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1.  Food allergy knowledge, attitudes and beliefs: Focus groups of parents, physicians and the general public 
BMC Pediatrics  2008;8:36.
Background
Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public.
Methods
Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs.
Results
Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy.
Conclusion
Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.
doi:10.1186/1471-2431-8-36
PMCID: PMC2564918  PMID: 18803842
2.  Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001611.
In a systematic review and meta-analysis, Bahi Takkouche and colleagues examine the associations between exposure to tobacco smoke and allergic disorders in children and adults.
Please see later in the article for the Editors' Summary
Background
Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.
Methods and Findings
We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children.
We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1.11]). Food allergy was associated with SHS (1.43 [1.12–1.83]) when cohort studies only were examined, but not when all studies were combined.
The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification.
Conclusions
We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The immune system protects the human body from viruses, bacteria, and other pathogens. Whenever a pathogen enters the body, immune system cells called T lymphocytes recognize specific molecules on its surface and release chemical messengers that recruit and activate other types of immune cells, which then attack the pathogen. Sometimes, however, the immune system responds to harmless materials (for example, pollen; scientists call these materials allergens) and triggers an allergic disease such as allergic rhinitis (inflammation of the inside of the nose; hay fever is a type of allergic rhinitis), allergic dermatitis (also known as eczema, a disease characterized by dry, itchy patches on the skin), and food allergy. Recent studies suggest that all these allergic (atopic) diseases are part of a continuous state called the “atopic march” in which individuals develop allergic diseases in a specific sequence that starts with allergic dermatitis during infancy, and progresses to food allergy, allergic rhinitis, and finally asthma (inflammation of the airways).
Why Was This Study Done?
Allergic diseases are extremely common, particularly in children. Allergic rhinitis alone affects 10%–30% of the world's population and up to 40% of children in some countries. Moreover, allergic diseases are becoming increasingly common. Allergic diseases affect the quality of life of patients and are financially costly to both patients and health systems. It is important, therefore, to identify the factors that cause or potentiate their development. One potential risk factor for allergic diseases is active or passive exposure to tobacco smoke. In some countries up to 80% of children are exposed to second-hand smoke so, from a public health point of view, it would be useful to know whether exposure to tobacco smoke is associated with the development of allergic diseases. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical approach for combining the results of several studies) to investigate this issue.
What Did the Researchers Do and Find?
The researchers identified 196 observational studies (investigations that observe outcomes in populations without trying to affect these outcomes in any way) that examined the association between smoke exposure and allergic rhinitis, allergic dermatitis, or food allergy. When all studies were analyzed together, allergic rhinitis was not associated with active smoking but was slightly associated with exposure to second-hand smoke. Specifically, compared to people not exposed to second-hand smoke, the pooled relative risk (RR) of allergic rhinitis among people exposed to second-hand smoke was 1.10 (an RR of greater than 1 indicates an increased risk of disease development in an exposed population compared to an unexposed population). Allergic dermatitis was associated with both active smoking (RR = 1.21) and exposure to second-hand smoke (RR = 1.07). In the populations of children and adolescents included in the studies, allergic rhinitis was associated with both active smoking and exposure to second-hand smoke (RRs of 1.40 and 1.09, respectively), as was allergic dermatitis (RRs of 1.36 and 1.06, respectively). Finally food allergy was associated with exposure to second-hand smoke (RR = 1.43) when cohort studies (a specific type of observational study) only were examined but not when all the studies were combined.
What Do These Findings Mean?
These findings provide limited evidence for a weak association between smoke exposure and allergic disease in adults but suggest that both active and passive smoking are associated with a modestly increased risk of allergic diseases in children and adolescents. The accuracy of these findings may be affected by the use of questionnaires to assess smoke exposure and allergic disease development in most of the studies in the meta-analysis and by the possibility that individuals exposed to smoke may have shared other characteristics that were actually responsible for their increased risk of allergic diseases. To shed more light on the role of smoking in allergic diseases, additional studies are needed that accurately measure exposure and outcomes. However, the present findings suggest that, in countries where many people smoke, 14% and 13% of allergic rhinitis and allergic dermatitis, respectively, among children may be attributable to active smoking. Thus, the elimination of active smoking among children and adolescents could prevent one in seven cases of allergic rhinitis and one in eight cases of allergic dermatitis in such countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001611.
The UK National Health Service Choices website provides information about allergic rhinitis, hay fever (including personal stories), allergic dermatitis (including personal stories), and food allergy (including personal stories)
The US National Institute of Allergy and Infectious Disease provides information about allergic diseases
The UK not-for-profit organization Allergy UK provides information about all aspects of allergic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on allergic rhinitis and allergic dermatitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and food allergy (in English and Spanish)
doi:10.1371/journal.pmed.1001611
PMCID: PMC3949681  PMID: 24618794
3.  Is Food Insecurity Associated with HIV Risk? Cross-Sectional Evidence from Sexually Active Women in Brazil 
PLoS Medicine  2012;9(4):e1001203.
Alexander Tsai and colleagues show that in sexually active women in Brazil severe food insecurity with hunger was positively associated with symptoms potentially indicative of sexually transmitted infection and with reduced odds of condom use.
Background
Understanding how food insecurity among women gives rise to differential patterning in HIV risks is critical for policy and programming in resource-limited settings. This is particularly the case in Brazil, which has undergone successive changes in the gender and socio-geographic composition of its complex epidemic over the past three decades. We used data from a national survey of Brazilian women to estimate the relationship between food insecurity and HIV risk.
Methods and Findings
We used data on 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. Self-reported outcomes were (a) consistent condom use, defined as using a condom at each occasion of sexual intercourse in the previous 12 mo; (b) recent condom use, less stringently defined as using a condom with the most recent sexual partner; and (c) itchy vaginal discharge in the previous 30 d, possibly indicating presence of a sexually transmitted infection. The primary explanatory variable of interest was food insecurity, measured using the culturally adapted and validated Escala Brasiliera de Segurança Alimentar. In multivariable logistic regression models, severe food insecurity with hunger was associated with a reduced odds of consistent condom use in the past 12 mo (adjusted odds ratio [AOR] = 0.67; 95% CI, 0.48–0.92) and condom use at last sexual intercourse (AOR = 0.75; 95% CI, 0.57–0.98). Self-reported itchy vaginal discharge was associated with all categories of food insecurity (with AORs ranging from 1.46 to 1.94). In absolute terms, the effect sizes were large in magnitude across all outcomes. Underweight and/or lack of control in sexual relations did not appear to mediate the observed associations.
Conclusions
Severe food insecurity with hunger was associated with reduced odds of condom use and increased odds of itchy vaginal discharge, which is potentially indicative of sexually transmitted infection, among sexually active women in Brazil. Interventions targeting food insecurity may have beneficial implications for HIV prevention in resource-limited settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
At the beginning of the AIDS epidemic, more men than women were infected with HIV, the virus that causes AIDS, but currently half of all HIV-positive adults are women. Most women become infected with HIV through unprotected sexual intercourse with an infected male partner. Biologically, women are twice as likely to become infected through unprotected heterosexual intercourse as men. Moreover, women are often unable to negotiate condom use because of unequal gender relations—men can insist on unprotected sexual intercourse in many relationships. Another factor often related to unequal gender relations that may shape women's risk of exposure to HIV is food insecurity—limited or uncertain access to enough nutritionally adequate and safe food for an active, healthy life. Recent studies done in sub-Saharan Africa suggest that food insecurity can affect women's engagement in risky sexual behaviors such as unprotected sex, transactional sex (sexual relationships that involve the giving of goods or services such as free lodgings), and commercial sex work.
Why Was This Study Done?
Policymakers planning HIV prevention strategies in resource-limited settings need to know whether food insecurity affects sexual risk taking among women. If it increases risk taking, then interventions that target food insecurity should improve the effectiveness of HIV prevention strategies. However, little is known about food insecurity and sexual risk taking outside sub-Saharan Africa. In this cross-sectional study (a study that characterizes a population at a single point in time), the researchers investigate whether food insecurity is associated with risky sexual behavior among sexually active women in Brazil, a country where the number of new heterosexually transmitted HIV infections among women is increasing. Condom promotion is the mainstay of Brazil's HIV prevention strategy, but less than half of the population reports the use of a condom whenever sexual intercourse occurs (consistent condom use) or at last sexual intercourse (recent condom use), and a greater proportion of men than women report condom use, possibly because of unequal power relations between men and women.
What Did the Researchers Do and Find?
The researchers obtained data on consistent condom use, recent condom use, and self-reported itchy vaginal discharge in the previous 30 days (used here as an indication that a woman may have a sexually transmitted infection) for 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. They then used multivariable logistic regression (a statistical method) to investigate the association between these outcomes and food insecurity, which was measured using the Escala Brasiliera de Insegurança Alimentar, an 18-item questionnaire that asks people to recall information about the quantity and quality of food available to them over the previous three months. Severe food insecurity with hunger (the most extreme category of food insecurity) was associated with an adjusted odds ratio (AOR) for consistent condom use of 0.67. That is, women who reported severe food insecurity were two-thirds as likely to use a condom whenever they had sexual intercourse as women who were food secure, after adjustment for other factors that might have affected condom use. The probability of consistent condom use was 15% among women who were food secure but only 10.5% among women who had the worst food security. Severe food insecurity with hunger was also associated with a reduced odds of recent condom use (AOR = 0.75), whereas all categories of food insecurity increased the odds of a recent itchy vaginal discharge.
What Do These Findings Mean?
