need thorough consideration in the development of an educational programme where both acceptance of the victim responsibility and perpetration by the partner of violence acts will need to be dealt with.The authors declare that they have no competing interests.All three authors contributed to the conception of the study design and data collection instrument. BH supervised and coordinated the data collection, entered and analysed the data, and co-authored the manuscript. MGF participated in the finalisation of the manuscript. LL took part in the data analysis and the writing-up of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients.3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis.Information on birth size  from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis.Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival.Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms. During the last two decades, it has been shown that birth size is positively associated with breast cancer risk later in life. Thus, birth weight, birth length, and head circumference have all shown positive associations with breast cancer risk in studies that employed measurements from birth records -3. In a Less attention has been given to these factors as predictors of the prognosis among breast cancer patients. Nonetheless, it has been shown that adult obesity is adversely related to prognosis, both indicated as survival and mortality from breast cancer, and this effect appears to be equally strong for women with pre- and postmenopausal disease . On the In this study, we have therefore assessed whether birth size is associated with survival of subsequent breast cancer, and in the analysis, we have adjusted for the influence of known prognostic factors such as lymph node status and tumour diameter.In order to have access to data on birth size, eligible breast cancer patients had to be born in Trondheim or Bergen, Norway. Therefore, we used data from the Norwegian Cancer Registry to identify women with breast cancer who were residents in Trondheim or Bergen at the time of diagnosis. The Central Person Registry, which is administered by Statistics Norway, provided the necessary information on place of residence at birth. That registry maintains continuously updated records on each woman's residential address and the identity of the mother.The information on birth weight and birth length for patients born in Trondheim was collected from the birth archive of EC Dahl's Foundation that served as the major birth clinic in Trondheim from 1910 to 1970. Birth data from Bergen were derived from archives of Bergen Birth Foundation and Midwife School, and later from the Maternity Hospital in Bergen. The information is stored at the Regional State Archives in Bergen. We further used information from the Central Person Registry of Norway to verify individual linkage between women of the study and their birth records.3). The correlation coefficient between ponderal index and birth length was 0.00, and between ponderal index and birth weight it was 0.66, indicating that birth length and ponderal index may be considered independent of each other.To be included, patients had to be singletons born at term; birth length was restricted to range from 46 to 55 cm, and birth weight could range from 2000 to 5000 grams. In the analysis, we only included patients who were treated with modified radical mastectomy. Among 373 potentially eligible patients, we could include 331 patients in the analysis for whom we had sufficient information from birth. Perinatal information was abstracted from birth records and included birth weight (grams) and birth length (centimetres). As a measure of body mass, independent of length, ponderal index was calculated as birth weight divided by the cubed value of birth length (kg/length(m)Breast cancer specimens were examined at the Department of Pathology, St Olav's University Hospital in Trondheim, or at the Department of Pathology, Haukeland University Hospital in Bergen. Information on tumour diameter and lymph node status at diagnosis was abstracted from the pathology reports.3 and 29.1 kg/m3.In the statistical analysis, birth length, birth weight and ponderal index were categorised into approximate quintiles, and in subsequent analyses, the second, third and fourth quintile were combined into one category because of the range between the second and the fourth quintile was small. Thus, each variable had three categories: the first category was the lowest quintile; the second category was a combination of the second, third, and fourth quintile, and the third category was the highest quintile. For birth weight, the first quintile included weights below or equal to 3050 grams, and the fifth quintile included birth weights above 3850 grams. The corresponding threshold values for the lowest and highest quintile of birth length were 48 cm and 52 cm, and for ponderal index, it was 25.0 kg/mAll patients were followed up by linkage to data from the Causes of Death Registry at Statistics Norway. Follow-up started at the date of diagnosis, and median follow-up was 108 months. Women