Blood and blood components are considered drugs because they are used in the treatment of diseases. As with any drug, adverse effects may occur, necessitating careful consideration of therapy. Like any other therapeutic decision, the need for transfusion should be considered on the basis of risks and benefits and alternative treatments available to avoid over- and under-transfusion. This review is focused on the blood transfusion protocol in trauma patients with hemorrhagic shock. Besides, issues related to emergency and massive transfusion have also been elaborated. We conducted a comprehensive MEDLINE search and reviewed the relevant literature, with particular reference to emergency medical care in trauma. Blood transfusion services are a vital and integral part of modern health care. Reducing patient morbidity and mortality is a key objective of any surgical or anesthetic practice. The decision to transfuse a patient can often be a difficult judgment. Resuscitation of a patient with trauma and hemorrhagic shock is the responsibility of the emergency physicians, surgeons, and anesthesiologists. Doctors in these specialties often have to manage life-threatening hemorrhage in addition to the underlying pathology and in such situations are forced to take complex decisions. A good understanding of the physiology of shock and the implications of treatment strategies is essential to achieve a favorable outcome in such patients. In some surgical procedures significant blood loss can be anticipated, and there is always the potential for unexpected blood loss during any type of surgery.Transfusion support is vital for a patient of trauma with hemorrhagic shock. The transfusion of the right component to the right patient in the right quantity and at the right time has been the main focus of attention for critical care doctors. Although blood is the ideal resuscitation agent from a physiological perspective, there are limitations to its use. The potential for disease transmission with blood and blood products is a major concern. In spite of stringent screening of the blood supply with modern sensitive techniques, there is no ‘zero risk’ transfusion. Besides, other concerns such as availability of components, cost, shelf life, and even religious prohibitions against transfusion of blood products limit the use of such components.Significant hemorrhage can overcome the normal compensatory mechanisms, compromise oxygenation and tissue perfusion, and lead to hemorrhagic shock. Besides trauma victims, surgical and obstetric cases constitute the majority of such patients. Acute hemorrhage triggers a series of physiologic responses involving multiple organ systems, including the cardiovascular, respiratory, renal, hematologic, and neuroendocrine systems. Pain, cognitive perception of an injury, and reduction of cardiac preload results in the fight or flight response. A fall in the blood pressure is one of the very first responses. This cannot be attributed only to the initial reduction in intravascular volume. There isWhen there is significant blood loss, there is stimulation of the endocrine system with release of antidiuretic hormone. This helps in conservation of sodium and water. With a drop in the blood pressure, there is activation of the juxtaglomerular apparatus, resulting in secretion of rennin. This forms angiotensin II, which is responsible for vasoconstriction and stimulation of the adrenal cortex to release aldosterone. Aldosterone helps in conservation of sodium and water and also stimulates hydrogen ion secretion, with reduction in acidosis.Other effects of acute hemorrhage are local activation of the coagulation system and adherence of platelets at the site of the damage in the vessels. This, in association with regional reduction in the blood flow by systemic hypotension and local vasoconstriction, can lead to the formation of a stable clot at the site of bleeding.All these compensatory mechanisms maintain critical organ perfusion even in severe hemorrhage. But persistent hemorrhage will overwhelm the capacity of systemic compensatory mechanisms and lead to a downward spiral in the pathophysiology. A decreaIf the hemorrhage is controlled, the outcome of an episode of shock is influenced by the rate and precision of fluid resuscitation, the cellular response of individual organ systems, and the balance of inflammatory mediators over the subsequent hours or days. The patient may survive acutely but die days to weeks later of multiple organ failure triggered by the initial episode of shock.Fluid resuscitation and achievement of hemostasis is the priority in a patient with hemorrhagic shock. Although reduction of the hematocrit is a marker of hemorrhage, it may be misleading in case of rapid hemorrhage. Rapid administration of fluid and blood products to support systemic perfusion can lead to excessive hemorrhage or rebleeding from previously hemostatic areas due to iThe choice of the resuscitation fluid is equally important; there must be maintenance of adequate intravascular volume, oxygen-carrying capacity, clotting function, and electrolyte balance and, at the same time, minimization of extravascular edema and immune system activation. Although crystalloid administration in the form of normal saline or Ringer’s lactate are the immediate means of resuscitation at most centers, careful titration of the quantity infused is required to avoid the negative consequences of over-infusion. Only about 30% of infused crystalloid remains intravascular and therefore the volume required to be infused is about three times that of the lost blood.vs colloid for resuscitation in critically ill patients  found no evidence that resuscitation with colloids reduces the risk of death compared to resuscitation with crystalloids. As colloids are not associated with an improvement in survival and, besides, are more expensive than crystalloids, their continued use in these patients is not advocated. 130/0.4), a new-generation HES product with low molecular weight, has been used for the treatment of traumatic and hemorrhagic shock. It is believed that early infusion of Voluven® is beneficial for maintenance of hemodynamic stability and to balance cerebral oxygen supply and consumption during the resuscitation phase of acute hemorrhagic shock.[Voluvenic shock. New theric shock.The decision to transfuse should not only be based on transfusion triggers but should be coupled with adequate knowledge of the clinical symptoms, rate and extent of ongoing blood loss, cardiac function, and the need for operative intervention. The end goal of transfusion is to restore volume and oxygen-carrying capacity. The type of component to be transfused depends on assessment of the clinical status of the patient.With the advent of blood component therapy, the use of whole blood as a resuscitation fluid has become obsolete. Whole blood is deficient in clotting factors and has high levels of potassium, ammonia, and hydrogen ions. Although it provides volume expansion along with increased oxygen-carrying capacity, there can be volume overload before the needed components are replenished.Since the central pathophysiology of hemorrhagic shock is failure of oxygen delivery, timely administration of red blood cells is the most important component of resuscitation. Blood loss greater than 25% to 30% usually requires transfusion of packed red blood cells in addition to crystalloids. Ensuringin vivo activity of the coagulation system,[Fresh frozen plasma (FFP) is utilized for its clotting factor content in trauma resuscitation. In the presence of massive hemorrhage or coagulopathy, 1 unit of FFP is given for every 4 or 5 units of red cells administered. Administn system, other men system, In additn system, The timiThe decision to transfuse platelets should be based on the etiology of the thrombocytopenia, the presence or absence of active bleeding, and the need for surgical intervention. The trigger for starting platelet transfusion is also undecided. Generally, when the platelet count is below 10 000/µl, platelets are transfused prophylactically to prevent spontaneous hemorrhage. If the patient is bleeding or if invasive intervention is planned and the count is between 10 000/µl and 50 000/µl, then platelet transfusion should be given. In such patients, the count should be maintained above 50 000/µl. Platelet therapy should be guided by monitoring of the post-transfusion platelet count. Patients with fever, infections, disseminated intravascular coagulation, excessive bleeding, and splenomegaly may not show the expected increase in platelet count following transfusion.Hemoglobin-based oxygen carriers (HBOCs) represent an attempt to create a resuscitative fluid with the oxygen-carrying capacity of red blood cells but without the need for cross-matching or the potential for viral transmission. These solutions are either human or bovine in origin and consist of hemoglobin dimers or tetramers. They have shorter half-lives than red blood cells (hours to days).24 Studie25Hemorrhagic shock leads to suppression of erythrocyte production due to the effect of cytokines released as a part of the systemic inflammatory response. High lev32Cryoprecipitate is obtained by slowly thawing FFP. It is rich in factor VIII, von Willebrand factor, and fibrinogen. If FFP iRecombinant factor VIIa is being used in the treatment of bleeding in trauma and non-trauma patients when all other measures fail. It can stop blood loss, reduce blood requirement, and improve clotting parameters. A randomDesmopressin acetate (DDAVP) initiates the release of von Willebrand factor and can increase von Willebrand factor and factor VIII levels in normal subjects 3–5 fold. It can bUrgent need for transfusion in a patient requiring immediate surgical intervention may preclude the performance of usual testing protocol. Adequate pretransfusion samples should be collected before infusion of any donor blood so that compatibility testing, antibody screening and, if necessary, identification studies can be performed subsequently. If blood must be issued in an emergency and there is no time for cross-matching, group-specific blood can be issued. In extreme emergencies, when there is no time to obtain and test a sample, group ‘O’ Rh-negative packed red cells can be released. In such a situation the clinician must sign a release authorizing and accepting responsibility for the use of incompletely tested products as a life-saving measure.Massive transfusion is defined as transfusion approximating or exceeding the patient’s blood volume, or transfusion of more than 10 units of blood within 24 h. ReplacemThe total volume and type of fluid infused during initial resuscitation has a strong influence on the outcome. Priority should be given to maintenance of intravascular volume and adequate oxygen-carrying capacity. Other parameters such as clotting factors and serum electrolyte levels should also be monitored.45 Admini46Initial resuscitation of a patient with hemorrhagic shock should be based on identification and correction of the source of bleeding and fluid administration to stop, and then reverse, the pathophysiology of shock. The rate of administration of resuscitation fluids should be adequate to support tissue perfusion. Early use of blood component therapy can help to preserve oxygen delivery and coagulation parameters. However, blood transfusion carries the added risk of transfusion reactions, infections, and several metabolic complications in massive transfusion. Hence, the indiscriminate or prophylactic use of blood products is not warranted.


