The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

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Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group

Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer

https://journal.chestnet.org/article/S0012-3692(12)60122-6/pdf

Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO 2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome

UNLABELLED In early August 2007, the Medical Advisory Secretariat began work on the Aging in the Community project, an evidence-based review of the literature surrounding healthy aging in the community. The Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the ministry's newly released Aging at Home Strategy.After a broad literature review and consultation with experts, the secretariat identified 4 key areas that strongly predict an elderly person's transition from independent community living to a long-term care home. Evidence-based analyses have been prepared for each of these 4 areas: falls and fall-related injuries, urinary incontinence, dementia, and social isolation. For the first area, falls and fall-related injuries, an economic model is described in a separate report.Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html, to review these titles within the Aging in the Community series.AGING IN THE COMMUNITY: Summary of Evidence-Based AnalysesPrevention of Falls and Fall-Related Injuries in Community-Dwelling Seniors: An Evidence-Based AnalysisBehavioural Interventions for Urinary Incontinence in Community-Dwelling Seniors: An Evidence-Based AnalysisCaregiver- and Patient-Directed Interventions for Dementia: An Evidence-Based AnalysisSocial Isolation in Community-Dwelling Seniors: An Evidence-Based AnalysisThe Falls/Fractures Economic Model in Ontario Residents Aged 65 Years and Over (FEMOR) OBJECTIVE: To identify interventions that may be effective in reducing the probability of an elderly person's falling and/or sustaining a fall-related injury. BACKGROUND Although estimates of fall rates vary widely based on the location, age, and living arrangements of the elderly population, it is estimated that each year approximately 30% of community-dwelling individuals aged 65 and older, and 50% of those aged 85 and older will fall. Of those individuals who fall, 12% to 42% will have a fall-related injury. Several meta-analyses and cohort studies have identified falls and fall-related injuries as a strong predictor of admission to a long-term care (LTC) home. It has been shown that the risk of LTC home admission is over 5 times higher in seniors who experienced 2 or more falls without injury, and over 10 times higher in seniors who experienced a fall causing serious injury. Falls result from the interaction of a variety of risk factors that can be both intrinsic and extrinsic. Intrinsic factors are those that pertain to the physical, demographic, and health status of the individual, while extrinsic factors relate to the physical and socio-economic environment. Intrinsic risk factors can be further grouped into psychosocial/demographic risks, medical risks, risks associated with activity level and dependence, and medication risks. Commonly described extrinsic risks are tripping hazards, balance and slip hazards, and vision hazards. NOTE: It is recognized that the terms "senior" and "elderly" carry a range of meanings for different audiences; this report generally uses the former, but the terms are treated here as essentially interchangeable. EVIDENCE-BASED ANALYSIS OF EFFECTIVENESS: RESEARCH QUESTION Since many risk factors for falls are modifiable, what interventions (devices, systems, programs) exist that reduce the risk of falls and/or fall-related injuries for community-dwelling seniors? INCLUSION AND EXCLUSION CRITERIA INCLUSION CRITERIA English language;published between January 2000 and September 2007;population of community-dwelling seniors (majority aged 65+); andrandomized controlled trials (RCTs), quasi-experimental trials, systematic reviews, or meta-analyses. EXCLUSION CRITERIA special populations (e.g., stroke or osteoporosis; however, studies restricted only to women were included);studies only reporting surrogate outcomes; orstudies whose outcome cannot be extracted for meta-analysis. OUTCOMES OF INTEREST number of fallers, andnumber of falls resulting in injury/fracture. SEARCH STRATEGY A search was performed in OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published between January 2000 and September 2007. Furthermore, all studies included in a 2003 Cochrane review were considered for inclusion in this analysis. Abstracts were reviewed by a single author, and studies meeting the inclusion criteria outlined above were obtained. Studies were grouped based on intervention type, and data on population characteristics, fall outcomes, and study design were extracted. Reference lists were also checked for relevant studies. The quality of the