This paper reviews what we know about prediction in relation to mood disorders from the perspective of clinical, biological, and physiological markers. It then also presents how information and communication technologies have developed in the field of mood disorders, from the first steps, for example, the transition from paper and pencil to more sophisticated methods, to the development of ecological momentary assessment methods and, more recently, wearable systems. These recent developments have paved the way for the use of integrative approaches capable of assessing multiple variables. The PSYCHE project stands for Personalised monitoring SYstems for Care in mental HEalth. Mood disorders are associated with high levels of morbidity and mortality, and they also engender enormous costs in society because of their high prevalence, early onset, and episodic course , 2. AccoThe estimated burden associated with mood disorders is essentially due to major difficulties with patients' care, namely, that pharmacological treatments usually have week-long onset latencies, and it is impossible to anticipate individual responses to treatment. Moreover, a substantial proportion of patients have relapses during their lifespan. It is also well known that compliance with drug treatments and specific lifestyle changes  are important issues for the long-term management of mood disorders.Some studies have identified the importance of sleep, stress, and other modifiers of daily routine in mood disorders –8. HowevIn the same context, the European PSYCHE project  has developed an interactive system based on the long-term recording of physiological and clinical parameters with user-friendly portable recording devices (smart fibers and interactive textile) and a smartphone for the outpatient environment –23.We present the PSYCHE project below and start by reviewing evidence with respect to objective markers in mood disorders . Then we describe how the use of information and communication technologies has developed in relation to mood disorders, right up to the development of wearable systems, and, more recently, integrative approaches allowing for the assessment of multiple variables.An “optimal” care approach to mental health involves the prediction of treatment response and the risk of relapse. Many great parameters, such as the clinical course, have been identified as potential predictors. For instance, the number of previous episodes and subclinical residual symptoms affect the risk of relapse in depression and bipolar disorder –26. StreIn addition to clinical factors, biological and neuroimaging data are also important sources of information for prediction purposes –34. HoweObjective measurements are rare with psychiatric conditions and are of very limited use in clinical settings. For instance, the most accurate correlates of mental disorders can be drawn from neurobiological studies involving electroencephalographic (EEG), functional magnetic resonance imaging (fMRI), or positron emission tomography (PET). These techniques are expensive and difficult to use on a regular clinical basis. Other measurements and variables, however, were also taken in consideration. For instance, poorer physical functioning and increased motor activity are associated with subclinical depressive and manic symptoms, respectively, and could predict relapses in these two clinical states –43. HoweHeart and respiratory rates are also potential markers for stress, sleep quality, and sleep/wakefulness transitions. The monitoring of heart rate variability (HRV) can serve to evaluate the mutual influence at play between the central and peripheral nervous systems and could be a promising way of tracking down mood variations in psychiatry –48. AlthEEG activity could be also an appropriate tool, especially for predicting the therapeutic response in depression  and bipoPlethysmography is a noninvasive technique used to assess vascular functioning and to obtain complex cardiorespiratory data . It is aElectrodermal activity (EDA) records biological electrical activity on the surface of the skin and is a technique known since the late 19th century. EDA reflects the activity of the autonomic nervous system, and EDA hyporeactivity has been described in many studies of depressive patients, but very little data is available with respect to bipolar patients . In a reThere is strong evidence in the literature of a link between dysregulation of the circadian rhythms and affective disorders , 5, 7, 8The relationship between mood and certain physical variables extracted from speech is also well established. Depressed speech, for instance, is traditionally defined as dull, monotone, monoloud, and lifeless . These pAmong these physiological parameters, heart and respiratory rates, nocturnal sleep, daytime activity measured by actigraphy, and voice analysis seem to be the most promising in terms of monitoring in clinical settings.The aforementioned studies, which focused on specific clinical or physiological aspects, show the limits of our knowledge of the biological counterpart of mood disorders, and such limited knowledge also has consequences for our ability to estimate and predict the clinical course of bipolar disorders. This is an observation, however, which specifically applies to studies that consider one physiological variable at a time and which thus argues in favour of using a multivariable approach. To achieve such a goal, there is a need for a multiparametric monitoring system that is easy to use in the clinical follow-up of patients with mood disorders. Technological progress towards the miniaturization of electronic devices, which become portable, and their integration in everyday objects such as items of clothing or mobile phones can contribute to achieving this aim. New-generation systems allow for devices that are more user friendly and more manageable and which can be used for long-term and long-lasting monitoring. Although this new kind of “remote medicine” has existed for more than 20 years, over the past five years it has experienced rapid development with the use of wellness wearable system (WWS) in many medical fields –79.The use of ICTs in the field of health has increased considerably in recent years. Computers and the Internet offer new possibilities for monitoring patients. These developments provide an incentive to rethink the organization of healthcare, with patients moving from a passive to an active role . In psycOptimum management of patients with mood disorders would include continuous assessment of their mood swings. Several paper-based mood charting devices  are currently used as self-reporting methods for following the clinical course of patients with bipolar disorder and for promoting their self-management skills . The traThere are two types of procedures with real-world and real-time assessment, usually referred to as “ecological momentary assessment” (EMA) and “experience sampling methodology” (ESM). The first focuses on phenomenological experience, whereas the second integrates objective data such as physiological parameters .Although “paper-pen” assessment may be accompanied by alarm devices, adherence to such procedures remains low . That isWearable health systems are already available as means of enhancing health care and combine biomedical technologies, microtechniques, and communication technologies. As Lymberis and Gatzoulis showed in their review , it is pAs of today, studies increasingly make use of high technology to record data and enhance care. The study by van den Berg et al.  developeAbove and beyond the collection of physiological data (included in ESM), wearable health systems may contribute towards the collection of clinical information and establish a continuous interaction with physicians, for example, via a mood diary posted on a website, software on a computer, or a smartphone application. Indeed, physiological monitoring is now possible using micro-noninvasive biosensors embedded in objects such as bracelets or clothing items and even smart t-shirts , 99. ActThe European Commission (EC) supports a number of mental health projects involving personal health systems under the 7th Framework Programme (FP7) , 101. ThIn recent years the transition from ordinary mobile phones to smartphones has transformed a simple telephone communication tool into a multifunctional object incorporating the possibility of more sophisticated means of communication such as Internet and Bluetooth connections. Furthermore, physiological monitoring has been simplified with features such as smart clothes which integrate very small biosensors and can be used to both multiply the number of parameters that can be measured and introduce physiological and psychological measurements into ambulatory practice. Thus, the progress made in EMA technology and physiological multiparameter monitoring over the past decade now makes it possible to combine these two strategies in a new generation of studies. This new area of medicine, especially in the field of mental health, needs to integrate and combine wireless psychological and physiological monitoring and rethink the roles and contributions expected of patients and clinicians.http://www.psyche-project.org/). Its goal is the development of a personal, cost-effective, multiparametric monitoring system based on textile platforms and portable sensing devices for the long-term and short-term acquisition of data from patients affected by mood disorders. The project has developed innovative portable devices for monitoring physiological markers, including voice analysis, and a behavioral index correlated to the patient's clinical state. The data acquired will be processed and analyzed on the dedicated platform so as to check the disease diagnosis and help with the prognosis. Finally, communication and feedback to the patient and physician will take place via a closed-loop approach that will facilitate disease management by fostering new collaboration, affording the patient more independence and empowerment. The physiological data collected with these noninvasive devices will include HRV, respiratory rate, activity, and movement, as well as voice. The devices are already available and have been successfully tested for managing diseases such as heart disease, chronic obstructive pulmonary disease, metabolic disorders, and diabetes.The European PSYCHE project associates 10 scientific partners from private industry, fundamental research, and academia  were used to select the parameters. They are based on clinical literature (as reviewed in the first section of this paper) and clinical experiences. The technical criteria are based on feasibility and wearability. For ethical and pragmatic reasons, we were at pains to ensure that the system does not stigmatize patients or constitute an intrusion or constraint with respect to their habits.The PSYCHE system consists of two prongs . The firThe PSYCHE system involves five main contributors: (i) the attending physician, who assesses the patient and together with the patient defines the parameters for the smartphone, (ii) the patient, who is assessed at the medical center and is the user of the system , (iii) the researcher, who downloads measurements and patient data for research purposes, (iv) the biosignal analysis specialist, who