The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a “biometric quality” tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a) the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b) the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture. The German decision maker Federal Joint Committee (FJC) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to perform a scientific evaluation on the relevance of variations in the opposing dentition for the functionality of fixed and removable partial dentures. On May 20, 2010 the FJC decided, on the basis of the present systematic review, that routine care cannot be made dependent upon whether the opposing arch is provided with fixed or removable partial dentures [In the Fourth German Dental Oral Health Study (DMS-IV) it was estimated that, without taking wisdom teeth into account, in persons aged between 35 and 44 years, on average about 2.7 teeth were missing; 48.5% of missing teeth had been replaced [With the exception of a shortened dental arch, every tooth gap requires the earliest possible prosthetic restoration in order to avoid secondary damage. When deciding upon the type of denture most suitable for the respective patient, besides the nature of the opposing dentition or the type of prosthetic restoration in the opposing arch , the folThe subsequent specifications define the aim of the investigation, which is as follows: assessment of the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. Following patient-relevant outcomes were evaluated: (1) “denture longevity” , (2) “chThe test intervention assessed was the treatment of residual dentition by means of fixed partial dentures depending on the nature of the opposing dentition. The comparator intervention assessed was the treatment of residual dentition by means of removable partial dentures or combined fixed/removable partial dentures, again depending on the nature of the opposing dentition. Implant-supported dentures  were also considered in the assessment of the test and comparator interventions. Control groups receiving no treatment at all were not considered.Adult patients with residual dentition who had an indication for restoration with partial dentures were included in the investigation. Residual dentition was classified as interdental (Kennedy Class III+IV) as well as free-end gaps (Kennedy Class I+II)  comprisiSystematic literature searches were carried out in the following databases: CENTRAL, MEDLINE, EMBASE, BIOSIS, SciSearch, CCMed, DARE, and HTA . In addition, a manual search was carried out in German dental journals and the search was extended topic specifically to the following databases: CDSR, CDMR, CDMS, NHS EED, CINAHL, AMED, CAB abstracts, GLOBAL Health, ISTPB + ISTP/ISSHP, Medikat, and the publisher databases of Karger (secondary search), Kluwer, Springer, Thieme, and Hogrefe (secondary search). Finally, the opportunity to cite additional topic-relevant studies for the timespan until middle of 2008 was provided in July 2008 when interested parties were invited to submit written comments on a preliminary version of the report.Randomized controlled trials (RCTs) together with prospective and retrospective studies without control groups were included for the patient-relevant outcomes, provided the patients were included in the study consecutively and the confounding variables were adequately monitored. Also included in the assessment were case reports and case series with a sample size of at least ten and of adequate biometric quality to avoid any bias in selection. The minimum observation time for all studies was a follow-up period of six months.https://www.iqwig.de/download/N05-02_Vorbericht_V_1_0_Relevanz_der_Beschaffenheit_der_Gegenbezahnung.pdf).The literature screening was carried out by two reviewers independently of each other. After assessing the biometric quality of the studies, the results from the individual studies were collated according to therapy goals and outcomes, compared, and described. IQWiG's preliminary benefit assessment, the preliminary report, was published on the Internet in German language and interested parties invited to submit written comments . The grades were defined a priori as follows: “minor flaws” exist if it is assumed that their correction would not substantially influence the results and therefore the overall conclusions of the study. In the case of “major flaws” the overall conclusions of the study would be called in question, as correction of the flaws might lead to different conclusions. Initially, a total of twenty five papers were identified that met the inclusion criteria. After more detailed screening, eight studies had to be excluded from the assessment, as the data provided could not be broken up on the basis of variations in the opposing dentition . In fiveThe overall study and publication quality of the relevant studies was for the most part inadequate . There wOf the eight studies identified for the “denture longevity” outcome, one had no detectable flaws, two had minor, and five had major flaws in the biometric quality of the studies and publication. A comparison between the longevity of fixed and removable partial dentures was only possible for one opposing dentition variant (complete dentures in the opposing arch) Tables  and 5.P value) in the subgroup analysis. Consequently, a significant difference cannot be considered as detected in the 5-year survival rate of fixed partial dentures (95.2%) and removable partial dentures (100%) with a complete denture in the opposing arch. Only one trial , describData on the longevity of fixed tooth-borne partial dentures with differing variations in the opposing dentition were found in two studies: in one publication , the 4-yData on the longevity of fixed implant-supported partial dentures with differing variations in the opposing dentition were found in two additional trials: the 3-year survival rate in case of natural opposing dentition is given as 97.8% in one publication ; the surNo conclusions can be drawn on the basis of the existing data regarding whether variations in the opposing dentition influence the longevity of fixed or removable partial dentures . Only twThere were major flaws in the quality of the biometric studies and publication in all 5 studies that contained data on the change in dietary habits in fixed and removable partial dentures in relation to variations in the opposing dentition. As no evaluable data were found on dietary habits in patients fitted with a fixed partial denture, it was not possible to compare with dietary habits in patients fitted with a removable partial denture Tables  and 8. Data on the relevance of opposing dentition for removable partial dentures could only be drawn from one trial . The valThe existing data does not allow any conclusion to be drawn on whether variations in the opposing dentition influence dietary habits when a fixed or removable partial denture is fitted. The data in another trial  show thaOut of the four identified trials, one  displayeP < 0.05) is indicated in patient satisfaction regarding stability in general and during chewing with fixed  and with removable partial denture . This effect cannot be viewed as proven due to the biometric flaws. However, the fact that fixed prostheses have greater stability than removable ones appears reasonable.One trial described as randomized controlled  containen = 102), and 65% for those with complete denture in the opposing arch (n = 147). However, due to the variable sampling size and the unequal age of prosthesis (one to 15 years), a comparison of these data would not appear to be worthwhile.Data on general patient satisfaction with removable partial dentures and differing variations in the opposing dentition were found in one trial : the perBased on the existing data, it is not possible to draw any conclusions on whether variations in the opposing dentition influence patient satisfaction when fitting fixed or removable partial dentures.Data on denture cleansability and aftercare required when fitting fixed and removable partial dentures were included in nine publications. Of these trials, two showed minor , 13 and Only one RCT  containeIn another trial , data weNo conclusions could be drawn on the basis of the existing data as to whether variations in the opposing dentition influence denture cleansability and aftercare in case of a fixed or removable partial denture.After a comprehensive literature search and an assessment of the evidence base on the relevance of variations in the opposing dentition for the functionality of fixed and removable partial dentures, no robust conclusions could be drawn. This is due both to the low quantity and the methodological weaknesses of the few studies identified. Only one of the 17 studies compared the two denture types investigated within the context of a controlled prospective study, even though this study cannot be regarded as an RCT either, due to its inadequately documented randomization procedure. All the remaining data extracted originated from prospectively or retrospectively planned studies without a control group (one-arm studies) or from one-off data collections by way of questionnaires. It should be noted, however, that all the studies included were not per se concerned with the question of the relevance of opposing dentition but addressed this question mostly in the form of subgroup analyses. For this reason the literature search for this report was particularly time intensive, as it could mostly be decided only on the basis of full-text screening whether a subgroup analysis considering opposing dentition had been performed. Within the framework of the quality assessment for the present systematic review, the serious biometric flaws in study and publication quality identified in nearly all studies refer to the research question investigated here, that is, the relevance of opposing dentition. This quality assessment is not an evaluation of the informative value of the individual studies with regard to their original research questions. The assessment of denture longevity, that is, the survival or success rate of dentures, should follow a clear definition. It must be quite evident what medical, functional, or even aesthetic requirements the dentures must fulfill in order to be classed as “functioning” or “successful.” In the present systematic review all irreparable damage was viewed as a failure (end of denture longevity) and all repairable damage was allocated to the outcome “Denture aftercare required.”Functional and medical reasons  account for 69.5% and 28.5% of fixed partial dentures failures, respectively ; removabStandardized procedures should also be defined for the assessment of dietary habits. First, some differentiations should be made between the objective chewing performance  and subjective chewing efficiency , depending on the status of the opposing dentition. Both parameters diminish linearly with the number of missing teeth . FurtherSome