were censored at the time of death, or at the end of follow-up. For patients in Trondheim, follow-up ended on December 31, 1999, and for patients in Bergen, follow-up ended on December 31, 2003. Death from breast cancer was the primary endpoint, and no patient was lost to follow-up. The Cox proportional hazards model was used to estimate the relative risk of dying (hazard ratio) from breast cancer related to the categories (see above) of birth weight, birth length and ponderal index. The Cox model is based on the assumption that death rates between categories of patients are constant over time. No serious deviations from the proportionality assumption were found, based on plots of the log minus log survival function (not shown). In a multivariable analysis, we adjusted for place of birth and year of diagnosis, and in additional analysis, we also took lymph node status and tumour diameter at diagnosis into account. All statistical analyses were done using SPSS, version 11.0 for Windows .The study was approved by the regional committee for ethics in medical research.Patient characteristics are presented in Table Since ponderal index and birth length play independent roles, both variables were included in the subsequent multivariable analyses Table . In addiWe have studied whether birth size is associated with the prognosis of breast cancer patients, and found that women with high birth length had poorer outcome than women with shorter length at birth. Specifically, women who were 52 cm or longer at birth had nearly twice the risk of dying from breast cancer compared to women who were shorter than 48 cm at birth. This association was not reduced after taking ponderal index, lymph node status, tumour diameter and place of birth into account. We found no association with survival related to birth weight or ponderal index.In prognostic studies, predictors are usually assessed at the time of diagnosis, and patients are subsequently followed up in relation to outcome, which is typically time to death  from the specified disease under study. In this study, however, measurements of birth size were made decades before the diagnosis (on average 50 years earlier). In the literature, there is no evidence that indicators of birth size have any influence on the prognosis of breast cancer once the diagnosis is established, and previously, no study has assessed survival of breast cancer related to birth size. However, given the magnitude of the association that we observed for birth length, sources of bias that may explain the finding should be carefully considered.It is conceivable that better prognosis in one subgroup of patients could be due to better treatment quality. Birth length is positively correlated with adult height, and hence with socioeconomic status ,11. If qAnother possible source of bias could be that the association of birth length with adult socioeconomic status, including higher education, could lead to earlier diagnosis in women with high birth length. This possibility could result in lead time bias, where survival from diagnosis to death would be longer among patients with high birth length compared to women with shorter birth length, who may be diagnosed at a later stage. Also under this scenario, however, the poorer outcome in patients with high birth length is likely to be underestimated.th century may also be a concern. In an attempt to take effects of calendar time (period) into account, we adjusted for year of birth, but this did not influence the estimates of effect. However, this adjustment may not be sufficient to account for secular changes in birth length.The secular increase in birth length that took place in the 20It is also possible that important but unmeasured confounding factors could explain the poorer outcome of patients with high birth length. For such a factor to be of practical interest, however, it would have to be strong, and substantially influence breast cancer survival. Few known prognostic factors meet these criteria, and they are typically variables that describe the stage of the disease at the time of diagnosis, and therefore, these are not factors that could influence birth lenth. In the analysis, we adjusted for lymph node status and tumour diameter, but the adjustment did not substantially influence the results. However, body weight is a factor that does influence the prognosis of breast cancer patients . Birth lin utero and the development and prognosis of later breast cancer, these results may be helpful in guiding investigators towards prognostic mechanisms. The relatively strong association of birth length, indicating longitudinal growth, may suggest that the insulin like growth factor (IGF) system is involved in the underlying mechanisms.It is difficult to see any practical implication of the finding that high birth length is associated with a poorer prognosis of breast cancer. Nonetheless, by establishing a link between conditions that operate The authors declare that they have no competing interests.BOM and LJV collected the data, and all three authors have contributed to the analysis of the data, interpretation of the findings, and to the writing of the manuscript. All authors have seen and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/115/prepub