evidence was assessed as high, moderate, low, or very low according to the GRADE methodology. SUMMARY OF FINDINGS The following 11 interventions were identified in the literature search: exercise programs, vision assessment and referral, cataract surgery, environmental modifications, vitamin D supplementation, vitamin D plus calcium supplementation, hormone replacement therapy (HRT), medication withdrawal, gait-stabilizing devices, hip protectors, and multifactorial interventions. Exercise programs were stratified into targeted programs where the exercise routine was tailored to the individuals' needs, and untargeted programs that were identical among subjects. Furthermore, analyses were stratified by exercise program duration (<6 months and ≥6 months) and fall risk of study participants. Similarly, the analyses on the environmental modification studies were stratified by risk. Low-risk study participants had had no fall in the year prior to study entry, while high-risk participants had had at least one fall in the previous year. A total of 17 studies investigating multifactorial interventions were identified in the literature search. Of these studies, 10 reported results for a high-risk population with previous falls, while 6 reported results for study participants representative of the general population. One study provided stratified results by fall risk, and therefore results from this study were included in each stratified analysis. Executive Summary Table 1:Summary of Meta-Analyses of Studies Investigating the Effectiveness of Interventions on the Risk of Falls in Community-Dwelling Seniors(*)InterventionRR [95% CI]GRADEExercise programs  1. Targeted programs        General population0.81 [0.67-0.98]Low      High-risk population0.93 [0.82-1.06]High      Short duration0.91 [0.73-1.13]High      Long duration0.89 [0.79-1.01]Moderate  2. Untargeted programs        General population0.78 [0.66-0.91]Moderate      High-risk population0.89 [0.72-1.10]Very low      Short duration0.85 [0.71-1.01]Low      Long duration0.76 [0.64-0.91]Moderate  3. Combined targeted vs. untargeted programs        General populationN/AN/A      High-risk population0.87 [0.57-1.34]Moderate      Short duration1.11 [0.73-1.70]High      Long duration0.73 [0.57-0.95]HighVision intervention      Assessment/referral1.12 [0.82-1.53]Moderate      Cataract surgery1.11 [0.92-1.35]ModerateEnvironmental modifications      Low-risk population1.03 [0.75-1.41]High      High-risk population0.66 [0.54-0.81]High      General population0.85 [0.75-0.97]HighDrugs/Nutritional supplements      Vitamin D (men and women)0.94 [0.77-1.14]High      Vitamin D (women only)0.55 [0.29-1.08]Moderate      Vitamin D and calcium (men and women)0.89 [0.74-1.07]Moderate      Vitamin D and calcium (women only)0.83 [0.73-0.95]Moderate      Hormone replacement therapy0.98 [0.80-1.20]Low      Medication withdrawal0.34 [0.16-0.74]†LowGait-stabilizing device0.43 [0.29-0.64]ModerateMultifactorial intervention      Geriatric screening (general population)0.87 [0.69-1.10]Very low      High-risk population0.86 [0.75-0.98]Low*CI refers to confidence interval; RR, relative risk.†Hazard ratio is reported, because RR was not available.Executive Summary Table 2:Summary of Meta-Analyses of Studies Investigating the Effectiveness of Interventions on the Risk of Fall-Related Injuries in Community-Dwelling Seniors*InterventionRR [95% CI]GRADEExercise programs      Targeted programs0.67 [0.51-0.89]Moderate    Untargeted programs0.57 [0.38-0.86]Low    Combined targeted vs untargeted programs0.31 [0.13-0.74]HighDrugs/nutritional supplements      Vitamin D plus calcium (women only)0.77 [0.49-1.21]ModerateGait-stabilizing device0.10 [0.01-0.74]ModerateHip protectors3.49 [0.68-17.97]†LowMultifactorial intervention      Geriatric screening (general population)0.90 [0.53-1.51]Low    High-risk population0.86 [0.66-1.11]Moderate*CI refers to confidence interval; RR, relative risk.†Odds ratio is reported, because RR was not available. CONCLUSIONS High-quality evidence indicates that long-term exercise programs in mobile seniors and environmental modifications in the homes of frail elderly persons will effectively reduce falls and possibly fall-related injuries in Ontario's elderly population.A combination of vitamin D and calcium supplementation in elderly women will help reduce the risk of falls by more than 40%.The use of outdoor gait-stabilizing devices for mobile seniors during the winter in Ontario may reduce falls and fall-related injuries; however, evidence is limited and more research is required in this area.While psychotropic medication withdrawal may be an effective method for reducing falls, evidence is limited and long-term compliance has been demonstrated to be difficult to achieve.Multifactorial interventions in high-risk populations may be effective; however, the effect is only marginally significant, and the quality of evidence is low.