objective tests indicate that by means of fixed and removable dentures the chewing function can be equally restored , whereasA further patient-relevant aspect is the change in the perception of taste through dentures. However, this affects only removable prostheses in the upper jaw. Studies were able to show that dissatisfaction due to a changed perception in taste was evident only for prostheses covering the entire palate , that isOral health-related quality of life was not analyzed in the studies identified; we therefore extended the outcomes investigated and also included patient satisfaction so as to be able, at least, to draw conclusions on this quality-of-life relevant parameter. Patient satisfaction with fixed or removable dentures should always be compared intraindividually. Every patient should first be provided with removable dentures and then, after assessment of satisfaction, with fixed ones. This approach is more costly than an interindividual assessment, but reduces uncertainty and contradictions in patients' statements. As an inverse approach is not feasible on practical grounds, an intraindividual approach would, however, have to dispense with randomization with regard to the sequence of the interventions, as the study would not have a cross-over design in the proper sense of the term. Particularly in view of the variety of patterns regarding the status of teeth and opposing dentition, this study design represents the most reliable comparison between fixed and removable dentures for the evaluation of patient satisfaction. This design was not found in any of the studies included.Independently of the nature of the opposing dentition, patient satisfaction has been found to be 96% for fixed dentures  and 90% P < 0.001) and the condition of those remaining [OR = 21.5) [In the studies included, patient satisfaction was exclusively assessed by means of nonvalidated questionnaires that enquired about patients' subjective satisfaction. The oral health-related quality of life (OHQoL) instrument is a validated tool. OHQoL also diminishes considerably with the number of intact teeth (emaining . In pati = 21.5) . However = 21.5) . Current = 21.5) . The outcome “Denture cleansability and aftercare required” covers four different patient-related aspects: (1) effort involved in the cleaning of the remaining teeth, as well as (2) effort involved in the cleaning of the denture (the third and fourth aspects are described further below). The first and second aspects cover all measures demanded of the patient with regard to oral or prosthesis hygiene. Fixed and removable dentures differ fundamentally here, as the cleansability of the remaining teeth is considerably facilitated after the removable dentures are taken out, while extra effort is required for prosthesis hygiene. Fixed dentures are to be cleansed within the context required for routine denture care; not only the demands in time but also the dexterity required by the patient is greater, however, in comparison to the care of natural teeth. In patients no longer possessing sufficient motor capacities due to age or illness, fixed dentures are for this reason often contraindicated. The question as to whether and what influence the nature of the opposing dentition has on oral and prosthesis hygiene could not be answered in the present analysis. In principle it can, however, be assumed that for every denture, independently of the opposing arch, certain efforts are necessary for hygiene, efforts which are doubled, for example, if the opposing arch is equipped with a similar denture. Without taking opposing teeth into account, numerous studies have shown that, assuming adequate care, patients with fixed as well as those with removable dentures bear no increased risk of caries –52 or peFurther aspects of the outcome “Denture cleansability and aftercare required” are (3) the level of repair required for dentures and (4) the effort involved in denture aftercare. For denture repairs, not only the potential costs incurred but also the often necessary deprivation of the denture during repair in a dental laboratory are relevant issues for patients.To be able to draw robust conclusions, a randomized controlled design of the study is essential. This cannot, however, be easily ensured in studies on dental prostheses. Stratified randomization should be used, at least with regard to the different opposing dentition groups. The problem of randomized allocation of patients to the fixed or removable denture group arises from the fact that fixed dentures are more expensive to produce. The “split-mouth” study design used in numerous denture studies, that is, the intraindividual comparison between the left- and right-hand halves of the jaw of the same patient, is only suitable for the assessment of fixed dentures, not removable dentures, which extend over the whole jaw for one-sided tooth gaps. 14 = 16,384 variations in tooth gaps are possible. To limit the number of subgroups, classification according to type, localization, and size of the gap, as practiced in this report, would be sensible, that is, specification of Kennedy class (I−IV) of the jaw, as well as gap width (number of missing teeth). By this classification the number of subgroups is reduced. These data should be supplemented by the number of intact teeth remaining, which should be similar between groups. In the case of non-RCTs, the intervention arches should be comparable. As an intact jaw has at least 14 teeth, not less than 2In the description of the opposing dentition, at least the five groups distinguished in this systematic review  should also be assessed separately. In many publications, these data are only reported within the framework of the demographic description of the patient population, but the results are not presented separately for groups according to opposing dentition. In part, for example, the natural opposing dentition is treated as equal to a fixed denture in the opposing arch. In the case of a follow-up period of ten years or longer, it should be noted that, over time, the condition of the opposing dentition may change. Due to the loss of teeth in the opposing arch, natural opposing dentition may turn into residual dentition and can eventually lead to a fully edentulous arch. All these changes must be documented. It should further be considered whether only patients with a constant status of their opposing dentition should be included in the assessment in terms of a per-protocol (PP) analysis or whether, parallel to that, patients with changes in this status should be evaluated during the follow-up period by way of an intention-to-treat (ITT) analysis. As a relevant comorbidity, the periodontal status of the remaining teeth should primarily be considered. Every type of denture—with the exception of implants—results in additional strain on the remaining teeth. If their stability is compromised by periodontal disease, this has an effect on the expected longevity of the denture. The presence of parafunctions such as bruxism is a second important factor, as dentures in people with such a condition are overstressed. Periodontitis and parafunctions should at least be adequately monitored. Prognostic factors include smoking habits and oral hygiene. As these are changeable risk factors, smokers and patients with inadequate oral hygiene need not necessarily be excluded from the study, but could receive counseling for smoking cessation or be given instructions in oral hygiene. As the compliance of study participants is important in every long-term study, this would also represent a preselection with regard to less cooperative patients. Suitable variables as indicators of patients' oral hygiene are plaque and bleeding indices . It is imperative that the prostheses are of uniform age. Many of the studies identified compared newly manufactured prostheses and others that had in part been used for over ten years. In prospective study designs, the age of the prostheses is equivalent to the follow-up period, which should not be subject to deviations. Furthermore, attention should be paid to a standardized manufacturing process of the prostheses. For fixed dentures this means the same preparation technique, the same molding material, the same alloy and ceramic material, and if possible the same dental laboratory. For removable dentures it would in principle be important to focus on a uniform, systematic design of the prosthesis, on the same materials, and on a standardized manufacturing process. Comparison of the level of repair required for differently fabricated dentures must be regarded as a methodological error in the study design. In retrospectively planned studies it can be assumed that the prostheses were not manufactured under standardized conditions. As a matter of principle, only dental indications should be compared in which both fixed and removable dentures are considered as treatment options. For one- or two-sided free-end gaps (Kennedy class I+II) with a gap width of one tooth, a fixed denture in the form of an extension bridge is possible, but due to the greater strain arising through the leverage effect, the longevity or level of repair of such bridges is, for example, not comparable to that of conventional bridges in patients with Kennedy class III gaps . RegardiThe assessment of outcomes must follow a standardized procedure. Although restrictions such as cost aspects, the impossibility of blinding, and the lack of randomization due to patient preferences play an important role in the conduct of dental care studies, some approximation to the state-of-the-art standards implemented in other areas of medical care would be desirable. Overcoming these restrictions represents a challenge that evidence-based dental medicine should successfully meet. Ultimately, the conduct of informative studies is urgently recommended in order to successfully clarify the present research questions.The following points were noted in the evaluation of the studies included.This systematic review assesses the relevance of variations in the opposing dentition for the functionality of fixed and removable partial dentures. There is currently no proof of sufficient certainty regarding the relevance of opposing dentition in removable and fixed partial dentures for any of the following patient-relevant outcomes: “denture longevity,” “change in dietary habits,” “oral health-related QoL,” condensed into “patient satisfaction,” and “denture cleansability and aftercare required.” No evidence-based statements could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture. There were only few indications of increased patient satisfaction in favor of the fixed partial denture in combination with the opposing dentition variant of complete denture in the opposing arch. However, these indications are based on a small number of methodologically weak studies, and this is characteristic of the field of prosthetic dentistry, as the systematic review shows.


