Hypovitaminosis D in the Middle East and North Africa A Treatment Trial of Vitamin D Supplementation in Breast-fed Infants: Universal Supplementation Is Not Necessary for Rickets Prevention in Southern Louisiana National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee Prospective study of vitamin D supplementation and rickets in China. Obesity in children. Part 2: Prevention and management The vitamin E debate: implications for ongoing trials of pre‐eclampsia prevention Abnormal uterine bleeding in pre-menopausal women. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Card Serum alkaline phosphatase and urinary hydroxyproline values in children receiving phenobarbital with and without vitamin D. Comparisons of oral calcium, high dose vitamin D and a combination of these in the treatment of nutritional rickets in children. Assessing Care of Vulnerable Elders: Methods for Developing Quality Indicators Comparison between daily supplementation doses of 200 versus 400 IU of vitamin D in infants Antenatal corticosteroid therapy for fetal maturation. Vitamin-D-deficiency rickets in Kuwait: the prevalence of a preventable disease. Comparative Effectiveness Research: A Report From the Institute of Medicine Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials Recommendations for Teaching about Racial and Ethnic Disparities in Health and Health Care Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus The Surgical Infection Society guidelines on antimicrobial therapy for intra-abdominal infections: evidence for the recommendations. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary.
Background : The Middle East and North Africa ( MENA ) region registers some of the highest rates of hypovitaminosis D worldwide . Aim : We systematic ally review ed the prevalence of hypovitaminosis D , rickets and osteomalacia , their predictors and impact on major outcomes , in the region . Methods : Medline , Pubmed and Embase search engines , entering keywords and concepts , combined with individual countries of interest , were used . Search was limited years 2000–2012 ; and review articles were used for the period preceding year 2000 . Results : Rickets and osteomalacia still occur in this sunny region . Hypovitaminosis D prevails , with rates varying 30–90 % , considering a desirable serum 25 hydroxy-vitamin D [ 25(OH)D ] of 20 ng/ml . Advancing age , female gender , multi-parity , clothing style , season , socio-economic status and urban living are recognized predictors of hypovitaminosis D in adults . Prolonged breastfeeding without vitamin D supplementation and low dietary calcium intake are the recognized risk factors for rickets and hypovitaminosis D in children .. Associations with pain score and disease activity in rheumatologic disorders , viral load and interleukins in hepatitis C , BMI , lipids and insulin sensitivity , blood pressure , heart failure and mortality are described . Sun exposure in adults decreased prevalence of metabolic syndrome in one study . Few r and omized vitamin D trials revealed that the majority of mothers or children failed to achieve a desirable 25(OH)D level , even with doses by far exceeding current recommendations . A trial in adolescent girls reveals substantial bone and lean mass increments . Conclusion : Hypovitaminosis D is prevalent in MENA . The lack of population s based studies , gaps in studies in infants , pre-pubertal children and pregnant women , hinder the development of region specific guidelines and constitute a major obstacle to impact this chronic and most often sub clinical disease This study was conducted to determine if vitamin D supplementation is required to prevent rickets in breast-fed infants . Breast-feeding rates are increasing , and there are concerns about whether the vitamin D content of breast milk is sufficient . There are a few treatment trials of vitamin D supplementation in breast-fed infants ; these were conducted in northern climates . The authors therefore performed a prospect i ve clinical trial comparing vitamin D supplementation with placebo as control in southern Louisiana . Blood sample s and question naires were collected at birth , 2 , 4 , and 6 months of age . There were no cases of rickets observed , and no differences in alkaline phosphatase levels between groups . Thus , there was no evidence that vitamin D supplementation reduced rickets risk in the authors ’ study population . This suggests that the current recommendations for universal vitamin D supplementation of breast-fed infants throughout the United States may need to be revised National Institutes of Health ( NIH ) consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1 ) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality ( AHRQ ) , 2 ) presentations by investigators working in areas relevant to the conference questions during a 2-day public session , 3 ) questions and statements from conference attendees during open discussion periods that are part of the public session , and 4 ) closed deliberations by the panel during the remainder of the second day and the morning of the third . This statement is an independent report of the panel and is not a policy statement of the NIH or the federal government . The statement reflects the panel 's assessment of medical knowledge available at the time the statement was written . Thus , it provides a snapshot in time of the state of knowledge on the conference topic . When reading the statement , keep in mind that new knowledge is inevitably accumulating through medical research . At least half of American adults take a dietary supplement , the majority of which are multivitamin/multimineral ( MVM ) supplements . As more and more Americans seek strategies for maintaining good health and preventing disease , and as the marketplace offers an increasing number of products to fulfill that desire , it is important that consumers have the best possible information to make their choices . Assessing the available scientific evidence on the benefits of MVM supplement use for chronic disease prevention , identifying the gaps in the evidence , and recommending an appropriate research agenda to meet the shortfalls are subjects considered in this report . The word vitamine was coined in 1912 , as an abbreviated term meant to capture the notion of important factors in the diet , or vital amines . This was preceded more than 150 years earlier by British navy physician James Lind 's discoveryin the first recorded controlled trialthat citrus juice , a good source of what was found 2 centuries later to be vitamin C , could prevent scurvy in sailors . In 1913 , the first vitamin was isolated : thiamin , the deficiency of which caused beriberi . Thirteen vitamins and 15 essential minerals have now been identified as important to human nutrition . Large-scale fortification of diets began in the United States with the addition of iodine to table salt in 1924 to prevent goiter , followed by the addition of vitamin D to milk in 1933 to prevent rickets and the addition of thiamin , riboflavin , niacin , and iron to flour in 1941 . Multivitamin/multimineral products providing more than vitamins A and D became available in pharmacies and grocery stores in the mid-1930s . In the early 1940s , the first MVM tablet was introduced . Although clinical deficiency of vitamins or minerals , other than iron , is now uncommon in the United States , growth in supplement use has accelerated rapidly with marketing spurred by cl aims some based on scientific studies that chronic conditions could be prevented or treated by supplement use . Annual sales of supplements to Americans are now reported at about $ 23 billion , a substantial share of which is spent on vitamins and minerals . Because of such widespread use of MVM , increasing public and medical confusion over apparently contradictory results from studies , and reports of possible adverse effects from overuse in certain circumstances , the Office of Dietary Supplements and the Office of Medical Applications of Research of the NIH convened a State-of-the-Science Conference on Multivitamin/Mineral Supplements and Chronic Disease Prevention , held on 1517 May 2006 , in Bethesda , Maryl and . The goal of the conference was to assess the evidence available on MVM use and outcomes for chronic disease prevention in the generally healthy population of adults and to make recommendations for future research . The conference focused on vitamins and minerals and did not deal with botanicals , hormones , or other supplements . It also did not address the treatment of vitamin or mineral deficiencies . Except for considerations of safety , the conference also did not review issues of primary relevance to pregnant women or children . Specifically , the conference explored the following key questions : 1 ) What are the current patterns and prevalence of the public 's use of MVM supplements ? 2 ) What is known about the dietary nutrient intake of MVM users versus nonusers ? 3 ) What is the efficacy of single vitamin/mineral supplement use in chronic disease prevention ? 4 ) What is the efficacy of MVM  in chronic disease prevention in the general population of adults ? 