These findings indicate that severe food insecurity with hunger is associated with reduced condom use and with increased occurrence of symptoms that may indicate sexually transmitted disease among sexually active women in Brazil. Because the study looked at women at only a single time point, these findings do not show that food insecurity causes risky sexual behavior. Moreover, these findings may not be generalizable to other settings, and they do not distinguish between regular condom use with a regular partner and regular condom use with casual partners. Also, although the researchers investigated two hypothesized explanations—lack of control in sexual relations and chronic energy deficiency—neither of these factors could explain why food insecurity is associated with risky sexual behavior. Nevertheless, these findings suggest that interventions that target sexual risk reduction behaviors are unlikely to be optimally effective if food insecurity is not taken into account, and, thus, the researchers conclude, HIV prevention strategies in Brazil should include interventions that target food insecurity.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001203.
Information is available from the US National Institute of Allergy and Infectious Diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, women, HIV, and AIDS, and HIV and AIDS in Brazil (in English and Spanish); personal stories of women living with HIV are available
HIV InSite provides comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California at San Francisco
Additional patient stories about living with HIV/AIDS are available through the charity website Healthtalkonline
A primer on food security from the Food and Agriculture Organization of the United Nations is available
Information about the 2006–2007 Brazilian national survey on health in women and children is available in Portuguese; a profile of food security in Brazil is also available (some information in English but mainly in Portuguese)
doi:10.1371/journal.pmed.1001203
PMCID: PMC3323512  PMID: 22505852
4.  TREATMENT OF ASTHMA AND FOOD ALLERGY WITH HERBAL INTERVENTIONS FROM TRADITIONAL CHINESE MEDICINE 
Prevalence of asthma and allergy has increased over the past 2–3 decades in Westernized countries. Despite increased understanding of the pathogenesis of asthma and allergic diseases, control of severe asthma is still difficult. Asthma is also associated with high prevalence of anxiety in particular adolescents. There is no effective treatment for food allergy. Food allergy is often associated with severe and recalcitrant eczema. Novel approaches for treatment of asthma and food allergy and comorbid conditions are urgently needed. Traditional Chinese medicine (TCM), used in Asia for centuries, is beginning to play a role in Western health care. There is increasing scientific evidence supporting the use of TCM for asthma treatment.
This review article discusses promising TCM interventions for asthma, food allergy and comorbid conditions and explores their possible mechanisms of action. Since 2005, several controlled clinical studies of “anti-asthma” herbal remedies have been published. Among the herbal medicines, anti-asthma herbal medicine intervention (ASHMI) is the only anti-asthma TCM product that is a US FDA investigational new drug (IND) that has entered clinical trials. Research into ASHMI’s effects and mechanisms of actions in animal models is actively being pursued. Research on TCM herbal medicines for treating food allergy is rare. The herbal intervention, Food Allergy Herbal Formula-2 (FAHF-2) is the only US FDA botanical IND under investigation as a multiple food allergy therapy. Published articles and abstracts, as well as new data generated in preclinical and clinical studies of ASHMI and FAHF-2 are the bases for this review. The effect of TCM therapy on food allergy associated recalcitrant eczema, based on case review, is also included.
Laboratory and clinical studies demonstrate a beneficial effect of ASHMI treatment on asthma. The possible mechanisms underlying the efficacy are multiple. Preclinical studies demonstrated the efficacy and safety of FAHF-2 for treating food allergy in a murine model. A clinical study demonstrated that FAHF-2 is safe, well tolerated, and exhibited beneficial immunomodulatory effects. A clinical report showed that TCM treatment reduced eczema scores and improved quality of life. Herbal interventions, ASHMI and FAHF-2 may be further developed as botanical drugs for treating asthma and food allergy. TCM may also be of benefit for comorbid conditions such as anxiety and recalcitrant eczema. More controlled studies are warranted.
In conclusion, novel approaches for treatment of asthma and food allergy and comorbid conditions such as anxiety and eczema are urgently needed. This article discusses promising interventions for such conditions from traditional Chinese medicine (TCM) and explores their possible mechanisms of action.
doi:10.1002/msj.20294
PMCID: PMC4118473  PMID: 21913200
Herbal interventions; traditional Chinese medicine; ASHMI; FAHF-2; asthma; food allergy
5.  Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods 
Background
Our aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow’s milk, hen’s egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed.
Methods
The disease-specific food allergy quality of life questionnaire (FAQLQ-AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ-5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy-nine patients participated (28 males, 51 females, mean-age 41 years).
Results
The domain with the most negative impact on HRQL was AADR, assessing the patients’ experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto-injector, was associated with low HRQL. These effects were not seen using EQ-5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies.
Conclusions
The FAQLQ-AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ-5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL.
doi:10.1186/2045-7022-3-21
PMCID: PMC3702411  PMID: 23816063
Food allergy; Adults; Health-related quality of life; Instrument; Questionnaire
6.  Duration of a cow-milk exclusion diet worsens parents’ perception of quality of life in children with food allergies 
BMC Pediatrics  2013;13:203.
Background
In Italy, rigorous studies obtained with specific and validated questionnaires that explore the impact of exclusion diets on health-related quality of life (HRQoL) in children with food allergies are lacking. In this cross-sectional study, we wished to validate the Italian version of a disease-specific quality of life questionnaire, and assess the impact of exclusion diets on the HRQoL in a cohort of Italian children with IgE-mediated food allergies.
Methods
Children on an exclusion diet for ≥1 food were enrolled consecutively, and their parents completed the validated Italian version of the Food Allergy Quality of Life Questionnaire–Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM).
Results
Ninety-six parents of children aged 0–12 years answered the FAQLQ–PF. The validity of the construct of the questionnaire was assessed by correlation between the FAQLQ–PF and FAIM–PF (r = 0.85). The Italian version of the FAQLQ had good internal consistency (Cronbach's α >0.70). Factors that mainly influenced the HRQoL were older age, severity of food allergy, and the duration of the cow milk-exclusion diet.
Conclusions
The FAQLQ–PF, validated in Italian, is a reliable instrument. Worse QoL scores were observed among older children, those with severe systemic reactions, and those with a prolonged cow milk-free diet. It is very important to consider the QoL assessment as an integral part of food-allergy management. These results emphasize the need to administer exclusion diets only for the necessary time and the importance of assessment of the HRQoL in these patients.
doi:10.1186/1471-2431-13-203
PMCID: PMC4233620  PMID: 24308381
Quality of life; Food allergy; Questionnaire; Diet; Milk; Egg; Food-related anxiety; Italian
7.  A Randomised Controlled Trial of Ion-Exchange Water Softeners for the Treatment of Eczema in Children 
PLoS Medicine  2011;8(2):e1000395.
In a randomized trial evaluating the effect of installation of ion-exchange water softeners in the households of children with eczema, the researchers found no evidence of improvement in eczema severity as compared to usual care in the study population.
Background
Epidemiological studies and anecdotal reports suggest a possible link between household use of hard water and atopic eczema. We sought to test whether installation of an ion-exchange water softener in the home can improve eczema in children.
Methods and Findings
This was an observer-blind randomised trial involving 336 children (aged 6 months to 16 years) with moderate/severe atopic eczema. All lived in hard water areas (≥200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. The primary outcome was change in eczema severity (Six Area Six Sign Atopic Dermatitis Score, SASSAD) at 12 weeks, measured by research nurses who were blinded to treatment allocation. Analysis was based on the intent-to-treat population. Eczema severity improved for both groups during the trial. The mean change in SASSAD at 12 weeks was −5.0 (20% improvement) for the water softener group and −5.7 (22% improvement) for the usual care group (mean difference 0.66, 95% confidence interval −1.37 to 2.69, p = 0.53). No between-group differences were noted in the use of topical corticosteroids or calcineurin inhibitors.
Conclusions
Water softeners provided no additional benefit to usual care in this study population. Small but statistically significant differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias, since participants were aware of their treatment allocation. A detailed report for this trial is also available at http://www.hta.ac.uk.
Trial registration
Current Controlled Trials ISRCTN71423189
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Eczema (sometimes referred to as atopic dermatitis) is a chronic, inflammatory skin condition that affects about 20% of school children in developed countries. Eczema is often associated with other conditions, such as asthma, hay-fever and food allergy and can cause intractable itching leading to thickened skin, bleeding, secondary infection, sleep loss, poor concentration, and psychological distress. Current topical treatments for eczema have side effects, for example, topical corticosteroids may cause skin thinning and the long term safety of topical tacrolimus and pimecrolimus has yet to be determined. Therefore, there is a lot of interest in exploring the benefits of non-pharmacological treatments that have no apparent side effects.
Water hardness (≥200 mg/l calcium carbonate) has become a recent focus of attention.
Why Was This Study Done?
In addition to some epidemiological evidence linking increased water hardness with increased eczema prevalence, there have been widespread anecdotal reports of improvement in the skin of children with eczema when the family has moved from a hard to a soft water area. In addition, some patients report how their eczema symptoms have rapidly improved following the installation of a water softener. However, to date there have been no relevant published trials evaluating the potential benefit of water softeners for eczema. Given the lack of evidence, the high public interest in their potential benefit and the low risk of adverse effects, the researcher conducted a study to assess whether the installation of an ion-exchange water softener reduces the severity of eczema in children with moderate to severe eczema.
What Did the Researchers Do and Find?