The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, important among which are the environment, circadian rhythms and time awake. Separating the roles played by these factors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results from such protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave and rapid eye movement sleep as well as to the development of models to determine the amount and timing of sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (and increases with time awake) and is attributed to a 'sleep homeostat'. Process S reverses during slow wave sleep . The second is process C, which shows a daily rhythm that is parallel to the rhythm of core temperature. Processes S and C combine approximately additively to determine the times of sleep onset and waking. The model has proved useful in describing normal sleep in adults. Current work aims to identify the detailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle is different from the norm in some way. These circumstances include: those who are poor sleepers or short sleepers; the role an individual's chronotype ; and changes in the sleep-wake cycle with age, particularly in adolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in old age. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes of these changes  are examined. Most adults take a consolidated 7-hour sleep during the night . The reaA good sleep is recuperative and removes the feelings of fatigue ; individuals then feel ready to face the rigors of a new day. Intuitively, the concept of increasing 'sleep pressure' with increasing time awake is not difficult to appreciate (even if the detailed nature of sleep pressure is not understood). However, the presence of daily rhythms in the desire to sleep, staying asleep and waking up might be less easy to understand. In fact, when repeated measurements are made over the course of 24 hours in subjects who are living normally (active in the daytime and sleeping at night), all physiological and biochemical variables show daily rhythms. Some properties of such rhythmicity need to be considered, and they will be illustrated by the rhythm of core temperature .A priori, it would be supposed that such rhythms result from the behavioral changes that are associated with the sleep-activity cycle. During the daytime, individuals are physically and mentally active, and eat and drink in an environment that is busy and stimulating; all of these factors will tend to raise core temperature. By contrast, at night, individuals fast, are inactive, sleep and choose a quiet, dark environment.Figure In fact, such an explanation is only partially correct; the standard method for demonstrating this is the 'constant routine'. In this protocol, a subject is required to remain awake and sedentary (or lying down) and relaxed for at least 24 hours in an environment of constant temperature, humidity and lighting; to engage in similar activities, generally reading or listening to music; and to take identical meals at regularly-spaced intervals. Such a protocol removes any rhythmic changes due to the individual's lifestyle or environment. When this protocol is undertaken, it is observed Figure  that theBy considering the two temperature profiles shown in Figure (i) The rhythm observed during the constant routine arises internally; it is the endogenous component of the temperature rhythm and its generation is attributed to a 'body clock'.(ii) Since the two rhythms are not identical, effects due to the environment and lifestyle are also present when the participants live conventionally; the difference between the two rhythms is the exogenous component of the rhythm. The exogenous component of core temperature is dominated by the sleep-wake cycle, activity raising temperature and lying down and sleeping decreasing it.(iii) The two components are in phase. During the daytime, body temperature is raised by the body clock acting in synchrony with a more dynamic environment and increased physical and mental activities; during the night, the clock, a more restful environment and relaxed lifestyle all act to reduce core temperature.These deductions are general, insofar as all rhythms show a mixture of endogenous and exogenous components when compared under normal living conditions and during a constant routine. However, when different rhythms are investigated, differences do exist, as described below.For example: the exogenous component is the sleep-wake cycle in the cases of heart rate and blood pressure, as with the rhythm of core temperature; it is the light-dark cycle for melatonin secretion; it is the rhythms of posture and fluid intake for urine flow; and it is the rhythm of food intake for plasma insulin concentration.As Figure The body clock consists of paired suprachiasmatic nuclei at the base of the hypothalamus; many details of its genetics and molecular biochemistry are now known -6. It isWhen individuals are studied in time-free environments (such as an underground cave), the body clock and rhythms produced by it continue to be manifest but with a period closer to 25 than 24 hours. Such rhythms are called circadian (Latin: about a day) and the timing system is described as 'free-running'. This period of about 25 hours does not reflect the intrinsic period of the body clock (tau) exactly, due to effects of light exposure during waking. Current evidence (from protocols using very dim light during waking or from blind subjects) indicates that the true value of tau averages about 24.3 hours .Whatever the exact value for tau in an individual, a body clock will be of value only if it and the rhythms it drives are synchronized to a solar (24-hour) day. This adjustment is due to zeitgebers (German: time-giver), rhythms in the environment and/or the individual's behavior which show a 24-hour period. For humans, the most important zeitgebers are the light-dark cycle and rhythmic secretion of pineal melatonin during the dark. Rhythms of physical activity, social factors and food intake appear to play comparatively minor roles -10. NeveThe effect of light exposure upon the body clock depends upon the time of exposure relative to the temperature minimum  and also indirectly (by suppressing melatonin secretion and so preventing the phase-delaying effect that melatonin would have exerted at this time) .A laboratory environment is advantageous in that conditions conducive to sleep  can be standardized. The standardization of such factors is equivalent to standardizing the exogenous components of the rhythms of sleep. Studies in sleep laboratories have systematically investigated the separate effects upon sleep and sleep architecture (the distribution of sleep stages) of time of day and time awake, which together constitute the endogenous component of the sleep rhythms. Several protocols have been used, including the constant routine, multiple sleep latency tests and modifying sleep-wake protocols (by changing the time of day while maintaining time awake constant or changing the amount of time awake at the same times of day). These protocols have been discussed in detail in Reilly and Waterhouse . Some ofFirstly, falling asleep is easiest if core temperature is falling or low (evening and night) and most difficult if it is high or rising (morning and afternoon). Secondly, waking up spontaneously tends to be the opposite of falling asleep; it is easiest if core temperature is rising or high, and most difficult when it is falling or low. These last results explain why, if individuals have gone to bed earlier or later than normal, even though they will feel less or more fatigued, respectively, than normal, they are likely to have a longer or shorter sleeps, respectively, than normal. Thirdly, the above two results stress that the ability to initiate and sustain sleep shows rhythmic changes during the course of the 24-hour day, and that these are associated with the rhythm of core temperature. However, superimposed upon these effects is that (if time-of-day effects are taken into account) sleep propensity - measured subjectively  or objectively (polysomnography) - increases in proportion to time awake. This finding means that the endogenous component of sleep rhythms, like those of alertness, fatigue and cognition, is a mixture of two main elements, time of day and time awake. Finally, combining these findings indicates that an unbroken sleep is most likely to occur if it starts in the late evening and ends sometime after 7 a.m., the individual having slept through the trough of core temperature  and the rhythm of core temperature has been interpreted as a causal link, incorporating temperature-induced changes in brain metabolism . HoweveThe value of the rhythms of core temperature and melatonin secretion as convenient markers of the timing of the body clock has already been mentioned. Alertness and fatigue, important indicators of sleep-mediated recuperation and the need for sleep, respectively, are also affected by the body clock. Once again, however, many other factors also contribute to these subjective feelings . The effects of boredom and interest mean that alertness and fatigue can be misleading indicators as to the physiological need for sleep (the build-up of sleep pressure) at any time. Even so, the principles involved in modeling the rhythm of sleep times (see below) have also been used to model rhythms of alertness, fatigue and mental activity .Sleep is not homogeneous, and this has been investigated by recording surface electrical activity on the scalp using an electroencephalogram (EEG). In normal sleep, there is an ultradian rhythm of cycling between slow wave sleep (SWS) and rapid-eye-movement (REM) sleep stages, the REM-nonREM cycle. This cycle lasts approximately 90 minutes, about five cycles occurring during the course of a normal night's sleep. The composition of successive cycles varies, with the amount of SWS decreasing and the amount of REM sleep increasing.One simple, and yet very effective, model of sleep rhythms is the two-process model of sleep homeostasis of Borbély  Figure . In thisSleep onset occurs when the rising value of S intercepts the upper C function, normally during the phase of rapid decline and some hours before the minimum of the upper C function. During sleep, the level of S' falls exponentially  until it meets the lower C function, at which point waking occurs and the cycle starts again. Waking normally occurs after about 7 hours of sleep, a few hours after the minimum of the lower C function when it is rising quickly. Factors S and C are assumed to act additively but see ,23)..23]).A three-component model of sleep regulation, based upon the two-component model but incorporating 'sleep inertia', has been developed. Sleep inertia is the phenomenon whereby, immediately after waking from sleep, the beneficial effects of sleep upon cognitive performance and mood are not immediately apparent -26.Many investigations have been performed to define the physiological and biochemical correlates of processes S and S' and the rhythmic function C, and others are in progress. As with investigations of sleep times, studies of processes S and S' generally consist of measuring