is the researcher who designs and analyzes the collected data, and (v) the system manager and administrator who are responsible for the system's functionality and maintenance.The data recording system is composed of a WWS and a smartphone. The WWS consists of a garment connected to a portable electronic device, the SEW (Side Electronics Wearable), via a standard 4-pin jack connector . The SEWThe PSYCHE garment  is composed of apposite textile interfaces designed to fulfil ergonomic as well as functional criteria to avoid any interference with user activities without invalidating sensor performances. The system design is easily worn as the patients' go about their daily life and during sleep. The aim was to guarantee a high level of comfort so that the patient is motivated to use the system. The sensing platform for use during the acquisition phase has been designed via a cut and sews process. Two fabric electrodes are placed on the patient's thorax, and a multilayer structure is used to increase the pressure and amount of sweat. Finally, the garment with the portable electronic device is able to collect the following parameters: heart rate, breathing rate, breathing amplitude, HRV, posture and/or activity classification , and estimation of energy expenditure .The PSYCHE system can be used to monitor physiological signals during daily activity. In particular during the night, the bra is comfortable, and the electronic portable device is small enough to be worn with the t-shirt in a small pocket on the sternum (the dimensions of the device are 63 mm × 65 mm × 15 mm). The correlation of the different signals provides important information, related to spikes registered by the 3 axis accelerometers, the ECG signal variation, and heart rate actigraphy , 23, 109The portable electronic device will record the physiological signals on a local memory, which will be downloaded for offline processing.The smartphone used for the study will be a special one, part of the technological developments of the PSYCHE project. It will include applications responsible for recording a sleep agenda, a mood agenda, and a more detailed clinical assessment of mood state in the form of visual analogue scales from the Bauer Internal State Scale . The smaThe smartphone will also be used to transmit the data collected from the SEW for sending to the central webserver of the knowledge management system. To reduce the size of the data transmission the data are already stored, calculated, and compressed at harvest before being sent .The smartphone will use a 3G or WiFi communication to send data to the knowledge management system, and then information will be sent to the disease management system. The data are encrypted using secure connections (HTTPS with trusted certificate), and all the information circulated is anonymous. The information on the professional web portal of the disease management system will only be accessible to the physicians and researchers involved in the clinical studies in the context of the PSYCHE project.Below is a brief overview of the preliminary studies developed during the first stages of the study.In a first study  the authA later analysis of a larger sample  confirmeHRV analysis was taken further in another study  which usAnother study  analysedDuring two initial pilot studies, healthy subjects or patients were asked to fill in a questionnaire devised to ascertain the acceptability and usability of the PSYCHE system, since the long-term aim of developing a WWS is to create a new clinical tool that can be used at home.In the first study, 11 female subjects were included in a clinical study of healthy volunteers with a view to validating the technical device . They filled in questionnaires on day 1, straight after wearing the WWS bra, and on day 3, just before leaving the study center. Personal use of the system was not tested in this study, since the volunteers did not use it by themselves. The analysis shows that the bra was perfectly tolerated. No difficulties were reported with setting up the system, except for one participant who had difficulty plugging the cable in the SEW. No participants indicated having had problems removing the bra or feeling constricted in their movements during the study. All of the subjects indicated that, based on medical advice, they would agree to wear the bra.In the other pilot study 5 bipolar patients  were asked to fill in a two-part questionnaire. The first part was filled in when the patient arrived at the study center for a day-time recording period (day 1), and the second part the following morning, after the night sleep spent at home wearing the system (day 2). All five patients indicated that they would agree to wear the WWS following medical advice.Qualitative feedback  suggests, however, that patients would not wear the WWS for long periods of time. Their major complaints arguing against long-term use were that the garment was hot to wear and felt “tight.”It is not surprising that bipolar patients might be slightly more apprehensive than healthy volunteers and might have more difficulty using the WWS. The prospect of wearing a WWS 24 hours a day and 7 days a week is clearly difficult for both volunteers and patients. Its acceptability seems to be related to very practical reasons, namely, the idea of wearing a t-shirt at all times and in all seasons and of always having a clean wearable system to hand.Following these early results, technological system improvements and adaptations were made, for example, regarding the size and flexibility of the garment. The study consortium was also prompted to abandon the prospect of wearing the WWS most of the time in the next generation of validation studies and to consider more limited use of the system (see below).The preliminary studies conducted during the first phase of the PSYCHE project, as described above, were limited to assessing the selected parameters to identify the subject's current mood state. In the next phase of the project, the aim will be to assess the feasibility of using the PSYCHE system to predict significant clinical changes for bipolar patients. These will be exploratory studies, and the number of patients will be limited by the availability of prototypes (the limiting factor being the electronic portable devices rather than the garments or smartphones). In the two studies that are planned each PSYCHE recording with the WWS will be accompanied in parallel by a clinician-based assessment of the patients' depressive and manic symptoms with the QIDS-C16 (16-item Quick Inventory of Depressive Symptomatology—clinician rating)  and YMRSThe first study will assess whether the PSYCHE system is able to predict how mood states evolve, and whether it can contribute in any way to clinical follow-up within the context of treatment of an acute bipolar episode. Ten in-patients will be recruited in Pisa , and they will be recorded during a 19-hour session (including during the night) once a week. The maximum duration of the session is determined by the battery life of the electronic portable device. Patients will be studied during clinical remission from the time they are admitted to hospital to the time when they leave.The second study will address the question of whether the PSYCHE system can detect and predict subjects' mood swings within the bipolar spectrum. To that end, 16 subjects with either a rapid-cycling bipolar disorder or cyclothymic disorder or temperament will be recruited in Geneva (Switzerland) and Strasburg (France). During the 14-week study patients will perform a twice-weekly night recording with the PSYCHE system (including a limited period of time in the evening before going to bed and in the morning after getting up). The clinical profile of subjects was chosen to maximize the number of fresh mood phases during the study. Subjects with cyclothymic disorder or temperament could be particularly interesting in this respect. The subjects will be recruited among both the clinical and the general population.This paper reviews what we know about objective physical correlates in the field of mood disorders and addresses this question from the perspective of clinical, biological, and physiological markers. Despite the dramatic increase in our knowledge in this field, it has to be said that there is still a lot that we do not know and, more importantly, no biological or physiological marker has yet emerged as a relevant contribution for helping clinicians. There may be several reasons for this. Some may be due to limitations that have to do with the cost or ease of data collection. Others are due to the lack of predictive power of a variable when considered alone. The development of ICTs in the field of health and in particular mood disorders opens up the prospect of integrative approaches whereby multiple variables can be assessed using the highly sophisticated solutions ICTs have to offer. The PSYCHE project as presented in the last section of this paper comes within the context of the ambitious prospect of overcoming the aforementioned limitations. The PSYCHE system offers an easy, comfortable, and user-friendly way of collecting multivariable multiparametric data. Preliminary studies conducted in the framework of the PSYCHE project show the potential of single parameters (such as HRV or voice characteristics) to identify current mood states and the usability and acceptability of the system for patients . The challenge facing the project, however, will be that of going beyond current mood state identification to try to predict short-term mood changes with a view to predicting how patients will respond to either treatment during an acute episode or the recurrence of new episodes.Such health systems derived from ICTs have the potential to promote deep changes in the way care is organized. Some authors have highlighted the partnership position of patient issues  and the Thanks to progress these past few decades in the field of communications and the use of biosensors for data capture purposes, it is now possible to consider actively promoting wearable health systems in many different branches of medicine and in particular in the mental health field. For a long time, studies of bipolar disorder have addressed the question of the benefits to be gained from monitoring physiological parameters and mood changes as potential predictors of relapses. There are now many great protocols in place for assessing the benefits of multiparameter monitoring via wearable health systems with respect to the different pathologies encountered along the bipolar disorder spectrum. The way the healthcare system is organised could look very different in the future if a role is assigned to this dynamic form of care that can contribute towards reshaping the relative positions of patients and clinicians and involves giving worthwhile thought to the questions of data security and the ethical dimension to healthcare.The PSYCHE project is part of the recent development of ICTs in the field of mood disorders. The exact future of this field remains to be seen. It is a way paved with many questions, many risks, many challenges, but also many opportunities. This paper has tried to give the reader an overall view of the current situation and to illustrate potential with a specific project by way of example.


