The gap between nationwide recommendations of cancer screening and the related evidences obtained from Korean adults should be filled. Estimation of the mean sojourn time (MST) in a specific cancer is important to determine the intervals of subsequent screening. This author arranged the methods for calculating MST into 5 categories based on the parameters used. Under the legal barrier for protection of individual privacy and confidentiality in a Korean academic situation, the methods involving the use of transition rates or prevalence/incidence ratio would be applicable among these methods. The leading cause of deaths in Korean as of 2012 is malignant neoplasm (hereafter cancer). Cancer is the primary culprit of the national disease burden as it results in more deaths than that caused by cardiac disorders and cerebrovascular diseases  combined . In addiUnderstanding the natural history of a specific cancer is essential to determine a valid screening interval for normal-risk groups . TherefoIn order to achieve the goal of the national early cancer detection project, which aims to decrease deaths by cancer, studies for Koreans are vital. Thus, some methodological reviews to deduce screening intervals needs to be established. The purpose of this review is to establish and suggest some research methodologies that fit the situation of South Korea to generate a basis for determining cancer screening intervals.0, during the cell differentiation process after cancer cells have generated. Periods prior to T0 are those in which there is no detectable disease. The second is the point detectable for cancer via clinical symptom or signs, T1, when they appear owing to cancer cell division. Thus [T0-T1] is the detectable pre-clinical phase (DPCP) in which cancer can be detected early through tests, although there are no clinical signs; this period in terms of time is called as the sojourn time (ST) of a certain cancer. For instance, if a member of the normal-risk group is diagnosed with gastric cancer after screening with a gastro-fiberscope, this gastric cancer was discovered in the DPCP, prior to appearance of any clinical signs. In addition, as the subject acquired knowledge as early as the time difference between the date of screening (T2) and T1, this is defined as the lead time. Therefore, the maximal lead time for members of the normal-risk group is considered the ST by minimizing delay time.Cancer, which is generated by somatic mutation during cell division , can be 0 and T1 need to be measurable; this, however, is a theoretical concept that is actually impossible to measure. As ST cannot be measured in reality, we instead measure the average ST i.e., the mean sojourn time (MST) of each subject through observations of whether cancer has occurred [To estimate ST of a certain cancer, the previously mentioned Toccurred . This MSoccurred -15.Interval cancer occurs when a normal-risk group, previously negative for cancer, is diagnosed with cancer within the screening interval suggested by the screening program . For insAs such, while the definition of interval cancer varies according to screening intervals, it is also affected by the accuracy of the screening modalities . TherefoMethods of determining screening intervals can be organized into 5 categories according to the basis of calculation.This is based on the argument that, after calculating the minimal size detectable by current screening methods, size is determined by the doubling time of the relevant cancer cell. In other words, the screening interval is determined by the differentiation speed of the tumor. For example, the doubling time of liver cancer is on average approximately 120 days. Considering small liver cancers take approximately 5 months to grow from 1 cm to 3 cm , along wHelicobacter pylori infection and mucosal change, is known to have a slow progression speed; therefore, the need for conducting screening less than 2 years for subjects with atopic gastritis and intestinal metaplasia has been questioned [In addition, the epidemiological characteristics of certain pathological types of cancer are utilized in determining screening interval. For example, the Lauren class of intestinal-type gastric cancer, which is greatly influenced by estioned .The purpose of the cancer screening programs is to decrease death rates by certain cancers and increase survival rates . The ideFor example, Morii et al.  argued tThis method determines screening intervals by examining the interval that minimizes interval cancer occurrence. In a study of Koreans, Nam et al.  found thAs aforementioned, the methods of determining interval by comparing cancer death rates, stage at time of diagnosis, and interval cancer incidence rate require the researcher to artificially establish a screening interval in advance and reflect it in the research plan. Such limitation can lead to somewhat confusing conclusions, such as screening intervals of 2 years for Nam et al.  and lessAttempts to directly estimate MST started after Zelen and Feinleib  suggesteAnother research task is to measure the sensitivity of the early diagnostic screening method in cancer screening. This is because determining sensitivity, which pertains to the ability to detect subjects with illness in screening , is onlyIn 2011, Brenner et al.  suggesteAs cancer screening is conducted in the ordinary person prior to disease emergence, not only are most of the premises of the formula derived by Brenner et al.  satisfieConsidering the characteristics of the screening sites that conduct biopsies in cases of suspected cancer, which are based on observation during gastroscopy for early detection of gastric cancer, pathologic findings rather than gross findings can be a basis for acquiring cancer incidence rates. On the other hand, as in mammography for early detection of breast cancer, tests for definite diagnosis are performed at a different time and location after imaging and the medical scientist has given his interpretation; therefore, diagnosis data alone cannot be used to calculate incidence rates. Considering the execution characteristics of gastroscopy, in an attempt to calculate the gastric cancer MST in Korean men, Bae et al.  organizeIn 2013, Draisma and von Rosmalen  suggesteWhen applying this method after establishing a cohort data that follows screening examinees, the positive detection rate at the first screening can be calculated and the incidence rate (I) can be acquired using national cancer data; then MST can be calculated by using the sensitivity suggested in existing papers. For instance, according to the study by Nam et al.  on screeIt is a fact that current national cancer screening guidelines lack supporting grounds. To determine screening intervals of early cancer detection, research on MST is vital. The present paper has divided MST calculation methods into 5 categories and observed the requirements for computation. In conclusion, to accurately calculate MST, incidence rate must be calculable, and sensitivity according to subject’s characteristics must be obtainable from the National Cancer Center. We hope to be able to conduct research of public value in line with the purpose of the ‘Act on Vitalizing Supply and Usage of Public Data’, enacted as of October 31, 2013.In reality, however, with the legal barriers of personal information protection limiting opportunities to conduct public research, such as MST calculation, utilizing the 2 simplified formulas belonging to the last categories may be an option. In particular, considering the author’s experience in attempting to calculate MST for gastric cancer through gastroscopy, the author would like to suggest attempting MST calculation for colorectal cancer in Koreans by using colonoscopy, despite the difficult environment in conducting research.