aspects of waking or sleep  after the sleep-wake schedules of volunteers have been altered in some way.The general view  is tHowever, the detailed nature of the links involved remains unresolved. Comments already made about other variables being temporally associated with core temperature , and all of them possibly being reflections of some more fundamental process, apply here also. The fundamental reasons why increased wake time leads to an increased need for sleep and change in sleep architecture remain to be elucidated. One approach to this problem has been to investigate substances that accumulate in the brain during the waking period and the neurophysiological changes that take place during this time . HoweverWith regard to adjustment of the body clock by zeitgebers, this process need not be precise on any particular day. Daily differences in detailed timing of biological rhythms will arise due to slight variations in the body clock and timing of the zeitgebers on a particular day. Moreover, different individuals will show biological variation with regard to the exact intrinsic period of their body clock (tau), their exposure to zeitgebers and details of their phase-response curves to different zeitgebers. That is, there will be both intra- and inter-individual variation in the timing of the circadian clock and the rhythms it drives.Such variation will also apply when considering either the sleep homeostat (S and S') or rhythmic (C) components of the two-component model of sleep Figure , all of These predicted changes can then form the basis of attempts to explain some abnormalities of sleep behavior, even though the understanding is incomplete in the absence of knowledge as to the exact correlates of the S, S' and C components (see above).Because, like any biological variable, the S, S' and C components will show inter- and intra-individual variation, there is the implication that the sleep-wake cycle will differ between individuals and between days in a single individual. It is common for individuals to delay their sleep-wake cycle over the weekend  and to find difficulty in readjusting it to weekday requirements on the Monday. There is also evidence that those with less regular lifestyles have more sleep problems . These aThere are differences in the amount of sleep habitually taken by individuals because individuals choose to do this , seem to need less sleep ('short sleepers'), or get less sleep than they want and so feel tired in the daytime ('poor sleepers'). Studies using bed-rest and sleep deprivation have been used to investigate if poor sleepers show systematic differences from 'normal' sleepers , but theEven though these differences from normal sleep generally produce no more than some degree of inconvenience, they can be more troublesome if daytime fatigue is marked and cognitive function impaired. In these cases, treatment is sometimes contemplated, which generally consists of attempts to strengthen the individual's exposure to zeitgebers (particularly bright light) or regular ingestion of melatonin a few hours before sleep is desired -34. In tThe measurement of a person's chronotype score is now commonplace, the original questionnaire having been translated into several languages  and also adapted for cultures that, for example, routinely rise early. A population's chronotype scores are distributed normally, with those who tend towards the 'morningness' part of the distribution choosing to perform important activities in the morning, and those tending towards 'eveningness' choosing to do them in the evening. The tails of the distribution - the extreme morning types (larks) and extreme evening types (owls) - can find normal lifestyles difficult to participate in fully and effectively. This difference might be due to habits (and so influence the times of exposure to zeitgebers) and/or the body clock  and/or to the phase response curves (which might differ in the size of advances and delays in the body clock that zeitgebers produce), but few data on this issue are available. What can be stated is that individuals are likely to have problems if they adopt an early lifestyle (retiring and rising earlier than average) but have a circadian system that tends to run later than average (for whatever reason), or vice versa. Such disparities can be important for those working shift systems.The observation  that temThe S and C components of the two-process sleep model have been compared in morning and evening types, using the core temperature rhythm (a reflection of the C component) and daytime measures of subjective sleepiness and alpha-theta activity (reflections of the S component). The core temperature was phased earlier, and the build-up of sleepiness and alpha-theta activity was more rapid, in the morning types; that is, both components of the two-component model were different . In otheThere is evidence that some of the differences between chronotypes and in processes S, S' and C have a genetic basis. Evidence from a large study upon adults in which sleepiness, chronotype, quality of life and sleep times were compared  indicateTwo comparatively rare syndromes have been described: delayed sleep phase syndrome and advanced sleep phase syndrome. In the former, the internal relationship between daily rhythms and the sleep-wake cycle is normal, except that the whole system is delayed with regard to external time; for example, the core temperature rhythm shows a minimum around 8 a.m., and melatonin secretion begins around midnight . Subjects tend to wish to retire around 4 a.m. and rise about noon, and this lifestyle can be very inconvenient . The oppIn summary, evidence is beginning to be obtained that indicates individuals' chronotypes partly reflect some aspects of the timing of their body clock and sleep homeostat, and that a genetic component contributes to these differences.Immediately after birth, neither full-term nor premature babies show clear circadian rhythms of the sleep-wake cycle or any other variable -45. InstEven if the sleep-wake rhythm and other circadian rhythms developed progressively during the first years of life, to become firmly established when the child is five years of age -52, therIn practice, therefore, the earliest age at which substantial amounts of data have been collected is when the child reaches adolescence, though here also experimental sleep-deprivation experiments have not been performed and no constant routine data are available. The data that are available for this age group (10 to 17 years) are dominated by the observation that they go to bed considerably later in the evening (particularly if they have access to television or live in latitudes where summer evenings can be very long) and so tend to be sleep-deprived on school days -64. At wP < 0.001; girls: r = -0.83, P = 0.041, Pearson's correlation coefficients). Female students older than 10 years tended to be more evening types than their male counterparts, but this difference decreased with age and was reversed in students aged18 years old. There was a clear linear relationship between the MEQ scores and age of male students, while this relationship was less clear in the female students and appeared to be affected other factors, especially around 10 years of age. This change in female MEQ scores at around 10 years might relate to menarche.Some of these points are illustrated by some of our unpublished data, which show changes in chronotype and sleep quality in primary and secondary school students in Japan . The Japanese versions of Horne and Ostberg's Morningness-Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI) were used. Figure P < 0.01; girls: r = 0.95, P < 0.01, Pearson's correlation coefficients), girls tending to be worse than boys. Given that all students had to rise at the same time in the morning to attend school, the poorer sleep observed in the older children was consistent with the tendency for the chronotype in older children to become progressively more orientated towards that of an evening type.Figure Attempts have been made to incorporate the findings regarding lifestyle and chronotype in adolescents into the two-component model of sleep regulation -74. It iWhy such changes should exist during and just after puberty is unclear; attributing them to the marked maturational changes, in the brain as well as the pituitary-gonadal axis, is an obvious possibility, but details of the mechanisms involved are unknown ,76. It iThere has been a large amount of research upon the sleep-wake cycle and associated rhythms in aged individuals, generally 55 years or older  could account for many of the observed changes, so too could, for example, decreased exposure to or perception of zeitgebers, daytime activity and exposure to the natural light-dark cycle being compromised by decreased mobility (not being able to venture outdoors) and/or poorer eyesight.Poorer vision might be particularly important, causing individuals to lack confidence and further restrict their daytime activities, both indoors  and outdoors . The cornea and lens become more opaque with age and light transmission, particularly of the shorter (bluer) wavelengths, decreases . This acLight of shorter wavelengths is also important in the control of body temperature, melatonin secretion and the sleep-wake rhythm. Melatonin secretion in the late evening and night promotes sleep, partly due to the fall in core temperature that it produces. This secretion is suppressed by light, particularly light at the blue end of the visible spectrum -108. AccTherefore, cataract surgery will not only improve individuals' sight but it might also alter the quality of their sleep. Asplund and Lindblad ,111 founWhilst the detailed implications of these results with regard to the link between light perception and sleep are still unclear, they do confirm that light, melatonin secretion and sleep are linked. It is also noteworthy that, in aged individuals who do not suffer visual problems, the phase shifts produced by exposure to bright light are the same as in younger controls . Also, aAttempts to interpret the causes of altered sleep patterns in the aged in terms of the two-component model of sleep provide some evidence that both the C and S components are altered, but interpretation of such results is not without problems. For example, whilst many circadian rhythms show decreased amplitude, this decline can be due to a fall in the endogenous or the exogenous component of the rhythm, or both. That is, the observed fall in amplitude of the rhythm of core temperature (which implies a change in the C component) might reflect decreased output from the suprachiasmatic nucleus (the endogenous component of the rhythm), decreased secretion of melatonin , or a decrease in the dichotomy between daytime activity and nocturnal inactivity (the exogenous component). Further, the tendency for aged individuals to become more morning-orientated might be due to an altered body clock and/or timing of individuals' lifestyles (factors that might reflect the C component of the two-component model in particular), or the more rapid build-up of sleep pressure (the S component). A further difficulty of interpretation