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1.  Evidence-Based Dentistry: What's New? 
The importance of evidence for every branch of medicine in teaching in order to orient the practitioners among the great amount of most actual scientific information's, and to support clinical decisions, is well established in health care, including dentistry.
The practice of evidence-based medicine is a process of lifelong, self-directed, problem-based learning which leads to the need for clinically important information about diagnosis, prognosis, therapy and other clinical and health care issues. Nowadays the practice of dentistry is becoming more complex and challenging because of the continually changing in dental materials and equipments, an increasingly litigious society, an increase in the emphasis of continuing professional development, the information explosion and the consumer movement associated with advances on the Internet.
The need for reliable information and the electronic revolution have come together to allow the “paradigm shift” towards evidence-based health care. Recent years have seen an increase in the importance of evidence-based dentistry, aiming to reduce to the maximum the gap between clinical research and real world dental practice. Aim of evidence-based practice is the systematic literature review, which synthesizes the best evidences and provides the basis for clinical practice guidelines. These practice guidelines give a brief review of what evidence-based dentistry is and how to use it.
PMCID: PMC1891443  PMID: 17589569
dentistry; evidence-based medicine; dental care/standards
2.  Sleep from an Islamic perspective 
Annals of Thoracic Medicine  2011;6(4):187-192.
Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allνh (God) and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh) promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh), Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry.
doi:10.4103/1817-1737.84771
PMCID: PMC3183634  PMID: 21977062
Circadian rhythm; dreams; Islam; Quran; sleep
3.  Marital quality and the marital bed: Examining the covariation between relationship quality and sleep 
Sleep medicine reviews  2007;11(5):389-404.
The majority of adults sleep with a partner, and for a significant proportion of couples, sleep problems and relationship problems co-occur, yet there has been little systematic study of the association between close relationships and sleep. The association between sleep and relationships is likely to be bi-directional and reciprocal—the quality of close relationships influences sleep and sleep disturbances or sleep disorders influence close relationship quality. Therefore, the purpose of the present review is to summarize the extant research on 1) the impact of co-sleeping on bed partner's sleep; 2) the impact of sleep disturbance or sleep disorders on relationship functioning; and 3) the impact of close personal relationship quality on sleep. In addition, we provide a conceptual model of biopsychosocial pathways to account for the covariation between relationship functioning and sleep. Recognizing the dyadic nature of sleep and incorporating such knowledge into both clinical practice and research in sleep medicine may elucidate key mechanisms in the etiology and maintenance of both sleep disorders and relationship problems and may ultimately inform novel treatments.
doi:10.1016/j.smrv.2007.05.002
PMCID: PMC2644899  PMID: 17854738
Marital quality; close relationships; sleep; sleep disorders
4.  Sleep medicine in Saudi Arabia: Current problems and future challenges 
Annals of Thoracic Medicine  2011;6(1):3-10.
Sleep medicine is a relatively new specialty in the medical community. The practice of sleep medicine in Saudi Arabia (KSA) began in the mid to late nineties. Since its inception, the specialty has grown, and the number of specialists has increased. Nevertheless, sleep medicine is still underdeveloped in the KSA, particularly in the areas of clinical service, education, training and research. Based on available data, it appears that sleep disorders are prevalent among Saudis, and the demand for sleep medicine service is expected to rise significantly in the near future. A number of obstacles have been defined that hinder the progress of the specialty, including a lack of trained technicians, specialists and funding. Awareness about sleep disorders and their serious consequences is low among health care workers, health care authorities, insurance companies and the general public. A major challenge for the future is penetrating the educational system at all levels to demonstrate the high prevalence and serious consequences of sleep disorders. To attain adequate numbers of staff and facilities, the education and training of health care professionals at the level of sleep medicine specialists and sleep technologists is another important challenge that faces the specialty. This review discusses the current position of sleep medicine as a specialty in the KSA and the expected challenges of the future. In addition, it will guide clinicians interested in setting up new sleep medicine services in the KSA or other developing countries through the potential obstacles that may face them in this endeavor.
doi:10.4103/1817-1737.74269
PMCID: PMC3023868  PMID: 21264164
Developing countries; Saudi Arabia; sleep; sleep centers; sleep disordered breathing; sleep laboratories; sleep medicine
5.  Sleep disturbances in Parkinson’s disease patients and management options 
Nature and Science of Sleep  2011;3:125-133.