Prevention of falls and fall-related injuries in community-dwelling seniors: an evidence-based analysis.

OBJECTIVE An application was received to review the evidence on the 'The Da Vinci Surgical System' for the treatment of gynecologic malignancies (e.g. endometrial and cervical cancers). Limitations to the current standard of care include the lack of trained physicians on minimally invasive surgery and limited access to minimally invasive surgery for patients. The potential benefits of 'The Da Vinci Surgical System' include improved technical manipulation and physician uptake leading to increased surgeries, and treatment and management of these cancers. The demand for robotic surgery for the treatment and management of prostate cancer has been increasing due to its alleged benefits of recovery of erectile function and urinary continence, two important factors of men's health. The potential technical benefits of robotic surgery leading to improved patient functional outcomes are surgical precision and vision. CLINICAL NEED Uterine and cervical cancers represent 5.4% (4,400 of 81,700) and 1.6% (1,300 of 81,700), respectively, of incident cases of cancer among female cancers in Canada. Uterine cancer, otherwise referred to as endometrial cancer is cancer of the lining of the uterus. The most common treatment option for endometrial cancer is removing the cancer through surgery. A surgical option is the removal of the uterus and cervix through a small incision in the abdomen using a laparoscope which is referred to as total laparoscopic hysterectomy. Risk factors that increase the risk of endometrial cancer include taking estrogen replacement therapy after menopause, being obese, early age at menarche, late age at menopause, being nulliparous, having had high-dose radiation to the pelvis, and use of tamoxifen. Cervical cancer occurs at the lower narrow end of the uterus. There are more treatment options for cervical cancer compared to endometrial cancer, however total laparoscopic hysterectomy is also a treatment option. Risk factors that increase the risk for cervical cancer are multiple sexual partners, early sexual activity, infection with the human papillomavirus, and cigarette smoking, whereas barrier-type of contraception as a risk factor decreases the risk of cervical cancer. Prostate cancer is ranked first in men in Canada in terms of the number of new cases among all male cancers (25,500 of 89,300 or 28.6%). The impact on men who develop prostate cancer is substantial given the potential for erectile dysfunction and urinary incontinence. Prostate cancer arises within the prostate gland, which resides in the male reproductive system and near the bladder. Radical retropubic prostatectomy is the gold standard treatment for localized prostate cancer. Prostate cancer affects men above 60 years of age. Other risk factors include a family history of prostate cancer, being of African descent, being obese, consuming a diet high in fat, physical inactivity, and working with cadium. THE DA VINCI SURGICAL SYSTEM: The Da Vinci Surgical System is a robotic device. There are four main components to the system: 1) the surgeon's console, where the surgeon sits and views a magnified three-dimensional image of the surgical field; 2) patient side-cart, which sits beside the patient and consists of three instrument arms and one endoscope arm; 3) detachable instruments (endowrist instruments and intuitive masters), which simulate fine motor human movements. The hand movements of the surgeon's hands at the surgeon's console are translated into smaller ones by the robotic device and are acted out by the attached instruments; 4) three-dimensional vision system: the camera unit or endoscope arm. The main advantages of use of the robotic device are: 1) the precision of the instrument and improved dexterity due to the use of "wristed" instruments; 2) three-dimensional imaging, with improved ability to locate blood vessels, nerves and tissues; 3) the surgeon's console, which reduces fatigue accompanied with conventional laparoscopy surgery and allows for tremor-free manipulation. The main disadvantages of use of the robotic device are the costs including instrument costs ($2.6 million in US