The researchers did a pilot study that showed that it was not possible to blind participants to their treatment allocation using real and “dummy” water softener units because the softened water produced more soap suds. So the researchers conducted an observer-blind randomised controlled trial in which they used trained research nurses to conduct an objective assessment of every participant's skin. The researchers recruited 336 children who all lived in hard water areas in England. Eligible children were aged 6 months to 16 years who had a diagnosis of eczema (in line with the UK working party's diagnostic criteria) and an eczema severity score of 10 or over. Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. Trained research nurses examined each child's skin at baseline and at 6, 12, and 16 weeks to record changes in eczema severity. The researchers also analysed any changes in symptoms over the study period such as, sleep loss and itchiness, the amount of topical corticosteroid/calcineurin inhibitors used, the Dermatitis Family Impact questionnaire and the health related Quality of Life (children's version).
Although both treatment groups improved in disease severity during the course of the trial, the researchers found no difference between the treatment groups in the main outcome—eczema severity. Similar finding were found for night movement (scratching) and the use of topical medications (creams/ointments applied to the skin), both of which were blinded to intervention status. Nevertheless, parents in the trial did report small health benefits, and just over 50% chose to buy the water softener at the end of the trial because of perceived improvements in the eczema and the wider benefits of water softeners. It is unclear how much of this effect can be explained by prior belief in the effectiveness of the water softeners for the treatment of eczema.
What Do These Findings Mean?
The results of this study suggest that water softeners provide no additional clinical benefit to usual care in children with eczema so the use of ion-exchange water softeners for the treatment of moderate to severe eczema in children should not be recommended. However, it is up to each family to decide whether or not the wider benefits of installing a water softener in their home are sufficient to consider buying one.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000395.
The UK's NHS presents information on eczema for patients and families
MedlinePlus gives information for patients, families, and caregivers on eczema and other similar conditions
The National Eczema Society in the UK provides information and a helpline for eczema patients, families, and caregivers
Medinfo provides information for eczema patients
Wikipedia has more information about water softening (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000395
PMCID: PMC3039684  PMID: 21358807
8.  Food Allergy and Increased Asthma Morbidity in a School-Based Inner-City Asthma Study 
Background
Children with asthma have increased prevalence of food allergies. The relationship between food allergy and asthma morbidity is unclear.
Objective
We aimed to investigate the presence of food allergy as an independent risk factor for increased asthma morbidity using the School Inner-City Asthma (SICAS), a prospective study evaluating risk factors and asthma morbidity among urban children.
Methods
We prospectively surveyed 300 children from inner-city schools with physician-diagnosed asthma, followed by clinical evaluation. Food allergies were reported including symptoms experienced within one hour of food ingestion. Asthma morbidity, pulmonary function, and resource utilization were compared between children with food allergies and without.
Results
Seventy-three (24%) of 300 asthmatic children surveyed had physician- diagnosed food allergy, and 36 (12%) had multiple food allergies. Those with any food allergy independently had increased risk of hospitalization (OR: 2.35, 95% CI: 1.30–4.24, p=0.005), and use of controller medication (OR: 1.99, 95% CI: 1.06–3.74, p=0.03). Those with multiple food allergies also had an independently higher risk of hospitalization in the past year (OR: 4.10 95% CI: 1.47–11.45, p=0.007), asthma-related hospitalization (OR: 3.52, 95% CI: 1.12–11.03, p=0.03), controller medication use (OR: 2.38 95% CI: 1.00–5.66, p=0.05), and more provider visits (median 4.5 versus 3.0, p=0.008). Furthermore, lung function was significantly lower (% predicted FEV1 and FEV1/FVC ratios) in both food allergy category groups.
Conclusions
Food allergy is highly prevalent in inner-city school-aged children with asthma. Children with food allergies have increased asthma morbidity and health resource utilization with decreased lung function, and this association is stronger in those with multiple food allergies.
doi:10.1016/j.jaip.2013.06.007
PMCID: PMC3777668  PMID: 24058900
asthma; food allergy; hospitalization; morbidity; prevalence; resource utilization; risk
9.  Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects 
Background
Food allergy (FA) negatively affects quality of life in caregivers of food-allergic children, imposing a psychosocial and economic burden. Oral immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT can be a source of anxiety as it carries risk for allergic reactions. The effect of OIT with multiple food allergens (mOIT) on FA-specific health-related quality of life (HRQL) has never been studied in participants with multiple, severe food allergies. This study is the first to investigate the effects of mOIT on FA-related HRQL in caregivers of pediatric subjects.
Methods
Caregiver HRQL was assessed using a validated Food Allergy Quality of Life – Parental Burden (FAQL-PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of participants in two single-center Phase I clinical trials receiving mOIT (n = 29) or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL-PB prior to study intervention and at 2 follow-up time-points (6 months and 18 months). Parents of subjects not receiving OIT (control group, n = 10) completed the FAQL-PB for the same time-points.
Results
HRQL improved with clinical (change < -0.5) and statistical (p < 0.05) significance in the mOIT group (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0; 18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean 3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow-up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the control group (n = 10).
Conclusion
Multi-allergen OIT with or without omalizumab leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the psychosocial and economic burden FA imposes on caregivers of food-allergic children.
doi:10.1186/1710-1492-10-25
PMCID: PMC4032627  PMID: 24860608
Oral immunotherapy; Omalizumab; Anti-IgE; Food allergy; Oral desensitization; Quality of life; Health-related quality of life
10.  A 24-h helpline for access to expert management advice for food allergy-related anaphylaxis in children: protocol for a pragmatic randomised controlled trial 
BMJ Open  2012;2(4):e001282.
Objectives
Anaphylaxis is an important, potentially life-threatening paediatric emergency. It is responsible for considerable morbidity and, in some cases, death. Poor outcomes may be associated with an inability to differentiate between milder and potentially more severe reactions and an associated reluctance to administer self-injectable adrenaline. This study aims to assess the effectiveness of a 24-h telephone access to specialist paediatric allergy expert advice in improving the quality of life of children and their families with potentially life-threatening food allergy (ie, anaphylaxis) compared with usual clinical care.
Methods and analysis
Children aged less than 16 years with food allergy and who carry an adrenaline autoinjector will be recruited from the Paediatric Allergy Clinic at Cork University Hospital, Ireland and baseline disease-specific quality of life will be ascertained using the validated Food Allergy Quality of Life Questionnaire (FAQLQ). Participants will be randomised for a period of 6 months to the 24-h telephone specialist support line or usual care. The primary outcome measure of interest is a change in FAQLQ scores, which will be assessed at 0, 1 and 6 months postrandomisation. Analysis will be on an intention-to-treat basis using a 2×3 repeated measures within-between analysis of variance. Although lacking power, we will in addition assess the impact of the intervention on a range of relevant process and clinical endpoints.
Ethics and dissemination
This trial protocol has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings will be presented at international scientific conferences and will be reported on in the peer-reviewed literature in early 2013.
doi:10.1136/bmjopen-2012-001282
PMCID: PMC3425896  PMID: 22893666
Accident & Emergency medicine; Immunology; Paediatrics; Paediatric A&E and ambulatory care
11.  Impact of maternal education about complementary feeding and provision of complementary foods on child growth in developing countries 
BMC Public Health  2011;11(Suppl 3):S25.
Background
Childhood undernutrition is prevalent in low and middle income countries. It is an important indirect cause of child mortality in these countries. According to an estimate, stunting (height for age Z score < -2) and wasting (weight for height Z score < -2) along with intrauterine growth restriction are responsible for about 2.1 million deaths worldwide in children < 5 years of age. This comprises 21 % of all deaths in this age group worldwide. The incidence of stunting is the highest in the first two years of life especially after six months of life when exclusive breastfeeding alone cannot fulfill the energy needs of a rapidly growing child. Complementary feeding for an infant refers to timely introduction of safe and nutritional foods in addition to breast-feeding (BF) i.e. clean and nutritionally rich additional foods introduced at about six months of infant age. Complementary feeding strategies encompass a wide variety of interventions designed to improve not only the quality and quantity of these foods but also improve the feeding behaviors. In this review, we evaluated the effectiveness of two most commonly applied strategies of complementary feeding i.e. timely provision of appropriate complementary foods (± nutritional counseling) and education to mothers about practices of complementary feeding on growth. Recommendations have been made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by Child Health Epidemiology Reference Group (CHERG).
Methods
We conducted a systematic review of published randomized and quasi-randomized trials on PubMed, Cochrane Library and WHO regional databases. The included studies were abstracted and graded according to study design, limitations, intervention details and outcome effects. The primary outcomes were change in weight and height during the study period among children 6-24 months of age. We hypothesized that provision of complementary food and education of mother about complementary food would significantly improve the nutritional status of the children in the intervention group compared to control. Meta-analyses were generated for change in weight and height by two methods. In the first instance, we pooled the results to get weighted mean difference (WMD) which helps to pool studies with different units of measurement and that of different duration. A second meta-analysis was conducted to get a pooled estimate in terms of actual increase in weight (kg) and length (cm) in relation to the intervention, for input into the LiST model.
Results
After screening 3795 titles, we selected 17 studies for inclusion in the review. The included studies evaluated the impact of provision of complementary foods (±nutritional counseling) and of nutritional counseling alone. Both these interventions were found to result in a significant increase in weight [WMD 0.34 SD, 95% CI 0.11 – 0.56 and 0.30 SD, 95 % CI 0.05-0.54 respectively) and linear growth [WMD 0.26 SD, 95 % CI 0.08-0.43 and 0.21 SD, 95 % CI 0.01-0.41 respectively]. Pooled results for actual increase in weight in kilograms and length in centimeters showed that provision of appropriate complementary foods (±nutritional counseling) resulted in an extra gain of 0.25kg (±0.18) in weight and 0.54 cm (±0.38) in height in children aged 6-24 months. The overall quality grades for these estimates were that of ‘moderate’ level. These estimates have been recommended for inclusion in the Lives Saved Tool (LiST) model. Education of mother about complementary feeding led to an extra weight gain of 0.30 kg (±0.26) and a gain of 0.49 cm (±0.50) in height in the intervention group compared to control. These estimates had been recommended for inclusion in the LiST model with an overall quality grade assessment of ‘moderate’ level.