I was so pleased to learn that the inaugural issue of the neonatology specialty section of Frontiers in Neonatology would highlight Mary Ellen “Mel” Avery’s contributions to decades of neonatal research. Mel was my mentor and friend for more than 30 years, and it is a great honor for me to write about some of her substantial accomplishments. Among her many contributions, three are especially notable because they have saved the lives and improved the health of countless newborns: identification of surfactant deficiency as the cause of respiratory distress syndrome (RDS), treatment of RDS with artificial surfactant, and prevention of RDS with antenatal steroids.In a paper she wrote about how it really happened, Mel dated her interest in respiratory physiology to the start of her pediatric internship at Johns Hopkins in 1952 , and now known as RDS. Nearly half of the affected infants died, usually in the first 3 or 4 days, with pathology characterized by atelectasis and hyaline membranes . InfantsMel wanted to learn more about the lungs of newborn infants, especially those with HMD. In 1957, following her residency, she moved to Boston to study respiratory physiology with Jere Mead in the Department of Physiology at the Harvard School of Public Health and to learn more about newborn infants from the pediatrician and physiologist Clement Smith who worked across the street at the Boston Lying-In Hospital. Military funding targeted at chemical warfare, especially the effects of nerve gas on the lung, supported many laboratories, including those of Jere Mead, who was studying pulmonary edema, and John Clements, who was interested in surface properties of lung extracts. Clements had modified a surface balance in order to measure changes in surface tension with changes in area, as occurs during breathing. He found that surface tension of the lung extracts was high when the area was large, corresponding to higher lung volumes, and very low when the area was small, similar to low lung volumes . This waMel visited Clements in Maryland soon after his publication to learn his techniques. When she returned to Boston, she and Mead modified Clements’ method to enable them to study minced extracts of lungs from human infants that they obtained from Kurt Benirshke, chief of pathology at the Boston Lying-In Hospital. Their observations led to their landmark publication . Using tA second key contribution was Mel’s role in the translation of her discovery of surfactant deficiency in HMD to its clinical application, treatment of affected newborns with artificial surfactant. In the 1970s, Dr. Tetsuro Fujiwara studied surfactant biology with Forrest Adams in Los Angeles before he returned to Japan to continue his study of experimental surfactant replacement. Hearing about his work, Mel visited Fujiwara in Japan in 1979. At the time, he was working with a pharmaceutical company to develop an artificial surfactant from bovine lungs. He subsequently performed the first study of surfactant replacement in human infants, reported the next year . Mel retThat study and others at the time led to a new era in neonatology. Between 1989 and 1990, infant mortality in the US declined more rapidly than any other year since 1977, when the rate was much higher. Most of the decline was in neonatal mortality which accounts for about two-thirds of infant deaths, and most in the categories involving respiration. This was clearly due to the wide availability of surfactant beginning in July 1989 and followed by rapid FDA approval in 1990.A third key contribution was Mel’s work on prevention of HMD. At a conference in New Zealand in 1968, she reported that lungs of fetal lambs less than approximately 126 days gestation (146 days is full term) did not retain air. At the same meeting, she heard the obstetrician Graham “Mont” Liggins report treating pregnant ewes with corticosteroids to stimulate early labor. The resultant lambs were born at a slightly earlier gestational age than Mel’s 117–123 days) and had well-aerated lungs, suggesting accelerated appearance of surfactant, possibly induced by the corticosteroids. With others, she confirmed Liggins’ finding of accelerated lung maturation with antenatal steroid administration in lambs and rabbits –123 days, and witMel received many awards for her extraordinary contributions that led to understanding the mechanism of RDS as surfactant deficiency, treatment with surfactant replacement, and prevention by antenatal corticosteroid treatment of women with anticipated preterm birth, as well as other accomplishments. These included the Edward Livingston Trudeau Medal from the American Lung Association, the E. Mead Johnson Award from the Society for Pediatric Research, the John Howland Award from the American Pediatric Society, and the Virginia Apgar Award from the American Academy of Pediatrics. In addition, she was the first pediatrician to receive the National Medal of Science.In summary, Mary Ellen Avery was an outstanding leader in pediatrics for both her scientific contributions and her sustained efforts to improve health of newborns and children in the US and around the world. In addition, her support and continued encouragement of the next generation provides another enduring legacy. Mel directly mentored at least 75 individuals and influenced many more scientists and clinicians who have made and continue to make important contributions and train others Figure . Those oThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Traditional efforts to deal with the enormous problem of workplace safety have proved insufficient, as they have tended to neglect the broader sociotechnical environment that surrounds workers. Here, we advocate a sociotechnical systems approach that describes the complex multi-level system factors that contribute to workplace safety. From the literature on sociotechnical systems, complex systems and safety, we develop a sociotechnical model of workplace safety with concentric layers of the work system, socio-organisational context and the external environment. The future challenges that are identified through the model are highlighted.Practitioner Summary: Understanding the environmental, organisational and work system factors that contribute to workplace safety will help to develop more effective and integrated solutions to deal with persistent workplace safety problems. Solutions to improve workplace safety need to recognise the broad sociotechnical system and the respective interactions between the system elements and levels. Interest in the sociotechnical systems approach to workplace safety reflects a growing belief that many dimensions of safety are emergent properties of such systems. This evolution has resulted partly from the realisation that traditional strategies to address the enormous global burden of occupational injury may be reaching the limit of their utility. The particular limitations of ongoing efforts appear to be two-fold. First, risk management models that underlie scientific and professional approaches have only a limited ability to address latent and/or emergent risks and a restricted capacity to address the complexity of current and proposed work systems. Second, the focus on the individual worker misses many important phenomena when viewed from the broader sociotechnical systems perspective. We propose that meaningful advances in safety can be made if (1) there is a shift in the unit of analysis to the sociotechnical system level, which will thus incorporate human interdependencies relative to important social and technical elements, and (2) there is a meaningful expansion of the measurement and analysis methodologies so that assessment of systems dimensions, such as resilience and the adaptive role of workers in creating safety, can be more readily and more apparently revealed. In order to frame our argument, we first need to set it within the wider historical context of safety research.De Morbis Artificum Diatriba (Diseases of Workers). It would take nearly 200 more years to spark further significant scientific advances in workplace safety. In the USA, the catalyst was the Triangle Shirtwaist Factory fire of 25 March 1911 in New York City that claimed the lives of 146 workers , The global burden of work injury is enormous and persistent. The World Health Organization has estimated that in the year 2000 there were 2.0 million work-related deaths. In the USA, the Bureau of Labor Statistics estimates that nearly one million severe occupational injuries and nearly 5000 work-related deaths occur annually. The Liberty Mutual Workplace Safety Index  that bear on the question of designing, planning and managing human interactions within complex work systems. These include, but are not limited to, macro-ergonomics, cognitive systems engineering, sociotechnical systems theory, anthropotechnology, psychodynamics of work, human-systems integration, organisational culture and safety climate, and resilience engineering. There are other traditions beyond HFE dealing with similar concerns within the management sciences, where the focus tends to be on organisational psychology, employee stress and behaviour. Many disparate scientific communities thus exist that deal with complex sociotechnical systems, and we need to create more opportunities for scientific contact and exchange between them. In the next section, we review and organise the various concepts, definitions and frameworks that relate to sociotechnical system safety, and describe their relevance to workplace safety.We describe two fundamental problems with the current research paradigm in workplace safety: (1) narrow identification of an injury event as a local failure in a system and (2) limited focus on exposure of the individual worker to workplace hazards.reactive and is based on the widely accepted hierarchy of controls. Hazards that are observed to cause injuries are dealt with in two steps: elimination if possible, and management of residual risk through administrative and/or engineering controls if not. The second level, characterised as preventive (or proactive) measures, recognises the value of anticipation over reactive approaches. In contrast to instituting measures in response to injury experience, the preventive approach integrates health and safety goals into an organisation's overall human resource and risk management strategy. However, this level, while embracing the proactive perspective, is also still fundamentally static in nature in the sense that it assesses present risks and develops interventions to manage those risks. The existing risk management paradigm, thus, effectively regards an injury event as a failure within the system (or a chain or confluence of