5 ) What is known about the safety of MVM  for the generally healthy population ? and 6 ) What are the major knowledge gaps and research opportunities regarding MVM use ? During the first 2 days of the conference , experts presented information on each of the key questions . After weighing the scientific evidence , including the data presented by the speakers and a formal evidence report commissioned through AHRQ , an independent panel prepared and presented a draft of this state-of-the-science statement addressing the conference questions . The evidence report prepared for the conference is available at www.ahrq.gov/clinic/tp/multivittp.htm . For the purpose of this statement , the term MVM refers to any supplement containing 3 or more vitamins and minerals but no herbs , hormones , or drugs , with each component at a dose less than the tolerable upper level determined by the Food and Nutrition Boardthe maximum daily intake likely to pose no risk for adverse health effects . Our review also included studies of the relationship of single-nutrient supplements and 2-nutrient supplements to certain disease outcomes . The term primary prevention refers to preventing the development of disease in a person who does not have the disease in question . The chronic conditions assessed include cancer ; age-related sensory loss ; and cardiovascular , endocrine , neurologic , musculoskeletal , gastroenterologic , renal , and pulmonary diseases . A word is warranted about the nature of the evidence base considered by the panel . The range of vitamins and minerals of possible interest was so broad that the conference planning committee chose to focus the evidence report on nutrients for which the potential for impact had been most strongly suggested and on conditions for which supplements were thought to have the most potential influence . The planning committee also limited the scope of the evidence report to consideration of r and omized , controlled trials ( RCTs ) , which are generally considered the gold st and ard for evidence -based decision making . These are studies in which participants are allocated by chance alone to receive or not to receive 1 of 2 or more clinical interventions . For example , while folate supplementation was initially shown to decrease the risk for neural tube defects in animal studies , outcome data in nonhuman models were not considered sufficient evidence on which to base policy recommendations . At the next level of evidence , observational studies in humans suggested efficacy of folate supplementation to prevent such defects . However , these were criticized because they were not r and omized and were potentially subject to bias . Not until these findings were confirmed by RCTs in humans was public policy implemented , including fortification of cereal grains with folate . An observational study is one in which the exposure or treatment of interest is not assigned to the participant by the investigator . Such studies suggested that -carotene intake might protect against the development of some types of cancer . However , RCTs of -carotene supplementation not only showed no benefit , they also found an increased risk for lung cancer in persons who smoked cigarettes or who were exposed to asbestos . These examples illustrate both the risk of relying only on observational studies and the advantage of RCTs in identifying both benefits and risks of MVM supplementation . Limiting the focus of our statement to RCTs has some inherent limitations , given the potential of other types of studies to provide important insights . Observational studies , for example , are particularly useful for generating hypotheses , defining adverse effects , and documenting long-term treatment consequences . They are often essential precursors to the well-conducted RCTs important for policy formation . Our principal recommendations focus on the compelling research activities that must be supported to better inform the decisions that millions of Americans are making each day to use or not to use MVM supplements to prevent chronic disease . At the same time , mindful of the constraints of the available evidence base , we have also taken care not to make premature recommendations about whether generally healthy Americans should or should not take MVM supplements . Because of the need for more reliable information on MVMs , we have made strong recommendations for research and for increased U.S. Food and Drug Administration ( FDA ) oversight of the MVM industry . 1 . What Are the Current Patterns and Prevalence of the Public 's Use of MVM Supplements ? More than half of American adults take dietary supplements in the belief that they will make them feel better , give them greater energy , improve their health , and prevent and treat disease . The use of supplements has been steadily increasing , and growth appears likely to continue . Currently , users spend more than $ 23 billion per year on supplements , and among this supplement-using population , MVM is the major category of supplements , used by about one third of Americans . Uncertainty remains in estimating prevalence of use because of problems defining these products ; increasing complexity in the formulation of supplements , including more non-MVM components and specialized formulas ; and varying frequency of use . It appears that use is higher Guidelines for clinical practice are aim ed to indicate preferred approaches to medical problems as established by scientifically valid research . Double-blind placebo controlled studies are preferable , but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine . When only data that will not withst and objective scrutiny are available , a recommendation is identified as a consensus of experts . Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aim ed to indicate the preferable but not necessarily the only acceptable approach to a specific problem . Guidelines are intended to be flexible and must be distinguished from st and ards of care , which are inflexible and rarely violated . Given the wide range of specifics in any health-care problem , the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision . Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees . Each has been intensely review ed and revised by the Committee , other experts in the field , physicians who will use them , and specialists in the science of decision analysis . The recommendations of each guideline are therefore considered valid at the time of composition based on the data available . New developments in medical research and practice pertinent to each guideline will be review ed at a time established and indicated at publication to assure continued validity . The recommendations made are based on the level of evidence found . Grade A recommendations imply that there is consistent level 1 evidence ( r and omized controlled trials ) , grade B indicates that the evidence would be level 2 or 3 , which are cohort studies or case – control studies . Grade C recommendations are based on level 4 studies , meaning case series or poor- quality cohort studies , and grade D recommendations are based on level 5 evidence , meaning expert opinion To determine whether amounts of vitamin D lower than recommended doses are effective in preventing rickets , 256 term infants from two northern and two southern cities in China were studied in a r and omized trial of vitamin D supplementation ( 100 , 200 , or 400 IU/day ) during the first 6 months of life . Cord blood and 6-month blood sample s were collected and radiographs were obtained at 3 to 5 days and at 6 months of age . Cord serum 25-hydroxyvitamin D concentrations were lower in the north than in the south ( 5 vs 14 ng/ml ( 12.5 vs 35.0 nmol/L ) ; p less than 0.01 ) . Wrist ossification centers were less likely to be present at birth in the northern children than in the southern children ( p = 0.009 ) and were more likely to be present in infants born in the fall who had higher cord serum concentrations of 25-hydroxyvitamin D ( p = 0.04 ) . Serum 25-hydroxyvitamin D concentrations were lower in northern children 6 months of age than in southern children ( p = 0.005 ) and were higher with an increasing supplemental dosage of vitamin D ( p less than 0.001 ) , particularly in infants in the north . None of the infants had rickets at 6 months of age . Because of the low serum 25-hydroxyvitamin D concentrations , especially among infants in the north , it may be prudent to supplement the diet with vitamin D at a dose of 400 IU/day # # # # Summary points In the first part of this article we described how obesity in children is measured , its prevalence , whether children should be screened , and the risk factors for and consequences of obesity.1 In this part we review the current evidence on the prevention and management of childhood obesity . # # # # Sources and selection criteria This review draws on the Foresight report , guidance from the National Institute for Health and Clinical Excellence and the Australian National Health Medical Research Council , and Cochrane review . In April 2008 we search ed the Cochrane Library data base of review s and the Centre for Review s and Dissemination data bases using the search term “ obesity ” . We also conducted a Medline search ( ( Child$ or paediatric or pediatric or adolescent ) and ( Obes$ or overweight ) ) limited to 1 January 2005 to 6 May 2008 and “ review articles ” ; this identified 1105 articles . We read the abstract s of these articles and retrieved relevant papers . We also used articles from our own bibliographies collected over the past 10 years . The evidence to support the measurement , prevention , and management of obesity in children is still relatively weak , with few r and omised controlled trials or systematic review s. The strength of evidence is developing and the up date d Cochrane review that will be published in 2009 A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia .  This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on  pre-eclampsia .  Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of  vitamin E  , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia BACKGROUND Abnormal uterine bleeding is the direct cause of a significant health care burden for women , their families , and society as a whole . Up to 30 % of women will seek medical assistance for this problem during their reproductive years . This guideline replaces previous clinical guidelines on the topic and is aim ed to enable health care providers with the tools to provide the latest evidence -based care in the diagnosis and the medical and surgical management of this common problem . OBJECTIVE To provide current evidence -based guidelines for the diagnosis and management of  abnormal uterine bleeding ( AUB ) among women of reproductive age . OUTCOMES Outcomes evaluated include the impact of AUB on quality of life and the results of interventions including medical and surgical management of AUB . METHODS Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of location in Canada , type of practice , subspecialty expertise , and general gynaecology background . The committee review ed relevant evidence in the English medical literature including published guidelines . Recommendations were established as consensus statements . The final document was review ed and approved by the Executive and Council of the SOGC . RESULTS This document provides a summary of up-to- date evidence regarding diagnosis , investigations , and medical and surgical management of AUB . The result ing recommendations may be adapted by individual health care workers when serving women with this condition . CONCLUSIONS Abnormal uterine bleeding is a common and sometimes debilitating condition in women of reproductive age . St and ardization of related terminology , a systematic approach to diagnosis and investigation , and a step-wise approach to intervention is necessary . Treatment commencing with medical therapeutic modalities followed by the least invasive surgical modalities achieving results satisfactory to the patient is the ultimate goal of all therapeutic interventions . EVIDENCE Published literature was retrieved through search es of MEDLINE and the Cochrane Library in March 2011 using appropriate controlled vocabulary ( e.g. uterine hemorrhage , menorrhagia ) and key words ( e.g. menorrhagia , heavy menstrual bleeding , abnormal uterine bleeding ) . Results were restricted to systematic review s , r and omized control trials/controlled clinical trials , and observational studies written in English and published from January 1999 to March 2011 . Search es were up date d on a regular basis and incorporated in the guideline to February 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology-related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies . VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care ( Table ) . BENEFITS , HARMS , AND COSTS Implementation of the guideline recommendations will improve the health and well-being of women with abnormal uterine bleeding , their families , and society . The economic cost of implementing these guidelines in the Canadian health care system was not considered BACKGROUND The purpose of this statement is to up date the recommendations by the American Heart Association ( AHA ) for the prevention of infective endocarditis that were last published in 1997 . METHODS AND RESULTS A writing group was appointed by the AHA for their expertise in prevention and treatment of infective endocarditis , with liaison members representing the American Dental Association , the Infectious Diseases Society of America , and the American Academy of Pediatrics . The writing group review ed input from national and international experts on infective endocarditis . The recommendations in this document reflect analyses of relevant literature regarding procedure-related bacteremia and infective endocarditis , in vitro susceptibility data of the most common microorganisms that cause infective endocarditis , results of prophylactic studies in animal models of experimental endocarditis , and retrospective and prospect i ve studies of prevention of infective endocarditis . MEDLINE data base search es from 1950 to 2006 were done for English- language papers using the following search terms : endocarditis , infective endocarditis , prophylaxis , prevention , antibiotic , antimicrobial , pathogens , organisms , dental , gastrointestinal , genitourinary , streptococcus , enterococcus , staphylococcus , respiratory , dental surgery , pathogenesis , vaccine , immunization , and bacteremia . The reference lists of the identified papers were also search ed . We also search ed the AHA online library . The American College of Cardiology/AHA classification of recommendations and levels of evidence for practice guidelines were used . The paper was subsequently review ed by outside experts not affiliated with the writing group and by the AHA Science Advisory and Coordinating Committee . CONCLUSIONS The major changes in the up date d recommendations include the following : ( 1 ) The Committee concluded that only an extremely small number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures even if such prophylactic therapy were 100 % effective . ( 2 ) Infective endocarditis prophylaxis for dental procedures is reasonable only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis . ( 3 ) For patients with these underlying cardiac conditions , prophylaxis is reasonable for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa . ( 4 ) Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of infective endocarditis . ( 5 ) Administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary or gastrointestinal tract procedure . These changes are intended to define more clearly when infective endocarditis prophylaxis is or is not recommended and to provide more uniform and consistent global recommendations Concentrations of serum alkaline phosphatase and total urinary hydroxyproline were measured in 36 children to study the effect of phenobarbital administration with respect to the development of rickets in patients receiving anticonvulsive medications over prolonged periods of time . Administration of phenobarbital led to the appearance of increased AP and HOP values very early in the course of treatment and without any obvious bone changes suggestive of rickets ; a single large oral dose of vitamin D had no appreciable effects in restoring the biochemical derangement . On the other h and , the administration of vitamin D in a daily dose of 4,000 IU for a period of two months hampered the appearance , or restored already existing changes of latent rickets , in children receiving anticonvulsive medication . The results in the present study favor the concept that phenobarbital administration is implicated in the development of rickets . The need for simultaneous daily administration of supplements of vitamin D in subjects receiving anticonvulsive drugs is stressed Nutritional rickets remains a common child health problem in Turkey and many other developing countries . Although vitamin D deficiency is accepted as the basic problem underlying the disease , others postulate that a deficiency of dietary calcium , rather than vitamin D , is often responsible for the nutritional rickets in sunny countries . We conducted a placebo-controlled study to determine the best treatment regimen for nutritional rickets in children residing in lower socioeconomic regions of a sunny city , Istanbul . Forty-two infants ( aged 6 - 30 months ) with rickets were divided into three groups and included in the study . In a r and omized fashion vitamin D ( 300 000 units , intramuscularly ) , calcium lactate ( 3 g daily ) or a combination of vitamin D and calcium were given to the children . Alkaline phosphatase , calcium , albumin , ionized calcium and phosphorus levels were measured each week . X-ray examinations of the left wrist and left knee were undertaken at the beginning of the study and were repeated at the 2nd and 4th weeks and were scored in order to assess the response to treatment . Treatment produced an increase in serum calcium and a decrease in alkaline phosphatase concentration in all three groups , but the most important increase was reached in the vitamin D plus calcium group . We conclude that vitamin D deficiency appears to be the primary etiologic factor of rickets in our study group , but a better response to treatment with vitamin D or in combination with calcium was obtained than to treatment with calcium alone Quality of care can be measured by using either