The present study seeks to describe and analyze the syntactic features of children with severely hearing loss who had access to the hearing aids compared with children with normal hearing, assigning them to the same separate gender classes. In the present study, eight children with severe hearing impairment who used a hearing aid and eight hearing children matched for age and gender were selected using an available sampling method based on the principles of auditory-verbal approach. Hearing children had an average age of 5.45 ±1.9 years and subjects had a mean age of 5.43±2.17 years and their rehabilitation had begun before they were 18 months old. The assessment instrument of the study included the language development test, TOLDP-3. The syntactic skills of these children were analyzed and compared with the hearing children of the same age based on gender. There was a significant difference between the syntactic scores of the hearing-impaired children and the scores of the hearing children of the same age in the “sentence imitation”  and “grammatical completion”  subtests, with no significant difference in the “grammatical understanding” subtest . Moreover, there was no significant difference between male and female children with hearing impairment in terms of syntactic skills development.With early diagnosis and timely rehabilitating intervention, children with hearing loss can perform in a similar way to children of their age with normal hearing in some syntactical areas. Furthermore, the gender factor in the present study had no effect on the development of syntactical skills of children with hearing loss.  Language is such a complex system that only humans have the capacity to learn it. Furthermore, language skills are acquired gradually and in specific steps. At the age of 5, a child’s linguistic system is almost identical to that of an adult to the extent that he/she can meditate and express thoughts accurately via language . The first 36 months of a child's life are critical for language learning, and are incomparable with any other periods of life in terms of language acquisition. Therefore, age is a crucial factor in the emergence and development of language . AccordiThe speech of children with hearing impairment, especially those with severe hearing loss (71– 90dB threshold), is barely comprehensible; an issue that can expose these children to a plethora of social, emotional, educational, and perceptive problems . The resLinguists define syntax as the organization or arrangement of the words in a sentence. In syntactic relations, two types of relations are usually mentioned: syntagmatic relations as well as hierarchical and paradigmatic relations. In a linear organization of the speech, we deal with the syntagmatic elements in a specific order, while in the hierarchical (syntagmatic) organization, the internalized structures are addressed. Both cases require grammatical knowledge, which, as pointed out by Chomsky, is innate and internalized in the human being, waiting to be recalled and utilized when the situation arises .Grammatical and syntactic problems are among the linguistic issues that children with hearing loss encounter. Studies have shown that children with hearing loss pass the growth stage of language development at a slower pace compared with their peers; a subject that has been investigated in different linguistic areas including syntax, semantics, pragmatics and even writing . The devBamford and Saunders also showed that the hearing impaired are more likely to use content words, nouns, and verbs in their speech while grammatical words such as prepositions, pronouns, auxiliary verbs and conjunctions are rarely used . Gray clIn this study, hearing-aid users were compared with hearing children matched in ability on one aspect of language; general syntactic ability. Unlike most studies which focus on the rate of language learning or extent of delay, this study compares the syntactic profile of hearing-aid users with that of hearing children. It is known that hearing-impaired children often demon- strate delays relative to their hearing peers; this study will allow us to compare the extent of those delays across different areas of syntax acquisition. Given the importance of hearing sense, as discussed earlier, this study defines the importance of syntax and identifies strategies to promote the development of syntax in spoken language through listening. Further, the current research seeks to examine the syntactic skills and the role of gender in children with hearing loss under training by adopting a descriptive-analytic perspective, and compares it with the normal children in order to identify the difference between these two groups and offer effective clinical strategies for the early rehabilitative intervention by speech and language pathologists, audiologist, and linguists. The present research is a cross-sectional descriptive-analytical study that draws on an available sampling method. The population included eight hearing children with an average age of 5.45 years and eight hearing-impaired children with a mean age of 5.43 years  with bilateral sensory-neural hearing loss who had been exposed to rehabilitative programs with an auditory-verbal approach. Subjects were selected for the study after completing a questionnaire to collect personal information and recording scores, including information about personal and family status as well as auditory and training state. For children with congenital hearing loss, the information was collected from the rehabilitation file. Monolingual and Persian-speaking children with normal hearing from the same class, who were the same age as the children with hearing loss and had no precedent of hearing problems, were also included in the study. Hearing-impaired children, with normal visual and hearing parents, whose mean hearing loss was between 71 and 90 dB (severe) were included in the study. Aside from hearing impairment, exclusion criteria included history of mental disability, cerebral palsy, and a background of any other related diseases. These children were examined by a psychologist through an IQ test by Wechsler Nonverbal and Good-Enough Scales and an occupational therapist using Infant Sensorimotor Development, infant sensorimotor development and the prediction of childhood IQ developed by Hogarty S and co-workers in 1972 , that diThe language development test, TOLDP-3, which includes syntactic subtests such as "grammatical understanding", "sentence imitation", and "grammatical completion", was used in this study. TOLDP-3 was introduced by Newcomer and Hammill in 1997 as a language development test. TOLDP-3 was developed for children aged 0–4 to 8–11 years. The test was normalized for the Iranian context by Saeid Hassan- zadeh and Asghar Minaee in 2001  ,20.Statistical analysisData obtained from syntactic subtests in the two classes of children with hearing loss and children with normal hearing as well as gender-segregated classes of male and female children with hearing impairment were analyzed by SPSS software based on Version 19. The mean and standard deviation were used for descriptive analysis, while the t-test was used for independent groups in the above classes because the distribution of data was normal according to the Kolmogrov-Smirnov test. P<0.05 was statistically considered significant. All children in the learning center have been taught by routine rehabilitation without any intervention. However, signed informed consent was provided by parents of all the children. According to As it can be seen, there was no notable difference between the two groups in the grammatical understanding subtest, while in the two other subtests  a considerable difference between the standard scores of the two groups was observed.A parametric test (t-independent) was used due to the normal distribution of the data to compare the syntactic skills of both male and female children with hearing impairment. In order to compare the syntactic skills between children with hearing loss and children with normal hearing, a parametric test (t-independent) was used due to the normal distribution of the data.The results of this study show that the performance of children with hearing loss and children with normal hearing in the two subtests of sentence imitation and sentence completion, which required proper use of vocabularies and sentences, were in line with the finding of Peters  and BamfConsidering that gender is one of the factors influencing the language of the children; the studies suggest that this effect is only significant in the early language learning stages. According to the present study, there was no significant difference between male and female children with hearing impairment in syntactic aspects in all three subtests, and they had almost similar standard scores and syntactic gains. This finding is in keeping with the studies of Clark and Stewart (1973), Roberts and Block (1972), Arshi (2000) on the difference between male and female children with hearing impairment in terms of linguistic capacities, which did not report any difference in this regard . The studies of Mofidi et al show that normal students who attended preschool language learning courses had a superior performance in syntactic skills such as grammatical understanding, sentence imitation, and grammatical completion compared with students who failed to attend these classes . This isOur study also had some limitations. Apart from limited sampling, the results were based on cross-sectional data instead of a longitudinal study. Another limitation was the range of our subjects with hearing loss, since all subjects had severe hearing loss. To investigate the hearing loss effect it also could be appropriate to evaluate cochlear implant. Syntax is one of the skills that is learned during growth, particularly the critical period. The development of language skills is influenced by the manner of speech of the people around the child, especially the mother, as well as sentence complexity, repetition and practice, and proper communicative events. Thus, the comparison of the syntactic skills of children with hearing loss and children with normal hearing in this paper shows that the earlier exposure of children with hearing loss to natural and appropriate environment as well as timely and proper rehabilitative education with emphasis on auditory sense can improve the performance of these children to the level of normal children in some syntactic areas, and minimize the delay in other areas through persistency and proper planning. We recommend that, in the future, studies include a large sample and a specific intervention. After a period of time, studies should also investigate children with a hearing aid with respect to other aspects of language skills such as speech production and speech perception.