failures of system components). Any solution involves iterating through the series of the following steps: identify priority hazards, isolate the causes, determine the mechanisms and develop countermeasures to protect workers from these hazards. If the hazard arises due to potential deficiencies in the interconnectedness of system components, it may well go undetected by current risk assessment approaches. We suggest that this paradigm, therefore, has limited ability to address emergent risks implicit in the whole system rather than any singular component.The first concern with current research in workplace safety is about the conceptualisation of an injury event as a failure that can be localised within the system. Workplace safety science and practice have evolved to encompass two distinct levels that may be in effect at any particular organisation. The first level can be characterised as A second problem, related to the first, is the traditional preoccupation with the exposure of the individual worker to workplace hazards. Much of the current literature in workplace safety focuses on identifying and mitigating factors that contribute to cumulative or traumatic injuries sustained by a particular worker performing a particular task. We recognise that the understanding of injury pathways, dose–response relationships and effectiveness of interventions to control such exposures has led to manifest reductions in injury frequency and disability. For example, between 1998 and 2006, occupational fatalities declined by nearly 20% in the 27 countries of the European Union Eurostat . Similarthe technology sub-system includes not only equipment, machines, tools and technology but also the work organisation;the social sub-system includes individuals and teams, and needs for coordination, control and boundary management.Sociotechnical Systems (STS) theory was initially developed by members of the Tavistock Institute in London, with the primary objective to improve the overall quality of working life . A sociThe goal of STS is a comprehension and accounting for the ‘joint optimisation of the social and technical systems’, i.e. the different sub-systems or different system components. Joint optimisation involves interactions among system components, and between the system and its external environment  and to develop work systems based on semi-autonomous groups , and contradictions between espoused and enacted priorities. How these conflicts are resolved  then influences the worker's perceptions of the true priority of safety in the organisation.Woods  has compDiscussion of the organisational aspects of STS and workplace safety would not be complete without commenting on the growing literature on safety culture and safety climate. This literature seeks to understand how organisational values cascade down to individual workers and what impact they have on safety outcomes  associated with a particular level of the hierarchy are related to constraints upon the degree of freedom of the interacting components at the level below. To effect control on emergent properties, the higher levels impose constraints on the behaviour of the level below.In systems theory, complex systems can be modelled as a Using systems theory as the basis for STAMP, safety is treated as an emergent property that results from the interactions among components in the system and controlled through the hierarchical safety control structure Leveson . An examUnsafe system behaviour stems from the behavioural safety constraints not being met Leveson . The proProcess Model. For human controllers, this model is usually called a mental model. Accidents in complex systems, particularly those with software or human controllers, often result from inconsistencies between the controller's process model and the actual process state. For example, the pilot fails to recognise that the aircraft is in a stall and applies incorrect control actions or the pilot thinks they have identified an aircraft as hostile and inappropriately shoots a missile at a friendly aircraft. A workplace safety example is when a worker thinks the catwalk will hold his or her weight but it will not.In basic systems and control theory, an effective controller must contain a model of the system it is controlling, i.e. the Often, these models of the controlled system become inconsistent with the true state of the system due to missing or inadequate feedback channels. Part of the challenge in designing effective safety controls is providing feedback and inputs necessary to keep the controller's model consistent with the actual state of the process. Here, the concept of process models provides a better explanation for the human contribution to accidents than a simple ‘operator failure’. Operators (and administrators) do not fail in the ways that hardware fails; their contribution to accidents is much more complex. The system operation and working conditions must be controlled through physical, procedural and social  controls where the system component may be physical or human. STAMP provides a conceptual framework for designing systems to reduce human error that does not treat human error like machine failure.In summary, while Rasmussen took an important step away from the traditional, overly simplistic, engineering models of accident causation, Leveson extended Rasmussen's conceptualisation to include an adaptive feedback function that fails to maintain safety as performance changes over time Leveson . The accThe STAMP model clearly outlines the relationship between system operations and system design or development. We need to complement this approach with a deeper understanding of work at the ‘sharp end’ and its relationship to the rest of the organisation and the external environment (see previous section on the role of workers in workplace safety). From a pictorial view, one can consider a sociotechnical system in the form of concentric layers, which we have illustrated in Figure local context in which work activities are performed. At this level, the system is viewed from a human-centric perspective and reflects the complexity of defining the multi-faceted role of the human in relation to the other elements of the system such as tasks, tools and technologies, physical environment and organisational issues  and structures, influence the behaviour of humans and, in particular, the manner in which they actually interact with existing system elements (as opposed to interacting in the way envisioned by system designers). In addition to the HFE literature, the relevant management science literature on behaviour in organisational management is voluminous and often relevant here. For instance, the literature on safety culture and climate can provide the concepts and measurement techniques to examine the impact of safety culture or climate on worker behaviours in the local work system. The literature on organisational design can help to describe the organisational structures of importance to workplace safety, such as location of the safety responsibility in the organisational structure.The second layer, termed the social-organisational context, refers to the prevailing social, economic, legal and political milieu or the external environment. The broader work and occupational demographic context influences individual enterprises, their organisational culture and the specific system interfaces. This is in line with the discussion of system levels in the previous section. For instance, the STAMP model describes two levels of the external environment  that such systems possess. Such emergence itself is non-linear and thus extremely hard to predict, even in engineered systems where the nominal initial conditions can be well understood. But even as we have engaged in this effort, systems themselves do not stand still. If complexity can be demarcated by the number of interacting elements, modern systems have increased their level of complexity at exponential rates. Nor can mere increased computational power alone contend with such developments since calculating faster, but on the wrong problem, actually takes us farther away, rather than nearer to, our goal of understanding.The current state of knowledge with respect to STS theory and application to workplace safety is underdeveloped. While a myriad of models and schemas depicting interactions among system elements exist (see Table For decades, we have developed and used physical, cognitive and psychosocial HFE methodologies to improve work systems, quality of working life and workplace safety. However, each well-meaning rule, regulation, advisory, design innovation or operational equation has met with only limited success as institutional, organisational, governmental and national barriers, beyond our apparent control or influence, have served to blunt, modulate, dissolve or simply ignore the product of our science. Sources of these constraints and barriers lie at levels of analyses beyond traditionally framed boundaries and, thus, the purview of HFE and safety professionals. With the growing interest in sociotechnical systems, we can now address these wider-scale issues. An example of this important work is that by Reason , on humaThe next significant step in improving workplace safety lies in looking beyond traditional approaches and exploring the potential of sociotechnical systems to address the fundamental challenges associated with new technologies, emerging industries and the ever-changing workforce (Dekker, Hancock, and Wilkin