Sleep disturbances are among the most common nonmotor complaints of patients with Parkinson’s disease (PD), and can have a great impact on quality of life. These disturbances manifest in a variety of ways; for instance, insomnia, sleep fragmentation, and excessive daytime sleepiness. Sleep-related movement disorders such as restless legs syndrome and periodic leg movements may share a common pathophysiology, and occurrence of rapid eye movement behavior disorder may predate the onset of PD or other synucleinopathies by several years. Medications for PD can have a significant impact on sleep, representing a great challenge to the treating physician. Awareness of the complex relationship between PD and sleep disorders, as well as the varied way in which sleep disturbances appear, is imperative for successful long-term management.
doi:10.2147/NSS.S18897
PMCID: PMC3630958  PMID: 23616723
sleep disorders; insomnia; restless legs syndrome; Parkinson disease; fatigue; REM behavior disorder
6.  Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer 
Nature and science of sleep  2012;4:151-162.
Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.
doi:10.2147/NSS.S18895
PMCID: PMC3593248  PMID: 23486503
cancer; sleep; chemotherapy; intervention; circadian rhythm; cognitive behavioral therapy
7.  Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer 
Nature and Science of Sleep  2012;4:151-162.
Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.
doi:10.2147/NSS.S18895
PMCID: PMC3593248  PMID: 23486503
cancer; sleep; chemotherapy; intervention; circadian rhythm; cognitive behavioral therapy
8.  REM Sleep Percentage in Children with Autism Compared to Children with Developmental Delay and Typical Development 
Objective
To compare objective polysomnographic parameters between three cohorts: children with autism, with typical development, and with developmental delay without autism.
Design
Overnight polysomnographic recordings were scored for sleep architecture according to American Academy of Sleep Medicine criteria by a board certified sleep medicine specialist blind to diagnosis for studies collected between July 2006, September 2009.
Setting
Subjects evaluated pediatric ward in Clinical Center of the National Institutes of Health.
Participants
First 60 consecutive children with autism, 15 with typical development, and 13 with developmental delay matched for non-verbal IQ to the autism group. Ranging in age from 2 to 13, selected without regard to the presence or absence of sleep problem behavior.
Main Outcome Measure
Total Sleep Time (TST), latencies to non-REM sleep and REM and percentages of total sleep time for stages 1, 2, slow wave sleep (SWS) and REM.
Results
There were no differences between typical v developmental delay groups. Autism v typical revealed shorter TST (p = .004), greater SWS percentage (p=.001), and much smaller REM percentage, 14.5 v 22.6 (p<.001). Autism v developmental delay revealed shorter TST (p=.001), greater stage 1 percentage (p= <.001), greater SWS percentage (p = <.001) and much less REM percentage, 14.5 v 25 (p= <.001).
Conclusions
A relative deficiency of REM may indicate an abnormality in neural organization in young children with autism that is not directly associated or related to inherent intellectual disability but may serve as a window into understanding core neurotransmitter abnormalities unique to this disorder.
doi:10.1001/archpediatrics.2010.202
PMCID: PMC3111973  PMID: 21041596
9.  Sleep disorders in children 
Clinical Evidence  2010;2010:2304.
Introduction
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for dyssomnias in children? What are the effects of treatments for parasomnias in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 28 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antihistamines; behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives; benzodiazepines alone; exercise; extinction and graduated extinction; 5-hydroxytryptophan; light therapy; melatonin; safety/protective interventions for parasomnias; scheduled waking (for parasomnias); sleep hygiene; and sleep restriction.
Key Points
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.
There is a paucity of evidence about effective treatments for sleep disorders in children, especially parasomnias, but behavioural interventions may be the best first-line approach.