Paracetamol  is the commonest available analgesic and anti-pyretic. It is readily accessed from pharmacy, patent medicine and provision shops as over the counter drug making it a potential drug of abuse, especially in children. We sought to find its use and/or misuse in children seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu.To determine the dosage, formulation, and frequency of paracetamol administration to children by caregivers and factors associated with its use and/or misuse.An observational prospective study involving 231 children and their caregivers seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital, Ituku - Ozalla, Enugu between June and November 2011 was undertaken. Data on paracetamol use before presentation to the clinic, in addition to demographic and other data were obtained from the caregivers using a structured questionnaire. Ethical consent for the study was obtained from the Hospital Ethics and Research Committee and informed consent was further obtained from the caregivers of the children.A total of 231 children aged six weeks to 16 years and their caregivers participated in this study. The mean ages of the children and their caregivers were 3.8 and 33.9 years, respectively. One hundred and thirty three of the children studied were males while 98 were females. Most of the children (75.6%) received paracetamol at home before presenting. Paracetamol tablet alone or in combination with the syrup was mostly used (60%) and this observation was made across all age groups. The commonest reason for using paracetamol tablet instead of the syrup was that it was more effective. Most caregivers relied on past experience (71.2%) rather than on enclosed information leaflet to decide the appropriate dosage. Half of the children also received other medications, mainly anti-malarials and antibiotics.Paracetamol was commonly given to children on “self prescription” basis and the tablet formulation was most frequently used, with the possibility of misuse and overdose. Caregivers need to be educated on age-appropriate formulations which are less likely to lead to overdose. Paracetamol  is the most widely used analgesic and antipyretic . It is fParacetamol is a weak inhibitor of the synthesis of prostaglandins. The in vivo effects of the drug are similar to those of selective cyclooxygenase −2 inhibitors . These dParacetamol abuse is said to have increased 5- folds between 1978 and 1988, and has worsened to more than 200 g/person/year in the US  and well informed. The use of paracetamol in therapeutic doses is generally safe although hepatotoxicity has occurred with recommended dosages in children in developing countries .This study reiterates the fact that majority of childhood febrile illnesses are first treated at home using past experience as a guide. This is not surprising as no caregiver worth his salt will sit put and watch his sick child in pain and/or discomfort without doing anything. It was also suggested that it gives the child rest and sleep and enables the family to rest too . In a crParacetamol is an invaluable over-the-counter medication which is safe, readily available and affordable; though given in appropriate dose in this study, however, it has great potential for misuse and overdose.More education concerning paracetamol should be given to caregivers and older children on its appropriate dosing to avoid serious adverse events when given inappropriately.A population based study or one carried out in a primary health care rather than hospital based may give a better picture of paracetamol use and/or misuse.The authors hereby declare that we have no competing interests.All the authors made substantial intellectual contributions to this study. OHA was involved in the conception, design, and data collection, interpretation of results, preparation of the manuscript, revision of the article at various stages and preparation of the final draft. Other authors made substantial contributions in the design, data collection, and interpretation of the results, preparation of the manuscript, revision and preparation of the final draft. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/12/103/prepub


The risk of developing a second primary tumour in patients with gastric carcinoma is higher than among the general population. The aim was to investigate the clinicopathological characteristics of the second primary cancers in patients with gastric cancer in this study.In the retrospective study, patients with gastric cancers were evaluated between 1995 and 2005 for primary tumours according to Warren and Gates’ criteria related with the second primary cancers.Nine of the 112 patients with gastric cancer had second primary cancers. Seven of the patients were males and two females. Six patients with gastric cancers had synchronous, and three had metachronous tumours. The age of the patients ranged from 53 to 78 years, and the mean age was 61 ± 8.3 years. The most frequent site of occurrence of the second tumours was the colo-rectum (33%) followed by the upper respiratory system (22%), and the urogenital system (22%) in descending order of frequency.The incidence of the second primary cancer in gastric cancer patients was 8% in the current report. It is recommended that careful preoperative and postoperative examinations for other primary cancers, as well as for the extent of the primary gastric carcinoma, are carried out. Because colorectal cancer was the most common carcinoma combined with gastric carcinoma, the surveillance for this carcinoma  would be appropriate after the diagnosis of gastric carcinoma. The first description of the term “multiple primary neoplasm” by Billroth in 1889 is defined as the development of more than one neoplasm in a patient.4Worldwide, gastric cancer is the fourth most common cancer in population.13The risk of development of a SPC in patients with cancer is increased considerably when compared to the general population.In this retrospective study, the aim was to investigate the frequency and clinicopathological characteristics of SPCs associated with gastric cancers.In this study, 112 patients who underwent the surgical treatment consecutively between 1995 and 2005 were evaluated retrospectively. Gastric cancer was diagnosed and confirmed by endoscopic biopsy in all patients. The patients were investigated through thoraco-abdominal imaging (CT and ultrasonography) following the routine examinations and clinical TNM staging was conducted. Clinical properties, operative findings and pathological results were evaluated from hospital records. The study were excluded those patients who were not operated on for gastric cancer due to the inoperability of their advanced gastric cancer stage.SPC was evaluated according to Warren and Gates criteria, requiring that both tumours should be histologically malignant. There should be minimum 2 cm of tumour free tissue between the two lesions; the duration between diagnoses should be minimum 5 years if the tumours are in the same localization; and it should be demonstrated that the second tumour is not metastasis.SPC was observed in nine of 112 patients with gastric cancer (8%). Six of these patients had synchronous cancer, while the remaining three had metachronous cancer. Seven of the patients were males and two females, and the mean age was 61.0 ± 8.3 years. According to the income, the patients had a lowest socioeconomic level and seven of them were consumed tobacco more than 20 pack-years. No data concerning the presence of malignant diseases was found in the family histories of the patients.synchronous SPC. In one patient, during the endoscopic retrograde cholangiopan-creatography (ERCP) performed while aetiology of extra hepatic cholestasis was being investigated, both antrum and ampulla Vater carcinomas were observed. As the second patient was being examined for complaints such as dysphonia and dysphagia, cancer of the larynx accompanying gastric cancer was observed. During the abdominal exploration, cancer of the appendix was observed in one of the patients who underwent the surgical treatment after the diagnosis of gastric cancer, while in another patient cancer of the colon was found. In a patient with gastric cancer, in the abdominal tomography performed for the preoperative evaluation, tumours were observed on both kidneys and the postoperative histopathological diagnosis was reported as renal cell cancer. The last patient in the synchronous tumour group was operated for cancer of the colon six months previously, and gastric cancer was found in the upper gastrointestinal system; endoscopy was performed during the postoperative follow-up period.Six patients had metachronous SPC: One patient had been followed in the urology department for urinary bladder cancer for three years. During laparotomy, it was found that local and at advanced stage (Stage IV). The second patient had gone through “modified radical mastectomy” due to breast cancer. In the third year of the follow up period, gastric cancer was observed. The third patient had undergone total laryngectomy and the radical cervical dissection because of cancer of the larynx five years previously.There were three patients with The clinical characteristics of patients, the treatment methods and survivals are summarized in The common use of further diagnostic methods has increased the rate of the early diagnosis of malignancy.3In the presence of multiple cancers, there has been no discussion on the patients’ prognosis being worse. However, although there have been plenty of clinical studies about such patients, the number of studies about treatment methods and how the prognosis is influenced has been quite limited. In patients with multiple cancers, cancer can be detected in different organs and their stagings are not homogenous. Furthermore, the patients cannot be classified in groups and comparative results cannot be deduced due to different methods of the treatment.It is well known that synchronous and/or metachronous cancers can be observed in the same or different organs. These include oesophageal with oropharyngeal cancer or gastric carcinoma, breast carcinoma with contralateral breast carcinoma or endometrial carcinoma, colon and rectal carcinoma with another colorectal primary or genitourinary primary tumour, and multiple primary cancers within the urinary tract. It is thought that the presence of cancer in the family history, genetic factors and chemotherapy and radiotherapy applications affect the formation of multiple cancers. Despite the fact that there have been studies showing that the synergy of gastric cancer and other cancers can be due to certain disorders, such as microsatellite instability, germ-line mutations and E-cadherin, TP53, RAS mutation; the molecular basis of the formation of tumours is still not understood completely.17The frequency of SPC-associated gastric cancer was found as 8% in the current study. As it can be seen in Concerning second primary cancers in gastric cancer patients, environmental factors, such as dietary habits or tobacco use, and genetic factors have also been suggested to be risk factors. In published series, it is seen that the frequency of finding SPC accompanying gastric cancer is higher in older male patients, as it is in other types of cancer.The tumour determining the prognosis in SPC is gastric cancer.5In a study in which gastric cancer was investigated as the SPC, an increase in gastric cancer development risk was observed within 10 years following cervical, ovarian, testicular cancers and Hodgkin and non-Hodgkin lymphoma. Treatments of the initial cancer, such as the radiation therapy or chemotherapy were found to be responsible for this increase in risk in gastric cancer and SPC.Hereditary conditions known to increase the risk of gastric cancer include: familial cancer syndromes such as hereditary non-polyposis colorectal cancer, Li-Fraumeni syndrome, breast-ovarian cancer syndrome, multiple endocrine neoplasia Peutz-Jegher syndrome and Cowden syndrome.Among the SPCs associated with gastric cancer, colorectal cancers are the most frequent and their rate is reported to be between 20% and 70%.25In the present series, the rate of SPC associated with gastric cancer is 8%. This relatively high rate indicates that it would be highly significant to pay attention to the development of SPC in the preoperative evaluation period, in the exploration during surgery, and in the postoperative follow up period. The systemic investigation and examination of patients with gastric cancer should be performed in detail, and all organs should be examined carefully during surgery. In addition, while investigating possible recurrence and metastasis of the primary cancer, all systems should be examined for the possible presence of SPC. Not only for patients with gastric cancer, but also for all malignant cases it is extremely necessary to inform the patients about signs and symptoms of other organs and to perform the systemic investigation and the full physical examination in each control in case multiple primary cancers develop. The early diagnosis of SPC provides a longer survival and a better quality of life.To conclude, the probability of the development of multiple primary cancers should be considered in the diagnosis and the treatment of all malignant tumours. Since gastric and colorectal cancer synergy is quite frequent, the importance of gastrointestinal panendoscopy should be highlighted. The treatment should be appropriate for observed synchronous or metachronous cancer and it is necessary to try to be treated with curative intent in combined radical resections.