Non-specific low back pain is a common cause for consultation with the general practitioner, generating increased health and social costs. This study will analyse the effectiveness of a multidisciplinary intervention to reduce disability, severity of pain, anxiety and depression, to improve quality of life and to reduce the incidence of chronic low back pain in the working population with non-specific low back pain, compared to usual clinical care.A Cluster randomised clinical trial will be conducted in 38 Primary Health Care Centres located in Barcelona, Spain and its surrounding areas. The centres are randomly allocated to the multidisciplinary intervention or to usual clinical care. Patients between 18 and 65 years old  and with a diagnostic of a non-specific sub-acute low back pain are included. Patients in the intervention group are receiving the recommendations of clinical practice guidelines, in addition to a biopsychosocial multidisciplinary intervention consisting of group educational sessions lasting a total of 10 hours. The main outcome is change in the score in the Roland Morris disability questionnaire at three months after onset of pain. Other outcomes are severity of pain, quality of life, duration of current non-specific low back pain episode, work sick leave and duration, Fear Avoidance Beliefs and Goldberg Questionnaires. Outcomes will be assessed at baseline, 3, 6 and 12 months. Analysis will be by intention to treat. The intervention effect will be assessed through the standard error of measurement and the effect-size. Responsiveness of each scale will be evaluated by standardised response mean and receiver-operating characteristic method. Recovery according to the patient will be used as an external criterion. A multilevel regression will be performed on repeated measures. The time until the current episode of low back pain takes to subside will be analysed by Cox regression.We hope to provide evidence of the effectiveness of the proposed biopsychosocial multidisciplinary intervention in avoiding the chronification of low back pain, and to reduce the duration of non-specific low back pain episodes. If the intervention is effective, it could be applied to Primary Health Care Centres.ISRCTN21392091 Low back pain (LBP), in any of its forms , is a common and important reason for consultation with the general practitioner (GP). The point prevalence rate of LBP has been estimated as 14.8% in a study carried out in the general Spanish population ,3.LBP has an important impact on the performance of daily tasks in individuals who present the condition and on their quality of life. It also has family and social repercussions, which are often ignored ,3. It isA study carried out in 36 Primary Health Care Centres (PHCC) in Spain describes the management of a patient with non-specific LBP. Courses of action taken include: 98% of the patients receive pharmacological treatment, 19% some kind of physical therapy and 10% are referred to surgery, while 43% of the patients are assessed through radiological techniques. This study showed that, although management of the patients is consistent with the recommendations based on evidence, after two months of treatment, the pain continued in 37% and had worsened in 10% of patients .Multi-causality of LBP limits, in some cases, the election of an approach strategy which improves symptomatology and obtains effective results. Little is known about effectiveness of primary prevention, both in the general population and in the work place. A systematic revision undertaken by Linton et al , observeNegative findings obtained in many preventive studies might be explained by various factors. For instance, some studies present methodological defects . Moreover, included populations represent a high variety of occupations, and interventions are too variable in content, frequency and duration .When the problem has already been established, early interventions are necessary to prevent chronicity. Selection procedures of psychosocial risk factors have been used to identify patients with a higher risk of developing long-term disability. In those patients, a cognitive-behavioural interventional approach has proved effective in diminishing that risk ,9. ThereThere is evidence of effectiveness of intensive biopsychosocial multidisciplinary intervention in patients with non-specific chronic LBP, according to a systematic review of randomised controlled trials .A Cochrane review, which assesses the same objective but in sub-acute LBP in adults, only includes two randomised clinical studies which meet criteria for sub-acute LBP (between 4 weeks and 3 months duration), and both studies are classified as being of a low methodological quality. The authors conclude that studies with a high methodological quality are necessary, which include bigger sample size and adequate duration of follow-up to test the objectives.It is generally accepted that LBP becomes chronic when the pain persists for longer than 3 months or