Extinction and graduated extinction in otherwise healthy children with dyssomnia may improve sleep quality and settling, and reduce the number of tantrums and wakenings compared with no treatment. Extinction and graduated extinction in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder with dyssomnia may be more effective at improving settling, reducing the frequency and duration of night wakings, and improving parental sleep compared with no treatment; however, we don't know whether it is more effective in improving sleep duration.Graduated extinction may be less distressing for parents, and therefore may have better compliance.
Sleep hygiene for dyssomnia in otherwise healthy children may be more effective in reducing the number and duration of bedtime tantrums compared with placebo, but we don’t know if it is more effective at reducing night wakenings, improving sleep latency, improving total sleep duration, or improving maternal mood. Sleep hygiene and graduated extinction seem to be equally effective at reducing bedtime tantrums in otherwise healthy children with dyssomnia.We don't know whether sleep hygiene for dyssomnia in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder is effective.
Melatonin for dyssomnia in otherwise healthy children may be more effective at improving sleep-onset time, total sleep time, and general health compared with placebo. Evidence of improvements in dyssomnia with melatonin is slightly stronger in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder.
Little is known about the long-term effects of melatonin, and the quality of the product purchased could be variable as melatonin is classified as a food supplement.
Antihistamines for dyssomnia may be more effective than placebo at reducing night wakenings and decreasing sleep latency, but we don’t know if they are more effective at increasing sleep duration. The evidence for antihistamines in dyssomnia comes from only one small, short-term study.
We don’t know whether behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives, exercise, light therapy, or sleep restriction are effective in children with dyssomnia.
We don’t know whether antihistamines, behavioural therapy plus benzodiazepines or plus chloral and derivatives, benzodiazepines, 5-hydroxytryptophan, melatonin, safety/protective interventions, scheduled waking, sleep hygiene, or sleep restriction are effective in children with parasomnia.
PMCID: PMC3217667  PMID: 21418676
10.  Biomedical semantics in the Semantic Web 
Journal of Biomedical Semantics  2011;2(Suppl 1):S1.
The Semantic Web offers an ideal platform for representing and linking biomedical information, which is a prerequisite for the development and application of analytical tools to address problems in data-intensive areas such as systems biology and translational medicine. As for any new paradigm, the adoption of the Semantic Web offers opportunities and poses questions and challenges to the life sciences scientific community: which technologies in the Semantic Web stack will be more beneficial for the life sciences? Is biomedical information too complex to benefit from simple interlinked representations? What are the implications of adopting a new paradigm for knowledge representation? What are the incentives for the adoption of the Semantic Web, and who are the facilitators? Is there going to be a Semantic Web revolution in the life sciences?
We report here a few reflections on these questions, following discussions at the SWAT4LS (Semantic Web Applications and Tools for Life Sciences) workshop series, of which this Journal of Biomedical Semantics special issue presents selected papers from the 2009 edition, held in Amsterdam on November 20th.
doi:10.1186/2041-1480-2-S1-S1
PMCID: PMC3105493  PMID: 21388570
11.  Investigation into the Influence of Physician for Treatment Based on Syndrome Differentiation 
Background. The characteristics of treatment based on syndrome differentiation (TBSD) cause great challenges to evaluate the effectiveness of the clinical methods. Objectives. This paper aims to evaluate the influence of physician to personalized medicine in the process of TBSD. Methods. We performed a randomized, triple-blind trial involving patients of primary insomnia treated by 3 physicians individually and independently. The patients (n = 30) were randomly assigned to receive treatments by the 3 physicians for every visit. However, they always received the treatment, respectively, prescribed by the physician at the first visit. The primary outcome was evaluated, respectively, by the Pittsburgh Sleep Quality Index (PSQI) and the TCM symptoms measuring scale. The clinical practices of the physicians were recorded at every visit including diagnostic information, syndrome differentiation, treating principles, and prescriptions. Results. All patients in the 3 groups (30 patients) showed significant improvements (>66%) according to the PSQI and TCM symptoms measuring scale. Conclusion. The results indicate that although with comparable effectiveness, there exist significant differences in syndrome differentiation, the treating principles, and the prescriptions of the approaches used by the 3 physicians. This means that the physician should be considered as an important factor for individualized medicine and the related TCM clinical research.
doi:10.1155/2013/587234
PMCID: PMC3830859  PMID: 24288563
12.  A Clinical Overview of Sleep and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents 
Introduction:
The relationship between attention-deficit/hyperactivity disorder (ADHD) and sleep is a complex one which poses many challenges in clinical practice.