Conclusion
Provision of appropriate complementary food, with or without nutritional education, and maternal nutritional counseling alone lead to significant increase in weight and height in children 6-24 months of age. These interventions can significantly reduce the risk of stunting in developing countries and are recommended for inclusion in the LiST tool.
doi:10.1186/1471-2458-11-S3-S25
PMCID: PMC3231899  PMID: 21501443
12.  Asthma and allergies in Jamaican children aged 2–17 years: a cross-sectional prevalence survey 
BMJ Open  2012;2(4):e001132.
Objective
To determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2–17 years.
Design
A cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units.
Setting
Jamaica, a Caribbean island with a total population of approximately 2.6 million, geographically divided into 14 parishes.
Participants
Children aged 2–17 years, who were resident in private households. Institutionalised children such as those in boarding schools and hospitals were excluded from the survey.
Primary and secondary outcome measures
The prevalence and severity of asthma and allergy symptoms, doctor-diagnosed asthma and risk factors for asthma.
Results
Almost a fifth (19.6%) of Jamaican children aged 2–17 years had current wheeze, while 16.7% had self-reported doctor-diagnosed asthma. Both were more common among males than among females. The prevalence of rhinitis, hay fever and eczema among children was 24.5%, 25% and 17.3%, respectively. Current wheeze was more common among children with rhinitis in the last 12 months (44.3% vs 12.6%, p<0.001), hay fever (36.8% vs 13.8%, p<0.001) and eczema (34.1% vs 16.4%, p<0.001). Independent risk factors for current wheeze (ORs, 95% CI) were chest infections in the first year of life 4.83 (3.00 to 7.77), parental asthma 4.19 (2.8 to 6.08), rhinitis in the last 12 months 6.92 (5.16 to 9.29), hay fever 4.82 (3.62 to 6.41), moulds in the home 2.25 (1.16 to 4.45), cat in the home 2.44 (1.66 to 3.58) and dog in the home 1.81 (1.18 to 2.78).
Conclusions
The prevalence of asthma and allergies in Jamaican children is high. Significant risk factors for asthma include chest infections in the first year of life, a history of asthma in the family, allergies, moulds and pets in the home.
Article summary
Article focus
The prevalence of asthma and allergies in both developed and developing countries is continuing to rise.
In some Caribbean countries, asthma is a public health problem associated with high economic costs.
This study determined the prevalence of asthma, allergy symptoms and associated risk factors.
Key messages
We demonstrated that the prevalence of asthma and allergy symptoms among Jamaican children aged 2–17 years is high.
Both the prevalence and severity of asthma symptoms are comparable to that reported among children in high-income countries.
Current wheeze and doctor-diagnosed asthma were more common in males and in children with allergies.
A history of asthma in the family, chest infections in the first year of life, allergies, exposure to moulds and pets in the home were associated with significant risk for asthma.
Identifying children at high risk for asthma and controlling modifiable risk factors is important in reducing the prevalence and morbidity related to asthma.
Strengths and limitations of this study
This is the first national study on asthma and allergies in Jamaica using a nationally representative sample of children with a response rate of 80%.
We used a modified ISAAC protocol in which sampling was done by household rather than by school. Using a population-based sampling strategy; we sampled one child and one adult per household. This approach enabled us to obtain national prevalence estimates for both adults and children in one survey at a reduced cost.
Limitations of this study include the fact that the prevalence of asthma and allergies was based solely on self-reports, no objective measures were done. Also in younger children, caregivers responded to questionnaires.
doi:10.1136/bmjopen-2012-001132
PMCID: PMC3400072  PMID: 22798254
13.  Health-related quality of life among adolescents with allergy-like conditions – with emphasis on food hypersensitivity 
Background
It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL). However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of self-reported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences.
Methods
In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13–21 years old (response rate 97%).
Results
Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino-conjunctivitis). A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p < 0.001). The adolescents with allergy-like conditions reported significantly lower HRQL (p < 0.001) in seven of the eight SF-36 health scales compared with adolescents without such conditions, regardless of whether the condition had been doctor-diagnosed or not. Most adolescents suffered from complex allergy-like conditions.
Conclusions
The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools.
doi:10.1186/1477-7525-2-65
PMCID: PMC534793  PMID: 15555064
Health-related quality of life; hypersensitivity; allergic disease; food hypersensitivity; adolescence; gender
14.  A global survey of changing patterns of food allergy burden in children 
While food allergies and eczema are among the most common chronic non-communicable diseases in children in many countries worldwide, quality data on the burden of these diseases is lacking, particularly in developing countries. This 2012 survey was performed to collect information on existing data on the global patterns and prevalence of food allergy by surveying all the national member societies of the World Allergy Organization, and some of their neighbouring countries. Data were collected from 89 countries, including published data, and changes in the health care burden of food allergy. More than half of the countries surveyed (52/89) did not have any data on food allergy prevalence. Only 10% (9/89) of countries had accurate food allergy prevalence data, based on oral food challenges (OFC). The remaining countries (23/89) had data largely based on parent-reporting of a food allergy diagnosis or symptoms, which is recognised to overestimate the prevalence of food allergy. Based on more accurate measures, the prevalence of clinical (OFC proven) food allergy in preschool children in developed countries is now as high as 10%. In large and rapidly emerging societies of Asia, such as China, where there are documented increases in food allergy, the prevalence of OFC-proven food allergy is now around 7% in pre-schoolers, comparable to the reported prevalence in European regions. While food allergy appears to be increasing in both developed and developing countries in the last 10–15 years, there is a lack of quality comparative data. This survey also highlights inequities in paediatric allergy services, availability of adrenaline auto-injectors and standardised National Anaphylaxis Action plans. In conclusion, there remains a need to gather more accurate data on the prevalence of food allergy in many developed and developing countries to better anticipate and address the rising community and health service burden of food allergy.
doi:10.1186/1939-4551-6-21
PMCID: PMC3879010  PMID: 24304599
Food allergy; Allergic disease; Allergy epidemic; Allergy prevention; Food allergens
15.  Long-term Outcomes in Pediatric-Onset Esophageal Eosinophilia 
Background
Pediatric eosinophilic esophagitis (EoE) is a newly recognized antigen-induced form of chronic esophagitis.
Objective
Characterization of long-term clinical outcomes in pediatric EoE patients is needed.
Methods
From histologic review of 3,817 pediatric esophageal biopsies from 1982–1999, we conducted a nested case-control study of patients with retrospectively-identified histologic eosinophilic esophagitis (rEoE) and chronic esophagitis (CE), as well as an age-matched control cohort. Participants were asked to complete validated health-related outcome questionnaires.
Results
After an average of 15 years following initial endoscopy, both cohorts, 42/198 rEoE and 67/468 CE patients (as well as 100 age-matched controls), completed questionnaires. Compared to control patients, quality of life was significantly decreased among rEoE patients (P<0.001) and CE patients (P<0.001). Rates of dysphagia (rEoE 49%; CE 37%; control 6%) and food impaction (rEoE 40%; CE 14%; control 3%) were significantly increased in the rEoE cohort compared to controls (P<0.001, P<0.001 respectively). Increased esophageal eosinophil counts (OR 1.6; 95% CI 1.1–2.5; P<0.05) during childhood were predictive of dysphagia during early adulthood. Food allergy (OR 2.7; CI 1.2, 6.0; P<0.01), allergic rhinitis (OR 3.5; CI 1.8, 6.8; P<0.001), and asthma (OR 2.1; CI 1.04, 4.3; P=0.04) were associated with dysphagia. Food impaction was more common among patients with reported food allergy than those without (OR 3.1; CI 1.2, 7.8; P=0.02).
Conclusions
Esophageal eosinophilia is associated with reduced quality of life and persistent symptoms 15 years after presentation. Elevated esophageal eosinophil counts and the occurrence of food allergy and atopy in childhood increase the rate of dysphagia in young adulthood.
doi:10.1016/j.jaci.2011.05.006
PMCID: PMC3130990  PMID: 21636117
eosinophilic esophagitis; pediatric; patient-reported outcomes; natural history; eosinophil
16.  A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay 
Background
Peanut allergy is relatively common, typically permanent, and often severe. Double-blind, placebo-controlled food challenge is considered the gold standard for the diagnosis of food allergy–related disorders. However, the complexity and potential of double-blind, placebo-controlled food challenge to cause life-threatening allergic reactions affects its clinical application. A laboratory test that could accurately diagnose symptomatic peanut allergy would greatly facilitate clinical practice.
Objective
We sought to develop an allergy diagnostic method that could correctly predict symptomatic peanut allergy by using peptide microarray immunoassays and bioinformatic methods.
Methods
Microarray immunoassays were performed by using the sera from 62 patients (31 with symptomatic peanut allergy and 31 who had outgrown their peanut allergy or were sensitized but were clinically tolerant to peanut). Specific IgE and IgG4 binding to 419 overlapping peptides (15 mers, 3 offset) covering the amino acid sequences of Ara h 1, Ara h 2, and Ara h 3 were measured by using a peptide microarray immunoassay. Bioinformatic methods were applied for data analysis.