occurs episodically within a 6 month period . Sub-acuThe introduction of clinical practice guidelines in the treatment of LBP ,17 has iThe main objective is to analyse the effectiveness of a biopsychosocial multidisciplinary intervention approach , to improve disability, reduce pain severity, improve quality of life and reduce incidence of chronic LBP in the working population with non-specific LBP, compared to the usual clinical care.The secondary objectives are:- To assess differences between both groups of patients, the group receiving biopsychosocial multidisciplinary intervention and the group receiving usual clinical care, in terms of duration in days of the LBP episode, work sick leave, duration in days of the period of sick leave and pharmacological treatment.- To assess the responsiveness of the Spanish version of the following questionnaires: Roland Morris disability (RDQ), Mc Gill Pain, Quality of Life (SF-12), Fear Avoidance Beliefs (FAB) and Goldberg questionnaires.- To compare patient satisfaction with care between both intervention arms..- To identify factors associated with chronification of a non-specific LBP episode: sociodemographic, clinical  and psychosocial signs of bad prognosis A cluster randomised controlled clinical trial will be carried out, analyst blinded, which compares patients with non-specific LBP treated with a multidisciplinary approach, with a control group receiving only usual clinical care.The trial will be conducted in a primary care setting, PHCCs located in Barcelona, Spain and its surroundings. We will contact all the PHCCs by presenting the study to their staffs and we will invite them to participate. The study will be comprised of at least 38 PHCCs.Eligible patients will be consecutively selected by their GP, who will inform them about the study objectives. All patients who agree to participate will be given written informed consent to sign.Patients will be included if the current episode of LBP occurs suddenly after a period of a minimum of 6 months without LBP and lasts between 15 days and 12 weeks .Furthermore, patients have to be between 18 and 65 years old, and understand Catalan or Spanish and will be accessible for at least twelve months.Patients will be excluded if: they are unwilling to participate in the multidisciplinary intervention trial; LBP coexists with cognitive impairment or severe psychiatric disorders such as psychosis, or if they have severe major depression; any other cause of disability which impedes answering the various questionnaires; they are pregnant or breast-feeding; they might have anti-inflammatory intolerance or allergy; treatment for physical problems in the preceding three months has been given; and they have been referred for intensive functional restoration programmes or if they have a confirmed diagnosis of fibromyalgia.Furthermore, the GP has to ensure that the patient has no red flag signs or symptoms that are frequently associated with specific LBP or potentially severe illnesses ,16,17.Red flags for possible specific spinal pathology are: oncologic disease during the previous 5 years; constitutional symptoms, unexplained weight loss, fever, chills, recent urinary tract infection; history of drug or alcohol abuse, or immunocompromised host; vertebral fracture ; inflammatory spondylarthropathy (SpA) .Red flags for surgical referral: saddle anaesthesia, recent onset of bladder dysfunction or anal sphincter impairment, major or progressive motor weakness, sensory level, or widespread neurological signs.In this study a cluster design is used because the intervention is delivered to groups. To minimise contamination, the unit of randomisation will be the PHCC. Those PHCCs who agree to participate will be randomly allocated to control or intervention groups by a random sequence generated by a computer programme in blocks of random size and prepared before recruitment of the PHCC by an independent statistician who will be blind to the PHCCs' identities. The blocking factor was randomly selected between an even number  and will vary as the recruitment continues. Primary care physicians will be informed about their allocation after giving final consent to participation.To minimise imbalance across intervention groups, randomisation was conducted stratifying by percentage of immigrants from developing countries registered in each district. We consider two strata, less than and more than 15% immigrants. This variable is taken as a proxy of socioeconomic level.During the recruitment, the GP will identify new episodes of sub-acute LBP in patients consulting for this reason and those who meet the inclusion criteria will be allocated to the intervention group corresponding to the centre. To avoid bias, consent to participate will be obtained before the allocation.Because of the nature of the intervention, GPs were not blind to the patients' allocations. Data analysis will be carried out so that the intervention groups allocated to the patients will be unknown to the analyst.Patients allocated to the control group will receive usual clinical care, and individual intervention based on the application