The primary health care sector delivers the majority of health care in western countries through small, community-based organizations. However, research into these healthcare organizations is limited by the time constraints and pressure facing them, and the concern by staff that research is peripheral to their work. We developed Q-RARA—Qualitative Rapid Appraisal, Rigorous Analysis—to study small, primary health care organizations in a way that is efficient, acceptable to participants and methodologically rigorous.Q-RARA comprises a site visit, semi-structured interviews, structured and unstructured observations, photographs, floor plans, and social scanning data. Data were collected over the course of one day per site and the qualitative analysis was integrated and iterative.We found Q-RARA to be acceptable to participants and effective in collecting data on organizational function in multiple sites without disrupting the practice, while maintaining a balance between speed and trustworthiness.The Q-RARA approach is capable of providing a richly textured, rigorous understanding of the processes of the primary care practice while also allowing researchers to develop an organizational perspective. For these reasons the approach is recommended for use in small-scale organizations both within and outside the primary health care sector. British Medical Journal [The primary health care sector delivers the majority of health care in western countries through small community-based organizations. In Australia, the vast majority of primary care is delivered through general practice. These small, busy organizations, composed of shifting configurations of staff, vary according to their local contexts, their size, their modes of funding, and the types of services they provide. To understand the processes that underpin the delivery of quality primary care, we need to have a nuanced idea of how individuals work within these organizations. But the methodological toolkit to collect and analyse data on staff and organizational function and activities is rather limited. Much research into primary care has relied on quantitative, or single-method qualitative research. Although the importance of qualitative research methods in primary care has been emphasized since the mid-1990s, spearheaded by the  Journal , studiesIn this paper we present an overview of a mixed-methods approach to researching small-scale primary care organizations that is rapid and rigorous . We developed this method to study nurses in general practice in Australia, at a time when nurses were moving into general practice in large numbers . We wishSeveral reasons have been put forward to explain the reliance on single-method studies, mainly interviews, focus groups and surveys in primary care research. As a rule, general practices are small businesses with few staff members all working under strict time constraints and pressure . BecauseAn additional challenge for researchers is the diversity of primary care organizations in terms of structure, funding, and function within and between countries . Such plqual methods). The approach takes into account the need to minimize the impact of conducting research in small organizations, while maximizing the capacity to produce rich, detailed contextual findings. In this article we present: (1) an overview of the background to the approach — rapid appraisal and qualitative mixed methods design (2) the approach itself, and (3) a critical discussion of the broader literature regarding mixed methods design and issues of rigor. We identify the strengths and weaknesses of the approach, as well as its potential contribution to researching primary care organizations by extending the use of a qualitative mixed methods design.Q-RARA draws on two main influences: rapid appraisal and qualitative mixed methods research design  . REAM isThe other antecedent for our method is mixed methods research. Mixed methods research is research that is informed by and situated along a spectrum of quantitative through to qualitative paradigms, and generally refers to the combination of quantitative and qualitative methods carried out “for the broad purposes of breadth and depth of understanding and corroboration” . It is nThe Research Act, Denzin [A particular strength of mixed methods research is the formal integration of individual methods at some point in the research process . Althoug, Denzin  populari, Denzin ,25 are bqual methods, can be considered mixed methods. QUAL-qual denotes a core project and a supplementary project whereby the latter cannot be a stand-alone project. According to Morse [Morse  challengto Morse  the dataQ-RARA attempts to marry the rapidity and limited intrusiveness of rapid appraisal methods with the rigour and integration of mixed methods research. In this paper, we subject the quality and rigor of Q-RARA to scrutiny through an assessment of its performance against Lincoln and Guba’s well-established frameworks of trustworthiness and authenticity .qual studies.The research approach was developed as the main mechanism to conduct the Australian General Practice Nurses Study. The methods are presented in detail here for the first time. We focus in our discussion of the methods on the ability to collect multiple forms of data, and the challenges of synthesis and quality assurance for QUAL-The AGPNS was conducted from 2005 to 2008. During this period there was a nationwide, government-led promotion of practice nurses in Australia including the provision of direct incentives, newly funded Medicare items, and the nursing workforce more than doubled to nearly 9,000 . This ch How do nurses operate within the structure of general practice? What are the local, individual and structural factors that determine the role development of nurses in different general practice settings? What contribution do practice nurses make to the safety and quality of general practice? and How might the development of new models of practice nursing be facilitated?The AGPNS research questions were:These questions have been answered in a series of publications ,30-35.qual method , and by individuals for the interviews and for the nurse observation components.This research was approved by the Human Research Ethics Committees of the Australian National University and the Royal Australian College of General Practitioners.The impact of the research conducted on the practices was minimized by the allocation of only one researcher to each research site and the completion of onsite data collection within one day. The two field researchers had disciplinary backgrounds in social science and community development and were not health professionals: a deliberate choice to optimize “naïve” or “fresh” observations of nurses in practices that were not obscured by prior professional experience. The field researchers scheduled the first observation early in the day because it demonstrated respect for the working hours of the practice and contributed to the development of rapport with staff. The background discussions prior to the visit and the daylong presence of a researcher meant that they were often invited to sit in on organizational activities, such as practice meetings or lunch breaks in the tearoom. The inclusion of the researchers in these ways demonstrated that the approach was acceptable to the research participants and contributed to the quality of the field notes.In-depth interviews were conducted with practice staff to generate participant accounts and to assay different perspectives on the nurses’ roles. Practice nurses provided insight into their lived experience, practice managers were able to reflect on the administrative and managerial aspects of the nurses’ work, and general practitioners recounted their experiences both before and after they had decided to employ a nurse, and the impact of this decision.The structured observation involved a small quantitative element in that observations were recorded in ten-minute lots. Some elements, such as the number of contacts with the nurse, were counted. The observations were undertaken in two one-hour periods using a paper-based system with a timer marking every ten minutes. If the practice employed more than one nurse, the field researcher attempted to observe a different nurse in the afternoon session. Preliminary trials in general practice revealed that some of the nurse contacts or activities over the period of an hour related to the same task, which were iteratively continued between other tasks . The observation tool was therefore adapted to capture the cyclical nature of a nurse’s work. The trials also indicated that recording observations at intervals of less than five minutes was technically impossible for observers using a pen-and-paper observation tool unless they provided very limited details on the activities themselves. The data collection tool comprised a table in landscape format over two pages, where each row represented a 10-minute interval and each column represented a task Table . The celAfter a two-day training workshop, and in tandem with a chief investigator, each field researcher trialled Q-RARA to check the quality of their interview and observational skills. The concordance rate between the field researcher and the chief investigators for the time-motion studies was between 94% and 96%. As each site was visited, the data were double checked by other researchers, and the field researchers were able to debrief on the process of data collection. Many practice nurses reflected upon their activities to the researcher, resulting in a slowed-down version of the nurses’ activities over an hour. Even so, the number of activities and contacts undertaken by nurses was very high, with an average of 28 discrete activities per hour (range 6 to 60). In addition to activities, nurses sometimes moved rapidly between the consulting rooms responding to doctors, as well as communicating with patients in the waiting room. One nurse had 36 direct brief contacts with staff and patients in the hour, an average of one every 100 