Tuberculosis is an infectious disease that continues to cause considerable morbidity and mortality globally. Only 65% of patients worldwide are currently diagnosed. Contact investigation is a strategy that aims to increase case detection and reduce transmission of tuberculosis, yet there is little evidence to show its effectiveness.We will conduct a cluster randomized controlled trial of contact investigation within the national tuberculosis control program of Vietnam. Household contacts of patients with smear-positive pulmonary tuberculosis will be invited to attend district tuberculosis units for symptom screening, examination, and chest radiography on four occasions over a two-year period. The primary endpoint is clinically confirmed tuberculosis among contacts during the 24 months of follow-up, ascertained using capture-recapture analysis. Microbiologically proven tuberculosis and treatment completion rates among contacts diagnosed with tuberculosis will be secondary endpoints. The incremental cost-effectiveness ratio will be estimated. The study will have 80% power to detect a 50% increase in the primary endpoint in the active intervention arm compared with the control arm. The study will include 8,829 contacts in each of the active screening and control groups, within 70 districts in 8 provinces in Vietnam, in both rural and urban settings.The effectiveness of contact investigation as a tool for improved tuberculosis case finding has not been established. This cluster randomized trial will provide valuable operational information for national tuberculosis programs in high-prevalence countries, in order to select the most cost-effective strategies to improve tuberculosis case detection.(ACTRN12610000600044).The ACT2 study has been registered with the Australian New Zealand Clinical Trials Registry  Tuberculosis (TB) is an airborne infectious disease that affects almost nine million people each year, mainly in resource-limited settings . The preM. tuberculosis, and reduce the prevalence of TB over time [Recent prevalence surveys in countries with a persistently high prevalence of TB have found that a substantial proportion of disease is not detected by conventional passive case-finding strategies -8. Stratver time ,10. Casever time  are mostContacts of patients with TB are known to have a high risk of developing the disease, particularly in the five years after exposure. A recent meta-analysis of studies including almost 900,000 contacts showed that 3.1% , 2.2 to 4.4%) of contacts in studies from resource-limited settings and 1.4%  of contacts in studies from high-income countries had co-prevalent TB . In VietAlthough contact investigation has been standard practice in most high-income countries for many years -17, it hStrategies for enhanced case detection in high-prevalence settings must be feasible and cost-effective, so that they are appropriate and affordable in the local context. It is important that countries considering implementing contact investigation have a high rate of DOTS coverage and consistently high treatment completion rates, so that additional cases identified by enhanced case detection are likely to be treated successfully ,26. In oVietnam is a middle-income country that is ranked eleventh in TB burden among the high-prevalence countries. A national survey in 2006 estimated that the prevalence of TB was 307 bacteriologically proven cases per 100,000 adults  [The Active Case Finding of Tuberculosis (ACT2) study is a cluster randomized controlled trial of contact investigation that is conducted by staff of the NTP, based at local district health facilities, and integrated within the management structure of the NTP.The hypothesis of this study is that, in countries that are highly endemic for TB, targeted active case finding among household contacts will result in more contacts being diagnosed with TB than will standard passive case finding alone.The primary aim of the study is to determine if household contact investigation is effective, by determining whether it increases the overall yield of active TB diagnosed among household contacts of patients with smear-positive TB compared with usual passive case detection. There are two secondary aims. The first is to estimate the cost effectiveness of this intervention by measuring the incremental cost-effectiveness ratio. The second is to determine the feasibility of implementing contact investigation within the NTP in a range of settings in Vietnam, including urban and rural environments. The screening strategy proposed in this study will be operationally nested within the NTP.This is a cluster randomized controlled trial with two arms comparing standard passive case detection with household contact investigation in eight provinces in Vietnam. In the active intervention clusters, household contacts of patients with TB will be assessed for the disease four times over a two-year period. The assessment comprises clinical evaluation, chest radiography and, in TB suspects, microbiological testing of sputum.All patients aged 15 years or over with pulmonary TB and at least one sputum sample positive for acid-fast bacilli on direct smear microscopy will be eligible to enter the study. Patients are excluded if they have no eligible household contacts.Household contacts of any age are eligible for inclusion if they lived in the same dwelling as the index patient during the two months prior to the diagnosis of the index patient. Pregnant women are eligible for inclusion, but women known to be pregnant are not offered a chest radiograph.The following endpoints are being measured in all contacts (in both groups). The primary endpoint is the proportion of contacts with clinically diagnosed TB. This will be ascertained based on the results of screening (in the active screening districts) and routine notifications to the NTP (in the active screening and control districts). Secondary endpoints, as indirect measures of study feasibility, are: (a) the weighted proportion of contacts with microbiologically proven TB (defined as either smear or culture positive TB), smear-positive TB and extrapulmonary TB; (b) cost effectiveness, determined by calculating the direct and indirect costs for each additional case diagnosed; and (c) the proportion of eligible contacts enrolling in the study, and the proportion of contacts participating in scheduled follow-up.Index cases with smear-positive pulmonary TB and their contacts are identified in both active and control study districts. The study intervention is only implemented for contacts in the active intervention districts.Consecutive patients with smear-positive pulmonary TB, who live in the study districts, are identified by TB staff working within district hospitals or district tuberculosis units. Those who agree to participate are given a participant information statement and asked to sign a written consent form.Contacts are identified using a screening questionnaire completed in consultation with the index case. Household contacts include all members of the household occupied by the index case, including children and infants, who were present during the period of recent infectivity, that is, two months up to the time of diagnosis. Household contacts are approached by the index patient in their family and given information explaining the study. Contacts are invited by the patient to enroll in the study at a district clinic.All contacts in the active intervention districts will be evaluated at the time they are first identified, and then 6, 12, and 24 months post-exposure. The procedures will be free of charge to the participants. On each occasion, the assessment will include a symptom questionnaire, physical examination, and chest X-ray. Contacts will have a chest X-ray at a local clinic or nearby private radiology service. X-ray films will be read by local clinical staff for routine clinical action and then be transferred to a central location for standardized re-reading by provincial level staff.Contacts will be defined as having possible TB if they have: (a) cough lasting for two weeks, (b) sputum for two weeks, (c) any hemoptysis, or (d) an abnormal chest X-ray meeting the criteria for possible TB. Contacts meeting one or more of these criteria will be asked to submit two spontaneous sputum specimens collected on consecutive days for acid-fast bacilli (AFB) examination. Two direct smear examinations and one culture test will be undertaken in the Provincial Hospital laboratory. For children younger than five years, the diagnosis of TB will be made on clinical and radiological grounds, in accordance with local policy at the time of commencement of the study. Treatment of active disease will be according to the policies of the NTP. An experienced clinician in each province will be available to advise district staff regarding the diagnosis of childhood TB and the investigation of suspected extrapulmonary disease.Contacts enrolled in control districts, will be given general information about the typical symptoms of TB and advised to report to the district hospital or TB unit if they develop these symptoms. During the study period, self-referring contacts with TB, who are participating in the study, will have two sputum specimens transferred to the reference laboratory for culture, in addition to any routine diagnostic procedures. This will allow comparison of rates of culture-confirmed TB between active and control districts. Contacts diagnosed with TB in both the control and active intervention groups will receive standard treatment for TB through the NTP.The study will be conducted in 70 districts within eight provinces. These provinces have been selected to include four provinces in the south , where the prevalence of TB is highest, two provinces from the central area , and two provinces from the north . This geographic and urban-rural stratification is important because the incidence of TB increases from the north to the south within Vietnam [Among the 97 districts within these eight provinces, 70 have been randomly selected for participation in the trial. These districts were selected with a probability proportional to their population size. The initially selected districts will enter a run-in period, prior to randomization, during which time they will be required to recruit two patients and six contacts and to demonstrate that they have the necessary resources to conduct the study. If districts fail or withdraw during this pre-randomization run-in period, they will be replaced by the next randomly selected district.We will randomly allocate districts to the active intervention or control group using the minimization method with predefined randomization lists . The minBased on an earlier meta-analysis, we estimated that the prevalence of confirmed active TB in close contacts of smear-positive cases would be 2.3% . In the The sample size was then adjusted for the clustered design of the study. The first level of clustering is at the level of the index case. We estimated that, on average, each index case would identify four close contacts who would consent to participate. Assuming that the intraclass correlation coefficient within households is 0.1, the design effect at this level will be 1.3. The second level of clustering is at the level of the districts. There were 152 cases of smear-positive pulmonary TB per district in 11 representative provinces in 2007. Assuming that 70% of smear-positive cases consent to participate in the study, there will be 106 index cases. If we assume an intraclass correlation coefficient for index cases within districts of 0.01, the design effect at this level will be 2.05. Hence, we anticipate an overall design effect of 2.67.On this basis, we estimate that we need to recruit a total of 3,338 index cases and 8,829 contacts  in each group. Based on our assumptions, this would require us to approach all available patients diagnosed with smear-positive