processes or outcomes . Each method has its strengths and limitations ( 1 ) . With the concurrence of the Assessing Care of Vulnerable Elders ( ACOVE ) Policy Advisory Committee [ 2 ] , we chose to assess the care of vulnerable elders by using processes rather than outcomes . We did so because 1 ) processes are a more efficient measure of quality ; 2 ) for most conditions there are insufficient information in the medical record and a paucity of vali date d models to adequately adjust outcomes for differences in case mix between providers ; and 3 ) ultimately , processes of care are amenable to direct action by providers . To be a valid measure of quality , a health care process must be strongly linked to an outcome that is important to patients . Ideally , high- quality published studies would link performance of all such processes to outcomes ; however , few health care processes are supported by high- quality evidence ( 3 ) . Even when a process is supported by strong evidence from r and omized clinical trials , the inclusion and exclusion criteria of the clinical trials leave the evidence directly applicable to only a narrow group of patients ( 4 , 5 ) . This is particularly true for vulnerable elders , who are typically excluded from clinical trials ( 6 ) . Therefore , as we developed the ACOVE quality indicators , we used expert opinion to interpret the available evidence for applicability to vulnerable elders . Our methods entailed a literature review and several levels of expert opinion ( Figure ) , which we explain in detail . Figure . Assessing  Care of Vulnerable Elders ( ACOVE ) method for developing quality indicators for vulnerable elders . Methods Development of Draft Process Indicators  For each ACOVE condition that we selected for quality improvement in vulnerable elders ( 2 ) , we identified a content expert , who worked as a team with another project member knowledgeable about systematic review s and quality indicator development . Together , the content expert and project member developed potential quality indicators from existing guidelines , review criteria , and expert opinion . Because practice guidelines and existing quality indicators are seldom referenced in the traditional scientific data bases , we used various search strategies to locate these material s. In addition to search ing MEDLINE , we search ed the following sources : CONQUEST 1.1 ( A Computerized Needs-Oriented Quality Measurement Evaluation System ) ( 7 ) ; DEMPAQ : A Project to Develop and Evaluate Methods to Promote Ambulatory Care Quality ( 8) ; Directory of Clinical Practice Guidelines ( 9 ) ; Guide to Clinical Preventive Services ( 10 ) ; HEDIS 3.0 : Health Plan Employer Data and Information Set ( 11 ) ; National Guideline Clearinghouse ( 12 ) ; National Library of Health Care Indicators ( 13 ) ; and The Medical Outcomes & Guidelines Source book ( 14 ) . We also h and search ed the tables of contents of all issues of The Journal of the American Medical Association and Medical Care published April through November 1998 for relevant practice guidelines and quality indicators . Furthermore , we requested practice guidelines and quality indicators from the following agencies and organizations : Administration on Aging ( AOA ) ; Agency for Health Care Policy and Research (AHCPR)now known as Agency for Healthcare Research and Quality ( AHRQ ) ; Centers for Disease Control and Prevention ( CDC ) ; Department of Health and Human Services ( DHHS ) ; Department of Veterans Affairs ; Foundation for Accountability ( FACCT ) ; Health Care Financing Administration ( HCFA ) ; HCFA/Connecticut Peer Review Organization ; Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) ; National Committee for Quality Assurance ( NCQA ) ; and National Institutes of Health ( NIH ) . By using the quality indicators identified through this process , as well as using expert opinion and existing guidelines , the content expert developed 20 to 30 preliminary quality indicators for further review . Potential indicators were constructed in an IFTHENBECAUSE format : IF refers to the clinical characteristics that describe persons eligible for the quality indicator ; THEN indicates the actual process that should or should not be performed ; and BECAUSE refers to the expected health impact if the indicator is performed . For example , IF a vulnerable elder has heart failure with an ejection fraction of 40 % or less , THEN an angiotensin-converting enzyme ( ACE ) inhibitor should be offered BECAUSE treatment with ACE inhibitors improves longevity . We circulated this initial set of potential quality indicators to other clinical experts for their review . On the basis of review ers ' comments , we narrowed down the initial set to the 10 to 25 most promising indicators for future development . Review of Scientific Literature Next , we assessed the published evidence supporting a link between the process specified in each quality indicator and patient outcomes . To do so , we performed a systematic review on each quality indicator by using the essence of the Cochrane Collaboration 's methods (15)except that we used a single review er to screen and assess studies . With the assistance of a reference librarian , we electronically search ed MEDLINE , EMBASE , The Cochrane Data base of Systematic Review s , HealthSTAR , Ageline , and other specialized data bases on a condition-specific basis by using keywords and free-text terms to identify potentially relevant studies . For most conditions , the search es were not restricted by language . The content expert review ed the retrieved citations by using a three-step process : First , the titles were review ed for possibly relevant studies ; the abstract s associated with the titles that passed the first round of screening were then review ed ; and , finally , the full articles of abstract s that passed the second round of screening were review ed . Abstract s and articles were not masked for review . To be accepted , titles and abstract s had to contain information indicating that the full article probably reported evidence on the potential relationship between the process in question and better outcomes in humans . We excluded animal studies , letters , review articles , and other articles that did not report original data . In review ing full articles , we gave priority to evidence from studies with the strongest design s that were relevant to the potential quality indicator being examined . In general , this meant that we chose r and omized clinical trials for questions about the efficacy or effectiveness of interventions and prospect i ve cohort studies to answer questions about risk or prognosis . We considered such evidence to be direct evidence , and we judged direct evidence in elderly persons to be the strongest level of evidence available . In the absence of direct evidence in elderly persons , we performed search es for direct evidence in other groups . Indirect evidence that from less rigorous design sin elderly or nonelderly persons was review ed if the available direct evidence was insufficient . When both direct evidence and indirect evidence were lacking , we included the statements of authoritative bodies ( for example , specialty societies , National Institutes of Health consensus development conferences , or Agency for Health Care Policy and Research practice guidelines ) . After review ing all of the relevant articles , the content expert prepared a monograph detailing each of the quality indicators and summaries of the evidence supporting them . This monograph was sent to one or more peer review ers , who were asked to assess the quality of the monograph according to the following guidelines : 1 ) Is the review complete in terms of both the proposed quality criteria and the evidence ? 2 ) Is the review fair ( that is , is the presentation of the evidence unbiased ) ? The authors subsequently revised the monographs on the basis of review ers ' comments in a manner analogous to the response to a critique of a journal article : Each comment was addressed in turn , and the author provided an appropriate revision or stated the reason why he or she believed that no revision was indicated . Expert Panels We convened two multidisciplinary groups , each composed of 12 clinical experts , to interpret the supporting evidence detailed in the monographs and to select quality indicators for further consideration . Each panel of experts considered a separate set of ACOVE conditions . Table 1 lists the members of the panels and the conditions they considered . Table 1 . ACOVE Expert Panels To assess the expert opinions of the panelists , we used a modified version of the R AND /UCLA Appropriateness Method ( 16 , 17 ) . In brief , the method entails two rounds of anonymous ratings on a riskbenefit scale ranging from 1 to 9 and a face-to-face group discussion between rounds . Each panelist has equal weight in determining the final ratings . The reproducibility of the R AND /UCLA Appropriateness Method is consistent with that of well-accepted diagnostic tests , such as the interpretation of coronary angiography and screening mammography ( 18 ) . It also has content , construct , and predictive validity ( 5 , 17 , 19 , 20 ) . In this application of the method , we sent each panelist the proposed quality indicators and the relevant condition-specific monographs . We asked the panelists to assess the validity of each proposed indicator on a scale of 1 to 9 , in which 1 was definitely not valid and 9 was definitely valid . We considered an indicator to be valid if 1 ) adequate scientific evidence or professional consensus supported a link between the process specified by the indicator and a health benefit to the patient ; 2 ) a physician or health plan with high rates of adherence to the indicator would be considered a higher- quality provider ; and 3 ) the physician or health plan influenced a majority of factors that determine adherence to the indicator ( such as smoking cessation ) . Each panelist was instructed to rate each potential quality indicator for validity and return the ratings to us before the face-to-face The daily supplementation of vitamin D is m and atory for infants . However , there are still conflicting opinions about the exact daily dose . Thus , we aim ed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day . One hundred and sixty-nine infants were r and omly assigned to two groups ( group1 , 200 IU/day ; group 2 , 400 IU/day ) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139 . The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months ( group 1 , 39.60 mcg/L ; group 2 , 56.55 mcg/L ; p < 0.0001 ) . We clearly demonstrated that at the age of 4 months , none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However , 21.3 % of the infants in group 1 had a level below 30 mcg/L. Thus , in order to avoid vitamin D deficiency and rickets , we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose OBJECTIVES To assess the benefits and risks of  antenatal corticosteroid therapy  for fetal maturation . OPTIONS To administer antenatal corticosteroids or not to women at risk of preterm birth . OUTCOMES Perinatal morbidity , including : respiratory distress syndrome , intraventricular hemorrhage , infection , adrenal suppression , somatic and brain growth ; perinatal mortality ; and maternal morbidity , including infection and adrenal suppression . EVIDENCE MEDLINE and PubMed search es 1996 to August 2002 for English- language articles related to  antenatal corticosteroid therapy for fetal maturation , the Cochrane Library , and national statements including that of the National Institutes of Health ( NIH ) , the American College of Obstetricians and Gynecologists , and the Royal College of Obstetricians and Gynaecologists . VALUES The evidence obtained was review ed and evaluated by the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada ( SOGC ) and recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Exam . BENEFITS AND HARMS : A single course of corticosteroids reduces perinatal mortality , respiratory distress syndrome , and intraventricular hemorrhage . Information regarding repeat courses of corticosteroids is limited and conflicting , with many studies being retrospective and non-r and omized . Some studies suggested a reduction in respiratory distress syndrome with repeat courses , but some found increased rates of neonatal and maternal infection ; fetal , neonatal , and maternal adrenal suppression ; decreased fetal or neonatal somatic and brain growth ; and increased perinatal mortality . RECOMMENDATIONS The SOGC supports the recommendations of the NIH Consensus Development Panel : 1 . All pregnant women between 24 and 34 weeks ' gestation who are at risk of preterm delivery within 7 days should be considered c and i date s for antenatal treatment with a single course of corticosteroids . ( I-A ) 2 . Treatment should consist of two 12 mg doses of betamethasone given IM 24 hours apart , or four 6 mg doses of dexamethasone given IM 12 hours apart ( I-A ) . There is no proof of efficacy for any other regimen . 3 . Because of insufficient scientific data from r and omized clinical trials regarding efficacy and safety , repeat courses of corticosteroids should not be used routinely ( II-2E ) but be reserved for women participating in r and omized controlled trials . VALIDATION This Committee Opinion has been review ed and approved by the Maternal-Fetal Medicine Committee of the SOGC and approved by SOGC Council Two hundred and fifty children with clinical , biochemical and radiological evidence of vitamin-D-deficiency rickets were studied over a period of 5 years . Their ages ranged from 1 month to 2 years . Breastfed infants formed 63 % of total cases . Intramuscular therapy with vitamin D in a dose of 600,000 IU , deep intramuscular , proved to be safe and effective . In contrast , oral vitamin D did not provide such satisfactory results , presumably owing to poor patient/parental compliance . This report reveals that vitamin-D-deficieny rickets is common in Kuwait in spite of abundant sunlight all through the year because children are wrapped up and kept indoors . Insufficient intake of vitamin D is another important factor in the pathogenesis of vitamin-D-deficiency rickets in Kuwait Join the dialogue on health care reform . Comment on the perspectives published in Annals and offer ideas of your own . All thoughtful voices should be heard . On 30 June 2009 , another milestone was achieved in progress toward a national system to promote medical research that focuses on decision making by physicians and patients . The first steps occurred in late 2007 and early 2008 with a seminal article ( 1 ) and an Institute of Medicine ( IOM ) report that called for a national initiative of research that would support better decision making about interventions in health care ( 2 ) . One of us was a coeditor of the IOM report . A third milestone was reached when both presidential c and i date s endorsed this concept . A fourth milestone came when the president signed into law the American Recovery and Reinvestment Act of 2009 ( ARRA ) ; this act allotted $ 1.1 billion to support this form of research , which had become known as comparative effectiveness research ( CER ) . The legislation created a federal council on CER and asked the IOM to elicit input from a broad array of stakeholders on which research topics should have the highest-priority for funding through the ARRA and to then develop a list of the highest-priority topics for the Secretary of Health and Human Services to consider . By law , the Federal Coordinating Council and the IOM committee to set priorities for comparative effectiveness research reported to the Secretary on 30 June 2009 . This issue contains both this article , which is a commentary on the IOM committee report ( 3 ) by the committee 's cochairs , and a perspective on better research methods for CER ( 4 ) . Definition of CER The IOM committee quickly settled on a working definition of CER , which consisted of the elements of earlier definitions reduced to 2 sentences : CER is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent , diagnose , treat and monitor a clinical condition , or to improve the delivery of care . The purpose of CER is to assist consumers , clinicians , purchasers , and policy makers to make informed decisions that will improve health care at both the individual and population levels . Two key elements that are embedded in this definition are the direct comparison of effective interventions and their study in patients who are typical of day-to-day clinical care . These features would ensure that the research would provide information that decision makers need to know , as would a third feature , research design ed to identify the clinical characteristics that predict which intervention would be most successful in an individual patient . The same research design would also help policymakers by identifying sub population s of patients that are more likely to benefit from one intervention than the other . High-Priority Research Topics The IOM committee sought advice from a broad range of stakeholders and received it in 3 forms : approximately 90 letters ; 54 oral presentations at a day-long hearing in Washington , DC ; and a Web-based nomination form . Overall , the committee received more than 2606 nominations from 1758 individual responders within 3 weeks . In a 3-step voting process , the committee identified 100 high-priority topics , which it ranked in quartiles . At each stage , the committee sought to have a balanced portfolio of topics . Table 5 - 1 in the report ( available at www.iom.edu/cerpriorities ) lists the 100 highest-ranked topics . Establishing a Sustainable National Program of CER The U.S. Congress is currently debating legislation that would guarantee health insurance to more Americans while reforming the U.S. health system . A key aim of the legislation is to moderate the rate at which the cost of health care increases while improving the quality of care . Many leaders believe that reaching this goal will require a sustained effort to produce better evidence to inform decision making . Government officials have characterized the $ 1.1 billion allocated to CER as a down payment on a national program of CER . As of this writing , the House of Representatives bill proposes a national program of CER , and the Senate Finance Committee white paper does likewise . Accordingly , the IOM committee made several