Methods:
Studies of sleep disturbances in children with academic and behavioral problems have underscored the role that primary sleep disorders play in the clinical presentation of symptoms of inattention and behavioral dysregulation. In addition, recent research has shed further light on the prevalence, type, risk factors for, and impact of sleep disturbances in children with ADHD.
Results:
The following discussion of the multi-level and bi-directional relationships among sleep, neurobehavioral functioning, and the clinical syndrome of ADHD synthesizes current knowledge about the interaction of sleep and attention/arousal in these children.
Conclusion:
Guidelines are provided, outlining a clinical approach to evaluation and management of children with ADHD and sleep problems.
PMCID: PMC2687494  PMID: 19495429
sleep; attention deficit hyperactivity disorder; sleep disorders; sommeil; trouble du déficit d’attention avec hyperactivité; troubles du sommeil
13.  Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model 
PLoS ONE  2011;6(3):e17594.
The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem.
doi:10.1371/journal.pone.0017594
PMCID: PMC3048172  PMID: 21407827
14.  An open architecture for medical imaging systems 
Journal of Digital Imaging  2000;13(2):60-69.
Integration of medical imaging is the goal of many standards. Interfile and Digital Imaging and Communications in Medicine (DICOM) standards have made great strides in this area. The impact of DICOM is greater owing to its wider acceptance. However, the lack of conformance testing makes interoperability difficult, often requiring expensive consulting teams in a mixed-vendor environment. DICOM is difficult to learn and deploy because it does not use modern software paradigms. Many hardware and software advances in computer architectures and communications could greatly enhance diagnostic imaging if they could be quickly incorporated into medical imaging standards. These problems led to consideration of a solution able to take advantage of state-of-the-art technology and to allow diverse implementations while ensuring the accurate interchange of information between health care providers. It is an objectoriented system information model, with the common object request broker architecture (CORBA) as the vehicle to ensure interoperability between different implementations of the model. This report presents the model.
doi:10.1007/BF03168370
PMCID: PMC3453194  PMID: 10843251
medical imaging; information model; CORBA; DICOM; interfile
15.  Multiscale modeling of the causal functional roles of nsSNPs in a genome-wide association study: application to hypoxia 
BMC Genomics  2013;14(Suppl 3):S9.
Background
It is a great challenge of modern biology to determine the functional roles of non-synonymous Single Nucleotide Polymorphisms (nsSNPs) on complex phenotypes. Statistical and machine learning techniques establish correlations between genotype and phenotype, but may fail to infer the biologically relevant mechanisms. The emerging paradigm of Network-based Association Studies aims to address this problem of statistical analysis. However, a mechanistic understanding of how individual molecular components work together in a system requires knowledge of molecular structures, and their interactions.
Results
To address the challenge of understanding the genetic, molecular, and cellular basis of complex phenotypes, we have, for the first time, developed a structural systems biology approach for genome-wide multiscale modeling of nsSNPs - from the atomic details of molecular interactions to the emergent properties of biological networks. We apply our approach to determine the functional roles of nsSNPs associated with hypoxia tolerance in Drosophila melanogaster. The integrated view of the functional roles of nsSNP at both molecular and network levels allows us to identify driver mutations and their interactions (epistasis) in H, Rad51D, Ulp1, Wnt5, HDAC4, Sol, Dys, GalNAc-T2, and CG33714 genes, all of which are involved in the up-regulation of Notch and Gurken/EGFR signaling pathways. Moreover, we find that a large fraction of the driver mutations are neither located in conserved functional sites, nor responsible for structural stability, but rather regulate protein activity through allosteric transitions, protein-protein interactions, or protein-nucleic acid interactions. This finding should impact future Genome-Wide Association Studies.