arises because older individuals might go to bed earlier because their body clock is running faster, their poorer eyesight restricts what they can do (read or watch television), their declining mental faculties mean they get bored more easily, sleep pressure builds up more quickly or they fear a poor sleep at night and so want to attempt it sooner.It is only the endogenous component of the rhythm of core temperature that is directly associated with component C. Since the endogenous and exogenous components of a circadian rhythm normally act together to produce a measured rhythm, it is necessary to distinguish between them. The constant routine protocol is believed to enable the circadian output from the body clock to be assessed more directly. However, it must be remembered that this protocol assumes that any effects of the sleep-wake cycle upon the amplitude and phase of the core temperature rhythm on normal days (when the exogenous component is present) do not continue into the constant routine but disappear immediately it is undertaken. There is some evidence to support this assumption, at least with regard to amplitude . HoweverThe changes in sleep with aging might be explained in terms of altered S and S' processes. Investigations of responses to altered sleep-wake schedules  have shown that changes similar to those found in younger adults under the same circumstances are found for many sleep variables, including sleep efficiency and time awake after sleep onset . The incIt has already been mentioned that those who seem to experience fewer difficulties with sleep also seem to have more regular lifestyles. It is stressed that this increased regularity might reflect a relatively stronger output from the body clock (process C) or stronger activity of the sleep homeostat (processes S and S') - or it might be that increasing the exogenous components of circadian rhythms, attempting to be active and so promote accumulation of sleep pressure when awake, and having regular exposure to zeitgebers, can all be considered as ways of combating a declining influence of endogenous components. Whatever the exact cause of the decreased daily variability in some aged individuals, it becomes translated into several ways of improving the quality of life of the aged, at least in those living in homes for the elderly .The general aim of these procedures is to increase the dichotomy between daytime activities in the light and nocturnal sleep in the dark ,126-137.Many of these treatments have been found to be effective; it often being stressed that individuals should be encouraged to see some form of regular daytime activity as a simple means of improving their quality of life. The possible mechanisms which might cause the treatments to be effective have been considered above; they might act on the exogenous or endogenous component of circadian rhythms by promoting accumulation of sleep pressure, and promote sleep pressure directly. Which mechanism(s) are important is not yet known.A rather different approach to the problem of improving sleep in older individuals is based upon the decline in efficiency of thermoregulation with age . Part ofThe two-process model of sleep has enabled the processes that determine sleep times and some aspects of sleep architecture to be described. Equally, the constant routine protocol remains the standard way of distinguishing between endogenous and exogenous components of circadian rhythms. Taken together, these concepts of a sleep homeostat and endogenous and exogenous components of circadian rhythms have enabled the quantity, timing and quality of sleep to be understood better. Such understanding has been applied successfully to understanding the timing of sleep in healthy individuals and in the changed circumstances of adolescence and old age. However, details of the nature of the S, S' and C components of the sleep model, and unraveling the interactions between these components and those of the circadian rhythms, are still required. Obtaining such details will improve our knowledge of differences between healthy individuals at different stages of their life-span and when suffering from some sleep disorders. Such deeper understanding will then give a firmer rationale to advice and treatment, with the hope that they will become more successful.The authors declare that they have no competing interests.The preliminary draft of part of the section on adolescents was written by YF, of part of the section on old persons by TM, and of the rest of the review by JW. Thereafter, all authors were equally involved in the several revisions that were undertaken. All authors read and approved the final manuscript.


Delirium occurs frequently in elderly hospitalised patients and is associated with higher mortality, increased length of hospital stay, functional decline, and admission to long-term care. Healthcare professionals frequently do not recognise delirium, indicating that education can play an important role in improving delirium care for hospitalised elderly. Previous studies have indicated that e-learning can provide an effective way of educating healthcare professionals and improving quality of care, though results are inconsistent.This stepped wedge cluster randomised trial will assess the effects of a complementary delirium e-learning course on the implementation of quality improvement initiative, which aims to enhance the recognition and management of delirium in elderly patients. The trial will be conducted in 18 Dutch hospitals and last 11 months. Measurements will be taken in all participating wards using monthly record reviews, in order to monitor delivered care. These measurements will include the percentage of elderly patients who were screened for the risk of developing delirium, use of the Delirium Observation Screening scale, use of nursing or medical interventions, and the percentage of elderly patients who were diagnosed with delirium. Data regarding the e-learning course will be gathered as well. These data will include user characteristics, information regarding use of the course, delirium knowledge before and after using the course, and the attitude and intentions of nurses concerning delirium care.The study will be conducted in internal medicine and surgical wards of eighteen hospitals that are at the beginning stages of implementing the Frail Elderly Project in the Netherlands.Better recognition of elderly patients at risk for delirium and subsequent care is expected from the introduction of an e-learning course for nurses that is complementary to an existing quality improvement project. This trial has the potential to demonstrate that e-learning can be a vital part of the implementation process, especially for quality improvement projects aimed at complex health issues such as delirium. The study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.NTR2885Netherlands Trial Register (NTR):  Given the growing number of elderly within most western countries, the increasing attention that has been paid to this subpopulation is not surprising. Combined with the relatively high use of care associated with elderly patients, this development makes the elderly an increasingly important subpopulation for healthcare organisations. Studies regarding patient safety have shown that elderly hospitalised patients are at greater risk for preventable adverse events than younger patients ,2, indicIn the Netherlands, the publication of a report regarding adverse events in Dutch hospitals ,3 led toDelirium occurs frequently in hospitalised patients, especially in the elderly: about 25% of hospitalised patients aged 65 and over experience a delirium during their hospital stay . DependiNevertheless, several studies have shown that a significant percentage of delirium cases are preventable, and different strategies have reduced by approximately one-third the incidence of delirious patients -18. The et al. [Because knowledge about delirium is relevant for virtually all nurses working within the hospital, an educational approach that can improve knowledge and skills for large groups of people is needed. E-learning is one method available for efficiently educating a large number of people. A review by Cook et al.  has showet al. . Computeet al. .The aim of the study is to assess the effects a complementary e-learning course has on the implementation of the delirium part of the Frail Elderly Project, and thus to see whether the use of e-learning improves the provision of delirium care by nurses. The hypothesis underlying this study is that use of e-learning will increase nurses' knowledge regarding delirium and their willingness to change their behaviour regarding at-risk patients. It is hypothesised that these effects will in turn lead to changes in the care provided: screening of elderly patients for risks, observing at-risk patients for delirium, and taking preventative or curative measures. This protocol describes the methodology used in this study and provides details of the stepped wedge cluster randomised controlled trial design .For this study, an e-learning course about delirium will be used that is aimed at nursing staff. This course  was deveThe aims of the e-learning course are on the one hand to create or increase awareness about delirium and the associated risks, and on the other hand to increase knowledge about delirium care. The content of the course consists of information regarding delirium, the risks involved for patients, the recognition of at-risk patients and delirious patients, and the prevention or treatment of delirium. By using fictional patient cases, information is provided in a context familiar to nurses. Throughout the course, users are presented with questions concerning previously given information, providing them with insight into the progress they have made.During the study, the e-learning course will be offered to nurses in the participating wards online for a period of three months. The estimated time needed per nurse to complete the course, including a knowledge test before and after, is four hours. Nurses can stop the course at any time and continue at a later time. When completing the course and the subsequent knowledge test successfully, nurses will be provided with a certificate stating the completed course and the credits awarded. In cooperation with implementation managers of the publisher, 'kick-off' meetings will be organised in each hospital in order to introduce the e-learning course to the users. The aim of these meetings will be to familiarise users with the way the e-learning works and to encourage them to use and complete the course within the three-month period. After one month and again after two months, users who have not completed the course will receive an e-mail reminder concerning the course to further encourage its use . In addiData will be gathered in 18 Dutch hospitals, all of which are at the beginning stages of the implementation of the Frail Elderly Project at the start of the study (self-reported status). These 18 hospitals include two university hospitals, five teaching hospitals, and eleven general hospitals, varying in size  and geographical location. One internal