seconds.The floor plan was obtained or drawn by the observer, with patient areas and nurse workspaces marked in, and nurses were asked to identify key work areas to be photographed. The observer also collected written material from the family practice, such as practice information leaflets, and practice websites supplemented the other material. Finally, each practice was subject to social contextual mapping, which involved obtaining local demographic and contextual information about the availability of health services. Details collected for each practice included: geographical classification, distance from nearest acute hospital and community based services, number of regional family practices, allied health service availability, population data, and regional socio-economic indicators such as unemployment rates.intra-case study, and, (3) each practice was compared with all other practices via an inter-case study.The researchers involved with the AGPNS had a range of disciplinary backgrounds including nursing, general practice, sociology and health policy, and they met regularly over twelve months to analyse the data and generate the findings. All data that were related to one general practice were combined to make a case. Analysis occurred in three stages: (1) All like data, such as interview data, were coded, (2) data that related to an individual general practice were examined as an Interviews and field-notes were coded using NVivo 7.0 software  by two researchers and two research assistants, employing a coding framework developed concurrently with the interview schedules. This framework was then continually revised throughout the analysis in response to research undertaken using emergent design.Observational data were coded using a framework that distinguished tasks as administrative, clinical, servicing (e.g. stocking and sterilizing), or communicative (e.g. brief contacts with colleagues), and were then presented as pictograms. Each pictogram captured four distinct elements of the nurse’s work world: time (when), tasks (what), people (who) and locations (where), and the relationships between these elements. Producing each pictogram was an integral part of the analytic process . Our picA researcher coded the practice floor plans and photographs using the principle that the floor plans functioned as a set for a theatrical performance, while the photographs gave insights into the way the set was used . The floIntra-case analysis. The purpose of this level of research was synoptic, because we sought coherences across the different data types to make a finding about a particular practice, and a nurse’s role in that practice. For example, comments about space in the interviews were matched to the floor plans and photos of nurse workplaces, and were considered in the light of the time and motion studies and researcher field-notes. The intra-case analyses were returned for comment to the participant practices to establish the credibility of our generated findings [findings .Inter-case analysis. Two team members from different disciplinary backgrounds working independently analysed in detail the data for each emergent finding, and subsequently presented their analyses to the rest of the team for discussion. A third team member was appointed to assist with the synthesis of data and identify discrepancies in the analysis; this prevented superficial synthesis of the data, or discordant analysis. The iterative approach of the multidisciplinary team drawing on a number of data sources was able to generate a more trustworthy interpretation than would have been achieved otherwise. An example of an evolving interpretation of data from the study from a range of disciplinary perspectives is presented in Case Study 1. In Case Study 2 we set out an example of integration of like analysis, and intracase and intercase analyses.The maps of general practices showed that nurses’ stations were located either in treatment rooms or in retrofitted areas like alcoves and areas off the reception desk. There were very few nurses who had their own dedicated consultation rooms.Initial interpretation. Our initial interpretation of this allocation of social space was that it reinforced the marginalization of nurses in general practice. Although it was recognized that urban practices had to retrofit their spaces to incorporate nurses, doctors on the research team felt that not having their own rooms indicated that nurses were marginalized. This view was supported on the online discussion board by some nurses.Second interpretation. The sociologist wondered if the location of nurses’ rooms reflected more than professional hierarchies. She noted that nurses’ stations were usually spatially central in the practice, and co-located with the patient bed upon which the most acutely ill patients would be located. The field researchers’ notes recorded numerous instances of nurses citing the treatment room as their ideal professional locale. Review of data showed that the treatment room and the waiting rooms were the two patient-centred spaces, and that nurses visited these the most.Revision of second interpretation. Field researcher reflections noted the reluctance of nurses to enter general practitioner spaces, except to find things. However, observation data and their reflections indicated that a reverse recognition was occurring with doctors reluctant to enter the treatment room without permission if it was occupied by the nurse.Final interpretation. Locating the nurse’s station in the treatment room (provided the treatment room was large enough) was not seen as inappropriate or demeaning by most nurses, but rather acted as a way of reinforcing their status as parallel clinicians within the practice.Like data  Table observation of one nurses’ activities. Figure spatial mapping of the practice. During the hour she moved from the treatment room, where her desk was located, to the reception desk. Her photographs had been of staff-only places: treatment and sterilising rooms, and the drug cupboard. Her observed activities included education, clinical work and scanning and distributing of results. She had seven brief contacts , and solved a problem at the front desk.Intra-case synthesis . The nurse was new to general practice, and described herself as increasingly aware of the exigencies of small business life; hence, she had arranged for a visit from the drug rep in return for servicing the electronic blood pressure monitor. She and the GP had a collegiate relationship. He had directly recruited her from hospital to “do the things I don’t know about” (he instanced immunisations and wound dressings). The manager and the nurse had different ideas of the nursing role, with the manager wanting her to provide more services that would meet a need in the community and generate income (e. g. chronic disease clinics). The nurse described a number of educative activities - infection control, using guidelines - as key roles. The RA notes recorded that as the nurse took her photographs she commented rather ruefully on her work being in the “unseen places”.Inter-case synthesis Comparisons across all practices were produced on lines of thought emerging from individual practices about nurses’ roles and their determinants. This case study produced as key lines of thought: “educator role”, “contribution to quality enhancement”, and “recognition”. The nurse’s workload was evolving towards education in addition to clinical work, without her employer recognising it. The drivers of connectivity identified in this study  are well-illustrated in this example. The case also illustrates the need to problematise the connectivity role. The amount of time devoted to e-connectivity may prevent the nurse from fully engaging in other work to expand her role.trustworthy data are credible, transferable, defendable and confirmable. Data should also be assessed for authenticity, a domain that includes fairness, and educative, ontological, tactical and catalytic authenticity. These assessments are presented in Tables We assessed the quality and rigor of the data and findings generated by Q-RARA, and interrogated its capacity to adequately reflect the stakeholders’ views, against the adequacy criteria suggested by McNall and Foster-Fishman  in theirOne of the clear challenges in assessing our approach against Guba and Lincoln’s criteria for trustworthiness was that they maintain that credible data are developed through prolonged engagement. Our method is predicated on short-term, intense engagement and cannot be compared with ethnography, which involves long-term (prolonged) engagement.Despite their short period in the practice, research assistants were allowed access to the backstage of general practice. They were invited to observe practice meetings, accompanied nurses on their rounds when they left the practice, and followed her as she moved across all the spaces in the practice, including into doctor’s rooms. We considered that within a short-term engagement we had achieved a sense of engagement that was sufficient to meet the goals of the larger project in terms of data collection, but that this time frame may not be suitable for some other types of projects.Against other criteria for the domain of trustworthiness the method performed well as outlined in Table The method was able to meet all the criteria contained within the domain of authenticity, as outlined in Table qual method, and (3) quality and rigor. First, the approach was well received by the research participants, particularly the practice nurses who believed that the interest of the researchers validated their work. In common with traditional rapid appraisal methods, Q-RARA in general practices was carried out with minimal disruption to the research site while gathering a large quantity and range of data. Feedback from the nurses collected at the time and after leaving the site, indicated that Q-RARA did not disrupt their work unduly beyond the issues described above. It also has relevance for research in other small organizations, or can be employed, as