However, current implementation is not optimal, leaving room for improvement. Based on barriers and facilitators for TEM that were recently identified among professionals and subfertile couples, we have developed a multifaceted implementation strategy. The goal of this study is to assess the effects of this implementation strategy on the guideline adherence on TEM.Prognostic models in reproductive medicine can help to identify subfertile couples who would benefit from fertility treatment. Expectant management in couples with a good chance of natural conception, in vitro fertilization (IVF) facilities . The effect of the implementation strategy, i.e., the percentage guideline adherence on TEM, will be evaluated by pre- and post-randomization data collection. Furthermore, there will be a process and cost evaluation of the strategy. The implementation strategy will focus on subfertile couples and their care providers i.e., general practitioners (GPs), fertility doctors, and gynecologists. The implementation strategy addresses three levels: patient level: education materials in the form of a patient information leaflet and a website; professional level: audit and feedback, educational outreach visit, communication training, and access to a digital version of the prognostic model of Hunault on a website; organizational level: providing a protocol based on the guideline. The primary outcome will be the percentage guideline adherence on TEM. Additional outcome measures will be treatment-, patient-, and process-related outcome measures.In a cluster randomized trial, 25 clinics and their allied practitioners units will be randomized between the multifaceted implementation strategy and care as usual. Randomization will be stratified for This study will provide evidence about the effectiveness and costs of a multifaceted implementation strategy to improve guideline adherence on TEM.http://www.trialregister.nlNTR3405. This study is sponsored by ZonMW. Subfertility is defined as the absence of conception after one year of unprotected intercourse . It affei.e., 36% of the couples with a good prognosis eligible for TEM  already started medically assisted reproduction (MAR) .The audit and feedback of the current care will consist of a feedback report based on the results of the baseline measurement. This feedback will report clinic’s guideline adherence on TEM in a twelve-month period prior to the randomization compared with the other participating clinics. It will give insight in how they are adhering to the guideline concerning the policy for couples with unexplained or mild infertility, In addition to this audit and feedback, an educational outreach visit will take place with fertility doctors and gynecologists (in training), in which background information about how and when to use the prognostic model of Hunault, and subsequent TEM will be given and in which the results of the baseline measurement and local barriers will be discussed. The result of this visit will be an individualized action plan per clinic.The supportive consultation tools are developed containing a digital version of the prognostic model of Hunault on a website and we will provide professionals with a summary of the guideline on TEM in the form of a pocket card.i.e., making clear it is not a waste of time). Consistent with functional models of medical communication described in the field [Finally, a video-based training strategy will be provided to improve the communication techniques to counsel the patients on their chance of spontaneous conception versus conception after treatment, the (dis)advantages of expectant management versus fertility treatment, and on the reason for TEM , identification of patients with mild or unexplained infertility, the use of the prognostic model of Hunault, and TEM . The clie.g., were patients referred according to the guideline recommendations.Furthermore, we will provide the GPs allied to the intervention clinics with feedback on their referral behavior, To include a representative patient group, we will select potential participating couples retrospectively in each clinic by means of the clinics’ financial registration database (Diagnosis Treatment Combination code). In this nationwide registration system, patients undergoing diagnostics or treatment for infertility are identified with a specific fertility code (F-code). For the baseline measurement, we will invite couples that were given the code for new fertility patients (F-11) between February 2011 to March 2012 to participate in this study. For the after measurement, we will invite the couples that were given the F-11 code during the ten- to twelve-month intervention period. We will invite couples to participate by giving their permission for a medical record study and filling out a questionnaire.The couples are eligible to participate when they have been diagnosed with unexplained or mild infertility, have a good prognosis (>30%) according to Hunault’s prediction model, did not have previous fertility treatment, and the female age is between 18 and 38 years. Couples with bilateral tubal pathology, severe male factor, or anovulation are not eligible to participate.The expected adherence to TEM in the control arm is estimated based on previous studies at 60% . To incrThe primary outcome measure of the proposed study for effectiveness will be the guideline adherence rate on TEM: the percentage of couples that are eligible for TEM  who actually agree upon the expectant management period of at least six months after the initial fertility assessment is concluded.1. Treatment-related measures: time to the start of fertility treatment and the number and types of fertility treatments that the couples received.2. Treatment outcome-related measures: (ongoing) pregnancy rate, miscarriage, extra uterine gravidity, multiple pregnancy rate, and time to pregnancy.3. Patient-related outcome measures : general experiences with fertility care such as information provision, respect for patients’ values and accessibility of care (to be measured with Patient Centeredness Questionnaire Infertility) , specifi4. Process related measures: percentage transition of patients to another fertility center.e.g., age, referral status, type of infertility, duration and cause of infertility).5. Background characteristics that could influence guideline adherence . The second part regards the patients’ experience with the prognostic model and TEM as well as the patients’ trust in both the GP as well as the fertility doctor/gynecologist. The third part is the Patient-Centeredness Questionnaire-Infertility, a validated instrument measuring patient-centeredness of fertility care by asking about patients’ experiences with care. The last part is the FertiQol questionnaire, We will only use the Core module, which involves questions about mind-body, emotional, relational, and social aspects.The questionnaire will be divided into four parts. The first part consists of background questions  and multiplied by reported or guideline prices according to Oostenbrink [We plan an economic evaluation alongside the clinical trial to investigate the cost-effectiveness of the multifaceted implementation strategy to improve guideline adherence on TEM. This economic evaluation compares the multifaceted implementation strategy to usual care and is done from a societal perspective. A distinction will be made between costs of the development and introduction of the implementation strategy and the costs of maintaining the implementation strategy. The input of resources is assessed by collecting volumes of consumed resources , and we expect it to reduce the physical and psychological burden. As a consequence, the costs for fertility treatment will decrease.This cluster RCT will compare a multifaceted implementation strategy to usual care on improving guideline adherence to TEM. If TEM is applied more frequently, it will reduce the number of performed IUI, IVF, and ICSI cycles, the incidence of treatment related complications . By doing so, and thus tailoring the patient-directed intervention to the infertility population, we hope to increase the effect of this intervention even more.For the specific interventions that will be used in the multifaceted implementation strategy, the review showed that audit and feedback and educational outreach visits can be effective  -34 and pAside from the multifaceted and barrier tailored aspects of the strategy, this study has several more strengths.First, the number of participating clinics is a great strength of this study. One-quarter of all Dutch clinics from all over the country participate in this study, ensuring the representativeness of the Dutch infertility population as well as the professionals who provide fertility care.Second, the process evaluation provides us with more information on the effectiveness and usefulness of the different interventions used in the strategy and not only of the multifaceted implementation strategy as a whole. We know that the multifaceted aspect of the intervention does not necessarily make the intervention more effective, therefore we need to assess the effectiveness of each individual intervention separately as well . This isThird, the cost evaluation that will take place is very important from a societal aspect. Healthcare is becoming increasingly expensive, and cost reduction is a very important and common topic in most governments and healthcare institutes. This economic evaluation will provide further information on how we can reduce costs in healthcare by following the current and already existing guidelines for best practice and care.A possible limitation of the study is the chance of contamination of the GPs between the intervention and control group. GPs can refer patients to more than one clinic; this makes it possible that a GP who is allied to an intervention clinic can also refer patients to a control clinic. However, we think that the occurrence of actual contamination will be very small because the participating clinics are very well spread over the country. In case contamination of GPs does occur, we expect the effect on the outcome to be very small or even undetectable because the multifaceted intervention strategy is mostly targeted at the secondary and tertiary care.In summary, the main contribution of this study is that it seeks to identify the most effective strategy for implementing the guideline on TEM in subfertile couples. Ensuring the appropriate uptake of guideline recommendations by both professionals and patients will improve the care for these patients.TEM: Tailored Expectant Management; ESHRE: European Society of Reproductive Medicine; NICE: National Institute of Health and Clinical Excellence; NVOG: Dutch Society for Obstetrics and Gynecology; MAR: Medically Assisted Reproduction.The authors declare that they have no competing interests.BWJM, WLN, PGH, FvdV, DB, RH, FAMK, and NvdB were involved in conception and design of the study. NvdB, FAMK, and WLN drafted the first manuscript. All authors read and approved the final manuscript and are local investigators in the participating centers.