of the "Clinical Practice Guidelines in the Pathology of the Lumbar Spine in Adults" recommendations, published by the "Institut Català de la Salut" . Topics Patients allocated to the intervention group will receive the same individual intervention described for the control group, in addition to an educational booklet "The Back Manual " . Details of the biopsychosocial multidisciplinary group intervention and the educational digital video disc (DVD) are included in Tables To guarantee the standardisation of the group sessions, only one qualified psychologist and one physiotherapist, both of them with extensive expertise in development of training groups, will apply the intervention in all PHCCs.During the intervention period, other non-pharmacological therapeutic measures which differ from those stated in the intervention design will be advised against. However, in the case of non-pharmacological therapeutic measures occurring, they will be registered and included in the analysis.In the follow-up visits at 3, 6 and 12 months, we will ask about the patient compliance of recommendations of treatment and the questionnaires will be completed. Furthermore, if the patient is unable to attend the follow-up visits, the data collection will be carried out by telephone call.Compliance to the group sessions will be assessed by registering the number of group sessions that patients attend.To ensure patients' adherence to the group sessions, they will be asked a time preference (morning or afternoon) to attend the sessions. One week prior to the group session, they will receive a phone call to report the date, time and location of the session and on the day before, an SMS message with the same information will be sent.At the end of the study, the control group will receive the compact disc of Jacobson's progressive relaxation technique, the educational booklet "The Back Manual" and the audiovisual.Primary outcomes are:Change in disability measured by Roland Morris disability questionnaire (RDQ) [- re (RDQ) ,21. The RDQ questionnaire is a reliable and sensitive measure to evaluate the disability which LBP may generate, namely the limitations in daily tasks which it may entail. Furthermore, the RDQ questionnaire may perform better in the general population [Our study will use the Spanish version of the questionnaire, trans-culturally adapted and validated by the Kovacs Foundation, in collaboration with a team of researchers from various hospitals, including the Kovacs Foundation and different PHCCs. Conducted studies demonstrate the pulation . Total sIntensity of Pain assessed by Pain Questionnaire Spanish version  [- c, 1975) -27, ThisQuality of Life measured by SF-12. We will use the Spanish version of SF-12 because for large group studies, the differences in measurement reliability between the SF-12 and SF-36 are not as important and the SF-12 is worthwhile for specific populations based on large sample sizes [- le sizes . The 12 Secondary outcomes are:Duration of the current episode of LBP (pre-study and study duration). We will consider the current episode finished when the pain and its impact on the person's daily life is reduced, even when the pain cannot be cured completely [- mpletely .Work sick leave (yes or no)- Duration in days of work sick leave- Percentage of change in pharmacological treatments.- Wrong beliefs, inadequate behaviour and work factors assessed by Fear Avoidance Beliefs Questionnaire (FAB) [- re (FAB) . Among pAnxiety and Depression measured by The Spanish version of the Goldberg questionnaire, the "Escala Ansiedad y Depresión de Goldberg" (E.A.D.G) [- E.A.D.G) . This waSatisfaction with care will be measured with VAS scale ranging from 0 to 10.- Patient's assessment of global perceived effect will be measured by self-assessment on a 7-point scale [- nt scale .The main independent variable is the intervention arm: biopsychosocial multidisciplinary group intervention, or usual clinical care.The following socio-demographic variables will be recorded: age; sex; educational level ; working situation ; profession; number of children or other relatives to care for; marital status. Clinical variables: weight and height; previous non-specific acute or sub-acute LBP episodes ; pre-study duration of the current episode of LBP; pain irradiation to the leg (yes or no); severity of pain irradiated to the leg ; stretching radicular test-Lasegue's maneuver ; prescribed pharmacological treatment: muscle relaxants, analgesics, AINEs, corticoids, ansiolitic drugs, gastric protectors, prescribed diagnostic tests: radiography, Nuclear Magnetic Resonance, Scanner; patient compliance of recommendations and treatments; referrals to other departments ; Primary Health Care and Hospital emergency visits due to current sub-acute LBP episode; non pharmacological therapeutic measure ; vigorous physical activity .All the outcomes will be measured at the individual level. All participants will be invited to attend the PHCC for outcome assessments. They will be assessed on his/her first visit to the PHCC, and at 3 months, 6 months, and 12 months after the onset of LBP. The timing for