pulmonary TB in 21 districts in each group: 42 districts in total. To ensure that we have a conservative sample size calculation, we will recruit all eligible and consenting index cases and their contacts from 70 districts.Specific quarterly recruitment targets will be set for each district, based upon the number of notified cases of smear-positive TB during the most recent year for which data were available, as a way of enabling districts to track their progress during the study.The effectiveness of the active case finding in contacts will be assessed by comparing the case detection rate between contacts of index cases in the active intervention and control districts. There are two levels of clustering in the selection of contacts: the district in which the contact lives and the index case with whom he or she was in contact. To account for these two levels of clustering, we will undertake a mixed model analysis in which districts and index cases within districts are random effects and active versus control status is the fixed effect. The measure of effect will be relative risk, estimated using a log link and binomial error distribution. In this primary analysis, there will be no adjustment for baseline characteristics. However, in a subsidiary analysis we will examine the impact of baseline characteristics of the districts, including geographical characteristics and baseline case notification rate, and individuals, including age and sex, on the risk of disease by testing these characteristics as potential effect modifiers.The primary endpoint will be the weighted proportion of contacts with clinically diagnosed TB in screening and control districts during the two-year follow-up period of the study. Secondary endpoints will include the weighted proportion of contacts with microbiologically proven TB, smear-positive TB, and extrapulmonary TB. We will also estimate the proportion of contacts with TB who complete treatment. Stratum specific weighted prevalence rates of clinically diagnosed and microbiologically proven TB will be determined for region and rurality.Direct costs of diagnosis and treatment will be determined based upon questionnaires for staff and patients at provincial and district level healthcare facilities. Indirect costs will be determined based upon detailed questionnaires for patients, contacts, and staff. Costs will be classified into one of two categories: those related to the identification of new TB suspects among the contacts of TB cases and those related to investigation and management of TB suspects. The former are costs that are unique to this intervention. The latter costs are already met by the NTP but these will be increased by the intervention because there will be more TB suspects.The incremental cost-effectiveness ratio will be calculated as the difference in total cost for TB control measures between the active and control districts divided by the difference in the number of cases detected.Data will be recorded on paper forms at district clinics and provincial hospitals. Each district will submit a monthly report on the recruitment index cases and contacts and the occurrence of study endpoints. These data will be entered within one month of collection into an online database. Written data and chest radiographs from each district will be digitally photographed, and the images transferred to the National Lung Hospital for electronic data entry and quality control. Data will be entered using a custom-designed, internet-based database, and monthly data checking and quality control will be performed at a central level. District staff will be provided regularly with a list of additional information required. A record of the proportion of children diagnosed with TB by chest X-ray will be compiled every three months, to ensure that the proportion of children receiving tuberculosis treatment does not exceed that recognized in the published literature.The technical quality of chest radiographs will be assessed at the National Lung Hospital by examining all radiographs labeled as abnormal and a random sample of all other radiographs. All radiographs read at the district level will be re-read at the provincial level, and the district staff will be informed of discrepancies. Quality control of laboratory testing will be performed according to the routine protocols of the NTP, including structured quarterly monitoring visits by staff from the National Lung Hospital.Members of the project research staff will conduct monitoring visits to each province every quarter, and to each district at least once each year. Provincial TB control staff will also conduct quarterly monitoring visits to each district in conjunction with routine monitoring for the NTP. Monitoring visits will include checking participant consent forms, confirmation that enrolled index patients have been included in the district notification registry, checking research forms for completeness, and compliance with study protocols.To verify subject consent, randomly selected contacts from each district will be telephoned by study staff to confirm they have consented to participate in the research. Irregularities in recruitment will be followed up by provincial staff and reported back to research staff.The protocol, patient information sheet, and patient consent form have been approved by the Human Research Ethics Committee at the University of Sydney, the Scientific Committee of the Vietnam Ministry of Health and the Scientific Committee of the Vietnam National Lung Hospital.Subjects may only enter the study if written informed consent is obtained. Written consent by parents will be required for children under 15 years of age. The healthcare worker enrolling the subject will be responsible for obtaining written informed consent and consent forms will be checked during regular monitoring visits by research staff.Research participants may voluntarily withdraw from the study for any reason. If they withdraw then there is to be no adverse impact upon the treatment of the TB patient within the NTP.A unique study code will be assigned to each research subject, and used to identify radiographs and laboratory specimens. Written records will be stored securely in the district clinics and provincial hospitals or at the National Lung Hospital. The online database and electronic records will be password protected.Investigation of TB contacts may be a valuable next step in controlling TB in countries that have achieved consistently good treatment outcomes under directly observed therapy (DOT). Household contacts of TB patients are recognized to have a high risk of disease . HoweverThis study will be limited to contacts of smear-positive patients because smear-positive index patients are more likely to transmit TB  and the There is limited evidence quantifying the extent to which disease among household contacts is actually caused by transmission within the household. Several studies in high-prevalence settings have shown that between 17% and 46% of households where two or more patients have TB share identical molecular fingerprints -35. ThisImportantly, this research is closely integrated with the existing national TB control program. This integration will ensure that experienced workers within the NTP assess contacts, and that affected contacts can readily be treated. This research design is essential to the general applicability of the research and its relevance to future policy decision-making and scale-up. The study is a form of operational research, which is a systematic approach to developing evidence for an intervention that is useful to policy makers . OperatiAlthough randomized controlled trials have often been considered overly ambitious in resource-limited settings, our study will combine the rigor of this design with the practicalities of routine TB control. It will also contribute to the capacity of local staff to conduct research, and support the supervision of the research within the structures of the NTP. By implementing the study within eight provinces, we will also learn valuable lessons about the practical challenges encountered in contact investigation throughout the country that will inform future policy development.Therefore, this cluster randomized controlled trial will provide an important evidence base to assist policy makers in Vietnam and comparable countries in their decisions about the programmatic implementation of active case finding in the future.Currently recruiting.AFB: Acid-fast bacilli; CI: Confidence interval; DOTS: Directly observed therapy short-course; IPT: Isoniazid preventive therapy; NHMRC: National health and medical research council; NTP: National tuberculosis program; TB: Tuberculosis; WHO: World Health Organization.The authors declare that they have no competing interests.GBM and GJF developed the study methods, drafted the manuscript, revised it for important intellectual content, and approved the final version. They currently provide management and oversight of the trial. GJF supervised staff implementing the research, and monitored and evaluated the research. GBM and WJB wrote the grant application to obtain funding. NVN and DNS provided intellectual input into the development of the study methods, supervised staff implementing the research, and obtained ethical approval for the research. They approved the final version. WJB contributed to the development of study methods, drafting the manuscript and revising it for important intellectual content, and provided approval for the final version. All authors reviewed and approved the final manuscript.GJF is a Respiratory Physician and Research Fellow at the Woolcock Institute of Medical Research. He was Country Director for the Woolcock Institute of Medical Research during the establishment of the trial. NVN is the Vice-Director of the National Lung Hospital and the NTP. He is an Associate Professor of Respiratory Medicine at Hanoi Medical University. DNS is the Director of the National Lung Hospital and the NTP. He is an Associate Professor of Respiratory Medicine at Hanoi Medical University. WJB is the Bosch Professor of Medicine and Professor of Immunology at Sydney Medical School, University of Sydney. He is the Director of the NHMRC Centre for Research Excellence in Tuberculosis in Control, Australia, and is also the head of the Tuberculosis Research Program at the Centenary Institute for Cancer Medicine and Cell Biology at the University of Sydney. GBM is a Clinical Professor at the University of Sydney and the Head of Respiratory and Environmental Epidemiology at the Woolcock Institute of Medical Research, Sydney. He is also a Senior Staff Specialist Respiratory Physician at Liverpool Health Service, Sydney.