medicine ward and one surgical ward of each hospital will participate in the study.Nearly all hospitals in the Netherlands were initially invited to participate in the study, excluding specialised hospitals such as eye clinics and cancer hospitals, and hospitals already participating in a separate study related to the Frail Elderly Project. The hospitals that responded most quickly to the invitation were included in the study.The study will be conducted using a stepped wedge cluster randomised trial design. The defining feature of this design is that the intervention will be introduced to all clusters -- or in this instance, hospitals -- in a sequential order ,30,31. AAfter every monthly data collection moment, one or two new hospitals will receive access to the intervention, as illustrated in Figure Monthly patient record reviews of patients 70 years or older will be the main source of data. During 11 months, research nurses will review approximately 10 records per ward per month , using both nursing and medical records. If a ward provides the research nurse with more than 10 records fitting the inclusion criteria, the nurse will take a random sample from the available records. All record reviews will take place within the same week of the month, using records of patients still in hospital or discharged during the previous week. From these records, data concerning provided delirium care will be gathered, which will offer the following information about the implementation of the delirium aspect of the Frail Elderly Project:1. Detection of risk for delirium, as well as screening for falls, malnutrition, and physical impairment. The Frail Elderly Project has provided hospitals with screening instruments to assess these risks  resulted in a power of 0.8, based on the following assumptions: 18 hospitals (36 wards); an improvement of delirium risk screening of 20% (from having 40% of the elderly patients screened to 60%) after the e-learning introduction; an alpha of 0.05; a total of 360 patient records for reviewing per month; an intracluster correlation coefficient (ICC) of 1.0.The power calculation for the part of the study focused on the effect of e-learning for nurses on provided care , with an e-learning effect size of 1.00 , an alphIn the Frail Elderly Project hospitals are advised to screen all elderly patients directly after admission for the risk of developing or the presence of delirium, falls, malnutrition, or physical impairment. The e-learning course educates nurses on screening for delirium. The percentage of elderly patients that are indeed screened for the risk of delirium is the primary outcome of this study. Secondary outcome measures include: the percentage of elderly patients with an increased risk of delirium that are observed with the Delirium Observation Screening scale; the percentage of elderly patients with (an increased risk of) delirium that receive care aimed to prevent or treat delirium; and the percentage of elderly patients that are diagnosed with delirium. Covariates that will be used in the analysis are: age, gender, living situation, comorbidity , and admThe data analysis will firstly consist of a comparison between hospitals that have received the intervention and hospitals that have not yet received the intervention, according to the stepped wedge schedule. This will be done using multilevel linear regression and multilevel logistic regression analyses. In these analyses, we will adjust for temporal trends and for clustering within hospitals using generalised estimating equations.Different organisational or system factors that might influence adherence to the intervention or might lead to differences between hospitals in delivered care will be analysed. These factors include hospital type , size, location , and type of records used (paper versus electronic).The Medical Ethics Review Committee of the VU University Medical Centre has approved the study protocol. Patients and representatives on the participating wards will be given the opportunity to object to the use of their (or their relative's) patient record.The number of studies using a stepped wedge design in order to evaluate the effectiveness of an intervention in routine practice is steadily increasing . The reaThis study has several potential limitations. The main limitation of the study is that data on provided care and the behaviour of care providers are gathered from patient records. The risk inherent to this method is that changes found are interpreted as actual changes in care and behaviour, while they might only indicate changes in registration. The e-learning course on delirium that nurses will use in this study does not focus on registration however, but educates nurses in improving the care they provide. Because the screening of patients for increased risks can only benefit patients when all relevant care professionals are aware of the outcomes, screening without proper registration would still imply poor quality of care. In this case, an improvement in registration would also suggest an improvement in care. Still, differences in quality of patient records between hospitals or wards might influence the outcome of this study. Records of poor quality could provide research nurses with insufficient information regarding provided care, which could result in the appearance of poor quality of care.The presence of the research nurse for the monthly record reviews might influence the professionals working on the wards. In order to minimise bias, hospitals will not be provided with information regarding their performance on the Frail Elderly Project during the research period. Another limitation is that the selection of participating hospitals was based on speed of response to the initial invitation. However, the final group of hospitals provide a fairly complete and balanced overview of hospitals within the Netherlands, varying in type of hospital, size, and geographical location. A final limitation is that hospitals were asked to participate in the study if they considered themselves to be at the beginning stages of implementation of the Frail Elderly Project. Which level of implementation had actually been achieved by the hospitals has not been measured or objectively determined before the start of the study. This indicates that the actual situation in each participating hospital regarding the implementation of the project might vary.Improving quality of care by implementing evidence-based practice is a difficult process. One way to support this process is by providing healthcare professionals with education regarding the desired change. Education can be a vital part of the implementation process, especially for complex health issues such as delirium. E-learning provides healthcare organisations with a potentially effective and simple way of educating large groups of professionals. This study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.The authors declare that they have no competing interests.CW, ML, and LS collectively developed the study plan. CW conceived of the study, and led the application for current funding through the Dutch Ministry of Health, Welfare and Sport. LS has drafted the initial form and final revision of this manuscript. All authors  have read drafted components of the manuscript, provided input into initial and final refinements of the total manuscript, and agreed to the final manuscript.Screening instruments Frail Elderly Project.Click here for file


This diagnostic tool permits the recognition of morphologic structures not visible by the naked eye, thus opening a new dimension in the analysis of the clinical morphologic features of PSLs. In order to reduce the learning-curve of non-expert clinicians and to mitigate problems inherent in the reliability and reproducibility of the diagnostic criteria used in pattern analysis, several indicative methods based on diagnostic algorithms have been introduced in the last few years. Recently, numerous systems designed to provide computer-aided analysis of digital images obtained by dermoscopy have been reported in the literature. The goal of this article is to review these systems, focusing on the most recent approaches based on content-based image retrieval systems (CBIR).Dermoscopy  is a non-invasive diagnostic technique for the  Human cutaneous melanoma, a deadly skin cancer that develops through the malignant transformation of melanocytes, can be a highly aggressive neoplasm, characterized by a rapidly growing incidence and an elevated mortality rate. Although early melanomas are locally controlled with surgical excision , up to 2in vivo observation of PSLs, allowing a better visualization of surface and subsurface structures (from the epidermis to the papillary dermis). This diagnostic tool permits the visualization of morphological structures of the epidermis an the dermo-epidermal junction until the papillary dermis, thus opening a new dimension in the analysis of the clinical morphologic features of PSLs. Several studies [Dermoscopy  is a non-invasive diagnostic technique for the  studies  have sho studies ,8,9. All studies  Recently studies . The pro studies ,13. Inde studies . This exet al. [et al. [et al. [A different experimental approach to demonstrate the feasibility and reliability of automated analysis of dermoscopic images in melanoma diagnosis has been described by Burroni et al. , using tet al.  has defi [et al.  has defi [et al.  defined In conclusion, all these studies have shown that the currently proposed image analysis systems are able to identify correctly the clinically obvious melanomas, but they have limited capabilities to discriminate between borderline lesions and early malignant melanoma . Therefoetc. More than patient data, the medical images by far represent the major amount of information collected for medical data. Picture Archiving and Communication Systems (PACS) deployed in hospitals today address some of the challenges related to medical data management. Yet, the possibility of aggregating the information stored in the imaging data to provide assistance for diagnostic activities is still not at all exploited, as medical practitioners still rely on atlases for support. With the advent of digital images, the production of digital atlases has become possible. Nevertheless, to provide the maximum benefit to diagnostic and analysis activities that rely on them, large digital atlases need to be effectively navigated in terms of content, providing the practitioner with just the information that most relates to the cases under examination. Rather than just relying on textual patient information or on subjective and error-prone annotations describing the images, this casting of generic image content into a summary of the atlas - in terms of the specific issues being analyzed - needs to be performed based on the actual contents of the data resulting from the imaging procedure.The convergence of the biological and information sciences is currently producing a paradigm shift in health care. Electronic processing of medical data has opened many possibilities for improving medical tasks such as diagnosis, surgical planning or therapy, both in daily