Universal access is one of the major aims in public health and social care. Services should be provided on the basis of individual needs. However, municipal autonomy and the fragmentation of services may jeopardize universal access and lead to variation between municipalities in the delivery of services. This paper aims to identify patient-level characteristics and municipality-level service patterns that may have an influence on the use and costs of health and social services of frail elderly patients.Hierarchical analysis was applied to estimate the effects of patient and municipality-level variables on services utilization.The variation in the use of health care services was entirely due to patient-related variables, whereas in the social services, 9% of the variation was explained by the municipality-level and 91% by the patient-level characteristics. Health-related quality of life explained a major part of variation in the costs of health care services. Those who had reported improvement in their health status during the preceding year were more frequent users of social care services. Low informal support, poor functional status and poor instrumental activities of daily living, living at a residential home, and living alone were associated with higher social services expenditure.The results of this study showed municipality-level variation in the utilization of social services, whereas health care services provided for frail elderly people seem to be highly equitable across municipalities.Another important finding was that the utilization of social and health services were connected. Those who reported improvement in their health status during the preceding year were more frequently also using social services. This result suggests that if municipalities continue to limit the provision of support services only for those who are in the highest need, this saving in the social sector may, in the long run, result in increased costs of health care. The population in European societies grows older and the importance of health and social services will increase. The elderly are disproportionate users of the health and social care system and this provides a major challenge to the planning of services for older people. Traditionally, the health care and social service sectors have operated separately. The growing demand for integrated services and the rising costs are leading to a more intensive collaboration between the health care and social service providers .In Finland, social and health services are largely financed with public funds, and the principal goal is that services are equitably accessible to everyone . The staWhen developing elderly care policies we need to know why people are using health and social care, and which factors are related to equitable access to care. Andersen’s behavioural model of health service use ,5 providPrevious studies have shown that age, functional ability, health status, chronic illnesses, and socio-economic factors have an influence on service utilization ,10-181919. The vAccess to care is a multidimensional concept, and the utilization of services describes the use as “realized access” ,20. EvenThe purpose of our study was to identify patient-level characteristics and municipality-level service patterns that may be associated with the use and costs of health and social services for frail elderly people.The individual-level data were obtained from a randomised controlled trial concerning a geriatric rehabilitation programme designed for frail elderly persons ,22, whicThe present study was approved by the Ethical Committees of the SII and Turku University Hospital. All of the study participants gave their written consent to the study. The individual-level data were linked with data from the national databases of the Care Registers of the National Institute for Health and Welfare (THL) and the Social Insurance Institution (SII). The registry data aren’t publicly available.The utilization of health care services covered both the public and private sector care. Data on inpatient care and day case surgeries were drawn from the National Care Registers of the THL. Data on the use of outpatient care services within the private sector and the use of medicines were obtained from the SII registers. A self-reported questionnaire was used to collect information about the number of visits to the public sector outpatient care during the preceding year.The utilization of social services covered institutional care and formal home-help services provided by municipalities. For those living in residential homes and sheltered housing, services such as home help, washing and cleaning were included in the analysis. For those who were living at home, formal home care, home nursing, and support services were included. Data on the utilization of social care services were obtained from questionnaires. We asked the municipal social and health care officials to collect data on service use from their clients’ individual care and service plans. The data derived from questionnaires were cross-sectional both at baseline and 12-month follow-up. For those cases where changes occurred in the use of services during the follow-up, the annual data consisted 6 months of services used at the baseline and 6 months of services used at the follow-up.The total expenditure of health and social services utilization was determined by multiplying the use of services by their standard unit costs. For the monetary valuation of health and social care services, we used Finnish standard costs information . BecauseTo estimate the effects of independent characteristics on the costs of service utilization, we used the following three models:Model 1: The costs of health care services and medicines Model 2: The use of social care services Model 3: The costs of social care services used Due to the fact that informal care is a common way to organize care for elderly, there were 240 subjects how did not use social services at all (‘No’ in MODEL 2). For those who used social services, living in sheltered housing causes stairwise effect to costs. Because the distribution was rising in steps and the assumptions of continuity did not hold, we categorized the costs of social care (MODEL 3).Functional ability was assessed by the Functional Independence Measure (FIM), with the total score ranging from 18 (the lowest) to 126 (the highest level of independence) , and by Health-related quality of life (HRQoL) was evaluated by using the 15D score, ranging 0–1  ,28. To eTo assess the living conditions, the subjects were asked “Is your residential environment rural or urban?” (yes/no) and “Are you living alone?” (yes/no). The dwelling circumstances were categorized into three categories: home without formal home-help, home with formal home-help, and residential home or sheltered housing.The municipal social and health care officials were asked to collect information on informal support and assistance from their clients’ personal care and service plans. They reported "yes" if the person received informal care that was considered as supplemental to formal care, and "no" if otherwise.A self-reported questionnaire was presented to the subjects to collect information on the availability and extent of informal care. Respondents were asked to answer the question “Is there any person who helps you when needed?” The answers were categorized into four categories; not available, occasionally, when needed shortly, as long as needed. Respondents were also asked whether they had been granted a Home Care Allowance by their local municipality.For the purposes of the Age Study, the subjects were randomly assigned to either an in-patient rehabilitation programme or standard social and health care. In this study, to standardize the effect of the rehabilitation programme, we included rehabilitation as an explanatory variable in all our models.At municipal level, we investigated if municipalities had integrated the administration of their health care and social services (joint budgets and management). We asked the municipal social and health care officials: “Is your local health and social care administration integrated or not?” (yes/no).A hierarchical analysis with fixed (patient level) and random  effects was used to estimate the effects of explanatory variables on the utilization and costs of health and social services. We used the SAS PROC GLIMMIX procedure to fit the models ,30.First, bivariate correlations between independent variables were examined to check for correlations. All correlations were low. The independent variables were included in the multivariate model using the entrance value of P < 0.05 in the univariate analysis. All multivariate analyses were adjusted for rehabilitation in order to standardize the effect of the rehabilitation in the randomized trial setting. The effect sizes as a result of linear and logistic analyses were expressed as estimates (β) or odds ratios (OR) or cumulative odds ratios (COR) with 95% confidence intervals (CL) and the corresponding p-values.For quantitative variables, skewness of distribution was analysed. Skewness was detected in health care costs, and a logarithm transformation was calculated to correct the distribution. In the analysis, we divided the variables concerning functional needs  by their standard deviation to make them commensurable and to make it easier to compare the odds ratios. Age was divided by five in order to highlight the impact of every five-year increment in age.At the baseline, the mean age of the subjects was 78 years (range 65–96 years). In the older age group (over 75-year-old subjects), the number of people living alone was higher and impaired cognitive capacity was found more often. Informal care and hospital admissions were also more common in the over 75-year-olds Table . Due to The mean total costs of the utilization of health and social services were 10300 euro during one year (median 5400 euro) Table . The proAn analysis was carried out in two steps. First, an intercept-only model without any explanatory variables was applied. The intraclass correlation of the total costs of health and social care services was 0.06, meaning that roughly 6% of the variance is attributable to the municipality level and 94% to the patient level. When costs were examined for the health care and social care sectors separately, the variance in the costs of health care services was totally explained by individual differences in health; the covariance estimate for the municipality variable was zero. In the use of social services, a null model with two levels showed that 9% of the variability in the social services costs was explained by the municipality level and 91% by the patient level.In the multivariate model, the health-related quality of life (15D score) appeared to be a powerful indicator for utilization of health care services (p = 0.0004) Table . A statiA logistic analysis was conducted to explain the use of social care services Table . In the The costs of received social care services were categorized into three groups: annual costs under 1500, 