Conclusions
Our studies demonstrate that the consolidation of statistical, structural, and network views of biomolecules and their interactions can provide new insight into the functional role of nsSNPs in Genome-Wide Association Studies, in a way that neither the knowledge of molecular structures nor biological networks alone could achieve. Thus, multiscale modeling of nsSNPs may prove to be a powerful tool for establishing the functional roles of sequence variants in a wide array of applications.
doi:10.1186/1471-2164-14-S3-S9
PMCID: PMC3665574  PMID: 23819581
16.  The use of sleep aids among Emergency Medicine residents: a web based survey 
Background
Sleepiness is a significant problem among residents due to chronic sleep deprivation. Recent studies have highlighted medical errors due to resident sleep deprivation. We hypothesized residents routinely use pharmacologic sleep aids to manage their sleep deprivation and reduce sleepiness.
Methods
A web-based survey of US allopathic Emergency Medicine (EM) residents was conducted during September 2004. All EM residency program directors were asked to invite their residents to participate. E-mail with reminders was used to solicit participation. Direct questions about use of alcohol and medications to facilitate sleep, and questions requesting details of sleep aids were included.
Results
Of 3,971 EM residents, 602 (16%) replied to the survey. Respondents were 71% male, 78% white, and mean (SD) age was 30 (4) years, which is similar to the entire EM resident population reported by the ACGME. There were 32% 1st year, 32% 2nd year, 28% 3rd year, and 8% 4th year residents. The Epworth Sleepiness Scale (ESS) showed 38% of residents were excessively sleepy (ESS 11–16) and 7% were severely sleepy (ESS>16). 46% (95 CI 42%–50%) regularly used alcohol, antihistamines, sleep adjuncts, benzodiazepines, or muscle relaxants to help them fall or stay asleep. Study limitations include low response and self-report.
Conclusion
Even with a low response rate, sleep aid use among EM residents may be common. How this affects performance, well-being, and health remains unknown.
doi:10.1186/1472-6963-6-136
PMCID: PMC1657010  PMID: 17052349
17.  Sleep disorders in children 
Clinical Evidence  2007;2007:2304.
Introduction
Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for dysomnias in children? What are the effects of treatments for parasomnias in children? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antihistamines, behavioural therapy plus benzodiazepines, or plus chloral and derivates, exercise, extinction and graduated extinction, light therapy, melatonin, safety/protective interventions for parasomnias, scheduled waking (for parasomnias), sleep hygiene, and sleep restriction.
Key Points
Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.
There is a paucity of evidence about effective treatments for sleep disorders in children, especially parasomnias, but behavioural interventions may be the best first-line approach.
Extinction and graduated extinction interventions improve settling and reduce night wakes compared with placebo in healthy children, and in children with learning disabilities. Graduated extinction may be less distressing for parents, and therefore may have better compliance.Sleep hygiene interventions may reduce bedtime tantrums in healthy children compared with placebo, with similar effectiveness to graduated extinction.Sleep hygiene plus graduated extinction may reduce bedtime tantrums in children with physical or learning disabilities.We don't know whether combining behavioural therapy with benzodiazepines or with chloral improves sleep or parasomnias.
Melatonin may improve sleep onset and sleep time compared with placebo in healthy children, but we don't know if it is beneficial in children with disabilities, if it improves parasomnias, or what its long-term effects might be. We don't know whether antihistamines, exercise, light therapy, or sleep restriction improve dysomnias or parasomnias in children.We don't know whether safety or protective interventions, scheduled waking, extinction, or sleep hygiene are effective in children with parasomnias.
PMCID: PMC2943792  PMID: 19450298
18.  The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial 
Purpose
Elderly with dementia are often afflicted with sleep problems. Recent studies have suggested that acupuncture may be a feasible alternative to traditional sleep medicine for treating sleep disturbance. This study investigated the effectiveness of acupuncture on sleep quality of elderly with dementia.
Patients and methods
Nineteen elders with dementia were followed through a control period and an acupuncture treatment period, each lasting 6 weeks. Outcome measures were subjects’ sleep quality and cognitive function. Sleep parameters were recorded by wrist actigraphy. Cognitive function was assessed by the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog). Pretests and posttests were conducted immediately before and after the control and treatment periods. Changes in the outcome measures between control and treatment periods were compared.