Murray [The approach to using Q-RARA, developed through the AGPNS, demonstrated three main features: (1) a high degree of acceptability in the field, (2) the operationalization of a modified QUAL-s Murray  has demoqual method, the original definition of mixed method design proposed by Morse and Neihaus [Second, in terms of the modification of the QUAL- Neihaus , p. 9 st Neihaus  went on  Neihaus , p. 281. Neihaus -47.qual method by adding more than one standard qualitative method central to the study; both the in-depth interviews and the structured observation were core components. We suggest that the successful operationalization of this extended version of the QUAL-qual method may require alternate wording for the definition of mixed qualitative method design that addresses the concerns outlined above: QUAL-qual method design comprises several different qualitative methods, the choice of which is driven by the researchers’ epistemological position and theoretical perspective, and the research objectives. One or more of the methods may be able to generate sufficiently coherent and convincing findings to be published alone, but the authenticity and trustworthiness of the findings are increased by the planned use of additional research strategies that are insufficiently robust to generate defensible findings alone. The data types, level of analysis, or participant perspectives must be sufficiently different to warrant separate handling prior to integration. However, the findings generated by the different methods must be combined at some point in the research process.In our approach we modified the QUAL-qual method that were made in our approach are a development from existing rapid appraisal studies in primary care in that they directly engage with epistemology and integration, unlike other studies—such as Murray et al. [The modifications to using the QUAL-y et al. ,48 wherey et al.  it is tyqual method also revealed the nuances of social life, particularly in the way that they relate to differences in power and authority. For instance, it became apparent that the general practitioners were unaware of the range of tasks undertaken by practice nurses and their corresponding skill set [Third, the use of exploratory mixed methods provided a range of data that would have been missing had we limited ourselves to the original definition proposed by Morse ,27. Theskill set .The conduct of the AGPNS and development of our approach, like any field-based method, can be derailed by major events. A site visit had to be curtailed because the general practice principal collapsed and had to be taken to hospital. Nevertheless, the field researcher was able to observe and comment on the way the organization functioned in a crisis. The most difficult component of data collection was securing an interview with the general practitioner due to time pressures on their work. Consequently, some interviews with GPs were conducted by telephone after the practice visit. In small general practices, GPs have the most difficulty disposing of their time freely. Our results suggest that if this method had focused on those with least flexible time schedules in the organization, we would have had to allow more time or additional participant-responsive methods, such as video, or specific attention to informal meeting sites, such as tea-rooms.The intensive nature of the day-long visits to practices could be draining for the field researchers, who were required to collect a great deal of data in a concentrated period of time, without disrupting the practice or losing rapport with practice staff. The two field researchers travelled very long distances to visit the sites, and were initially over-scheduled. Sufficient time between site visits is needed to collate field-notes, to recover from the trip and to prepare for the next one. Consequently, the 25 site visits were undertaken over a period of four months, equivalent to one site visit by each researcher every 10 days.We believe that the one-day visit design is defensible even though it means that intra-clinic variation in workload across the week was not captured. All staff were asked if the observation day was typical for them, and how they structured their working week. Interviews were able to flesh out and extend the insights gained through observation; thus although there would have been differences in the observational data on different days, these did not change the broad categories of role expressions and determinants that were identified in each practice.We noted that the structured observation tool could be improved by using more advanced technology. Nurses could be trained to use personal digital assistants or smart phone applications to record their own time use patterns. This may result in more valid data on the time use of nurses  but at tFocus groups were not included in our version of Q-RARA because of the very small size of the health care teams, and concerns that setting up a focus group would take away too many people from the workplace. We have subsequently used them in another study using Q-RARA where we were interested in the interaction between patients and volunteer-leaders in a falls prevention program .The structured observations were also limited because the researcher was not permitted to observe patient-nurse interactions. This meant that our analysis under-represented clinical care aspects of the nurse’s role. However, the fact that the nurse-patient interactions were not observed made the presence of the researcher more acceptable to the family practice itself. A method of this nature, where the researcher is only present for a short period, does not allow the researcher to develop trusting relationships with patients as, for example, an ethnographer may be able to do. To observe patient-nurse interactions would have imposed the burden of explaining the study to successive patients upon the reception and nursing staff, and slowed down the work of the practice.qual methods, integrated these into a practical approach that is efficient, acceptable and rigorous and successfully trialled the resultant rapid QUAL-qual method in primary health care settings, an area that has seen little field-based research. We found our Q-RARA approach to be acceptable to participants and effective in collecting data on organizational function in multiple sites without disrupting the practice, or requiring the researcher to have a long-term presence in the practice. It was also able to strike a balance between speed and trustworthiness. Q-RARA seems capable of providing a richly textured rigorous understanding of the processes of the primary care practice while also allowing researchers to develop an organizational perspective. We have since used Q-RARA to explore community-based falls prevention activities, incorporating both movement-mapping and focus groups with patients.The dominance of interviews in qualitative general practice research typically drives researchers to explore one cadre within the practice, such as patients or healthcare providers. Consequently, there is a need for methods with proven utility that enable researchers to undertake studies of the organization itself and consider the health policy environment. We adapted and formalized REAM within a mixed-methods approach by taking the broad area of REAM and QUAL-For these reasons we believe the approach has merit for studying small-scale organizations both within and outside the primary health care sector, and bounded areas of larger health institutions.


The incidence and severity of endometriosis in adolescent are comparable with the incidence in adult women. The mean delay between the onset of symptoms and the final diagnosis varies between 6.4 and 11.7 years. The longer the diagnosis is delayed, the more the endometriosis can progress to a more severe stage certainly in the group of patients with pelvic pain. The evolution of endometriosis and its progressivity are not predictable, and the severity of the disease is not directly related to the degree of pain. Endometriotic cysts have a detrimental effect on the ovarian reserve by the evolution in time and the surgical excision technique. Already, in small endometriotic cysts (<4 cm), loss of follicular reserve is present together with the formation of fibrosis in the cortex of the ovary. Early diagnosis of endometriosis in the adolescent deserves our full attention. Non-invasive imaging techniques like 2-D and 3-D ultrasound are helpful in the early diagnosis. Early ablative surgery is recommendable. Although laparoscopy is traditionally recommended, transvaginal laparoscopy has been shown to be most effective in ablating endometriomas with a maximum diameter of 3 cm. Early detection and intervention will contribute to a better quality of life in these adolescents and also to a lower damage of the ovarian tissue by a less invasive ablative surgery. Ovarian endometriosis, a disease similar to the Mona Lisa face, fails to be grasped and identified by current descriptions. At present, the diagnosis requires an invasive surgical technique, whether laparotomy or laparoscopy, to diagnose the presence of ectopic endometrium-like tissue. In the young woman, the symptoms may be suggestive, but vary greatly and elicit frequent compassion rather than investigation and treatment. Nevertheless, understanding endometriosis in the young woman may shed light on the more complex appearance in the adult woman and improve early-stage management . This reEndometriosis is described as premenarchal and distinguished from adolescent when symptoms and lesions occur during the phase of telarche before the menarche.Marsh and Laufer  identifiOriginally described more than a century ago, endometriosis is thought of as a disease that affects adult women, but there is increasing awareness of its presence in young women. The disorder represents already in the young woman a vague and perplexing entity that frequently results in chronic pelvic pain, adhesive disease, and infertility. Differences exist between adolescent