the second assessment was chosen because it would detect the patients' situation near the point at which they would become chronic. The timing for the last assessment was chosen because adequate follow-up time has been recommended by many authorsAt each assessment, an expert trained fellow (a psychologist) will make up to three phone calls at different times during the day to make the appointments. During the visit, he/she will fill out the questionnaires by interviewing the participant, will do Lasegue's maneuvre test, will collect information by reviewing medical records, will contact the patient's GP to inquire about their development  and will resolve any questions about the conduct of research.On January 2009, a pilot study was carried out. Its completion with 14 participants allowed us to: discuss the inclusion and exclusion criteria and the questionnaires used : plan the recruitment of patients to achieve a suitable number of participants per group ; redefine the length and distribution of the contents of the intervention and assess adherence to the intervention.The recruitment period is six months.Table The sample-size calculation is based on change in RDQ at three months after onset of LBP. It is recommended that a change in 2 to 3 points on the RDQ should be considered the minimum clinically important change . To alloData will be analysed in accordance with CONSORT guidelines, extension to cluster randomised trial. Data will be analysed by intention-to-treat. To address potential biases due to incomplete follow-up, we will analyse patients with complete data at all time points and those with data at any time point, using the last known value carried forward to replace missing values. Bias due to non-response will be assessed at each follow-up.The primary end points for the trial will be 3 months (short term), 6 months and 12 months (long term).We will obtain descriptive statistics for the outcome measures, baseline characteristics and clinical measures as mean (standard deviation) or numbers (percentages), with 95% confidence intervals at each assessment for all the patients and for each group.t tests or Mann-Whitney U tests for continuous data and Χ2 tests or Fisher's exact probability test for categorical data for unadjusted comparisons between groups at each assessment.The distribution of data will be checked to ensure that parametric assumptions are met, and non-parametric analyses will be used when appropriate. We will use independent Continuous data for change in scores from baseline will be compared between groups and for each group. The paired t-test for difference will be used to compare the change between pre- and post- intervention.To decide on an important change in individuals, we will contrast the distributions of changes in all the questionnaires and in each assessment, in individuals who change to chronic state and in individuals who do not . We willTo detect changes in groups, the intervention effect will be calculated through the effect-size for each questionnaire and at each assessment. Effect-size was calculated following the method of Kazis et al We will evaluate responsiveness of each scale by standardised response mean (SRM)  and receSimple correlations between the scores of the different scales  will be obtained through the Pearson linear correlation coefficient or the Spearman correlation, in the case of parametric assumptions not being met, at each assessment.Since the unit of randomisation is the PHCC, we will use a regression analysis of individual level data using methods for clustered data . For adjA multilevel Cox regression model will be used to evaluate the association between the main independent variable, the prognostic factors and the time of subsiding of the current episode of LBP or return to work at 3 months. The patients for whom the duration of the current episode is more than 3 months or those who do not return to work at 3 months will be censored at that time. Kaplan-Meier survival curves will be used to compare the rate of evolution to chronicity and return to work between both groups. Logrank and Breslow test will be used for testing the equality of survival among groups.The differences in medication prescription at baseline and at each assessment in the interventions and control groups will be compared.We will calculate the relative risk reduction (RRR) and number needed to treat (NNT) to facilitate development of clinical guidelines for future management.We will study the interactions and the collinearity. The collinearity of the maximal models will be evaluated using the criteria proposed by Belsley . The sigThe SPSS statistical package for Windows, version 17  and the SAS 9.1.3 for Windows , will be used for statistical analysis.The study will be conducted according to Guidelines of the Helsinki Declaration and of Good Clinical Research Practice. The project/study protocol has been approved by the Ethical and Clinical Research Committee of IDIAP Jordi Gol, Institute of Research in Primary Health Care.Informed Consent: The information will be provided orally as well as written. Study subjects will have sufficient