The majority of patient contacts occur in general practice but general practice patient safety has been poorly described and under-researched to date compared to hospital settings. Our objective was to produce a set of patient safety tools and indicators that can be used in general practices in any healthcare setting and develop a ‘toolkit’ of feasible patient safety measures for general practices in England.A RAND/UCLA Appropriateness Method exercise was conducted with a panel of international experts in general practice patient safety. Statements were developed from an extensive systematic literature review of patient safety in general practice. We used standard RAND/UCLA Appropriateness Method rating methods to identify necessary items for assessing patient safety in general practice, framed in terms of the Structure-Process-Outcome taxonomy. Items were included in the toolkit if they received an overall panel median score of ≥7 with agreement (no more than two panel members rating the statement outside a 3-point distribution around the median).Of 205 identified statements, the panel rated 101 as necessary for assessing the safety of general practices. Of these 101 statements, 73 covered structures or organisational issues, 22 addressed processes and 6 focused on outcomes.We developed and tested tools that can lead to interventions to improve safety outcomes in general practice. This paper reports the first attempt to systematically develop a patient safety toolkit for general practice, which has the potential to improve safety, cost effectiveness and patient experience, in any healthcare system. The publication of the Institute of Medicine’s 2000 report ‘To Err is Human’ was a seminal moment in the discussion of patient safety. The report revealed that more people in the US were dying from medical errors than from road accidents . Since tOne reason for this situation may be that general practice is thought of as inherently low-risk, so safety is not considered a critical problem. However, serious errors leading to morbidity and mortality do occur in general practice, sometimes over long periods of time. Understanding the epidemiology of hospital errors was crucial for improving safety in hospitals and gaining public support for efforts to improve safety. There needs to be a similar focus on general practice . While rIn 2011, the American Medical Association’s (AMA) ten year report concluded that major gaps remain in our understanding of primary care patient safety with virtually no credible studies on how to improve safety .Pubmed, Medline (Ovid 1996 onward), Embase, CINAHL, Health Management Information Consortium and Web of Science. The resulting studies were too heterogeneous to conduct a meta-analysis, so the authors used a taxonomy-based approach to extract information from the identified tools, sets of indicators or individual indicators to create statements that could be rated by an expert panel.As described in best practice documents for the RAND/UCLA Appropriateness Method , we condPotential criteria that described good practice in patient safety in general practice were identified by both reviewers during data extraction. The statements were taken verbatim from the source document or derived from the key finding of the paper. Inclusion and exclusion criteria are shown in Table From this literature, we generated a list of identified tools that were categorised according to the taxonomy of structures, processes, and outcomes ,17. In aWe used the RAND/UCLA Appropriateness Method ,19, whicWe recruited nine internationally-recognised experts who had expertise in patient safety in general practice. A wide range of perspectives and personal characteristics were represented with participants coming from the US, England, Scotland, the Republic of Ireland, Switzerland, Germany, Belgium, and the Netherlands. The group contained seven men and two women with seven GPs, one pharmacist, and one academic (implementation science) on the panel. It was estimated that each member of the panel committed 3 days of work to the consensus-building exercise.This study adhered to the RAND/UCLA Appropriateness Method  by conduIn both rounds, panellists were asked to rate each statement on a 9-point scale. In round 1, panellists rated ‘clarity’ and the ‘necessity to include the item in a general practice patient safety toolkit’. A clear item was defined as a ‘tool/indicator/criterion that was expressed in clear, precise and unambiguous language’. In round 2 the panellists re-rated ‘necessity’ and also rated ‘feasibility’. The necessity rating scale related to any general practice in any healthcare setting/country. The feasibility scale allowed participants to rate how feasible it would be to collect reliable data within UK settings, as this is the setting in which the toolkit will be initially applied.There are two aspects to the rating process for each scale for each scenario within a consensus technique: the overall panel median rating and also the level of agreement or consensus within a panel . The levA total of 205 statements, summarising the tools, sets of indicators or individual indicators identified in the review, were rated in round 2. The full list of indicators can be obtained from the authors upon request. Summary statistics for these items are provided in Table The Additional file Understanding the epidemiology of safety in general practice needs addressing as rigorously as in hospitals . There iMost safety incidents can be categorised into four main areas: diagnosis, prescribing, communication between health care providers and patients, and organisational issues . Significantly, 20% of errors could have serious consequences . Set witThis set of tools and indicators has resonance with the findings of the recent review by the Health Foundation in the UK, which emphasised that there can be no one single measure of patient safety and the importance of knowing what methods, tools and indicators are currently being used in primary care to measure patient safety . The litWe have presented all the statements felt necessary for inclusion in a general practice safety toolkit, as well as those felt to be feasible to collect data reliably in the UK, in order to make our toolkit as applicable as possible to the widest range of primary health care settings. While the ratings of feasibility relate to UK settings, many of the statements originated from US publications, which were felt not to be applicable to the UK . We have combined individual statements to produce a preliminary checklist consisting of items relating to information flow (both within the practice and between the practice and other providers), providing safety information about the practice, and achieving safer prescribing by working with patients. We produced the preliminary checklist in response to areas that we identified from our literature review as supported by relatively weak published evidence but in areas rated necessary by the panel, such as the handling of test results. We chose deliberately to exclude items related to well- established legal precepts, such as health and safety legislation and infection control, as practices should already be achieving the goals contained in these documents. The preliminary checklist attempts to bridge the gaps in our toolkit in relation to our taxonomy of patient safety.This study adhered to a validated systematic consensus method . AlthougTo improve patient safety we need to determine how to measure safety accurately, and identify ways of avoiding, preventing and ameliorating patient harm. This study, by focusing on tools and indicators of general practice patient safety, helps identify a range of measures that can be used by general practices to measure safety. The intended consequences of such an approach are to help quantify and measure existing safety levels and subsequently to develop interventions to improve safety outcomes in general practice. To meet this aim we must understand and meet the needs of service providers, patients and the public. The success of such a toolkit will be predicated on engaging with and helping practice staff deliver safety improvements, which are aligned to their own identified needs. Our intention is to develop and test tools that can lead to interventions akin to a list of top strategies for adoption in general practice, not unlike what has been done in hospital settings . On-goinThere is a recognised lack of tools available to prevent, monitor and improve patient safety in primary care settings.Understanding the epidemiology of safety in general practice needs addressing as rigorously as in hospitals.We developed and tested tools that can lead to interventions to improve patient safety outcomes in general practice akin to what has been done in hospital settings.The intended consequences of such an approach are to help quantify and measure existing safety levels and subsequently to develop interventions to improve safety outcomes in general practice.The authors declare that they have no competing interests.Professors Campbell and Avery had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: BB, RS, AA and SC. Acquisition of data: BB, RS, AA and SC. Analysis and interpretation of data: BB, RS, AA and SC. Drafting of the manuscript: BB, RS, AA and SC. Statistical analysis: BB and RS. All authors read and approved the final manuscript.The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/15/110/prepubThree stem search strategy. The starting point for determining the search terms used in the review was a 3 point definition of our search question and exploration of Medical Subject Heading (MeSH) terms resulting in the following three stems.Click here for fileStatements rated necessary for inclusion in a general practice patient safety toolkit relevant to any country. *Statements with median of 9 in bold.  Statements considered both necessary and feasible are in italics.  number in brackets = median rating by the panel [he panel ,32,33,34Click here for file


This paper describes early results of an integrated maternal, newborn, and child health (MNCH) program in Northern Nigeria where child mortality rates are two to three times higher than in the southern states. The intervention model integrated critical health systems changes needed to reinvigorate MNCH health services, together with community-based activities aimed at mobilizing and enabling women to make changes in their MNCH practices. Control Local Government Areas received less-intense statewide policy changes.The impact of the intervention was assessed using a quasi-experimental design, comparing MNCH behaviors and outcomes in the intervention and control areas, before and after implementation of the systems and community activities. Stratified random household surveys were conducted at baseline in 2009  and in 2011 at follow-up (n = 2310), with women with births in the five years prior to household surveys. Chi-square and t-tests were used to document presence of significant improvements in several MNCH outcomes.Between baseline and follow-up, anti-tetanus vaccination rates increased from 69.0% to 85.0%, and early breastfeeding also increased, from 42.9% to 57.5%. More newborns were checked by trained health workers (39.2% to 75.5%), and women were performing more of the critical newborn care activities at follow-up. Fewer women relied on the traditional birth attendant for health advice (48.4% to 11.0%, with corresponding increases in advice from trained health workers. At follow-up, most of these improvements were greater in the intervention than control communities. In the intervention communities, there was less use of anti-malarials for all symptoms, coupled with more use of other medications and traditional, herbal remedies. Infant and child mortality declined in both intervention and control communities, with the greatest declines in intervention communities. In the intervention communities, infant mortality rate declined from 90 at baseline to 59 at follow-up, while child mortality declined from 160 to 84.These results provide evidence that in the context of ongoing improvements to the