and adult types of endometriosis, but it is likely that diagnosis and treatment during adolescence decrease disease progression and prevent subsequent reproductive failure. The first study of adolescent endometriosis by Hanton et al.  covered P = 0.044). The authors concluded that the presence of lesions at multiple sites is a risk factor of recurrence and that GnRHa can effectively prevent the recurrence.A recent Chinese study by Yang et al.  includedRecent studies of endometriosis in adolescents show clearly that the disease is no longer characterized by subtle superficial lesions, but also by the presence of ovarian adhesions and endometriomas . CompariThe presence of peritoneal and ovarian endometriosis in premenarchal girls without an obstructive anomaly has supported the concept that endometriosis may result from an etiology other than retrograde menses as proposed by Sampson in 1927 . Batt anFollowing the current available evidence regarding stem/progenitor cells in the human endometrium, Oliveira et al.  suggesteProgression of the endometriotic lesion is characterized by two stages of morphological activities. In the first phase, the superficial endometriotic implant responds like eutopic endometrium to ovarian steroid hormones resulting in proliferation, secretory changes, and decidualization followed by superficial desquamation and bleeding. In the later phase, the interstitial implant is associated with smooth muscle metaplasia and formation of deep or adenomyotic nodules. In the ovary, progression of endometriosis leads to bleeding and adhesions resulting in endometrioma formation, while interstitial smooth muscle metaplasia and fibrosis affect the cortical zone and decrease the follicular reserve.Superficial endometriosis is characterized by adhesion formation. It is now well accepted that the typical ovarian endometrioma is caused by encapsulation of endometrial tissue between the ovarian cortex and the posterior leaf or the parametrium as originally described by Hughesdon in 1957 . In an iCareful inspection by ovarioscopy , 27 alloOne of the subtle and poorly appreciated changes associated with ectopic endometrium is smooth muscle metaplasia (SMM). According to Anaf et al. , deep inAt present, Sampson  and HughThe question arises to which extent the SMM associated with the ovarian endometrioma affects the follicular reserve. In a recent study, Kuroda at al.  obtainedThe morphological data on follicle loss in women with endometrioma has been confirmed by the impact of endometrioma on serum anti-Mullerian hormone (AMH), which is proposed as a marker of ovarian reserve. In a retrospective study comparing serum AMH levels in 1642 infertility patients without endometrioma and 141 patients with endometrioma, Hwu et al.  found thKitajima et al.  demonstrFibrosis of the endometriotic cyst was also frequently observed (9/13) in the study of Schubert et al.  while thAccording to the endometriosis literature, the two main reasons why medical advice is sought are chronic pelvic pain and infertility. However, several studies have shown that the onset of symptoms precedes by several years the diagnosis of endometriosis. In a study comparing demographic, epidemiological, and medical data, Dmowski et al.  noted thThe study also found that the majority of women with endometriosis and infertility had either mild or no pelvic pain symptoms, suggesting the possibility of asymptomatic endometriosis. According to previous studies, unsuspected endometriosis is found in multiparous women undergoing laparoscopic tubal sterilization with a prevalence ranging between 2  and 3.7 Early-stage management of endometriosis in the adolescent involves exclusion of reproductive tract anomaly, monitoring the response of pelvic pain to medical treatment and the early ultrasound diagnosis of an endometrioma and, in such cases, full ablative surgery of the ectopic endometrial tissue. The combined oral contraceptive pill has been used for the treatment of endometriosis-associated pain, such as dysmenorrhea for several years. The treatment may also relieve deep dyspareunia, non-cyclic pelvic pain, and dyschezia. While adolescent endometriosis is a hidden, progressive, and severe disease, the medical and surgical tools for diagnosis and treatment should be effective, but minimally invasive.Two studies have evaluated in detail the benefits of early diagnosis for the patient. Ballard et al. , 47 inveNnoaham et al.  assessedIt is clear that supportive and comprehensive treatment should be provided until the completion of childbearing.Transvaginal ultrasound is the first choice for monitoring the ovaries for early-stage development of a uni- or bilateral endometrioma. In the study of Holland et al. , the sen2 pneumoperitoneum at standard laparoscopy enables not only a better visualization of superficial adhesions and vascularization, but the procedure is also performed in the absence of a status of intra-abdominal hypoxia present at standard laparoscopy. It is questionable if such a long time exposure to the hypoxia caused by the CO2 pneumoperitoneum is finally not detrimental for the ovarian reserve and is a co-factor for the diminished AMH concentration after surgery.Atraumatic ovarian surgery, to avoid loss of ovarian reserve, is based on early-stage diagnosis when cystectomy can be avoided. Although laparoscopy is traditionally recommended, transvaginal endoscopy has been shown to be safe and most effective in ablating ovarian endometriomas that are not larger than 3 cm in diameter , 55. As In young patients with severe dysmenorrhea, we suggest the following decision tree: In a first step, presence of rectovaginal endometriosis and/or ovarian endometrioma should be excluded by a clinical examination and transvaginal ultrasound. In case of negative examination, patient can be put upon oral contraception and/or NSAID with yearly follow-up; in case of persistence or aggravation of pain, a transvaginal hydrolaparoscopy (THL) or in case of contraindication for a vaginal access standard laparoscopy (SL) should be performed and endometriotic lesions should be treated. In case of diagnosis of ovarian endometriosis in the absence of rectovaginal pathology at clinical examination, a six monthly follow-up under a contraceptive pill is advocated to exclude the increase of the ovarian endometrioma and to evaluate the regression of pain. In case of non-regression of the pain and/or increase of the size of the endometrioma, endoscopic exploration and treatment by THL or SL are mandatory. In the presence of rectovaginal endometriosis, the necessary exploration must be done before referring patient for an operative laparoscopic procedure Fig. .Fig. 2DeIn the absence of contraindications for a vaginal access  and if tAt present, there is no evidence that in the adolescent all subtle peritoneal endometriosis can be visualized at laparoscopy. A variety of subtle lesions have been described , but theFrom the early onset of female neonatal life, due to neonatal bleeding and retrograde menstruation, endometrial cells invade the pelvis and are possibly at the origin of the presence of premenarchal and adolescent endometriosis.It is hard to understand why the diagnosis of endometriosis is so long delayed resulting in severe stages of endometriosis including a frozen pelvis. As health practitioners, we have to question ourselves why we are missing the development of this disease in individual women. Not only the patient herself is unaware of objective symptoms like severe dysmenorrhea and superfluous or frequent menstruation resulting in a late medical advice but also the general practitioners or gynecologist is not sufficiently sensitized for the importance of the symptoms. Furthermore, diagnosis is impaired as there is not a good correlation between the severity of the disease and the symptoms. All these results are a delay of an accurate diagnosis between the onset of symptoms and the final diagnosis. Certainly, in adolescents with chronic pelvic pain such as dysmenorrhea resistant to medication, the incidence of endometriosis is around 70 % , 66. It The purpose of an early intervention is the treatment of pain, prevention of the progression, and protection of the fertility . As endoAs ablative surgery of small endometrioma intends to be more accurate and complete, reasonably, we could expect, although not proven, that this will result in a lower recurrence rate, being easier to perform and minimal invasive. Pados et al.  and DonnThe use of the transvaginal endoscopic approach adds to the minimally invasiveness of the procedure. The use of a watery distension medium allows an accurate visualization and early detection. Ablative surgery is done using a micro 5 fr bipolar probe causing minimal damage. In the absence of a panoramic view, the transvaginal endoscopic procedure is limited to the treatment of small endometrioma (<3 cm).Endometriotic cysts differ from other benign cysts as they are extra-ovarian pseudocysts with the absence of a clear delineated capsule and not restricting the disease to the cyst itself but affecting the surrounding cortex by SMM and fibrosis. This explains the difference in ovarian reserve between patients with a dermoid cyst and an endometriotic cyst, with a negative impact on the latter.Early diagnosis of endometriosis in the adolescent deserves our full attention. Early ablative surgery can contribute to a lower morbidity, a relief of symptoms, and a better quality of life. Treatment in early stage will result in less damage to the ovary caused by the disease itself and by a less invasive surgical procedure. Endometrial cells on the surface of the ovary carry the risk to affect the ovary in two ways: first by causing ovarian adhesions and pseudocysts and secondly by causing mesenchymal cell metaplasia in the interstitial ovarian tissue, sclerosis, and follicle loss. Similar as in oncology, there is no reason to wait.Further research has to be done to elucidate if such early treatment will result in lower recurrence rates and less severe forms of the disease.