Results
Individuals with peanut allergy showed significantly greater IgE binding and broader epitope diversity than did peanut-tolerant individuals. No significant difference in IgG4 binding was found between groups. By using machine learning methods, 4 peptide biomarkers were identified and prediction models that can predict the outcome of double-blind, placebo-controlled food challenges with high accuracy were developed by using a combination of the biomarkers.
Conclusions
In this study, we developed a novel diagnostic approach that can predict peanut allergy with high accuracy by combining the results of a peptide microarray immunoassay and bioinformatic methods. Further studies are needed to validate the efficacy of this assay in clinical practice.
doi:10.1016/j.jaci.2012.02.012
PMCID: PMC3631605  PMID: 22444503
Epitope mapping; peptide microarray; peanut allergy; bioinformatics; machine learning; allergy diagnosis; epitope biomarker
17.  Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial 
Lancet  2014;383(9925):1297-1304.
Summary
Background
Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts.
Methods
We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244.
Findings
The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant).
Interpretation
OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group.
Funding
MRC-NIHR partnership.
doi:10.1016/S0140-6736(13)62301-6
PMCID: PMC4255069  PMID: 24485709
18.  Food Access and Diet Quality Are Associated with Quality of Life Outcomes among HIV-Infected Individuals in Uganda 
PLoS ONE  2013;8(4):e62353.
Background
Food insecurity is associated with poor nutritional and clinical outcomes among people living with HIV/AIDS. Few studies investigate the link between food insecurity, dietary diversity and health-related quality of life among people living with HIV/AIDS.
Objective
We investigated whether household food access and individual dietary diversity are associated with health-related quality of life among people living with HIV/AIDS in Uganda.
Methods
We surveyed 902 people living with HIV/AIDS and their households from two clinics in Northern Uganda. Health-related quality of life outcomes were assessed using the Medical Outcomes Study (MOS)-HIV Survey. We performed multivariate regressions to investigate the relationship between health-related quality of life, household food insecurity and individual dietary diversity.
Results
People living with HIV/AIDS from severe food insecurity households have mean mental health status scores that are 1.7 points lower (p<.001) and physical health status scores that are 1.5 points lower (p<.01). Individuals with high dietary diversity have mean mental health status scores that were 3.6 points higher (p<.001) and physical health status scores that were 2.8 points higher (p<.05).
Conclusions
Food access and diet quality are associated with health-related quality of life and may be considered as part of comprehensive interventions designed to mitigate psychosocial consequences of HIV.
doi:10.1371/journal.pone.0062353
PMCID: PMC3630150  PMID: 23638049
19.  The diagnosis of food allergy: protocol for a systematic review 
Background
The literature on diagnostic tests for food allergy currently lacks clear consensus regarding the accuracy and safety of different investigative approaches. The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform the formulation of clinical recommendations. The aim of this systematic review will be to assess the diagnostic accuracy of tests aimed at supporting the clinical diagnosis of IgE-mediated food allergy.
Methods
The following databases from inception to September 30, 2012 will be searched for studies of diagnostic tests: Cochrane Library (Wiley&Sons); MEDLINE (OVID); Embase (OVID); CINAHL (Ebscohost); ISI Web of Science (Thomson Web of Knowledge); TRIP Database (web http://www.tripdatabase.com); and Clinicaltrials.gov (NIH web). These database searches will be supplemented by contacting an international panel of experts. Studies evaluating APT, SPT, specific-IgE, and component specific-IgE in participants of any age with suspected food allergy will be included. The reference standard will be DBPCFC in at least 50% of the participants. Studies will be quality assessed by using the QUADAS-2 instrument. We will report summary statistics such as sensitivity, specificity, and/or likelihood ratios. We will use the hierarchical summary ROC (HSROC) model to summarize the accuracy of each test and to compare the accuracy of two or more tests.
Discussion
Decisions on which tests to use need to be guided by availability of tests, populations being cared for, risks, financial considerations and test properties. This review will examine papers from around the world, covering children and adults with suspected food allergy in varying populations and concentrated on four type of tests: APT, SPT, specific-IgEs, and component specific-IgEs.
doi:10.1186/2045-7022-3-18
PMCID: PMC3679851  PMID: 23742215
Food allergy; IgE-mediated; Diagnosis; Diagnostic tests
20.  Peanut allergy in relation to heredity, maternal diet, and other atopic diseases: results of a questionnaire survey, skin prick testing, and food challenges. 
BMJ : British Medical Journal  1996;313(7056):518-521.
OBJECTIVES: To determine rates of other atopic manifestations in people with peanut allergy and the prevalence of such allergy in their families. DESIGN: A survey of people with self reported peanut allergy and people referred by their general practitioner for suspected peanut allergy; survey and skin testing of 50 children with reported peanut allergy and their available first degree relatives. SUBJECTS: 622 adults and children with reported, suspected, or known peanut allergy. MAIN OUTCOME MEASURES: Prevalence of peanut allergy and other allergies in the families of people with peanut allergy. RESULTS: 622 valid completed questionnaires were returned out of the 833 questionnaires dispatched (74.7%). All forms of atopy were both more common in successive generations (P < 0.0001) and more common in maternal than paternal relatives (P < 0.0001). Peanut allergy was reported by 0.1% (3/2409) of grandparents, 0.6% (7/1213) of aunts and uncles, 1.6% (19/1218) of parents, and 6.9% (42/610) of siblings. Consumption of peanuts while pregnant or breast feeding was more common among mothers of probands aged < or = 5 years than mothers of probands aged > 5 years (P < 0.001). Age of onset correlated inversely with year of birth (r = -0.6, P < 0.001). Skin prick testing of 50 children with reported peanut allergy and their families: 7 probands (14%) had a negative result for peanut. Peanut allergy was refuted by food challenge in all those tested (5/7). No parent and 13% (5/39) of siblings had a positive result on skin prick testing for peanut. Two of these siblings had negative challenge with peanuts. The prevalence of peanut allergy in siblings is therefore 3/39 (7%). CONCLUSIONS: Peanut allergy is more common in siblings of people with peanut allergy than in the parents or the general population. Its apparently increasing prevalence may reflect a general increase of atopy, which is inherited more commonly from the mother. Peanut allergy is presenting earlier in life, possibly reflecting increased consumption of peanut by pregnant and nursing mothers.
PMCID: PMC2351952  PMID: 8789975
21.  The Effect of Adding Ready-to-Use Supplementary Food to a General Food Distribution on Child Nutritional Status and Morbidity: A Cluster-Randomized Controlled Trial 
PLoS Medicine  2012;9(9):e1001313.
Lieven Huybregts and colleagues investigate how supplementing a general food distribution with a fortified lipid-based spread during a seasonal hunger gap in Chad affects anthropometric and morbidity outcomes for children aged 6 to 36 months.
Background
Recently, operational organizations active in child nutrition in developing countries have suggested that blanket feeding strategies be adopted to enable the prevention of child wasting. A new range of nutritional supplements is now available, with claims that they can prevent wasting in populations at risk of periodic food shortages. Evidence is lacking as to the effectiveness of such preventive interventions. This study examined the effect of a ready-to-use supplementary food (RUSF) on the prevention of wasting in 6- to 36-mo-old children within the framework of a general food distribution program.
Methods and Findings
We conducted a two-arm cluster-randomized controlled pragmatic intervention study in a sample of 1,038 children aged 6 to 36 mo in the city of Abeche, Chad. Both arms were included in a general food distribution program providing staple foods. The intervention group was given a daily 46 g of RUSF for 4 mo. Anthropometric measurements and morbidity were recorded monthly. Adding RUSF to a package of monthly household food rations for households containing a child assigned to the intervention group did not result in a reduction in cumulative incidence of wasting (incidence risk ratio: 0.86; 95% CI: 0.67, 1.11; p = 0.25). However, the intervention group had a modestly higher gain in height-for-age (+0.03 Z-score/mo; 95% CI: 0.01, 0.04; p<0.001). In addition, children in the intervention group had a significantly higher hemoglobin concentration at the end of the study than children in the control group (+3.8 g/l; 95% CI: 0.6, 7.0; p = 0.02), thereby reducing the odds of anemia (odds ratio: 0.52; 95% CI: 0.34, 0.82; p = 0.004). Adding RUSF also resulted in a significantly lower risk of self-reported diarrhea (−29.3%; 95% CI: 20.5, 37.2; p<0.001) and fever episodes (−22.5%; 95% CI: 14.0, 30.2; p<0.001). Limitations of this study include that the projected sample size was not fully attained and that significantly fewer children from the control group were present at follow-up sessions.
Conclusions
Providing RUSF as part of a general food distribution resulted in improvements in hemoglobin status and small improvements in linear growth, accompanied by an apparent reduction in morbidity.
Trial registration
ClinicalTrials.gov NCT01154595
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Good nutrition during childhood is essential for health and survival. Undernourished children are more susceptible to infections and are more likely to die from common ailments such as diarrhea than well-nourished children. Globally, undernutrition contributes to about a third of deaths among children under five years old. Experts use three physical measurements to determine whether a child is undernourished. An “underweight” child has a low weight for his or her age and gender when compared to the World Health Organization Child Growth Standards, which chart the growth of a reference population. A “stunted” child has a low height for his or her age; stunting indicates chronic undernutrition. A “wasted” child has a low weight for his or her height; wasting indicates acute undernutrition and can be caused by disasters or seasonal food shortages. Recent estimates indicate that about a fifth of young children in developing countries are underweight, and one third are stunted; in south Asia and west/central Africa, more than one tenth of children are wasted, a condition that markedly increases the risk of death.
Why Was This Study Done?