1500–6000, and over 6000 euro Table . When coWe found that, problems of access to services were concentrated in social care services rather than in health care in frail elderly population in Finland. No differences were observed in the utilization of health care services at municipality level, whereas in the social services, 9% of the variation was explained by the municipality-level factors. Since informal care could be substituting for formal social care services, it is possible that differences in the municipalities’ policies to support informal care explain, to some extent, the variability in social service use.At the patient level, we found that living alone and availability of informal care were strong explanatory variables of the costs of social services. There is a growing trend that older people live alone, and the female informal care-giving potential is declining due to rising female employment rates . A reducIn our study, a connection was found between the utilization of social care services and perceived health. Those who reported improvement in their health status during the preceding year were more frequent users of social care services. According to Andersen, effective access to care is established when use of services is connected with improves in health status . Our finThis is consistent with the literature emphasizing the significance of integrated care for the elderly -35. StilOur findings indicate that the administrative structure alone does not ensure that integration of care has positive effects. Earlier studies have suggested that community based integrated health and social care services might better meet the multiple demands of the population, especially among frail elderly population ,36,37. BIn the multivariate models, we introduced explanatory variables mostly at the patient level. At the municipality level, we focused on the question of integrated services. We measured integration with one question concerning the administrative integration, and this may be insufficient to describe the multidimensional phenomena of integration.No other specific variables – such as proportion of elderly people, economical situation, or population size – were introduced at the municipality level, because we did not aim to explain differences between municipalities. Such variables should, however, be taken into consideration in future studies.While frail aged people with deteriorated health must be provided care as soon as any need occurs, the results of this study cannot necessarily be generalized to apply to the aged population as a whole.In lack of national registers, data on municipal primary health care and social care services were collected through questionnaires that were completed by the elderly participants and by the representatives of the local social and health care units. In Finland, municipalities are the main provider of services for the elderly, and therefore, municipal records on service use are comprehensive and reliable. Furthermore, a vast majority of the costs were calculated from registry data, which in Finland are regarded to be very reliable .Municipality-level variation was observed in the utilization of social services, whereas health care services provided for frail elderly people seem to be highly equitable at the municipal level. Nevertheless, there may be differences in access to services at the patient level due to factors which we did not measure, for example, socio-economic factors.We found that the utilization of social and health services were connected. Those who reported improvement in their health status during the preceding year were more frequently also using social services. This result suggests that if municipalities continue to limit the provision of support services only for those who are in the highest need, this saving in the social sector may, in the long run, result in increased costs of health care. In order to control the expenditure, it is necessary to ensure that the integration of services provided for the elderly residents is not only an administrative but also a practical measure. Another important determinant of care expenditure is informal care. Informal care and single households can have a major impact on the demand for formal care in the future.The authors have no financial or non-financial competing interests.SK participated in the design and coordination of the study, performed the statistical analysis and drafted the manuscript. IA-R participated in the design and coordination of the study and drafted the manuscript. KH participated in the design and coordination of the study and helped draft the manuscript. HH tutored and participated in the statistical analysis and helped draft the manuscript. MV participated in statistical analysis and helped draft the manuscript. PR participated in the design of the study and drafted the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/204/prepub


Social, political, and economic factors are directly and indirectly associated with the quality and distribution of health resources across Canada. First Nations (FN) women in particular, endure a disproportionate burden of ill health in contrast to the mainstream population. The complex relationship of health, social, and historical determinants are inherent to increased cervical cancer in FN women. This can be traced back to the colonial oppression suffered by Canadian FN and the social inequalities they have since faced. Screening – the Papinacolaou (Pap) test – and early immunization have rendered cervical cancer almost entirely preventable but despite these options, FN women endure notably higher rates of diagnosis and mortality due to cervical cancer. The Anishinaabek Cervical Cancer Screening Study (ACCSS) is a participatory action research project investigating the factors underlying the cervical cancer burden in FN women. ACCSS is a collaboration with 11 FN communities in Northwest Ontario, Canada, and a multidisciplinary research team from across Canada with expertise in cancer biology, epidemiology, medical anthropology, public health, virology, women’s health, and pathology. Interviews with healthcare providers and community members revealed that prior to any formal data collection education must be offered. Consequently, an educational component was integrated into the existing quantitative design of the study: a two-armed, community-randomized trial that compares the uptake of two different cervical screening modalities. In ACCSS, the Research Team integrates community engagement and the flexible nature of participatory research with the scientific rigor of a randomized controlled trial. ACCSS findings will inform culturally appropriate screening strategies, aiming to reduce the disproportionate burden of cervical disease in concert with priorities of the partner FN communities. Cervical cancer incidence and mortality has reduced dramatically since the introduction of cervical cancer screening using cervical cytology 50 years ago, particularly in developed nations . InternaClinician administered Pap tests are currently the standard screening tests in Ontario, though strategies that target HPV are making their way into practice , 13. Recqualitative interviews and focus groups that helped shape the subsequent quantitative two-armed, community-randomized controlled screening trial.The relationship between socio-economic disparities and poor health outcomes in Aboriginal populations is well-established in the literature, though poorly acknowledged in Canadian healthcare , 19. TheUnder a participatory action research (PAR) framework, ACCSS collaborates with partner FN communities to reflect on existing cervical screening knowledge, attitudes, and behaviors (KAB). This process complements the rigor of the subsequent cervical cancer screening trial , 27. ACCThe ACCSS is a mixed-methods research project that is taking place in 11 FN communities in the Robinson-Superior Treaty area of Northwest Ontario, Canada. The qualitative data collection of the project was completed in the first 2 years  following the signing of the Research Agreements with Chiefs and Councils of each community. This procedure and the following meet and greet visits to the community health centers are described in detail elsewhere  with loQualitative results paired with input from the CSC and CBRAs informed the development of the epidemiological questionnaires of the screening trial. With this quantitative trial, we will assess whether screening participation increases when offering HPV testing based on self-sampling instead of Pap screening. In communities randomized to arm A, Pap cytology taken by a health professional is initially offered, and women who do not accept will then be offered HPV testing based on self-sampling in the second phase of the screening trial. In communities randomized to arm B, the reverse order is applied such that HPV self-testing is first offered, then the women who do not accept will then be offered Pap screening. We will measure whether self-sampling can increase screening attendance, and we will assess the psychosocial impact of the uptake of Pap testing compared to the uptake of HPV self-testing.During the first offer of screening, CBRAs organize and facilitate educational events to recruit women into the CRCT, and later followed up with individual appointments to work through the informed consent, questionnaire, and offer of cervical screening with participants. After a 3-month period of screening, those who did not respond to the first offer of cervical screening are offered the reverse method of screening by the CBRAs.At the completion of the first 3-month screening phase, the Research Team and community members took a 1- to-2-month reflection period as an opportunity to evaluate the methods and processes from the first round of screening, to inform the implementation of the second phase of the trial; the CBRAs will also use this opportunity to reconnect with participants from the first phase to conduct the follow-up questionnaire.ethical space helped to open dialog between the Research Team and community partners and has been described in detail elsewhere . Meeting attendees agreed to advise the Research Team on the design and implementation of the project in their community, establishing a CSC. CSC teleconferences occurred every 1 or 2 months from that meeting forward, or more frequently when more input was required . The CSC was particularly focused on increasing awareness about cervical cancer and HPV within their communities, and ensuring that appropriate medical follow-up was offered to participants once the “research results” were obtained.In collaboration with the CSC, we hired local and whenever possible Aboriginal CBRAs to implement the study in their community, acting as a link between the Research Team in Thunder Bay and their community. After coming to an agreement on a job description, CSC members posted the advertisements in the community and provided the Research Team with names of candidates for the position.The CBRAs were hired in early 2013 after an in-person or phone interview with the Research Team. Some CSC members identified their preferred candidate for the CBRA position, though they left the ultimate decision to the Research Team. Some CSC members initially experienced difficulty finding local candidates who would be suitable when we first began searching for a CBRA. In some communities, women who were already employed at the on-reserve Health Center were recruited by the Health Director. In one community, an FN woman from a different community met with Health Directors to apply for the CBRA position when there were no local applicants. This CBRAs also suggested that we include off-reserve urban FN women in our recruitment strategy, which was agreed upon by the CSC and remaining CBRAs.Most CBRAs were recruited within 3 months of our job offer posting, and they attended a welcome dinner and a full-day intensive training in Thunder Bay. At the training, CBRAs participated in a presentation about the biology and epidemiology of cervical cancer, led by the pathologist/colposcopist on the Research Team Dr. Nicholas Escott, and learned about ACCSS rationale, study design, and the research protocol through the principal investigator Dr. Ingeborg Zehbe and the research coordinator Brianne Wood. At the end of the day, deliverables that were required to implement the project were identified and delegated to the Research Team, the CBRAs, the CSC, and their political leaders.