opportunity to ask questions regarding study details. Informed consent follows the guidelines of the Helsinki Declaration.Data confidentiality: Confidentiality and anonymity of the data will be ensured according to the law 15/1999 of data confidentiality, both in the implementation phase of the project and in presentations or publications resulting there from. Individual data will be codified to ensure anonymity. Only researchers and monitors will have access to the data.This trial is registered as Current Controlled Trials ISRCTN21392091Non-specific LBP is a prevalent disorder and a common reason for patient visit to GPs. For about 6% to 10% of patients, the disease may recur or become chronic and the demand on the health-care system is costly. Early identification of clinical, psychosocial and professional risk factors is important to prevent the progression to chronic LBP. Throughout this study, we hope to provide evidence on the effectiveness of the proposed biopsychosocial multidisciplinary intervention in reducing non-specific LBP episodes and its personal, social and economic impact. If the intervention is effective, it could be applied to PHCCs.There are some limitations in this study. The participants are persons attending a PHCC. Although this aspect can pose a threat to the external validity of the data, the Spanish National Service is universal and free and more than 70% of the general Spanish population seek attention every year in the PHCC , and thiAcute, sub-acute and chronic LBP is a very common complaint in PHCC. We have assumed that the usual clinical care is homogeneous among clinicians that will participate in the study, namely, the standardized clinical guidelines of the Catalan Health Institute, "Clinical Practice Guidelines in the Pathology of the Lumbar Spine in Adults", to which most of the GPs taking part in the study will belong. These guidelines will be mentioned as the usual clinical care to follow at the presentation session of the study. Moreover, it is known that professionals who participate in research projects tend to be more motivated and experienced. Therefore, we assume that their medical practice involving the studied condition does not differ from that indicated by the guidelines of the Catalan Health Institute. In any case, the effects of a possible variability in the usual clinical practice will be attenuated by our study design, as it will be provided to both groups.As other studies have found a higher rate and lack of compliance, another possible limitation will be the dropout of follow-up. In the present study, the dropout rate was estimated at 20%, since the recruitment and follow-up of the patients is done by their GPs, and patients tend to visit them when they feel pain. However, we will perform recall mechanisms, and we hope that these strategies will facilitate follow-up and compliance.It is important to point out some strengths in the research. The literature on risk factors for chronic LBP is abundant with numerous prospective studies done with relatively small samples and assessing only a specific category of chronic LBP risk factors. In the present study, we will recruit a large sample size (n = 932), with a short and long term follow-up assessment and focused on achieving the adherence of the preventive interventions as many authors have emphasized . MoreoveAnother strength is the variety of the risk factors addressed , which enables an analysis of interrelations and allows identification and/or confirms the risk factors for chronic LBP.Furthermore, the sample size is calculated taking into account the intraclass correlation coefficient and the design effect. Cluster specific methods and multilevel analyses will be used, because the PHCC rather than the patients were randomised. Because responsiveness is not an immutable characteristic, but may vary according to population and context , each quFinally, one notable aspect of the biopsychosocial multidisciplinary intervention is the promotion of the transdisciplinarity  between The authors declare that they have no competing interests. The study sponsors have no role in the study design, the collection, analysis, or interpretation of the data, the writing of the report, or the decision to submit the paper for publication.All authors were responsible for the conception of the project and drafting the first study proposal. TRB, IFSM, MBC, AB and EPR were involved in writing the manuscript, and all authors critically revised and approved the final manuscript. TRB, IFSM, MBC, JM, ENJ and EPR designed the methodology and TRB designed the statistical analysis. IFSM, MJGM, RMP, MRO and EPR contributed to the description of the background, designed the questionnaires and made the presentation for the recruitment of the PHCC. TRB, MBC, JM, EMM, ENJ, MJGM, MPO, RMP, MNJ and EPR designed the biopsychosocial multidisciplinary intervention and elaborated the educational DVD. AB is the trained fellow and designed the questionnaires and the centralized database. AB, JM, EMM, MJGM and MPO performed the pilot study.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/12/prepub