dollars), cost per use ($200 per use), the costs associated with training surgeons and operating room personnel, and the lack of tactile feedback, with the trade-off being increased visual feedback. RESEARCH QUESTIONS For endometrial and cervical cancers, 1. What is the effectiveness of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers?2. What are the incremental costs of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers?For prostate cancer, 3. What is the effectiveness of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer?4. What are the incremental costs of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer? RESEARCH METHODS LITERATURE SEARCH SEARCH STRATEGY A literature search was performed on May 12, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, Wiley Cochrane, CINAHL, Centre for Reviews and Dissemination/International Agency for Health Technology Assessment for studies published from January 1, 2000 until May 12, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. INCLUSION CRITERIA English language articles (January 1, 2000-May 12, 2010)Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a primary data source (e.g. obtained in a clinical setting)Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a secondary data source (e.g. hospital- or population-based registries)Study design and methods must be clearly describedHealth technology assessments, systematic reviews, randomized controlled trials, non-randomized controlled trials and/or cohort studies, case-case studies, regardless of sample size, cost-effectiveness studies EXCLUSION CRITERIA Duplicate publications (with the more recent publication on the same study population included)Non-English papersAnimal or in-vitro studiesCase reports or case series without a referent or comparison groupStudies on long-term survival which may be affected by treatmentStudies that do not examine the cancers (e.g. advanced disease) or outcomes of interest OUTCOMES OF INTEREST For endometrial and cervical cancers, Primary outcomes: Morbidity factors- Length of hospitalization- Number of complicationsPeri-operative factors- Operation time- Amount of blood loss- Number of conversions to laparotomyNumber of lymph nodes recoveredFor prostate cancer, Primary outcomes: Morbidity factors- Length of hospitalization- Amount of morphine use/painPeri-operative factors- Operation time- Amount of blood loss- Number of transfusions- Duration of catheterization- Number of complications- Number of anastomotic stricturesNumber of lymph nodes recoveredOncologic factors- Proportion of positive surgical marginsLong-term outcomes- Urinary continence- Erectile function SUMMARY OF FINDINGS Robotic use for gynecologic oncology compared to:LAPAROTOMY: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations.The beneficial effect of robotic surgery was shown in pooled analysis for complications, owing to increased sample size.More work is needed to clarify the role of complications in terms of safety, including improved study designs, analysis and measurement.LAPAROSCOPY: benefits of robotic surgery in terms of shorter length of hospitalization, less blood loss and fewer conversions to laparotomy likely owing to the technical difficulty of conventional laparoscopy, in the context of study design limitations.Clinical significance of significant findings for length of hospitalizations and blood loss is low.Fewer conversions to laparotomy indicate clinical effectiveness in terms of reduced morbidity.Robotic use for urologic oncology, specifically prostate cancer, compared to:RETROPUBIC SURGERY: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss/fewer individuals requiring transfusions. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations. There was a beneficial effect in terms of decreased positive surgical margins and erectile dysfunction. These results indicate clinical effectiveness in terms of improved cancer control and functional outcomes, respectively, in the context of study design limitations.Surgeon skill had an impact on cancer control and functional outcomes.The results for complications were inconsistent when measured as either total number of complications, pain management or anastomosis. (ABSTRACT TRUNCATED)