In emergency situations, international organizations support affected populations by providing “general food distributions.” Recently, there have been claims that the provision of targeted nutritional supplements within a general food distribution framework effectively prevents child wasting, but there is little evidence to support these claims. In this cluster-randomized controlled trial, the researchers investigate the effect of a targeted daily dose of a “ready-to-use supplementary food” (RUSF; a lipid-based nutrient supplement) on indicators of undernutrition in 6- to 36-month-old, non-wasted children in Chad, a country beset by a severe food crisis. Political instability in this central African country has severely reduced the nutritional status of children, and annual droughts, which affect crop production, cause a “hunger gap” between June and October. In a recent survey, one fifth of children in Chad were wasted at the beginning of this hunger gap. A cluster-randomized trial randomly assigns groups of people to receive alternative interventions and compares the outcomes in the differently treated “clusters.”
What Did the Researchers Do and Find?
The researchers randomly assigned fourteen household clusters in the city of Abeche, Chad, to the trial's intervention or control arm. All the households received a general food distribution that included staple foods; eligible children in the intervention households were also given a daily RUSF ration between June and September 2010. The researchers regularly measured the children's weights and heights, recorded illnesses reported by caregivers, and measured each child's blood hemoglobin level before and after the intervention to assess their risk of anemia, an indicator of poor nutrition. The addition of RUSF to the household food rations did not significantly reduce the cumulative incidence of wasting. That is, although fewer children in the intervention group became wasted during the trial than in the control group, this difference was not statistically significant—it could have happened by chance. However, compared to the children in the control group, those in the intervention group had a significantly greater gain in height-for-age (equivalent to a difference in height gain of 0.09 cm/month), slightly higher hemoglobin levels at the end of the study, which significantly reduced their anemia risk, and a significantly lower risk of self-reported diarrhea and fever.
What Do These Findings Mean?
Although targeted RUSF provided as part of a general food distribution had no significant effect on wasting in young children in Abeche, Chad, the intervention improved their hemoglobin status and linear growth, and reduced illness among them. Why didn't targeted RUSF prevent wasting effectively in this trial? Maybe the effect of RUSF was diluted out by the effect of the general food distribution or maybe the trial was too short to see a clear effect. Most importantly, though, the trial may have been too small to see a clear effect—the researchers were unable to enroll as many children into their trial as they had planned because of political instability in Chad, and this probably limited the trial's ability to detect small differences between the control and intervention groups. Nevertheless, because these findings provide no clear evidence that adding RUSF to a household food ration effectively prevents wasting, alternative ways to prevent acute malnutrition in Chad and other vulnerable regions of the world should be investigated.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001313.
This study is further discussed in a PLOS Medicine Perspective by Kathryn Dewey and Mary Arimond
Action Contra la Faim–France has a web page that describes the situation in Chad
The United Nations Childrens Fund, which protects the rights of children and young people around the world, provides detailed statistics on child undernutrition; it has detailed information, including videos, about the current food crisis in Chad and the Sahel
The WHO Child Growth Standards are available (in several languages)
The United Nations provides information on ongoing world efforts to reduce hunger and child mortality
The World Food Programme is the world's largest humanitarian agency fighting hunger worldwide; its website provides detailed information about malnutrition in Chad, including a video of the current food crisis in the country
Starved for Attention is an international multimedia campaign launched in 2010 by Médecins Sans Frontiéres (MSF) and the VII Photo agency to rewrite the story of childhood malnutrition; information about MSFs work in Chad to tackle malnutrition is available
doi:10.1371/journal.pmed.1001313
PMCID: PMC3445445  PMID: 23028263
22.  Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of multidisciplinary care (MDC) compared with usual care (UC, single health care provider) for the treatment of stable chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Chronic obstructive pulmonary disease is a progressive disorder with episodes of acute exacerbations associated with significant morbidity and mortality. Cigarette smoking is linked causally to COPD in more than 80% of cases. Chronic obstructive pulmonary disease is among the most common chronic diseases worldwide and has an enormous impact on individuals, families, and societies through reduced quality of life and increased health resource utilization and mortality.
The estimated prevalence of COPD in Ontario in 2007 was 708,743 persons.
Technology
Multidisciplinary care involves professionals from a range of disciplines, working together to deliver comprehensive care that addresses as many of the patient’s health care and psychosocial needs as possible.
Two variables are inherent in the concept of a multidisciplinary team: i) the multidisciplinary components such as an enriched knowledge base and a range of clinical skills and experiences, and ii) the team components, which include but are not limited to, communication and support measures. However, the most effective number of team members and which disciplines should comprise the team for optimal effect is not yet known.
Research Question
What is the effectiveness and cost-effectiveness of MDC compared with UC (single health care provider) for the treatment of stable COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on July 19, 2010 using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 1995 until July 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.
Inclusion Criteria
health technology assessments, systematic reviews, or randomized controlled trials
studies published between January 1995 and July 2010;
COPD study population
studies comparing MDC (2 or more health care disciplines participating in care) compared with UC (single health care provider)
Exclusion Criteria
grey literature
duplicate publications
non-English language publications
study population less than 18 years of age
Outcomes of Interest
hospital admissions
emergency department (ED) visits
mortality
health-related quality of life
lung function
Quality of Evidence
The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six randomized controlled trials were obtained from the literature search. Four of the 6 studies were completed in the United States. The sample size of the 6 studies ranged from 40 to 743 participants, with a mean study sample between 66 and 71 years of age. Only 2 studies characterized the study sample in terms of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria, and in general the description of the study population in the other 4 studies was limited. The mean percent predicted forced expiratory volume in 1 second (% predicted FEV1) among study populations was between 32% and 59%. Using this criterion, 3 studies included persons with severe COPD and 2 with moderate COPD. Information was not available to classify the population in the sixth study.
Four studies had MDC treatment groups which included a physician. All studies except 1 reported a respiratory specialist (i.e., respiratory therapist, specialist nurse, or physician) as part of the multidisciplinary team. The UC group was comprised of a single health care practitioner who may or may not have been a respiratory specialist.
A meta-analysis was completed for 5 of the 7 outcome measures of interest including:
health-related quality of life,
lung function,
all-cause hospitalization,
COPD-specific hospitalization, and
mortality.
There was only 1 study contributing to the outcome of all-cause and COPD-specific ED visits which precluded pooling data for these outcomes. Subgroup analyses were not completed either because heterogeneity was not significant or there were a small number of studies that were meta-analysed for the outcome.
Quality of Life
Three studies reported results of quality of life assessment based on the St. George’s Respiratory Questionnaire (SGRQ). A mean decrease in the SGRQ indicates an improvement in quality of life while a mean increase indicates deterioration in quality of life. In all studies the mean change score from baseline to the end time point in the MDC treatment group showed either an improvement compared with the control group or less deterioration compared with the control group. The mean difference in change scores between MDC and UC groups was statistically significant in all 3 studies. The pooled weighted mean difference in total SGRQ score was −4.05 (95% confidence interval [CI], −6.47 to 1.63; P = 0.001). The GRADE quality of evidence was assessed as low for this outcome.
Lung Function
Two studies reported results of the FEV1 % predicted as a measure of lung function. A negative change from baseline infers deterioration in lung function and a positive change from baseline infers an improvement in lung function. The MDC group showed a statistically significant improvement in lung function up to 12 months compared with the UC group (P = 0.01). However this effect is not maintained at 2-year follow-up (P = 0.24). The pooled weighted mean difference in FEV1 percent predicted was 2.78 (95% CI, −1.82 to −7.37). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
Hospital Admissions
All-Cause
Four studies reported results of all-cause hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 4 studies were pooled to determine a summary estimate. There is a statistically significant 25% relative risk (RR) reduction in all-cause hospitalizations in the MDC group compared with the UC group (P < 0.001). The index of heterogeneity (I2) value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
COPD-Specific Hospitalization
Three studies reported results of COPD-specific hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically significant 33% RR reduction in all-cause hospitalizations in the MDC group compared with the UC group (P = 0.002). The I2 value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
Emergency Department Visits
All-Cause
Two studies reported results of all-cause ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically nonsignificant reduction in all-cause ED visits when data from these 2 studies are pooled (RR, 0.64; 95% CI, 0.31 to −1.33; P = 0.24). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
COPD-Specific
One study reported results of COPD-specific ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically significant 41% reduction in COPD-specific ED visits when the data from these 2 studies are pooled (RR, 0.59; 95% CI, 0.43−0.81; P < 0.001). The GRADE quality of evidence was assessed as moderate for this outcome.
Mortality
Three studies reported the mortality during the study follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically nonsignificant reduction in mortality between treatment groups (RR, 0.81; 95% CI, 0.52−1.27; P = 0.36). The I2 value is 19%, indicating low statistical heterogeneity between studies. All studies had a 12-month follow-up period. The GRADE quality of evidence was assessed as low for this outcome.
Conclusions
Significant effect estimates with moderate quality of evidence were found for all-cause hospitalization, COPD-specific hospitalization, and COPD-specific ED visits (Table ES1). A significant estimate with low quality evidence was found for the outcome of quality of life (Table ES2). All other outcome measures were nonsignificant and supported by low or very low quality of evidence.
Summary of Dichotomous Data
Abbreviations: CI, confidence intervals; COPD, chronic obstructive pulmonary disease; n, number.
Summary of Continuous Data
Abbreviations: CI, confidence intervals; FEV1, forced expiratory volume in 1 second; n, number; SGRQ, St. George’s Respiratory Questionnaire.
PMCID: PMC3384374  PMID: 23074433
23.  IgE mediated food allergy in Korean children: focused on plant food allergy 
Asia Pacific Allergy  2013;3(1):15-22.