recommendations aim ed at a sustainable , trustworthy national CER initiative . The Appendix provides the full text of these recommendations . Governance The 2008 IOM committee recommended establishing a national program with authority , overarching responsibility , sustained re sources , and adequate capacity to ensure production of credible , unbiased information about what is known and what is not known about clinical effectiveness ( 2 ) . The current committee exp and ed this recommendation by calling upon the secretary of the Department of Health and Human Services to establish a mechanismsuch as a coordinating advisory bodywith the authority to strategize , organize , monitor , evaluate , and report on the implementation and impact of the CER Program . The committee recognized that many agencies of the federal government are engaged in research that fits some or all of the key elements of CER . To make the best use of the funds allocated for CER , these agencies should be jointly accountable for spending CER funds on research that reflects the same conceptualization of CER . Therefore , these disparate efforts should use a single definition of CER and the same definitions of outcomes and measures of function and illness . This form of cross-agency coordination is compatible with each agency focusing on the form of research with which it has the greatest experience . Active Involvement of Consumers in CER The 2009 ARRA created a means for coordinating federal CER efforts : the Federal Coordinating Council . Seeking to complement the functions of the Council , the IOM committee focused on the potential contribution of consumers of health care to CER and recommended involving them at all levels of the national CER initiative . The recommendation is as follows : The CER Program should fully involve consumers , patients and their caregivers in key aspects of CER , including strategic planning , priority setting , research proposal development , peer review , and dissemination . The concept that animates this recommendation is a radical but logical departure from past practice : When a principal aim of research is to inform decision makers , listen to the decision makers . Meaningful participation will require consumers to learn more about research , just as they will teach research ers about how to frame their investigations to satisfy the needs of consumers who are also decision makers . This approach has precedent . For example , the National Institute for Health and Clinical Effectiveness in the United Kingdom teaches decision making to consumers who participate in the institute 's program . Methodology of CER Remembering that the purpose of CER is to inform decision making , consider the principal forms of clinical research . Systematic review s of the literature summarize a body of evidence . Over the past 2 decades , they have become indispensable to expert panels that formulate practice guidelines or policymakers who make insurance coverage decisions . These macro decision makers are starting to use decision models for the same purpose s ( 5 ) . Two broad categories of research are the starting point for systematic review s : observational research and r and omized trials . Large established data bases provide an opportunity to link current health care practice s to the outcome of care . These data bases are representative of critical groups often omitted from r and omized trials , but they contain limited data ; of note , they seldom specify the rationale for medical decisions . These observational research methods have many advantagesspeed , real-world decisions , large numbers of decisions and outcomes , and low costbut they can not escape a key limitation : Characteristics of the patient that drive real-life clinical decisions may also influence clinical outcomes , leading to uncertainty about whether they or the intervention itself causes the outcomes . Overcoming the limitations of observational research is the most important frontier of research on study methods . To overcome these limitations , research ers often r and omly assign patients to different interventions . This simple action eliminates much of the uncertainty that plagues the interpretation of observational research . However , we have too often used the conceptual elegance of r and omization to answer the wrong questions . We ask , Does this work ? when our readers want to know , Is this better than that ? Thus , too often , r and omized trials are so-called efficacy studies : They are design ed to create near-ideal circumstances to see whether the intervention can possibly work . To this end , research ers exclude many types of patients from efficacy trials and often compare the intervention with a placebo . In these respects , efficacy trials are unlike the conditions that physicians and patients face in daily practice . Another article in this issue ( 4 ) describes several exciting new methods for making r and omized trials more suitable for CER . The examples of observational research and new r and omized trial methods are the basis for the IOM committee 's strong recommendation that a national CER program should support research in the methods of clinical research . The Infrastructure for Observational Research The committee believes that very large collection s of the electronic records of patients can be a valuable re source for CER . Using these data sets , it is possible to compare the outcomes of using several effective interventions in a population that is representative of daily care , 2 features that are aligned with the goals of CER . The great numbers of patients in these data sets also makes it possible to study subgroups with precision and perhaps identify key predictors of response to an intervention , both of which would facilitate decision making at the individual and population Background Subgroup analyses in r and omized trials examine whether effects of interventions differ between subgroups of study population s according to characteristics of patients or interventions . However , findings from subgroup analyses may be misleading , potentially result ing in suboptimal clinical and health decision making . Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered . The objectives of this study are : 1 ) to describe the reporting of subgroup analyses and cl aims of subgroup effects in r and omized controlled trials , 2 ) to assess study characteristics associated with reporting of subgroup analyses and with cl aims of subgroup effects , and 3 ) to examine the analysis , and interpretation of subgroup effects for each study 's primary outcome . Methods We will conduct a systematic review of 464 r and omized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine . We will r and omly select journal articles , stratified in a 1:1 ratio by higher impact versus lower impact journals . According to 2007 ISI total citations , we consider the New Engl and Journal of Medicine , JAMA , Lancet , Annals of Internal Medicine , and BMJ as higher impact journals . Teams of two review ers will independently screen full texts of reports for eligibility , and abstract data , using st and ardized , pilot-tested extraction forms . We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with cl aims of subgroup effects for the primary and any other outcomes . Discussion A clear underst and ing of subgroup analyses , as currently conducted and reported in published r and omized controlled trials , will reveal both strengths and weaknesses of this practice . Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses , and cl aim and interpretation of subgroup effects in r and omized trials The health and life expectancy of Americans has dramatically improved during the past several decades , but racial and ethnic minorities have not benefited equally from this progress . Differences in health outcomes between majority and minority population s , commonly referred to as racial or ethnic disparities in health , are the result of several factors operating in complex sociologic , cultural , political , economic , and health care context s. Until recently , curricula addressing racial and ethnic health disparities focused on factors outside the health care system , including socioeconomic disadvantage and lack of health insurance ( 1 ) , but some publications ( 25 ) , culminating in 2002 with the Institute of Medicine report , Unequal Treatment : Confronting Racial and Ethnic Disparities in Health Care , have highlighted the fact that racial and ethnic minoritieseven those with equivalent access to the health care systemreceive lower- quality care than white patients for many medical conditions ( 6 ) . As a result , increased attention is now focused on addressing racial and ethnic disparities in health care ( hereafter referred to as health care disparities ) as a component of addressing racial and ethnic disparities in health ( hereafter referred to as health disparities ) ( 7 , 8) . Emerging consensus among national experts suggests that without new and more effective interventions , health disparities will be difficult to eliminate ( 9 ) , and they may become an even larger problem as racial and ethnic minorities become a larger proportion of the U.S. population ( 10 ) . Key stakeholders