primary health care system, the participatory and community-based interventions focusing on improved newborn and infant care were effective at changing infant care practices and outcomes in the intervention communities. In 2011, two-thirds of the 7 million deaths of children under the age of five could have been prevented by low-cost, integrated newborn and child heath (NCH) interventions . It has However, in Sub-Saharan Africa, reductions in childhood mortality have been slower than in the rest of the world . While tIn Nigeria, the most populous country in Africa and a country with the second highest burden of child deaths in the world, the need to improve child survival is paramount . FurtherA key element of this integrated strategy is the development of a network of CHWs, who bridge between the household and the health facility. To date, there has been relatively little attempt to incorporate community health workers into community-based promotion of primary care in Nigeria, although there is evidence that they would be effective . NigeriaThis combination of participatory group discussions with a CHW has been piloted in Nepal and other parts of Asia and Africa, but seldom in the context of a functional primary health care system, and mixed results regarding the combined effect of participatory women’s group and CHW may relate to the low level of functionality of the health care system -27. The The study was conducted in the three northern Nigerian states where PRRINN has expanded its MNCH activities, namely Katsina, Yobe, and Zamfara, with respective populations of 5.8, 2.3, and 3.3 million, according to the 2006 population census of Nigeria. These states are part of the Sahelian zone, with an alternation of dry and wet seasons. The program focuses on the rural communities, where most of the residents are subsistence farmers, pastoralists, or traders. The level of literacy is low, particularly among women, where over 80% are unable to read or write. Half or more of the women do not listen to the radio or watch television at least once a week. Compared to the southern zones of Nigeria where primary care use is widespread, there is very little primary care service use in the northern zones of Nigeria. In these states, less than 50% of women had any antenatal care in their last pregnancy, over 85% delivered at home without assistance of a skilled attendant, and about 75% had no postnatal care. These states had the lowest immunization coverage rates, under 10% of 12–23 month olds, and the lowest rates of utilization of health care services for treating sick children.The intervention design reflects the integration of two different approaches to the improvement of health care. First, the design uses the PRECEDE-PROCEDE framework for health promotion through system-wide changes in health planning and implementation which facilitate changes in MNCH health knowledge, practices, and outcomes, incorporating participatory methods and operations research to assess progress in achieving changes at each stage . Second,In addition to the development of EOC capabilities, the health system strengthening component of the intervention included midwife training and posting through the Nigerian government’s Midwife Service Scheme, establishment of planning and management techniques within existing facilities, strengthening distribution of essential drugs to PHC facilities, refurbishment of PHC equipment (as needed), training in IMCI for the PHC clinical staff, and establishing the “Primary Health Care Under One Roof,” which consolidates and coordinates the different components of primary care in one health clinic or post.Complementing these supply-side changes, are activities that create demand for MNCH services. Selected groups of villages served by primary care facilities linked to the upgraded EOC facility participate in a community engagement process, which aims to increase awareness, knowledge and practices of healthy behaviors in response to MNCH barriers. Core to this process is a participatory, community discussion group, facilitated by trained community volunteers (CVs).The community volunteers have been recruited and trained in each community, using a cascade or train the trainers model, with core trainers training CVs who in turn train new volunteers. The participatory training methodology is underpinned by key principles of adult learning, starting with discussions and reflection on personal experiences, which in turn are used to discuss potential responses/solutions women could adopt. Body memory tools  help trainees remember key facts. By 2011 CVs, primarily women, had been recruited, mobilized and supported in their work in all the intervention communities. The primary responsibility of the CV is to facilitate community discussion groups through the use of jingles and other visual-auditory cues to educate about critical MNCH issues, such as danger signs for a pregnancy. In addition, the CVs also aid in identifying at risk women and children and referring them to the nearest facility.These dialogues provide an opportunity for reflection and problem solving on the most prevalent MNCH problems affecting the community. Members of the discussion groups are encouraged to share what they know with their families and peers between sessions. Community discussion group participants are encouraged to put what they have learned into practice by tackling key barriers of access to and affordability of MNCH services, including establishment of blood donor groups, community emergency savings schemes, community emergency transport schemes and a “mother’s helpers” system. This work is reinforced by mass communication activities, including the use of radio “jingles” to promote birth preparedness or childhood immunizations.The CV have been complemented by a small cadre of CHWs, community-based health workers providing selected primary health services directly to families through rotating visits or extended availability through residence in the communities, similar to the models used in other countries with volunteers and paid CHWs. These CHWs were recruited among unemployed Junior Community Health Extension Workers, previously trained by the state Schools of Health Technology, who were then given two weeks of additional training and toolkits to enable them to make home visits, engage mothers using supportive communication techniques, provide basic preventive antenatal, newborn, and child care, basic treatment and referral to the PHC, according to the Integrated Management of Newborn and Childhood Illnesses protocol. These CHW-Community Based Service Delivery (CBSD) are provided with transport to enable them to visit communities on a regular schedule, and they spend most of their time visiting families in the community.The assessment of the impact of the CBSD programs uses a quasi-experimental design using pre- and post-intervention household surveys in the intervention and control communities. The pre-intervention or baseline household survey (BHS) was conducted in 2009 and the post-intervention household survey, the follow-up household survey (FHS) was conducted in 2011. The evaluation of the impact of this integrated MNCH package takes into account both availability of program and actual individual participation in any of the program’s community-based service activities. Availability of the program activities was assessed by comparison of intervention and control areas. Individual exposure to the program was assessed by the woman’s responses to questions eliciting sources of information or health care advice. The study was approved by State Ethics Review Committees in each of the three states, as both a cross-state and individual state approval. These ethics review committees are certified by the Nigerian Federal Government’s National Health Research Ethics Committee to review and approve health research protocols for their states.The sampling plan was a stratified two-stage cluster sample, with oversampling of individuals in the MNCH intervention clusters. Individuals from MNCH clusters were oversampled using a ratio of 2:1, because MNCH clusters cover a significantly lower proportion of the population of each state. Oversampling therefore provided a sufficient sample in the intervention areas to assess the impact of key elements within the intervention package on the key MNCH outcomes. The PSU for this sample was the Local Government Area (LGA), for which there were 24 in the BHS and 15 in the FHS. For the FHS, the same intervention LGAs as the BHS were included, with the exception of LGAs of the state capitals . The LGAs comprising the state capitals were included only during the baseline to assess the differences in services provided to residents patronizing urban versus rural facilities. This enabled the team to devise appropriate strategies for referral from rural to urban facilities. The state capitals were excluded in the analyses reported here. The number of households selected per LGA was proportional to the size of the LGA.The study was designed with an 80% power to detect a 2.5% change in the percentage of women delivering with the assistance of skilled birth attendants between the BHS (11%) and the FHS. The BHS was designed to be representative of all ever-married women in the household and required a sample of 5,560 households, while the FHS was designed to be representative only of ever-married women with a birth in the previous 5 years, requiring a sample of only 2,310 households. In the BHS, the sample of 5,560 households was 0.7% to 9.8% per LGA, while for the FHS the 2,310 households comprised 3.1% to 13.1% of all households.Within the LGA, the sample of households was allocated to intervention and control communities in proportion to the size of the community or village. The sampling fraction for each community was determined by information on the total households from the community leadership. Households within each selected community were randomly sampled using a procedure similar to that used in the WHO-EPI cluster surveys, namely by numbering then sampling households according to the community sampling fraction along randomly selected paths leading out from the center of the village.The household was the ultimate sampling unit. In compounds that comprised one to three households, one household was randomly chosen for interviews; in compounds with four to six households, two were surveyed; in compounds with seven or more households, three were surveyed. Within each randomly selected household, in the baseline survey, all ever-married women of childbearing age (15–49 years) were interviewed, whereas in the FHS only one ever-married women with at least one child born in the last 5 years was selected for interview. The inclusion criteria were changed for the follow-up survey because of the need to focus on women with pregnancies and births during the time period during which the intervention was implemented. In the BHS there were 6,842 women with successfully completed interviews, while in the FHS there were 2,310 completed interviews.Interviewers who had completed secondary school or higher were selected and trained to visit the selected women at home and administered a questionnaire that included translation of key concepts and terms in the local languages . Most of the interviewers were females, responding to cultural expectations and beliefs that encourage female interviewers to interview female respondents. In both the BHS and FHS, the questionnaires used adopted some of the close-ended questions from the 2008 Demographic and Health Survey  to allowAt the analysis stage, the inclusion criteria for both surveys was narrowed to ever-married women, aged 15–49, with a birth in the previous five years. Respondents were assigned to the control or intervention groups based on the level of PRRINN-MNCH program intervention at the time of the survey. For the BHS, which was pre-intervention, the intervention LGAs included all LGAs in the first cluster receiving CEOC upgrades and related community engagement activities, while the balance were control LGAs. The FHS included the same intervention