clinical practice and clinical research. Medical diagnosis and intervention increasingly relies upon images, of which there is a growing range available to the clinician: X-ray , ultrasound, MRI, CT, PET scans, An image retrieval system is part of a digital asset management system for browsing, searching and retrieving images from a large database. Digital asset management is concerned with the ingestion, annotation, cataloging, storage, retrieval and distribution of assets such as photographs, animations, videos and music. Generally, the "asset" being managed is constituted of a binary stream of data that can be stored in a file and that represents actual content that can be, for instance, visualized or listened to. As an addition to the data stream itself, the asset is accompanied by its "metadata". Metadata is a description of the asset that can detail among others asset content (what is in the package?); the means of encoding/decoding ; provenance (history to point of capture); ownership; rights of access. While metadata content can be quite extensive, it is not meant to represent a complete description of the contents of the data stream in textual terms. Its main purpose is instead normally to capture information about the context of the acquisition.etc. Like text search, it is designed to help users find information in large archives using keywords or search phrases sorting results by relevancy.Most traditional and common methods of image retrieval utilize some method of adding metadata such as captioning, keywords, or descriptions to the images so that retrieval can be performed over the annotation words. Manual image annotation is time-consuming, laborious and expensive; to address this, there has been a large amount of research done on automatic image annotation: image meta search is a type of search engine specialized on finding pictures, images, animations etc.A common misunderstanding when it comes to image search is that the technology is based on detecting information in the image itself, whereas most image search works as other textual search engines. The metadata of the image is indexed and stored in a database, and when a search query is performed the image search engine looks up the index, and queries are matched with the stored information. Some search engines can automatically identify a limited range of visual content, e.g., faces, trees, sky, buildings, flowers, colors, CBIR intends overcoming the limitations inherent in metadata-based systems: textual information about images can be easily searched using existing technology, but requires humans to personally describe every image in the database. This is impractical for very large databases, or for images that are generated automatically. It is also possible to miss images that use different synonyms in their descriptions. Systems based on categorizing images in semantic classes like "cat" as a subclass of "animal" avoid this problem, but still face the same scaling issues. Without the ability to examine image content, searches must rely on metadata such as captions or keywords, which may be laborious or expensive to produce. In contrast, CBIR is the application of computer vision to the image retrieval problem. "Content-based" means that the search will analyze the actual contents of the image. The term 'content' in this context might refer to colors, shapes, textures, or any other information that can be derived from the image itself. A parallel field is that of content-based video indexing and retrieval and automatic annotation: similar issues and objectives are shared, while the video domain has specific issues of its own as well as specific possibilities to exploit additional information related to the temporal dimension of the video stream.A large volume of scientific research has been produced in the last 20 years about CBIR, starting around February 1992 when the US National Science Foundation organized a workshop in Redwood, California, to identify major research areas that should be addressed by researchers for visual information management systems that would be useful in scientific, industrial, medical, environmental, educational, entertainment, and other applications [Two central review papers have been published in the literature about the subject.etc. The first one dates to the year 2000  and repoThe second fundamental review paper in CBIR dates to 2008  and repoThe many issues related to the unsatisfactory performance of general-purpose CBIR and the objective of object recognition are addressed among others in . The keyThe added simplicity produced by prior knowledge about the context of search is the fundamental reason why specialized CBIR systems are in widespread use in real-world environments ranging from biometrics (the IAFIS fingerprint matching system in use at FBI) to industrial applications. CBIR represents an effective solution, especially in cases in which the similarity evaluation between the images depends on the measurement of small details (as in the case of fingerprint minutiae) or of quantities that are difficult for human observers to quantify . The steady increase in processing power and the inherently parallel nature of the problem render instead less a limiting factor than in the past any near real time requirements.A further issue is the need to take into account application-domain terms in the analysis, effectively bridging the gap between the plain image signal level  and the higher level semantic one. This is both an applicative necessity and a possibility for regularizing the visual signal analysis with the structure inherent in human language.A number of review articles have been published about CBIR in specialized domains and the issues they present. Specific attention has been paid to the domain of medical CBIR  and the The large volume of scientific research produced on the topic of CBIR is unfortunately not paralleled as of 2010 by an equally significant availability of actually operational tools. Nevertheless, a number of systems for general-purpose CBIR have been developed over the last ten years. A significant subset of these can be used via the Internet for testing purposes  in tThe process of describing picture content in textual terms takes on a specific meaning in the case of image-based diagnostic activities e.g., in dermatological settings. Documenting this image interpretation process for repeatability, educational as well as legal issues is essential to reducing diagnostic errors and improving effectiveness at different levels of medical organizations.Although their significance is specific to the applicative setting, the techniques that can be employed to answer this need bear a broader meaning related to the well-established, general field of digital media asset management. Automatic image-based diagnosis attempts have been the subject of active research in biomedical image analysis for a number of years ,36,37,38Abstract features and machine learning methodologies or problem oriented model-based systems have been employed. Yet, the main problem with automated diagnostic analysis is the disproportionate cost of false negatives. The role of the expert interpreter and the related responsibilities should not be abdicated.The approach of our CBIR system for dermoscopic images, that is FIDE , is to dIn the FIDE system, the statistical analysis performed in order to assess the similarity among image items is based on a hierarchical Bayesian model-based data analysis approach. The RGB signal level model p(D) is linked to a high-dimensional primitive descriptor level p(P) taking into account color as well as geometric information extracted from the data and in turn to a secondary, lower-dimensionality, independent synthetic descriptor level p(S) by conditional probabilistic links p(P|S), p(S|P). Inference is conducted in order to obtain the posterior density p(S|P) p(P|D) p(D). The obtained densities are compared with each other taking into account a bank of distance and divergence measures to carry out an association level search procedure. Category search is employed to limit search results discriminating among retrieval outcomes of different natures. Standard measures of retrieval performance that are considered in the development and evaluation of the system performance. Clusters are defined by the available supervised diagnoses attached to each of the items. The centers of mass of each of the clusters can be calculated, as the relative distances of the different centers of mass provide a further a measure of the quality of the ranking output by the retrieval system.The FIDE system is effective in retrieving PSL images with known pathology visually similar to the image under evaluation giving a valuable and intuitive aid to the clinician in the decision making process. Indeed, we argue that a system, able to retrieve and present cases with known pathology similar in appearance to the lesion under evaluation, may provide an intuitive and effective support to clinicians which potentially can improve their diagnostic accuracy. In addition, this CBIR system can be useful as a training tool for medical students and inexpert practitioners given its ability to browse large collections of PSL images using their visual attributes. The system will allow the user to mark retrieved images as positive and negative relevance feedback. This very important feature will permit both to better evaluate the performance of the proposed system and, consequently, to further tune the weighting factor parameters in order to improve the relevance of the retrieved PSL images. Furthermore, the proposed system can be used to create appropriate CBIR Web Services that can be used remotely to perform query-by-example in various PSL image databases around the world and can be a very good complement to text-based retrieval methods. etc.), which could be supported by the huge amount of information available in medical archives.Dermoscopy actually has higher discrimination power than naked-eye examination to detect melanoma, if performed by trained physicians. Computer-assisted automated diagnosis of PSL by means of CBIR systems is a promising research field, that probably will change the future management of skin tumors. FIDE represents, indeed, the first CBIR system successfully applied to dermoscopic images . The ins