Robotic-assisted minimally invasive surgery for gynecologic and urologic oncology: an evidence-based analysis.

OBJECTIVE The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario. CLINICAL NEED TARGET POPULATION AND CONDITION Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies. THE TECHNOLOGY BEING REVIEWED There is no 'gold standard' for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs. In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as "The Sleep Book." The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered. Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective. Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value. At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments. METHODS REVIEW STRATEGY There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature. To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed. DIFFUSION OF SLEEP LABORATORIES: To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases. SUMMARY OF FINDINGS LITERATURE REVIEW A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study. PREVALENCE Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men. Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups. DIAGNOSTIC VALUE OF POLYSOMNOGRAPHY: It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined. Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population. OBSTRUCTIVE SLEEP APNEA AND OBESITY: Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m(2)) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals. OBSTRUCTIVE SLEEP APNEA AND CARDIOVASCULAR DISEASES: Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values. A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m(2); range = 32.30-68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension. (ABSTRACT TRUNCATED)

Polysomnography in patients with obstructive sleep apnea: an evidence-based analysis.

The objective of this analysis was to evaluate the effectiveness and cost-effectiveness of the bispectral index (BIS) monitor, a commercial device to assess the depth of anesthesia. Conventional methods to assess depth of consciousness, such as cardiovascular and pulmonary measures (e.g., heart rate, systolic/diastolic blood pressure, mean arterial pressure, respiratory rate, and level of oxygen in the blood), and clinical signs (e.g., perspiration, shedding of tears, and limb movement) are not reliable methods to evaluate the brain status of anesthetized patients. Recent progress in understanding the electrophysiology of the brain has led to the development of cerebral monitoring devices that identify changes in electrophysiologic brain activity during general anesthesia. The BIS monitor, derived from electroencephalogram (EEG) data, has been used as a statistical predictor of the level of hypnosis and has been proposed as a tool to reduce the risk of intraoperative awareness. Anesthesia that is too light can result in the recall of events or conversations that happen in the operation room. Patients have recalled explicit details of conversations that happened while under anesthesia. This awareness is frightening for patients and can lead to post-traumatic stress disorder. Conversely, anesthesia that is too deep can cause hemodynamic disturbances necessitating the use of vasoconstrictor agents, which constrict blood vessels, to maintain normal blood pressure and cardiac output. Overly deep anesthesia can also result in respiratory depression requiring respiratory assistance postoperatively. Monitoring the depth of anaesthesia should prevent intraoperative awareness and help to ensure that an exact dose of anaesthetic drugs is given to minimize adverse cardiovascular effects caused by overly large doses. Researchers have suggested that cerebral monitoring can be used to assess the depth of anesthesia, prevent awareness, and speed early recovery after general anesthesia by optimizing drug delivery to each patient. Awareness is a rare complication in general anesthesia. The risk of intraoperative awareness varies among countries, depending on their anesthetic practices. In the United States, the incidence of intraoperative awareness is 0.1% to 0.2% of patients undergoing general anesthesia. The incidence of intraoperative awareness depends on the type of surgery. Trauma patients have reported the highest incidence of intraoperative awareness (11%-43%) followed by patients undergoing cardiac surgery (1.14%) and patients undergoing Cesarean section (0.9%). The BIS monitor, licensed by Health Canada, is the first quantitative EEG index used in clinical practice as a monitor to assess the depth of anesthesia. It consists of a sensor, a digital signal converter, and a monitor. The sensor is placed on the patient's forehead to pick up the electrical signals from the cerebral cortex and transfer them to the digital signal converter. A BIS score quantifies changes in the electrophysiologic state of the brain during anesthesia. In patients who are awake, a typical BIS score is 90 to 100. Complete suppression of cortical activity results in a BIS score of 0, known as a flat line. Lower numbers indicate a higher hypnotic effect. Overall, a BIS value below 60 is associated with a low probability of response to commands. There are several alternative technologies to quantify the depth of anesthesia, but only the BIS and SNAP monitors are licensed in Canada. The list price of the BIS monitor is $13,500 (Cdn). The sensors cost $773 (Cdn) for a box of 25. Because intraoperative awareness and recall happen rarely, only 1 randomized controlled trial of all the studies reviewed, was adequately powered to show the impact of BIS monitoring. This was a large prospective, randomized, double-blinded, multicentre study that was designed to investigate if BIS-guided anesthesia reduces the incidence of intraoperative awareness. The study confirmed 2 cases of intraoperative awareness in the BIS group and 11 cases in the standard practice group. This difference was statistically significant (P =.022). There were 36 reports of possible awareness that were not confirmed by the study group (20 patients in the BIS group and 16 in the standard practice group). Additionally, the results of small randomized controlled trials and prospective cohort studies show that, overall, BIS monitoring is relatively good at indicating the state of being alert; however, its algorithm does not accurately predict an unconscious state. BIS monitoring has low sensitivity for the detection of the state of being asleep, and it may show values higher than 60 in those already asleep. Therefore, an unknown percentage of patients will not be identified as being asleep and will receive anesthetics unnecessarily. Based on the literature review, the Medical Advisory Secretariat concludes the following: Prevention of awareness should remain a clinical decision for anesthesiologists to make based on their experience with intraoperative awareness in their practices.Although BIS monitoring may have a positive impact on reducing the incidence of intraoperative awareness in the general population, its negative impact on individual patients may overshadow this positive outcome.BIS monitoring is good at indicating an "alert" state, which is why it can reduce the incidence of intraoperative awareness; however, its algorithm does not accurately predict an "asleep" state. This means an unknown percentage of patients who are already asleep will not be identified because of falsely elevated BIS values. These patients will receive unnecessary dosage of anesthetics resulting in a deep hypnotic state.Adherence to the practice guidelines will reduce the risk of intraoperative awareness.