(i)Identify and recruit eligible women into the screening trial.(ii)Interact with and assist the potential participants.(iii)Administer the study questionnaires , and provide women with the opportunity to participate in cervical screening.(iv)Communicate frequently with Research Team members  to provide updates and engage in discussions to guide future actions and improve study methodology.(v)Continue to engage the CSC, Chiefs, and Council with ACCSS, and ensure constant communication between all community partners.The CBRAs returned to their communities with five primary objectives:In partnership with the CSC, we eventually hired a CBRA for the community who did not find a candidate prior to the training, and held a one-on-one training session at the Research Team’s central office in Thunder Bay that mirrored the agenda of the group training. At the time of publication, four CBRAs had left their positions for personal reasons and new candidates were suggested by the local CSC representatives. These CBRA candidates were similarly interviewed, and then brought into the Research Team’s central office for one-on-one training.After the training, CBRAs began to plan an educational event to launch the trial in their community, to the first phase of cervical screening offers in their community. The research coordinator and each CBRA spoke every 1–2 weeks to discuss progress with the trial, and group teleconferences were held every 1–2 months to hear overall feedback from the CBRAs and address individual and group concerns or questions.In Ontario, Canada, to access the health system for Pap tests or other “medically necessary” procedures, all Ontario residents must have a health card that indicates they have Ontario Health Insurance and that they are eligible for Ontario health benefits –37. SomeThe sample collection methodology, interpretation of results, and follow-up communication in our study follows the current Ontario Cervical Screening protocol for primary care practitioners , 33. In Participants pick up self-screening kits when they meet with the CBRA to complete the questionnaire and informed consent. The HPV sampling swabs are distributed to participants along with the collaboratively designed, instructional pamphlet  for collecting a vaginal sample and a pre-postaged envelope to send off for testing. At the appointments, the CBRAs encourage participants to collect the sample while at the clinic  and to immediately mail their samples, though taking the kit home remains an alternative.Swabs are tested at the British Columbia Center for Disease Control and positive high-risk HPV results from these tests are communicated with participants. Samples are then sent to the Dr. Alberto Severini’s laboratory at the National Microbiology Laboratory in Winnipeg, MN, Canada where genotyping of the samples are completed –44.As suggested by the CSC, the Research Team has partnered with local healthcare providers who may provide medical care to women from our participating communities. On the ACCSS consent forms, participants are asked how they would like to have positive results communicated back to them, and the Research Team ensures that these wishes are met. Collaborating nurse practitioners and physicians work with the Research Team to communicate positive high-risk HPV results back to women and recommending them to attend a follow-up Pap test , 34–36.This project is conducted in accordance with the Tri-Council Policy Statement on Ethical Conduct for Research Involving HumansResults are summarized in Table Prior to the two-armed screening trial, a qualitative exploration was conducted between July 2011 and July 2012 by Ingeborg Zehbe and Marion Maar to shape the design and implementation of the trial [.We have successfully launched a two-armed CRCT through the contributions of our FN community partners. Recruitment strategies and the offer of the cervical screening intervention have been tailored to the unique social and political environments in each community, shaping how ACCSS is implemented in each FN community. CBRAs and the CSC have identified the social and health disparities that their communities face with cervical cancer screening. In addition to the design, content, and presentation of our educational pamphlet , the CSC and CBRAs were instrumental in engaging community women to participate in ACCSS. Through transcript analyses, teleconferences, one-on-one discussions, and in-person group meetings, our community partners were actively involved in the determination of incentives, the execution of the recruitment strategies, and the planning of the second offer of cervical screening in the communities. The development and implementation of ACCSS is guided by the theory of al space , 29 in aIntegrated efforts with the Research Team and CSC led to the construction of the ACCSS protocol for the randomized trial. Promotion of the educational event and study invitations, data collection processes, and disseminating research results were discussed and agreed upon by the CSC and Research Team. This approach also ensured that the research process was transparent and understandable by lay individuals. The CSC relayed that incentives are essential for engaging women from our partner FN communities to participate in ACCSS. We jointly decided on a lottery incentive system such that we would award a $50 gift card for a large discount department store to 1 person for every 10 consent forms we received from each community. The lottery method allowed the Research Team to give out larger incentives and the CSC felt that the store selection would encourage winners to purchase groceries and supplies that are not easily accessible on-reserve. To encourage participation in follow-up, a grand prize draw will be held after the final data collection point for all participants who completed all three questionnaires .The questionnaire for the randomized controlled trial was designed by the Research Team and the CSC, with final review conducted by the CBRAs. Heavily informed by the qualitative results, the baseline questionnaire aims to collect data on the following domains: social-demographic information, personal health behavior, feelings toward women’s healthcare, psychosocial health, and knowledge of HPV and cervical cancer. The influence of social circumstances on women’s health choices became abundantly clear during the qualitative component of ACCSS, and as a result, we aimed for the questionnaire to collect detailed information about the impact of cultural, social, and political environments on their cervical screening choices. Follow-up questionnaires are tailored to each community in terms of study timeframe and method of cervical screening first offered. We will repeat measurements of psychosocial health and gather information about the participants’ experiences of cervical screening from the trial through these follow-up questionnaires. Similar to the baseline questionnaire, many questions are open-ended to provide flexibility to truly capture the depth of ACCSS participants’ experiences. Please see Data Sheet S1 in Supplementary Material for the baseline questionnaire, and a follow-up questionnaire for a community first offered HPV self-sampling.only if the participant explicitly agrees to include their story. To avoid exploiting the personal and trusting space built between the CBRA and the participant, we and our community partners agreed that the participant should be asked if they wish to include their experiences in the questionnaire. On the other hand, some participants agreed to complete the questionnaire under the condition that they could fill it out without the CBRA seeing the responses. Because the CBRAs were known within the community, this offered some benefits, but also some drawbacks as some potential participants worried about their confidentiality.Most notably, after the completion of the first round of cervical screening offers, the CBRAs have indicated that some participants are questioning the lack of questions surrounding sexual abuse, substance abuse, and violence in the ACCSS questionnaire, during the interview between the CBRA and the participant. Because this topic is highly sensitive and stigmatized, we have discussed strategies with the CBRAs and the CSC for capturing this information that some participants express as a major influence in their cervical screening preferences, without offending other participants. Consequently, we have several open-ended questions that we have guided our CBRAs to fill in with these additional supplied details At the training, CBRAs started to develop their proposals for educational events that would launch the trial in their community. Once the CBRAs had received training about HPV, cervical cancer, and the study protocol, we shared the community randomization result with the Chiefs, Councils, Health Directors, and the CBRAs. Potential participants were not informed that the reverse cervical screening method would be offered in their community in the second screening phase to prevent preference bias.With these outlines, CBRAs indicated the resources they needed from the Research Team and from their community organizations and institutions, and how they would execute these educational events in the following months. The CBRAs created community educational events that reflected their local conditions and programing . Members of the CSC  and political leaders also helped to integrate these events into the already established community health programing. These events were promoted in the community by the CBRA using a variety of methods, including social media, posters around the community and band offices, door-to-door visits, phone calls, attendance at community celebrations and Pow-Wows, and newsletter inserts.