Research about the relationship between premenstrual syndrome (PMS) and major depression is limited. This study examined the relationship between moderate to severe PMS and major depression in a population-based sample of women of reproductive age. The objectives of the study were to assess the association between premenstrual syndrome and major depression, to analyse how PMS and major depression differ and to characterise the group of women who report both PMS and major depression.Data were obtained from the Swiss Health Survey 2007. Included in the analysis was data from women under the age of 55 without hysterectomy and who answered the questions on PMS symptoms. The population-based sample consisted of 3518 women. Weighted prevalence rates were calculated and relative risk ratios for PMS, major depression and women who reported both PMS and major depression, were calculated with logistic multinominal logit regression.The prevalence of major depression was 11.3% in women screening positive for moderate PMS and 24.6% in women screening positive for severe PMS. Compared to women without any of these conditions, women who reported moderate to severe alcohol consumption had a lower risk for PMS. Women reporting use of antidepressants, and use of oral contraceptives had a higher risk for major depression compared to women without any of these conditions. Women reporting work dissatisfaction had a higher risk for PMS. A higher relative risk to report both PMS and major depression compared to women without PMS or major depression was related to factors such as high psychological distress, low mastery, psychotropic drug consumption, and low self-rated health.The results suggested that women who suffer from both PMS and major depression are more impaired compared to women with only one disorder. The results further indicated that PMS and major depression are different disorders that can, however, co-occur. Premenstrual syndrome (PMS) and premenstrual dysphoric disorders (PMDD), as a severe form of premenstrual syndrome, have shown to be associated with several psychological conditions, such as reduced psychological wellbeing -6, mood The temporal relationship between PMS and major depression has been investigated in several studies yielding conflicting results. Some studies have shown that women with PMS or PMDD have a higher percentage of past major depression than women without PMS or PMDD ,11,18, wThere is also some evidence that women with PMDD might be at a higher risk to develop major depression in the future than women without PMDD ,21.Besides investigating the relationship between the two disorders, examination of whether and how the two disorders can be differentiated from each other is also of relevance. For PMDD, the criteria of the DSM-IV require the disturbance not to be merely an exacerbation of the symptoms of another disorder, such as major depression. Nevertheless, a clear distinction between PMDD and depression seems not always as clear as wished, and some symptoms, such as depressed mood, feelings of hopelessness, decreased interest in usual activities, concentration difficulties, lack of energy, change in appetite, hypersomnia or insomnia are included in measures for both disorders ,23. SomeTo our knowledge, little is known about the group of women who report both major depression and premenstrual symptoms. Comorbidity could be related to higher impairment which would make appropriate treatment for this group of women particularly relevant. Soares et al.  have shoThere is a paucity of data from population-based studies on the association between and the distinction of PMS and major depression, and especially knowledge about the group of women reporting to suffer from both is also limited. The first aim of this study was therefore to assess the prevalence of women reporting both major depression and premenstrual symptoms in a large population-based sample and to analyse how women with PMS and depression differ from each other. A second aim was to characterise women who report both major depression and premenstrual symptoms.Data presented in this study was assessed for the nationwide Swiss Health Survey 2007 (SHS), which is conducted every five years since 1992 as a cross-sectional study by the Swiss Federal Office of Statistics. The SHS aims to give information about health status, health related behaviors, prevalence and consequences of diseases, and health care utilization. The data of the SHS are available from the Swiss Federal Office of Statistics upon request. For this study, a permission to analyse the data was obtained (Contract Number 30.23-2008). For the SHS 2007, a random sample of adults living in Switzerland aged 15 years or older was drawn. The assessment consisted of two parts, a telephone interview and an additional written questionnaire. The response rate for the telephone interview was 66% (18760). The written questionnaire was sent to all participants of the telephone interview. It was completed by 80% of the participants who had taken part in the telephone interview . The questions about premenstrual symptoms were included in the written part of the questionnaire.The sample for this study was restricted to women under the age of 55 with no history of hysterectomy and who answered the questions on PMS symptoms (N = 3522). Mean age was 35.46 years.To assess premenstrual symptoms and to differentiate between women with or without moderate to severe PMS, a slightly modified version of the premenstrual symptoms screening tool (PSST)  was usedMajor depression was assessed with the World Health Organization's Composite International Diagnostic Interview Short Form (CIDI-SF) . The CIDChi-square tests and multinominal logit regression were conducted using STATA 10 to compare the four groups: women without major depression or PMS, women with major depression only, women with PMS only and women with both major depression and PMS. The statistical analyses were considered to be significant with p < 0.05. For the chi-square tests weighted dated was used.Table Table Differences in health status and health behaviour between the four groups  are shown in Table Table Women taking oral contraception were at higher risk of suffering from major depression than women with none of the two conditions (reference group) . Women who reported taking antidepressants were more likely to suffer from depression  and from depression and PMS . The consumption of both tranquillizers/sleeping pills and antidepressants, was more likely in women with depression and PMS . Women who reported having moderate to severe alcohol consumption were at lower risk of screening positive for PMS than the reference group . Differing associations in alcohol consumption were found for women with PMS (RRR below 1) and women with major depression (RRR above 1).Women with medium or high psychological distress showed a higher risk of suffering from major depression  and an even higher risk of suffering from PMS plus major depression  than women of the reference group. High mastery and good self-rated health were protective factors. Women who reported high mastery had a lower risk of screening positive for PMS , from major depression  and from both  than women of the reference group. Good self-rated health was highly protective against major depression  and PMS plus major depression . Dissatisfaction at work was a significant risk for PMS .Results of this population-based study showed that there was a considerable percentage of women who reported both moderate PMS and major depression (11% of women with moderate PMS) or severe PMS and major depression (25% of women with severe PMS). Women with PMS and women with major depression differed mainly in alcohol consumption, psychotropic drug consumption, oral contraception and work dissatisfaction. Factors that were related with a higher relative risk to report both disorders were high psychological distress, low mastery, psychotropic drug consumption, and low self-rated health.Women who reported using oral contraceptives were more likely to suffer from major depression than the reference group (women without major depression or PMS). Although not significant, they were also less likely to screen positive for PMS, which also has been found in other studies . These rThe prevalence of women who reported both disorders was comparable with prevalence rates found by Wittchen et al. , with slThe results suggest that the group of women who suffered from both PMS and major depression, were the most impaired group, with women with high psychological distress and consumption of antidepressants or a combination of psychotropic drugs having the highest risk to report both conditions. The high impairment and high psychological distress suggests that for treatment an interdisciplinary approach including psychologists or psychiatrists might be beneficial. Good self-rated health and high mastery were protective factors against both conditions (PMS and major depression together). Soares et al.  found thWhen considering the discussion about gender differences in depression, the findings about the association between PMS and depression are also of significance. It has been suggested that reproductive hormones might contribute to the increased risk in women of suffering from depression compared to men . The relA limitation of our study is the cross-sectional design. The results can therefore only be interpreted as associations. No causal relationships can be deduced and the history of the development of symptoms is unclear. We can therefore not distinguish if premenstrual symptoms became more severe due to a major depression or if depressive symptoms got worse due to premenstrual symptoms. Furthermore, we used self-reporting measures which might result in an underreporting of the proportion of women with major depression. Assuming that women with major depression tend not to take part in surveys and may be underrepresented in our sample, the prevalence of major depression and of women reporting both disorders may be lower in our study than in the population. The associations between the predictors and the groups may as a result be rather conservative. However, we do not expect a reporting bias between the two affected groups given the observed pattern of associations. The gold standard for the assessment of PMS and PMDD is prospective daily rating. The cross-sectional design and the used screening tools did, however, not allow this procedure and the validity of the diagnosis PMS in our study is therefore not entirely clear. For this reason, we did not to use the term PMDD, but the terms moderate and severe PMS. Furthermore, without prospective daily rating it is also not clear whether some of the women reporting PMS suffered from premenstrual exacerbation of major depression and might therefore falsely be included in the group of women with PMS. Strengths of our study were the large population-based sample as well as the use of two standardized screening tools in the Swiss Health Survey allowing us to address their relationship with additional indicators of health status and health behaviour, and to control for confounds.The results of this study suggest that for the group of women who suffer from both major depression and PMS, treatment might be particularly important and needed given that they have been found to be more impaired than women with one condition only. The risk for low self-rated health was highest in women with both conditions, which indicates that they are not only impaired on a psychological level but also feel physically unwell. As Breaux et al.  have staThe authors declare that they have no competing interests.CFK undertook the statistical analysis, did the literature searches, and wrote the draft of the manuscript. CW contributed to the writing. EZS and ST contributed to the interpretation of the results, the writing, finalizing of the manuscript and provided additional literature. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/795/prepub