Results
Wilcoxon signed rank tests revealed that the subjects gained significantly more resting time and total sleep time in the treatment period than in the control period (P < 0.05). A nonsignificant trend for improvement in sleep efficiency was observed. Improvement in cognitive function was not statistically significant. A total of 86% of the subjects completed the treatment regime.
Conclusion
Results reveal that acupuncture was effective in improving some domains of sleep quality of elderly with dementia, and the subjects showed acceptance towards the intervention. Strengths and limitations of the present study as well as suggestions for further studies were considered.
doi:10.2147/CIA.S45611
PMCID: PMC3736969  PMID: 23940415
acupuncture; sleep disturbance; patients with dementia
19.  Conceptualization of category-oriented likelihood ratio: a useful tool for clinical diagnostic reasoning 
BMC Medical Education  2011;11:94.
Background
In the diagnostic reasoning process medical students and novice physicians need to be made aware of the diagnostic values of the clinical findings (including history, signs, and symptoms) to make an appropriate diagnostic decision. Diagnostic reasoning has been understood in light of two paradigms on clinical reasoning: problem solving and decision making. They advocate the reasoning strategies used by expert physicians and the statistical models of reasoning, respectively. Evidence-based medicine (EBM) applies decision theory to the clinical diagnosis, which can be a challenging topic in medical education.
This theoretical article tries to compare evidence-based diagnosis with expert-based strategies in clinical diagnosis and also defines a novel concept of category-oriented likelihood ratio (LR) to propose a new model combining both aforementioned methods.
Discussion
Evidence-based medicine advocates the use of quantitative evidence to estimate the probability of diseases more accurately and objectively; however, the published evidence for a given diagnosis cannot practically be utilized in primary care, especially if the patient is complaining of a nonspecific problem such as abdominal pain that could have a long list of differential diagnoses. In this case, expert physicians examine the key clinical findings that could differentiate between broader categories of diseases such as organic and non-organic disease categories to shorten the list of differential diagnoses. To approach nonspecific problems, not only do the experts revise the probability estimate of specific diseases, but also they revise the probability estimate of the categories of diseases by using the available clinical findings.
Summary
To make this approach analytical and objective, we need to know how much more likely it is for a key clinical finding to be present in patients with one of the diseases of a specific category versus those with a disease not included in that category. In this paper, we call this value category-oriented LR.
doi:10.1186/1472-6920-11-94
PMCID: PMC3341573  PMID: 22094044
20.  Predictors of continuous positive airway pressure adherence 
Continuous positive airway pressure (CPAP) is the leading treatment for obstructive sleep apnoea (OSA), a prevalent disorder of breathing in sleep strongly associated with obesity. OSA has serious adverse health, social and community effects arising from disturbed breathing, loud snoring, poor quality sleep and cardiovascular sequelae. When used appropriately, CPAP treatment is highly effective in normalising breathing and sleep, improving symptoms and lowering adverse event risk. However, patients do not necessarily accept, tolerate or comply with treatment, with many factors influencing CPAP uptake and longer term use. Although knowledge to address challenges affecting CPAP adherence and CPAP mask and machine technologies continue to improve incrementally, optimising CPAP treatment adherence is an ongoing challenge in sleep medicine.
doi:10.3410/M2-70
PMCID: PMC2954420  PMID: 20948830
21.  Increased Cerebral Blood Flow Velocity in Children with Mild Sleep-Disordered Breathing 
Pediatrics  2006;118(4):e1100-e1108.
Objective
Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits.
Design
Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended polysomnography. Weight, height, and head circumference were measured in all of the children. BMI and occipitofrontal circumference z scores were computed. Resting systolic and diastolic blood pressure were obtained. Both sleep-disordered breathing children and the age- and BMI-similar controls were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), Neuropsychological Test Battery for Children (NEPSY) visual attention and visuomotor integration, and IQ assessment (Wechsler Preschool and Primary Scale of Intelligence Version III). Transcranial Doppler was performed using a TL2-64b 2-MHz pulsed Doppler device between 2 PM and 7 PM in all of the patients and the majority of controls while awake. Time-averaged mean of the maximal cerebral blood flow velocities was measured in the left and right middle cerebral artery and the higher used for analysis.