-An introduction of the CBRA as a representative of the local health team and the Research, and an introduction of Research Team members who attended (Brianne Wood and Ingeborg Zehbe)-A presentation about HPV, cervical cancer, available cervical screening options, and how individuals can participate in the study using a life-size model of the female genital tract for demonstration purposes-A question and answer period for study-related or health-related questions-A complimentary meal or refreshments, often prepared by someone in the community-Additional ACCSS resources, including our ACCSS pamphlets, study t-shirts featuring our logo painted by a local artist with copyright obtained exclusively by the ACCSS Research Team, and information sheets-An invitation for eligible women to contact their CBRA about participating in cervical screening.Beginning in May 2013, our 11 partner communities started the trial locally with these community educational events, led by the CBRAs. Though each event was unique to the local community and environment, common to all sessions were:At the end of the events, women who were interested in learning more about the study provided their names and contact information to the CBRA, who would follow-up with them to make appointments to complete the consent forms and questionnaires.Community-Based Research Assistants would ensure that the women were eligible when scheduling individual appointments with these women after the event, and would bring a study package to their meeting. The study packages included an informed consent form, a questionnaire, and an HPV self-sampling kit with a pre-addressed, postage-paid envelope for the HPV-test assigned communities. The CBRAs also brought study information pamphlets and a small model of the female reproductive system to meetings so that they could try to answer questions during the meeting, or would have the contact information of the Research Team if any difficult questions arose. The informed consent process was explained thoroughly, and the baseline epidemiologic questionnaire was administered by the CBRA to consenting women. Women were then offered to take part in the cervical screening modality that their community was randomly assigned through the trial. In HPV-randomized communities, participants were encouraged to take their samples during their meetings with the CBRA, and packages were either handed back to the CBRA to mail or the participants mailed the samples themselves. In Pap test communities, the CBRAs offered participants help with scheduling an appointment with their personal healthcare provider or one of the project’s collaborating health care providers.The CBRAs continued to reach out to eligible women in their community for 3 months following their initial educational event, using some of the same methods described above and working in congruence with the programs run by the community Health Directors. All of the promotional and recruitment efforts are recorded in the CBRA logbooks, which are submitted to the Research Team at the end of each phase.The CBRAs, members of the CSC, and the Research Team met in September 2013 to reflect on the progress of the first phase and to inform the implementation strategy for the second phase. By identifying the site-specific cervical screening participation barriers, we decided to intensify the recruitment offer in Phase 2 of ACCSS. We heard that “in-person” communication was the most effective way to reach FN women , which was subsequently incorporated into our Phase 2 protocol. At the reflection meeting CBRAs decided schedules to invite non-responders to participate through door-to-door communication, personalized phone calls with help from the band offices, and frequent newsletter messages. This more aggressive recruitment approach will standardize recruitment strategies between communities, and the in-person approach represents the “ideal” conditions for inviting women to participate in cervical screening. These attempts to reach more women with the offer of cervical screening are important to our partner communities and offer methods of health promotion in FN communities.Our community partners also emphasized the importance of disseminating our current findings with community stakeholders and members prior to offering the second round of screening. Communicating the progress, findings, and future directions of ACCSS was stressed during the meeting as another method of engaging women from the community. Re-establishing ties with the political leaders and other stakeholders in the community was described as important for laying the foundation for future partnerships with the communities but also to ensure that the priorities of the project and the communities are congruent.Flexibility and open dialog are not only important to the internal study structure, but also to encourage communication between external policy-makers. With the support of community political leaders and healthcare professionals, the strategic collaborations with key stakeholders such as the SOGC and the Assembly of FN (AFN) will ensure a fast translation of ACCSS results into FN Health policy and practice so that this study can inform a larger scale application in other FN communities. At least three women from our partners and community members are selected to participate in the Publication Steering Committee (PSC) to critique each publication or report. The PSC members are offered the position of an author. PSC members will help plan dissemination at scientific meetings and conferences; notes in special-interest newsletters or magazines; articles and features. For community/regional dissemination, the CBRAs and CSC provide insight about a schedule of dissemination events that fit the needs and situations of their respective communities. Presentations will also be offered at community meetings, regional Chiefs’ Meetings, and/or FN health planning meetings. To ensure that results will influence policy, programs, and practice, a multi-pronged policy impact dissemination strategy will be designed with the aforementioned key stakeholders, the CSC, and respective Chiefs and Councils. These strategies will include educational sessions with the local medical school as well as nation dissemination with women’s healthcare professionals. Additionally, we will ask our community partners to translate their learned knowledge back to the Research Team, to inform future research processes.ethical space of the project, and ensuring a rich exchange of knowledge between community partners and the Research Team . These three distinct community-based representations offer distinct and significant perspectives that are critical for transforming the cancer screening culture and reducing the burden of HPV and cervical cancer in our partner communities. The CBRAs represent the innermost circles of the socio-ecological model, reflecting the individual and family knowledge, attitudes, and beliefs toward cervical cancer screening. The CBRAs are committed to reaching out to women and families, recruiting women to participate in cervical screening and promoting health behaviors at the individual level. It then follows that the CSC – composed of healthcare providers and community health representatives – should be focused on capacity building at the organizational level. The members of the CSC are committed to improving the health of their community and have the knowledge, experience, and drive to execute ACCSS at the community level. Additionally, they are careful and protective when communicating with the Research Team, and demand transparency and compromises between scientific rigor and the implementation of public health programing. At the outermost level, the political leaders of the FN communities reflect individuals who can advocate for policy and structural change. The Chiefs and Councils of our partner communities want assurance that the direction and overall objectives of the project remain clear – to improve the health and overall welfare of FN people. With the insight and support from these stakeholders, as well as the other community partners, ACCSS can effectively advocate for improved healthcare at the policy level.Anishinaabek Cervical Cancer Screening Study is the first community-randomized trial in Canada under a PAR framework to explore how knowledge, attitudes, and behaviors of FN women influence cervical screening preferences. We continued to build relationships beyond the pilot study and the formal execution of the study , 30 throBy acknowledging local conditions and unique healthcare systems, the PAR process provides us with a deeper understanding of the factors that are important for improving cervical screening uptake in FN women. ACCSS can provide generalizable evidence through its mixed-methods design that can inform cervical screening guidelines and policy for high-risk populations, such as Canadian Aboriginal women, by considering the complexities that are inherent to their surrounding environment , 46. BuiInvolving community-based representatives to implement the trial within their community is important for engaging individual women and the community in cervical screening and the research project, though there are considerable challenges and limitations to the integrated community engagement and controlled trial approach . SchedulThe integrated participatory and CRCT design also invited potential threats to internal validity if there were deviations from the protocol. However, CBRAs were usually well-known in their community and they were usually able to create a trusting environment in which they reach potential participants, and provide support for their local health program. These personalized and intensive recruitment efforts of the CBRAs within the communities respect the dynamic nature of healthcare systems and allow changes to be made from inside the communities. These “soft” outcomes require flexibility on the academic side when interpreting ACCSS results and measurements of “success.”Because socio-economic, historical, and cultural variables have a well-established link to health outcomes and quality of life , 19, 21,The project was initially conceived by Ingeborg Zehbe. These authors  all have contributed to the design and implementation of the ACCSS study: Ann N Burchell, Julian Little, Marion Maar, Gina Ogilivie, Alberto Severini and Ingeborg Zehbe. Nicholas Escott has contributed to the implementation of ACCSS and has a role as clinical advisor in ACCSS. These authors  have contributed to the writing of the manuscript: Ann N Burchell, Brianne Wood and Ingeborg Zehbe. Kyla Morrisseau and Lisa Bishop were part of the Publication Steering Committee and helped shape the manuscript and member-checked reported details. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.http://www.frontiersin.org/Journal/10.3389/fonc.2014.00027/abstractThe Supplementary Material for this article can be found online at Click here for additional data file.Click here for additional data file.