Bispectral index monitor: an evidence-based analysis.

UNLABELLED This report from the Medical Advisory Secretariat (MAS) was intended to evaluate the clinical utility of vitamin D testing in average risk Canadians and in those with kidney disease. As a separate analysis, this report also includes a systematic literature review of the prevalence of vitamin D deficiency in these two subgroups.This evaluation did not set out to determine the serum vitamin D thresholds that might apply to non-bone health outcomes. For bone health outcomes, no high or moderate quality evidence could be found to support a target serum level above 50 nmol/L. Similarly, no high or moderate quality evidence could be found to support vitamin D's effects in non-bone health outcomes, other than falls. VITAMIN D: Vitamin D is a lipid soluble vitamin that acts as a hormone. It stimulates intestinal calcium absorption and is important in maintaining adequate phosphate levels for bone mineralization, bone growth, and remodelling. It's also believed to be involved in the regulation of cell growth proliferation and apoptosis (programmed cell death), as well as modulation of the immune system and other functions. Alone or in combination with calcium, Vitamin D has also been shown to reduce the risk of fractures in elderly men (≥ 65 years), postmenopausal women, and the risk of falls in community-dwelling seniors. However, in a comprehensive systematic review, inconsistent results were found concerning the effects of vitamin D in conditions such as cancer, all-cause mortality, and cardiovascular disease. In fact, no high or moderate quality evidence could be found concerning the effects of vitamin D in such non-bone health outcomes. Given the uncertainties surrounding the effects of vitamin D in non-bone health related outcomes, it was decided that this evaluation should focus on falls and the effects of vitamin D in bone health and exclusively within average-risk individuals and patients with kidney disease. Synthesis of vitamin D occurs naturally in the skin through exposure to ultraviolet B (UVB) radiation from sunlight, but it can also be obtained from dietary sources including fortified foods, and supplements. Foods rich in vitamin D include fatty fish, egg yolks, fish liver oil, and some types of mushrooms. Since it is usually difficult to obtain sufficient vitamin D from non-fortified foods, either due to low content or infrequent use, most vitamin D is obtained from fortified foods, exposure to sunlight, and supplements. CLINICAL NEED CONDITION AND TARGET POPULATION Vitamin D deficiency may lead to rickets in infants and osteomalacia in adults. Factors believed to be associated with vitamin D deficiency include: darker skin pigmentation,winter season,living at higher latitudes,skin coverage,kidney disease,malabsorption syndromes such as Crohn's disease, cystic fibrosis, andgenetic factors.Patients with chronic kidney disease (CKD) are at a higher risk of vitamin D deficiency due to either renal losses or decreased synthesis of 1,25-dihydroxyvitamin D. Health Canada currently recommends that, until the daily recommended intakes (DRI) for vitamin D are updated, Canada's Food Guide (Eating Well with Canada's Food Guide) should be followed with respect to vitamin D intake. Issued in 2007, the Guide recommends that Canadians consume two cups (500 ml) of fortified milk or fortified soy beverages daily in order to obtain a daily intake of 200 IU. In addition, men and women over the age of 50 should take 400 IU of vitamin D supplements daily. Additional recommendations were made for breastfed infants. A Canadian survey evaluated the median vitamin D intake derived from diet alone (excluding supplements) among 35,000 Canadians, 10,900 of which were from Ontario. Among Ontarian males ages 9 and up, the median daily dietary vitamin D intake ranged between 196 IU and 272 IU per day. Among females, it varied from 152 IU to 196 IU per day. In boys and girls ages 1 to 3, the median daily dietary vitamin D intake was 248 IU, while among those 4 to 8 years it was 224 IU. VITAMIN D TESTING: Two laboratory tests for vitamin D are available, 25-hydroxy vitamin D, referred to as 25(OH)D, and 1,25-dihydroxyvitamin D. Vitamin D status is assessed by measuring the serum 25(OH)D levels, which can be assayed using radioimmunoassays, competitive protein-binding assays (CPBA), high pressure liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). These may yield different results with inter-assay variation reaching up to 25% (at lower serum levels) and intra-assay variation reaching 10%. The optimal serum concentration of vitamin D has not been established and it may change across different stages of life. Similarly, there is currently no consensus on target serum vitamin D levels. There does, however, appear to be a consensus on the definition of vitamin D