Food allergy (FA) is a worldwide problem, with increasing prevalence in many countries, and it poses a clearly increasing health problem in Korea. In Korea, as a part of International Study of Asthma and Allergy in Childhood (ISAAC), a series of nation-wide population studies for prevalence of allergic disease in children were carried out, with the Korean version of ISAAC in 1995, 2000, and 2010. From the survey, the twelve-month prevalence of FA showed no significant differences from 1995 to 2000 in both age groups (6-12 years-old, 6.5% in 1995 and 5.7% in 2000; 12-15 year-olds, 7.4% in 1995 and 8.6% in 2000). The mean lifetime prevalence of FA which had ever been diagnosed by medical doctor was 4.7% in 6-12 year-olds and 5.1% in 12-15 year-olds respectively in 2000. In Korean children, the major causes of FA are almost same as in other countries, although the order prevalence may vary, a prime example of which being that peanut and tree nut allergies are not prevalent, as in western countries. Both pediatric emergency department (ED) visits and deaths relating to food induced anaphylaxis have also increased in western countries. From a study which based on data from the Korean Health Insurance Review and Assessment Service (KHIRA) from 2001 to 2007, the incidence of anaphylaxis under the age of 19 was 0.7-1 per 100,000 person-year, and foods (24.9%) were the most commonly identified cause of childhood anaphylaxis. In another epidemiologic study, involving 78889 patients aged 0-18 years who visited the EDs of 9 hospitals during June 2008 to Mar 2009, the incidence of food related anaphylaxis was 4.56 per 10,000 pediatric ED visits. From these studies, common causes of food related anaphylaxis were seafood, buckwheat, cow's milk, fruits, peanut and tree nuts. Although systematic epidemiologic studies have not reported on the matter, recently, plant foods related allergy has increased in Korean children. Among 804 children with moderate to severe atopic dermatitis, we reveals that the peanut sensitization rate in Korea reaches 18%, and that, when sensitized to peanut, patients showed a significant tendency to have co-sensitization with house dust mites, egg white, wheat, and soybean. The higher specific IgE to peanut was related to the likelihood of the patient developing severe systemic reactions. In another study, based on the data analysis of 69 patients under 4 years of age who had suspected peanut and tree nut allergy, 22 (31.9%) were sensitized to walnut (>0.35 kU/L, 0.45-27.4 kU/L) and 6 (8.7%) experienced anaphylaxis due to a small amount of walnut exposure. Furthermore, in this review, clinical and immunological studies on plant food allergies, such as buckwheat allergy, rice allergy, barley allergy, and kiwi fruit allergy, in Korean children are discussed.
doi:10.5415/apallergy.2013.3.1.15
PMCID: PMC3563016  PMID: 23403730
Food allergy; Korean children; Anaphylaxis; Plant food allergy
24.  Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study 
PLoS Medicine  2013;10(10):e1001542.
Using data from the ARROW trial, Joanna Lewis and colleagues investigate the CD4 cell count recovery profiles of children infected with HIV starting antiretroviral therapy in Sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Background
Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery.
Methods and Findings
CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4–17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization–recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled.
Conclusions
Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, about 3.3 million children under 15 years old are infected with HIV, the virus that causes AIDS. More than 90% of these children live in sub-Saharan Africa, where nearly 600 children become infected with HIV every day, usually acquiring the virus from their mother during pregnancy, birth, or breastfeeding. HIV gradually reduces the numbers of CD4 lymphocytes in the immune system, leaving infected individuals susceptible to other infections. HIV infection can be kept in check but not cured with antiretroviral therapy (ART)—cocktails of drugs that have to be taken every day throughout life. ART reduces the amount of virus in the blood (viral load), which allows the immune system to recover (long-term immune reconstitution). Unfortunately, ART is very expensive, but concerted international efforts over the past decade mean that about a third of children who need ART are now receiving it, including half a million children in sub-Saharan Africa.
Why Was This Study Done?
World Health Organization (WHO) guidelines recommend initiation of ART at age-related CD4 cell count thresholds based on the risk of short-term disease progression. The guidelines recommend that all HIV-positive children under two years old begin ART as soon they receive a diagnosis of HIV infection. For children aged 2–5 years, ART initiation is recommended once the CD4 count drops below 750 cells/µl blood, whereas for older children the threshold for ART initiation is 350 CD4 cells/µl. Because of improved ART coverage, many more HIV-infected children now survive into adulthood than in the past. It is therefore important to know how the timing of ART initiation in childhood affects long-term immune reconstitution. Unfortunately, although several studies have examined the effect of ART on immune reconstitution in adults, the results of these studies cannot be extrapolated to children because of age-related differences in immune reconstitution. In this cohort-based modelling study, the researchers investigate long-term CD4 recovery in a cohort (group) of HIV-infected children initiating ART in Uganda and Zimbabwe, and present statistical models that predict patterns of long-term CD4 status based on age and CD4 count at ART initiation.
What Did the Researchers Do and Find?
To investigate long-term CD4 reconstitution in children, the researchers used CD4 counts collected during the ARROW trial, a study designed to investigate monitoring strategies during first-line ART in 1,206 HIV-positive children. In three-quarters of the children, CD4 reconstitution following ART initiation was asymptotic—CD4 counts increased rapidly immediately after ART initiation, then slowed before eventually reaching a constant level of about 80% of the CD4 count expected in an uninfected child of the same age. Using a nonlinear mixed-effects statistical model that fitted this pattern of immune reconstitution, the researchers predicted CD4 trajectories for children starting ART at different ages and with different CD4 counts. Higher long-term counts were predicted for children starting ART earlier and with higher CD4 counts. Thus, to achieve a CD4 count greater than 700 cells/µl at age 20 years, CD4 counts of at least 96 cells/µl, 130 cells/µl, and 557 cells/µl are needed for children aged two, five, and 12 years, respectively, when they initiate ART. Qualitatively distinct reconstitution patterns were seen in the remaining children in the study.
What Do These Findings Mean?
These findings suggest that young HIV-positive, ART-naïve children can achieve high CD4 counts in later life, provided ART is initiated as recommended in the current WHO guidelines. However, the recommended CD4 count thresholds for ART initiation are unlikely to maximize immune reconstitution in treatment-naïve children over ten years old. Rather, these findings suggest that ART initiation should be considered in these older children when their CD4 count is still high—even though they have a low risk of immediate disease progression—in order to achieve higher long-term CD4 levels. The omission of viral load measurements in the researchers' model may limit the accuracy of these findings. Moreover, although the predictions made by the model apply to children who will go on to experience asymptotic recovery, they are less relevant to those with different recovery profiles, who cannot currently be accurately identified. Further exploration of the immunological mechanisms underlying the CD4 recovery profiles described here should improve our understanding of the factors that determine the response of HIV-positive children to ART and provide information to guide the management of HIV infections in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001542.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa and on HIV infection in children (in English and Spanish)
The UNAIDS World AIDS Day Report 2012 provides up-to-date information about the AIDS epidemic and efforts to halt it; the UNAIDS's 2013 Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children by 2015
The World Health Organization provides information about universal access to AIDS treatment (in several languages); its 2010 guidelines for ART in infants and children can be downloaded
Information about the ARROW trial is available
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001542
PMCID: PMC3812080  PMID: 24204216
25.  Clinical Utility of Vitamin D Testing 
Executive Summary
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, and
genetic 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 & 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 English
Publications that reported the prevalence of vitamin D deficiency in Canada
Studies that included subjects from the general population or with kidney disease
Studies in children or adults
Studies published between January 1998 and July 17th 2009
Exclusion Criteria
Studies that included subjects defined according to a specific disease other than kidney disease
Letters, comments, and editorials
Studies 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/L
Prevalence of serum vitamin D less than 40 to 50 nmol/L
Serum 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.
Summary of Findings
Fourteen prevalence studies examining Canadian adults and children met the eligibility criteria. With the exception of one longitudinal study, the studies had a cross-sectional design. Two studies were conducted among Canadian adults with renal disease but none studied Canadian children with renal disease (though three such US studies were included). No systematic reviews or health technology assessments that evaluated the prevalence of vitamin D deficiency in Canada were identified. Two studies were published in grey literature, consisting of a Canadian survey designed to measure serum vitamin D levels and a study in infants presented as an abstract at a conference. Also included were the results of vitamin D tests performed in community laboratories in Ontario between October 2008 and September 2009 (provided by the Ontario Association of Medical Laboratories).
Different threshold levels were used in the studies, thus we reported the percentage of subjects with serum levels of between 25 and 30 nmol/L and between 37.5 and 50 nmol/L. Some studies stratified the results according to factors affecting vitamin D status and two used multivariate models to investigate the effects of these characteristics (including age, season, BMI, vitamin D intake, skin pigmentation, and season) on serum 25(OH)D levels. It’s unclear, however, if these studies were adequately powered for these subgroup analyses.
Study participants generally consisted of healthy, community-dwelling subjects and most excluded individuals with conditions or medications that alter vitamin D or bone metabolism, such as kidney or liver disease. Although the studies were conducted in different parts of Canada, fewer were performed in Northern latitudes, i.e. above 53°N, which is equivalent to the city of Edmonton.
Adults
Serum vitamin D levels of < 25 to 30 nmol/L were observed in 0% to 25.5% of the subjects included in five studies; the weighted average was 3.8% (95% CI: 3.0, 4.6). The preliminary results of the Canadian survey showed that approximately 5% of the subjects had serum levels below 29.5 nmol/L. The results of over 600,000 vitamin D tests performed in Ontarian community laboratories between October 2008 and September 2009 showed that 2.6% of adults (> 18 years) had serum levels < 25 nmol/L.