Sexual function is an essential component of life. For this reason, sexual dysfunction can have a negative impact on the wellbeing of men and women alike. Since the turn of the 21st century, research on female sexual dysfunction (FSD) has gained momentum. While FSD is often assessed in people with ill health, sexual dysfunction is an illness of its own entity and is also prevalent in non-patient populations. A critical review of current literature on female sexual dysfunction in general populations will shed light on possible determinants as well as at-risk groups. Thus, the aim of this systematic review is to assess the prevalence and the predictors of female sexual dysfunction in general populations.A systematic review of current literature on FSD will be performed. Studies will be considered for review if they report quantitative data on the prevalence of female sexual dysfunction. Outcome measures will include the prevalence of FSD, the time period assessed, and significant predictors for each domain of FSD. The scientific databases MEDLINE, EMBASE, PsycINFO, and Web of Science will be systematically searched in cooperation with a medical research librarian. Hand searches for further relevant publications will also be undertaken. Screening of search results and extraction of data from included studies will be conducted cooperatively by two authors. The quality of the studies will be appraised and documented. Results will be compiled and presented in evidence tables.In the past decade, population-based studies on female sexual dysfunction have increased in number and grown more varied in their cultural settings. This review aims to provide a current overview of the prevalence of female sexual dysfunction in populations from various countries, cultures, and age groups in order to provide a better understanding of its effect on women's lives today. Sexual function is an essential component of life. For this reason, sexual dysfunction can have a negative impact on the wellbeing of an individual. According to the Diagnostic and Statistical Manual of Mental Diseases (DSM), sexual dysfunction is characterized by a disturbance in the processes that characterize the sexual response cycle or by pain associated with sexual intercourse . Among wFemale sexual dysfunction (FSD) has attracted more interest in the past few decades . At the In 2004, West et al. performed a systematic review of global literature on the prevalence and predictors of FSD in general populations, starting with studies from 1966 to 2004 [Since 2004, further studies on FSD have been performed around the globe in general populations. Therefore, we see the need for a renewed systematic review of the current literature on the prevalence of FSD in general populations. Through this review, we also intend to identify significant predictors of FSD, as well as the psychometrically validated assessment tools which have been used to assess FSD.Recent systematic reviews focus on FSD primarily in clinical populations, for example, in patients with diabetes , cardiovIn 2013, Pontiroli et al. established that FSD is indeed significantly more frequent among women with diabetes than those without . These wAnother review in 2013 examined sexual dysfunction in male and female patients with cardiovascular disease. Based on 24 studies, Nascimento et al. discovered that among women, all domains of sexual function  were affected by the disease . FurtherIn 2012, Kurizky et al. compiled a review of studies related to patients  with psoriasis. A multilingual search of literature between 1966 and 2011 resulted in only eight eligible studies . ResultsAnother recent review from 2012 measured the bidirectional association of depression and sexual dysfunction among men and women . AtlantiWe have identified only two systematic reviews that addressed FSD in the general population: Spector and Carey in 1990  and WestIn Spector and Carey's critical review of 23 studies, the incidence and prevalence of sexual dysfunction among men and women were assessed. Incidence was seldom reported; therefore, the prevalence of dysfunction for men and women was presented. Due to the limited number of community studies, prevalence rates in the domains of FSD varied considerably  or were non-existent (no data on the pain disorder vaginismus) . HoweverA systematic review by West et al. over 10 years later highlighted similar study limitations as those reported by Spector and Carey. West et al. stated that there still seems to be a lack of data on general populations, since finding a large representative sample is challenging and expensive. West et al. reiterated that the varying definitions of dysfunction as well as the lack of standardized, valid assessment tools present a challenge in comparing prevalence across studies . AlthougThere is substantial justification for a systematic review of the prevalence and predictors of FSD. First of all, the most recent systematic literature review is 10 years old, beckoning a new systematic review of all currently available literature. Secondly, as indicated by some of West et al.'s determinants of FSD, the predictors of sexual dysfunction may vary over time, in response to cultural shifts, as well as generational and societal norms. Furthermore, within the past few years, first-ever population studies have been performed in countries in which the topic of female sexuality has generally been taboo. Studies on FSD among Iranian ,12 or EgThe methods for this systematic review have been developed according to recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements . This prThis study aims to assess the prevalence and predictors of FSD among various age groups of women in general populationsWe will begin by developing a comprehensive database containing all published studies addressing the prevalence of FSD in general populations. A systematic search of MEDLINE, EMBASE, PsycINFO, and Web of Science will be undertaken. Because our focus is on more recent studies on FSD, we will examine publications from 2000 to 2014. For a list of terms which will be searched, see Additional file The population of interest will include adult women in the general population, from menarche to menopause. Cross-sectional, cohort, and case-control studies will be included in this systematic review. The study should report the prevalence of at least one domain of FSD. There will be no geographical limitation on the included studies. Only publications in the English language will be included.Search results will be imported into Endnote. One reviewer will screen titles and abstracts for their potential relevance. If there is any uncertainty at this stage, the article will remain included until the full text is reviewed. Articles identified through reference lists of included studies and relevant systematic reviews will be considered for inclusion on the basis of their title.Two reviewers (MEM and MAT) will then assess the full text of all articles identified in the screening process for potential inclusion. Where information pertinent to inclusion criteria is not contained within the article text, the effort will be made to contact the listed corresponding author. Where no reply is received, the article will be excluded. Consensus between the two authors undertaking review of the study will need to be reached before the article is included. Inclusion disagreement will be discussed and resolved by consensus or arbitration by a third investigator (CA). A PRISMA flow chart of the study selection procedure will be prepared, and a log of rejected studies will be maintained.Data will be extracted from the included studies using a pre-designed, pilot-tested electronic data form (Microsoft Access). The form has been pilot-tested on ten randomly selected publications on the prevalence and predictors of FSD. Based on the results of the pilot test, the form was revised by the authors. Using the electronic form, one review author (MEM) will extract the data from the included studies and a second author (MAT) will validate the extracted data. Disagreements will be resolved by discussion between the two reviewers; if no agreement can be reached, consensus will be sought through discussions with the third author (CA). Data will be extracted on the following:1. Publication details: title, journal, author(s), year, city, and country in which the study was conducted, type of publication, and source of funding2. Design: type of study , aims of study, method of data collection, response rate, recruitment methods, eligibility (inclusion and exclusion criteria), name of assessment tool(s), validation of assessment tool(s)3. Study participant details: number of persons interviewed or surveyed, population characteristics including age, relationship status, demographic information4. Data for outcome measures: prevalence of FSD, time period referenced in assessment, significant predictors for each domain of FSD5. Limitations: selection bias, response bias, information bias, limitations of assessment tool(s) usedAt the time of the review in 2004, West et al. lacked a tool for assessing the quality of observational studies. However, evaluation of study quality was based on (1) how women were recruited and (2) how the information was obtained. West et al. described that both selection and information bias had an impact on the results of her review. For this review, we will use the Newcastle-Ottawa Scale for the quality assessment of non-randomized studies . QualityRelevant data extracted from eligible studies will be presented in evidence tables (see Additional files In the past decade, population studies on FSD have increased in number and grown more varied in their cultural setting. The proposed systematic review aims to provide a current overview of the prevalence of FSD in general female populations from various countries, cultures, and age groups in order to allow a better understanding of its effect on women's lives today.The strengths of this review include clearly established purpose, as well as a systematic and transparent approach. Our search will be performed in close cooperation with a specialized research librarian with a medical degree; the screening and extraction will be performed cooperatively by two researchers employing pretested, standardized extraction forms. Unlike the previous reviews, this review will provide significant results on the predictors for each domain of FSD. Furthermore, quality assessment of each study will be performed and presented in a table. While the review may include novel studies from a wide variety of cultures, a limitation of the study is its restriction to the English language. Despite a predefined systematic approach, the study will also involve judgments made by review authors, which can result in bias.Findings will be disseminated through publication in peer-reviewed journals and conference presentations at relevant conferences.FSD: Female sexual dysfunction.The authors declare they have no competing interests in relation to the planned systematic review.MEM initiated and conceptualized the study, reviewed previous systematic reviews, and wrote the manuscript. CA advised on background and methodology section and revised the manuscript for important intellectual content. MAT provided insight on epidemiological aspects of the review and helped draft the manuscript. All authors read and approved the final manuscript.Search strategy. Proposed search terms to be used in the systematic search of literature databases.Click here for fileEvidence table. Proposed table for presenting the extracted data from eligible studies.Click here for filePredictor table. Significant predictors of female sexual dysfunction.Click here for file