need to engage at many levels to eliminate disparities , including at the community and societal levels . However , considering the significance of the physicianpatient relationship in health care delivery , interventions by individual physicians will be an important component of an overall strategy to reduce health care disparities . Several surveys show that many physicians remain unaware of health care disparities nationally and in their own practice s ( 1113 ) . The Institute of Medicine 's report recommends that health professionals receive training to better underst and and address disparities ( 6 ) . However , few curricula on health disparities exist , and there are no well-accepted guidelines on what and how to teach about this complex topic . This report presents the work of the Society of General Internal Medicine Health Disparities Task Force to develop guidelines for medical education on disparities in health and health care . We provide learning objectives , suggested content , methods for teaching , and a set of current re sources . Although they were developed primarily for teaching medical students , residents , and practitioners in primary care , our general recommendations should apply to learners in any specialty . The Task Force has also developed recommendations for system-level and environment-of-care interventions to eliminate health care disparities , which are as important as recommendations for training individual practitioners but are beyond the scope of this report . Methods The Society of General Internal Medicine is an international organization that comprises internal medicine physicians and others who combine patient care with education and research in primary care internal medicine . The Task Force includes volunteers from the Society of General Internal Medicine membership , many of whom teach about ethics , health disparities , and cross-cultural care at their institutions . The Task Force convened a series of meetings from 2002 to 2005 , which included several conference calls , e-mail exchanges , and 4 face-to-face meetings . After the first meeting , Task Force teams completed a needs assessment and literature review . The entire Task Force then contributed to several versions of the recommendations . Subsequent meetings served to refine and tailor iterative versions of both the literature review and recommendations , which informed each other . Final recommendations were developed by a consensus , although various interpretations remain among members of the Task Force in the application of specific principles . Needs Assessment Few studies have formally assessed the need for health disparities training . Recent surveys on cross-cultural care demonstrate that resident physicians ' self-reported preparedness to deliver cross-cultural care lags well behind preparedness in other clinical and technical areas ( 14 , 15 ) . A national study on resident physicians reported that residents were receiving the message that health care disparities are important and that physicians should play a role in eliminating them , but they had not received guidance on how to do so . As a result , they developed coping behaviors rather than skills ( 16 ) . To supplement these studies , the Task Force conducted its own brief needs assessment survey with the assistance of the Institute for Ethics at the American Medical Association . The survey was sent to 60 r and omly selected internal medicine program directors nationwide , 22 of whom responded within the 1-month time frame ( 37 % response rate ) . Most of the 22 respondents ( 86 % ) reported teaching some information about health disparities , and none reported offering a lot of training . However , 77 % agreed that learning about health disparities was associated with better quality of care , and 73 % reported that a resident 's level of interest was not a barrier to teaching : health disparities . Rather , shortages of qualified faculty and lack of st and ardized curricula were often noted as barriers . Adding to the need for concrete guidance in this domain , the Liaison Committee on Medical Education , which sets st and ards for undergraduate medical education , required in 2004 that medical schools document objectives relating to the development of skills in cultural competence , indicate where in the curriculum students are exposed to such material , and demonstrate the extent to which the objectives are being achieved ( 17 ) . The Accreditation Council on Graduate Medical Education , which accredits residency training programs , has also included cultural sensitivity as a skill set in its core competencies for residency training : Programs must teach and monitor residents ' ability to demonstrate sensitivity and responsiveness to patients ' culture , age , gender , and disabilities ( 18 ) . The American Board of Medical Specialties and the Accreditation Council on Graduate Medical Education have created a toolbox of re sources for monitoring professionalism that includes useful material s for assessing residents in these domains ( 19 ) . Because these accreditation requirements have been implemented , new curricula ( 2022 ) and suggested st and ards for training programs ( 2325 ) have begun to emerge , although none are widely accepted yet . Literature Review Task Force members search ed for published curricula focused on health disparities but found very little documentation . We search ed MEDLINE ( 1966 to 2005 ) , EMBASE ( 1980 to 2005 ) , and the Cochrane Library of Systematic Review s ( all years ) and article bibliographies for curricula on health disparities or cross-cultural medical care by using various search terms . For example , by using the Medical Subject Headings and text terms health disparities and curriculum , our search yielded 39 articles . However , none of these reports on curricula explicitly focused on disparities by discussing the multifactorial causes of health disparities ; describing health care disparities as a component of health disparities ; targeting the elimination of health disparities as a professional goal for medicine ; or teaching learners how to help eliminate disparities . In contrast , several cross-cultural care curricula often prominently mentions the existence of health disparities and some root causes of disparities ( 26 ) . Various studies have summarized these curricula and evaluations of their effectiveness . A 1978 survey of medical school curricula concluded that courses on cross-cultural care in U.S. medical schools had substantial deficits ( 27 ) . A comprehensive review of U.S. and British medical school curricula in 1999 showed little apparent improvement ( 28 ) . At that time , only 13 criteria ; 11 were for first- or second-year medical students , 7 were part of core ( required ) curricula , and we only found 1 curriculum that reported any postteaching evaluation of learners . A survey of all U.S. and Canadian medical schools in 2000 concluded that most schools provided inadequate instruction about cultural issues ; separate courses addressing cultural issues were identified in only 8 % of U.S. schools and in no Canadian schools ( 29 ) . Good evidence indicated that cross-cultural care training can improve a professional 's knowledge , attitude , and skill , but there is little documented evidence of an effect on patient adherence and no evaluations of effects on patient health status ( 3032 ) . Recommendations Recommended Goals of a Curriculum The ultimate aim of a curriculum on disparities is that learners develop a professional commitment to eliminating inequities in health care quality and underst and and accept their role in eliminating racial and ethnic health care disparities . The curriculum should accomplish this by meeting 3 core teaching goals : 1 ) to help learners examine and underst and attitudes , such as mistrust , subconscious bias , and stereotyping , that practitioners and patients may bring to the clinical encounter ; 2 ) to impart knowledge of the existence and magnitude of health disparities , including the multifactorial causes of health disparities and the many solutions required to eliminate them ; and 3 ) to provide the learner with the skills required to effectively communicate and negotiate across cultures , language s , and literacy levels , including the use of key tools to improve communication . Attitudes Helping learners acquire knowledge and skills is commonly the primary goal of teaching ; however , teachers may give little explicit attention to the goal of Guidelines for the diagnosis and treatment of Barrett ’s esophagus were published by the American College of Gastroenterology in 1998 ( 1 ) . These and other guidelines undergo periodic review . Significant advances have been made in the area of Barrett ’s esophagus over the past several years , leading us to review and revise our previous guidelines statements . These advances have included more information on the natural history of high- grade dysplasia and the chronic use of proton pump inhibitors . These and the original guidelines are intended to apply to all physicians who address Barrett ’s and are intended to indicate the preferable , but not only acceptable , approach . Physicians must always choose the course best