The prevalence of serum vitamin D levels below 37.5-50 nmol/L reported among studies varied widely, ranging from 8% to 73.6% with a weighted average of 22.5%. The preliminary results of the CHMS survey showed that between 10% and 25% of subjects had serum levels below 37 to 48 nmol/L. The results of the vitamin D tests performed in community laboratories showed that 10% to 25% of the individuals had serum levels between 39 and 50 nmol/L.
In an attempt to explain this inter-study variation, the study results were stratified according to factors affecting serum vitamin D levels, as summarized below. These results should be interpreted with caution as none were adjusted for other potential confounders. Adequately powered multivariate analyses would be necessary to determine the contribution of risk factors to lower serum 25(OH)D levels.
Seasonal variation
Three adult studies evaluating serum vitamin D levels in different seasons observed a trend towards a higher prevalence of serum levels < 37.5 to 50 nmol/L during the winter and spring months, specifically 21% to 39%, compared to 8% to 14% in the summer. The weighted average was 23.6% over the winter/spring months and 9.6% over summer. The difference between the seasons was not statistically significant in one study and not reported in the other two studies.
Skin Pigmentation
Four studies observed a trend toward a higher prevalence of serum vitamin D levels < 37.5 to 50 nmol/L in subjects with darker skin pigmentation compared to those with lighter skin pigmentation, with weighted averages of 46.8% among adults with darker skin colour and 15.9% among those with fairer skin.
Vitamin D intake and serum levels
Four adult studies evaluated serum vitamin D levels according to vitamin D intake and showed an overall trend toward a lower prevalence of serum levels < 37.5 to 50 nmol/L with higher levels of vitamin D intake. One study observed a dose-response relationship between higher vitamin D intake from supplements, diet (milk), and sun exposure (results not adjusted for other variables). It was observed that subjects taking 50 to 400 IU or > 400 IU of vitamin D per day had a 6% and 3% prevalence of serum vitamin D level < 40 nmol/L, respectively, versus 29% in subjects not on vitamin D supplementation. Similarly, among subjects drinking one or two glasses of milk per day, the prevalence of serum vitamin D levels < 40 nmol/L was found to be 15%, versus 6% in those who drink more than two glasses of milk per day and 21% among those who do not drink milk. On the other hand, one study observed little variation in serum vitamin D levels during winter according to milk intake, with the proportion of subjects exhibiting vitamin D levels of < 40 nmol/L being 21% among those drinking 0-2 glasses per day, 26% among those drinking > 2 glasses, and 20% among non-milk drinkers.
The overall quality of evidence for the studies conducted among adults was deemed to be low, although it was considered moderate for the subgroups of skin pigmentation and seasonal variation.
Newborn, Children and Adolescents
Five Canadian studies evaluated serum vitamin D levels in newborns, children, and adolescents. In four of these, it was found that between 0 and 36% of children exhibited deficiency across age groups with a weighted average of 6.4%. The results of over 28,000 vitamin D tests performed in children 0 to 18 years old in Ontario laboratories (Oct. 2008 to Sept. 2009) showed that 4.4% had serum levels of < 25 nmol/L.
According to two studies, 32% of infants 24 to 30 months old and 35.3% of newborns had serum vitamin D levels of < 50 nmol/L. Two studies of children 2 to 16 years old reported that 24.5% and 34% had serum vitamin D levels below 37.5 to 40 nmol/L. In both studies, older children exhibited a higher prevalence than younger children, with weighted averages 34.4% and 10.3%, respectively. The overall weighted average of the prevalence of serum vitamin D levels < 37.5 to 50 nmol/L among pediatric studies was 25.8%. The preliminary results of the Canadian survey showed that between 10% and 25% of subjects between 6 and 11 years (N= 435) had serum levels below 50 nmol/L, while for those 12 to 19 years, 25% to 50% exhibited serum vitamin D levels below 50 nmol/L.
The effects of season, skin pigmentation, and vitamin D intake were not explored in Canadian pediatric studies. A Canadian surveillance study did, however, report 104 confirmed cases1 (2.9 cases per 100,000 children) of vitamin D-deficient rickets among Canadian children age 1 to 18 between 2002 and 2004, 57 (55%) of which from Ontario. The highest incidence occurred among children living in the North, i.e., the Yukon, Northwest Territories, and Nunavut. In 92 (89%) cases, skin pigmentation was categorized as intermediate to dark, 98 (94%) had been breastfed, and 25 (24%) were offspring of immigrants to Canada. There were no cases of rickets in children receiving ≥ 400 IU VD supplementation/day.
Overall, the quality of evidence of the studies of children was considered very low.
Kidney Disease
Adults
Two studies evaluated serum vitamin D levels in Canadian adults with kidney disease. The first included 128 patients with chronic kidney disease stages 3 to 5, 38% of which had serum vitamin D levels of < 37.5 nmol/L (measured between April and July). This is higher than what was reported in Canadian studies of the general population during the summer months (i.e. between 8% and 14%). In the second, which examined 419 subjects who had received a renal transplantation (mean time since transplantation: 7.2 ± 6.4 years), the prevalence of serum vitamin D levels < 40 nmol/L was 27.3%. The authors concluded that the prevalence observed in the study population was similar to what is expected in the general population.
Children
No studies evaluating serum vitamin D levels in Canadian pediatric patients with kidney disease could be identified, although three such US studies among children with chronic kidney disease stages 1 to 5 were. The mean age varied between 10.7 and 12.5 years in two studies but was not reported in the third. Across all three studies, the prevalence of serum vitamin D levels below the range of 37.5 to 50 nmol/L varied between 21% and 39%, which is not considerably different from what was observed in studies of healthy Canadian children (24% to 35%).
Overall, the quality of evidence in adults and children with kidney disease was considered very low.
Clinical Utility of Vitamin D Testing
A high quality comprehensive systematic review published in August 2007 evaluated the association between serum vitamin D levels and different bone health outcomes in different age groups. A total of 72 studies were included. The authors observed that there was a trend towards improvement in some bone health outcomes with higher serum vitamin D levels. Nevertheless, precise thresholds for improved bone health outcomes could not be defined across age groups. Further, no new studies on the association were identified during an updated systematic review on vitamin D published in July 2009.
With regards to non-bone health outcomes, there is no high or even moderate quality evidence that supports the effectiveness of vitamin D in outcomes such as cancer, cardiovascular outcomes, and all-cause mortality. Even if there is any residual uncertainty, there is no evidence that testing vitamin D levels encourages adherence to Health Canada’s guidelines for vitamin D intake. A normal serum vitamin D threshold required to prevent non-bone health related conditions cannot be resolved until a causal effect or correlation has been demonstrated between vitamin D levels and these conditions. This is as an ongoing research issue around which there is currently too much uncertainty to base any conclusions that would support routine vitamin D testing.
For patients with chronic kidney disease (CKD), there is again no high or moderate quality evidence supporting improved outcomes through the use of calcitriol or vitamin D analogs. In the absence of such data, the authors of the guidelines for CKD patients consider it best practice to maintain serum calcium and phosphate at normal levels, while supplementation with active vitamin D should be considered if serum PTH levels are elevated. As previously stated, the authors of guidelines for CKD patients believe that there is not enough evidence to support routine vitamin D [25(OH)D] testing. According to what is stated in the guidelines, decisions regarding the commencement or discontinuation of treatment with calcitriol or vitamin D analogs should be based on serum PTH, calcium, and phosphate levels.
Limitations associated with the evidence of vitamin D testing include ambiguities in the definition of an ‘adequate threshold level’ and both inter- and intra- assay variability. The MAS considers both the lack of a consensus on the target serum vitamin D levels and assay limitations directly affect and undermine the clinical utility of testing. The evidence supporting the clinical utility of vitamin D testing is thus considered to be of very low quality.
Daily vitamin D intake, either through diet or supplementation, should follow Health Canada’s recommendations for healthy individuals of different age groups. For those with medical conditions such as renal disease, liver disease, and malabsorption syndromes, and for those taking medications that may affect vitamin D absorption/metabolism, physician guidance should be followed with respect to both vitamin D testing and supplementation.
Conclusions
Studies indicate that vitamin D, alone or in combination with calcium, may decrease the risk of fractures and falls among older adults.
There is no high or moderate quality evidence to support the effectiveness of vitamin D in other outcomes such as cancer, cardiovascular outcomes, and all-cause mortality.
Studies suggest that the prevalence of vitamin D deficiency in Canadian adults and children is relatively low (approximately 5%), and between 10% and 25% have serum levels below 40 to 50 nmol/L (based on very low to low grade evidence).
Given the limitations associated with serum vitamin D measurement, ambiguities in the definition of a ‘target serum level’, and the availability of clear guidelines on vitamin D supplementation from Health Canada, vitamin D testing is not warranted for the average risk population.
Health Canada has issued recommendations regarding the adequate daily intake of vitamin D, but current studies suggest that the mean dietary intake is below these recommendations. Accordingly, Health Canada’s guidelines and recommendations should be promoted.
Based on a moderate level of evidence, individuals with darker skin pigmentation appear to have a higher risk of low serum vitamin D levels than those with lighter skin pigmentation and therefore may need to be specially targeted with respect to optimum vitamin D intake. The cause-effect of this association is currently unclear.
Individuals with medical conditions such as renal and liver disease, osteoporosis, and malabsorption syndromes, as well as those taking medications that may affect vitamin D absorption/metabolism, should follow their physician’s guidance concerning both vitamin D testing and supplementation.
PMCID: PMC3377517  PMID: 23074397

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