Gratitude is an important aspect of human sociality, and is valued by religions and moral philosophies. It has been established that gratitude leads to benefits for both mental health and interpersonal relationships. It is thus important to elucidate the neurobiological correlates of gratitude, which are only now beginning to be investigated. To this end, we conducted an experiment during which we induced gratitude in participants while they underwent functional magnetic resonance imaging. We hypothesized that gratitude ratings would correlate with activity in brain regions associated with moral cognition, value judgment and theory of mind. The stimuli used to elicit gratitude were drawn from stories of survivors of the Holocaust, as many survivors report being sheltered by strangers or receiving lifesaving food and clothing, and having strong feelings of gratitude for such gifts. The participants were asked to place themselves in the context of the Holocaust and imagine what their own experience would feel like if they received such gifts. For each gift, they rated how grateful they felt. The results revealed that ratings of gratitude correlated with brain activity in the anterior cingulate cortex and medial prefrontal cortex, in support of our hypotheses. The results provide a window into the brain circuitry for moral cognition and positive emotion that accompanies the experience of benefitting from the goodwill of others. How would you feel if in the middle of your most distraught moment, unbound from your every day comforts and scared for your survival, a complete stranger saved your life? When we are the beneficiaries of good human conduct, we can experience feelings of gratitude. The importance of gratitude and its benefit to sociality is stressed in philosophy and in religion. Cicero cited gratitude as the mother of all virtues, and the Roman Stoic Seneca conceived of gratitude as a fundamental motivational drive, critical for building interpersonal relationships. As a research theme, however, empirical investigations of gratitude are relatively rare .The reasons for adopting this approach are as follows. In previous studies of the determinants of gratitude, participants have read texts describing scenarios and placed themselves in specific settings while receiving gifts  with moral cognition; (2) with reward from the pleasure of receiving a benefit in social interactions; and (3) with social cognitive processes such as perspective-taking and theory of mind. Specifically, we hypothesized that the experience of gratitude would relate to changes in activity in the posteromedial and insular cortices, medial prefrontal cortices and nucleus accumbens  were recruited using USCs psychology subject pool as well as posted fliers and advertisements on USCs University Park Campus. Three participants were removed due to computer and scanner malfunctions, leaving a final sample of 23 participants . All research participants gave informed consent and all activities were done in accordance with and with approval from USCs Institutional Review Board policies on human subjects research. Participants were right-handed, native English speakers. The participants filled out an open-ended questionnaire regarding their personal experience with the Holocaust. No participants in this sample reported having extensive contact with anyone who went through the Holocaust, or significant educational experience with the Holocaust greater than a single lecture or exposure to the historical events beyond movies or books.The experiment was designed to immerse the participants in the events of the Holocaust, helping them respond to written gift-related stimuli (detailed below) using their own reactions. The experiment took place in four parts; each part dedicated to a different phase of the Holocaust. This approach was designed to mimic the experience of the United States Holocaust Museum, where visitors are asked to imagine living through the events of the Holocaust in the order that they occurred, often categorized into four chronological phases. The four phases were: 1. The rise of Nazism and Persecution, 2. Internment, 3. The Final Solution, 4. Final Months and Liberation. To enhance the context of the stories, the stimuli were designed to be specific to each phase. For example, stories of being helped by the Red Cross during liberation took place in the fourth phase. We chose to present the four phases in chronological order to provide historical context to the participants, to enhance the ecological validity of the experiment, and to maintain the participant's engagement.Inside the scanner, each phase began with a short, in-house created documentary detailing the events of that phase of the Holocaust. The documentaries were about 2 min long and were created in collaboration with students from the USC School of Cinematic Arts. The documentaries relied on powerful images as well as a professional actor providing a voice-over description. We did not collect fMRI data during the viewing of the documentaries. After each documentary, participants viewed the stimuli related to that phase while we collected fMRI data.The task  in a separate behavioral experiment. In this testing, the participants worked with a booklet of the stimuli and rated each gift according to how much gratitude they felt after receiving the gift, as well as how much they needed the gift and how much effort it took to provide the gift. The testing verified that the stimuli effectively and reliably elicited varied feelings of gratitude and that the stimuli were clear and understandable.TR = 1950 ms. For functional scans, 250 volumes were acquired, with 37 slices per volume. The TR used was 2000 ms, with an interslice time of 54 ms and a TE of 30 ms. Inplane resolution was 64 x 64. Voxel resolution was 3.5 x 3.5 x 3.5 mm, with no slice gap and the flip angle was 90°.Functional and structural fMRI were performed at the Dana and David Dornsife Cognitive Neuroscience Imaging Center at USC on a Siemens 3T trio with TIM scanner. Four functional runs, one anatomical magnetization-prepared radio-frequency and rapid gradient-echo (MPRAGE) image and one T2 weighted image were acquired for each subject. Prior to performing the functional scans, structural images were collected with 176 slices, dimensions: 224 x 256 x 176 and then resampled with voxel dimensions 1 x 1 x 1 mm, www.fmrib.ox.ac.uk/fsl). Registration to high resolution structural and standard space images was carried out using FLIRT to coregister the participant's structural data to the MNI template space  were combined using a fixed effects analysis. This parametric regressor was orthogonalized with respect to the main reflection period regressor; thus, the results presented for this regressor represent the variance explained in the blood oxygenation level dependent (BOLD) response by the subjects ratings of gratitude. Ratings were included on a trial-by-trial basis after being mean-corrected for each subject. In a follow-up analyses to visualize the percent BOLD signal chance for each rating in the participants, an ROI was created using the activity found in the MPFC in the whole brain analyses. This ROI was used to interrogate each participant's brain activity for each rating using FSL's Featquery package. The mean percent signal change was extracted for each level from each participant. The mean of all participant's percent signal change was calculated for each rating. In separate analyses, the ratings of need and effort were also used as regressors to examine if and how these ratings explain variance in brain activity. Subject level maps were then fed into a random effects analysis to estimate group level effects.sd = 0.334). The participants ratings on the post-experiment questionnaires revealed that participants felt involved in the experiment , felt that their feelings were similar to if they were in the same situation  and that they had an increase in their empathy and understanding for the Holocaust . The participants reported that putting themselves in the situations of the experiment was not very difficult . See Table Participants rated their gratitude for each gift on a scale of 1–4. The mean of the participants' gratitude ratings was 2.62 . The local maxima within the cluster included the left perigenual ACC, the right ACC, the left subgenual cingulate cortex, the left and right orbitofrontal cortex and the dorsal mPFC  = 0.799, p < 0.001] and with effort  and effort correlated with gratitude . These correlations confirm findings from previous studies on the determinants of gratitude , reward (vMPFC), and theory of mind , and basic emotion (insula). In support of the hypotheses, ratings of gratitude correlated with activity in a region of the MPFC that encompassed the peri-genual ACC and the ventral and dorsal MPFC. Activity in these regions has been linked to reward and moral cognitive processes, such as reward from the relief of removing a stressor . The MPFC is also known to be active during social support and pain relief associated with viewing a loved one (Eisenberger et al., . The MPFIt has been said that it is the thought behind a gift that drives gratitude (Ames et al., If gift-giving is partly related to understanding others, it stands to reason that some aspect of self-processing must also be involved. The MPFC is critical for self-processes (Araujo et al., Finally, gratitude as a social emotion is related to general affective processing. Meta-analyses of neural networks involved in affective processing have found data that overlap with the present study, pointing to gratitude as an emotion at the intersection of social processing and other more general affective processes. In a meta-analysis to determine networks involved in emotional processes, it was found that the MPFC, in a region similar to ours, functioned at the intersection of core affect and cognitive context, and was connected to the core limbic group (Kober et al., per se. The stimuli were designed to involve a more or less uniform amount of context and complexity such that the correspondence between how much gratitude the gifts elicited was not inherently scaled to the amount of perspective-taking needed to understand the gift. We cannot exclude the possibility that participants were better able to generate gratitude when they were successful in perspective-taking. But while that may be the case, it should be noted that effort ratings, which may serve as a proxy for perspective-taking, did not correlate with brain activity. In fact, the ratings for how much a gift was needed were better predictors for the ratings of gratitude overall, which helps minimize the potential confound of perspective-taking as a primary component in explaining variance in brain activity during the experiment.Given the important role of the MPFC in perspective-taking, we must consider the possibility that the regions active in our data correlate with task-related perspective-taking demands and not with feelings of gratitude The gifts in our study are aimed, generally, at restoring life-functions. In other words, the gifts are designed to relieve the recipient of a stressor, to some varying degree. Interestingly, insular activity during the reflection period was decreased compared with the resting baseline. If we conceive of each stimulus as capable of relieving some degree of stress, then perhaps the insula's activity is mapping some aspect of this relief, although it is unclear why activity in the insula was not correlated with gratitude ratings. This is commensurate with recent studies showing that insula activity decreases when pain decreases through analgesia or long-term meditation training, respectively (Schmid et al., One limitation to the study is that the participants did not receive gifts themselves, and instead were asked to imagine the experience. Nevertheless, we believe that participants in our study felt real gratitude for a number of reasons. Participants were told to use their own reactions to rate the stimuli and to feel based on their own perspective; these responses were the bases for the analyses, thus decreasing the chance that experimenter bias would influence their responses. In addition, participants reported that their feelings during the study were similar to what they would have felt if they were in the same situation, that they felt involved in the experiment, that the experiment was not difficult, and even that the experience increased their empathy for and understanding of the Holocaust. Given our study design, the results can also be compared to prior results on gratitude in the context of gift-giving (Tesser et al., In the historical setting of the Holocaust, in which receiving even a small gift could mean another day of survival, our results serve as reminders that in the midst of tragedy there can be acts of compassion, sacrifice, and profound human dignity.GF designed the study and conducted the research, analyzed the data, and wrote the manuscript. JK contributed to study design, data analysis and manuscript preparation. HD and AD contributed to study design and manuscript preparation.This study was supported by the Oskar Schindler Humanities Foundation, the Shoah Foundation Institute, and a Dissertation Research Award from the Greater Good Science Center's Expanding the Science and Practice of Gratitude Initiative.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.