LGAs, but control LGAs in 2009 were shifted into the intervention category if they had started to receive the primary health care and community health worker interventions by the time of the FHS. The dependent variables are the key health behaviors pertaining to maternal, newborn care and care of sick children. Infant and child mortality rates were calculated using standard demographic estimation methods. The infant and child mortality rates were calculated using the retrospective reports of births and deaths in the previous 12 months and five years, per the standardized format of the Demographic and Health Surveys. Rates were calculated separately for each survey period, aggregating the reported births and deaths per household. We first verified the number of births and deaths for the appropriate reference period (one or five years) using the built-in cross-referencing between questions, excluding implausible values , and then calculated the mortality rates using the appropriate births denominator. The bi-variate and multi-variate analyses of the two sets of survey data were conducted separately, each using sampling weights based on the intervention and control areas. We examined changes in the proportion with the designated MNCH behaviour or outcome, contrasting all pre-intervention responses  versus the post-intervention responses from the FHS, intervention versus control. We assessed the degree to which the intervention and control groups differed using the Chi-square statistic. Analyses were performed using Stata 12.0  and SPSS version 19.0 .After including only ever married women with births in the previous five years, there were fairly small differences between the two groups (See Table The majority of the households (about 80% both surveys) included only one family, but if the household had more than one family in the compound, there was an average of 2.5 families living together. There are an average of four women living in each household, and of these women, on average 1.5 had given birth in the past year.In 2011, more infants were protected from tetanus. The proportion of women who had received anti-tetanus vaccinations had increased from 69.0% to 85.0%, with the increases equal in the control and the intervention areas. There was a significant increase in the proportion newborns first breastfed within 24 hours from birth, from 42.9% to 57.5%, with significantly more (60.5%) in the intervention areas  of the households reported a sick child (under age 5 years) in the month prior to the interview. The average duration of illness was 7.8 days. The most common illnesses were fever  (26.5%), diarrhea (17.4%), cough (13.3%), and malnutrition or weight loss (13.7%). One in ten (11.2%) children had both fever and cough, as did another 10.1% who had diarrhea and malnutrition  to reduce fever at both baseline and mid-term follow-up, with more using analgesics for diarrhea at mid-term than at baseline Table . ApproxiBetween 2009 and 2011, there was a decline in both the infant and the under-five mortality rates (see Figure Although the PRRINN-MNCH Programme only had been underway for just over two years when the FHS was conducted, there already was evidence of significant improvement in several of the key newborn, and child health behaviors and outcomes. The level of newborn and child morbidity remains high in these communities, with almost half of all newborns reported to show one of the danger signs and one-third of young children experiencing an illness episode in the previous month. Nonetheless, we observed a significant decline in infant and child mortality at follow-up. Further, the mortality decline was greater in the intervention than the control areas. This is a remarkably fast period of time to observe a mortality decline, and particularly when there was not a huge change in the proportions delivering in a health facility where newborn care would be included as part of the delivery. We believe that the change in infant mortality may result from how women respond to their infant’s health when they realize that health is threatened. Compared to the baseline in 2009 when women were less likely to seek advice and respond as quickly to infant danger signs or advice about newborn care, at follow-up in 2011 women in the intervention communities were very much alert to and responding to these dangers.Fairly consistently, the intervention communities displayed improved neonatal and newborn care practices. More women in the intervention than control communities started breastfeeding immediately and exclusively, had their newborn checked by a health worker, washed their baby in warm water, kept the infant warm with kangaroo care, and knew to watch the infant for fever or other danger signs. These all were topics addressed in the community discussion groups organized by community volunteers recruited and trained by the project, and the changes in care of the newborn immediately after delivery reflect this increased community dialogue, awareness and support for the need to keep an eye on the mother and newborn during this critical period. Our findings of the increased knowledge about danger signs and improved care for newborns is consistent with the findings of other programs which include community volunteers leading participatory dialogue groups ,27,32,33Our study, however, also documents changes in interactions with staff of the primary health care facility. The community dialogue encouraged women to go to the community health worker or the health worker at the closest health post instead of the TBA, because these trained individuals can do more to help the mother recognize and respond to any problems that might develop. The follow-up survey documented the increased reliance on community health workers care of the newborn or sick child. At baseline, almost half of all newborns were checked by a TBA, whose activities generally were limited to assistance with cord care and cleaning up the baby. At the follow-up two years later, hardly any women took their newborn to be seen by a TBA. Instead, they had their babies checked by the midwife or CHW at the health post or by a CHW making an outreach visit to the community. A similar pattern is seen for seeking advice on the care of sick children, with the intervention group showing increased reliance on the midwives and CHWs and less on the TBA or family and friends. At follow-up, women in the intervention communities also were more likely to have received anti-tetanus vaccinations at the health post. We believe that the simultaneous improvement in the quality of care provided by the CHW and nurse-midwives at the health post gave women the confidence that they could go to the health post to seek advice and care. Thus, our study shows that when the participatory community dialogues are accompanied by supportive primary health care structures, including community health workers reaching out to families and improved quality of service in the clinics, women are more likely to adopt both the clinical and at-home newborn care recommendations, as suggested in earlier reviews of newborn care interventions ,33.Another critical change in newborn care is the increased understanding and ability to observe newborn danger signs. In the intervention communities, more women knew newborn danger signs and they also knew more of them. Mothers in the intervention communities reported higher incidence of some of the newborn danger signs, but this likely reflects their new found understanding that these signs are not “normal” and require the mother to have her child treated quickly. Women reported that almost half of their newborns had shown at least one of these danger signs, with the most common being a high fever. It is likely that this level of observation was connected to taking steps to obtain urgent care, as that is what the danger sign message is all about. The higher quality and availability of care at the primary health centers would have given women confidence that arriving their with their newborn could indeed be a life-saving trip.At follow-up, mothers also were responding with more home care for their sick children. When their children had fever and diarrhea, at follow-up one in ten women in the intervention communities reported treatment with home mixed sugar-salt solution, as instructed by the CHW. In the control communities, there was hardly any use of ORS in 2011. The mothers in the intervention communities also reported giving more fluids to their children, though the differences were not significant between the control and intervention areas. Both changes reflect the influence of the community discussions in the intervention areas, where women in the community learned about the importance of rehydration and then through CHW home visits how to mix the sugar-salt solutions. Our results suggest that the combination of community dialogues plus CHW home visits can address one of the priority problems identified by the Child Health and Nutrition Research Initiative, namely to identify methods to increase the practice of home care to prevent and treat newborn infections .This study has several limitations. First, we did not combine the datasets for an integrated analysis of the behavior change between baseline and midterm, which limits the analysis to a comparison of means and proportions. The pre-post comparison between the BHS and the End-of-Project Survey will include this merger of data, enabling regression analyses to be used to identify the predictors of behavior change and health outcomes. Second, all behaviors and health outcomes are by self-report, with no medical verification of the health events or deaths. As in any retrospective self-report, particularly of infant and child deaths, there is likely to be under-reporting. We assume that the level of under-reporting for these events is comparable across both surveys, but with the increased push for birth registration by the programme, it is possible that the reporting of births and deaths is higher in the FHS, which would tend to upwardly bias the mortality estimates relative to the BHS. Third, and most importantly, the CHW intervention components were only operational for approximately one year prior to the FHS, and hence the period of exposure is more limited for these elements of the intervention. The lack of change for some indicators between the BHS and FHS may therefore be due to limited exposure to the intervention. The End-of-Project Survey will permit a longer duration of exposure to be assessed, and it will include a more detailed set of measures of program participation. These limitations notwithstanding, the net result of the changes in understanding about newborn and sick child care were evident in the observed declines in infant and child mortality rates during this short time period. Declines in both rates were observed in both the control and intervention areas, but they were significantly greater in the intervention communities.Prior to launching the PRRINN-MNCH program, infant and child mortality rates were very high; there was very little use of the primary health care system, and virtually no community-based services. The program used an integrated approach which simultaneously matched quality improvements in the primary health care system with community-based health promotion activities which built confidence and communitysupport for women learning about and taking care of their children, including through use of primary health care services. This comparison of newborn and infant care practices in the intervention and control communities provides evidence that in the context of ongoing improvements to the primary health care system, the participatory and community-based interventions focusing on improved newborn and infant care were effective at changing infant care practices and outcomes in the intervention communities.Authors declare that there are no competing interests.SF, OU, HD, CG, FA, and GYA participated in the conception of the study, assisted with the analysis, interpretation, drafting, and revision of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/1034/prepub