Results
Twenty-one snoring children had an apnea/hypopnea index <5, consistent with mild sleep-disordered breathing below the conventional threshold for surgical intervention. Compared with 17 nonsnoring controls, these children had significantly raised middle cerebral artery blood flow velocities. There was no correlation between cerebral blood flow velocities and BMI or systolic or diastolic blood pressure indices. Exploratory analyses did not reveal any significant associations with apnea/hypopnea index, apnea index, hypopnea index, mean pulse oxygen saturation, lowest pulse oxygen saturation, accumulated time at pulse oxygen saturation <90%, or respiratory arousals when examined in separate bivariate correlations or in aggregate when entered simultaneously. Similarly, there was no significant association between cerebral blood flow velocities and parental estimation of child’s exposure to sleep-disordered breathing. However, it is important to note that whereas the sleep-disordered breathing group did not exhibit significant hypoxia at the time of study, it was unclear to what extent this may have been a feature of their sleep-disordered breathing in the past. IQ measures were in the average range and comparable between groups. Measures of processing speed and visual attention were significantly lower in sleep-disordered breathing children compared with controls, although within the average range. There were similar group differences in parental-reported executive function behavior. Although there were no direct correlations, adjusting for cerebral blood flow velocities eliminated significant group differences between processing speed and visual attention and decreased the significance of differences in Behavior Rating Inventory of Executive Function scores, suggesting that cerebral hemodynamic factors contribute to the relationship between mild sleep-disordered breathing and these outcome measures.
Conclusions
Cerebral blood flow velocities measured by noninvasive transcranial Doppler provide evidence for increased cerebral blood flow and/or vascular narrowing in childhood sleep-disordered breathing; the relationship with neuropsychological deficits requires further exploration. A number of physiologic changes might alter cerebral blood flow and/or vessel diameter and, therefore, affect cerebral blood flow velocities. We were able to explore potential confounding influences of obesity and hypertension, neither of which explained our findings. Second, although cerebral blood flow velocities increase with increasing partial pressure of carbon dioxide and hypoxia, it is unlikely that the observed differences could be accounted for by arterial blood gas tensions, because all of the children in the study were healthy, with no cardiorespiratory disease, other than sleep-disordered breathing in the snoring group. Although arterial partial pressure of oxygen and partial pressure of carbon dioxide were not monitored during cerebral blood flow velocity measurement, assessment was undertaken during the afternoon/early evening when the child was awake, and all of the sleep-disordered breathing children had normal resting oxyhemoglobin saturation at the outset of their subsequent sleep studies that day. Finally, there is an inverse linear relationship between cerebral blood flow and hematocrit in adults, and it is known that iron-deficient erythropoiesis is associated with chronic infection, such as recurrent tonsillitis, a clinical feature of many of the snoring children in the study. Preoperative full blood counts were not performed routinely in these children, and, therefore, it was not possible to exclude anemia as a cause of increased cerebral blood flow velocity in the sleep-disordered breathing group. However, hemoglobin levels were obtained in 4 children, 2 of whom had borderline low levels (10.9 and 10.2 g/dL). Although there was no apparent relationship with cerebral blood flow velocity in these children (cerebral blood flow velocity values of 131 and 130 cm/second compared with 130 and 137 cm/second in the 2 children with normal hemoglobin levels), this requires verification. It is of particular interest that our data suggest a relationship among snoring, increased cerebral blood flow velocities and indices of cognition (processing speed and visual attention) and perhaps behavioral (Behavior Rating Inventory of Executive Function) function. This finding is preliminary: a causal relationship is not established, and the physiologic mechanisms underlying such a relationship are not clear. Prospective studies that quantify cumulative exposure to the physiologic consequences of sleep-disordered breathing, such as hypoxia, would be informative.