deficiency at 25(OH)D < 25 nmol/l, which is based on the risk of diseases such as rickets and osteomalacia. Higher target serum levels have also been proposed based on subclinical endpoints such as parathyroid hormone (PTH). Therefore, in this report, two conservative target serum levels have been adopted, 25 nmol/L (based on the risk of rickets and osteomalacia), and 40 to 50 nmol/L (based on vitamin D's interaction with PTH). ONTARIO CONTEXT: VOLUME #ENTITYSTARTX00026; COST: The volume of vitamin D tests done in Ontario has been increasing over the past 5 years with a steep increase of 169,000 tests in 2007 to more than 393,400 tests in 2008. The number of tests continues to rise with the projected number of tests for 2009 exceeding 731,000. According to the Ontario Schedule of Benefits, the billing cost of each test is $51.7 for 25(OH)D (L606, 100 LMS units, $0.517/unit) and $77.6 for 1,25-dihydroxyvitamin D (L605, 150 LMS units, $0.517/unit). Province wide, the total annual cost of vitamin D testing has increased from approximately $1.7M in 2004 to over $21.0M in 2008. The projected annual cost for 2009 is approximately $38.8M. EVIDENCE-BASED ANALYSIS: The objective of this report is to evaluate the clinical utility of vitamin D testing in the average risk population and in those with kidney disease. As a separate analysis, the report also sought to evaluate the prevalence of vitamin D deficiency in Canada. The specific research questions addressed were thus: What is the clinical utility of vitamin D testing in the average risk population and in subjects with kidney disease?What is the prevalence of vitamin D deficiency in the average risk population in Canada?What is the prevalence of vitamin D deficiency in patients with kidney disease in Canada?Clinical utility was defined as the ability to improve bone health outcomes with the focus on the average risk population (excluding those with osteoporosis) and patients with kidney disease. LITERATURE SEARCH A literature search was performed on July 17th, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1998 until July 17th, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Observational studies that evaluated the prevalence of vitamin D deficiency in Canada in the population of interest were included based on the inclusion and exclusion criteria listed below. The baseline values were used in this report in the case of interventional studies that evaluated the effect of vitamin D intake on serum levels. Studies published in grey literature were included if no studies published in the peer-reviewed literature were identified for specific outcomes or subgroups. Considering that vitamin D status may be affected by factors such as latitude, sun exposure, food fortification, among others, the search focused on prevalence studies published in Canada. In cases where no Canadian prevalence studies were identified, the decision was made to include studies from the United States, given the similar policies in vitamin D food fortification and recommended daily intake. INCLUSION CRITERIA Studies published in EnglishPublications that reported the prevalence of vitamin D deficiency in CanadaStudies that included subjects from the general population or with kidney diseaseStudies in children or adultsStudies published between January 1998 and July 17(th) 2009 EXCLUSION CRITERIA: Studies that included subjects defined according to a specific disease other than kidney diseaseLetters, comments, and editorialsStudies that measured the serum vitamin D levels but did not report the percentage of subjects with serum levels below a given threshold OUTCOMES OF INTEREST Prevalence of serum vitamin D less than 25 nmol/LPrevalence of serum vitamin D less than 40 to 50 nmol/LSerum 25-hydroxyvitamin D was the metabolite used to assess vitamin D status. Results from adult and children studies were reported separately. Subgroup analyses according to factors that affect serum vitamin D levels (e.g., seasonal effects, skin pigmentation, and vitamin D intake) were reported if enough information was provided in the studies QUALITY OF EVIDENCE The quality of the prevalence studies was based on the method of subject recruitment and sampling, possibility of selection bias, and generalizability to the source population. The overall quality of the trials was examined according to the GRADE Working Group criteria. (ABSTRACT TRUNCATED)

Medical Advisory Secretariat

Papers

Prevention of falls and fall-related injuries in community-dwelling seniors: an evidence-based analysis.

Robotic-assisted minimally invasive surgery for gynecologic and urologic oncology: an evidence-based analysis.

Polysomnography in patients with obstructive sleep apnea: an evidence-based analysis.

Bispectral index monitor: an evidence-based analysis.

Clinical utility of vitamin d testing: an evidence-based analysis.