suited to the individual patient and the variables that exist at the moment of the decision . These guidelines are intended to apply to adult patients with the diagnosis of Barrett ’s esophagus defined in the guidelines . Both these and the original guidelines were developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees . The world literature was review ed extensively for the original guidelines and was once again review ed using the National Library of Medicine data base . All appropriate studies were review ed , and any additional studies found in the reference list of these papers were obtained and review ed . Evidence was evaluated along a hierarchy , with r and omized controlled trials given the greatest weight . Abstract s presented at national and international meetings were only used when unique data from ongoing trials were presented . When scientific data were lacking , recommendations were based on expert consensus . During preparation , the guidelines were review ed by the American Gastroenterological Association and the American Society for GI Endoscopy . Recommendations and comments obtained from these review s were incorporated into the final document whenever possible Revised guidelines for the use of antimicrobial therapy in patients with intra-abdominal infections were recently developed by the Therapeutic Agents Committee of the Surgical Infection Society ( Mazuski et al. , Surg Infect 2002;3:161 - 173 ) . These were based , insofar as possible , on evidence published over the past decade . The objective of this document is to describe the process by which the Committee identified and review ed the published literature utilized to develop the recommendations and to summarize the results of those review s. English- language articles published between 1990 and 2000 related to antimicrobial therapy for intra-abdominal infections were identified by a systematic MEDLINE search and an examination of references included in recent review articles . If current literature with regard to a specific issue was lacking , relevant articles published prior to 1990 were identified . All prospect i ve r and omized controlled trials , as well as other articles selected by the Committee , were evaluated individually and collectively . Data with regard to patient numbers , types of infections , and results of interventions were abstract ed . Studies were categorized according to their design , and all included trials were grade d according to quality . On the basis of this evidence , the Committee formulated recommendations for antimicrobial therapy for intra-abdominal infections and grade d those recommendations . After receiving comments from invited review ers and the general membership of the Society , the guidelines were finalized and su bmi tted to the Council of the Surgical Infection Society for approval . The final recommendations related to the selection of patients needing therapeutic antimicrobials , acceptable antimicrobial regimens , duration of antimicrobial use , and the identification and treatment of higher-risk patients . Although numerous publications pertaining to these topics were identified , but nearly all of the prospect i ve r and omized controlled trials represented comparisons of different antimicrobial regimens for the treatment of intra-abdominal infections . A few prospect i ve trials evaluated the need for  therapeutic antimicrobial therapy  in patients with peritoneal contamination following abdominal trauma . The quality of these prospect i ve trials was highly variable . Many did not limit enrollment to patients with complicated intra-abdominal infections , lacked blinding of treatment assignment , did not provide a complete description of the criteria used to determine therapeutic success or failure , failed to identify the reasons why patients were excluded from analysis , or did not include an intention-to-treat analysis . For many issues , no prospect i ve r and omized controlled trials were encountered , and guidelines had to be formulated using evidence from studies with historical controls or uncontrolled data , or on the basis of expert Cluster r and omized trials r and omly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals . Recent emphasis on quality improvement , comparative effectiveness , and learning health systems has prompted exp and ed use of pragmatic cluster r and omized trials in routine health-care setting s , which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address . The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic cluster r and omized trials but challenges remain , including some arising from the current US research and health-care regulations . In order to examine the ethical , regulatory , and practical questions facing pragmatic cluster r and omized trials in health-care setting s , the National Institutes of Health Health Care Systems Research Collaboratory convened a workshop in Bethesda , Maryl and , in July 2013 . Attendees included experts in clinical trials , patient advocacy , research ethics , and research regulations from academia , industry , the National Institutes of Health Collaboratory , and other federal agencies . Workshop participants identified substantial barriers to implementing these types of cluster r and omized trials , including issues related to research design , gatekeepers and governance in health systems , consent , institutional review boards , data monitoring , privacy , and special population s. We describe these barriers and suggest means for underst and ing and overcoming them to facilitate pragmatic cluster r and omized trials in health-care setting BACKGROUND Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight . Some postulate that a deficiency of dietary calcium , rather than vitamin D , is often responsible for rickets after infancy . METHODS We enrolled 123 Nigerian children ( median age , 46 months ) with rickets in a r and omized , double-blind , controlled trial of 24 weeks of treatment with vitamin D ( 600,000 U intramuscularly at enrollment and at 12 weeks ) , calcium ( 1000 mg daily ) , or a combination of vitamin D and calcium . We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex , age , and weight . We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks . RESULTS The daily dietary calcium intake was low in the children with rickets and the control children ( median , 203 mg and 196 mg , respectively ; P=0.64 ) . Treatment produced a smaller increase in the mean ( + /-SD ) serum calcium concentration in the vitamin D group ( from 7.8+/-0.8 mg per deciliter [ 2.0+/-0.2 mmol per liter ] at base line to 8.3+/-0.7 mg per deciliter [ 2.1+/-0.2 mmol per liter ] at 24 weeks ) than in the calcium group ( from 7.5+/-0.8 [ 1.9+/-0.2 mmol per liter ] to 9.0+/-0.6 mg per deciliter [ 2.2+/-0.2 mmol per liter ] , P<0.001 ) or the combination-therapy group ( from 7.7+/-1.0 [ 1.9+/-0.25 mmol per liter ] to 9.1+/-0.6 mg per deciliter [ 2.3+/-0.2 mmol per liter ] , P<0.001 ) . A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets ( 61 percent , 58 percent , and 19 percent , respectively ; P<0.001 ) . CONCLUSIONS Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone OBJECTIVE This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension ( http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext ) to provide a reasonable approach to the diagnosis , evaluation , and treatment of the hypertensive disorders of pregnancy . EVIDENCE Published literature was retrieved through search es of Medline , CINAHL , and The Cochrane Library in March 2012 using appropriate controlled vocabulary ( e.g. , pregnancy , hypertension , pre-eclampsia , pregnancy toxemias ) and key words ( e.g. , diagnosis , evaluation , classification , prediction , prevention , prognosis , treatment , postpartum follow-up ) . Results were restricted to systematic review s , r and omized control trials , controlled clinical trials , and observational studies published in French or English between January 2006 and February 2012 . Search es were up date d on a regular basis and incorporated in the guideline to September 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology-related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies . VALUES The quality of evidence in the guideline summarized here was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care ( Table 1 )
Whether or not outcomes such as osteoporosis ( or low bone mass ) and specific types of cancer may be prevented by ' generous ' vitamin D supplementation is unclear and mostly based on indirect epidemiologic data not clearly substantiated by r and omized controlled trials SUMMARY The dose of daily vitamin D supplements needed to prevent rickets is probably much lower than that recommended by most expert committees .
PURPOSE OF REVIEW To underst and the basis for current recommendations for  vitamin D supplementation in childhood and the differences between the recommendations published by major expert committees , using the Medline engine of the US National Library of Medicine and the National Institutes of Health .
Most trials have examined the question of whether a specific daily vitamin D dose is capable or not to prevent rickets ( by study ing surrogate markers of rickets ) .