doi:10.1542/peds.2006-0092
PMCID: PMC1995426  PMID: 17015501
sleep disordered breathing; cerebral blood flow; transcranial Doppler; executive function; neuropsychological function
22.  Astrocyte regulation of sleep circuits: experimental and modeling perspectives 
Integrated within neural circuits, astrocytes have recently been shown to modulate brain rhythms thought to mediate sleep function. Experimental evidence suggests that local impact of astrocytes on single synapses translates into global modulation of neuronal networks and behavior. We discuss these findings in the context of current conceptual models of sleep generation and function, each of which have historically focused on neural mechanisms. We highlight the implications and the challenges introduced by these results from a conceptual and computational perspective. We further provide modeling directions on how these data might extend our knowledge of astrocytic properties and sleep function. Given our evolving understanding of how local cellular activities during sleep lead to functional outcomes for the brain, further mechanistic and theoretical understanding of astrocytic contribution to these dynamics will undoubtedly be of great basic and translational benefit.
doi:10.3389/fncom.2012.00065
PMCID: PMC3428699  PMID: 22973222
glia; astrocytes; sleep; ATP; adenosine; neuronal networks; slow oscillations; computational models
23.  Musculoskeletal diseases—tendon 
British Medical Bulletin  2011;99(1):211-225.
Introduction
Tendons establish specific connections between muscles and the skeleton by transferring contraction forces from skeletal muscle to bone thereby allowing body movement. Tendon physiology and pathology are heavily dependent on mechanical stimuli. Tendon injuries clinically represent a serious and still unresolved problem since damaged tendon tissues heal very slowly and no surgical treatment can restore a damaged tendon to its normal structural integrity and mechanical strength. Understanding how mechanical stimuli regulate tendon tissue homeostasis and regeneration will improve the treatment of adult tendon injuries that still pose a great challenge in today's medicine.
Source of data
This review summarizes the current status of tendon treatment and discusses new directions from the point of view of cell-based therapy and regenerative medicine approach. We searched the available literature using PubMed for relevant original articles and reviews.
Growing points
Identification of tendon cell markers has enabled us to study precisely tendon healing and homeostasis. Clinically, tissue engineering for tendon injuries is an emerging technology comprising elements from the fields of cellular source, scaffold materials, growth factors/cytokines and gene delivering systems.
Areas timely for developing research
The clinical settings to establish appropriate microenvironment for injured tendons with the combination of these novel cellular- and molecular-based scaffolds will be critical for the treatment.
doi:10.1093/bmb/ldr025
PMCID: PMC3202301  PMID: 21729872
tendon injury; tissue engineering; regenerative medicine; stem cells; scleraxis; mechanical force
24.  Transdisciplinarity as an Inference Technique to Achieve a Better Understanding in the Health and Environmental Sciences 
The problems of the world are not categorised into disciplines. They are far more complex, a reality that the tradition of transdisciplinary research has recognised. When faced with questions in public health and sustainability, the traditional scientific paradigm often seems inadequate, and, at least in medicine, transdisciplinary research has not yet been fully appreciated or acknowledged. This lack of recognition may be partly caused by a lack of cooperation between disciplines and between science and society. In this paper, I discuss some of the challenges that scientists and policymakers face in public health and environment within a methodological context. I present transdisciplinarity as a modern research tool that should be applied in research in health and the environment and argue that these topics can be approached beyond the inherent obstacle of incommensurability between disciplines. Thus, a small step might be taken in this immense research arena.
doi:10.3390/ijerph7062692
PMCID: PMC2905573  PMID: 20644696
integrative patterns; cooperation; ecology; human behaviour; philosophy of science; collaboration; sustainability; methodology; globalisation
25.  Crossing the Quality Chasm: It Takes a Team to Build the Bridge 
The Ochsner Journal  2012;12(4):389-393.
The paradigm shifts in healthcare delivery now more than ever call for interdisciplinary teamwork to deliver the best patient care. The lessons from the Institute of Medicine's To Err Is Human: Building a Safer Health System report are painful but elucidate the problems with training and working in silos and the consequent inconsistent communication between healthcare providers. We review the literature regarding interprofessional training and describe some strategies and innovations. This article proposes that healthcare professional schools embed interprofessional education into the curriculum to meet the challenges of providing high-quality, efficient, and safe patient care.
PMCID: PMC3527871  PMID: 23267270
Interprofessional training; professional development; quality improvement teamwork

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